Download Research Center for Radiation Therapy

The Swedish Competence Centres Programme
First generation of Competence Centres in Sweden
Research Center for Radiation Therapy
Final Report
1 March 1995 – 30 June 2007
December 2007
Anders Brahme, Center director
Professor Medical Radiation Physics
Department of Oncology-Pathology
Research Center for Radiation Therapy - Final Report
Contents
Executive Summary...........................................................................................1
Sammanfattning.................................................................................................3
1.
1.1
1.2
1.3
1.4
Basic Facts................................................................................................5
The participating parties ...........................................................................5
Financing of the Center ............................................................................9
Organisation ...........................................................................................10
External collaborators outside the center ...............................................11
2.
2.1
2.2
2.3
The Development of the Center during the Last Decade .......................12
Research program development .............................................................12
Organization and ways of collaboration within the Center ....................13
Added value of the Competence Center structure ..................................14
3.
3.1
3.2
3.3
Technical-Scientific and Clinical Results...............................................16
Project overview .....................................................................................16
Detailed project descriptions ..................................................................16
Key values ..............................................................................................26
4.
Industrial Results and Effects .................................................................30
5.
5.1
5.2
Conclusion ..............................................................................................31
Comments from the principal industrial partners ...................................31
Summary and conclusions ......................................................................34
Enclosure 1
Examinations
•
Doctoral theses
•
Licentiate theses
•
MSc theses
Enclosure 2
Publication list
•
Papers in scientific journals
•
Books and reports
•
Conference contributions
1
Executive Summary
Scientific and Technological Developments
During the 12 years of support from NUTEK and VINNOVA the Research Center for Radiation
Therapy has had a very dynamic development and strengthened its interaction with Swedish and
international Biomedical Engineering Industry. Initially the Center started several bi- and
multilateral collaborations on a number of well-defined projects on a pre-competition level.
Rather soon, the work condensed into a number of more general research programs focused on
areas such as Treatment Planning and Radiation Biology, and the development of new advanced
treatment techniques and procedures such as Dosimetry, Scanned Beams Therapy, Beam
Collimation, Adaptive Therapy, Patient Positioning, Intensity Modulation, Electron and Photon
Beam Therapy and Light Ion Therapy. The research has been very successful in most of these
areas and has resulted in many publications, MSc and PhD theses, industrial and hospital
recruitments, new products and even new companies.
Development of the Interaction between Biomedical Industry and the
Society
One of the most important structural developments has been the understanding that a more
clear-cut collaboration between the major actors in the biomedical arena is needed to get a well
functioning health care sector, and consequently, a better functioning society. The major actors
are:
1) Academia with well-developed biomedical and clinical research and education, in our case
Karolinska Institutet and Karolinska University Hospital.
2) Medical care with well-developed clinical research and developmental programs, here
Karolinska University Hospital was our partner.
3) Biomedical Industry with well-developed production, research and development
departments, in our case some twenty companies were involved.
4) Biomedical Research Councils that support the development of new procedures and
technologies, in our case NUTEK and VINNOVA but also other local, national and
international research councils.
5) A well functioning Market Place, where the products of the companies reaches the
members of the public – the consumers. In our case, this is largely located in the hospitals
where new treatment methods are tested and new ideas are brought to the companies to
improve function.
For a well functioning society, it is thus fundamental that all these players of the biomedical
market have a constructive and well functioning collaboration.
During our program we saw clearly how the possibility to form new companies, in close
collaboration with the five actors, became of key importance in the global development. The
new companies were needed in order to develop and produce new products for the national and
global market, not only for local hospital needs, when the established ones where uncertain
about their profitability, capacity or product profile. The companies were formed in close
collaboration between Biomedical Research and Hospital Care to ensure long-term product
development, continued clinical evaluation, and feedback for continued product and procedure
improvements. Generally, active and supportive research councils concerned are needed and
essential when more complex and systematic developments need to be conducted. Several of the
active research areas during the last part of the VINNOVA support have been of this character,
2
with extensive technological and scientific developments, such as the new range of Scanned
Beam treatment units for Photon and Electron Therapy and for Light Ion Therapy, and the
development of Basic Radiation Biology for advanced treatment planning.
Development of the Biomedical University Structure
The mechanisms and new areas of activity described above will most likely make the present
Center and others survive, continue and prosper far beyond the supported 12-year period in
close collaboration with biomedical industry, hospital care and biomedical research.
Interestingly, during the last decade Karolinska Institutet has significantly developed its
Research & Development side by forming an infrastructure and innovation system - Karolinska
Enterprise, with a holding company and venture capital structure - largely in response to the
observed clinical needs, for efficient scientific research and the improvement and development
of improved clinical methods and applications.
3
Sammanfattning
Vetenskaplig och teknisk utveckling
Under 12 år med stöd från NUTEK och VINNOVA har Forskningscentrum för Strålbehandling
haft en dynamisk utveckling och stärkt sin interaktion med svensk och internationell biomedicinsk industri och forskning. Initialt startade centret många bi- och multilaterala
samarbeten inom ett antal väldefinierade projekt med låg konkurrensfaktor. Rätt snart
koncentrerades arbetet på mer generella forskningsprogram med fokus på områden såsom
behandlingsplanering och strålningsbiologi, samt utveckling av nya behandlingstekniker och
procedurer inom dosimetri, svepstråleterapi, strålkollimering, adaptiv terapi, patientpositionering, intensitetsmodulation, elektron- och fotonstrålterapi och lättjonterapi. Forskningen har
varit mycket framgångsrik inom flera av dessa områden och har resulterat i många
publikationer, magister- och doktorsexamina, rekryteringar till industrin och sjukhus, nya
produkter och också till flera nya företag.
Utveckling av interaktionen mellan biomedicinsk industri och klinisk
forskning
En viktig insikt har varit förståelsen av att samarbetet mellan huvudaktörerna inom den biomedicinska arenan behöver renodlas och effektiviseras för att vi ska kunna få en välfungerande
sjukvårdssektor och därmed ett bättre samhälle. Huvudaktörerna är:
1. Akademin med välutvecklade kliniska program, här har Karolinska Institutet och
Karolinska Universitetssjukhuset varit våra partners.
2. Medicinsk vård med välutvecklade kliniska utvecklingsprogramprogram, även här har
Karolinska Universitetssjukhuset varit vår partner.
3. Biomedicinsk industri med välutvecklade produktions-, forsknings- och utvecklingsavdelningar, i vårt fall har ett tjugotal företag varit involverade.
4. Biomedicinska forskningsråd som stöder utvecklingen av nya procedurer och teknologier,
i vårt fall NUTEK och VINNOVA men även lokala, nationella och internationella
forskningsråd.
5. En välfungerande marknadsplats, i vårt fall oftast sjukhus, dit företagens produkter når
konsumenterna. Där testas nya behandlingsmetoder och idéer till funktionsförbättringar
framförs till företagen.
För ett välfungerande samhälle är det fundamentalt att alla dessa aktörer inom det biomedicinska området har ett konstruktivt och välfungerande samarbete. Under vårt projekt såg vi
också tydligt att möjligheten till att starta nya företag, i nära samarbete med ovan nämnda
aktörer, var av avgörande betydelse för den globala utvecklingen och samverkan.
De nya företagen behövs för att kunna utveckla och producera nya produkter för nationell och
globala marknad, inte enbart för de lokala sjukhusens behov. Företagen bildades i nära
samarbete mellan biomedicinsk forskning och sjukhusvård för att under lång tid säkerställa
produktutveckling och fortsatt klinisk utvärdering och tillhörande feedback för fortsatt produktoch procedurförbättring i klinisk samverkan. I allmänhet är de associerade forskningsråden
väsentliga när mer komplexa och systematiska utvecklingar är önskvärda eller nödvändiga.
Många av forskningsprogrammen under den senare delen av VINNOVA-stödet har kännetecknats av en systematisk utveckling med omfattande tekniska och vetenskapliga utvecklingar,
t.ex. nya svepstrålebaserade behandlingsenheter för foton- och elektronterapi, samt för
lättjonterapi och utveckling av basal strålningsbiologi för avancerad behandlingsplanering.
4
Utveckling av den biomedicinska universitetsstrukturen
De ovan beskrivna mekanismerna och nya aktivitetsområdena kommer med största sannolikhet
göra att det nuvarande forskningscentret och de avknoppade företagen kommer att överleva och
fortsätta att ha framgång långt efter den stödda 12-årsperioden i nära samarbete med den biomedicinska industrin, sjukvården och biomedicinska forskningen. Bland annat för att tillmötesgå behoven av effektiv forskning och klinisk utveckling har Karolinska Institutet under det
senaste decenniet byggt ut sin R&D genom att skapa en infrastruktur och ett innovationssystem,
Karolinska Enterprise. Detta bolag är uppbyggt som ett holdingbolag och venture capitalbolag.
5
1. Basic Facts
1.1
The participating parties
NUTEK and VINNOVA
Stage
NUTEK
VINNOVA
1
x
2
x
3
4
x
x
The University participation
Karolinska Institutet - the host institute of the Center - has been represented by the following
institutions and departments during the four stages.
Departments
Medical Radiation Physics, Dept of Oncology-Pathology, KI
Medical Radiation Physics, Stockholm University
Department of Hospital Physics, Karolinska University Hospital
Department of Radiation Sciences, Umeå University
Department of Oncology, Radiumhemmet
1
x
x
x
Stage
2
3
x
x
x
x
x
x
x
x
4
x
x
x
The Industrial participation
Companies
Applied Medical Imaging (AMI) AB
Comair AB
C-RAD Imaging AB (RayTherapy Imaging)
C-RAD Innovation AB (PencilBeam Technologies)
C-RAD Positioning AB (RayTherapy Positioning)
CTI PET Systems, Inc (CPS)
Elekta Instrument AB
Eurona Medical AB
IBA-Scanditronix AB / Scanditronix Medical
Latronix AB
Nucletron Scandinavia AB (MDS Nordion/Helax-Precitron)
Precitron AB
RaySearch Laboratories AB
Reachin Technologies AB
Sangtec Medical AB
ScandiNova Systems AB
Sectra AB
SenseGraphics AB
Studsvik Medical AB
Stage
1
x
x
2
x
3
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
4
x
x
x
x
x
6
The Companies
Applied Medical Imaging AB: Image processing.
AMI left the Center because of its low level of internal activity but contributed indirectly to our
own whole body atlas project.
Comair AB: Ultrasound.
On advice from its legal advisor Comair left the Center after stage 1 to avoid leakage of internal
know-how to other partners.
C-RAD Imaging AB (former name RayTherapy Imaging): Gas Electron Multipliers.
C-RAD Imaging develops a fast, sensitive and cost effective radiation detector based on GEMtechnology (Gas Electron Multiplier). The company has shown proof-of-principle with their
technology. Shares are now traded on Aktietorget.
C-RAD Innovation AB (acquired PencilBeam Technologies in spring 2007): Diagnostic and
IMRT focused radiation therapy units.
C-RAD Innovation is still a pure research company and tries to raise funding for their
accelerator projects. Close collaboration exists with IBA-Scanditronix and the scanning beam
machine is of key interest to combine with light ions. Shares are now traded at Aktietorget.
C-RAD Positioning AB (former name RayTherapy Positioning): Laser Camera
C-RAD Positioning AB develops a unique laser camera, formerly known as a Ladar System, for
speedy patient positioning and synchronization with organ movements during radiation therapy.
The company has developed a prototype, which has been tested clinically with positive results
at both Karolinska University Hospital and Uppsala University Hospital. The company has
attended large international oncology conferences where great interest has been shown,
especially for adaptive radiation treatment. The sales of the laser camera started during fall
2006 under the name C-RAD Sentinel. Shares are now traded on Aktietorget.
CTI PET Systems, Inc (CPS): PET imaging.
CPS was acquired by Siemens Molecular Imaging in April 2005, and has not participated in the
Center since then. A new detector that can be used both for PET and CT is under development
at the Center through the integrated project of the EU 6th framework program, BIOCARE. This
detector system may be of great importance for tumor imaging in the future, and the close
collaboration with the Center has been very interesting and productive.
Elekta Instrument AB: Radiation therapy.
A main interest for Elekta is projects focused on improvements of their Gamma Knife®. This
includes hardware and software development as well as clinical research in order to find new
indications for use and to improve the outcome for current indications. Another field of interest
is the image guided radiation therapy with their Synergy™ system, which makes it possible to
acquire CT-images with the treatment machine. There may be an interest at Elekta to raise their
photon energy so that effective PET-CT dose delivery verification can be performed.
Eurona AB: Molecular biology.
Eurona has not been actively working in the Center, partly due to alterations in company
priorities.
7
IBA-Scanditronix AB (IBA acquired Scanditronix Medical, February 1999): Accelerator
technology and dosimetry.
The main focus of IBA-Scanditronix is dosimetry and accelerator technology, such as new
dosimetric detectors like silicon diodes and CVD-diamonds, new dosimetry systems for medical
use on the IMRT market, as well as improvements of their Racetrack accelerator system. The
accelerator development is largely done in collaboration with C-RAD Innovation. Since IBAScanditronix also is one of the leading suppliers of proton therapy systems, they follow the
Center’s efforts with light ions with great interest and we hope to collaborate more closely on
scanning beam therapy and compact ion gantry designs.
Latronix AB: Laser technology.
Latronix was closely involved in the development of a 3D laser camera for patient positioning.
The company is now collaborating with C-RAD Positioning.
Nucletron Scandinavia AB (acquired Helax and Precitron from MDS Nordion during stage 3.
MDS Nordion acquired Helax and Precitron during stage 2): Treatment planning, dosimetry.
Nucletron’s treatment planning system is in clinical use today at the Karolinska University
Hospital. The company has recently signed an agreement with RaySearch Laboratories for the
development of their future IMRT modules. An improvement of this system, especially towards
radiobiological treatment planning for light ions, which is one of the main areas of research for
the Center, has high priority and collaboration with former center companies may be beneficial.
Precitron AB (merged with Helax and acquired by MDS Nordion during stage 2 and by
Nucletron during stage 3): Medical engineering.
The company had little interaction during the early phase of the Center.
RaySearch Laboratories AB: Treatment optimization.
RaySearch is the world-leading producer of IMRT modules used in treatment planning systems
that are mainly based on early developments at the department of Medical Radiation Physics
before the Center was formed. They have close collaboration with the center member Nucletron
Scandinavia AB, Philips and most recently Varian. The strong focus on radiobiological
optimization at our center will most likely be of importance for RaySearch in the future
development of their software modules such as for light ion therapy planning. Several bilateral
collaborations are already ongoing outside the Center.
Reachin Technologies AB: Haptic systems and devices.
Reachin Technologies was involved in the early discussions on the use of haptic devices in
radiation therapy but was not participating in any projects.
Sangtec Medical AB: Molecular biology.
Sangtec Medical has not been actively working in the Center partly due to alterations in
company priorities.
ScandiNova Systems AB: Microwave modulators.
ScandiNova Systems primarily develops modulators for microwave sources used for highenergy electron accelerators. In our IMRT project, the company has studied the design for an
integrated CT- and radiation therapy gantry. The design is based on their own modulator design,
the dynamic collimator of the Center, the laser camera and Gas Electron Multiplier
8
SECTRA-Imtec AB: PACS-image processing.
SECTRA-Imtec was not actively participating in projects during stage 3, but was closely
involved in new developments
SenseGraphics AB: Haptic systems
SenseGraphics develops a multimodality 4D (3D+T) imaging workstation. The purpose is to
evaluate the advantages with a haptic interface in effective image processing during 3D
treatment planning and treatment optimization. A so-called haptic phantom has been procured to
the Center and has been used in one Master thesis for 3D visualization with haptic. Advantages
in efficiency have been established in 3D treatment planning using a haptic interface.
Studsvik Medical AB: Radiation engineering.
Studsvik Medical started to commercialize BNCT (Boron Neutron Capture Therapy) with the
Studsvik nuclear reactor and accelerator based neutron sources. The interesting projects are
basic radiobiological research on this kind of therapy and development of a dedicated BNCT
treatment planning system in collaboration with the Center. The BNCT treatment activities
discontinued in 2005 and the rest of Studsvik Medical was sold to Hammercap AB.
9
1.2
Financing of the Center
Contributions from the partners (kSEK)
Stage 1
Stage 2
Stage 3
Stage 4
Stage 1-4
NUTEK/VINNOVA*
6 300
14 163
18 000
12 000
50 463
KI
5 164
12 454
15 871
15 108
48 597
Companies
5 481
15 740
18 020
13 549
52 790
16 945
42 357
51 891
40 657
151 850
Total contribution
The KI contribution (cash 17, in kind 45 580) includes research funding from: EU, The Swedish Cancer
Society, Swedish Research Council, Swedish Foundation for Strategic Research, The Knowledge
Foundation, The Cancer Research Funds of Radiumhemmet, Stockholm University, Umeå University and
FoUU.
The contributions from each company split into cash and in kind (kSEK)
Companies
Stage 1
cash
Stage 2
in kind
cash
Applied Medical Imaging
Stage 3
in kind
cash
Stage 4
in kind
in kind
cash
67
Comair
530
530
3 724
Elekta Instrument
716
228
3 810
166
1 689
2 705
99
2 736
186
921
IBA-Scanditronix
983
472
6 277
373
4 021
Latronix
247
136
1 600
Nucletron Scandinavia
C-RAD Innovation
RaySearch Labs
138
150
1 627
532
7 842
2 260
285
8 622
5 013
995
16 294
136
1 847
1 095
390
125
1 485
3 889
1 485
81
5 374
568
0
568
1 270
0
1270
150
0
150
0
615
0
298
146
1 604
ScandiNova Systems
315
SenseGraphics
298
Studsviks Medical
146
0
5 481
935 14 805
3 924
81
C-RAD Positioning
300
200
125
C-RAD Imaging
SECTRA-Imtec
in kind
67
CTI PET Systems (CPS)
Total contribution
cash
Stage 1-4
1 604
1 077 16 943
* Surplus from stage 1 (kSEK 847) was repaid to NUTEK during stage 2.
288 13 261
2 300 50 490
10
1.3
Organisation
Center Director
Professor Anders Brahme has been Director during the whole period of the Center. He has been
supported by a deputy director, Patric Källman (stage 1), and Bengt Lind (stage 2-4).
Board of Directors
Stage 1
Hans Svensson, Umeå University, chairman
Hans Dahlin, Helax
Erik Hedlund, Scanditronix
Tomas Puusepp, Elekta Instrument
Anders Brahme, Karolinska Institutet
Rolf Lewensohn, Karolinska Institutet
Stage 2
Erik Hedlund, Scanditronix/IBA, chairman
Björn Andersson, Elekta Instrument (from May 2000)
Hans Dahlin, Helax
Tomas Puusepp, Elekta (to May 2000)
Rolf Lewensohn, Karolinska Institutet
Gerald Q. Maguire Jr, Royal Institute of Technology (Oct 2000-Feb 2001)
Hans Svensson, Umeå University
Ingela Turesson, Uppsala University (to Sept 2000)
Stage 3
Erik Hedlund, RaySearch Laboratoaries, chairman
Anders Ahnesjö, MDS Nordion
Björn Andersson, Elekta Instrument
Yves Jongen, IBA Scanditronix (to Dec. 2002)
Rolf Lewensohn, Karolinska Institutet
Jonas Bergh, Radiumhemmet
Sten Nilsson, Radiumhemmet
Hans Svensson, Professor emeritus
Stage 4
Erik Hedlund, RayTherapy Imaging, chairman
Anders Ahnesjö, Nucletron Scandinavia
Björn Andersson, Elekta Instrument
Erik Jöreskog, IBA-Scanditronix (to Aug. 2005)
Bernt Nordin, IBA Belgien (from Aug. 2005)
Jonas Bergh, Radiumhemmet
Sten Nilsson, Radiumhemmet
Ingemar Näslund, Radiumhemmet
Hans Svensson, Professor Emeritus
Per Ekström, Nucletron Scandinavia, deputy member
Per Kjäll, Elekta Instrument, deputy member
Yves Jongen, IBA-Scanditronix, deputy member
Project Committee
Bengt Lind, Karolinska Institutet, chairman
Ingmar Lax, Radiumhemmet
Ingmar Näslund, Radiumhemmet
One representative from each company
The Project Committee was set up during stage 2, with the major task of treating, evaluating,
and suggesting project porposals for the board of directors.
11
International Scientific Committee (Reviewer Committee)
Tomas Bortfeld, DKFZ, Heidelberg
Zvi Fuks, Memorial Sloan Kettering Cancer Center, New York
Michael Goitein, Mass. General Hospital, Boston
Cliff Ling, Memorial Sloan Kettering Cancer Center, New York
Ingela Turesson, Sahlgrenska University Hospital, Gothenburg
1.4 External collaborators outside the Center
National research groups and departments
Department of Oncology, Uppsala University
Section of Experimental Particle Physics, Royal Institute of Technology
Department of Optimization and System Theory, Royal Institute of Technology
Department of Radiation Sciences, Umeå University
International research groups and departments
Center of Oncology (CO), Krakow, Poland
Center for Radiation Physics (CRP), Sichuan University, China
Clinical Physics Department , Daniel Den Hoed CC (DDMCC), Rotterdam, The Netherlands
Department of Physics (ECM), Barcelona University, Barcelona, Spain
Department of Radiation Oncology, Un. Michigan Medical Center (UMMC), Ann Arbor
Department of Radiation Therapy, Tampere University Hospital (TYKS), Finland
Department of Radiology, NY University, School of Medicine (NYU), New York, USA
Deutsche Krebsforschung Zentrum (DKFZ), Heidelberg, Germany
European Organization for Nuclear Research (CERN), Geneva, Switzerland
European Society for Therapeutic Radiology and Oncology (ESTRO), Brussels, Belgium
Fondazione per Adroterapia (TERA), Novara, Italy
Forschungszentrum Rossendorf (FZR), Dresden, Germany
Gesellschaft für Schwererionenforschung (GSI), Darmstadt, Germany
Institute of Nuclear Physics (INP), Krakow, Poland
Institute for Nuclear Research of the Russian Academy of Science (INRRAS), Moscow, Russia
Institute for Radiation Oncology, St. Vincenz-Hospital (SVH), Limburg, Germany
Institute of Radiotherapy, University of Nijmegen (UN), The Netherlands
Marie Sklodowska Curie Institute (CI), Krakow, Poland
Medical Physics Department, Memorial Sloan-Kettering Cancer Center (MSKCC), NY, USA
Medical Physics Department, University of Larissa (UL), Greece
Medical Physics Department, University of Patras (UP), Greece
Radiation Oncology Department, Institute Gustave-Roussy (IGR), Villejuif, France
University Claude Bernard (UCB), Lyon, France
University of Vienna (UV), Austria
12
2. The Development of the Center during the Last Decade
2.1
Research program development
The Center was proposed to allow a more systematic interaction between research and
development at the Karolinska Institute and University Hospital and Biomedical Industry. Such
spontaneous interactions have taken place now and then during the 20th century. However,
during the last decade a much closer systematic collaboration was developed, not only between
Academia and Industry, but also between the different Industrial partners taking part in the
Center, largely in accordance with the vision of the Center. Since several complementary
companies were involved it was possible to better integrate products from them for hospital use
by more well defined interfaces and connections to different hospital systems and procedures.
For example, improved treatment planning algorithms were developed for electron and photon
therapy treatment planning and Intensity Modulated Radiation Therapy (IMRT) with one
company, could be used directly for treatment optimization with accelerators manufactured by
one of the other companies. Previously, only the largest international companies could provide
complete clinically integrated systems and then often with much fewer possibilities and weaker
performance.
Initially the program was focused on improving and developing a few products that were of
general interest for one or several of the companies, such as new improved dosimeters,
improved detection systems for patient setup during radiation therapy and improved treatment
planning algorithms. However, the last half of the 11-year period, more systematic programs
were started to improve the development of a whole field and sometimes completely new area
of research and clinical development. For example, was a new kind of treatment unit developed
that was 100% dedicated to the new dynamic field of IRMT, which is an advanced treatment
technique developed at Karolinska in the early eighties. So far, no treatment units were
developed that were dedicated to IMRT and at the same time also allowed optimal use for
conventional conformal radiation therapy. In fact two different treatment units were developed,
one for low energy treatments for areal absorber IMRT, and one for high energy scanned photon
and electron therapy that was integrated with a PET-CT detection system to allow PET-CT
detection of the tumor before treatment, followed by treatment planning and treatment in direct
connection with the diagnostic procedure. Then after the treatment, the patient could again be
PET-imaged but now with the delivered dose distribution produced by the treatment unit
overlaid on the tumor image to really verify that the dose was delivered to fully enclose the
tumor spread. Obviously, such complex equipment is very expensive to develop and
manufacture, almost beyond the reach of large international companies. However, we now hope
to be able to build it in connection with one of the other major programs for radiation therapy
development run at our center and strongly encouraged by our international evaluation teams.
This is the development of cost efficient light ion radiation therapy.
In our initial program eight years ago, proton therapy was planned for the late phase of the
center development. Since the success of photon IMRT, to a considerable part through
developments at the Center, there are very few cases where protons really have a therapeutic
advantage over modern and not least radiobiologically optimized IMRT. Furthermore, the cost
of protons is about three times larger, making our interest in light ions much stronger, not least
since it has recently been shown that local control can be achieved in hypoxic tumors by only a
few treatments fractions by ions. This and our new gantry design which can be used
sequentially in four different treatment rooms make light ions at least as cost effective as
photon IMRT. Ultimately essentially three ion species: helium 4, lithium 7 and carbon 11, will
be available to modulate the intensity and radiation quality and to fit the treatment to the degree
13
of hypoxia and the tumor cell density but also to the location of associated sensitive normal
tissues.
Light ions have the best possible dose distributions for curing cancer. Not only do they give a
very high and efficient cell kill of tumor cells, but also at the same time, they save all normal
tissues in front of and beyond the tumor. They are therefore ideal for maximizing the
complication free tumor cure also for very radioresistant tumors that are difficult to treat with
photons, electrons and protons. Unfortunately, the light ions are more difficult to produce and
bend to reach the tumor in the patient. However, we have developed a very small and cost
effective light ion gantry, which allows the treatment of tumors in four different rooms placed
around the gantry. This makes beams with a large range of angels of incidence available in each
of the four rooms so practically any tumor can be effectively treated in a suitable selected room.
By this technique up to 16 patients can be treated per hour or as many as 128 per eight hour day.
Of these about 10 are completing their treatment since with light ions only about 12 treatment
fractions are needed instead of the about 30 required with electron, photon and proton therapy.
This makes the treatment cost comparable to advanced IMRT but with a much better treatment
outcome. For example, conventional conformal photon therapy gives a 21% biochemical
relapse-free control at five years for PSA > 20 prostate cancer patients. This value increases to
45% by protons and photon IMRT treatments, and almost reaching 90% by light ion therapy.
The ultimate modality for radiation therapy of cancer is therefore the light ions from lithium to
carbon, but for microscopically invasive tumors we still need the low ionization density photons
and electrons. In the planned Light Ion Center at Karolinska we therefore plan to include also
the new type of high energy scanned beam treatment unit with integrated PET-CT tumor and
dosedelivery diagnostics mentioned above.
To allow 1) accurate high resolution imaging of the delivered carbon 11 ions stopping
distribution as well as 2) a determination of the initial tumor cell distribution 3) the tumor
responsiveness distribution, and 4) the photonuclear dose delivery, a large field of view fully
integrated PET-CT camera is being designed. To speed up the imaging time and allow imaging
of half the body in a few minutes a 78 cm axial imaging width is planned with mm size LSO
crystals and fast photo multipliers based on Gas Electron Multipliers or avalanche photo diode
array read out. The aim is to achieve mm resolution in the patient with the detector used both as
a PET and CT-camera to get fully coherent tumor and normal tissue data sets.
2.2
Organization and ways of collaboration within the Center
In the early phase of the Center, the board was appointed with 50% members each from
Industry and Academia, and the chairman happened to be elected from one of the academic
representatives. After the first 18-month period, this was changed on suggestion from NUTEK
so the chairman since then was always one of the industrial representatives. At that occasion, a
more formal preparatory working group was formed to develop and suggest new projects for the
board. The working group included representatives from all the industrial partners, which made
it able to take all ideas and interest from the industry into account when designing new projects
for consideration of the board of directors. This structure worked very well for the remaining
11-year period.
After about one year, the Center decided to arrange a first international meeting with
internationally renowned scientist from the field to stimulate interaction with other researchers
in the radiation therapy field. Most of our early projects got good criticism at this occasion.
However, already at this occasion it was realized that we should strengthen the clinical
interaction within the Center and two research representatives from the Karolinska University
Hospital was included in the board of directors. This made several of the new projects highly
14
clinically relevant but it was hard to get closer clinical interaction with the hospital in several
different project. This was mainly due to the high clinical workload of most medical doctors and
hospital physicists, and an endless reduction of hospital resources (several percent per year
during most of the 11-year period) which significantly reduced their ability to interact in the
projects. In retrospect, if we have had a chance to continue with external support, we should
have been allocated more resources to purely clinical research positions to improve the
translational research within the Center. This normal mechanism inside the hospital was now
largely lost during a period of continuously reduced budget for hospital care. To some extent,
the introduction of more extensive research programs and the interaction with other national and
international hospitals compensated rather well for the lack of local translational interaction.
2.3
Added value of the Competence Center structure
From a fundamental point of view the whole is worth more than the sum of its constituent parts
only if there is a very good, or more exactly an improved, integration between the parts.
Alternatively put, there is an added value if the collaboration between the companies and the
Center works well. In Research Center for Radiation Therapy this was achieved already during
the first year when many new projects were started and a new atmosphere of collaboration was
formed between many of the participating companies. What made this process work unusually
well for our center is that it contains all key parties in the development of a part of our society.
Not only are the research departments and the companies taking part in the Center but also the
hospital care system, and thus the patients and the public. The Center therefore covers most
aspects of an important function of our society. In a way the Center creates an integration of
applied and theoretical radiation physics, clinical radiation therapy, and even clinical oncology
in general, and industrial production development and distribution. This is important since
development of new radiation therapy equipment and techniques should be made within the
framework of a Comprehensive Cancer Therapy Center taking into account new therapeutic
strategies that integrate radiation therapy with other therapies like gene therapy, chemotherapy,
kinase inhibitors etc.
In this context also the need and importance of developing diagnostic tools both for radiotherapy planning and tumor diagnosis in general should be emphasized. Such an integration of
needs will be of benefit to the hospital care system and by that also for the patients as well as
the industrial partners. In the short term perspective the principal aim of the Center is to
improve the situation for the industrial partners and the research but in the longer perspective it
is really the patients, the members of the public and the hospital care system that benefit the
most. Thus, for the third phase it is absolutely essential to have all these parties present in the
Center to allow a more global optimization of the activities of the Center. The aspects are
discussed in further detail below. More specifically our center has observed the following added
values during the first five-year period:
•
The long-term commitment in the Competence Center program has started a new kind of
dialog between research and industry allowing a more serious engagement in a well-planned
research and development program of mutual interest.
•
An increased willingness to improve the interface between different products from different
companies, for example the chain from tumor diagnostics to radiation dosimetry systems
and treatment planning systems to treatment units and new treatment verification methods..
•
Improved environment for the development of new products and ideas where several of the
companies are involved. Such projects were difficult if not impossible to start before.
•
Through the larger critical mass, more far reaching projects that require a wider range of
expertise is now possible and feasible.
15
•
Through the wider range of expertise and technological experience, quite often, we see
cross-fertilization benefits between different projects.
•
As a wider range of solutions and new methods are being developed and it is very common
that many results are mutually stimulated. An increasing degree of collaboration, both
between projects in the Center and other projects at the host department, but also with
external projects even at other Competence Centers, is continuously seen.
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3. Technical-Scientific and Clinical Results
3.1
Project overview
Some of the key research oriented achievements of the Center so far are:
•
The development of a new technique for producing narrow scanned photon beams for
efficient delivery of intensity modulated radiation therapy.
•
The development of a new fast laser, scanner for 3-dimentional patient imaging for
integration with high accuracy tumor diagnostics and treatment delivery systems (patent
pending).
•
The development of a high resolution, high sensitivity detector array for portal imaging in
radiation therapy (patent).
•
The development of a new radiation dosimeter of unprecedented geometrical resolution and
negligible angular dependence.
•
The development of a new synergistic treatment technique where high intensity ultrasound
is producing X-raylike DNA-damage.
•
The development of a dedicated low energy treatment unit for intensity modulated conformal radiation therapy (patent pending).
•
Bayesian method for fast update of new treatment results into radiobiological treatment
optimization algorithms.
•
The development of a new approach to light ion therapy employing Deuterium, Lithium,
Beryllium, Boron, Oxygen and Fluorine ions in a biologically optimized treatment.
•
The development of new transport codes for electron and light ion transport in tissue.
•
The development of new low-noise high-resolution methods for MRI, SPECT, PET and CT.
•
The development of a dedicated diagnostic high energy treatment unit for intensity
modulated conformal radiation therapy and in vivo dose delivery monitoring.
3.2
Detailed project descriptions
Optimization of external radiation therapy
"Classical" optimization of the dose distribution during treatment planning i.e. with physical
objective functions is insufficient for most advanced tumors. The use of accurate radiobiological
models is the only feasible way to achieve a major increase in complication free tumor control.
The aim is to incorporate the current state of the art radiobiological models with modern
treatment planning systems to allow fast and flexible dose delivery optimization also in
situations with a huge number of free variables in the order of 105. These include: beam
modality, energy and energy spectral distribution, the number of beam portals and angles of
incidence, intensity modulation and time dose fractionation and the associated radiobiological
models.
Compact racetrack accelerator for dynamic treatment with narrow photon and
electron beams
The goal of radiation therapy is to deliver the highest possible dose to the target volume so that
all clonogenic tumor cells are eradicated and at the same time keep the dose in the healthy
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normal tissues as low as possible to avoid severe complications in normal tissues. This goal is
most effectively achieved by using a compact and efficient treatment unit capable of delivering
fully intensity modulated beams in a short treatment time. In this project such a new powerful
compact treatment unit design for flexible conformal dose delivery is under development. With
an optimized bremsstrahlung target it is possible to generate photon beams with full width at
half maximum (FWHM) of about 3 cm at a source to isocenter distance (SID) of 100cm and an
initial electron energy of 50MeV. By making a more compact treatment head and shortening the
SID, it is possible to reduce the FWHM even further and still have sufficient clearance between
the collimator head and the patient. For instance, at a SID of 70 cm the FWHM is about 20mm
for photons and 8mm for electrons suitable for precision spot beam scanning. It is possible to
increase the electron energy up to about 60MeV to get a photon beam of around 15mm FWHM
and an electron beam as narrow as 5mm. The overall gantry size is reduced to occupiy less
space and the isocentric height is reduced so it is more efficient and ergonomic to work with, at
the same time the price is lowered. In most cases a few collimator segments with individually
optimized scan patterns are sufficient and often only one segment for each beam portal may
suffice when narrow scanned photon beams are employed and they can be delivered
sequentially with negligible time delay. The pencil beam is only scanned where the leaf
collimator is open, hence tongue and groove as well as edge leakage effects are reduced. Fast
scanning techniques, combined with good treatment verification systems, have the possibility to
counteract patient and internal organ motions in real time. The aim of this project is to evaluate,
from a technical and scientific point of view, the possibility of developing a compact and
reliable treatment machine capable of delivering the described treatment. During the last few
months we have been able to show experimentally that the scattered electrons from the target
and their produced bremsstrahlung can be eliminated in a new effective electron stopper to get a
clean high energy photon beam.
Accurate electron dose planning in heterogeneous media
In radiation therapy, it is very important to use both accurate and fast transport codes for
computations of the delivered dose as a function of the penetration depth and lateral beam
spread. Electron beams pose particular problems in radiation therapy due to their extensive
multiple scattering in tissue. The exact solution of the particle transport equation is, in principle,
possible but with an excessive computer time demand, which becomes formidable in practice
due to the mathematical and implementation complexity of the problem. To bypass this
obstacle, most of the current clinical dose computational algorithms resort to some rudimentary
approximations with semi-analytical expressions aimed at achieving a sufficient speed.
However, as expected, such simplified models often lack the required accuracy due to
incomplete physical descriptions. Modern dose computation algorithms can approximately
account for the scatter in homogeneous or layered semi-infinite slab shaped heterogeneity. In
the human body, air cavities and bony structures are often of a more complex shape and, as
such, may severely impair the accuracy of the delivered dose distribution. The most commonly
used dose algorithms for electron beams in commercial radiation therapy treatment planning
systems are the Gaussian and generalized Gaussian beam 3D codes that are based upon the
analytical Fermi-Eyges multiple scattering theory which is limited to small angles. There are
several basic deficiencies in these algorithms in clinical use, such as: (i) inability to compute
accurately the dose distributions whenever a small inhomogeneity is located at larger depths at
which the width of the pencil beam is considerable, (ii) lack of accurate predictions for the dose
distributions at the edges of inhomogeneity whose boundaries run in parallel to the direction of
the incoming beam, (iii) neglect of all the back-scatterings at interfaces among different tissues.
To circumvent these difficulties, and to bridge the gap between the CPU (central processing
unit) time expensive codes (the deterministic finite element method or the stochastic Monte
Carlo simulations) and the clinically used algorithms with crude approximations, we designed a
new model as a hybrid of the Fermi-Eyges theory and the higher-order kernels at large
18
scattering angles from the linearized Boltzmann equation. The leading higher-order terms are
collected together as the Taylor expansion and subsequently analytically summed up by means
of the special properties of the Hermite polynomials. Alternatively, we numerically solve the
Boltzmann integral equation within an improved bipartition model which can gain a factor of
~100 in speed relative to the modern Monte Carlo methods. Improvements are in avoiding the
so-called narrow energy spectral approximation (NESA) and also in introducing a more flexible
bipartition condition. It should be emphasized that these major advances in accurate dose
computations should be followed by adeqaute improvements in the electron beam
characterization, which is strongly dependent upon the treatment head (taking into account
applicators, block- and multileaf-collimators, etc.) and the electron energy used. Some photons
are also generated in the collimators that need to be included for high-precision planning of
radiotherapy. One of the goals of this project is to construct methods that are superior to the
currently existing techniques for the clinical beam exiting the treatment head, especially for
those components scattered by the collimating elements. Therefore, we will attempt to provide a
better description of the properties of the incoming beam itself. These features are various
distributions of electrons incident on the patient surface and they are taken with respect to
energy, angular deviations and fluence intensity.
Dosimetry in narrow photon beams
From a physicist's perspective, stereotactic radiation therapy is a radiological procedure by
which energy is focused into a well-localized and well-delineated small volume of tissue. This
concentration of energy is necessary in order to affect this volume of tissue – the target volume selectively. The treatment successfully occludes pathological vessels, inhibits tumor growth or
hormone production, or destroys selectively volumes of "normal tissue" as small as 1 cm3 or
less. Any cerebral structure is accessible by radiation therapy without risk of hemorrhage or
infection. Prior to the irradiation, the treatment is pre-planned by means of dose distributions
calculated individually for each case. Considering the small volumes to be treated and the
delicate structures adjacent to these target volumes, it is also critically important that the hypothetical dose distribution on which the treatment is based is realized. Fundamentally for correct
dose calculations is a correct description of the characteristics of the narrow photon beams used
in stereotactic radiation therapy. There is a number of beam characteristics, which are specific
for the narrow photon beams. These characteristics impose special requirements on the detectors
used to measure the beam as well on the interpretation of the obtained data. With this project we
have the ambition to find suitable detectors to describe the radio-physical characteristics of
narrow photon beams. A selected number of detectors will be investigated mainly by means of
experiments, regarding energy dependent and direction dependent geometrical resolution.
Methods for dosimetry and biological modeling in brachytherapy treatment
planning
The aim of this project is to develop improved methods for absorbed dose calculation in brachytherapy treatment planning. Presently used algorithms generally do not separate the dose into
components from direct and scattered radiation and therefore do not account for the reduced
scatter contribution arising in the case of finite tissue extensions, patient heterogeneities and the
presence of high-density, high-atomic number shielding materials. The aim is also to integrate
general biological models for tumor and normal tissue reactions to allow an accurate integration
and optimization of clinical external beam and brachytherapy effects. This poses special
problems for the models to account for the large variations in dose rate and fractionation
schedules in the respective treatment techniques.
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DNA-damage by the combination of ultrasound and radiotherapy: directs
effects and sensitization
At present it is not possible to cure all cancer patients. In order to find new treatment regimes
for resistant tumors, attempts have been made to combine radiotherapy with ultrasound, but
most reports from such studies are inconclusive. Ultrasound exposures are frequently used
within kidney medicine (disruption of kidney stones), brain medicine (burning of brain tumors),
gynecology (protect the mucous membrane of cervix from bleeding) and in combination with
chemotherapy (increase drug uptake). To bring more information to this field we have studied a
combined treatment of ionizing radiation and continuous-wave ultrasound both producing DNA
damage with negligible thermal effects. Cell suspensions from the Chinese hamster fibroblast
cell-line V79-379A were exposed to ultrasound alone, or they were exposed to ultrasound either
before or after X-ray exposures (2.06 Gy/minute). Different methods were used to study various
endpoints such as clonogenic survival, DNA damage, viability and membrane damage. The
results shown with all the endpoints studied that there is a dose dependent effect of ultrasound
exposure (12.5 to 125 Wcm-2). A significant synergistic effect could be seen after the combined
treatment when studying DNA breaks induced and membrane damage regardless of the
exposure order. But when considering the survival tests, ultrasound on its own had hardly any
effect and there is not yet enough data to conclude whether there is an enhanced cell killing or
not when using the combined treatment for the whole X-ray dose region. A small synergistic
interaction is suggested at lower X-ray doses (< 5 Gy). However, the DNA breaks and
membrane damages induced by ultrasound on its own seem to be reparable by the cells to some
extent since the damage induced does not correspond well to the survival tests. The principal
aim of the project is to use focused ultra-sound as a synergistic addition to radiation therapy,
such that normal tissues in front of the tumor are left unaffected by the ultrasound component.
A laser scanner system for improved patient positioning
In radiation therapy it is important to achieve high precision in the alignment of the therapeutic
beams and the target volume. Improved radiotherapy equipment and new methods for treatment
planning make it possible to tailor the dose distribution to the shape of the target volume. With
increasing accuracy of the planned dose distribution, the treatment inevitably becomes more
sensitive to inaccuracies in patient set-up. As the patient must be repositioned 20-30 times
during the course of a treatment, it is very important to improve both the speed and the accuracy
of the set-up. The aim is to have a system that provides millimeter accuracy over the relevant
part of the body, within a few seconds. This is currently within the reach of the project.
Development of a novel detector for portal imaging
Alignment of the radiation field relative to the tumor is of paramount importance. The trend in
radiation therapy is towards conformal intensity modulated treatments and also hyperfractionation that reduces the dose per treatment field. This increases the demands on electronic
portal imaging devices in terms of efficiency and image quality. Ideally high quality images for
alignment checks should be available at dose levels of 0.01 Gy, corresponding to an image
acquisition time of 0.25 s. Today mainly film is used for portal verification and the image
quality for the film and existing electronic detectors is fairly poor. We plan to develop a first
prototype of a novel portal imager with several appealing features. The efficiency would be an
order of magnitude higher compared to portal imagers that are commercially available today.
Moreover the sensitivity is high over a wide range of photon energies, from diagnostic energies
at 30 keV all the way to 50 MeV. The sensitivity to low energy x-rays would enable the capture
of high contrast images, thus enabling accurate determination of the position of internal organs
and the tumor.
20
Development of a dedicated conformal radiotherapy system
Contemporary radiotherapy equipment are not designed to automatically deliver intensity
modulated treatments. The current gantry designs are not even suited for the new treatment
techniques that are proposed and being developed today. Safe and precise delivery of intensity
modulated treatment requires a more rigid and reproducible patient positioning and accurate
verification of the delivered dose. The advent of 3D treatment planning makes it possible to use
non-coplanar beams. This technique is difficult to perform fully automatically with current
treatment machines due to the increased risk of collisions and the loss of positioning accuracy
when moving the patient. The aim of this project is to propose and optimize the design of a new
treatment machine with the primary goal to deliver fully automatic and safe intensity modulated
treatments. This together with the requirement on verification of the patient position might
eventually lead to an entirely new treatment paradigm where the curative outcome per treatment
unit at the clinic is maximized.
Comparative study of electron, photons and ion beam therapy
When improving existing or developing new radiation treatment techniques the aim is to
conform the physical dose more closely to the target volume by using different beam
modulation techniques and radiation. The possible benefits for the patients provided by such
increased dose conformity will be investigated and quantified using biological criteria.
Treatment techniques of varying complexity like simple one-dimensional techniques, focused
multi-beam techniques (gamma-knife) and techniques using few, narrow beams scanned over
the patient surface with optimized, varying intensity will be investigated. Treatment plans using
the three radiation modalities (electrons, photons and ion) separately and in combinations will
be considered, and different tumors located at different sites will be included in this study.
Brachytherapy techniques will also be studied. Treatment plans using different treatment
techniques and modalities are to be ranked and compared to each other. Different treatment
techniques require different treatment facilities, and in the comparison the total cost of the
treatment, the workload for the clinical staff and the patient comfort will be considered. With
the use of optimization techniques it is possible to determine the most optimal configuration of
treatment parameters, using either physical or biological objective functions. When biological
objective functions are used the influence of the varying radiobiological effects (RBE) in a iton
beam will be accounted for in the calculations.
Treatment optimization for the GammaKnife
Stereotactic Radiotherapy with one or several fractions has been standardized for some years
now as the treatment of choice for small intracranial benign and primary or metastatic malignant
tumors and AVMs. The high precision in target localization as well as in dose delivery enables
stereotactic radiotherapy to achieve high conformity to the majority of the target volumes while
sparing the surrounding structures and critical structures from doses above the tolerance level.
The aim of the project is to improve the current methods of treatment planning for the
multicobalt unit and to incorporate optimization both with physical and radiobiological
objective functions.
Standardized organ database and whole body atlas for image fusion and
optimized external radiation therapy
Accurate optimization external beam radiation therapy requires relevant information on radiation physical and biological parameters such as photon and electron scattering and interaction
properties, onco- and tumor suppressor genes, cell cycle control, DNA-repair genes, and
oxygenation. While physical data may be obtained from conventional CT-images, radio-
21
biological information about various structures can only be obtained if different organs and
structures in the body can be isolated and identified. The identification of organs may be
performed if images from different imaging modalities can be matched to an organ atlas via
well-behaved geometric transformations. Furthermore, the geometric transformations may be
used to reformat pre-calculated optimized dose plans from the atlas to the individual patient's
geometry. The preliminary reformatted dose plans may then be used to increase the convergence
rate of the patient specific dose plans. Advanced geometric transformations together with the
organ atlas may also be used to match the functional and anatomical images obtained from
different imaging modalities. The matched and fused images together with advanced 3Dvisualization routines may be used for improved definition of target and risk areas in advanced
3D-dose planning. The introduction of the new highly innovative image acquisition and
resolution enhancement system, with simultaneous suppression of noise, called the Fast Padé
Transform (FPT) have been originally developed and implemented at our department. To
improve static and dynamic anatomical imaging of the human body, we convert the original
image from a commercial scanner into its digital counterpart which is afterwards subjected to
post-processing via FPT. Our method is a nonlinear parametric spectral and digital image
estimator which is capable of incorporating the modern knowledge about the molecular basis of
cancer. The FPT is a versatile software which outperforms other competitive algorithms including the commercially used Fast Fourier Transform (FFT), Maximum likelyhood, or maximum
entropy methods.
Radiobiological tools
The majority of the projects within the Center depends to a large extent on the further
development of models for radiation response in order to achieve an optimal treatment for every
patient. The aim is to coordinate all the different developments needed to reach this goal. A
strengthening of the basic radiobiological modeling and tool development is therefore of major
importance.
Radiobiology on the cellular level
A large number of processes determines the dose response on the cellular level and they need
better quantification.
• Cell survival models. A very interesting model of the cell survival in terms of the DNA
repair process has recently been developed, namely S=e-aD+bDe-CD. It can describe low dose
hypersensitivity and remove the unrealistic cell kill at high doses by the LQ model. Most
interestingly it can be used to determine the cell kill when combining low and high LETdamage which is fundamental for light ion interactions.
• Low dose hypersensitivity. It is very essential to accurately describe the low dose
hypersensitivity since it influences the response of a large part of the body receiving subtherapeutic doses during treatment. We are developing new unique cell survival models for
this purpose.
• RBE variation in low LET beams. We will also make a more accurate model for the RBE
variation in low and high LET beams (e-, X, ions) based on the slowing down spectrum of low
energy δ-electrons (150 eV – 1.5 keV).
• Hypoxia in tumors and normal tissues. New models for the clinical effect of hypoxia in
tumors and normal tissues are also being developed and they are fundamental for tumor and
normal tissue responses. Also other factors contributing to the heterogeneity are important to
model.
• Repair of sublethal damage for different tissues and radiation modalities. Damage repair
is fundamental for all cell survival models. A rather general repair model based on a fast intra
allel (t1/2 ≤ 103 sec) and a slow inter allel (t1/2 ≥ 104 sec) process describe the response of most
organs quite well.
22
•
•
Accelerated repopulation. After the first two weeks of treatment the tumor experiences an
accelerated repopulation to compensate for severe cell loss. This repopulation can be
compensated for by an extra dose of 0.3 – 0.6 Gy/day of prolonged treatment beyond the
normal 6 weeks. This factor is important to include in the design of the dose fractionation
schedule.
The dose rate dependence. Both for low dose rate external beam (< 2 Gy/min) and HDR &
LDR brachytherapy it is essential to model the response of the tumor and the normal tissues.
It is important to combine the low dose hypersensitivity with the dose rate modeling not least
in intensity modulated- and brachytherapy-techniques.
Radiobiology on the system / organ level
The knowledge about the radiosensitivity on the cellular level and the models developed has to
be synthesized into compound responses of organs, organ systems and tumors, preferable on a
patient individual basis. Important research areas needed for this synthesis are shown below.
• Object functions for radiotherapy. The models for tumor response and damage of healthy
tissues should be combined to produce a measure of the treatment result. This could be done
e.g. with P+ the probability of complication free tumor control. A problem to be investigated
is how the probabilities should be weighted together. One way would be to use graded
response functions P(D, S), where D is the dose and S is the severity of the response, instead
of the binary ones used so far.
• Kit for in-vivo prediction of radio-sensitivity. There is some evidence today that one can
predict the tumor response by looking at the healthy tissue response to radiation. This
correlation is probably due to genetic effects that raises or lowers the radiosensitivity
generally for all kinds of tissues in the body. This effect seems to hold even for early reacting
tissues like skin. A simple device like an e- emitter taped on the skin could thus be used to
produce a detectable erythemea. The intensity of the erythema could then be used as a
predictor for the radio-sensitivity.
• Accelerated repopulation. The accelerated repopulation seen in especially head and neck
tumors have an important effect on the choice of an optimal fractionation schedule. The
response models in common use today like the Poisson and Binomial models cease to be valid
as soon as the tumor repopulates. Thus, new models, that in a consistent way incorporate
accelerated repopulation have to be developed and their implications on the fractionation
schedule have to be investigated.
• The use of compound distributions in response models. The over dispersion seen in clinical
data are partly due to the fact that the data are a result from an averaging procedure of patients
with different sensitivities, stages, grades of heterogeneitys, etc. This adds to the variance of
fundamental Binomial distribution. One way of effectively modeling this is to use a
compound distribution like Binomial-Normal or Beta-Binomial, which in a coherent way
incorporates all the different sources of uncertainties.
• Improved models for the response of healthy tissue. To accurately model the response of
healthy tissues to irradiation it is not sufficient to know the response on a cellular level. The
structure of the cells into a functional tissue and organ has to be considered. One way that has
been explored is to simplify this into volume effects and the introduction of a seriallity
parameter in the models. Future developments could be fractal models or tensor models for
the response of different parts of an organ. We developed a new time-dependent model with
the analytical expression for probability PB based upon the ab initio birth-and-death YuleFury stochastic process which dynamically includes two key opposite and competitive
mechanisms, cell killing and cell repair.
• Tumor - normal tissue response correlation. The genetic expressions controlling the
response to radiation are most likely causing a correlation of the response in the tumor and
healthy tissues. Retrospective and prospective studies verifying this have to be done.
Statistical models that describe this effect have already been developed at the Center but need
to be tested against more clinical data.
23
•
•
•
Patient individual optimization. The prospective of predicting the response on an individual
basis by assays opens up the possibility of an individualized radiotherapy. The response,
health status and needs of each individual patient will thus become vital inputs in the
optimization of the treatment outcome. It is important to be able to estimate the response of an
individual from the mean values of a population.
Fractionation optimization with intensity modulation. By incorporating models for low
dose hypersensitivity; repopulation of the tumor and non-complete repair of healthy tissues it
will be possible to optimize the fractionation schedule and speed up the treatment using
indensity modulation.
Fast systematic feedback of follow-ups. To be able to continuously refine the models and
the parameters used in the models new results has to be incorporated as soon as possible. This
can be done for instance by a feedback through a Bayesian technique where prior knowledge
is continuously adjusted by the accumulated new follow-up data.
Significance
The vast amounts of the improvements that can be achieved in the field of radiation therapy
depend on the modeling and quantification of radiation responses. The project will, in a
coherent way, coordinate the effects of radiation responses within the different projects in the
Center. This will lead to an enhanced precision and outcome of the treatment results.
Development of light ion accelerator facility for radiation therapy
A proposal has been presented to build a light ion accelerator facility for radiation therapy in
Stockholm. The rationale behind the proposal is to use the radiobiological advantages of light
ions alone or as boost therapy for resistant tumors. The aim of this study is to investigate the
following aspects of a light ion accelerator facility for radiation therapy: accelerator design,
gantry design, treatment room and treatment technique design, radiobiological advantages and
treatment plan optimization and radiation protection. The results of the preliminary study are to
be used for the final planning and request for quotation of the proposed light ion accelerator
facility. The light ion accelerator facility will offer significant advantages for cancer therapy
both with regard to tumor cure and normal tissue morbidity. New technologies will be tested in
the construction of different parts of the facility. The preliminary study will provide evidence of
the potential benefits, give guidelines for the final planning process and identify the potential
role of the industrial partners of the Center in the completion of the project. Ion therapy has
considerable advantages over electrons and photons for radiation resistant a hypoxic tumor close
to radiation sensitive tissues of serial organization like the spinal cord. A compact ion-gantry
based on the same scanning beam principles as developed for the racetrack accelerator has been
worked out for protons using a super conducting bending magnet. There is interest both in
Japan, US, Holland and Sweden for this compact form of ion therapy unit. The goal is do
develop the gantry structure since suitable cycrotrons and cyclotrons are already available for
ion and proton beam delivery.
Interactions of light ions with tissue are much more complex than those involving electron or
photon beams while penetrating the human body during cancer therapy. This is because many
more transition channels are open to ions than to electrons or photons. Knowledge of electron
production cross sections is crucial for modeling transport of ions in tissue, relative biological
effectiveness (RBE), ionizing break-up of DNA, etc. To investigate the basic mechanisms in
these key phenomena, we implemented the most advanced distorted wave multiple-center
atomic and nuclear scattering theories, by going beyond the usual Born-Bethe model, which has
severely limited the past conclusions in radiotherapy. Atomic collisions dominate in the keV/u
and low MeV/u energy region where excitation, ionization and electron transfer must properly
be described for reliable predictions of ion energy losses, a goal which has not been achieved
before. Atomic interactions of light ions with tissue at the keV/u and sub-keV/u energies are
essential for adequate estimates of RBE, and this, together with the stopping power related
24
quantity called linear energy transfer (LET), determines which ions should be selected for the
most beneficial cancer therapy with the maximal eradication of clonogenic cells and minimal
damage of the healthy tissue. To reach the deep-seated tumors at the depth of the order of some
25cm in tissue, very high energies of the ion beam are necessary, e.g. 360 MeV/u for 12Cq with
the charge state q=6+ (a nucleus). At these energies, nuclear reactions must be considered, as the
neutron losses dominate over atomic processes. We developed a unified distorted wave multiple
scattering theory for atomic and nuclear collisions that can quantitatively explain, e.g., an
important recent experimental finding that, just like the K-shell atomic ionization, inactivation
cross sections attain their maxima for the matching resonance condition, vi=veK, between the
velocities of the incident ion, vi, and that of K-shell electron, veK. This could trigger possible
radiation damage of DNA in the tumor, a process which must be enhanced to stop the
production and proliferation of clonogenic cells. Our theory of ion-tissue interactions can yield
the needed cross sections for one or two neutron losses from ionic projectiles, an important
phenomenon which widens the Bragg peak beyond the tumor area. The dose delivery by ions
that are beta+ emitters can be accurately monitored via PET imaging of the Bragg beak within
the tumor area. Here, we use our high-resolution, noise-reduced signal and image processing
method, the FPT, to enhance performance of the overall diagnostic-therapeutic procedures in
dealing with the cancer problem. There has been no comprehensive 3D code available thus far,
which simultaneously employs the best existing atomic and nuclear physics theories for the
most accurate modeling of light ion transport in tissue, with the subsequent production of the
secondary delta electrons, and an interactive follow-up via improved PET imaging. Our
physically and biologically optimized algorithm, in the versatile setting of the FPT, from
treatment planning and ion transport to imaging, fills in this gap and provides a powerful tool
which is expected to be come a part of a future clinical protocol for cancer therapy by light ions.
Computerized tele radiation therapy planning and dose delivery
Radiation therapy is best conducted on a large scale to allow a large number of advanced
experts and a fast recruitment of patients of a given state of the disease. This implies that in
areas of lower population density it is advantageous to work with a clinical cancer center
connected to treatment satellites. The whole problem of integrating information technology and
other methods to improve the collaboration in such center satellite systems is the goal of this
project. Fast image, virtual reality treatment planning and simulation, and treatment delivery
communication systems combined with a centralized follow-up of treatment outcome and complications are among the prime activities in the project.
Optimal Scanning and dosimetry for radiotherapy
Optimized radiation therapy (inverse planning), that maximizes the treatment outcome has today
reached the point where it is sufficiently mature to be clinically implemented. The optimization
process uses both physical and biological objective functions and it turns out that the incoming
beams should be heavily intensity modulated spatially. Such beams can for instance be
generated by allowing the multileaf collimator to sequentially deliver a sufficient number of
small uniform beams from each portal. One of the fastest methods to modulate a uniform beam
is by dynamic multileaf collimation, i.e. the leaves are moving over the field with a varying
aperture. Even with such effective methods the irradiation time can be prolonged by a factor of
2 to 5 depending on how complex the delivered beams should be. Such prolonged treatment
times are not cost effective, even though they are beneficial for the patient. Another drawback
of only using dynamic collimation techniques is that when only a small part of the field should
be modulated the integral collimator leakage increases a lot which may cause injuries in some
parts of the body or even induce secondary cancers. The most flexible way to deliver intensity
modulated beams in a minimum of time is to scan the elementary photon, electron, proton or
heavy ion beam. This project will fully exploit the possibilities with scanned beams and address
25
particular problems in dosimetry and treatment planning. For photon therapy the scanned beam
should preferably be used in combination with the multileaf collimator. Obviously, the most
effective way to deliver the beam is to scan the elementary beam only where the collimator is
open. Preferably this should be done in a dynamic way such that the scan pattern is changed
gradually so the pencil beams are always impinging on the moving collimator aperture. In this
way the therapeutic photon beam is most effectively used and both time and leakage are reduced
and the dose distribution truly optimal. In this project the racetrack installed at Radiumhemmet
at KS will be used as the main trial system for scanned beams. Today, the dose content in each
elementary beam can be varied by changing the pulse length in combination with spatial
modulation to place pulses at the same position. Full flexibility in both amplitude and pulse
length modulation is possible with a grid electron gun as an electron source to the racetrack. The
advantage by installing a newly developed electron gun is twofold. Full flexibility in IMRT can
be achieved at the same time as there are several biological advantages with short pulses (10ns)
during scanned electron beam treatment such as lowering the biological effect at shallow depths
for a given effect in the tumor. Dynamic scanning will therefore give the Racetrack an
unbeatable advantage compared to all standard treatment units without scanning beam
capability.
BioArt
A major technical and scientific achievement has been the development of a new radiation
therapy optimization approach called BIOART. The new scientific approach to high quality
radiation therapy, using 3-dimensional in vivo predictive assay of the tumor clonogen density
and tumor radiation responsiveness assay (BIOART), opens the door to a truly scientific
approach to biologically optimized radiation therapy. This is achieved by repeated PET-CT
imaging early on in the treatment and the response can be used to correct most types of
treatment errors and to some extent even treatment planning errors and uncertainties in
historical dose response data.
InVivo dose delivery imaging
The new approach to truly 3-dimensional in vivo dose delivery verification by photonuclear
activation further increases our ability to do adaptive radiation therapy based on the averaged
dose delivery to the patient over the treatment session. This capability combined with the
monitoring of the tumor responsiveness may really allow a unique patient individual adaptive
dose optimization in 3-dimensions.
Whole body tumor PET-CT camera
A project of high clinical and scientific importance is the design of a dedicated, fully integrated
PET-CT based tumor camera with high resolution high sensitivity wide field of view. The
camera will be about 50 times more sensitive than existing cameras with a resolution of about
1-2 mm for the PET part and about 1 mm for the CT. This is required to really resolve small
tumor metastasis and image the dose delivery in a few minutes.
Excentric light ion gantry
A major innovation is the new “excentric” light ion gantry which allows treatment in four
different rooms around the gantry with full flexibility in beam orientation. The first single room
light ion gantry for Heidelberg will weigh about 650 tons whereas the ”excentric” gantry usable
in four rooms will only weigh around 100 tons and make the whole ion installation as cost
effective as advanced IMRT.
26
3.3
Key values
Examinations (Enclosure 1)
Type of theses
Doctoral theses
Licentiate theses
MSc degrees
Number of examinations
Stage 1
3
10
Stage 2
4
1
12
Stage 3
5
1
25
Stage 4
6
1
12
Stage 1-4
18
3
59
14 doctoral students where registered at the end of stage 4. Several of these will defend their
thesis during 2008.
Publications (Enclosure 2)
Type of publications
Papers in scientific journals
Books and reports
Conference contributions
Number of publications
Stage 1
16
1
13
Stage 2
48
6
34
Stage 3
54
2
55
Stage 4
58
3
57
Stage 1-4
176
12
159
In addition, several manuscripts are under production and will be published during 2008.
International cooperation
Guest researcher visiting the center
During the Center period, 17 international researchers visited the center, many of them
returning regularly.
Scientist
Institution
Visiting period
Prof. Rodrigo Arriagada
Institute Gustave Roussy, Paris
Department of Physics (ECM),
Barcelona University
Center of Oncology, Krakow
1 month 2004-2006
Prof. José Fernandez-Varea
Prof. Anna Gasinska
Physist Maria Gavrilenka
Dr Quing Hou
Ass prof. Simo Hyödynmaa
Dr Mark Katz
Ass. Prof. Woochul Kim
Dr Mauriusz Kopek
Prof. Zengming Luo
Dr Panayiotis Mavroidis
Dr Katsumasa Nakamura
Ukranian Research Institue of
Oncology and Radiology, Kiev
Center for Radiation Physics,
Sichuan University
Department of Radiation Therapy,
Tampere University Hospital
Theoretical and Experimental
Physics, Moskow
Department of Radiation Oncology,
Inha Univ. South Korea
AGH University of Science and
Technology, Krakow
Center for Radiation Physics,
Sichuan University
Medical Physics Department,
University of Larissa
Faculty of Medicine, Kushu
University, Fukuoka
5 months during 2000-2006
8 months during 2001-2003
6 months in 1998
6 months in 1996
2 years during 1995-2001
1 month in 2005
1 year in 2004-2005
2,5 months during 2001-2004
8 months during the whole
period
2 months during 2004-2006
6 months in 1997
27
Prof. Marilyn Noz
Prof. Nicolai Sobolevsky
Dr Kiki Theodouru
Prof. Hirohoko Tsuii
Prof. Michael Waligorski
Department of Radiology, NYU,
School of Medicine, New York
Inst. Nuclear Research, Russian
Academy of Science, Moscow
Medical Physics Department,
University of Patras,
National Institute of Radiological
Sciences, Chiba
Center of Oncology, Krakow
1,5 year during the whole
period
6 months during 2001-2005
3 months during 2003-2006
1 week in 2006
4 month during 2001-2004
Guest students at the center
17 foreign students have been studying for MSCs and/or PhD exams during the Center period.
After graduation, many of the MSc students continued as PhD students.
Magdalena Adamus-Gòrka
Home
country
Poland
Bahram Andisheh
Iran
Anna Baran
Poland
Brigida Da Costa Ferreira
Portugal
Rüdiger Felke
Germany
Bartosz Gorka
Poland
SoYoung Kim
South Korea
Magdalena Kodura
Poland
2003
Panayiotis Mavroidis
Greece
1996
Xiangkiu Mu
China
Marianne Mähle-Smidth
Denmark
2002
Sharif Qatarneh
Jordan
2002
Alexandra Zapotoczna
Poland
Graduated students
MSc
Lic.
PhD
2001
Planned
PhD
2008 April
2008 fall
2003
2004
1998
2008 spring
2010
2001
2001
2001
2006
2001
2009
Students in training for shorter periods
Erik Koorevar
Netherlands
2 months 1997
Wojciech Maciejuk
Poland
6 months 1997
Wilailak Panphae
Tailand
5 months 1995
Taweap Sanghangthum
Tailand
10 months 2006-2007
Collaborating universities
The Center has collaborated with 24 international universities. See paragraph 1.4 for detals.
CO, CRP, DDMC, ECM, UMMC, TYKS, NYU, DKFZ, CERN, ESTRO, TERA, FZR, GSI, INP,
INRRAS, SVH, UN, CI, MSKCC, UL, UP, IGR, UCB, UV
EU-projects
The Center has been part of 10 different EU-projects.
DYNARAD
Tempere
ENLIGHT
DIAMOND
INTAS
Stage 1-2
Stage 1-3
Stage 2-4
Stage 3-4
Stage 3-4
Marie Curie
P53
BIOCARE
MAMMI
Stage 3 (two projects)
Stage 3-4
Stage 3, ongoing
Stage 4, ongoing
28
Commercialization
New Companies
8 new companies based on innovations made at the Center started during stage 2-4.
BIOATLAS
C-RAD Innovation AB
C-RAD Imaging AB
C-RAD Positioning AB
RayInnovations AB
RaySearch Laboratories AB
RayTherapy Scandinavia AB
RayClinic AB
Patents
9 patents were filed during stage 2-4 as a direct result of inventions made in the Center.
Body supporting stereotoactic couch
Diagnostic and therapeutic image detector system
Excentric light ion gantry
Method for accurate patient positioning
Multi-layer image converter
Radiation sensory device
Radiation system
Stable rotational radiation therapy gantry
Surface intensity modulator
Technology transfer projects
6 technology transfer projects were conducted during stage 2-4.
BIOART
BIOATLAS
BIOCARE
Light Ion therapy planning
Nordic Light Ion Therapy Center
MAMMI
Movement between the university and industrial partners
Senior researchers from the partners acting as project leaders or supervisors
Anders Ahnesjö, Nucletron
Jürgen Arndt, Elekta Instrument
Jasek Cappela, Studsvik Medical
Kjell Eriksson, RaySearch Laboratories
Per Kjäll, Elekta Instrument
Johan Löf, RaySearch Laboratories
Johan M Beskow, SenseGraphics
Roger Svensson, PencilBeam Technologies
Hans Wiksell, Comair
Hans Wiksell, Comair was appointed Associated Professor at KI in 1996.
Industrial PhD students
Pierre Barsoum, Elekta, Instrument
Åsa Carlsson-Tedgren, Helax
Anders Gustafsson, Helax
Arash Rezai, Studsvik Medical
Björn Skatt, Latronix
Johan Uhrdin, RaySearch Labs
Minna Wedenberg, RaySearch Labs
Janina Östling, C-RAD
PhD students employed by the partners during their education
Åsa Carlsson, Helax
Anders Liander, RaySearch Labs
Olof Sjörs, Helax
Björn Skatt, Latronix
Johan Uhrdin, RaySearch Labs
Janina Östling, C-Rad Imaging
29
MSc students and Exam workers employed by the partners after graduation
Helga Ernerfeldt, Latronix
Rickard Holmberg, RaySearch Labs
Jonas Jonasson, Helax
Malin Larsson, RaySearch Labs
Jonas Mann, Scanditronix
Kirash Moaierifar, Scanditronix
Peter Nyman, Elekta
Kerstin Weckström, Elekta
PhDs’ employment after graduation
Since its start, 18 persons at the Center obtained PhD degree.
Name
Massoud alAlbany
Åsa Carlsson-Tedgren
Brigida Da Costa Ferreira
Anders Eklöf
Anders Gustafsson
Annica Jernberg
Johan Löf
Panayiotis Mavroidis
Joakim Medin
Younes Mejaddem
Johan Nilsson
Linda Persson
Sharif Qatarneh
Bruno Sorcini
Roger Svensson
Nina Tilly
Mats Åsell
Janina Östling
Current affiliation
Karolinska University Hospital
Linköpings University
Coimbra University, Portugal
Dept. of Oncology-pathology, KI
Nucletron
studying at Lärarhögskolan Stockholm
RaySearch Laboratories (founder)
University of Larissa, Greece
Rigshospitalet, Copenhagen
Karolinska University Hospital
unknown
Swedish Radiation Protection Authority
King Husseins Cancer Center, Jordan
Karolinska University Hospital
RayClinic (founder)
Nucletron
Nucletron
C-RAD
30
4. Industrial Results and Effects
Impact on the industrial partners and their R&D-performance
Beside the concrete collaboration on specific projects, the Center is frequently used as a source
for scientific information and consultant for the members. The good collaborative atmosphere of
the companies in the Center has stimulated many projects between the companies without the
presence of the university. Before the Center started such contacts were scarce and even hostile.
Beside numerous technical developments and innovations, the perhaps most important and
dynamic effect of the Center during recent years has been the formation of a handful of spin-off
companies, directly or indirectly dependent on the activities at the Center. Two of these companies are already active members of the center. The new companies include RaySearch
Laboratories, PencilBeam Technology, RayClinic, RayEducation, C-RAD Positioning, and
C-RAD Imaging, and more are in the process of being formed.
During the stage 4 we have seen more bilateral projects focused on the particular needs of each
participating company. In addition, we have to see a closer and also wider collaboration on some
of the more large scale and long term projects with consequence beyond the 10 year period.
Some of the new companies are formed to facilitate the production of these new devices in
collaboration with some of the existing companies of the Center. Participation in the Venture
Cup Business Plan Competitions has been useful in starting these activities when existing
companies have been reluctant or inable of starting an advanced new production.
In order to handle the IPR-issues in a simple way an agreement was signed in stage 3.
According to this agreement the inventor (if from academia) must give the participating
companies a first right of refusal. If the companies chose to exploit the invention they are liable
to pay compensation. Since some of the projects from the early stages was not exploited by any
of the partners the inventors used their own right (“Lärarundantag”, a Swedish university
employee owns the IPR himself) with informed consent from the participating companies and
formed new companies taking over the projects. Karolinska Institutet has a very good infra
structure for entrepreneur activities through Karolinska Innovation which aids inventors with
patents, business plan and the startup procedure. Karolinska Institutet has also a holding
company (KIH AB) which has a minority post in all spin-offs formed from our center. It is even
possible to reach venture capital money within the campus through the Karolinska Investment
Fund. Another important stimulus for the commercialization of research ides is Venture Cup
which is a business plan competition that helps students, researchers and others to take their
business idea from concept to actual startup. Through this channel very professional help by
commercial companies is obtained for leading project proposals making the competition
extremely realistic. McKinsey & Company started the competition together with Swedish
universities. Our center has over the past years participated with five different plans (three
during Stage 3) and was awarded 3rd place three times and 4th place twice. Four new companies
have been started as result of these successes.
31
5. Conclusion
5.1
Comments from the principal industrial partners
Elekta Instrument AB
The interaction and collaboration between industry and academia is imperative in order to
develop our industrial as well as our academic abilities; an entity such as the Research Center
for Radiation Therapy is therefore a central part of this progress. Elekta - as a progressive actor
in the fields of neurosurgery, strereotactic radiosurgery and radiation therapy - including
computerized patient management systems - is therefore much in favor of such collaborations.
Due to the fortunate constellation of the Center and its management over the years, the
innovation atmosphere has been very good. Such an environment, consisting of a mixed
academic and industrial participation, has the potential to be very fruitful for all involved
because of the different points of view and agendas of the participants. At the same time as it
always runs the risk that the positions - due to the different agendas - can become looked; this
has not been the case with the Center. Regular meetings and an open discussion atmosphere has
been prevailing over the years enabling the flow of ideas and projects; it has succeeded despite
sometimes changing constellations, resource constraints and tight schedules.
Elekta’s participation in the Center has been fruitful for a number of reasons:
•
the projects and discussions have been pursued within academic areas mapping Elekta’s
business areas very well giving us up to date and comprehensive information about ongoing
research,
•
the composition of commercial and academic representatives have been well balanced and
fortunate enabling a fruitful dialog,
•
access to graduate as well as undergraduate students for projects,
•
the geographical closeness of the participants is always beneficial.
Latronix AB
We are carrying through a project (a Laser Scanner System for Improved Patient Positioning) in
co-operation with members of the research team at KI. Other industrial partners in the Research
Center for Radiation Therapy have not participated actively in the project so far, although they
have confirmed the value of it. The co-operation with the scientists from the Center has worked
very well. Their participation has been of vital importance in the project not only to provide the
necessary clinical input but also to develop the extensive software programs needed. The project
utilizes Latronix proprietary technology in a medical application. For the commercialization of
the results of the project we will primarily explore the possibilities to obtain co-operation with
the industrial members of the Center. Independent of how the further development of the project
results will be organized, we shall be very interested in maintaining a close co-operation with
the scientific team of the Institute. Since 2003 a close collaboration with C-RAD Positioning
has been established. It has been demonstrated in the project that the technical design chosen is
accurate and flexible enough to meet the required performance specifications. Based on these
results, clinically useful products can be developed that can help improve radiation therapy.
Latronix will seek competent partners for the task to commercialize the results. Two patent
applications were made to protect the technology. In the project Latronix uses the same
technology as applied in the design of systems for industrial applications. Our development
work for the project has therefore given very valuable contributions to the further development
32
of our technology. Also the co-operation with the skilled and inventive participants from the
Center has been very stimulating for us.
Nucletron AB
The most beneficial experience with our participation in the Center has been the possibility to
interact directly with PhD students in projects, by supervising and reviewing their work. The
expectation was to strengthen our own research through collaborating directly in the academic
environment. The outcome has varied considerably between projects, depending on the degree
of personal involvement. Day to day interactions require center project members to spend time
at company facilities and vice versa. Over the years we have recruited five persons through the
Center and this channel of recruitment is of immense importance! We would like to use the
Center more for technical assistance and problem solving, but the geographical distance
Uppsala-Stockholm is sometimes a burden. Ideas flow though, many routes and those who keep
coming back are maybe the most important ones.
IBA-Scanditronix AB
A significant part of the research and development projects at Scanditronix are run through the
Research Center for Radiation Therapy. Our company is dependent on a close contact with
clinical research and development and a large part of our needs are covered by the ongoing
research projects. We also appreciate the close interaction between the other major companies
and the research representatives in the board of directors. Very often the meetings start with an
unofficial discussion of changes in our field and what possible effects they may have for the
companies and our research and development activities. Several employees have been recruited
from the activities at the Center but not yet on the post Ph.D. level. Our company has become
dependent on the Center - it fulfills a fair part of our R&D needs. We are even trying to find
new ways to develop new product ideas and technologies, such that are of mutual interest for
industrial and scientific development. A number of patents have already been filed and some are
pending. It has not always been deemed necessary to file a patent as this necessity means that
the new procedure is disclosed. Obviously it is hard to quantify the benefits in absolute
economic terms. However, the interaction with the Center has been very important in building
up the competence of our own personnel. This has been of importance in product development
and also during negotiations with customers where a broader knowledge of the field and the
competitive edge of our products is essential. It is also valuable for our personnel, both on the
dosimetry and radiotherapy side, to take part in the seminars arranged by the Center. For special
projects, more dedicated review seminars have been successfully carried out together with the
Center and personnel from the radiotherapy clinic, e.g. seminars focusing on the requirement on
new radiotherapy equipment.
The new MM50 Scan Controller has successfully completed the testing phase, conforming to
the requirements. The Scan Controller has been used clinically for the first time, by now having
treated more than 50 patients. Additional PET scans have been taken of patients just been
treated for cancer with 50 photon beam. The results indicate the promising potential of verifying
and improving the IMRT treatment by using PET. Just recently an improvement to the thin
target pencil photon beam has been found. This result is crucial in making the pencil beam
photon IMRT technique clinically effective. The efforts of the Center have been crucial in
evaluating and finding ways to improve the effectiveness of photon IMRT for treatment of
cancer. This work holds the promise of further improving treatment techniques and treatment
results, in our common fight against cancer.
33
C-RAD AB
C-RAD AB is a group of companies based on innovations originating from the Karolinska
Institutet and the VINNOVA Center of Excellence at KI: Research Center for Radiation
Therapy. The rights to these innovations were in 2002 outsourced and later on transferred to the
C-RAD AB group. After a first capital raise operation was started in December 2004. The first
product, a 3-D laser camera imaging system, was released end of 2006. C-RAD AB is since July
2007 listed on one of the stock exchange markets in Sweden called Aktietorget. The company
has 20 employees.
The operations of the C-RAD-group are running in three fully owned subsidiaries C-RAD
Positioning AB, C-RAD Imaging AB and C-RAD Innovation AB with operations in Uppsala,
north of Stockholm and Östersund in the northern part of Sweden.
C-RAD Positioning has developed a laser scanner system for accurate and fast positioning of
the patient at radiation therapy centers. The system will also be further developed for:
•
monitoring the patient during the treatment,
•
respiratory gating where system will be used to generate the gating parameters and as a
control and interlock device for the accelerator system during the treatment,
•
image fusion to align 3D images from different image modalities like CT, MR and PET,
•
adaptive radiation therapy where deviations from the reference patient contour will be
transferred to patient treatment planning system to correct for misalignments and dose
delivery deviations during the last part of the treatment.
At the end of 2007 15 systems were sold to main markets in Europe, North- America and Asia.
C-RAD Imaging is developing a detector system based on GEM- technology (Gas- ElectronMultipliers, originally developed and CERN, Geneva) and high energy photon transport theory
(C-RAD patented detector design). The technology can at the same time be used for diagnostic
cone beam CT and high energy portal imaging. The first test installation is planned for 3 quarter
2007.
C-RAD Innovation has filed patents for two types of delivery systems, one high energy system
with PET-CT integration and one 6 MV-system with cone beam CT for fast and accurate
delivery of intensity modulated radiation therapy (IMRT). Research and development are going
on in collaboration with Karolinska Institutet.
A combination of factors at the Research Center for Radiation Therapy was instrumental in
forming what later became the C-RAD group, namely:
•
the innovative climate at the Karolinska Institutet based on advanced research and
development of new radiation therapy techniques,
•
close cooperation between the Karolinska Institutet and the Karolinska Hospital in radiation
therapy and fundamental oncology,
•
the membership of larger and smaller companies with long term experience in radiation
therapy and oncology,
•
a climate of stimulated entrepreneurship supported by the former president of Karolinska
Institutet, and finally
•
an infrastructure (KI Enterprises including: KI Holding, KIAB, KD (I, II and III)) for
starting, helping, and supporting new companies, mainly in the medical arena.
34
The C-RAD group continues and will continue to work in close cooperation with professor
Brahme and his group, especially for the design and development of new accelerator systems at
C-RAD Innovation.
RaySearch Laboratories AB
Due to RaySearch’s involvement in the Research Center for Radiation Therapy we have gained
insight and know-how as stated below.
•
Insight in the fundamentals, use and limitations of biological models used for treatment
planning optimization. This increased knowledge has been of importance in the ongoing
development of methods for biological optimization, including the release of a product for
biological evaluation of treatment plans. Specifically, various optimization strategies for
minimizing organ at risk damage or maximizing tumor control probability were studied, and
biological optimization was compared to the more common physical optimization.
•
Knowledge of a quality assurance process for IMRT treatments, based on phantom studies
and film measurements. This is of importance as this process is one of the reasons for why
some clinics are reluctant to introduce IMRT.
•
Insight in basic principles for the physics and biology of light ion therapy. A study of
analytical methods for fast calculation of the influence of multiple scattering and range
straggling, on the energy deposition distribution of light ion pencil beams in water resulted
in the development of energy based proton radiation treatment optimization algorithms. The
biological effect of light ion therapy was also considered. As light ion therapy treatment
planning software is a potential future product, this increased knowledge has been of
importance for us.
Through the Research Center for Radiation Therapy, RaySearch has gained some valuable insights into biological modeling, quality assurance and light ion therapy and has generally
benefited from knowledge transfer by collaborating with the Karolinska Institutet.
5.2
Summary and conclusions
In summary, the Center has not just been stimulating an important area of Swedish research and
industrial development but also strengthened the fundamental research and development in this
area and improved the interaction between the five key players in the biomedical arena. It is
clear that this interaction is of key importance for the development of our society and new ways
to further establish improved collaborations between them will continue to be an important goal
for the future as discussed in more detail in the Executive Summary above.
1
Exams Stage 1 - 4
Enclosure 1
Doctoral theses
1996-2007
GUSTAFSSON A. Development of a versatile algorithm for optimization of radiationtherapy. Thesis,
Stockholm University, ISBN 91-7153-534-9, 1996.
SORCINI B.B. Improvement of electron beam dosimetry using accurate energy-range and photon background
models. Thesis, Stockholm University, ISBN 91-7153-428-8, 1996.
MEDIN J. Studies of clinical proton dosimetry using Monte Carlo simulation and experimental techniques.
Thesis, Stockholm University, ISBN 91-7153-572-1, 1997.
SVENSSON R. Development of a compact high energy treatment unit combining narrow pencil beam scanning
and multileaf collimation. Thesis, Stockholm Univerisity, 1998.
SVENSSON R. Development of a compact high energy treatment unit combining narrow pencil beam scanning
and multileaf collimation. Thesis, Stockholm University, 1998.
EKLÖF A. Development and application of composite energy deposition kernels for photon therapy planning.
Thesis, Stockholm University, 1999.
ÅSELL M. Development of optimized radiation therapy using external electron and photon beams. Thesis,
Stockholm University, 1999.
LÖF J. Development of general framework for optimization of radiation therapy. Therapy, Stockholm
University, 2000.
MAVROIDIS P. Determination and use of radiobiological response parameters in radiation therapy optimization. KI 2001
TILLY N. Radiobiological investigations of proton and light ion therapy. KI-SU-UU 2002
PERSSON LM. Cell survival at low and high ionisation densities investigated with a new model. KI-SU 2002
CARLSSON-TEDGREN ÅK. Development of dose calculation methods for brachytherapy treatment planning.
KI-SU 2003.
MEJADDEM Y. Photon and electron transport calculations for development of intensity modulated radiation
therapy. KI-SU 2003.
AL-ABANY M. Towards elimination of anal-spincter and rectal dysfiunction afater radiation therapy for
prostate cancer. Doctoral thersis, Karolinska Institutet, 2004.
COSTA FERREIRA B. Biological optimization of angle of incidence and intensity modulation in breast and
cervix cancer radiation therapy. Thesis, Stockholm University, 2004.
NILSSON J. Accurate description of heterogeneous tumors for biologically optimized radiation therapy. Thesis,
Stockholm University, 2004.
QATARNEH S. Development of a whole body atlas for radiation therapy planning and treatment optimization.
Doctoral thesis in Medical Radiation Physics, Stockholm Uiversity 2006.
ÖSTLING J. New efficient deteactor for radiation therpay imaging using gas electron multipliers. Doctoral
thesis in Medical Radiation Physics, Stockholm Uiversity 2006.
JERNBERG ANNICA. Ultrasound, ions and combined modalitites for increased local tumour cell death in
radiation therapy. Doctoral thesis in Medical Radiation Physics, Karolinska Institutet 2007.
2
Expected Doctoral theses 2008
ADAMUS-GÓRKA M. Dose response modeling for normal tissue damage. Stockholm University, 4 April 2008.
ANDREASSEN B. Development of scanning photon, electron and ion beam systems.
GÓRKA B. CVD-dosimetry.
HOLLMARK M. Ion dose distributions.
KEMPE J. Light ion transport calculations.
JANEK S. In vivo PET-CT dosimetry.
Licentiate theses
2001-2004
MAVROIDIS P. Use of radiobiological models for treatment evaluation and clinical outcome optimization.
Stockholm University, 2001.
MAEHLE-SMITH M. A Bayesian approach for sequential updating of dose-response relations in radiation
therapy. Stockholm University, 2002.
QATARNEH S. Development of a whole body atlas data base and organ segmentation procedures for radiation
therapy planning. Stockholm University, 2004.
MSc theses
1996-2007
ENGLUND A. Investigation of the photon beam penumbra of the multileaf collimator of a MM50 racetrack
accelerator. KI-SU Int. Rep. 1996-8.
ERIKSSON L-O. Optimering av GammaKnivens dosplan. KTH Rapport 7 1996.
MANN J. Intrinsic beam monitoring in the racetrack microtron at the Karolinska Hospital. KI-SU Int. Rep.
1996-3.
DAHLBÄCK E. Real time control of a portal imaging device and image reconstruction. KTH/KI 1997.
ERIKSSON F. Ischemic heart disease death following radiation therapy for Hodgkin’s desease. KI-SU Int. Rep.
1997-6.
KÅVER GEREON. Optimal radiation beam profiles in fractionated radiation therapy considering uncertainties
in radiation sensivity. KTH/KI/SU 1997.
LIANDER A. Implication of using nanoseconds pulses of high energy electrons in radiation therapy. KTH/KI/SU
1997.
NILSSON S. Electron transport using the bipartition model on the two-dimensional Boltzmann equation.
KTH/KI/SU 1997.
WECKSTRÖM K. Investigation of multibeam treatment units considering physical characteristics and
radiobiological implication. KI-SU Int. Rep.1997-3.
WESTERMARK M. Detectors and measurement techniques in narrow photon beams. KI-SU Int. Rep. 1997-4.
FELKE R. Biologically based radiation therapy optimization using the linear and an extended linear-quadratic
dose response model. KI/SU 1998.
JÖNSSON E. Automatic Matching of 3D MR images with organ database. KTH/KI 1998.
LARSSON B. Patient positioning at radiotherapy by surface registration using the local Gausssian similarity
metric. KTH/KI 1998.
BERGSTAM S. Hearat desease following radiation therapy for Hodgkin’s desease. A dose-complication
analysis. KI-SU Int. Rep. 1999-4.
3
NILSSON J. The dose-response relation for hypoxic tumors. UPTEC/KI 1999.
PETTERSSON J. Organ and tissue segmentation in medical images using deformable contours and region
analysis. KTH/KI 1999.
HASHEMI A, MOAIERIFAR K. Development of radiation biology, radiation therapy and biologically
optimized treatment techniques. KTH/KI 2000.
MISAGHI-PANAH R. 3D-modelling of a gantry mounted racetrack for radiation therapy. KTH/KI 2000.
ORONEZ T. Use of 3D visualization platforms in radiotherapy treatment. KTH/KI 2000.
RAFAEL R. Design of a fast and strong purging magnet for narrow scanned photon beam therapy. KTH/KI
2000.
WALLMARK M. Operating range of a gas electron multiplier for portal imaging. KTH/KT 2000.
ADAMUS-GORKA M. Modelling normal tissue complications – study of the radiobiological models suitable
for radiobiologically optimized radiotherapy. KI-SU Int. Rep. 2001-4.
AXELSSON S. The influence of positioning uncertainty and breathing effect on the dose distribution and lung
complications after radotherapy of the breast. KI-SU Int. Rep. 2002-1.
HOLLMARK M. Influence of multiple scattering on the dose distributions of ion beams for radiation therapy.
KTH-KI-SU 2001.
PARSON P. Deformation calculations on a gantry mounted Racetrack for advanced radiation. KI-SU Int. Rep.
2001-2.
SIEGBAHN A. Calculations of electron fluence correction factors using true Monte Carlo code PENELOPE.
KI-SU Int. Rep. 2001-3.
SVENNBERG JONAS. Stereotactic treatment-couch for diagnostic imaging and radiation therapy. Konstfack/KI
2001.
ZAPOTOCZNA A. Verification of intensity modulated scanned photon and electron beams for optimised
radiation therapy. KI-SU Int. Rep. 2001-5.
EKELUND M. Design av optimalt strålbehandlingsgantry för lätta joner. LTU – EX.02/167, 2002.
ERNERFELDT Helga. Accuracy of a laser scanner for patient positioning. KTH/KI 2002.
FREDRIKSSON M. Biological fractionation effects in radiation therapy optimization. KI-KTH 2002.
KARLSSON K. Influence of oxygen concentration and nutrition on cell survival after irradiation. KTH-KI 2002.
KIMSTRAND P. Calculation of the relative biological effectiveness of light ion beams. KI-UU 2002.
LARSSON S. Radiation transport calculations for narrow scanned photon beams using Geant4. LTU 2002.354
CIV 2002.
UHRDIN J. Optimization of radiation therapy considering internal organ motion. KI-KTH 2002.
ÖSTLING JANINA. First test of a new gas electron multiplier based portal imaging device. Umeå Un./SU 2002.
ANDREASSEN B. Design of a scan and purging magnet system for narrwo photon beams. KTH - KI 2003.
BARAN A. The use of quality of life as an objective function for optimized radiation therapy. KI-SU Int. Rep.
2003-7.
DAGTUN L, LARSSON M: Introduction of IMRT at Soder Hospital. KI-SU Int. Rep. 2003-8
FALK F, LARSSON M. Design of concepts for two gantries. LTU – DUPP-03/23.
GLÖCKNER C. Characterisation of high and low LET radiation-induced apoptosis in human tumour cells. SUKI 2003.
JANEK S. 3-dimensional in vivo dose delivery verification by PET-CT imaging of photonuclear reactions in
50MV scanned photon beams. KI-KTH 2003.
KODURA M. Radiobiological optimization in radiotherapy of breast cancer. KI-SU Int. Rep. 2003-5.
HULTGREN A. Dependence of Chromosome Organization for Cell Survival after Exposure to Densely Ionizing
Radiation. KTH-KI 2004.
4
WIKLUND K. DEVELOPMENT of a semi-analytical method for calculation of the radial secondary dose
profile around light-ion beams in water. KI - LTU 2004.
YOUSEF S. A common point for administration for windows and unix. KTH-KI 2004.
NELLDAL P. Design of a dynamic beam intensity modulator for radiation therapy. KTH-KI 2005.
NYMAN P. Laser camera system for accurate 3D patient positioning in radiation therapy. KTH-KI 2005.
ANDERLIND E. Haptic Feedback for medical imaging and treatment planning. KTH-KI 2006.
BENGTSSON C. Corrrelation studies on human genome alterations. KTH-KI 2006.
EDSTRÖM F. Design and optimization of a positron emission tomography detector uing gas electron
multipliers. KTH/KI 2006
IGLESIAS E. Breathing corrections in PET imaging. KTH/KI 2006.
HOLMBERG R. Geant4 simulaitons of photonuclear beta-plus activation in radiotherapy. UU/KI 2007.
HULTQVIST M. Analysis of the uncertainties in the IAEA/WHO TLD postal dose audit programme. SU-KI
Internal report. KI-SU Int. Rep. 2006-14.
NILSSON C. Quantification of the influcence of blood flow on in vivo dose in radiation therapy using PET-CT
imaging. UU/KI2006.
SASSENBERG F. Quantification of breast cancer variability, using representational oligonucleotide analysis
(ROMA). KTH-KI 2006.
1
Publications Stage 1 - 4
Enclosure 2
Papers in scientific journals
1996
BRAHME A. Recent developments in radiation therapy planning and treatment optimization. Australian
Physical & Engineering Sciences in Medicine 19. 1-14, 1996.
GAGLIARDI G, LAX I, OTTOLENGHI A, RUTQVIST LE. Long term cardiac mortality after radiotherapy of
breast cancer - Application of the relative seriality model. Br. J. Radiol. 69. 839-846, 1996.
GUDOWSKA I. and BRAHME A. Neutron radiation from high-energy X-ray medical accelerators. Nucleonika
41. 105-118, 1996.
HYODYNMAA S, GUSTAFSSON A, BRAHME A. Optimization of conformal electron beam therapy using
energy- and fluence modulated beams. Med. Phys. 23. 659-666, 1996.
RADIVOYEVITCH T, CEDERVALL B. Mathematical analysis of DNA fragment distribution models used
with pulsed field gel electrophoresis for DNA double-strand break calculations. Review. Electrophoresis 17.
1087-1093, 1996.
SORCINI BB, HYODYNMAA S, BRAHME A. The role of phantom and treatment head generated
Bremsstrahlung in high energy electron beam dosimetry. Phys. Med. Biol. 41. 2657-2677, 1996
SVENSSON R, BRAHME A. Effective source size, yield and beam profile from multi-layered bremsstrahlung
targets. Phys. Med. Biol. 41. 1353-1379, 1996.
SODERSTROM S, BRAHME A. Small is beautiful - and often enough. Int. J. Radiat. Oncol. Biol. Phys. 34.
757-758, 1996.
TILIKIDIS A, LIND B, NAFSTADIUS P, BRAHME A. An estimation of the relative biological effectiveness
of 50 MV bremsstrahlung beams by microdosimetric techniques. Phys. Med. Biol. 41. 55-69, 1996.
AGREN-CRONQVIST A-K, KALLMAN P, BRAHME A. Determination of the relative seriality of a tissue
from its response to non-uniform dose delivery. In. Modelling in Clinical Radiobiology, Ed. D. Baltas, 1996.
1997
BRAHME A, RYDBERG B, BLOMQUIST P. Dual spatially correlated nucleosomal double strand breaks in
cell inactivation. In. Goodhead DT, O´Neill P, Menzel HG, editors. Microdosimetry An Interdisciplinary
Approach. Cambridge. The Royal Society of Chemistry, 1997.
CARLSSON A, ANDREO P, BRAHME A. Monte Carlo and analytically calculated proton pencil beams for
treatment planning. Phys. Med. Biol. 42.1033-1053, 1997.
KYLLONEN JE, LINDBORG L, SAMUELSON G. Paired TEPCS for variance measurements. In.
Microdosimetry, An interdisciplinary approach. Ed. D T Goodhead, P O' Neill, H G Menzel. The Royal Society
of Chemistry, Cambridge pp 361-364, 1997.
LOW DA, RONG ZHU X, PURDY JA, SODERSTROM S. The influence of angular misalignment on fixedportal intensity modulated radiation therapy. Med. Phys. 24. 1123-1139, 1997.
LOF J, LIND BK, BRAHME A. A general code for dynamic and stochastic optimization of radiotheraputic
treatment plans. Med. Biol. Engin. Comp. 35. 920, 1997.
NILSSON B, MONTELIUS A, ANDREO P, JOHANSSON J. Correction factors for parallel-plate chambers
used in plastic phantoms in electron dosimetry. Phys. Med. Biol. 42. 2101-2118, 1997.
1998
BRAHME A. Aspects on the development of radiation therapy and radiation biology since the Early Work of
Rolf Wideroe. The First Scandinavian Symp. in Radiation Oncology, Rosendal, Norway. Acta Oncol. 37. 593602, 1998.
CARLSSON AK, AHNESJO A. Scatter dose calculations in brachytherapy using the collapsed cone
superposition algorithm. Radiother. Oncol. 48 (Suppl. 1) S152, 1998.
2
EKLOF A, BRAHME A. Composit energy deposition kernels for focused point monodirectional photon beams.
Phys. Med. Biol. 44. 1655-1668, 1998 .
LÖF J, LIND BK, BRAHME A. An adaptive control algorithm for optimization of intensity modulated
radiotherapy considering uncertainties in beam profiles, patient setup, and internal organ motion. Phys. Med.
Biol. 43. 1605-1628, 1998.
SVENSSON R, LIND B, BRAHME A. Beam characteristics and clinical possibilities of a new compact
treatment unit design combining narrow pencil beam scanning and segmental multileaf collimation. Med. Phys.
25. 2358-2369, 1998.
SVENSSON R, ASELL M, NAFSTADIUS P, BRAHME A. Target, purging magnet and electron collector
design for scanned high energy photon beams. Phys Med Biol 43. 1091-1112, 1998.
1999
BRAHME A. Biologically based treatment planning. In. Mustakallio Centennial Symposium Helsinki. Acta
Oncol. Suppl. 13. 61-68, 1999.
BRAHME A. Modern developments in radiotherapy. Fourth Radiat. Physics Conf. Nov. 15-19 1998,
Alexandria, Egypt. Arab J. Nucl. Sci. Appl, eds A Gomaa and A M El-Naggar, p 344-361, 1999.
BRAHME A. Optimized radiation therapy based on radiobiological objectives. In. Seminars in Radiat. Oncol. 9.
35-45, 1999.
BRAHME A, LIND BK. Qantification of the steepness of the dose response relation. Int. J. Radiat. Oncol. Biol.
Phys., Vol 45. 243-245, 1999.
EKLOF A, BRAHME A. Composite energy deposition kernels for focused point monodirectional photon beams.
Phys. Med. Biol. 44. 1655-1668, 1999.
GUDOWSKA I, BRAHME A, ANDREO P, GUDOWSKI W, KIERKEGAARD J. Calculation of absorbed dose
and biological effectiveness from photonuclear reactions in a bremsstrahlung beam of end point 50 MeV. Phys.
Med. Biol. 44. 2099-2125, 1999.
KIMIAEI S. Evaluation of polynomial image deformation using anatomical landmarks for matching of 3Dabdominal MR-images and for atlas construction. IEEE Transact. Nucl. Sci. 46.1110-1113, 1999.
KOREVAAR EW, HEIJMEN BJM, WOUDSTRA E, HUIZENGA H, BRAHME A. Mixing intensity
modulated electron and photon beams. combining a steep dose fall-off at depth with sharp and depthindependent penumbras and flat beam profiles. Phys. Med. Biol. 44. 2171-2181, 1999.
KAVER G, LIND BK, LOF J, LIANDER A, BRAHME A. Stochastic optimization of intensity modulated
radiotherapy to account for uncertainties in patient sensitivity. Phys. Med. Biol. 44. 2955-2969, 1999.
LIND BK, MAVROIDIS P, HYODYNMAA S, KAPPAS C. Optimization of the dose level for a given
treatment plan to maximize the complication-free tumor cure. Acta Oncol. 38. 787-798, 1999.
NAKAMURA K, BRAHME A. Evaluation of fractionation regimens in stereotactic radiotherapy using a
mathematical model of repopulation and reoxygenation. Radiat. Med. 17. 219-225, 1999.
NILSSON B. Perturbation effects in ionisation chamber dosimetry. Fourth Rad. Physics Conf., Nov. 15-19,
1998, Alexandria, Egypt. Arab J Nucl Sci Appl, eds A Gomaa and A M El-Naggar. 296-311, 1999.
SODERSTROM S, EKLOF A, BRAHME A. Aspects on the optimal photon beam energy for radiation therapy.
Acta Oncol. 38. 179-187, 1999.
TILLY N, BRAHME A, CARLSSON J, GLIMELIUS B. Comparison of cell survival models for mixed LET
radiation. Int. J. Radiat. Biol. 75. 233-243, 1999.
ASELL M, HYODYNMAA S, SODERSTROM S, BRAHME A. Optimal electron and combined electron and
photon therapy in the phase space of complication free cure. Phys. Med. Biol. 44. 235-252, 1999.
2000
BELKIC Dz, DANDO PA, MAIN J, TAYLOR HS. Three novel high-resolution nonlinear methods for fast
signal processing, J. Chem. Phys. 113.6542-6565, 2000.
BELKIC Dz, DANDO PA, MAIN J, TAYLOR HS SHIN SK. Decimated signal diagonalization for Fourier
transform spectroscopy, J. Phys. Chem. A 4, 11677-11684, 2000.
3
BELKIC Dz, BRAHME A. Stopping power vs stopping force. ICRU neews, electronic publication
(www.icru.org) 2000.
BRAHME A. Development of radiation therapy optimization. Acta Oncol. 39. 579-595, 2000.
CARLSSON AK, AHNESJO A. The collapsed cone superposition algorithm applied to scattter dose calculations
in brachytherapy Med. Phys. 27. 2320-2332, 2000.
CARLSSON AK, AHNESJO A. Point kernels and superposition methods for scatter dose calculations in
brachytherapy. Phys. Med. Biol. 45. 357-382, 2000.
CRAFOORD J, SIDDIQUI FM, KRAMER EL, MAGUIRE JR. GQ, NOZ ME, ZELEZNIK MP. Comparison of
two landmark based image registration methods for construction of a body atlas. Physica Medica , XVI(2). 7582, 2000.
DECHAMPS M, BURGHARDT I, DEROUET C, BODENHAUSEN G, BELKIC DZ. Nuclear Magnetic
Resonance Study of Xenon-131 Interacting with Surfaces. Effective Liouvillian and Spectral Analysis. J. Chem.
Phys. 113. 1630-1640, 2000.
ERIKSSON F, GAGLIARDI G LIEDBERG A, LAX I, LEVITT S, LIND B, RUTQVIST LE. Long-term
cardiac mortality following radiation therapy for Hodgkin's disease. analysis with the relative seriality model.
Radiother. Oncol. 55. 153-162, 2000.
IACOBAEUS C, BRAHME A, DANIELSSON, M FONTE P, OSTLING J, PESKOV V, WALLMARK M. A
novel portal imaging device for advanced radiation therapy. Proceeding of IEEE NSS-MIC. IEEE Transactions
on Nuclear Science, Lyon, 2000.
MAHMOUD F, TON A, CRAFOORD J, KRAMER EL, MAGUIRE JR. GQ, NOZ ME, ZELEZNIK MP.
Comparison of three image methods for registration of abdominal/pelvic volume data sets from functionalanatomic scans. Proceedings of the SPIE Medical Imaging 2000. SPIE - The International Society for Optical
Engineering, 3979. 10pp, February, 2000.
MAIN J, DANDO PA , BELKIC DZ, TAYLOR HS. Decimation and harmonic inversion of periodic Orbit
signals. J. Phys. A. Math. Gen. 33. 1247-1263, 2000.
MAVROIDIS P, LIND BK, VAN DIJK J, KOEDOODER K, DE NEVE W, DE WAGTER C, PLANSKOY B,
ROSENWALD JC, PROIMOS B, KAPPAS C, DANCIU C, BENASSI M, CHIEREGO G BRAHME A.
Comparison of conformal rad. therapy techniques within the dynamic radiotherapy project "Dynarad". Phys Med
Biol 45. 2459-2481, 2000.
MEJADDEM Y, HYODYNMAA S, BRAHME A. Photon scatter in intensity modulating filters evaluated by
first compton scatter and Monte Carlo calculations and experiments in brad beams. Phys. Med. Biol. 45, 27472760, 2000.
TILLY N, CARLSSON J, BRAHME A, GLIMELIUS B. Modelling cell survival with mixed LET radiation.
Rad. Res. 2000.
WESTERMARK M, ARNDT H, NILSSON B, BRAHME A. Comparative dosimetry in narrow high-energy
photon beams. Phys Med Biol 45 685-702, 2000.
2001
BELKIC Dz. Fast Pade Transform (FPT) for magnetic resonance imaging and computerized tomography. Nucl
Instr Meth A, 471. 165-169, 2001.
BELKIC Dz. Leading distorted wave theories and computational methods for fast-ion atom collisions. J Comp
Meth Sci Eng 1. 1-74, 2001.
BELKIC Dz. Quantum Mechanics in Signal Processing. J Comp Meth Sci Eng 2. 1-79, 2001.
BELKIC Dz, DANDO PA, TAYLOR HS. High-Resolution processing of arbitrarily long time signals. J Comp
Meth Sci Eng. 2. 81-100, 2001.
BRAHME A. Individualizing cancer treatment. Biological optimization models in treatment planning and
delivery. Int J Radiat Oncol Biol Phys 49. 327-337, 2001.
BRAHME A, NILSSON J and BELKIC DZ. Biologically optimized radiation therapy. Nobel Conf. 2000, Acta
Oncol 40. 725-734, 2001.
BRAHME A, LEWENSOHN R, RINGBORG U, AMALDI U, GERARDI F, ROSSI S. Design of a centre for
biologically optimised light ion therapy in Stockholm. Nucl Instr Meth IN Phys Res B 184. 569-588, 2001.
4
JERNBERG A, EDGREN MR, LEWENSOHN R, WIKSELL H and BRAHME A. Cellular effects of highintensity focused continuous wave ultrasound alone and in combination with X-rays. Int J Radiat Biol 77. 127135, 2001.
MAVROIDIS P, LIND BK, BRAHME A. Biologically effective uniform dose ( D ) for specification, report and
comparison of dose response relations and treatment plans Phys Med Biol 46. 2607-30, 2001.
MEIJER A.E, EKEDAHL J, JOSEPH B, CASTRO J, HARMS-RINGDAHL M, ZHIVOTOVSKY B,
LEWENSOHN R. High-LET radiation induces apoptosis in lymphoblastoid cell lines derived from ataxia
telangiectasia patients. Int J Radiat Biol 77. 309-317, 2001.
MEJADDEM Y, BELKIC DZ, HYODYNMAA S, BRAHME A. Calculations of electron energy loss straggling.
Nucl Instr Meth B, 173. 397-410, 2001
MEJADDEM Y, HYÖDYNMAA S, SVENSSON R and BRAHME A. Photon scatter kernels for intensity
modulating radiation therapy filters. Phys Med Biol 46. 1-14, 2001.
LIND B K, NILSSON J, LÖF J and BRAHME A. Generalization of the normalized dose-response gradient to
non-uniform dose delivery. Nobel Conf. 2000, Acta Oncol 40. 719-724, 2001.
PERSSON LM. LIND BK, EDGREN MR and BRAHME A. Clonogenic survival for two human glioma cell
lines (M059J7K) after exposure to low and high LET radiation. Radiother Oncol 60, S5, 2001.
PESKOV P, FONTE P, DANIELSSON M, IACOBAEUS C, OSTLING J, WALLMARK M.The study and
optimization of new micropattern gaseous detectors for high rate applications. IEEE T NUCL SCI 48 (4). 10701074, 2001.
QATARNEH SM, CRAFOORD J, KRAMER EL, MAGUIRE GQ, BRAHME A, NOZ ME, HYÖDYNMAA S.
A whole body atlas for segmentation and delineation of organs for radiation therapy planning. Nucl Instr Meth
Phys Res A 471. 160-164, 2001.
WALLMARK M, BRAHME A, DANIELSSON M, FONTE P, IACOBAEUS I, PESKOV V, OSTLING J,
Operating range of a gas electron multiplier for portal imaging. Nucl. Instr. and Meth. in Physics Research A
471. 151-155, 2001.
2002
CEDERVALL BE and McMILLAN TJ. The fraction of DNA released on pulsed-field gel electrophoresis gels
may differ significantly between genomes at low levels of double-strand breaks. Radiat Res 158. 247-249, 2002.
GASINSKA A, URBANSKI K, ADAMCZYK A, PUDELEK J, LIND BK and BRAHME A. Prognostic
significance of intratumour microvessel density and hemoglobin level in carcinom of the uterine cervix. Acta
Oncol 41, 437-443, 2002.
HASSAN Z, HELLSTRÖM-LINDBERG E, ALSADI S, EDGREN M, HÄGGLUND H and HASSAN M. The
effect of modulation of glutathione cellular content on busulphan-induced cytotoxicity on hematopoietic cells in
vitro and in vivo. Bone Marrow Transplantation 30. 141-147, 2002.
IACOBAEUS C, DANIELSSON M, FONTE P, FRANCKE T, OSTLING J and PESKOV V. Sporadic electron
jets from cathodes – the main breakdown-triggering mechanism in gaseous detectors. IEEE Trans Nucl Sci 49,
4.1622-1628, 2002.
KOREVAAR EW, HUIZENGA H, LÖF J, STROOM JC, LEER JWH and BRAHME A. Investigation of the
added value of high-energy electrons in intensity-modulated radiotherapy. Four clinical cases. Int J Radiat Oncol
Biol Phys 52. 236-253, 2002.
MATTSSON S, BRAHME A, CARLSSON J, et al. Swedish Cancer Society radiation therapy research
investigation. Acta Oncol 41, 596-603, 2002.
MAVROIDIS P, THEODOROU K, LEFKOPOULOS D, NATAF F, SCHLIENGER M, KARLSSON B, LAX I,
KAPPAS C, LIND BK, BRAHME A. Prediction of AVM obliteration after stereotactic radiotherapy using
radiobiological modeling. Phys Med Biol 47.2471-2494, 2002.
MAVROIDIS P, AXELSSON S, HYÖDYNMAA S, RAJALA J, PITKÄNEN MA, LIND BK, BRAHME A.
Effects of positioning uncertainty and breathing on dose delivery and radiation pneumonitis prediction in breast
cancer. Acta Oncol, Vol. 51 No. 5. 471-485, 2002.
MEIJER AE, JERNBERG ARM, HEDLÖF I HEIDEN T, EDGREN MR, PERSSON LM, TILLY N, LIND BK,
CEDERVALL B, BRAHME A. Maximum apoptotic response to light ions around 50 ev/nm in p53 wt human
melanoma cells. Int J Radiat Biol p73, 2002.
5
MEJADDEM Y, BELKIC Dz, BRAHME A. HYÖDYNMAA S. Development of the electron transport theory
and absorbed dose computation in matter. Nucl Instr Meth Phys Res B 187. 499-524, 2002.
NILSSON J, LIND BK and BRAHME A. Radiation response of hypoxic and generally heterogeneous tissues.
Int J Radiat Biol 78. 389-405, 2002.
PALM Å, CZAP L, ANDREO P and MATTSSON O. Performance analysis and determination of the pwall
correction factor for 60Co -ray beams for Wellhöfer Roos-type plane-parallel chambers. Phys Med Biol 47.
631-640, 2002.
PERSSON LM, EDGREN MR, STENERLÖW B, LIND BK, HEDLÖF I, JERBERG A, MEIJER AE and
BRAHME A. Relative biological effectiveness of boron ions on human melanoma cells. Int J Radiat Biol, 78.
743-748, 2002.
PERSSON LM, LIND BK, EDGREN MR, HEDLÖF I and BRAHME A. RBE of 50 MV scanned bremsstrahlung beams determined using clonogenic assay. Int J Radiat Biol 78 No 4. 275-284, 2002.
SOBOLEVSKY N, GUDOWSKA I, ANDREO P, BELKIC Dz, BRAHME A. Interaction of ion beams with
tissue-like media. simulations with the SHIELD-HIT Monte-Carlo transport code. Proc Shielding Aspects of
Accelerators. Stanford Linear Accelerator Center, California, 2002.
TILLY N, FERNÁNDEZ-VAREA, GRUSELL E, BRAHME A. Caomparison of Monte Carlo calculated
electron slowing-down spectra generated by 60Co gamma-rays, electrons, protons and light ions. Phys. Med.
Biol, 47. 1303-1319, 2002.
2003
BELKIC Dz. Exact analytical expressions for any Lorentzian spectrum in the fast Pade transform (FPT), Journal
of. Comput. Meth. Sci. Eng. (JCMSE), Cambridge International Science Publishing, Vol 3, pp 109-186, 2003
(review).
BELKIC Dz. Mathematical physics of magnetic resonance spectroscopy (MRS) Journal of Comput. Meth. Sci.
Eng. (JCMSE), Cambridge International Science Publishing, Vol 3, pp 505-590, 2003 (review).
BELKIC Dz. Strikingly stable convergence of the fast Pade transform. applications to magnetic resonance
spectroscopy (MRS). Journal of Comput. Meth. Sci. Eng. (JCMSE), Cambridge International Science
Publishing, Vol 3. 299-382, 2003 (review).
BELKIC Dz. Unique virtues of the Pade approximant for high-resolution signal processing. Comput. Meth. Sci.
Eng. (CMSE), World Scientific Publishing, Vol 1. 87-89, 2003.
BELKIC Dz, BELKIC K. A new mathematical framework for "Surveillance spectroscopic imaging" in tumour
diagnostics. Comput. Meth. Sci. Eng. (CMSE), World Scientific Publishing, Vol 1. 701-703, 2003.
BELKIC Dz. Strikingly stable convergence of a nonlinear parametric estimator. medical applications to
magnetic resonance spectroscopy. Comput Meth Sci Eng. (CMSE), Vol 1. 727-733, 2003.
BRAHME A. Biologically optimized 3-dimensional in vivo predictive assay based radiation therapy using
positron emission tomography-computerized tomography imaging. Acta Oncol 42. 123-136, 2003.
BRAHME A. Recent advances in light ion radiation therapy. Int J Rad Onc Biol Phys 58. 603-616, 2003.
CEDERVALL B, EDGREN MR, LEWENSOHN R. X-ray-induced DNA double-strand breaks in mouse L1210
cells. A new computational method for analyzing neutral filter elution data. Rad Research 159. 495501, 2003.
CEDERVALL B, MCMILLAN TJ. Short communication. The fraction of DNA released on pulsed-field gel
electrophoresis gels may differ significantly between genomes at low levels of double-strand breaks. Rad
Research 15. 247-249, 2003.
CEDERVALL B, EDGREN MR, LEWENSOHN R. X-ray-induced DNA double-strand breaks in mouse L1210
cells. A new computational method for analyzing neutral filter elution data. Rad Res 159. 495-501, 2003.
FERREIRA B C, SVENSSON R, LÖF J, BRAHME A. The clinical value of non-coplanar photon beams in
biologically optimized intensity modulated dose delivery on deep-seated tumours. Acta Oncol, Vol 42. 852-864
2003.
HOLGERSSON Å, JERNBERG ARM, PERSSON LM, EDGREN MR, LEWENSOHN R, NILSSON A,
BRAHME A, MEIJER AE. Low and high LET radiation-induced apoptosis in M059J and M059K cells. Int J
Radiat Biol, Vol 79. 611-621, 2003.
6
JOHANSSON K-A, MATTSSON S, BRAHME A, et al. Radiation therapy dose delivery. Acta Oncol 42. 85-91,
2003.
LAURELL G, KRAEPELIEN T, MAVROIDIS P, LIND BK, FERNBERG JO, BECKMAN M, LIND MG.
Stricture of the proximal esophagus in head and neck carcinoma patients after radiotherapy. Cancer 97(7). 16931700, 2003.
LIND BK, PERSSON LM, EDGREN MR, HEDLÖF I, BRAHME A. Repairable-conditionally repairable
damage model based on dual Poisson processes. Radiat Res 160. 366-375, 2003.
MAVROIDIS P, LAURELL G, KRAEPELIEN T, FERNBERG JO, LIND BK, BRAHME A. Determination
and clinical verification of dose-response parameters for esophageal stricture from head and neck radiotherapy.
Acta Oncol 42. 865-881, 2003.
POLISCHOUK AG, STENERLÖW B, EDGREN MR, LEWENSOHN R. Difference in the induction, but not in
the repair, of X-ray-and nitrogen ion-induced DNA- single-strand breaks as measured using human cell extracts.
Int J Radiat Biol 79. 965-971, 2003.
QATARNEH, S, NOZ ME, HYÖDYNMAA S, MAGUIRE GQ, KRAMER EL, CRAFOORD. Evaluation of a
segmentation procedure to delineate organs for use in construction of a radiation therapy planning atlas. Int. J. of
Med Info 69. 39-55, 2003.
ROSIER JF, MICHAUX L, AMEYE G, CEDERVALL B, et al. The radioenhancement of two human head an
neck squamous cell carcinomas by 2’ -2’ difllluorodeoxycytidine (gemcitabine; dFdC) is mediated by an
increase in radiation-induced residual chromosome aberrations but not residual DNA DSBs. Mutation Research
Vol. 527 15-26, 2003.
ROSSIER JF, MICHAUX L, AMEYE G, CEDERVALL B, et al. The radioenhancement of two human head and
neck squamous cell carcinomas by 2´2´ difluorodeoxycytidine is mediated by an increase in radiation-induced
residual chromosome aberrations but not residual DNA DSBs. Mutation Research 527. 15-26, 2003.
SANCHEZ-CRESPO A, ANDREO P, LARSSON SA. Positron flight in human tissues and its influence on PET
image spatial resolution. Eur J Nucl Med Mol Imaging. PMID. 14551751, 2003.
SANCHEZ-DOBLADO F, ANDREO P, CAPOTE R, et al. Ionization chamber dosimetry of small photon
fields. a Monte Carlo study on stopping-power ratios for radiosurgery and IMRT beams. Phys Med Biol 48.
2081, 2003.
SIEGBAHN EA, NILSSON B, FERNANDEZ-VAREA JM, ANDREO P. Calculations of electron fluence
correction factors using the Monte Carlo code Penelope. Phys Med Biol 48. 1263-1275, 2003.
TELL R, EDGREN MR, SVERRISDOTTIR A, CASTRO J, FORNANDER T, HANSSON LO, SKOG S,
LEWENSOHN R. Radiation-induced cell cycle response in lymphocytes is not related to clinical side-effects in
breast cancer patients. Anticancer Res 23. 3077-3084, 2003.
TURESSON I, CARLSSON J, BRAHME A, et al. Biological response to radiation therapy. Acta Oncol 42. 92106, 2003.
ÖSTLING J, BRAHME A, DANIELSSON M, FRANCKE T, IACOBAEUS I, PESKOV V. Study of hole-type
gas multiplication structures for portal imaging and other high counting rate applications. IEEE T Nucl Sci 50 4.
809-819 Part 1, 2003.
2004
AL-ALBANYM, HELGASON AR, CRONQVIST AK, LIND B, MAVROIDIS P, et al. Dose to the anal
sphincter region and risk of fecal leakage. Acta Oncol Vol 43.118-118, 2004.
BELKIC D, BELKIC K. Spectroscopic imaging through magnetic resonance for brain tumour diagnostics. resent
achievements, dilemmas and potential solutions via advances in signal processing. J Comp Meth Sci Eng. 4,
157-207, 2004.
BELKIC D. Strikingly stable convergence of the fast Pade tranform (FPT) for high-resoulution parametric and
non-parametric signal processing of Lorentzian and non-Lorentzian spectra. . Nucl Instr Meth in Physics
Research. A. 525, 366-371, 2004.
BELKIC D. Analytical continuation by numerical means in spectral analysis using the fast Pade transform
(FPT). Nucl Instr Meth in Physics Research. A. 525, 372-378, 2004.
BELKIC D. Error analysis through residual frequency spectra in the fast Pade transform (FPT). Nucl Instr Meth
in Physics Research. A. 525, 392-386, 2004.
7
BRAHME A, SVENSSON H, NÄSLUND I, RINGBORG U. Tre kostnadsbesparande innovationer vid strålbehandling av cancer. Incitament. 13 457-460, 2004.
DANIELSSON M, FONTE P, FRANCKE T, IACOBAEUS C, ÖSTLING J, PESKOV V. Novel gaseous
detectors for medical imaging. Nucl Instr Meth in Physics Research. 518 406-410, 2004.
EDGREN MR, MEIJER AE, JERNBERG AR-M, HOLGERSSON Å, PERSSON LM, HEIDEN T, LIND BK.
Decreased difference in radiosensitivity between different human cell lines after exposure to high LET radiation.
Central Eur J Occupational and Environmental Medicine. 10 51, 2004.
ERSMARK T, CARLSSON P, DALY E, FUGLESANG C, GUDOWSKA I, LUND-JENSEN B, NARTALLO
R, NIEMINEN P, PEARCE M, SANTIN G, SOBOLEVSKY NM. Status of the DESIRE Project. Geant4
Physics Validation Studies and First Results from Columbus/ISS Radiation Simulations. IEEE Transactions
Nucl Sci. 51 1378-1384, 2004.
GASINSKA A, FOWLER JF, LIND BK, URBANSKI K. Influence of overall treatment time and
radiobiological parameters on biologically effective doses in cervical cancer patients treated with Acta Oncol
Vol. 43. 657-777, 2004.
GUDOWSKA I, SOBOLEVSKY NM, ANDREO P, BELKIC D, BRAHME A. Ion beam transport in tissue-like
media using the Monte Carlo code SHIELD-HIT. Phys Med Biol 49. 1933-1958, 2004.
GUDOWSKA I, SOBOLEVSKY NM. Neutron production in tissue during radiotherapy with high energy
photon and ion beams. Proc of the Workshop on Neutron Spectrometry and Dosimetry. Experimental Techniques and MC Calculations, Italian Institute of Culture, Stockholm, Sweden, 18-20 October, 2001, Eds. A.
Zanini and C. Ongaro, ISBN 88-87503-86-9, pp. 35-42, 2004.
HOLLMARK M, UHRDIN J, BELKIC DZ, GUDOWSKA I, BRAHME A. Influence of multiple scattering and
energy loss straggling on the absorbed dose distributions of therapeutic light ion beams. I Analytical pencil beam
model. Phys Med Biol. 49 3247-3265, 2004.
IACOBAEUS C, BRESKIN A, DANIELSSON M, FRANCKE T, MÖRMANN D, ÖSTLING J, PESKOV
V.Advances in capillary-based gaseous UV imaging detectors. Nucl Instr Meth in Physics Research. A. 525 4248, 2004.
IACOBAEUS C, DANIELSSON M, FRANCKE T, ÖSTLING J, PESKOV V. Study of capillary-based gaseous
detectors. IEEE T Nucl Sci. 51(3) Part 1, 2004.
MAVROIDIS P, THEODOROU K, LAURELL G, FERNBERG JO, LIND BK, BRAHME A. Statistical
methods for clinical verification of dose-response parameters related to esophageal stricture and AVM
obliteration from radiotherapy. Phys Med Biol 49. 3797-3816, 2004.
MEIJER AE, GLÖCKNER C, BODENNEC J, RODRIGUEZ-LAFRASSE C, EDGREN MR. Different
molecular pathways for apoptosis in cells exposed to high and low LET radiation. Central Eur J Occupational
Environmental Medicine. 10 131, 2004.
MEIJER AE. Apoptosis in human cells exposed to accelerated ions. Research and application in radiobiology
with swift ions and 4th Enlight wp4 meeting. Caen France, 2004.
QATARNEH S.M., KIRICUTA I.C., BRAHME A, LIND B.K.. “3D Lymph Node Topography. An Atlas for the
Definition of Clinical Target Volumes in 3D & 4D IMRT Planning”. Proceedings of Takahashi International
Conference on 3D Conformal Radiotherapy, Nagoya Japan, 2004.
SOBOLEVSKY NM, GUDOWSKA I, ANDREO P, BELKIC DZ, BRAHME A. Interaction of ion beams with
tissue-like media. Simulations with the SHIELD-HIT Monte Carlo transport code. Proc of the Sixth Meeting of
the Task Force on Shielding Aspects of Accelerators, Targets and Irradiation Facilities (SATIF-6), SLAC USA,
10-12 April, 2002, OECD NEA. No. 3828 367-375, 2004.
URBANSKI K, GASINSKA A, PUDELEK J, FOWLER JF, LIND B, BRAHME A. Bioloigcally effective doses
in radiotherapy of cervical carcinoma. Neoplasma 51(3). 228-38, 2004.
WALIGORSKI MPR, HOLLMARK M, LIND B, GUDOWSKA I. Cellular parameters for track structure
modelling of radiation hazard in space. Advanced in Space Research 34. 1378-1382, 2004.
ÖSTLING J, BRAHME A, DANIELSSON M, IACOBAEUS C, PESKOV V. A radiation tolerant electronic
readout system for portal imaging. Nucl Instr Meth in Physics Research. A 525/1-2 308-312, 2004.
8
2005
al-ABANY M, HELGASON AR, ÅGREN A, LIND BK, MAVROIDIS P, WERSÄLL P, LIND H, QVANTA
E, STEINECK G. Towards a definition of a threshold for harmless doses to the anal-sphincter region and the
rectum. Int J Radiat Oncol Biol Phys. 61(4) 1035-44, 2005.
BELKIC D, BELKIC K. The fast Padé transform in magnetic resonance spectroscopy for potential improvements in early cancer diagnostics. Phys. Med. Biol 50. pp 4385-4408, 2005.
BELKIC D, BELKIC K. Fast Padé Transform for Optimal Qualification of Time Signals From Magnetic Resonance Spectroscopy. International Journal of Quantum Chemistry, vol 105 pp 493-510, 2005.
BRAHME A, SVENSSON S. Hög tid att introducera klinisk lättjon-behandling av cancer I Sverige. Incitament 5
pp. 421428, 2005.
BRAHME A, GUDOWSKA I, LARSSON S, ANDREASSEN B, HOLMBERG R, SVENSSON R, et al. Application GEANT4 in the development of new radiation therapy treatment metohods. In. Astroparticle, Particle and
Space Physics, Detectors and Medical Physics Applications. Proc. of 9th Conf. p 451-461, 2005
BRAHME A. Fractionation & Biologically Optimized IMRT using in Vivo predictive Assay based Radiation
Therapy (BioArt). Proc. Fifth Int. Symp. on the Lymphatic system, Limburg 2005
BRAHME A. Development of biologically optimized light ion therapy. Proc. Seventh Int. Conf. On Time Dose
Fractionation in Radiation Oncology, Madison Wisconsin 2005; 50-67, 2005.
GUDOWSKA I, SOBOLEVSKY NM. Simulation of secondary particle production and absorbed dose to tissue
in light ion beams. Radiation Protection Dosimetry, vol 116 1-4 pp 301-306, 2005.
HOLGERSSON Å, HEIDEN T, CASTRO J, EDGREN MR, LEWENSOHN R AND MEIJER AE. Different
G2/M ackumulation in M059J and M059K cells after exposure to DNA double-strand break-inducing agents. Int
J Radiat Oncol Biol Phys. 61(3) 915-921, 2005
LARSSON S, SVENSSON R, GUDOWSKA I, IVANCHENKO V, ANDREASEN B, BRAHME A. Radiation
transport calculations for narrow scanned photon beam therapy using the Monte Carlo code Geant4. Radiation
Protection Dosimetry, vol 115 1-4 pp 503-507, 2005
MAVROIDIS P, al-ABANY M, HELGASON AR, ÅGREN CRONQUIST AK, WERSÄLL P, LIND H,
QVANTA E, THEODOROU K, KAPPAS C, LIND BK, STEINECK G, BRAHME A. Dose-Response
Relations for Anal Sphincter Regarding Fecal Leakage and Blood or PhLegm in Stools after Radiationtherapy
for Prostate Cancer Radiobiological Study of 65 Consecutive Patients. Strahlenther Onkol. 181(5) 293-306,
2005.
MEIJER AE, JERNBERG AR-M, HEIDEN T, STENERLÖW B, PERSSON L-M, TILLY, LIND BK,
EDGREN M. Dose and time depentent apoptotic response in a human melanoma cell line exposed to accelerated
boron ions at four different LET. Int J Radiat Oncol Biol Phys. 81(4) 261-272, 2005.
MEIJER M, GLÖCKNER C, CZENE S, BODENNEC J, RODRIGUEZ-LAFRASSE, EDGREN MR. Differences in the induction of apoptosis after high and low LET radiation. Proc. of 9th Int Wolfsberg meeting on
molecular radiation biology/oncology, 2005.
PROCHAZKA P, HALL P, GAGLIARD GI, GRANATH F, NILSSON B, SHIELDS PG, TENNIS M, CZENE
K. Ionizing radiation and tobacco use increases the risk of a subsequent lung carcinoma in women with breast
cancer. Case-Only Design Journal of Clinical Oncology 23 nr 30, p 7467-7474, 2005
TOMA-DASU I, DASU A, BRAHME A. Influence of acute tumour hypoxia on radiation therapy outcome.
Physical, Chemical and Biological Targeting in Radiation Oncology. In AAPM Symposium Proceedings No. 14.
ed M Mehta, B R Paliwal and S Bentzen pp 111-117, 2005.
TSOUGOS I, MAVROIDIS P, RAJALA J, THEODOROU K, JÄRVENPÄÄ R, PITKÄNEN MA, HOLLI K,
OJALA AT, LIND BK, HYODYNMAA S, KAPPAS C. Evaluation of dose-response models and parameters
predicting radiation induced pneumonitis using clinical data from breast cancer radiotherapy. Phys Med Biol.
50(15) 3553-54, 2005.
2006
BRAHME A, GUDOWSKA I, LARSSON S, ANDREASSEN B, HOLMBERG R, SVENSSON R. Application
of Geant4 in the development of new Radiation TherapyTreatment Methods. In. Proc. 9th Conf. on Astroparticle,
Particle and Space Physics, Detectors and Medical Phsyics Applications. 451-461 Ed. Barone, Borchi Gaddi et
al. World Sci. Publ. Singapore, 2006.
9
BRAHME A. Development of light ion therapy. The ultimate stereotactic treatment modality. SBRT 2006 3rd
Acta Oncologica symposium on Steroetactic Body Radiotherapy, Copenhagen 15-17 June, 2006.
DASU A, TOMA-DASU I. Theoretical simulation of tumour oxygenation - practical applications. Advances in
Experimental Medicine and Biology 578, 2006.
FERREIRA BC, SVENSSON R, LIND BK, JOHANSSON J, BRAHME A. Effective beam directions using
radiobiologically optimized IMRT of node positive breast cancer. Phys Medica XXII.1. 3-15, 2006.
GORKÁ B, NILSSON B, FERNÁNDEZ-VAREA JM, SVENSSON R, BRAHME A. Influence of electrodes on
the photon energy deposition in CVD-diamond dosimeters studied with the Monte Carlo PENELOPE. Phys Med
Biol 51.3607-3623, 2006.
GUDOWSKA I, KEMPE J, SOBOLEWSKY N. Low-and high LET dose components in therapeutic carbon
beams. Rad Prot Dos, Vol. 122 No 1-4. 483-484, 2006.
GUDOWSKA I, SOBOLEVSKY N. Calculations of Particle and Heavy Ion Interactions with Space Shielding
Materials using the SHIELD-HIT Transport Code. Radiation Measurements 41.1091-1096, 2006.
JANEK S, SVENSSON R, JONSSON C, BRAHME A. Development of dose delivery verification by PET
imaging of photonuclear reactions following high energy photon therapy. Phys Med Biol 51. 5769-5783, 2006.
MAVROIDIS P, FERREIRA BC, PAPANIKOLAOU N, SVENSSON R, KAPPAS C, LIND BK, BRAHME A.
Assessing the difference between planned and delivered intensity-modulated radiotherapy dose distributions
based on radiobiological measures. Clin Oncol 18. 529-538, 2006.
MAVROIDIS P, PLATANIOTIS G, ADAMUS-G M, LIND B. Comments on Reconsidering the definition of a
dosemass histogram (DMH) versus dosevolume histogram (DVH) for predicting radiation-induced pneumonitis.
Phys Med Biol 5. L43-L50, 2006.
QATARNEH SM, KIRICUTA IC, BRAHME A, TIEDE U, LIND BK. 3D Atlas of lymph node topography
based on the visible human dataset. The Anatomical Record (Part B. The New Anatomist).98-111, 2006.
TOMA-DASU I, DASU A, KARLSSON M. Theoretical simulation of tumour hypoxia measurements. Advances
in Experimental Medicine and Biology 578, 2006.
TSOUGOS I, MAVROIDIS P, THEODOROU K, RAJALA J, PITKANEN MA, HOLLI K, OJALA AT,
HYÖDYNMAA S, JARVENPAA R, LIND BK, KAPPAS C. Clinical validation of the LKB model and
parameter sets for predicting radiation-induced pneumonitis from breast cancer radiotherapy. Phys Med Biol 51
(3).L1-9, 2006.
WALIGORSKI MP, HOLLMARK M, LESIAK J. A simple track dtructure model of ion beam radiotherapy.
Rad Prot Dos 122(1-4). 471-4, 2006.
2007
ANDISHEH B, LIND BK, BITARAF MA, MAVROIDIS P, BRAHME A. Clinical and radiobiological
advantages of stereotactic light ion beam radiation therapy for large intracranial arteriovenous malformations. Int
J Radiosurgery. In press, 2007
BRAHME A, LIND BK. A Systems Biology Approach to Radiation Therapy Optimization. Radiation and
Environmental Biophysics. In press, 2007.
BRAHME A. Development of Highly Specific Molecular Cancer Therapy with the Lightest Ions. 5th Takahashi
Memeorial Int Symp, Japan Book of Abstract p57, 2007.
DASU A, TOMA-DASU I. Treatment modelling; the influence of microenvironmental conditions. Acta Oncol.
In press, 2007.
DASU A, TOMA-DASU I. What is the clinically relevant RBE? A warning for fractionated treatments with high
LET-radiation. Int J Rad Onc Biol Phys 20. Epub ahead of print, 2007.
GUDOWSKA , KOPEC M, SOBOLEVSKY N. Neutron production in tissue-like media and shielding materials
irradiated with high energy ion beams. Rad Prot Dos, doi.10.1093/rpd/ ncm132. 1-5, 2007.
KEMPE J, BRAHME A. Energy Range Relation and Mean Energy Variation of Therapeutic Particle Beams.
Med Phys. In press, 2007.
LIND BK, BRAHME A. The radiation response of heterogeneous tumors. Physica Medica, In press, 2007.
10
QATARNEH SM, KIRICUTA IC, BRAHME A, NOZ ME, FERREIRA B, KIM WC, LIND BK. Lymphatic
Atlas-Based Target Volume Definition for Intensity Modulated Radiation Therapy Planning. Nuclear
Instruments and Methods in Physics Research A. 580. 1134-1139, 2007.
SVENSSON R, LARSSON S, GUDOWSKA I, HOLMBERG R, BRAHME A. Design of a fast multi-leaf
collimator for radiobiologically optimized IMRT with scanned beams of photons, electrons and light ions. Med
Phys 34(3). 877-888, 2007.
Books and Reports
1996-2007
BRAHME A. Inverse methods for planning radiation therapy. Europhysics News 27. 206-209, 1996.
SVENSSON R, LIND BK, BRAHME A Danared H. Design of a strong and fast purging magnet of a compact
high energy treatment unit. Manne Siegbahn Lab., Annual Report. 94-96, 1998.
BRAHME A. Radiation Biology. In. Encyclop. of Life Support Systems (EOLSS), Unesco 1999.
SVENSSON R, LIND B, BRAHME A. A compact high energy treatment unit using narrow beam scanning for
photon and electron therapy. Manne Siegbahn laboratory report, 1999.
BELKIC Dz. The principles and methods of quantum scattering with application to interactions of light ions
with tissue; BRAKET - KTH Report 31. 11-18, October 6, 2000.
BELKIC Dz. Resolution enhancement in signal and image reconstructions with applications to MRI, PET,
SPECT and CT; BRAKET - KTH Report 34. 10-14, October 27, 2000.
BRAHME A. Radiation Therapy. In. Encyclop. of Life Support Systems (EOLSS), Unesco 2000.
BRAHME A. Biologically optimized light ion therapy. Report to The Swedish Cancer Society. 2003.
SVENSSON H, RINGBORG U, NÄSLUND I AND BRAHME A. A Nordic center of Excellence for radiation
therapy. Internal report, RI 2003-6.
BELKIC D. Principles of quantum scattering theory. IOPP, Bristol England, 2004.
BELKIC D. Quantum-mechanical signal processing and spectral analysis. IOPP, Bristol England, 2005.
MEIJER AE, EDGREN MR, ERIKSSON BS et al. Possible molecular pathways involved in cell death in human
normal and tumour cells after exposure to carbon ion beams. Implication of TP53, ceramide and AIF. Cancerfonden 2007.
11
Conference contributions
1996
BRAHME A. Dosimetric precision requirements and quantities for characterizing the response of tumors and
normal tissues. In. Radiation Dose in Radiotherapy from Prescription to Delivery, Rio de Janeiro, IAEATECDOC-896. 49-65, 1996
BRAHME A, KALLMAN P, AGREN A. Tumor and normal tissue responses to fractionated non uniform dose
delivery. In. Radiation Dose in Radiotherapy from Prescription to Delivery, Rio de Janeiro, IAEA-TECDOC896. 9-25, 1996
1997
BRAHME A. Development of radiation biology and radiation therapy since the first betatrons. The First
Scandinavian Symp. in Radiation Oncology, Rosendal, Norway. Acta Oncol, 1997
BRAHME A. Towards inverse radiation therapy planning and multidimensional cancer treatment optimization.
Swedish Symp. on Image Analysis, KTH, Stockholm, March, 1997
BRAHME A. Radiobiological dose optimization. Volume & Kinetics in Tumor Control & Normal Tissue
Complication, Madison, Wisconsin, USA, September 10-13, 1997
BRAHME A. Comparison of the clinical properties of low LET treatment modalities. electrons, photons and
protons. World Congr. on Medical Physics and Biomedical Engineering, Nice, September 14-19, 1997
BRAHME A, LIND BK. The importance of biological modelling in intensity modulated radiotherapy
optimization. XIIth ICCR, May 27-30, Salt Lake City, USA, p 5-8, 1997
BRAHME A, LIND BK. New technological developments for radiotherapy equipment. World Congr. on
Medical Physics and Biomedical Engineering, Nice, September 14-19, 1997
CARLSSON A, AHNESJO A. Development of a superposition algorithm for improved scatter dose calculations
in complex geometries. Radiother. Oncol 43 suppl 1. 9, 1997
CARLSSON A, AHNESJO A. Calculation of distributions around a clinical 192Ir-source in the presence of
heterogeneities using scatter dose superposition, XII ICCR p. 119-121, 1997
LIND BK, BRAHME A. The effect on tumor response due to inter-patient variability in sensitivity and clonogen
number. XIIth ICCR, May 27-30, Salt Lake City, USA, p 379-382, 1997
LOF J, LIND BK, BRAHME A. An adaptive feedback algorithm for robust dose delivery in fractionated
radiotherapy. XIIth ICCR, May 27-30, Salt Lake City, USA, p 227-230, 1997
SVENSSON R, LIND BK, BRAHME A. Biologically optimized dose delivery with narrow scanned photon
beams - can the expected clinical outcome be improved by shortening the SSD? XIIth ICCR, May, Salt Lake
City, USA, p 402-405, 1997
1998
BRAHME A. Modern developments in radiotherapy. Fourth Radiation Physics Conference, Alexandria,
November 15-19. 1-17, 1998
KAVER G, LIND BK, LOF J, LIANDER A, BRAHME A. Optimal rad beam profiles in fractionated radiation
therapy considering uncertainties in radiation sensitivity. ESTRO Edinburgh. Radiother. Oncol. 48 Suppl 1.
S124, 1998
LIANDER A, LOF J, KAVER G, LIND BK, BRAHME A. Scanned beam optimization with a preselected
number of beam pulses. ESTRO Edinburgh. Radiother. Oncol. 48 Suppl 1. S98, 1998
LIND B. The response of partially irradiated organs of parallel organization. ESTRO Edinburgh. Radiother.
Oncol. 48 Suppl 1. S95, 1998
LOF J, Lind B, Brahme A. An adaptive control algorithm for optimal dose delivery in the presence of setup
uncertainies and organ motions. Proc. 8th Varian users meeting, Vilamoura Portugal, 1998
LOF J, LIANDER A, KAVER G, LIND BK, BRAHME A. ORBIT - A general object oriented code for
radiotherapy optimization. ESTRO Edinburgh. Radiother. Oncol. 48 Suppl 1.S69, 1998
12
NILSSON B, WESTERMARK M, ARNDT J. Dosimetry in narrow photon and electron beams using
semiconductor detectors. (Abstract). Proc 5th Int Conf. Application of Semiconductors in Nuclear Physicsal
Problems, Riga, May 1998
SVENSSON R, LIND BK, BRAHME A. A new compact treatment unit design for conformal therapy
combining narrow pencil beam scanning and segmental multileaf collimation. ESTRO Edinburgh. Radiother.
Oncol. 48 Suppl 1. S99, 1998
1999
BRAHME A, LIND BK. Approaches to intensity modulated radiation therapy. Patras Medical Physics 99 Conf.,
Patras Greece, Aug 31-Sept 4, 1999
BRAHME A, LIND BK. Radiobiological objectives for treatment optimization. Patras Medical Physics 99
Conf., Patras Greece, Aug 31-Sept 4, 1999
LOF J, LIANDER A, LIND BK, BRAHME A. ORBIT Optimization of radiation therapy beams by iterative
techniques, a new universal object oriented optimization code. Patras Medical Physics 99 Conf, Patras Greece
Aug 31-Sept 4, 1999
MAEHLE-SCHMIDT M, PALMGREN J, LIND B, BRAHME A. A Bayesian sequential model for updating
radio-biological parameters in radiation therapy. In. Second European Conf. on Highly Structured Stochastic
Systems, Pavia, Book of Abstracts. 180-181, 1999
MAVROIDIS P, LIND BK, PROIMOS B, KAPPAS C, BRAHME A. Dosimetric information from films
irradiated in the conformal therapy test phantom of the "Dynarad" project. VI Int. Conf. on Medical Physics,
Patras, Greece 1-4 Sept 1999. Monduzzi Editore S.p.A. - Bologna (Italy). 127-134, 1999
SVENSSON R. A new compact treatment unit design combining narrow pencil beam scanning and segmental
multileaf collimator. 5th Biennal ESTRO Meeting on physics and clinical radiotherapy, Gottingen 7-11 April,
1999
OSTLING J, BRAHME A, DANIELSSON M, IACOBAEUS C, PESKOV V. Amplification and conditioning
pro-perities of GEM and CAT detector for beam monitoring., Proc. Of Intern. Workshop on Micro-pattern
gaseous detectors, Orsay, France , 1999
2000
BELKIC Dz. Fast Padé transform for spectroscopy and collision. Int. Conf. “Many-Particle spectroscopy of
atoms, molecules and surfaces”. Halle Germany. Book of Abstracts. 55-56, July26-29, 2000
BELKIC Dz. Noise reduction technique in generic signals and spectra. Int. Conf. "Many-Particle spectroscopy of
atoms, molecules and surfaces”. Halle, Germany. Book of Abstracts. 75-77, July 26-29, 2000
BELKIC Dz. Fast Pade transform for magnetic resonance imaging. Int. Conf. "Imaging 2000", Stockholm, June
28-July 1, 2000
CARLSSON AK, AHNESJO A. Accounting for heterogeneities and shields in brachytherapy dose calculation
by use of collapsed cone superposition. XIII International Conference on the Use of Computers in Radiation
Therapy. ed W Schlegel, T Bortfeldt (Heidelberg Germany. Springer). 474-476, 2000
GUDOWSKA I, SORCINI B, SVENSSON R. Evaluation of a 50 MV photon therapy beam from a racetrack
microtron Using MCNP4B Monte Carlo code. Accepted for Proc. Monte Carlo 2000 Int. Conf. on Advanced
Monte Carlo for Radiation Physics, Particle Transport Simulation and Applications, October, 2000
IACOBAEUS C, BRAHME, DANIELSSON M, FONTE P, ÖSTLING J, PESKOV V,WALLMARK M: A
novel portal imaging device for advanced radiation therapy. Proceeding of IEEE NSS-MIC, Submitted to IEEE
Transactions on Nuclerar Science, Lyon 2000.
LIND B, BRAHME A. A generalized normalized dose response gradient. ESTRO, Istanbul Turkey, 2000
MAEHLE-SCHMIDT M, PALMGREN J, LIND B, BRAHME A. A Bayesian approach for sequentially
improving the accuracy of radiobiological models used in radiation therapy. Proc. XXth Int. Biometric Conf.,
University of California at Berkely, Vol. I, 2000
MAVROIDIS P, THEODOROU K, LEFKOPOULOS D, SCHLIENGER M, LIND B, KAPPAS C. Extraction
of biological parameters for AVM stereotactic radiotherapy treatment. IOMP, Chicago, 2000
PERSSON L, LIND B, EDGREN M, BRAHME A. RBE of 50 MV brehmsstrahlung beams measured in vivo by
clonogenic cell survival technique. ESTRO, Istanbul Turkey, 2000
13
RUSSELL KR, AHNESJO A, CARLSSON AK. Derivation of dosimetry data for brachytherapy sources using
Monte Carlo for primary and scatter dose separation XIII Int. Conf. on the Use of Computers in Radiation
Therapy. ed W Schlegel, T Bortfeldt (Heidelberg. Springer). 495-497, 2000
SKOLD K, KIERKEGAARD J, GUDOWSKA I, HAKANSSON R, CAPALA J. The Swedish facility for boron
neutron capture therapy, accepted for Proc. "Ninth Int. Symposium on Neutron Therapy for Cancer", Osaka,
Japan October 2-6, 2000
WALLMARK M, BRAHME A, DANIELSSON M, IACOBAEUS C, FONTE P, PESKOV V OSTLING J.
Operating range of a gas electron mulitplier for portal imaging. Submitted to Nucl. Instr. and Meth. in Physics
Research A via the conference Imaging 2000, Stockholm, 2000
WALLMARK M, BRAHME A, DANIELSSON M, IACOBAEUS C, FONTE P, OSLING J, PESKOV V.
Study of a new planar gaseous detector for EPI and other high radiation rate applications", Abstract Book of the
6th International Workshop on Electronic Portal Imaging, EPI2K, No 82 poster, Brussels Belgium, 2000
WESTERMARK M, NILSSON B, ARNDT J. Influence of detector characteristics on measured dose profiles
nad output factors. 5th Biennieal Meeting on Physics for clinical radiotherapy. Gottingen April 8-11, 2000
OSTLING J, WALLMARK M, BRAHME A, DANIELSSON M, IACOBAEUS C, FONTE P, PESKOV V.
Novel detector for portal imaging in radiation therapy. Proc. of SPIE's Medical Imaging 2000, Vol 3977, San
Diego USA, 2000
OSTLING J, WALLMARK M, BRAHME A, DANIELSSON M, IACOBAEUS C, PESKOV V. A novel portal
imaging device for advanced radiation beam therapy, Abstract Book of the 6th International Workshop on
Electronic Portal Imaging, EPI2K, No 63 oral, Brussels Belgium, 2000
2001
GUDOWSKA I, SOBOLEVSKY N. Neutron production in tissue during radiotherapy with high energy photon
and ion beams. Neutron Spectrometry and Dosimetry. Experimental Techniques and MC calculations workshop,
Italian Institute of Culture, Stockholm, Sweden, 18-20 October, 2001
PERIALE L, PESKOV V, CARLSSON P, IACOBAEUS C, FRANKE T, PAVLOPOULUS N,
PIETROPAOLO F, SOKOLOVA T. Evaluation of various planar gaseous detectors with CsI photo cathodes for
the detection of primary scintillation light from noble gases, Proc. of The first Topical Symposium on
Functional Breast Imaging with Advanced Detectors, Rome, 2001
PERSSON L M, LIND B K, EDGREN M R and BRAHME A. Clonogenic survival for two human glioma cell
lines (M059/K) after exposure to low and high LET radiation. 1st ESTRO workshop on biology in radiation
oncology, Fuglsö, Denmark, 10-12 June 2001. Abstract printed in Radiotherapy and Oncology Vol 60 Suppl. 2,
July 2001, p S5
PESKOV V, FONTE P, DANIELSSON M, IACOBAEUS C, OSTLING J, WALLMARK M. Fundamentals of
Gas Micropattern Detectors. Laboratorio De Instrumentacao E Fisica Experimental De Particulas, Preprint
LIP/01-05, Coimbra, Portugal, 2001
OSTLING J. Development of a novel portal imaging device. Workshop on Dosimetry with Electronic Portal
Imaging Devices, 13 March 2001, Uppsala University, 2001
2002
ADAMUS-GÓRKA M, MAVROIDIS P, LIND BK, BRAHME A. Comparison of normal tissue damage models
for radiobiologically optimized radiation therapy. 21st ESTRO meeting, Radiother Oncol Vol 64 Suppl 1.S200,
2002.
AL-ABANY M, HELGASON A, AGREN A, LIND B, MAVROIDIS P, WERSÄLL P, QVANTA E,
STEINECK G. Anal sphincter dose and faecal leakage after radiotherapy for prostate cancer. 21st ESTRO
meeting, Radiother Oncol 64 Suppl 1.S282, 2002.
BRAHME A. The development of radiation therapy. from IMRT to radiobiologically optimized adaptive ion
therapy. Boston, May 2002
BRAHME A, LIND BK. Development of a center for light ion therapy and accurate tumor diagnostics at
Karolinska Institutet and Hospital. Proc Int Nucl Phys Conf 2001, Berkeley Ca. Eds. Norman E et al. AIP Conf
Proc 610 315-319, 2002.
CEDERVALL B, WEINER R. Radioprotection of plants and animals. What are the issues? 2002 Annual
Meeting of the American Nuclear Society. Transactions, TANSAO, Vol. 86 82-83, 2002.
14
EDGREN MR, PERSSON LM, LIND BK. Dna-PK-dependency for the sensitivity to different types of DNA
damage. Radiother Oncol 64 Suppl 1.S309, 2002.
ERIKSSON Å, JERNBERG A, EDGREN MR, HEIDEN T, NILSSON A, LEWENSOHN R, BRAHME A,
MEIJER AE. High and low LET radiation induce apoptosis in DNA-PKcs deficient and proficient human glioma
cells. AACR 93 annual meeting, San Fransico, 2002.
ERIKSSON Å, HEDLÖF I, JERNBERG A, PERSSON LM, EDGREN MR, HEIDEN T, NILSSON A,
LEWENSOHN R, BRAHME A, MEIJER AE, DNA-dependent protein kinase is not important in the response
to low nor high LET radiation induced apoptosis. 32th Annual of the European Society for Radiation Biology
(ESRB), Belgium 2002.
HOLLMARK M, KIMSTRAND P, UHRDIN J, GUDOWSKA I, SOBOLEVSKY N, BELKIC D, ANDREO P,
BRAHME A. Influence of Multiple Scattering and Energy Loss Straggling on the Dose Distribution in Ion
Therapy. 21st ESTRO meeting, Radiother Oncol Vol 64 Suppl 1.S52, 2002.
JERNBERG A, HEIDEN T, LEWENSOHN R, EDGREN, M. Maximum apoptotic response of light ions around
20 ev/nm in p53 wt human melanoma cells/Induction of apoptosis after high LET accelerated boron ions. 32th
Annual Meeting of the European Society for Radiation Biology (ESRB), Belgium, 2002.
LIND B. Objective functions for optimization of intensity modulation and beam orientations. 21st ESTRO
meeting, Radiother Oncol Vol 64 Suppl 1.S10, 2002. invited
MAVROIDIS P, LIND BK, BRAHME A. Biologically effective uniform dose for appropriate dose prescription
and treatment plan comparison. 21st ESTRO meeting, Radiother Oncol 64 Suppl 1.S224, 2002.
NILSSON J, LIND BK, BRAHME A. The response of heterogeneous tumors at low and high ionization
densities. 21st ESTRO meeting, Radiother Oncol 64 Suppl 1.S189, 2002.
PERSSON LM, LIND BK, HEDLÖF I, EDGREN MR. Low-dose hypersensitivity might be dependent on cell
size selection criteria. 21st ESTRO meeting, Radiother Oncol 64 Suppl 1.S311, 2002.
UHRDIN J, LÖF J, BRAHME A. Biologically based stochastic optimized radiation therapy considering internal
organ motions. 21st ESTRO meeting, Radiother Oncol 64 Suppl 1.S225, 2002.
ZAPOTOCZNA A, SVENSSON R. Optimized scanned beam dose delivery, real time dose monitoring and
treatment verification in radiation therapy. 21st ESTRO meeting, Radiother Oncol 64 Suppl 1.S205, 2002.
ÖSTLING J, BRAHME A, DANIELSSON M, FRANCKE T, IACOBAEU CS, PESKOV V. Study of hole-type
gas multiplication structures for portal imaging and other high counting rate applications, CR at IEEE NSS/MIC
2002 conference, Norfolk USA, 2002.
2003
ADAMUS-GÓRKA M, MAVROIDIS P, LIND BK, BRAHME A. Normal tissue damage models with particular
attention on the volume dependence. 2nd ESTRO Workshop Biol in Rad Onc, 2003.
ADAMUS-GÓRKA M, LIND BK, BRAHME A. Comparing the radiosensitivity of cervical and thoracic spinal
cord using the relative seriality model. 12th Intern. Congress of Radiation Research (ICRR), Brisbane, 2003.
ADAMUS-GÓRKA M LIND BK, BRAHME A. Monte Carlo determination of single event spectra for betaemitters bound to cell surfaces. World Congress on Medical Physics and Biomedical Engineering, Sydney, 2003.
BELKIC Dz, BELKIC K. Surveillance spectroscopic imaging within molecular imaging in tumour diagnostics,
Symp. Dept. Onc. Path. Karolinska Institute Challenges in cancer therapy. from experimental models to man,
Book of Abstracts, pp 1-3, Stockholm March 6-7, 2003.
BELKIC Dz. Fast Pade transform (FPT) as opposed to conventional fitting for signal and image processing, Int.
Conf. Imaging 2003, Book of Abstracts, Stockholm June 24-27, 2003.
BELKIC Dz. Reduction of long to short time signals with no loss of information in a given bandwidth, Int. Conf.
Imaging 2003, Book of Abstracts, Stockholm, June 24-27, 2003.
BELKIC Dz. Spectroscopic positron emission tomography (sPET) for monitoring radiation therapy, Int. Conf.
Imaging 2003, Book of Abstracts, Stockholm June 24-27, 2003.
BELKIC Dz, BELKIC K. Quantum-mechanical resonant scattering for signal processing in medical physics.
Proc. XXIII ICPEAC, Stockholm . Abstract of contributed paper, Mo202, Eds J Anton et al., 2003
15
BELKIC Dz. Double electron detachment in [H+] - [H-] collisions. Proc. XXIII ICPEAC, Stockholm, 2003.
Abstract of contributed paper, Mo138, Eds J Anton et al.
BELKIC Dz. High-resolution parametric estimation of two-dimensional magnetic resonance spectroscopy. 20th
Annual Meeting of European Soc. Magn. Res. Med. Biol. (ESMRMB), Abstract No. 365 (CD) Rotterdam, 2003.
BELKIC Dz. Reduction of long to short free induction decays with no loss of information. 20th Annual Meeting
of European Soc. Magn. Res. Med. Biol. (ESMRMB), Abstract No. 396 (CD), Rotterdam 2003.
BELKIC Dz, BELKIC K. High-resolution magnetic resonance imaging (MRI). IEEE Medical Imaging
Conference (MIC), Abstract No 1971 (CD), Portland Oregon, 2003.
BELKIC K, BELKIC Dz. The fast Pade transform (FPT) for magnetic resonance spectroscopic imaging (MRSI)
in oncology. IEEE Medical Imaging Conference (MIC), Abstract Number 1918 (CD), Portland Oregon, 2003.
CEDERVALL B. Perspective on electromagnetic fields as potential genotoxic risk - where are we today?
STUK-A195, (W. Paile, Ed.) Radiation Protection in the 2000s - Theory and Practice, Nordic Society for
Radiation Protection, Proceedings of the XII ordinary Meeting, 222-225, June 2003.
EDGREN MR, PERSSON L, JERNBERG A, GLÖCKNER C, ERIKSSON B, MEIJER AE, HOLGERSSON Å,
LEWENSOHN R, BRAHME A. Biological effects of accelerated nitrogen ions in the two human glioma cell
lines M059J and M059K. TSL Workshop on Applications, Uppsala, 2003.
FERREIRA DA COSTA B, SVENSSON R, BRAHME A, LIND B, JOHANSSON J. Radiobiologically
optimized intensity modulated radiation therapy for early breast cancer. World Congress on Medical Physics and
Biomedical Engineering, Sydney, 2003.
FERREIRA DA COSTA B, SVENSSON R, BRAHME A, LIND B, JOHANSSON J. Radiobiologically
optimized intensity modulated radiation therapy for early breast cancer. 7th Biennial ESTRO Meeting on Physics
and Radiation Technology for clinical radiotherapy, Geneva 2003.
GUDOWSKA I. PET radionuclei production in tissue by light ions – Monte Carlo evaluation. 1st Nordic meeting
on Light Ion and Advanced Rad Therapy, Stockholm, 2003.
GUDOWSKKA, I, ANDREO P, SOBOLEVSKY N, BELKIC D. Monte Carlo simulations of light ion dose
distribution in tissue-like media. Int Conf Current Achievements in Oncology, Poznan, 2003. Reports of
Practical Onc and Radiother, Journal of the Polish Soc of Rad Onc, Vol 8 (2), 2003.
IACOBAEUS C, DANIELSSON M, FRANCKE T, OSTLING J, PESKOV V. Study of capillary-based
detectors. CR at IEEE NSS/MIC 2003, Portland Oregon, 2003.
IACOBAEUS C, DANIELSSON M, FRANCKE T, OSTLING J, PESKOV V. Capillary-based gaseous
detectors for imaging UV photons. Submitted to NIM A for the conference Imaging 2003.
MEIJER AE, JERNBERG A, PERSSON LM, HEIDEN T, TILLY N, LIND BK, STENERLÖF B, EDGREN
MR, BRAHME A. Light ions in radiation therapy-studies on the effects of boron ions on a human tumour cell
line. TSL Workshop on Applications, Uppsala , 2003.
MEIJER AE, JERNBERG ARM, PERSSON LM, CEDERVALL B, EDGREN MR, Is it possible to correlate the
apoptotic response to the clonogenic cell survival after exposure to high and low LET radiation? 12th Intern.
Congress of Radiation Research (ICRR), Brisbane, 2003.
QATARNEH SM, NOZ ME, LIND B, BRAHME A. A whole body atlas database for radiation therapy planning
and optimization. World Congress on Medical Physics and Biomedical Engineering, Sydney, 2003
SIDDIQI M, BRAHME A, LIND BK, UHRDIN J. Fractionation effects in radiation therapy optimization. 2nd
ESTRO Workshop on Biology in Radiation Oncology, Berg en Dal/Nijmegen, 2003
OSTLING J, BRAHME A, DANIELSSON M, IACOBAEUS C, PESKOV V. First images with a new portal
imaging device. Submitted to NIM A for the conference Imaging 2003.
2004
BRAHME A. Development of radiobiologically based therapy optimization and target definition. 4th Int Symp
on the Lymphatic System – New developments in oncology and IMRT. Limburg. Ed Kiricuta, p155, 2004.
BRAHME A. Biological modelling for 3-dimensional in vivo predictive assay based adaptive radiation therapy
(BioArt). ESTRO 23 Amsterdam The Netherlands. Radiotherapy Oncology. 73 Suppl 1 S62, 2004.
16
COSTA FERREIRA B, MAVROIDIS P, SVENSSON R, LIND BK, BRAHME A. The influence of patient
radiosensivity on biological treatment plan optimization for early breast cancer with positive lymph nodes.
ESTRO 23 Amsterdam The Netherlands. Radiotherapy Oncology. 73 Suppl 1 S249, 2004.
EDGREN RM, MEIJER AE, JERNBERG AR-M. Decreased difference in radiosensitivity between different
human cell lines after exposure to high LET radiation. Central Eur J of Occupational and Environmental
Medicine. 10 S51, 2004.
GUDOWSKA I, SOBOLEVSKY I. Secondary particle production from heavy-ion interactions in shielding
materials of interest for space missions. 3rd Int Workshop on Space Rad Research, Long Island, 2004
GUDOWSKA I, SOBOLEVSKY N. Simulation of secondary particle production and absorbed dose to tissue in
light ion beams. Tenth International Conference on Radiation Shielding (ICRS-10) and Thirteenth Topical
Meeting on Radiation Protection and Shielding, Madeira Portugal, 2004.
GUDOWSKA I, SOBOLEVSKY N. Secondary particle production from heavy-ion interactions in shielding
materials of interest for space missions; comparison of Monte Carlo simulations using SHIELD-HIT with the
experimental data. The 3rd International Workshop on Space Radiation Research, Port Jeffersson, Long Island
USA, May 16-20, 2004
GUDOWSKA I, Accuracy of the Bragg peak position in light ion therapy – Monte Carlo simulations using
SHIELD-HIT. ESTRO 23 Amsterdam The Netherlands. Radiotherapy Oncology. 73 Suppl 1 S321, 2004.
GUDOWSKA I, IVANCHENKO VN, LARSSON S, SORCINI B. Radiation Transport Calculations for Beam
Therapy with Geant4 Toolkit. The 2004 Nuclear Science Symposium, Rome Italy, October 16-22, 2004.
GUDOWSKA I. Energy distribution of primary and secondary particles in light ion beams – MC simulations
with SHIELD-HIT. Mini workshop Current Trends in Nanodosimetry and Track Structure Calculations,
Karolinska Institutet, Nobel Forum, Stockholm, December 2-3, 2004.
HEILBRONN L, NAKAMURA T, IWATA Y, KUROSAWA T, GUDOWSKA I, SOBOLEVSKY N, IWASE
H, TOWNSEND LW. Overview of secondary neutron production relevant to shielding in space. Tenth Int.Conf.
Radiation Shielding (ICRS-10) and Thirteenth Topical Meeting on Radiation Protection and Shielding (RPS2004), Madeira Island (Portugal), May 9-14, 2004.
HOLLMARK M, GUDOWSKA I, BELKIC DZ, BRAHME A. Fast semi-analytical algorithm for pencil beam
dose distributions in ion therapy. ESTRO 23 Amsterdam The Netherlands, Radiotherapy Oncology. 73 Suppl
1S319, 2004.
JANEK S, SVENSSON R, GUDOWSKA I, BRAHME A. In vivo PET-CT-imaging of the delivered 3D-dose
distribution for adaptive radiobiological optimized photon beam therapy. ESTRO 23 Amsterdam The
Netherlands. Radiotherapy Oncology. 73 Suppl 1 S223, 2004.
KEMPE J, BRAHME A, GUDOWSKA I, HOLLMARK M. Depth dose distribution of 7Li-ions in tissue-like
media. ESTRO 23 Amsterdam The Netherlands. Radiotherapy Oncology. 73 Suppl 1 S320., 2004.
KIRICUTA IC, QATARNEH SM, BRAHME A. Normal head and neck lymph nodes topography based on the
dataset on the visible human. 4th Int Symp on the Lymphatic System – New developments in oncology and
IMRT. Limburg. Ed Kiricuta, p87, 2004.
KIRICUTA IC, QATARNEH SM, BRAHME A. Topography of the lymphatic of the breast based on the visible
human dataset. 4th Int Symp on the Lymphatic System – New developments in oncology and IMRT. Limburg.
Ed Kiricuta, p97, 2004.
KIRICUTA IC, QATARNEH SM, BRAHME A. Evaluation of normal mesorectal lymph nodes based on the
dataset on the visible human. 4th Int Symp on the Lymphatic System – New developments in oncology and
IMRT. Limburg. Ed Kiricuta, p125, 2004.
KIRICUTA IC, QATARNEH SM, BRAHME A. Pelvic lymph nodes topography based on the dataset on the
visible human male. 4th Int Symp on the Lymphatic System – New developments in oncology and IMRT.
Limburg. Ed Kiricuta, p139, 2004.
KIRICUTA CI, QATARNEH SM, BRAHME A. The 3D model of the neck lymphatics. ESTRO 23 Amsterdam
The Netherlands. Radiotherapy Oncology. 73 Suppl 1 S18, 2004.
LARSSON S, SVENSSON R, GUDOWSKA I, IVANCHENKO V, BRAHME A. Radiation transport
calculations for 50 MV photon therapy beam using the Monte Carlo code GEANT4. 10th Intern. Conf on
Radiation shielding and 13th Topical Meeting on Radiation Protection and Shielding, Funchal, 2004.
17
LARSSON S, SVENSSON R, GUDOWSKA I, IVANCHENKO V, ANDREASSEN A, BRAHME A. Radiation
transport calculations for narrow scanned photon beam therapy using the Monte Carlo code GEANT4. 10th
Intern. Conf on Radiation shielding and 13th Topical Meeting on Radiation Protection and Shielding, Funchal,
2004.
LARSSON S, SVENSSON R, GUDOWSKA I, IVANCHENKO V, BRAHME A. Simulation and validation of
photon beam therapy. GEANT4 workshop, Catania Sicily Italy, 2004.
MAVROIDIS P, LAURELL G, THEODOROU K, FERNBERG JO, LEFKOPOULOS D, KAPPAS C, LIND
BK, BRAHME A. Clinical verification of derived dose-response parameters for AVM obliteration and esophageal stricture using statistical methods. ESTRO 23 Amsterdam The Netherlands. Radiotherapy Oncology. 73
Suppl 1 S367, 2004.
QATARNEH SM, KIRICUTA IC, BRAHME A, LIND BK. 3D atlas on lymph node topography based on the
visible human dataset. 4th Int Symp on the Lymphatic System – New developments in oncology and IMRT.
Limburg. Ed Kiricuta, p59, 2004.
QATARNEH S.M., KIRICUTA I.C., BRAHME A, LIND B.K., “3D Atlas on lymph node topography based on
the Visible Human Dataset”. Proceedings of ASTRO 46th Annual Meeting, American Society for Therapeutic
Radiology and Oncology, 2004.
QATARNEH SM, KIRICUTA IC, BRAHME A, LIND BK. 3D Atlas topography of the lymph nodes based on
the visible human dataset. ESTRO 23 Amsterdam The Netherlands. Radiotherapy Oncology. 73 Suppl 1.S440,
2004.
SIDDIQI M, LIND BK, BRAHME A. Optimal dose fractionation of lung cancer using biologically optimized
IMRT. ESTRO 23 Amsterdam The Netherlands. Radiotherapy Oncology. 73 Suppl 1S235, 2004.
SVENSSON H, RINGBORG U, NÄSLUND I AND BRAHME A. Development of light ion therapy at the
Karolinska Hospital and Institute. ESTRO 23. Radiotherapy Oncology. 73 Suppl 2 206-210, 2004
TSOUGOS I, MAVROIDIS P, RAJALA J, JÄRVENPÄÄ R, THEODOROU K, HYÖDYNMAA S,
PITKÄNEN MA, HOLLI K, LIND BK, KAPPAS C. Is NTCP modelling really useful for the prediction of
radiation induced pneumonitis? Dose-response parameters from breast radiotherapy. ESTRO 23 Amsterdam The
Netherlands Radiotherapy Oncology., 73 Suppl 1 S53, 2004.
UHRDIN J, JANEK S, SVENSSON R. 3D dose distribution in tissue calculated based on PET-CT imaging for
high energy scanned photon therapy. ESTRO 23 Amsterdam The Netherlands. Radiotherapy Oncology. 73
Suppl 1 232, 2004.
2005
ADAMUS-GORKA M, LIND B, BRAHME A. Influence of the effective size of the functional subunit (FSU)
on rat spinal cord paralysis. ESTRO Lisboa Portugal. Radiotherapy Oncology: 76 Suppl 2 S24, 2005.
ANDREASSEN B, SVENSSON R, DANARED H, BRAHME A. Development of a scanning system for intensity modulated radiation therapy with photon pencil beams. ESTRO Lisboa Portugal. Radiotherapy Oncology.
76 Suppl 2 S106, 2005.
GÓRKA B, NILSSON B, SVENSSON R, FERNÁNDEZ-VAREA J M, BRAHME A. Monte Carlo study of the
fluence perturbation in CVD diamond detector due to electric contacts. ESTRO Lisboa Portugal. Radiotherapy
Oncology. 76 Suppl 2 S204, 2005.
GUDOWSKA I, HOLLMARK M, GARELLI E. Three-dimensional distribution of absorbed dose in therapeutic
light ion beams. 10th workshop on Heavy Charged Particles in Biology and Medicine (HCPBM) and 4th
meeting of the European Network ENLIGHT, Oropa Italy, Book of Abstracts pp 202-207, 2005.
GUDOWSKA I, BAGULYA A, IVANCHENKO V, STARKOV N. Simulation of light ion transport in a water
phantom using Geant4. 10th User Conf and Collab workshop. Bordeaux France. Book of Abstracts pp. 28-29,
2005.
GUDOWSKA I., KEMPE J, SOBOLEVSKY N. Low- and high LET dose components of primary and secondary particles in the therapeutic light ion beam. 14th Int Symp on Microdosimetry (MICROS) Venezia Italy.
Book of Abstracts A12, 2005.
KEMPE J, GUDOWSKA I, BRAHME A. Depth dose and LET distributions of 1H, 7Li and 12C ions for
radiation therapy. 10th workshop on Heavy Charged Particles in Biology and Medicine (HCPBM) and 4th
meeting of the European Network ENLIGHT, Oropa Italy. Book of Abstracts pp 160-169, 2005
18
KEMPE J, GUDOWSKA I, SOBOLEVSKY N, BRAHME A. Fluence, Energy Fluence and Absorbed Dose in
therapeutic light ion beams. ESTRO Lisboa Portugal. Radiotherapy Oncology. 76 Suppl 2 S62, 2005.
MEIJER AE. From damage to apoptotic signalling in response to different radaition qualities. 10th workshop on
Heavy Charged Particles in Biology and Medicine (HCPBM) and 4th meeting of the European Network
ENLIGHT, Oropa Italy. Book of Abstracts pp 10-14, 2005.
MAVROIDIS P, al-ABANY M, HELGASON AR, ÅGREN- CRONQVIST A-K, WESÄLL P, LIND H,
QVANTA E, KAPPAS C, LIND BK, STEINECK G, BRAHME A. Dose-response relations for faecal leakage
and blood or phlegm in stools related to anal sphincter irradiation from prostate cancer radiotherapy. ESTRO
Lisboa Portugal. Radiotherapy Oncology. 76 Suppl S22, 2005.
MAVROIDIS P, COSTA FERREIRA B, SVENSSON R, THEODOROU K, LIND B, BRAHME A. Quantification of differencesbetween planned and delivered IMRT dose distributions in terms of complication-free tumor
cure. ESTRO Lisboa Portugal. Radiotherapy Oncology. 76 Suppl 2 S98, 2005.
MAVROIDIS P, TSOUGOS I, HYÖDYNMAA S, PAPANIKOLAOU N, AXELSSON S, RAJALA J,
PITKÄNEN MA, LIND BK, KAPPAS C, BRAHME A. The effects of breathing and setup uncertainties on the
prediction of radiation pneumonitis from breast cancer radiotherapy. ESTRO Lisboa Portugal. Radiotherapy
Oncology. 76 Suppl 2 S157, 2005.
MAVROIDIS P, TSOUGOS I, RAJALA J, THEODOROU K, JÄRVENPÄÄ R, PITKÄNEN MA, HOLLI K,
OJALA AT, LIND BK, HYÖDYNMAA S, KAPPAS C . Clinical evaluation of dose-response models and
parameter sets predicting radiation induced pneumonitis from breast cancer radiotherapy. ESTRO Lisboa
Portugal. Radiotherapy Oncology. 76 Suppl 2 S70, 2005.
TOMA-DASU I, DASU A, BRAHME A. Simulation of the effect of acute tumour hypoxia on treatment outcome (oral). Seventh Int Conf on Dose, Time and Fractionation in Radiation Oncology, Madison Wisconsin,
2005.
WALIGORSKI MPR, HOLLMARK M, MULTAN M, LESIAK J. A simple track structure model of ion bem
radiotherapy. 14th Int Symp on Microdosimetry (MICROS). Venezia Italia. Book of abstracts Oral pres, 2005
WIKLUND K, LIND B K, BRAHME A. Radial secondary dose profiles from light ion beams in water calculated with a semi-analytical pencil beam method. 14th Int Symp on Microdosimetry (MICROS) Venezia Italy.
Book of abstracts A20, 2005.
ZAPOTOCZNA A, FERREIRA BC SVENSSON R, BRAHME A. Influence of number of multileaf collimator
segments and beam portals on the treatment outcome in radiobiologically optimized radiation therapy. ESTRO
Lisboa Portugal. Radiotherapy Oncology. 76 Suppl 2 S173, 2005.
2006
BRAHME A, KEMPE J, LARSSON S, ANDEASSEN B, HOLMBERG R. Application of GEANT 4 in biological treatment planning. NIRS-MedAustron Joint Symposium on Carbon Ion Therapy in Cancer, Medical
University of Innsbruck Austria, 2006.
BRAHME A. Bioart – Radioresistance imaging and treatment optimization. ESTRO 25 Leipzig Germany,
Radiotherapy and Oncology. 81 Suppl 1 S276, 2006.
DASU I, DASU A, BRAHME A. Quantifying tumour hypoxia from PET for the biological optimised treatment
planning. ESTRO 25 Leipzig Germany, Radiotherapy and Oncology. 81 Suppl 1 S247, 2006.
EDGREN MR, KIM W-C, ERIKSSON BS, MEIJER AE. Apoptotic and cell cycle responses following exposures to different LET of boron and nitrogen ions. Joint meeting in Radiation Biology and Radioecology,
Marstrand Sweden, Book of Abstracts 2006.
ERIKSSON BS, MEIJER AE, JERNBERG AR-M, EDGREN MR. The radiosensitivity differences among
different human cell lines disappear after exposure to high LET radiation. Joint meeting in Radiation Biology
and Radioecology, Marstrand Sweden, Book of Abstracts 2006.
GUDOWSKA I, KOPEC M. Absorbed and effective doses in tissues evaluated for human phantom irradiated
with heavy chatged ion beams. ESTRO 25 Leipzig Germany, Radiotherapy and Oncology. 81 Suppl 1 S356,
2006.
HATZILOANNOU K, KOMISOPOULOS K, MISAILIDOU M, PLATANIOTIS P,LIND B, MAVROIDIS M.
Statistical methods for determination and validation of does-response relations from clinical patient datasets.
ESTRO 25 Leipzig Germany, Radiotherapy and Oncology. 81 Suppl 1 S415, 2006.
19
JERNBERG AR-M, ERIKSSON BS, LIND BK, MEIJER AE, EDGREN MR. Synergistic effects in cell
survival after combined high and low LET radiation exposure in two human tumour cell lines. Joint meeting in
Radiation Biology and Radioecology, Marstrand Sweden, Book of Abstracts 2006.
KEMPE J, BRAHME A. Simple analytical approaches on light ion fragmentation in matter. Department of
Mathematical Sciences, Chalmers Göteborg University, 2006.
KEMPE J, LIND B, BRAHME A. Comparsion of MonteCarlo and analytical models for light ion secondary
particle production. ESTRO 25 Leipzig Germany, Radiotherapy and Oncology. 81 Suppl 1 S359, 2006.
KIRICUTA C, QATARNEH S, BRAHME A. Reconstruction of the human visible Lymph nodes. ESTRO 25
Leipzig Germany, Radiotherapy and Oncology. 81 Suppl 1 S494, 2006.
KOMISOPOULOS G, AL-ABANY M, PLATANIOTIS G, HELGASON A, AGREN CRONQVIST A.K,
WERSÄLL R, LIND B, STEINECK G, MAVROIDIS P. Comparsion of Dose_response Relations of Anal
Sphincter and anal Canal ragarding the radiation effects of farcal leakage and blood or phlegm in stools from
prostate cancer radiotherapy. ESTRO 25 Leipzig Germany, Radiotherapy and Oncology. 81 Suppl 1 S441, 2006.
MAVROIDIS P, COSTA FERREIRA F, SHI S, PENAGARICANO P, LIND BK, PAPANIKOLAOU P.
Comparison of dose distributions from tomotherapy and imrt treatment plsns using the biologically effective
uniform dose. ESTRO 25 Leipzig Germany, Radiotherapy and Oncology. 81 Suppl 1 S1245, 2006.
MEIJER AE, ERIKSSON BS, JERNBERG AR-M, EDGREN MR. From damage to cell death – Is the gene
status of the exposed cell crucial after exposure to high LET radiation? Joint meeting in Radiation Biology and
Radioecology, Marstrand Sweden. Book of Abstracts 2006.
PLATANIOTIS G, MAVROIDIS P, ADAMUS GORKA M, HYODYNMAA S, LIND BK. Comparison of the
Dose-Mass-Histogram (DMH) and Dose-Volume histogram (DVH) concepts in predicting radiation induced
pneumonitis from breast cancer radiotherapy. ESTRO 25 Leipzig Germany, Radiotherapy and Oncology. 81
Suppl 1 S281, 2006.
TOMA-DASU I, DASU A. Estimation of carcinogenesis risk following radiotherapy - dose-effect models (oral).
Joint meeting in Radiation Biology, for the Netherlands Radiobiological Society, the Association for Radiation
Research in UK and the Swedish Radiobiology Society, Marstrand Sweden, 2006.
TOMA-DASU I, DASU A. Estimation of carcinogenesis risk following radiotherapy – relationship to survival
parameters. ESTRO 25 Leipzig Germany, Radiotherapy and Oncology. 81 Suppl 1 S136, 2006.
WIKLUND K, BRAHME A, LIND K. Energy Depositions on the nanometer scale from low energy electrons.
ESTRO 25 Leipzig Germany, Radiotherapy and Oncology. 81 Suppl 1 S510, 2006.
2007
ANDREASSEN B. Development of a center with multiple simultaneous treatments for the Karolinska university
hospital in Stockholm. Gantry Workshop Wien, 2007.
Research Center for Radiation Therapy
Department of Oncology-Pathology, Karolinska Institutet