Download A Single Institution`s Experience In Developing A

UNIVERSITY OF WISCONSIN-LA CROSSE
Graduate Studies
A SINGLE INSTITUTION’S EXPERIENCE IN DEVELOPING A PURPOSEFUL AND
EFFICIENT OFF-LINE TECHNIQUE FOR ADAPTIVE RADIOTHERAPY IN A CLINICAL
ENVIRONMENT
A Research Project Report Submitted in Partial Fulfillment of the Requirements for the Degree
of Master of Science in Medical Dosimetry
Charles E. Poole, CMD, B.S.
College of Science & Health
Medical Dosimetry Program
August, 2012
2
A SINGLE INSTITUTION’S EXPERIENCE IN DEVELOPING A PURPOSEFUL AND
EFFICIENT OFF-LINE TECHNIQUE FOR ADAPTIVE RADIOTHERAPY IN A CLINICAL
ENVIRONMENT
By Charles E. Poole, CMD, B.S.
We recommend acceptance of this project report in partial fulfillment of the candidate's
requirements for the degree of Master of Science in Medical Dosimetry
The candidate has met all of the project completion requirements.
Nishele Lenards, M.S.
Graduate Program Director
Date
3
The Graduate School
University of Wisconsin-La Crosse
La Crosse, WI
Author:
Poole, Charles E.
Title:
A Single Institution’s Experience in Developing a Purposeful and
Efficient Off-line Technique For Adaptive Radiotherapy in a Clinical
Environment
Graduate Degree/ Major: MS Medical Dosimetry
Research Advisor:
Nishele Lenards, M.S.
Month/Year:
August, 2012
Number of Pages:
Style Manual Used: AMA, 10th edition
Abstract
Adaptive Radiotherapy (ART) strategies evolved from advances in Image-Guided
Radiation Therapy (IGRT) technologies. The purpose of this study is to develop a purposeful and
efficient technique to adapt a patient’s radiation therapy (RT) plan utilizing a computed
tomography on rails (CTOR) image guidance system and to describe the experiences
incorporating this technique into a single institution’s clinical environment. Adapting a patients’
course of RT may be necessary because of tumor growth or regression, biological changes in
anatomy or tumor volume and positional or localization changes observed in patients.
This study was a retrospective review of nine patients treated for lung carcinoma
comparing CTOR data sets to the initial planning CT data sets from the 10th, 20th, and 30th
fractions of RT. Tumor volumes, dose changes, and coverage from CTOR data sets compared
against initial CT data sets were analyzed and a percent deviation was used to report these
changes. Adaptation of the initial RT plan to reflect these changes provided a precise RT plan
and avoided any potential overdosing or under dosing of target volumes. ART will continue to
benefit the patient and improve their overall survival as the field of radiation oncology continues
to adapt to rapidly changing technology.
4
The Graduate School
University of Wisconsin - La Crosse
La Crosse, WI
Acknowledgments
I would like to thank Sicong Li, D.Sc., at the University of Nebraska Medical Center,
Omaha, Nebraska for his contributions in assisting on this study and helping me to further my
education in medical dosimetry.
5
Table of Contents
.................................................................................................................................................... Page
Abstract ............................................................................................................................................3
List of Tables .....................................................................................................................................
List of Figures ....................................................................................................................................
Chapter I: Introduction ....................................................................................................................6
Statement of the Problem .....................................................................................................8
Purpose of the Study ............................................................................................................9
Assumptions of the Study ....................................................................................................9
Definition of Terms..............................................................................................................9
Limitations of the Study………………………………………………………………….12
Methodology ......................................................................................................................13
Chapter II: Literature Review ........................................................................................................14
Chapter III: Methodology ..............................................................................................................28
Sample Selection and Description .....................................................................................28
Instrumentation ..................................................................................................................30
Data Collection Procedures................................................................................................30
Data Analysis .....................................................................................................................30
Limitations .........................................................................................................................31
Summary ............................................................................................................................31
Chapter IV: Results ............................................................................................................................
Item Analysis ........................................................................................................................
Chapter V: Discussion .......................................................................................................................
Limitations .............................................................................................................................
Conclusions ............................................................................................................................
Recommendations ..................................................................................................................
References ......................................................................................................................................32
6
Chapter I: Introduction
Adaptive Radiotherapy (ART) is an emerging technique that has been incorporated into
many clinical radiotherapy applications. Due to the advances in radiation therapy (RT) planning
and treatment delivery techniques, the field of radiation oncology has advanced as new
multimodality imaging techniques have been developed and incorporated into RT treatment
delivery.1 Innovations in computed tomography (CT), magnetic resonance imaging (MRI), and
positron emission tomography (PET) have made tumor volumes easier to delineate and nearby
critical structures identifiable.1 The goal of RT is to irradiate the tumor volume while minimizing
radiation to the surrounding critical structures. With better tumor volume and critical structure
delineation, RT techniques enable dose to be escalated to tumor volumes.2 The advancements of
three-dimensional conformal radiation therapy (3DCRT), intensity modulated radiation therapy
(IMRT), and stereotactic body radiotherapy (SBRT) have paved the way for more precise tumor
delineation and localization methods.3 These highly conformal RT techniques deliver high doses
of radiation to the tumor volume and enable rapid dose falloff near critical structures.4 High
radiation doses and rapid dose falloff have been the driving force behind developing more
accurate imaging for tumor delineation and localization.4 Eliminating the uncertainties in
positioning due to intra- and inter-fractional motion, respiratory motion, and daily tumor volume
changes are needed to prevent a geometric miss and thereby underdosing the tumor volume.2
Image guided radiation therapy (IGRT) technologies enable accurate imaging for tumor
delineation and localization, reduce the uncertainties in tumor and respiratory motions, reduce
daily patient setup errors, and allow for accurate dose escalation to the tumor volume.1 IGRT
technologies combine the developments and innovations made in multimodality imaging with
RT treatment planning and delivery.1 IGRT technologies that have had a significant impact over
the last decade include electronic portal imaging devices (EPID), megavoltage (MV) and
kilovoltage (KV) cone beam CT (CBCT), and in treatment room CT scanners.1 The impact of
these technologies facilitates more precise RT planning and delivery to patients by allowing for
daily or weekly adaptations of the treatment plan. The various IGRT technologies can be
classified into a two-dimensional (2D) planar approach such as EPID or a 3D volumetric
approach like (KVCBCT).1 Volumetric 3D IGRT approaches can facilitate online or off-line
corrections to treatment plans to account for any adaptations due to motion or reductions of the
tumor volume.5 IGRT techniques allow for daily adaptations of the RT target volumes within a
7
fraction or between fractionations to account for patient positioning or motion and anatomical or
tumor volume changes by image registration.4
Image registration and fusion of the RT planning images and the daily or weekly IGRT
images are integral components for ART. Image registration and fusion can be used frequently in
treatment planning for tumor localization, treatment delivery, and assessing tumor responses.6
The registering of multiple sets of images requires finding common geometric coordinates, lines
and surfaces, or using an intensity-based grayscale system between the image sets to measure
how they registered.6 The idea behind multiple image registration is to be able to map
information from one set of images to another (set of images) by fusing the image sets together.7
Fusing multiple image sets together helps to delineate tumor volume changes, critical structures,
and tumor volume localization. By using the process of image registration and fusion, ART can
improve RT to limit tumor volume margins, escalate tumor doses, and reduce patient toxicities
during treatment.
The ART technique is a process that incorporates IGRT and image registration and fusion
to adapt a patient’s initial radiation treatment plan by assessing tumor volume changes, tumor
motion, and critical structure changes in response to radiation. This adaptation can be either an
online approach or off-line approach that utilizes various IGRT technologies. If IGRT images are
evaluated before a RT treatment and these images are compared and corrected against a
reference image set, the adaptation is considered to be online.4 The off-line approach to ART is
acquiring multiple IGRT image sets during a small number of RT treatments without
immediately evaluating the image set against a reference image set, but instead adapting the RT
plan after a number of RT treatments.4 The rationale for ART is to adapt the RT plan to the
changes that are observed anatomically either by an online or off-line strategy. Online ART can
provide immediate adjustments to the RT plan by verifying setup accuracy, organ motion, and
tumor volume changes.1 Off-line ART adjustments can be made after several RT treatments
while still verifying setup accuracy, organ motion, and volume changes to the tumor.1 The
difference in the off-line ART strategy is making adjustments for future RT treatments, whereas,
the online ART strategy is making immediate adjustments within a given fraction of treatment.1
The online ART strategies can be interpreted as making intra-fractionation changes to a
treatment plan, whereas, off-line ART strategies imply making inter-fractionation changes to the
plan at certain intervals that may occur over the whole course of the treatment.
8
One of the most prevalent disease sites the strategies of ART has made a difference is in
the treatment of lung cancer. The most important factor in treating lung cancer is the
management of moving tumor volumes and respiratory motion. Geometric uncertainties have a
big impact on the accuracy of treatment planning, imaging, and treatment delivery in lung
cancers.8 The uncertainties stem from respiratory motion, both inter-fractional or intra-fractional
setup errors, and microscopic disease growth that is unseen.8 To account for these geometric
uncertainties larger margins are constructed and irradiated in lung patients.8 Typically, generous
safety margins are incorporated around the target to allow for tumor coverage and ensuring
geometric uncertainties are accounted for.8
The role ART plays in the treatment of lung cancer has evolved with the advancements of
IGRT, IMRT, and four-dimensional (4D) image based motion management.2 With 4D motion
management, respiratory motion of the tumor volume is delineated on multiple CT scans to
acquire a motion encompassing internal target volume (ITV) from the patients breathing cycle.8
The concept of generating an ITV is to capture the gross tumor volume (GTV), clinical target
volume (CTV), and internal motion (IM) of the tumor volume in all phases of the respiratory
cycle. The internal motion takes into account any physiological movements and variations in
size, shape, and position of the tumor volume.9 An additional volume called a planning target
volume (PTV) is expanded from the ITV and this PTV is a representation of all phases of the
patients breathing cycle and it is often used in treatment planning as the volume to be irradiated.
This volume ensures that when the radiation beam is turned on, the radiation will hit the tumor
volume no matter what phase the patients breathing cycle is in. ART strategies play significant
roles in the treatment of lung cancer and the focus of this paper is to develop a method to
incorporate an ART strategy at one institution.
Statement of the Problem
The increasing challenge in radiation therapy is keeping up with the dynamic
technologies. One of these challenges is creating an efficient method of ART using IGRT
technologies. Several studies have been done incorporating IGRT technologies with ART in
patients’ with bladder cancer.(11,14,15) IGRT technologies are being utilized prior to a patients’
daily RT treatment for localization and positioning. The CTOR technology enables tumor
localization and patient positioning daily or even weekly prior to a patients’ radiation treatment.
The soft tissue delineation and the accurate tumor localization components are benefits of the
CTOR technology. However, very few studies have been done incorporating the CTOR
9
technology for the adaptation of lung tumors. Developing an ART strategy utilizing CTOR
technology periodically to monitor tumor volume changes in order to adapt the treatment plan
potentially benefits the patients’ long term outcome. This is a single institution’s experience in
developing a purposeful and efficient off-line technique to incorporate ART in a clinical
environment for the treatment of lung cancer.
Purpose of the Study
The goal of this study is to develop a purposeful and efficient technique to incorporate
ART in a clinical setting for the treatment of lung cancer. This study reviews retrospective data
on patients with lung cancer who have undergone definitive radiation treatments utilizing IGRT
at the University of Nebraska Medical Center (UNMC). The goal of this study is not only to
implement a simple off-line ART technique that is practical and efficient to use for adaptation of
RT plans, but also to produce a more conformal treatment plan through adaptation during the
patient’s course of treatment.
Assumptions of the Study
No assumptions have been made about this study in terms of tumor volume response or
the dose threshold at which a tumor response indicates an adaptation to the treatment plan. All
patients had CT on rails (CTOR) image guidance in conjunction with their RT treatments. The
adaptive re-planning of the patient’s treatment plan was done with the CTOR data set on every
tenth fraction throughout the patient’s course of RT. The initial RT plan the patient began
treatment with was consistent throughout all of the adaptive re-plans over the course of the
patients treatment. The results of this ART strategy were analyzed using measured tumor
volumetric data.
Definitions of Terms
Active Breathing Coordinator (ABC) – A respiratory device which monitors and
controls a patient’s respiratory cycle during RT for tumors that demonstrate internal motion.
Tumors that are located in the chest and breast move with the patient’s respiratory cycle. An
ABC device can minimize the internal motion and immobilize these tumors which allows for
greater accuracy of the RT delivery.
Adaptive Radiotherapy (ART) – The adaptation of a RT treatment plan in response to
the changes in the tumor volume, shape, and position observed by daily or weekly IGRT
techniques.10 A technique utilized when a patient’s RT is re-optimized during the course of the
treatment.11
10
Clinical Target Volume (CTV) – The demonstrated tumor and any other microscopic
tissue with presumed tumor.9 The volume which includes the gross visible tumor and an
additional margin for possible microscopic disease extension that may not be visible or
palpable.39
Computed Tomography (CT) – An ionizing radiation technique that uses an x-ray
source and computer technologies combined to produce a radiographic image.39 The x-ray source
moves in an arc around a body part and as the x-ray beams pass through the body part the
radiation is converted into signals that are projected on a computer screen which appears as a
radiograph.39
Computed Tomography on Rails (CTOR) - A form of IGRT in which a diagnostic CT
scanner moves on a rail system in the treatment room. The CT scanner is opposite of the
treatment machine and has a common couch arrangement.27
Cone-Beam Computed Tomography (CBCT) – Volumetric imaging comprised of
planar projection images acquired from a CT scan with flat panel detectors rotating around the
patient.1 The single image projections are acquired with each rotation of the gantry which is
slightly offset from the prior rotation to generate a 3D reconstruction data set.39
Electronic Portal Imaging Device (EPID) – A linear accelerator-mounted electronic
diagnostic imaging device that assists in patient setup, positioning, and verification of treatment
fields.1
Four-Dimensional Computed Tomography (4D CT) – CT scans acquired at the same
time as a respiratory signal that are reconstructed into 3D data sets which represent a patients’
anatomy during different phases of a respiratory cycle. These 3D CT data sets are known as 4D
CT images.9
Free Breathing Motion – The displacement or motion of a tumor located in the lung
during a patient’s normal respiratory cycle. A patient’s normal breathing motion has an effect on
lung tumor coverage and setup error and must be considered when deriving treatment margins.
Gross Tumor Volume (GTV) – The gross demonstrable, palpable, or visible extent and
location of the malignant tumor39 It is the volume of known disease which includes the primary
tumor and any involved lymph nodes.2
Image Fusion – The process of combining the enhanced capabilities of different imaging
modalities with a CT data set. Fusing different image modalities with a CT data set enables
anatomy to be defined on those image sets and displayed on the CT data set.39
11
Image Guided Radiation Therapy (IGRT) - An imaging technique that uses a
computer that creates images of a tumor to help guide the radiation beam for radiation therapy.
IGRT makes radiation therapy more accurate.26
Image Registration – The process of geometrically registering multiple image data sets
to a common coordinate system in order to utilize the information from these multiple data sets.7
Intensity Modulated Radiation Therapy (IMRT) – An RT technique using nonuniform fluence (beam intensity profiles) to optimize a composite dose distribution.9
Internal Motion (IM) – Variations in the size, shape, and position of a tumor volume in
relation to the physiological movements and respiratory motion of the patient.9
Internal Target Volume (ITV) - A margin added to a CTV to account for any organ
motion or changes in the size, shape, and position of the target during RT treatment.2
Kilovoltage Cone Beam Computed Tomography (KVCBCT) – An imaging system
that utilizes kilovoltage (KV) x-rays generated by an x-ray tube mounted on a retractable arm
90° to the treatment beam line of a linear accelerator.9 A flat panel x-ray detector is opposite of
the x-ray tube and multiple KV radiographs are acquired as the gantry rotates 180° around the
patient.9
Magnetic Resonance Imaging (MRI) - Computerized images of soft tissues in the body
through the use of magnetic resonance of atoms in the body and applied radio waves. It is a noninvasive diagnostic technique.26
Mean Lung Dose (MLD) – Average radiation dose to the total lung volume minus the
GTV.9 It has been found to be associated with pneumonitis of the lung.9
Megavoltage Cone Beam Computed Tomography (MVCBCT) – An imaging system
that uses the megavoltage (MV) energy of the linear accelerator and an EPID mounted on a
retractable support.9 This system uses a flat panel adapted for MV photons and images are
acquired by a continuous 200° arc of the gantry.9 Image reconstruction is completed following
the acquisition.9
Organs at Risk (OR) - Critical organs inside the body, near or within the radiation fields
that have specific radiation dose tolerances. The dose is limited to these organs.
Planning Target Volume (PTV) – A geometric volume which includes the CTV and all
geometric uncertainties.39 The margin around the CTV to account for patient motion and setup
uncertainties.9
12
Positron Emission Tomography (PET) - Radioactive glucose is injected into the body
and a scanner is used to make detailed computerized images inside the body where the glucose is
used. Cancer cells often use more glucose than normal cells.26
Respiratory-Correlated Cone Beam Computed Tomography (rcCBCT) – Similar to
4D CT and used to visualize breathing motion and to correct for motion artifacts.28 The CBCT
images are reconstructed at certain fractions during RT treatment which represented full
exhalation of respiration.28 These data sets may be used to access volumetric tumor changes or
positional changes.28
Stereotactic Body Radiotherapy (SBRT) - A form of radiation therapy that delivers
high doses of radiation to tumor volumes in few fractions. This type of treatment concentrates a
high degree of dose conformality in the target volume and spares normal tissue.9 The SBRT
technique delivers RT with great accuracy with rapid dose falloff sparing surrounding normal
tissues.39
Three dimensional conformal radiation therapy (3DCRT) – RT that is based on 3D
anatomic information that conforms to the tumor volume and limits dose to normal tissues.9
Treatment Planning System (TPS) – Computer systems that are utilized for the
planning of RT treatment plans. Treatment planning systems have software that allow for 3D
data input and processing, dose calculations, and 3D graphics.9 The TPS allows for the design,
calculation, and evaluation of RT plans for patients who undergo treatment.
Tumor Control Probability (TCP) – A biologic index that can be used in evaluating a
treatment plan which assumes that a tumor is destroyed if all tumor cells are killed.9 The TCP
model assumes that tumor cells in a tumor are evenly distributed and have identical
radiosensitivities.9 If the radiation dose to each tumor cell produces a response independently in
a partial tumor volume, then the TCP can be inferred for the whole tumor volume.9
Limitations of the Study
A limitation of this study is inter-observer variations of tumor volumes. The
segmentation of tumor volumes was completed and reviewed by two or more radiation oncology
professionals and may be subject to interpretation. The positional and rotational accuracy of the
image registration based on inter-observer variations may affect the tumor volume propagation
of the original tumor volumes on the CTOR data sets. Another limitation was tumor volume
response from neo-adjuvant or concurrent chemotherapy agents introduced either prior to or
during RT treatments. The effects these drug regimens have on tumor response were not be taken
13
into consideration for adaptive re-planning of the treatment volume over the course of RT. The
influence of the patients’ respiratory motion and its effects on the delineation of tumor volumes
is beyond the scope of this research study.
Methodology
This study included a retrospective review of lung cancer patients treated with definitive
radiation therapy at the UNMC. Retrospective patient data sets including CTOR images and the
initial radiation planning CT data sets were used to develop a purposeful and efficient off-line
ART strategy that can be incorporated into treatments for lung cancer. This study examined the
bi-weekly CTOR data sets tumor volumes in comparison to the initial planning CT data set to
discern if tumor volume reduction has taken place. Tumor volumes were measured and
comparatively evaluated. The rationale is to compare volumetric target changes with the
anticipation that tumor volumes and treatment margins could be decreased to order to limit
toxicity to surrounding normal tissues. Finally, an analysis of the experience and feasibility of
utilizing CTOR in conjunction with ART for lung cancer patients at the UNMC were performed
and the results were discussed.
14
Chapter II: Literature Review
Introduction
The advanced RT imaging and emerging technologies in IGRT have enabled techniques
for ART strategies for lung cancer treatments. Advanced image guided systems like CTOR have
the ability to visualize the tumor and OR in three dimensions (3D).5 This visualization can
facilitate tumor delineation and localization, observe biological changes occurring in tumor
volumes and OR during the course of RT, and provide information to adapt a patients treatment
plan daily or periodically. Adaptations can be intra-fractional which are considered online
approaches or inter-fractional which are considered off-line approaches. An online approach
makes adjustments to patient position or treatment parameters using data during the current
treatment session.1 Whereas, an off-line approach makes adjustments from an accumulation of
information from previous treatment sessions.1 These two ART approaches can be used
independently or in conjunction with each other and can provide many benefits to patients with
lung cancer. The benefit of using IGRT combined with strategies of ART for lung cancer
patients is an effective approach to reducing tumor volumes and treatment fields to limit dose to
OR. These online and off-line ART strategies utilizing IGRT technologies not only benefit RT
patients, but also minimize the patient’s exposure to long term toxicities.
Computed Tomography on Rails (CTOR)
A 3D volumetric IGRT system known as CTOR may be used to incorporate ART
strategies into the treatment of lung carcinoma. A CTOR system enables the introduction of ART
by optimizing treatment fields from inter-fractional changes in position and shape of the target.19
This IGRT system is comprised of a CT scanner and a linear accelerator positioned at opposite
ends of each other in a treatment vault and they both share the same patient couch.11 When the
couch is rotated 180° from the linear accelerator to the CT scanner the linac isocenter on the
couch matches the origin of the coordinate system on the CT scanner.12 These coordinates are
aligned through image registration between the treatment planning CT data set and the daily CT
data set. The data sets are registered by the radiation therapist daily to localize the isocenter as
well as the treatment target volume. By sharing the same patient couch, the x-axis, y-axis, and zaxis are identical between machines and these coordinates can be used to position the patient
isocenter and target region accurately for RT treatments.
Kuriyama et al12 investigated the positional accuracy of the common treatment couch
technique between a linear accelerator and a CT scanner. They described a linear accelerator and
15
a CT scanner called a Smart Gantry CT placed on opposite ends of a treatment couch. The Smart
Gantry CT scanner had undergone slight modifications so the gantry of this scanner could move
with a special driving device. With this modification, the Smart gantry was designed to move
along a rail system consisting of three rails. Two side rails allowed for horizontal movements of
the gantry and one middle rail guided the CT gantry forward and backward. Along the middle
guide rail, a magnetic strip with magnetic data was placed to indicate a reference point when the
gantry is at zero degrees. The gantry moved using magnetic data and this reference point for
accurate scanning. By rotating the couch 180°, the position of the linear accelerator isocenter on
the couch correlated with the origin of the Smart Gantry CT scanner. The accuracy of the entire
CT and linear accelerator system was investigated by using an 8 mm acrylic ball positioned at
the isocenter on the treatment couch and moving the couch in multiple directions including
laterally, longitudinally, and vertically. They described the accuracy of this system was
determined by measuring the displacement in three axes while moving the treatment couch in
different directions. They reported results of these measurements and determined the couch
positional accuracy was 0.20 mm in the lateral direction, 0.18 mm in the longitudinal direction,
and 0.39 mm in the vertical direction. The rotational accuracy of the common treatment couch
was determined to be less than 0.4 mm in all three directions. It was noted in this study that
stereotactic irradiation should be carried out with accuracy no greater than 1 to 2 mm. Treatment
to a patient’s body or trunk region should have margins of several millimeters to account for
respiration with an accuracy of 0.4 mm being adequate. The conclusions made from this study
are that linear accelerators with CTOR systems are a very accurate form of IGRT especially for
stereotactic irradiation, IMRT, and 3DCRT. In RT of the body or trunk of a patient, internal
target and organ motion, respiratory motion, and setup errors are taken into account with larger
treatment fields. The CTOR system is a very effective IGRT technique for reducing setup errors
and inter-fractional tumor motion, as well as, positional verification of the target.12
Amies et al38 examined four IGRT technologies that can be utilized in an ART process in
a clinical environment. The four IGRT technologies that were presented were: CTOR,
MVCBCT, Mobile KV C-arm, and an In-line KV and MV cone beam technology. They accessed
the potential benefits and challenges with each of these technologies in relation to the clinical
and technical perspectives each incorporates into the ART process. Of particular interest in this
study was the CTOR technology and how it may be utilized for all disease sites, but is preferred
for anatomical regions that require soft tissue contrast.38 Other benefits CTOR offers are the 4D
16
CT component to evaluate respiratory motion and quality of the image data sets to offer rigid and
non-rigid registration approaches between the planning and pretreatment CT for evaluation of
anatomy in adaptive targeting.38 In addition, CTOR offers automatic structure segmentation from
the planning data set to the CTOR data set.38 CTOR presents several challenges such as the
movement of the patient between the imaging and the RT delivery, the imaging cannot be done
during treatment, and CT image artifacts from high density metal objects have an effect on image
quality.38 Each of these four IGRT technologies contribute to the ART process and each offers a
different set of possibilities to improve accuracy of RT to the patient.
Adaptive Radiotherapy (ART) Strategies
Adaptive radiotherapy (ART) strategies facilitate many components. This includes
precise RT planning and treatment delivery to patients and thereby reducing OR exposures. The
ability to reduce OR exposures enables dose escalation, and improve local control and overall
survival.8 ART strategies can be categorized into off-line techniques or online techniques that
both utilize IGRT and image registration as the basis for adaptations to a RT treatment plan. In
addition, ART strategies can be paired with respiratory motion techniques to continue to
accurately delineate target volumes as it pertains to motion in lung tumors. The inability to track
the changes in volume and location in lung tumors causes a geometric miss. Geometric misses in
lung tumors can be attributed to the lack of increased local tumor control irrespective of tumor
doses and lung function.
Foroudi et al11 evaluated two ART strategies compared to a conventional treatment
protocol for invasive bladder cancer. The study examined benefits of off-line ART strategy for
bladder cancer using CBCT to determine treatment accuracy and also examined the possible
benefits of an online adaptive process for treating bladder cancer. The off-line ART strategy of
this study utilized the first five daily CBCT scans, as well as, a CBCT scan on a weekly basis on
five patients with invasive bladder cancer. The first five daily CBCT scans were used to create a
single adaptive plan for treatment starting on fraction number eight in the course of RT.
Conversely, the study proposed a theoretical online ART strategy to investigate using the
planning CT and the first five daily CBCT to create small, medium, and large bladder volumes
which correlated to small, medium, and large adaptive bladder treatment plans of the day. The
basis for this strategy is to use daily IGRT imaging to determine the size of the bladder and select
a similar plan based on bladder size prior to treatment. This approach aims to improve target
volume coverage while minimizing dose to normal healthy tissue using daily imaging. The
17
coverage was calculated based on the percentage of the CTV that is covered by 95% of the
prescription dose.
The results of this study comparing the off-line ART strategy to the conventional
treatment was an improvement of CTV coverage from 60.1% for conventional radiotherapy to
94.7% for off-line ART. The off-line strategy also demonstrated a higher conformality index
compared to the conventional treatment regimen. In reference to normal tissue irradiation, the
study demonstrated a reduction in both ART strategies. More normal tissue was irradiated
outside of the CTV using the conventional treatment regimen than the adaptive plans and the
rectal D50 was considerably lower for each adaptive plan compared to conventional treatment
planning.11 The proposed theoretical online ART strategy which utilized small, medium, and
large bladder volumes to choose a plan of the day approach needed further research. Online
adaptive techniques need more research to reduce systematic errors, random day to day
variations, and more education for personnel to delineate soft tissue organs on IGRT images.11
Another study by Foroudi et al14 further investigated the advantages and disadvantages of
daily online adaptive IGRT compared to conventional RT for invasive bladder cancer. In this
study, a plan of the day approach as previously described was examined further and a
comparison of CTV dose coverage, as well as, the volume of normal tissue irradiated between an
online adaptive treatment technique and a conventional technique was done. The adaptive plan of
the day approach incorporated small, medium, and large bladder volumes. Each volume was
contoured from the planning CT and the first five daily CBCT scans. The plan of the day
approach selects a plan from the small, medium, or large bladder volumes that were created to
encompass the target on a daily basis. By imaging the bladder volume each day with IGRT, a
plan based on the size of the bladder, small, medium, or large could be chosen for treatment. The
results of this study indicated the plan of the day ART approach is feasible and the V95 CTV
coverage for the ART technique is similar to the conventional technique. However, the use of an
adaptive technique significantly reduces the volume of normal tissue being irradiated.14
Vestergaard et al15 compared three different ART strategies for bladder cancer treatment
using CBCT imaging and plan selection from a library consisting of three IMRT plans
corresponding to small, medium, and large tumor volumes. This study compared integral dose
and the normal tissue sparing of different ART strategies. Each of these methods was compared
to a standard non-adaptive plan. Each of the three ART methods derived different treatment
margins that corresponded to small, medium, and large tumor volumes. ART method A utilized
18
population-based treatment margins calculated from a previous study that used an algorithm to
determine treatment margins based on CTV coverage. ART method B utilized the first five
CBCT scans and did not delineate a target and ART method C utilized the CBCT scans from the
first four treatments to delineate a target CTV. In each these methods, three corresponding PTVs
were derived with a 3 mm expansion to account for intra-fractional changes of the bladder. The
results of this study determined that differences of these three ART methodologies are small
compared to each other however; the ART methodology differences compared to a non-adaptive
plan methodology is significant. Treatment volumes reduced from 30% - 40% with ART
methodologies and all three ART methods had considerable reductions in volumes of normal
tissue being irradiated. These large reductions may enable significant dose escalation and keep
morbidity level tolerable.15
Benefits of ART
Fox et al16 conducted a study that incorporated multiple CT scans during the course of
RT to assess the possibility of reducing treatment volumes in patients with non-small cell lung
cancer. An initial planning CT scan and two additional CT scans were used at 30Gy and 50Gy to
assess GTV changes. The findings reported a mean GTV reduction of 25% when the patient
reached a dosage of 30Gy and a mean reduction of 43% at 50Gy. They found no significant
difference in tumor reduction from the location of the GTV in the mediastinum or in the lung
parenchyma. Also, the use of chemotherapy did not impact the tumor volume reductions. They
reported the data suggested greater tumor volume changes occurred at the front part of a course
of RT treatment and these changes could not be used as a prediction model for the remainder of
the RT course. From this data, they inferred that an adaptive planning strategy could be utilized
to escalate dose to the tumor volumes and minimize dose to normal tissues.16
Siker et al17 performed a study that assessed the tumor volume changes in non-small cell
lung cancer patients using MVCBCT scans. An initial planning CT was performed and multiple
MVCBCT scans were done weekly. The twenty-five patients had a different number of
MVCBCT scans however; all patients had at least an initial MVCBCT scan at the beginning,
middle, and end of the RT course. A gross tumor volume (GTV) was contoured on each
MVCBCT scan and was assessed for volume reduction. They reported by the end of treatment
none of the patients had a complete response however; 12% of the patients had a partial
response, 20% of the patients had a marginal response, and the remainder of the patients 68%
had stable disease in terms of tumor volume changes. They concluded that the clinical
19
significance of this tumor volume regression was questionable. The study found that MVCBCT
offers a viable way to measure tumor volume regression and enables accurate assessment of lung
tumor volume changes.17
Guckenberger et al18 conducted a study to evaluate the potential of ART for advanced
stage non-small cell lung cancer. The study incorporated weekly CT images to analyze tumor
regression and used the CT images from the second and fourth weeks of treatment to simulate
ART for weeks three and five. The ART simulation was performed once on week three and week
five and a double ART simulation was performed on weeks three and five. This study reported a
continuous tumor regression by 1.2% per day which resulted in a remaining GTV of 49% after
six weeks of treatment. The data for a single plan adaptation in week three and in week five
reported a mean lung dose (MLD) reduction of 5.0% and 5.6% respectively. A double plan
adaptation performed with CT data and weekly CT images in weeks three and five combined
resulted in a MLD reduction of 7.9%. Plan adaptation to tumor volume shrinkage once or twice
during the RT course significantly reduced the MLD which enabled dose escalation to the tumor
volumes.18
Another study by Guckenberger et al10 which incorporated data from a previous study
by Guckenberger et al18 evaluated if dose coverage was compromised to microscopic disease
from adapting the radiotherapy treatment plans in response to a shrinking GTV in patients with
non-small cell lung cancer. The concern is that areas of microscopic disease might become under
dosed if radiation fields are adapted to GTV reduction and the microscopic disease exhibits no
response and remains stationary in the lung tissue.10 In this retrospective study of 13 patients, the
influence of ART planning on dose distributions was simulated for two scenarios concerning
microscopic disease. One scenario was the reduction of microscopic disease at the same rate as
the GTV reduction, and the second scenario was that the microscopic disease exhibited no
response while the GTV reduced. Tumor control probability (TCP) calculations were utilized to
evaluate the clinical potential of ART.10 The results of this study demonstrated that dose
coverage of microscopic disease at 50Gy was not compromised in either scenario by ART.
Adapting the radiation field sizes once or twice in response to GTV reductions during a course of
radiotherapy for non-small cell lung carcinoma does not compromise dose coverage or TCP of
microscopic disease.10 ART has the potential to increase TCP by greater than 40% compared to
radiotherapy planning without ART.10
20
Kupelian et al20 reported on the rate of tumor regression of non-small cell lung cancer in
10 patients by evaluating serial megavoltage CT images. The patients in this study had multiple
MVCBCT scans performed over the course of treatment however; all patients had a scan at the
start of RT and at the end of treatment. A GTV was delineated on each MVCBCT scan to assist
in evaluating tumor regression. The results of this study documented tumor regression in all 10
patients and the decrease in volume was seen throughout the entire course of RT, not just at the
beginning of treatment or the end of treatment. It was reported that individual tumor regression
rates ranged from 0.6% to 2.3% and the average decrease in volume for all 10 patients was 1.2%
per day.20
Woodford et al21 reported on the daily GTV changes and GTV variations in 17 patients
treated for non-small cell lung cancer. The daily imaging for each patient was completed using a
megavoltage CT on a helical tomotherapy machine prior to each patient’s radiotherapy
treatment. To evaluate changes and variations of the GTV, the contours were retrospectively
delineated on the daily MVCBCT scan for each patient. The average GTV change this study
reported over 30 fractions of treatment was -38%, ranging from -12% to -87% decrease in GTV
volume. In addition, no significant correlation was observed between GTV change and the
patients physical or tumor features.21 This study also investigated the potential benefits of
adaptive radiotherapy re-planning with different GTV regression characteristics. By evaluating
the 17 patients, three general patterns of tumor volume changes were observed. In the 17 patients
sampled, five patients experienced a small tumor volume change followed by a sharp decrease in
tumor volume, eight patients experienced a gradual tumor volume decrease, and four patients
experienced variable volume changes with no clear trend in volume reduction.21 The time frame
of when tumor volumes change during the course of radiotherapy can be a strong indicator of
whether or not to adapt the treatment plan. The study concluded that adaptive planning can
improve cumulative doses to OR, the therapeutic ratio, and the clinical results after the GTV
decreases approximately 30% or more and if the decrease occurs within 15-20 fractions of
treatment.21
Spoelstra et al22 designed a prospective study to investigate the dosimetric consequences
of volume changes over time and used 4DCT scans to evaluate the possibility of plan adaptation
in lung cancer patients. The study followed 24 patients who all received a course of
chemotherapy in conjunction with RT. Each patient underwent two 4DCT scans, one for the
initial RT planning and the second was completed after the patient received a dose of 30Gy and
21
approximately 3 weeks of chemotherapy. The new PTV generated after 15 fractions of chemoradiation was compared with an initial PTV that was created from select 4DCT phases. The
results of this prospective study stated that 8% or 15 patients had an average PTV reduction after
30Gy. However, the PTV increased in 6 patients and one patients PTV increased dramatically. In
addition, the study also reported no change in the mean 95% isodose coverage among all
patients. The study also reported total lung volumes after 30Gy both increased and decreased and
the V5, V20, and mean lung dose did not significantly change after 30Gy. Finally, the study
reported one patient need re-planning due to disease progression during the course of RT and the
PTV actually increased 39% in size which resulted in a dosimetric target miss. It was concluded
that ART and 4DCT scanning have a limited role in lung cancer patients undergoing
conventional radiotherapy.22
Barker et al23 conducted a study that employed CTOR imaging to assess the anatomical
changes in patients receiving RT for head and neck cancer. This study followed 15 patients with
head and neck cancer that employed a CTOR system to scan patients three times per week. Each
patient averaged 18-21 CTOR scans throughout their course of RT. A GTV and normal tissues
such as the parotid glands were contoured on each CTOR scan by one radiation oncologist to
limit inter-observer variations in contouring. The results of this study demonstrated that the GTV
decreased at a median rate of 1.8% per day in comparison with the initial GTV and the center of
this volume decreased asymmetrically. At the end of RT, the GTV reduced roughly 70% from
the initial GTV. The study also stated the parotid glands decreased, as a result of patient weight
loss from RT, with a median volume decrease of 0.19 cm3 per day or 0.6% per day. The total
median parotid volume decrease was 28.1% compared to the initial volumes. An interesting
observation was pointed out in this study: patient weight loss and the decrease in volume of the
parotid glands actually shift the center of these glands medially into the high dose region being
treated in the patient. In addition, the investigators inferred that ART may be needed after a
certain amount of weight loss the patient may experience due to significant tumor volume
reductions and the medial displacement of the parotid glands. This study concluded that ART
may be needed to account for the measureable anatomic changes that occurred in the targets and
critical structures after 4 weeks or RT.23
Ahn et al24 reported the results of a study on an ART protocol to assess the anatomic
changes and positional variability during IMRT for head and neck cancer. In the study, each
patient had an initial planning CT scan followed by repeat CT scans on the 11th, 22nd, and 33rd
22
fraction of RT. These repeat CT scans were assessed for anatomical and positional changes to
determine if these changes warranted an adaptation to the patients RT course. GTV and PTV
were contoured on each scan. This study observed 65% of patients had a lack of dose coverage to
the tumor volumes and an increase in dose to critical structures. These patients actually
benefitted from ART. The study concluded that no single anatomical change and positional
variability change, such as weight loss, fraction number, or skin separations, can reliably
predicted the need for ART. They concluded that it is important to use IGRT to monitor anatomy
and positional variability during the patient’s course of RT to decide to re-plan.24
Renaud et al25 conducted a study that employed MVCBCT scans to access the ART
benefits in mesothelioma patients who received RT treatment with helical tomotherapy. By
utilizing the Tomotherapy Planned Adaptive software, the variations of gross tumor volume
(GTV), planning target volumes (PTV1 and 2), and OR contours on daily MVCBCT scans could be
evaluated. Two strategies for adapting the radiotherapy plan were investigated. The first strategy
focused on reducing dose and improving sparing to OR and the second strategy concentrated on
dose escalation to the GTV while maintaining normal tissue sparing. In addition, IMRT and
3DCRT plans were generated and used for comparison to the helical tomotherapy plan. In the
first strategy, GTV reduction was observed after 22 fractions and the PTV margins were reduced
by 4 mm which decreased the mean lung dose (MLD) by 19.4%.25 The results from the dose
escalation strategy reported the prescribed doses were increased from 50.0Gy to 58.7Gy in PTV1
and from 60.0Gy to 70.5Gy in PTV2.25
The previously stated study also compared the IMRT plan and the 3DCRT plan results
with the helical tomotherapy plan and reported that the IMRT plan spared normal tissues better
than the helical tomotherapy plan but, lacked adequate tumor volume coverage. For the IMRT
plan, the D30 of the heart was reduced by 40% and the V20 of the total lung volume was reduced
by approximately 10%. However, the D99 and D95 of both PTV’s were lower than the helical
tomotherapy plan. The 3DCRT plan and the helical tomotherapy plan were both comparable in
target coverage and normal tissue sparing was comparable for both modalities. The D30 of the
heart was reduced by approximately 45% and the total lung volume V20 was lower by 5% in the
3DCRT plan. However, the spinal cord dose was a limiting factor in the 3DCRT plan and it was
too high to be clinically acceptable. The conclusions from this study re-affirm that dose
escalation and normal tissue sparing can be achieved by ART.25
23
As previously stated, IGRT technologies have advanced and enabled the use of ART
strategies in many types of cancer patients. The use of IGRT technologies can be beneficial for
lung cancer patients in assessing tumor volume changes, tumor volume reductions, and
anatomical or positional changes during the patient’s course of RT. These technologies enable
ART strategies to be incorporated into a patients RT regimen to account for these changes in
order to deliver precise RT and minimize dose to normal tissues. ART improves the accuracy of
RT considerably and with improved accuracy dose escalation to the tumor volume is achievable
without compromising on limiting the dose to the OR.2
Respiratory Motion and ART
Lim et al28 analyzed respiratory-correlated cone beam computed tomography (rcCBCT)
in 60 patients to evaluate the tumor size, shape, and location during radiotherapy for non-small
cell lung carcinoma. Each patient underwent a KVCBCT that was used for patient positioning
prior to treatment. The CBCT was reconstructed off-line using the position of the diaphragm into
10 data sets which produced a serial rcCBCT data set which was then registered with a 4DCT
scan. Cone beam images collected offline at fraction 1, 5, 10, 15, 20, 25, and 30 were
reconstructed into a serial rcCBCT data set. The primary tumor volume was contoured on each
fraction of the rcCBCT data set. The registration of the serial rcCBCT with the planning 4DCT
data set represented the respiratory phase which could be evaluated for volumetric and positional
tumor changes. More than 30% tumor regression was reported in 40% of the patients through
mid-treatment and 67% by the completion of treatment.28 This study also indicated greater tumor
regression rates earlier in the radiotherapy treatment course. The study concluded that through
the use of rcCBCT significant tumor regression was observed and that patients would benefit
from ART.
Mechalakos et al29 conducted a study to access the effects of free breathing motion on
GTV and PTV treatment margins in patients undergoing RT for non-small cell lung cancer. This
study evaluated 12 patients who utilized free breathing motion obtained from fluoroscopic
studies to examine the effect of simulated breathing motion and setup uncertainties incorporated
onto an original treatment plan. In this study, the GTV volumes had a margin of 1-2 cm added to
generate a PTV margin in the original plan. Additional components were modeled into the
original treatment plan to model breathing motion and setup uncertainty. A setup error
component, a breathing motion component, and an intrafractional breathing component all added
additional margins onto the original treatment plan. The results of this study indicate that GTV
24
with volumes of 60 cm3 or more show a stronger sensitivity to breathing especially if the tumor
shape is irregular. The effects of normal breathing on PTV margins are small with a 4% or less
chance of a 10% or greater decrease in dose to the GTV.29 The conclusions from this study
indicated special consideration should be observed in patients with irregular tumors treated with
the free breathing technique and efforts to reduce breathing motion should be done for heavy
breathers.29
van Sörnsen de Koste et al30 conducted a study to characterize the 3D movement of lung
tumors from multiple spiral CT scans in patients with stage I non-small cell lung cancer. The
multiple CT planning scans were comprised of three “rapid” scans and three “slow” scans. A
total of 29 data sets were analyzed. All CT scans were co-registered with the GTV’s contoured
on the co-registered CT data sets which automatically propagated onto the initial treatment
planning CT scan. A clinical target volume (CTV) was generated by adding a 5 mm margin on
the GTV contour to account for microscopic tumor extension. An optimal CTV which
encompassed all six CTVs for each patient was generated and was representative of the tumor
position during respiration. This study reported that the location of the tumor within the different
lobes of the lung did not correlate with mobility in x, y, and z directions. The study also
concluded that “slow” CT scans capture most of the tumor mobility during respiration for
peripheral lung tumors.30
Bosmans et al31 conducted a study investigating the changes in tumor volume, tumor
motion, and breathing frequency during the first 2 weeks of an accelerated course of
radiotherapy for non-small cell lung carcinoma. The study evaluated 23 patients that were
simulated for radiotherapy using a CT-PET simulator. The GTV was delineated from CT-PET
data before treatment began. The CTV was defined as the GTV plus a 5 mm margin which
represented microscopic disease and the PTV was defined as the CTV plus a 1 cm margin which
represented internal respiratory motion and setup error. In addition, all patients also underwent a
respiration-correlated CT scan that was reconstructed in 10 phases from 0% to 100%. This
respiration-correlated CT scan represented the tumor motion in the respiratory phase. The tumor
volume changes that this study reported were mostly moderate volume changes under 30%. Only
3 of 23 patients experienced a tumor volume decrease that was greater than 30% and 4 of 23
patients experienced a tumor volume increase greater than 30%. In addition, tumor motion and
breathing frequency were reported to have no significant effect during radiotherapy. The study
concluded that repeated imaging is necessary during radiotherapy due to the large variability of
25
changes in tumor volumes and respiratory correlated imaging during radiotherapy may not be
necessary because changes in tumor motion are small.31
Weiss et al32 conducted a study which analyzed tumor volume and tumor motion during
respiration and also the respiratory relationship in volume and position of normal tissues utilizing
4DCT scans of 14 patients with lung carcinoma. Each patient underwent a respiration-correlated
4DCT scan where the respiratory cycle was recorded in 10 phases with T0 representing
maximum inspiration and T5 representing the middle of the respiratory cycle or 50% inspiration.
The GTV and the spinal cord, esophagus, heart, lungs, trachea, and the diaphragm on the side of
the tumor were contoured in all phases of the respiratory cycle. The structures were evaluated for
volume changes relative to the respiratory cycle. The results of this study indicated that during
the respiratory cycle contoured volumes varied as much as 62.5% for GTV and 25.5% for lungs,
and 12.6% for hearts. Also, during respiration the central positions of the normal tissues varied
significantly from the central positions of the GTV’s in individual patients. This study concluded
that the central distance between the GTV and the center of the normal tissues during respiration
may affect the discussion regarding which phase of the respiratory cycle allows for optimal
normal tissue sparing.32
Britton et al33 reported on the changes in size, shape, and motion of the GTV and ITV
utilizing four-dimensional computed tomography (4DCT) during radiotherapy in eight patients
with non-small cell lung cancer. In the study, patient simulation was done with a 4DCT scan
initially and then a 4DCT scan was completed every week until the radiation therapy course was
complete. In each 4DCT data set, contours of GTV’s, CTV’s, and ITV’s were delineated. The
primary tumor volume was considered the GTV, the CTV was an expansion of the GTV by 8
mm to account for microscopic disease, and the ITV was created to encompass the CTV’s. The
center of the GTV’s and ITV’s served as the reference for motion analysis. The data from this
study reported that tumor volume reduction varied from 20% to 71% at the end of inspiration and
15% to 70% at the end of expiration.33 Tumor mobility increased in the superior-inferior
direction and the anterior-posterior direction.33 Tumor motion was significantly greater in the
superior-inferior direction compared to all other directions. The conclusions drawn from this
study indicated that repeat 4DCT scans may be warranted to quantitatively assess tumor changes
and respiratory tumor motion during radiotherapy treatment.
Burnett et al34 assessed the most effective way to manage lung tumor motion in patients
undergoing radiotherapy treatment for lung carcinoma. This study utilized a formula that
26
combines tumor motion measurements and setup errors in seven patients to determine adequate
PTV margins for treatment using data from previous studies. This study compared individualized
PTV margins to those PTV margins obtained through motion management. The percent volume
of the lung receiving 20Gy or V20 was analyzed. The study concluded that any form of motion
management used to derive PTV margins is more beneficial than using a standardized PTV
margin.34 The benefits of gating compared to ungated PTV margins demonstrated a modest
advantage unless the tumor is highly mobile.34
Li et al35 conducted a study to compare the positional and volumetric differences of
PTV’s based on axial 3DCT and 4DCT scans for non-small cell lung cancer tumors.35 This study
consisted of 28 patients diagnosed with non-small cell lung cancer. Each patient underwent an
axial 3DCT scan followed by a 4DCT free breathing scan. During the 4DCT scan, images were
reconstructed in 10 respiratory phases and GTV was delineated on each of the 10 respiratory
phases. The extent of the GTV center was measured in each of the 10 respiratory phases and a
three-dimensional vector was calculated. This PTVvector was defined by the GTV’s contoured on
the 3D image set using the individual tumor motion measured on the 4DCT scan.35 Whereas, a
PTV4D was generated from the motion of the CTV’s on all phases of the respiratory cycle on the
4DCT scan. In addition, this study categorized these 28 patients in Group A which consisted of
patients whose lesions were in the upper lobe of the lung and Group B which represented
patients whose lesions were in the middle or lower lobes of the lung. The differences in target
position, volume, and coverage between PTVvector and PTV4D were evaluated for tumors in
different lobes.35 The results of this study indicated that the average motion for tumors in Group
A was 2.8 mm and Group B was 7 mm. The motion of cranial-caudal direction is larger in Group
B than for Group A. The conclusions drawn from this study indicated that 3DCT based PTV’s
which represent tumor motion encompass large normal tissue volumes, especially in Group B,
and should not be used treatment planning.35
Brock et al36 compared lung dosimetry parameters between free-breathing (FB) treatment
plan and an Active Breathing Coordinator (ABC) treatment plan and also evaluated the
feasibility and reproducibility of an ABC in patient undergoing radiotherapy for non-small cell
lung cancer. This study reported 18 patients underwent a FB CT scan and instructed to breathe
normally. In addition, an ABC mouthpiece and nose clip were attached to the patients and three
CT scans were acquired. In each scan the patient was instructed to breath hold at 70% lung
inspiration capacity. The visible tumor and lymph nodes made up the GTV which was delineated
27
on both the ABC and FB scans. The PTV was generated by expanding the GTV by 1.0 cm
axially and 1.5 cm in the superior-inferior direction. In addition, OR were contoured on each
scan and included the spinal cord, normal lung minus GTV, heart, and esophagus. This study
evaluated lung volumes, the percentage of lung volume treated at 20Gy (V20), and mean lung
dose (MLD) between each plan. The results of this study reported that all but one patient was
able to complete radiotherapy using ABC daily. The average reduction in GTV was 25% from
planning to the end of treatment. The ABC plan reduced the V20 by 13%, V13 by 12% and the
MLD by 13% when compared to the FB plan. Furthermore, the conclusions from this study
indicated that ABC is well tolerated by patients and using ABC reduces the dose-volume
parameters in lung toxicity which may allow for dose escalation.36 Panakis et al37 further
evaluated ABC and its effect on physical lung parameters. The findings reported that the MLD
was reduced by 25%, the V20 was reduced by 21%, and the V13 was reduced by 18% compared
to FB plan in their study sample. These findings support the study done by Brock et al36 that
ABC is tolerable for non-small cell lung cancer patients, PTV margin reduction can spare normal
lung, and dose escalation may be achieved.37
The ability to evaluate, quantify, and manage respiratory motion in the treatment of nonsmall cell lung cancer is an integral part of the ART process. IGRT technologies evaluate the
changes in tumor volumes, the positions of tumor volumes, and tumor volume respiratory
motions throughout the course of radiotherapy. These are all key components of the adaptive
planning process. The respiratory motion management of lung tumors can facilitate better patient
outcomes in radiation therapy treatments. All of the previously stated respiratory motion
techniques continue to benefit patients with non-small cell lung cancer and will advance ART
strategies in the treatment of lung cancer.
28
Chapter III: Methodology
Advances in IGRT have propelled ART strategies to the forefront as a means of
providing patients with the most accurate RT plans for many types of cancers. Adaptations in a
patient’s RT plan may be needed as result of tumor growth or regression, biological changes in
anatomy or tumor volumes, and positional or localization changes observed during the course of
RT. Various IGRT techniques and adaptive strategies may account for these changes, enable
dose escalation, improve local control, as well as, overall survival for patients.8 The purpose of
this study is to present a single institution experience in developing a purposeful and efficient
off-line technique to incorporate ART in a clinical environment for the treatment of lung cancer.
This chapter examines the sample selection and description of patients for this study, the
instrumentation that was used, a description of how data was collected and analyzed in this
study, and a discussion of study limitations.
Sample Selection and Description
A purposive sampling technique was used to select patients for this study. The sample
included patients that have undergone RT for lung carcinoma at the UNMC. For this study, a
retrospective review of nine patients that were treated with external beam radiation therapy to the
thoracic region and underwent a daily CTOR scan for localization prior to RT during the time
frame of November 2008 to May of 2012. The sample selection was based on patients who were
diagnosed with non-small cell lung carcinoma in various disease stages. Five patients received a
prescription dose of at least 60Gy or greater and four patients received a preoperative
prescription dose of 45Gy.
Patient 1 – A 45 year old female diagnosed with non-small cell carcinoma of the left upper lobe
of the lung and mediastinum, T3, N2, M0, stage IIIA. The patient has a significant smoking
history of 1/2 pack to 1 pack a day for 30 years. The patient was referred to the radiation
oncology department and the recommendation from the radiation oncologist (RO) was for the
patient to receive a definitive course or RT prescribed to 70Gy at 2Gy per fraction for 35
fractions with concurrent chemotherapy.
Patient 2 – An 81 year old female diagnosed with non-small cell lung carcinoma of the right
lung invading the hilum, chest wall and ribs, T3, N2, M0, stage IIIA. The patient has a
significant smoking history of a pack a day for 70 years. The recommendation from the RO was
a definitive course of RT prescribed to 70Gy at 2Gy per fraction for 35 fractions with concurrent
chemotherapy.
29
Patient 3 – A 79 year old female diagnosed with non-small cell lung carcinoma of the right
upper lobe of the lung with pretracheal lymph node involvement, T2, N0, M0, stage IB. The
patient denies any smoking history however; her spouse has a 20 year smoking history. The
recommendation from the RO was a definitive course of RT prescribed to 70Gy at 2Gy per
fraction for 35 fractions.
Patient 4 – A 55 year old female diagnosed with non-small cell lung cancer of the right lower
lobe of the lung with mediastinal involvement, stage IIIB. The patient had a significant smoking
history or 1 ½ packs per day for 27 years and stated she quit at age 42. The recommendation
from the RO was a definitive course of RT prescribed to 60Gy at 2Gy per fraction for 30
fractions with concurrent chemotherapy.
Patient 5 – A 65 year old female diagnosed with non-small cell carcinoma of the right lower lobe
of the lung with mediastinal involvement, stage IIIA The patient has had a significant smoking
history for the last 45 years and just recently quit. The recommendation from the RO was a
definitive course of RT prescribed to 61.2Gy at 1.8Gy per fraction for 34 fractions with
concurrent chemotherapy.
Patient 6 – An 80 year old male diagnosed with non-small cell lung carcinoma of the left upper
lung with mediastinal involvement, T1, N2, M0, stage IIIA. The patient has a smoking history
dating back to his early twenties of 1 ½ packs per day for 30 years, but states he quit smoking
approximately 25 years ago. The recommendation from the RO was a preoperative course of RT
prescribed to 45Gy at 1.8Gy per fraction for 25 fractions with concurrent chemotherapy followed
by surgery.
Patient 7 – A 63 year old male diagnosed with non-small cell carcinoma of the left upper lobe of
the lung with mediastinal involvement, T3-T4, N0, M0, stage IIIB. The patient had a smoking
history of 1 pack per day for 20 years and quit smoking 27 years ago. The recommendation from
the RO was a preoperative course of RT prescribed to 45Gy at 1.8Gy per fraction for 25 fractions
with concurrent chemotherapy followed by surgery.
Patient 8 – A 57 year old male diagnosed with non-small cell lung carcinoma of the left lung
with mediastinal involvement, stage IIIA. The patient has a smoking history of 2 packs per day
for 30 years and quit smoking 10 years ago. The recommendation from the RO was a
preoperative course of RT prescribed to 45Gy at 1.8Gy per fraction for 25 fractions with
concurrent chemotherapy followed by surgery.
30
Patient 9 – A 55 year old female diagnosed with non-small cell lung carcinoma of the right lung
with mediastinal involvement, stage IIIA. The patient has a smoking history of 1 ½ packs per
day for 18 years and quit smoking 3 years ago. The recommendation from the RO was a
preoperative course of RT prescribed to 45Gy at 1.8Gy per fraction for 25 fractions with
concurrent chemotherapy followed by surgery.
Instrumentation
This off-line ART technique utilizes the Philips Pinnacle3 v.9.0 treatment planning
system (TPS) and involve rigid image registration of the treatment planning CT data set to the
CTOR data sets obtained from a Siemens Somatom Sensation Open CT scanner. This study is a
retrospective review of nine patient case studies who received RT for non-small cell lung
carcinoma. Additional research included incorporating IGRT technologies with ART strategies
of lung cancer patients. For each patient, an off-line ART re-planning technique was
demonstrated using CTOR data sets and the original planning CT data sets. Observations and
measurements of the changes in tumor volumes using this adaptive technique were compared.
Information and findings from this retrospective patient review were discussed.
Data Collection
Data collected in this study consisted of tumor volume comparisons and measurements
from the original radiation therapy data set and treatment plan to a CTOR data set on every tenth
fraction of RT. A fusion of the original tumor volume on the CTOR data set from every tenth
fractionation was compared and measured. Once this registration and fusion are validated for
accuracy, tumor volumes from the initial treatment planning CT data set were propagated onto
the CTOR data sets. The initial propagated tumor volumes on the CTOR data set were adapted to
any tumor volume changes, tumor volume reductions, or anatomical changes and measured in
reference to the initial tumor volumes. The measurement of tumor volume changes due to RT
treatment (expansions or reductions) and any dosage changes to the tumor volumes were
analyzed and discussed.
Data Analysis
The retrospective patient reviews compared data sets obtained from a CTOR system to
the initial planning CT data sets used in the patients RT plan on the 10th, 20th, and 30th treatment
fraction. As stated above, the tumor volumes were analyzed by comparing the treatment planning
CT data set volumes to the CTOR data set volumes and measuring the changes of the target
volumes. These measurements were reported as percentage deviations compared to the original
31
RT treatment plan. In addition, dose changes and tumor dose coverage on the target volumes
were accessed. An adaptation of the initial RT plan due to these changes in tumor volume, shape
and position was done. The intent was to measure the target volumetric changes in anticipation
that the target volume and treatment margins would significantly change and adapt the patient’s
RT to these changes. Overall, these reductions should benefit the patient’s RT treatment by
allowing for tumor dose escalation, limiting the toxicities from RT, and hopefully a better long
term outcome.
Limitations
One limitation of this methodology is the accuracy of the image registration and fusion of
the CTOR data sets to the initial CT data set. The positional and rotational accuracy of the image
registration based on inter-observer variations may affect the tumor volume propagation of the
original tumor volumes onto the CTOR data sets. Another possible limitation of this
methodology is the tumor volume definition uncertainty due to the patients’ respiratory cycle.
The methodology of adapting the contours of tumor volumes and assessing treatment field
margins is based on GTV’s and PTV’s. The influence of the patients’ respiratory motion and the
effects it has on the delineation of the tumor volumes and the OR is beyond the scope of this
research study.
Summary
This retrospective study presented a single institution’s experience with an off-line ART
technique using a CTOR system. The retrospective study compared data sets obtained from a
CTOR system to the initial planning CT data sets used in the patients RT plan on the 10th, 20th,
and 30th treatment fraction. These data sets were analyzed to assess tumor volume changes and
develop an ART technique. A discussion of the advantages and disadvantages, results, and the
experiences in implementing this technique will determine if it is purposeful, practical, and
efficient in order to benefit lung cancer patients at UNMC.
32
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Gomez D, Chang J. Adaptive radiation for lung cancer. J Oncol. 2011;2011: 898391.
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