Download Imaging e Radioterapia

Imaging e
Radioterapia:
presente e futuro
Umberto Ricardi
Università di Torino
Radiation therapy is targeted therapy
• Technological advances in treatment planning and
delivery provide unique opportunities for improving
the precision and, potentially, also the locoregional
effectiveness of RT
• Radiation treatment “failure” occurs if and only if…
– the biologically equivalent dose is not sufficiently
high OR …
– there is disease outside the high-dose volume
– excessive dose to normal healthy tissues
Role of imaging in radiotherapy
How to improve radiotherapy results?
Treatment simulation:
all relevant informations on target definition are incorporated
Treatment planning:
involves selection of delivery technique and approach for
optimizing target coverage and normal tissue avoidance
Radiation delivery and treatment verification
Summary of abbreviations and terms commonly used in
modern thoracic radiation oncology
4D-CT
Four-dimensional CT scan: respiration-correlated CT can used to visualize and account for tumor
motion. The fourth dimension is time
4D-RT
Four-dimensional RT is the explicit inclusion of the temporal changes in anatomy during the
imaging, planning and delivery of radiotherapy
CBCT
Cone-beam CT refers to the use of a cone shaped Kilovoltage X-ray beam and a flat panel
imaging device integrated into a linear accelerator to generate CT images. CBCT permits
visualization of the tumor position durignt reatment
Coaching
Audio-coaching is used to optimize breathing regularity during RGRT. Video-coaching provides
visual feedback of the breathing pattern to the patient to optimize breathing depth during RGRT
IGRT
Image-guided RT: modern linear accelerators have integrated X-ray imaging devices and conebeam CT scanners, making it possible to verify tumor position before and during treatment. The
ability to check the tumor position during treatment allows for smaller safety margins and better
sparing of normal tissues
MVCT
See cone-beam CT: megavoltage CT is a cone-beam CT scanner integrated in a linear accelerator
using the megavoltage treatment beam instead of a separate Kilovoltage source
RGRT
Respiration gated radiation therapy: also known as Gating. Advanced treatment technique that
switches the radiation beams on and off according to respiration, allowing for smaller radiation
fields in moving tumor
SRT
Stereotactic radiation therapy is a high precision technique used to deliver high-dose fractions of
radiation in only 3-8 sessions
Clinical proof of malignancy
Histology is missing in:
Nyman (2006)
9/45 pts (20%)
Wulf (2004)
4/20 pts (20%)
Beitler (2006)
17/75 pts (23%)
diameter 8 mm
diameter 12 mm
24/72 pts (33%)
SUVmax 1.8
SUVmax 4.8
Role of imaging in radiotherapy
How to improve radiotherapy results?
Treatment simulation:
all relevant informations on target definition are incorporated
Treatment planning:
involves selection of delivery technique and approach for
optimizing target coverage and normal tissue avoidance
Radiation delivery and treatment verification
Terminology used for defining target volumes in radiotherapy
Gross tumor volume (GTV): the volume encompassing
all recognized tumor volume
Irradiated Volume
Clinical target volume (CTV): the GTV volume + an
extra margin for potential microscopic tumor extension
and inaccuracies in target definition; this margin can
be symmetrical around the tumor (typically 5 mm), or
asymmetrical, for example lesser margins in the
direction of an adjacent bony structure
Internal target volume (ITV) : the CTV volume + an
extra margin to account for intra-fractional movement
of lung tumors and pathological nodes (organ motion)
Planning target volume (PTV): the CTV or ITV plus an
extra margin for planning and patient setup
inaccuracy. The PTV is the volume used for treatment
planning.
Treated Volume
GTV
ICRU
EORTC recommendations
• patient positioning
• CT scanning
• tumor mobility
• generating target volumes
• treatment planning
• treatment delivery
• scoring response and toxicity
Target Contouring recommendations
(EORTC Radiotherapy Group)
• The optimal CT window settings for contouring tumors in lung
parenchyma or mediastinum should ideally be preset at the planning
workstation
• The Naruke scheme should be referred in Rt planning, and nodes with
a short-axis diameter of > 1 cm should be included in the GTV
•PET scans are superior to CT scans for staging mediastinal nodes, and
incorporating PET findings into CT-based planning scan results in
changes to Rt plans in a significant proportion of patients
Senan, Radiotherapy and Oncoogy, 2004
Imaging for RT planning
Challenges for RT planning:
- Atelectasis
- Effusion
- Nodal involvement
- Movements (respiration, cardiac)
Imaging for RT planning
Challenges for RT planning:
- Atelectasis
- Effusion
- Nodal involvement
- Movements (respiration, cardiac)
CT for RT planning
PET: Why?
“Delineation, differentiation”
- Combination of high sensitivity and high spatial resolution
- Exact measure of regional tracer concentration: higher
glucose metabolism in tumour cells
- Combination with anatomic detail (PET/CT)
Imaging for RT planning
Challenges for RT planning:
- Atelectasis
- Effusion
- Nodal involvement
- Movements (respiration, cardiac)
Impact of PET scan on RT planning
Improved accuracy on nodal target volume Æ
need for redefining the GTV
PTV is expanded to encompass PET positive
mediastinal node
PET-CT information for nodal volume (GTV)
Defining the Target
Imprecision in clinical target volume definition
remains an obstacle for high-precision RT
Functional imaging may reduce the GTV definition’s
inter-clinician variability
Interobserver variability in target volume delineation
CT: large interobserver variability
PET-CT: reduction in interobserver variability
Steenbakkers et al., 2006
FDG-PET: methodological aspects and pitfalls
4D CT-PET imaging
Introduction of systematic error:
mismatches in position between two imaging modalities
From GTV to CTV
“ The Clinical Target Volume (CTV) is a tissue volume that contains the GTV(s) and/or subclinical
malignant disease at a certain probability level”
The relevant data to consider are the
probability of microscopic extension at different
distances around the GTV, and the probability
of subclinical invasion of regional lymph nodes
or other tissues
From GTV to CTV
NSCLC: In specifying the CTV….
International consensus (Choi, 2001)
• CTV for involved nodes consists of a 1
cm margin of normal tissue around the
involved hilar nodes, a 2 cm
circumferential and a 2.5 cm
craniocaudal margin for the coverage of
one sentinel node station beyond the
involved mediastinal lymph nodes
• CTV-N for involved nodes at stations 7
and 4R should include stations 4L, 5, 6,
2R and 2L
1
2
A
B
NSCLC: In specifying the CTV….
ƒ Evaluation of microscopic tumor extension in
NSCLC for 3D-CRT…
..The microscopic extension
between ADC and SCC…
was
different
..The mean value of microscopic extension was
2.69 mm for ADC and 1.48 mm for SCC (p=0.01)
..A margin of 8 mm and 6 mm must be chosen for
ADC and SCC respectively….
Giraud, 2000
ƒ 10 radiation oncologists,
particularly expert in
thoracic oncology,
contoured the postoperative CTV in 2
representative resected
NSCLC patients (pT2pN2)
Even among
experts,
significant
interclinician
variations are
observed in
PORT fields!!!
Literature-based recommendations for treatment planning and execution for highprecision radiotherapy in lung cancer.
S. Senan, D. DeRuysscher et al., Radiother Oncol ‘04
High-precision radiotherapy is a multi-step process,
which is only as good as the weakest component
How to improve radiotherapy results?
Treatment simulation:
all relevant informations on target definition are incorporated
Treatment planning:
involves selection of delivery technique and approach for
optimizing target coverage and normal tissue avoidance
Radiation delivery and treatment verification
New Potentials of Radiotherapy in NSCLC: IMRT
Complex dose distribution with steep dose gradients
3D‐CRT
IMRT
Mean dose to critical organ according to different
treatment technique
NN+
Intensity-modulated radiotherapy and motion
IMRT fluence maps for one out of five beams used for a treatment
of lung tumor and the resulting dose distributions in an axial plane.
Theoretical fluence map (a,d); Fluence map obtained in motion (b, e)
Fluence map in motion but acquired in respiration-gated mode (c,f)
Breathing motion and tumor position
Jiang, Semin Radiat Oncol 2006
Lung tumor mobility
- 100 lymph-nodes from 14 patients (Stage I)
and 27 patients (Stage III) were manually
contoured in all 4D CT respiratory phases.
- Motion was derived from changes in the
nodal center-of-mass position.
- Primary tumors were also delineated in all
phases for 16 patients with Stage III disease.
- Average 3D nodal motion during quiet
breathing was 0.68 cm (range, 0.17–1.64 cm)
Motion was greatest in the lower mediastinum (p = 0.002), and bulky nodes showed
motion similar to that in smaller nodes
- In 11/16 patients studied, at least one node moved more than the corresponding
primary tumor
- No association between 3D primary tumor motion and nodal motion was observed
Respiratory motion results in imaging artifacts
- One CT scan is not sufficient to delineate the GTV
- Motion should be taken into account:
- 4D CT
How can we use 4D-CT informations in RT planning?
Individualized margins based on motion of tumor and nodes
Respiration correlated (4-D) CT
During 4D-CT image acquisition, the respitatory waveform
is recorded and ‘time-stamped’ on each of the many images
that are acquired at each couch position, for the duration of
at least one full respiratory cycle
Respiration correlated (4D) CT
All acquired images are resorted in order to derive multiple
3DCT sets which represent the patient’s anatomy during
each specific phase of the respiratory cycle
The 4D-CT is reconstructed in 8 or 10 phases, yelding 8 or 10 3D CT datasets
Respiration correlated (4D) CT
The 4D-CT is reconstructed in 8 or 10 phases, yelding 8 or 10 3D CT datasets
4D-CT: University of Turin
Geometrical differences in target volumes between
conventional CT and 4D CT imaging in stereotactic body
radiotherapy for lung tumours
The mean target volumes of
conventional CT and 4D-CT
were 19.40 cm3 and 13.14 cm3 ,
respectively
Conventional CT (with 10 mm in CC Conventional CT (with 2. 5 mm in all
and 5 mm in all directions of margin)
directions of margin)
Respiration correlated (4D) CT
MIPs can help to individualize the RT treatment for
lung cancer patients
How to improve radiotherapy results?
Treatment simulation:
all relevant informations on target definition are incorporated
Treatment planning:
involves selection of delivery technique and approach for
optimizing target coverage and normal tissue avoidance
Radiation delivery and treatment verification
Role of imaging in radiotherapy
Improving Radiation Therapy in Lung Cancer
Highly Conformal RT
Multimodality Imaging
IGRT
Image Guided Radiation Therapy
Modern linear accelerators have integrated X-ray
imaging devices and cone-beam CT scanners, making it
possible to verify tumor position before and during
treatment
•
Cone-beam CT refers to the use of a cone shaped
Kilovoltage X-ray beam and a flat panel imaging device
integrated into a linear accelerator to generate CT
images (MV-CBCT: using megavoltage treatment beam)
•
CBCT permits visualization of the tumor position before
each fraction, allowing on-line repositioning and daily
assessment of changes in tumour volume and patient’s
anatomy
•
Image Guided Radiation Therapy (IGRT)
Image-guided radiotherapy (IGRT) is defined as
frequent imaging in the treatment room (treatment
position) that allows treatment decisions to be made
on the basis of these images
‰
‰ IGRT aims at decreasing CTV-to-PTV margins
(allowing for smaller safety margins around the
tumor)
V25, V20, V30 and Pneumonitis
(Volume receiving d or higher doses)
Author (year)
Armstrong (1995)
Graham (1999)
Hernando (2001)
Pt#
31
99
201
Grade
≥III
≥II
Any
Vd
%
V25 ≤30%
4
>30%
38
V20 <22
22-31
32-40
>40
0
7
13
36
V30 ≤18
6
V30 >18
24
Advanced-Technology RT
Intra-cranial
SRS
Conformance
Extra-cranial
SRS/SRT
IGRT
IMRT
3D-CRT
Conventional
Radiotherapy
Accuracy
What CBCT Guidance RT can do for you
- Check tumor motion shortly before treatment
- Reduce interfraction patient set-up errors
- Discover tumor baseline shifts
- Detect anatomical changes within the thorax
- Quantify intrafraction patient stability
Image Guided Adaptive Radiotherapy (IGART)
Interactive adaptation of the treatment on the basis of daily assessment
of changes in tumour volume and response to therapy
Megavolt Computed Tomography imaging (blue)
superimposed on the reference CT data set (grey) showing
a large deformation in the patient’s anatomy
Adaptive IGRT
- 22 pts underwent RT for Stage I-III NSCLC with conventional fractionation;
15 received concurrent chemotherapy
- Two repeat CT scans were performed at a nominal dose of 30 Gy and 50 Gy
- Respiration-correlated 4D-CT scans were used for evaluation of respiratory
effects in 17 pts
- The gross tumor volume (GTV) was delineated on simulation and all
individual phases of the repeat CT scans
The median GTV reduction was 24.7% (p<0.001) at the first
repeat scan and 44.3% (p<0.001) at the second repeat scan
Tumor evolution during radiotherapy
Pre-RT
4th week of RT
Atelectasis resolved
Dose distribution before and after re-planning
What CBCT Guidance RT can NOT (yet) do for you
- Monitor tumor motion variability during a treatment fraction
Lung Tumour Baseline Shift
Managing tumor motion
Encompass motion: increased risk of
normal tissue toxicity
Breath‐hold: freeze movement
John R. van Sörnsen de Koste, PhD
Tumor tracking: implanted marker
Gating: respiratory cycle as surrogate of tumor position Viscoil
Gold seed
Although marker geometry can
be affected by tumor shrinkage,
implanted markers are stable
within tumors throughout the
treatment duration
Planning Concepts For Breathing
Conventional
free
breathing
Maximum
exhale
Geometrical
average
position
Maximum
inhale
Internal
target
volume
CTV
GTV
PTV
ITV
Gating or
breath
holding
Respiration-gated radiation therapy (RGRT)
Breathing synchronized irradiation requires a technology to monitor the
breathing motion and its relationship with the actual tumor position
(infrared reflective markers placed on the patients’surface)
This information is then used to trigger the treatment beam
When the patient’s respiratory signal coincides with the treatment window
or “gate”, triggers the beam for treatment (on)
Gating Challenges
Breathing
cycle
Gating Challenges
Breathing
cycle
Gating Challenges
Breathing
cycle
Planning Concepts For Breathing
Conventional
free
breathing
Maximum
Timeexhale
weighted
Geometrical
average
average
position
position
Maximum
inhale
Internal
target
volume
CTV
GTV
PTV
ITV
Gating or
breath
holding
Mid-position
Lung Tumour Baseline Shift
4D VolumeView Imaging
Breathing
cycle
4D VolumeView Imaging
Breathing
cycle
4D Image Registration
4D Image Registration
Patient Shift And Delivery
Treatment Process
Planning
4D planning CT
4D Volume View
Mid-ventilation
4D image reg.
Treatment plan
Patient shift
Treatment
Delivery
- Retrospective study compares disease outcomes and toxicity in pts
treated with concomitant CT and either 4DCT/IMRT or 3DCRT
- A total of 496 NSCLC were enrolled (318 treated with CT/3DCRT and
91 with 4DCT/IMRT)
- Median dose of 63 Gy
- Disease end points were LRP, distant metastasis, and OS
- Disease covariates were GTV, nodal status, and histology
- The toxicity end point was Grade3 radiation pneumonitis; toxicity
covariates were GTV, smoking status, and dosimetric factors
Role of imaging in radiotherapy
FDG-PET as a predictor of response
FDG-PET as a predictor of response
• Because glucose uptake, which is directly related to tissue metabolic activity, can
be affected before changes in tumour size, there is potential for detection or
prediction of early response
• However, difficulties arise when comparing studies because of the variable
quantification methods used and post-therapy imaging delays Æ EORTC PETstudy Recommendations
Weber et al. J Clin Oncol, 2003
Monitoring Response
… The Past
• By using tumor skrinkage as a standard endpoint of
response, current conventional imaging follow-up is based
on morphological criteria Æ RECIST (Response Evaluation
Criteria In Solid Tumors) criteria
RECIST Criteria
Complete Response
(CR):
Disappearance of all target lesions
Partial Response
(PR):
At least a 30% decrease in the sum of the LD of target lesions,
taking as reference the baseline sum LD
Progressive Disease
(PD):
At least a 20% increase in the sum of the LD of target lesions,
taking as reference the smallest sum LD recorded since the
treatment started or the appearance of one or more new lesions
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient
increase to qualify for PD, taking as reference the smallest sum
LD since the treatment started
Limitations of RECIST
- Line lengths can fail to account for:
– complex shapes
– changes in non-transaxial extent of disease
– total tumor burden
- Assumes uniform contraction or expansion
- Inter-rater reliability decreases as disease becomes more complex
- Inter-observer variability
- Assumes spheroid growth of tumors
- Arbitrary number of measurable lesions
Radiation pulmonary injury
Pre-SBRT
6-12 months after SBRT
No evidence of tumor recurrence on PET at 24 months
Hi-Tech Radiotherapy in thoracic oncology
•
•
•
An armada of advanced technology is becoming clinically
available: PET-CT imaging, IMRT treatment, respirationgated beam delivery, Image Guided Radiotherapy
Advanced radiotherapy technology has the potential to
lead to significant improvement in the local control (to be
proven)
Radiation Oncology family should be aware of the new
technical developments and to critically assess their
potential impact upon clinical outcome
Thoracic Oncology Unit
Radiation Oncology
University of Turin
Andrea Filippi, M.D.
Alessia Guarneri, M.D.
Cristina Mantovani, M.D.
Riccardo Ragona, Ph.D.