Imaging e Radioterapia: presente e futuro · 2010-04-22 · Summary of abbreviations and terms...

Imaging e Radioterapia:

presente e futuro

Imaging e Radioterapia:

presente e futuro

Umberto Ricardi

Università di Torino

• Technological advances in treatment planning and delivery provide unique opportunities for improving the precision and, potentially, also the locoregionaleffectiveness 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

Radiation therapy is targeted therapy

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

SummarySummary of of abbreviationsabbreviations and and termsterms commonlycommonly usedused in in modernmodern thoracicthoracic radiationradiation oncologyoncology

4D4D--CT CT Four-dimensional CT scan: respiration-correlated CT can used to visualize and account for tumormotion. The fourth dimension is time

4D4D--RTRT Four-dimensional RT is the explicit inclusion of the temporal changes in anatomy during the imaging, planning and delivery of radiotherapy

CBCTCBCT 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 permitsvisualization of the tumor position durignt reatment

CoachingCoaching Audio-coaching is used to optimize breathing regularity during RGRT. Video-coaching providesvisual feedback of the breathing pattern to the patient to optimize breathing depth during RGRT

IGRTIGRT Image-guided RT: 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. The ability to check the tumor position during treatment allows for smaller safety margins and bettersparing of normal tissues

MVCTMVCT See cone-beam CT: megavoltage CT is a cone-beam CT scanner integrated in a linear acceleratorusing the megavoltage treatment beam instead of a separate Kilovoltage source

RGRTRGRT Respiration gated radiation therapy: also known as Gating. Advanced treatment technique thatswitches the radiation beams on and off according to respiration, allowing for smaller radiationfields in moving tumor

SRTSRT Stereotactic radiation therapy is a high precision technique used to deliver high-dose fractions of radiation in only 3-8 sessions

Histology is missing in:

Nyman (2006) 9/45 pts (20%)

Wulf (2004) 4/20 pts (20%)

Beitler (2006) 17/75 pts (23%)

24/72 pts (33%)

diameter 8 mm diameter 12 mm

SUVmax 4.8SUVmax 1.8

Clinical proof of malignancyClinical proof of malignancy

TerminologyTerminology usedused forfor definingdefining target target volumesvolumes in in radiotherapyradiotherapy

ICRU

GTV

Treated Volume

Irradiated Volume

Gross tumor volume (GTV): the volume encompassingall recognized tumor volume

Clinical target volume (CTV): the GTV volume + anextra margin for potential microscopic tumor extensionand 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 + anextra margin to account for intra-fractional movementof lung tumors and pathological nodes (organ motion)

Planning target volume (PTV): the CTV or ITV plus anextra margin for planning and patient setupinaccuracy. The PTV is the volume used for treatmentplanning.

• patient positioning• CT scanning• tumor mobility• generating target volumes• treatment planning• treatment delivery• scoring response and toxicity

EORTC recommendations

• 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

Target Contouring recommendations(EORTC Radiotherapy Group)

Target Contouring recommendations(EORTC Radiotherapy Group)

Senan, Radiotherapy and Oncoogy, 2004

Challenges for RT planning: - Atelectasis- Effusion- Nodal involvement- Movements (respiration, cardiac)

Imaging for RT planning Imaging for RT planning

CT for RT planning CT for RT planning

PET: Why?PET: Why?PET: Why?

- Combination of high sensitivity and high spatial resolution- Exact measure of regional tracer concentration: higherglucose metabolism in tumour cells- Combination with anatomic detail (PET/CT)

““Delineation, differentiationDelineation, differentiation””

Challenges for RT planning: - Atelectasis- Effusion- Nodal involvement- Movements (respiration, cardiac)

Imaging for RT planning Imaging for RT planning

Impact of PET scan on RT planningImpact of PET scan on RT planningImpact of PET scan on RT planning

Improved accuracy on nodal target volume need for redefining the GTV

Improved accuracy on nodal target volume Improved accuracy on nodal target volume need for redefining the GTVneed for redefining the GTV

PTV is expanded to encompass PET positive mediastinal node

PTV is expanded to encompass PET positive mediastinal node

PETPET--CT information CT information forfor nodalnodal volume (GTV)volume (GTV)

Imprecision in clinical target volume definition remains an obstacle for high-precision RT

Functional imaging may reduce the GTV definition’s inter-clinician variability

Defining the TargetDefining the Target

InterobserverInterobserver variabilityvariability in target volume in target volume delineationdelineation

Steenbakkers et al., 2006

CT: CT: largelarge interobserverinterobserver variabilityvariability

PETPET--CT: CT: reductionreduction in in interobserverinterobserver variabilityvariability

FDGFDG--PET: PET: methodologicalmethodological aspectsaspects and and pitfallspitfalls

4D CT4D CT--PET PET imagingimaging

IntroductionIntroduction of of systematicsystematic error: error: mismatchesmismatches in position in position betweenbetween twotwo imagingimaging modalitiesmodalities

“ 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

From GTV to CTVFrom GTV to 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

12

A

B

NSCLC: In specifying the CTV….

Evaluation of microscopic tumor extension in NSCLC for 3D-CRT…..The microscopic extension was different between ADC and SCC…..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

NSCLC: In specifying the CTV….

10 radiation oncologists, particularly expert in thoracic oncology, contoured the post-operative CTV in 2 representative resectedNSCLC patients (pT2pN2)

Even amongexperts,

significantinterclinicianvariations are observed in

PORT fields!!!

HighHigh--precision radiotherapy is a multiprecision radiotherapy is a multi--step process, step process, which is only as good as the weakest componentwhich is only as good as the weakest component

Literature-based recommendations for treatment planning and execution for high-precision radiotherapy in lung cancer.

S. Senan, D. DeRuysscher et al., Radiother Oncol ‘04

IMRT

3D‐CRT

New Potentials of Radiotherapy in NSCLC: IMRTNew Potentials of Radiotherapy in NSCLC: IMRTComplex dose distribution with steep dose gradients

N -

N +

Mean dose to critical organ according to different treatment technique

Theoretical fluence map (a,d); Fluence map obtained in motion (b, e) Fluence map in motion but acquired in respiration-gated mode (c,f)

IntensityIntensity--modulated radiotherapy and motionmodulated radiotherapy and motionIMRT fluence maps for one out of five beams used for a treatmentof lung tumor and the resulting dose distributions in an axial plane.

Jiang, Semin Radiat Oncol 2006

Breathing motion and tumor position Breathing motion and tumor position

Lung tumor mobility 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

- One CT scan is not sufficient to delineate the GTV- Motion should be taken into account:

- 4D CT

Respiratory motion results in imaging artifactsRespiratory motion results in imaging artifacts

How can we use 4DHow can we use 4D--CT informations in RT planning?CT informations in RT planning?

Individualized margins based on motion of tumor and nodes

Respiration correlated (4Respiration correlated (4--D) CT 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

RespirationRespiration correlatedcorrelated (4D) CT(4D) CT

The 4DThe 4D--CT is reconstructed in 8 or 10 phases, yelding 8 or 10 3D CT datCT is reconstructed in 8 or 10 phases, yelding 8 or 10 3D CT datasetsasets

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 4DThe 4D--CT is reconstructed in 8 or 10 phases, yelding 8 or 10 3D CT datCT is reconstructed in 8 or 10 phases, yelding 8 or 10 3D CT datasetsasets

RespirationRespiration correlatedcorrelated (4D) CT(4D) CT

4D-CT: University of TurinGeometrical 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 and 5 mm in all directions of margin)

Conventional CT (with 2. 5 mm in all directions of margin)

Respiration correlated (4D) CTRespiration correlated (4D) CT

MIPs can help to individualize the RT treatment for MIPs can help to individualize the RT treatment for lung cancer patients lung cancer patients

Improving Radiation Therapy in Lung Cancer

Highly Conformal RT Multimodality Imaging IGRT

Image Guided Radiation Therapy 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 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)

Image Guided Radiation Therapy (IGRT)

Author (year) Pt# Grade Vd %

Armstrong (1995) 31 ≥IIIV25 ≤30% 4

>30% 38

Graham (1999) 99 ≥IIV20 <22 0

22-31 732-40 13>40 36

Hernando (2001) 201 AnyV30 ≤18 6V30 >18 24

V25, V20, V30 and PneumonitisV25, V20, V30 and Pneumonitis

(Volume receiving d or higher doses)

Con

form

ance

Intra-cranial SRS

Extra-cranial SRS/SRT

IGRT

ConventionalRadiotherapy

IMRT

3D-CRT

Accuracy

Advanced-Technology RT

What CBCT Guidance RT can do for you 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) 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

Pre-RT 4th week of RT

Atelectasis resolved

Tumor evolution during radiotherapyTumor evolution during radiotherapy

Dose distribution before and after re-planning

What CBCT Guidance RT can NOT (yet) do for youWhat CBCT Guidance RT can NOT (yet) do for you

- Monitor tumor motion variability during a treatment fraction

Lung Tumour Baseline ShiftLung Tumour Baseline Shift

Managing tumor motionManaging tumor motionEncompass motion: increased risk ofnormal tissue toxicity

Tumor tracking: implanted marker

Breath‐hold: freeze movement

Gating: respiratory cycle as surrogate of tumor position

John R. van Sörnsen de Koste, PhD

Although marker geometry can be affected by tumor shrinkage,

implanted markers are stable within tumors throughout the

treatment duration

Viscoil

Gold seed

Maximumexhale

Geometricalaverageposition

Maximuminhale

Planning Concepts For BreathingConventional

freebreathing

Internaltarget

volume

Gating orbreathholding

PTV

GTV

ITV

CTV

RespirationRespiration--gated radiation therapy (RGRT) 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)

Breathingcycle

Gating Challenges

Planning Concepts For BreathingPlanning Concepts For Breathing

Maximumexhale

Geometricalaverageposition

Maximuminhale

Conventionalfree

breathing

Internaltarget

volume

Gating orbreathholding

PTV

GTV

ITV

CTVTime-weightedaverageposition

Mid-position

Lung Tumour Baseline ShiftLung Tumour Baseline Shift

4D VolumeView Imaging4D VolumeView Imaging

Breathingcycle

4D VolumeView Imaging

Breathingcycle

4D Image Registration

Patient Shift And Delivery

Treatment Process

4D planning CT4D planning CT Mid-ventilationMid-ventilation Treatment planTreatment plan

4D Volume View4D Volume View 4D image reg.4D image reg. Patient shiftPatient shift DeliveryDelivery

PlanningPlanning

TreatmentTreatment

- 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

FDG-PET as a predictor of responseFDG-PET as a predictor of response

FDG-PET as a predictor of responseFDG-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 EORTC PET-study Recommendations

Weber et al. J Clin Oncol, 2003

Monitoring ResponseMonitoring ResponseMonitoring Response

… The Past

• By using tumor skrinkage as a standard endpoint of response, current conventional imaging follow-up is based on morphological criteria RECIST (Response Evaluation Criteria In Solid Tumors) criteria

RECIST CriteriaRECIST CriteriaComplete 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 sumLD since the treatment started

Limitations of RECISTLimitations 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

6-12 months after SBRT No evidence of tumor recurrence on PET at 24 months

Pre-SBRT

Radiation pulmonary injuryRadiation pulmonary injury

• An armada of advanced technology is becoming clinically available: PET-CT imaging, IMRT treatment, respiration-gated 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

HiHi--Tech Radiotherapy in thoracic oncologyTech Radiotherapy in thoracic oncology

Thoracic Oncology UnitRadiation OncologyUniversity of Turin

Andrea Filippi, M.D.Alessia Guarneri, M.D.Cristina Mantovani, M.D.

Riccardo Ragona, Ph.D.

Imaging e Radioterapia: presente e futuro · 2010-04-22 · Summary of abbreviations and terms...

Documents

Transcript of Imaging e Radioterapia: presente e futuro · 2010-04-22 · Summary of abbreviations and terms...