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Advances in Advances in Thoracic Radiation Thoracic Radiation
TherapyTherapy
Advances in Advances in Thoracic Radiation Thoracic Radiation
TherapyTherapyShilpen Patel MD, FACRO
Department of Radiation Oncology, University of Washington, Seattle, WA
Objectives
• Understand the basics on Lung Cancer
• Discuss the new techniques and technologies in radiation oncology
• Understand current data available using these techniques
Roadmap• Background
• SBRT
• Calypso
• Intensity Modulated Radiation Therapy (IMRT)
• Neutrons
• Protons
Worldwide Incidence
ACS Global Facts and Figures, 2007
Background: EpidemiologyEstimated Incidence
Jemal et al. CA Cancer J Clin. 2008 Mar-Apr;58(2):71-96
Background: EpidemiologyEstimated Deaths
Jemal et al. CA Cancer J Clin. 2008 Mar-Apr;58(2):71-96
Leading Cancer Sites US Death Rate estimated
SBRT
Conventional Radiation Therapy
• For Medically Inoperable Tumors with 60-66 Gy:
• 15% long term survivors• 25% death from intercurrent illness• 30% death from metastatic disease• 30% death from local failure only
Sibley, Cancer 1998
Conventional Radiation Therapy• What is the influence of dose?
– Retrospective studies show local and distant failures decrease with increasing dose <65 Gy vs ≥ 65 Gy in Stage I patients
– In a prospective dose-escalation study, doses ≥ 80 Gy resulted in improved local control and overall survival in stage I/II patients
• So increased dose may IMPROVE SURVIVALKaskowitz L et al. IJROBP 1993Dosoretz D et al. IJROBP 1992
Sibley G et al. IJROBP 1998Rosenzweig et al. Cancer 2005
An extension of existing technologiesIntracranial SRS 3D-CRT
Overview SBRT•Used in primary or metastatic lesions of lung, liver, spine, retroperitoneum, pelvis
Key Features SRS SBRTLocation Cranial Extracranial
Immobilization Rigid head frame Body Frame
Max tumor diameter 3-4 cm 6-7 cm
Dose Regimen 15-24 Gy,
single fraction
36-60 Gy,
3-5 fractions
Targeting accuracy 1 mm 5 mm
Respiratory Control No Yes
Selecting patients for SBRT
• Staging of patient must be optimal– IA, IB (<=5-7cm), select IIB i.e. (T3N0 involving chest
wall)– CT chest (hi-res)/abdomen with contrast– PET (sensitivity, specificity and accuracy ~90%)
• Confirm suspicious nodes by mediastinoscopy• Caution with centrally located tumors
SBRT Results – Local ControlAuthor # pts Dose/Fx 2 yr
(%) 3 yr (%) 5 yr
(%)Timmerman 70 60-66/3 95 - -
Xia 43 50/10 - 95 -
Onishi
(multi-inst)
300 18-75/1-22 - - 80
Uematsu 50 50-60/5-10 - 94 -
Nagata 45 48/4 - 98 -
RTOG 0238 59 54/3 - 98 -
Nyman 45 45/15 - - 80
IU Phase II Local Control• Median
follow-up = 18 months
• One year local control = 98%
• Two year local control = 95%
Local Tumor Control
0 12 24 36 48
Months from Therapy
100
80
60
40
20
0
Pe
rce
nt L
oca
lly C
on
tro
lled
n=5
n=60 n=32n=70
RTOG 0236 Phase II• Median
follow-up = 34 months
• Three year local control = 98%
• Median Overall Survival = 48 months
Timmerman et al JAMA 2010
Calypso
Calypso :Limitations with Current Methods
Setup Errors
Patient Motion
Organ Motion
Tumor GeometryChanges
Barriers
Highly Conformal Radiation Therapy
• Tight Margins
• Increased Dose
Therapeutic Technologies
Goals
Improve DiseaseControl
Reduce Complications
Organ Motion Limits Effectiveness
Platform Technology — GPS for the Body®
Beacon® Electromagnetic Transponder
Wireless miniature Beacon® Electromagnetic Transponders
Accurate, objective guidance for target localization and continuous, real-time tracking
Wireless miniature Beacon® Electromagnetic Transponders
Accurate, objective guidance for target localization and continuous, real-time tracking
Actual size: ~8.5 mm
Platform Overview
Implanted Beacon® Electromagnetic
Transponders
Implanted Beacon® Electromagnetic
Transponders
4D Tracking Station™
4D Tracking Station™
4D Console™
4D Console™
Infrared Cameras
Optical Targets
Optical SystemOptical System
4D Electromagnetic Array™
4D Electromagnetic Array™
System Overview – Monitoring
0.00
0.00
0.05
0.050.10
0.10
0.100.150.200.25
0.050.000.15
Tumor bed motion monitoring
Post-treatment reports
Tumor bed motion monitoring
Post-treatment reports
What about IMRT?
Lung IMRT (primary)
Wedge-Pair Conventional 6MV 9-Field
Reasons to wait
• Tumor motion• Dose calculations
– Small field heterogeneity
• NTCP– Large volume low dose
• But sometimes you can’t– Consider radioprotectors
Neutrons
Relative Biologic Effectiveness
Salivary Gland Protocol 80-01
Salivary Gland: Local Control
Example of Tumors Treated
Adenoid Cystic Ca Trachea
Protons
• Protons behave differently than x-rays:
– Protons
– X-Rays do not
• Protons improve the “therapeutic ratio”
– maximizing tumor control while minimizing side effects
• At a given radiation dose to a tumor protons deliver, on average, less than half the radiation dose to normal tissues than do x-rays 1
The Value of Protons
Evidence of Distal Range Stopping
Before treatment Treatment plan After treatment
35
3D 5 fields6x Parallel
opposed fields
tumor
Improvements in radiation dose distribution
Protons 4 field
IMRT 9 fields
EVOLUTION?
x-rays x-raysx-rays protons
Why Protons for Lung Cancer?• Paradigms for lung cancer and radiation
therapy– More dose leads to improved outcomes?– Retrospective analysis shows that >70 Gy
is desirable– Larger volumes to low and intermediate
doses are associated with high rates of esophagitis and pneumonitis
36
Why Protons for Lung Cancer?X-rays have reached its dose limits
Trials showing that the maximum tolerated dose is 74 Gy with chemotherapy
• Protons allow dose escalation while reducing toxicity compared to x-rays
• Dose escalation can be achieved with protons without exceeding known indicators of lung toxicity
37
Lung/Mediastinum – IIIA NSCLCProtons IMRT
IMRT-Protons
38
Lung with tumor (dose to healthy tissue only)
Lung without tumor
Both lungs
Volume receiving dose Volume receiving Integral dose
Mean Dose 5 Gy 10 Gy 20 Gy 5 Gy
IMRT 24.2 Gy 61.5% 49.0% 37.1% 49.7% 8.1 Gy
Proton 21.2 Gy 44.0% 39.3% 33.3% 27.1% 5.4 Gy
Absolute improvement 3.0 Gy 17% 10% 4% 23% 33%
• Radiation-induced pneumonitis can result from even low doses of excess radiation in the lungs
Excess Radiation Causes Long-Term Side Effects
Comparison of Dose Escalated Proton Therapy and IMRT, both 74 Gy, for Stage III Lung Cancer
39
Lung with tumor (dose to healthy tissue only)
Lung without tumor
Both lungs
Volume receiving dose Volume receiving Integral
Dose Mean Dose 5 Gy 10 Gy 20 Gy 5 Gy dose
Conventional Dose IMRT 60-63 Gy 20.1 Gy 58.5% 45.3% 34.5% 45.5% 6.8 Gy
Escalated Dose Proton 74 Gy 21.1 Gy 44.0% 39.3% 33.3% 27.1% 5.4 Gy
Absolute improvement - (1.0) Gy 14.5% 6.0% 1.2% 18.4% 21%
Excess Radiation Causes Long-Term Side Effects
Comparison of Dose Escalated Proton Therapy (74 Gy) and Conventional Dose IMRT (60-63 Gy) for Stage III Lung Cancer
40
Lung toxicity for inoperable NSCLC
3D CRT IMRT Protons
Dose 63 Gy 63 Gy 74 CGE
% patients stage IIIA-B22 87% 91% 87%
Toxicity
Esophagitis – G3+ 18% 44% 5%
Pneumonitis – G3+ 30% 9% 2%
NSCLC treated with radiation therapy + chemotherapy1
41
Protons outcomes and toxicity for radiation + chemo
RTOG 0117 M.D. Anderson
Trial type Phase II Phase II
Type of radiation 3D CRT Protons
Dose 74 Gy 74 CGE
Median follow up (months) 19.34 19.7
Survival
Median months 21.64 29.4
1-year overall rate 72.7%4 86%
1-year progression free rate 50.0%4 63%
Toxicity
Esophagitis – G3+ 40% (G2+)5 11%6
Pneumonitis – G3+ 23% 2%
Comparison of Phase II results from RTOG 0117 and M.D. Anderson– radiation and chemotherapy
Selection criteria
Protons+SBRT?
Proton SBRT for Stage I NSCLC• Better than photon therapy?• Are photons limited?
– Centrally located– Previously irradiated– Close to the Chest Wall– Large Tumors?
45
Proton SBRT for Stage I NSCLC• Dose:42-50 Gy in 3 to 5 fractions• Toxicity:
• Median Follow-up of 24 months– 2 year Overall Survival 64% and LC 100%
46
Radiation Associated Toxicity (n = 20)Graded Toxicity Grade 1 Grade 2 Grade 3Chest wall pain 0 1 0Dermatitis 3 1 0Dyspnea 0 0 0Fatigue 1 1 0Pneumonitis 6 0 1
Take Home Points
• Technology will help our patients• Efficacy and side effects will improve• Careful attention to detail will be required to
optimally implement new technologies• Proton therapy is promising and should be
considered in select patients