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

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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

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Lung/Mediastinum – IIIA NSCLCProtons IMRT

IMRT-Protons

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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

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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

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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

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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