Stereotactic Involving (being, utilizing, or used) a surgical - - PDF document

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Walter J Curran, Jr, MD Executive Director Winship Cancer Institute of Emory University Group Chairman Radiation Therapy Oncology Group

Stereotactic RT in Early Stage Lung Cancer Is the Evidence Compelling???

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Stereotactic

Involving (being, utilizing, or used) a surgical technique for precisely directing the tip of a delicate instrument (as a needle) or beam

• f radiation in three planes (?) using

coordinates provided by medical imaging in

• rder to reach a specific locus in the body

(as a tumor in the brain, lung or liver)

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What enabled the Stereotactic Body Radiation Therapy (SBRT) ?

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David Jablons’ Mentors in Thoracic Surgery

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David Jablons’ Mentors in Thoracic Surgery

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David Jablons’ Mentors in Thoracic Surgery

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Technology Enabling SBRT

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What is SBRT?

• Potentially highly effective
• Potentially extremely dangerous

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RT Fractionation Options

• Conventionally Fractionated RT
• small daily doses
• go to very high cumulative doses
• tolerable for most normal tissues
• Hypofractionated RT
• larger daily doses (3-8 Gy)
• used mostly for palliation
• Ablative RT (Stereotactic)
• very high daily doses (8-20 Gy)
• overwhelm tumor repair
• causes “late” effects that may be intolerable

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Hypofractionation Benefits

• Reduce number of trips

– Increases convenience for patients – Decreased costs to system

• Hospital staffing and equipment Payors
• Biological

– Radiation at a specified dose is more tumorcidal if given in fewer “fractions”/High Dose

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Survey: 9 out of 10 Tumor Cells Prefer Conventional Fractionation

100 2 4 6 8 Survival Dose (Gy) 10-1 10-2

single fraction multiple 2 Gy fractions

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Ablative Treatments (Stereotactic) Must Exclude Normal Tissue

• Requirements for ablative hypofractionation:

–Abandon prophylactic treatment –Account for organ motion –Achieve sharper dose fall-off gradients to normal tissue (mimic radiosurgery)

• These requirements need advanced technology

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Ablative Treatments (Stereotactic) Must Exclude Normal Tissue

• Requirements for ablative hypofractionation:

–Abandon prophylactic treatment –Account for organ motion –Achieve sharper dose fall-off gradients to normal tissue (mimic radiosurgery)

• These requirements need advanced technology

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Phase I Dose Response for Local Control

20 40 60 80 100 20 40 60 80 Total Dose (Gy) in 3 Fractions 17 Month Local Control (%)

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• First North American cooperative group trial

testing SBRT

• Non-small cell lung cancer - biopsy proven
• T1, T2 ( 5 cm) and T3 (chest wall only,  5 cm), N0,

M0

• Medical problems precluding surgery

(e.g. emphysema, heart disease, diabetes)

• No other planned therapy

Robert Timmerman, MD; Rebecca Paulus, BS; James Galvin, PhD; Jeffrey Michalski, MD; William Straube, PhD; Jeffrey Bradley, MD; Achilles Fakiris, MD; Andrea Bezjak, MD; Gregory Videtic, MD;David Johnstone, MD; Jack Fowler, PhD; Elizabeth Gore, MD; Hak Choy, MD

:RTOG 0236

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Stereotactic Body Radiation Therapy

Pulmonary Vein Bronchus Esophagus Cord Skin Chestwall Lu ng

Stereotactic Body Radiation Therapy

RTOG 0236: 20 Gy X 3 60 Gy in 3 Treatments

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Local Control (%) 25 50 75 100 Months after Start of SBRT 6 12 18 24 30 36 25 50 75 100 6 12 18 24 30 36 Patients at Risk 55 54 47 46 39 34 23 Fail: 1 Total: 55

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RTOG 0236: Local Control (JAMA 2010)

36 month local control = 98% (CI: 84-100%) 1 failure within PTV, 0 within 1 cm of PTV

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Disseminated Recurrence (%) 25 50 75 100 Months after Start of SBRT 6 12 18 24 30 36 25 50 75 100 6 12 18 24 30 36 Patients at Risk 55 51 44 43 38 33 21 Fail: 11 Total: 55

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RTOG: 0236 Disseminated Recurrence

36 month disseminated recurrence = 22% (CI: 12-38%)

• 6 patients (11%) disseminated within 1 year of Rx

Timmerman: JAMA 2010

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n=55 Complete Response 23 (42%) Partial Response 22 (40%) Stable 9 (16%) Not evaluated 1 (2%)

RTOG 0236 : Best Observed Response

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Post-SBRT Treatment Lung Reaction

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Grade 3-5 Toxicity: Location, Location

p = 0.003

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• RTOG 0618: SBRT for Operable Stage I NSCLC: Accrual complete
• RTOG 0813: SBRT for Central Early Stage NSCLC: Nearly done

Other RTOG Phase I/II Trials SBRT

20 40 60 80 100 20 40 60 80 Total Dose (Gy) in 3 Fractions

Future Plans

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Japanese Pooled Retrospective Experience with SBRT in OPERABLE Patients

stage IA (n=63) 5y OS 75% (95% C.I. 63-87%) stage IB (n=24) 5y OS 70% (95% C.I. 49-90%) Overall Survival Time (years) Slide Courtesy of H. Onishi

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Legitimate Alternative to Lobectomy for Stage I NSCLC??????

• Requirements:
• Local control 90% or more at 5 years (acturarial)
• Survival 60-80% at 5 years (acturarial)
• Grade III or higher toxicity <15-20%
• Ideally less invasive than thoracotomy
• Ideally more convenient
• Ideally less costly
• All proven by prospective testing

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Phase III Study of Sublobar Resection (SR) versus SBRT in High Risk Patients with Stage I NSCLC Z4099 / R1021

• Joint Trial between ACOSOG and RTOG
• To ascertain whether patients treated by SBRT

have 3-year overall survival (OS) rate that is no more than 10% less than patients treated with Surgery.

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Phase III Study of Sublobar Resection versus SBRT in High Risk Patients with Stage I NSCLC Z4099 / R1021

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Phase III Study of Surgery vs SBRT in High Risk Pts with Stage I NSCLC: Z4099 / R1021

• Non-Inferiority Survival Design: 80% +/-10%
• 420 Pts to be Enrolled
• Activated 3/11
• Brachytherapy with Sublobar Resection

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What is the Real Debate Question?

• Are American Docs Disciplined Enough to Enroll

and Randomize Patients into this Surgery vs SBRT Trial?

• Historic Record is Spotty
• Likely Possible at Lower Velocity than Projected
• NCI Early Stopping Rules will be an Issue!

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Development of rat orthotopic model for SBRT treatment

BIOLUMINIESCENCE IMAGING + Micro CT

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Image guided stereotactic radiotherapy

• f orthotopic lung tumor

8/19/2011 31

Center of beam

• A. Reference

Tumor

• B. Verification

Tumor/center of beam

• C. Overlaid

Size of beam

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• SBRT is a new Standard for Medically

Inoperable Stage I NSCLC

• Operable Patients: Data from Phase II and

Phase III Trials Necessary

• Central Lesions: Data on RT Dose Pending

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