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Case History

84-year-old with poor pulmonary function, smoking history, and recent thromboembolic event

Underwent serial CT scans with these findings

CP1066773-47

Case History

PET Positive there at SUV 10.1

OK elsewhere

FNA performed: Result C/W NSCLC

Patient considered unsuitable for lobectomy due to co-morbidities

Treatment Options

1. Observation?

2. Wedge Resection (VATS or Not)?

3. Radiofrequency Ablation?

4. Systemic Therapy?

Chemo or Oral TKI?

5. Radiosurgical Ablation?

Subsequent Course

The patient received SBRT at 18 Gy times 3 without difficulty. On six -month follow-up, CT chest revealed a new moderate-sized ipsilateral pleural effusion and “scarring” at the primary tumor.

Final Question

This pleural effusion should be:

1.Tapped

2.Drained and Treated

3.Evaluated with PET

4.Evaluated with Thoracoscopy

5.Treated with Chemotherapy

Walter J Curran, Jr, MDExecutive DirectorWinship Cancer Institute of Emory University

Group ChairmanRadiation Therapy Oncology Group

Stereotactic RT in Early Stage Lung Cancer Current and Future Applications???

Technology Enabling SBRT

What is SBRT?

• Potentially highly effective

• Potentially extremely dangerous

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

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

Phase I Dose Response for Local Control

0

20

40

60

80

100

0 20 40 60 80

Total Dose (Gy) in 3 Fractions

17 Month

Local Control (%)

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

:RTOG 0236:RTOG 0236:RTOG 0236:RTOG 0236

Compact Dose Deposition

Pulmonary VeinPulmonary VeinPulmonary VeinPulmonary VeinBronchusBronchusBronchusBronchus

EsophagusEsophagusEsophagusEsophagus

CordCordCordCord SkinSkinSkinSkin

ChestwallChestwallChestwallChestwall

LungLungLungLung

Local Tumor Control Rate: RTOG 0236

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

Regional and Disseminated Recurrence: RTOG 0236

• 2 patients have reported a regional failure, both after 2 years (2.8 and 3.0 years)

• Eleven patients (20%) have experienced disseminated failure

n=55

Complete Response 23 (42%)

Partial Response 22 (40%)

Stable 9 (16%)

Not evaluated 1 (2%)

RTOG 0236 : Best Observed Response

Post-SBRT Treatment Lung Reaction

Grade 3-5 Toxicity: Location, Location

• 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

0

20

40

60

80

100

0 20 40 60 80

Total Dose (Gy) in 3 Fractions

17 Month Local Control

Future PlansFuture Plans

Japanese Pooled Retrospective Experience with SBRT in

OPERABLE Patients

• Stage IA (n=63), 5y OS 75% (95% CI 63-87%)

• Stage IB (n=24), 5y OS 70% (95% CI 49-90%)

• Stage IA (n=63), 5y OS 75% (95% CI 63-87%)

• Stage IB (n=24), 5y OS 70% (95% CI 49-90%)

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

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

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.

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

Z4099 / R1021

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

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!

Summary

• 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

Sunday, February 12, 2012Hollywood, Florida

Co-ChairsRogerio C Lilenbaum, MDMark A Socinski, MD

Co-Chair and ModeratorNeil Love, MD

Faculty

Walter J Curran Jr, MDDavid Jablons, MDMark G Kris, MD

Suresh Ramalingam, MDAlan B Sandler, MD