Surgery versus stereotactic body radiation therapy in

All Rights Reserved, Duke Medicine 2011

Surgery versus stereotactic body radiation therapy in medically operable NSCLC

David H Harpole Jr, MD Professor of Surgery

Associate Professor in Pathology Vice Chief, Division of Surgical Services

Duke University School of Medicine Durham, North Carolina

90 year old female, 40 pack-year former smoker CAD with drug-eluting stents (clopidogrel bisulfate) 4 cm right upper lobe lung mass PET SUVmax 3.4, Otherwise (-) PFDs FEV1 75%; DLCO 70% ECOG 0-1

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Surgery versus stereotactic body radiation therapy in medically operable NSCLC

David H Harpole Jr, MD Professor of Surgery

Associate Professor in Pathology Vice Chief, Division of Surgical Services

Duke University School of Medicine Durham, North Carolina


Disclosure

No relevant conflicts of interest to disclose


Stereotactic Body Radiotherapy

•  Multiple radiation beams focused on a single tumor

•  Doses are usually 5-10 times traditional daily radiation doses


Stereotactic Radiosurgery

•  Treated tumor control 85-95%

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Study n Dose (Fractionation) Survival (year)

Local Failure (year)

Nagata (Japan) 45 48 Gy (12 Gy×4) 83%- T1 (5) 72%-T2 (5)

5%-T1 (5) 0%-T2 (5)

Bauman (Sweden) 57 45 Gy (15 Gy×3) 60% (3) 8% (3)

Fakiris (Indiana) 70 60-66 Gy(20–22 Gy×3) 43% (3) 12% (3)

Ricardi (Italy) 62 45 Gy (15 Gy×3) 57% (3) 12 (3)

Bral (Belgium) 40 60 Gy (20 Gy×3)* 60 Gy (15 Gy×4)†

52% (2) 16% (2)

Hoyer (Denmark) 40 45 Gy (15 Gy×3) 47% (2) 15% (2)

Timmerman (RTOG) 55 54 Gy (18 Gy×3)º 56% (3) 2% (3)

SBRT for early stage NSCLC: Retrospective Single Institution Series


SBRT Toxicity: SBRT for early stage NSCLC: Pulmonary Toxicity

9 Bongers E et al. Radiotherapy and Oncology 2013;109:95-99


SBRT Toxicity:Centrally Located Tumors

•  Grade 5=6 –  PNA x 4 –  Pericardial effusion –  Hemoptysis

•  Grade 3-4: –  Decline in PFTs –  Pleural Effusion –  Apnea –  PNA –  Skin reaction

Timmerman R et al. JCO 2006;24:4833-4839

All Rights Reserved, Duke Medicine 2011 Timmerman R et al. JCO 2006;24:4833-4839

©2006 by American Society of Clinical Oncology

SBRT Toxicity: Centrally Located Tumors


Primary Endpoint: 1 year rate of > Grade 3 definitely, possibly, or probably treatment related toxicity Secondary: 1 year primary tumor control rate, 1 year OS and DFS, FDG PET changes

Correlative biomarker for toxicity and control

SBRT: What is the Optimal Dose Schema? RTOG 0915: Randomized Phase II

All Rights Reserved, Duke Medicine 2011 Grills I S et al. JCO 2010;28:928-935


Surgical Resection vs SBRT for High Risk Operable Early Stage NSCLC

All Rights Reserved, Duke Medicine 2011 Grills I S et al. JCO 2010;28:928-935




•  JCOG 0403: – 3 year PFS: 55% – 3 year OS: 76%

•  RTOG 0618: – Accrual completed – Data maturing

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SBRT for Medically Operable Early Stage NSCLC



Register/Randomize Peripheral tumor < 4 cm High-risk surgical candidate N=7/420 (goal)

Limited resection +/- brachytherapy

SBRT • • 

ACOSOG Z4099

Primary Endpoint: Survival with SBRT < 10% limited resection Secondary: Tumor control, toxicity(PFTs, by Charlson CI), DFS


Surgical Resection vs SBRT for Operable Early Stage NSCLC: ROSEL

SBRT 18 Gy x 3

Primary Endpoint: Local and Regional Control, Treatment Costs, QOL Secondary:Total Costs, Quality Adjusted Life Years, Overall Survival


Surgical Resection vs SBRT for Operable Early Stage NSCLC: VALOR

SBRT: BED > 100 Central 5-8 doses

Primary Endpoint: 5 year OS •  25 Federal hospitals •  Resources being allocated at end of 2014


Ablative Radiotherapy (SBRT) •  Ablative Radiotherapy results in high rates of treated

tumor control and survival •  Toxicity profile varies between central and peripheral

tumor locations •  Randomized comparisons ongoing:

–  Surgery: •  High risk operable patients •  Medically operable patients

–  Conventional Radiotherapy •  Patterns of Progression have changed

–  Distant progression most common

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Surgery versus stereotactic body radiation therapy in