Approaching early stage disease Surgery vs SBRT vs

Approaching early stage disease Surgery vs SBRT vs RFA Ramesh Rengan MD Ph. D Chief, Thoracic Service Assistant Director of Clinical Operations Department of Radiation Oncology November 16, 2012

DISCLOSURES w Speaker Honoraria • Philips Healthcare 2

Introduction: The Scope of the Problem w 213, 380 patients are diagnosed yearly with lung cancer in the US with approximately 160, 390 deaths 3

What is “Early Stage” Disease? IA T 1 N 0 M 0 IB T 2 a. N 0 M 0 IIA T 2 b. N 0 M 0 T 1 N 1 M 0 T 2 a. N 1 M 0 IIB T 2 b. N 1 M 0 T 3 N 0 M 0 w Technically resectable disease without evidence of mediastinal involvement 4

Prognosis 5 yr OS Stage IA 75% Stage IB 55% Stage IIA 50% Stage IIB 40% Stage IIIA 10 -35% Stage IIIB 5 -8% Stage IV <5% 5

Medical Operability 2007 ACCP Guidelines w Age alone is not a reason to deny resection. w Operative mortality for a lobectomy: ~2% for age < 60, ~8% for age > 70 w General targets: • • • FEV 1 > 1. 5 L FEV 1 > 80% pred DLCO > 60 -80% pred w Danger signs: • • • FEV 1 or DLCO < 40% predicted FEV 1/FVC < 50% PCO 2 > 50 mm. Hg Cor pulmonale VO 2 < 15 cc/kg/min Or, ability to walk 1 flight of stairs 6

Treatment for Early Stage Operable Disease Lobectomy + Mediastinal LND or LNS w Remains current standard of care • ACOSOG Z 0030 w With appropriate pt selection, periop mortality rates are low • Pneumonectomy 5% • Lobectomy 1 -3% • Smaller Resections < 1% 7

Treatment for Early Stage Operable Disease: ACOSOG Z 0030 w 1111 patients enrolled; 1023 randomized • Extensive MLNS followed by observation vs MLND w No difference in overall survival Darling et al J Thoracic and CV Surgery, 2011 8

Treatment for Early Stage Operable Disease: Is there a lumpectomy for the lung? 9

Treatment for Early Stage Operable Disease: Is there a lumpectomy for the lung? w LCSG showed trend towards increased likelihood of death with limited resection w LCSG showed three-fold increase in local failure with wedge resection vs. lobectomy 10

Medically Inoperable Early Stage: Role of RT w Cor pulmonale w Severe coronary artery disease w Renal failure w Poor pulmonary function • DLCO <50% • FEV 1/FVC ratio < 50 – 75% of predicted w Impaired nutritional status 11

Medically Inoperable Early Stage: Role of RT Study Author Dosoretz n Dose (Gy) 5 -yr survival 152 60 -69 10% Krol 108 60 -65 Kaskowitz 53 Sibley Rosenzweig 5 -yr CSS 5 -yr local 15% 31% 25% 63 6% 13% 0% 141 55 -70 13% 32 70. 2 33% 39% 43% 12

Medically Inoperable Early Stage: SBRT Nyman et al Lung Cancer 2006 13

Fractionation Options w Conventionally fractionated radiotherapy - small daily doses - go to very high cumulative doses w Ablative radiotherapy - very high daily doses (8 -20 Gy) - overwhelm tumor repair - causes “late” effects that may be intolerable 14

Dose Fractionation: Implications for Tumor Control 100 Survival multiple 2 Gy fractions 10 -1 single fraction 10 -2 2 4 Dose (Gy) 6 8 15

Early Stage Disease: Stereotactic Body Radiation Therapy Pretreatment 6 -weeks Post-treatment 16

Medically Inoperable Early Stage: SBRT Author # of Patients Local Control Overall Survival Onishi et al. 245 85% 56% (3 -yr) Timmerman 70 98% 55% (2 -yr) Nyman 45 80% 71% (2 -yr) Baumann 57 92% 60% (3 -yr) Nagata 31 98% 79% (2 -yr) Uematsu 50 94% 66% (3 -yr) Koto 31 78% 72% (3 -yr) Fakiris 70 88% 43% (3 -yr) 17

Dose Fractionation: Implications for Tumor Control 100 Survival multiple 2 Gy fractions 10 -1 single fraction 10 -2 2 4 Dose (Gy) 6 8 18

Medically Inoperable Early Stage: Toxicity of SBRT Corradetti et al NEJM 2012 JCO 2006 w RTOG 0813 is currently accruing w Would not treat centrally located tumors with SBRT off-protocol p = 0. 003 w Standard of care for peripheral medically inoperable NSCLC 19

SBRT: Emerging toxicity data 20

Treatment of Early Stage Inoperable Disease: RFA 21

Treatment of Early Stage Inoperable Disease: RFA w Multicenter prospective trial of 106 patients with 183 lung tumors w 33 patients with NSCLC w 48% 2 -year survival • 73% 2 -year CSS w 10% pneumothorax rate w Median hospital stay 3 days Lancioni Lancet Oncol 2008 22

RFA: Emerging toxicity data 23

Early Stage NSCLC: Conclusions Lobectomy + MLNS or MLND With adjuvant chemotherapy +/- RT in high risk cases NCCN Guidelines, 2012 24

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