Approaching early stage disease

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

2. DISCLOSURES • Speaker Honoraria • Philips Healthcare

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

4. What is “Early Stage” Disease? • Technically resectable disease without evidence of mediastinal involvement

5. Prognosis

6. Medical Operability 2007 ACCP Guidelines • Age alone is not a reason to deny resection. • Operative mortality for a lobectomy: ~2% for age < 60, ~8% for age > 70 • General targets: • FEV1 > 1.5L • FEV1 > 80% pred • DLCO > 60-80% pred • Danger signs: • FEV1 or DLCO < 40% predicted • FEV1/FVC < 50% • PCO2 > 50mmHg • Cor pulmonale • VO2 < 15cc/kg/min • Or, ability to walk 1 flight of stairs

7. Treatment for Early Stage Operable Disease Lobectomy+ Mediastinal LND or LNS • Remains current standard of care • ACOSOG Z0030 • With appropriate pt selection, periop mortality rates are low • Pneumonectomy 5% • Lobectomy 1-3% • Smaller Resections < 1%

8. Treatment for Early Stage Operable Disease: ACOSOG Z0030 • 1111 patients enrolled; 1023 randomized • Extensive MLNS followed by observation vs MLND • No difference in overall survival Darling et al J Thoracic and CV Surgery, 2011

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

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

11. Medically Inoperable Early Stage: Role of RT • Corpulmonale • Severe coronary artery disease • Renal failure • Poor pulmonary function • DLCO <50% • FEV1/FVC ratio < 50 – 75% of predicted • Impaired nutritional status

12. Medically Inoperable Early Stage: Role of RT

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

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

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

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

17. Medically Inoperable Early Stage: SBRT

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

19. Medically Inoperable Early Stage: Toxicity of SBRT • RTOG 0813 is currently accruing • Would not treat centrally located tumors with SBRT off-protocol • Standard of care for peripheral medically inoperable NSCLC Corradetti et al NEJM 2012 JCO 2006 p = 0.003

20. SBRT: Emerging toxicity data

21. Treatment of Early Stage Inoperable Disease: RFA

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

23. RFA: Emerging toxicity data

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