Dr. Thomas D Amico serves as a consultant for Scanlan. The other authors have no conflicts of interest to report.

Transcription

1 Adjuvant Radiation is Not Associated with Improved Survival in Patients with Positive Margins Following Lobectomy for Stage I & II Non-Small Cell Lung Cancer Brian C Gulack, MD; Jeffrey Chi-Fu Yang, MD; Paul J Speicher, MD, MHS; H. Volkan Kara, MD; Thomas A D Amico, MD; Mark F Berry, MD, MHS; Matthew G Hartwig, MD 1

2 Disclosures Dr. Thomas D Amico serves as a consultant for Scanlan. The other authors have no conflicts of interest to report. The National Cancer Data Base is a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society. The COC and the ACS are not responsible for the analytic or statistical methodology employed, or the conclusions drawn from these data. 2

3 Background Lobectomy Most common surgical procedure performed for stage I or II NSCLC. 4-6% associated with positive margins. Current NCCN guidelines for positive margins: Re-resection +/- chemotherapy (preferred). Adjuvant radiation +/- chemotherapy. Based on limited data. Reviewed the National Cancer Data Base (NCDB) in order to better guide therapy for this clinical scenario. Hypothesis: Significant benefit from adjuvant XRT 3

4 Methods National Cancer Data Base Collects information from over 1500 Commission-on- Cancer accredited hospitals. Captures roughly 70% of newly diagnosed cancers in the United States each year. 4

5 Methods Inclusion Criteria: Lobectomy or Pneumonectomy for Clinical Stage I or II NSCLC from Exclusion Criteria: Unknown follow-up. Known neoadjuvant therapy. Patient receiving a lobectomy who died within 30 days of surgery. 5

6 Methods Lobectomy for Stage I or II NSCLC Negative Margins Positive Margins Included: -R1 Disease -R2 Disease -Positive Margins NOS 6

7 Methods Lobectomy for Stage I or II NSCLC Negative Margins Positive Margins Adjuvant Radiation No Adjuvant Radiation 7

8 Methods Lobectomy for Stage I or II NSCLC Negative Margins Positive Margins Adjuvant Radiation No Adjuvant Radiation Adjuvant Radiation Pneumonectomy Propensity Match 8

9 Negative Positive Variable Margins Margins P-value N (96.1%) 1959 (3.9%) Age (years) 68 (61, 74) 68 (61, 75) 0.28 Female Sex 50.2% 45.9% < 0.01 Race <0.01 White 90.1% 87.8% Black 7.0% 9.1% Other/Unknown 2.9% 3.1% Private Insurance Status 35.3% 34.6% 0.55 Academic Center 33.8% 27.5% <

10 Negative Positive Variable Margins Margins P-value N (96.1%) 1959 (3.9%) Age (years) 68 (61, 74) 68 (61, 75) 0.28 Female Sex 50.2% 45.9% < 0.01 Race <0.01 White 90.1% 87.8% Black 7.0% 9.1% Other/Unknown 2.9% 3.1% Private Insurance Status 35.3% 34.6% 0.55 Academic Center 33.8% 27.5% <

11 Negative Positive Variable Margins Margins P-value N (96.1%) 1959 (3.9%) Age (years) 68 (61, 74) 68 (61, 75) 0.28 Female Sex 50.2% 45.9% < 0.01 Race <0.01 White 90.1% 87.8% Black 7.0% 9.1% Other/Unknown 2.9% 3.1% Private Insurance Status 35.3% 34.6% 0.55 Academic Center 33.8% 27.5% <

12 Negative Variable Margins Positive Margins P-value N (96.1%) 1959 (3.9%) Tumor Size > 5.0 cm 11.8% 21.7% < 0.01 Clinical Stage II 10.5% 28.7% <

13 Negative Variable Margins Positive Margins P-value N (96.1%) 1959 (3.9%) Tumor Size > 5.0 cm 11.8% 21.7% < 0.01 Clinical Stage II 10.5% 28.7% <

14 Negative Variable Margins Positive Margins P-value N (96.1%) 1959 (3.9%) Tumor Size > 5.0 cm 11.8% 21.7% < 0.01 Clinical Stage II 10.5% 28.7% <

15 Negative Margin 57.2% Positive Margin P < Adjusted HR: 1.46 (95% CI: 1.33, 1.60) 34.5% Covariates included in adjustment: age, sex, race, insurance status, Charlson/Deyo comorbidity index, pathologic grade, pathologic stage.

16 Variable No Adjuvant Adjuvant p-value Radiation Radiation N 949 (61.8%) 587 (38.2%) Age 70 (62, 76) 67 (60, 73) < Female 47.0% 41.6% Academic Center 30.9% 19.6% < Tumor Size > 5.0 cm 19.0% 27.5% < Clinical Stage II 20.4% 37.5% < Pathologic Stage II 36.4% 61.4% < Adjuvant Chemotherapy 27.3% 57.1% <

17 Variable No Adjuvant Adjuvant p-value Radiation Radiation N 949 (61.8%) 587 (38.2%) Age 70 (62, 76) 67 (60, 73) < Female 47.0% 41.6% Academic Center 30.9% 19.6% < Tumor Size > 5.0 cm 19.0% 27.5% < Clinical Stage II 20.4% 37.5% < Pathologic Stage II 36.4% 61.4% < Adjuvant Chemotherapy 27.3% 57.1% <

18 Variable No Adjuvant Adjuvant p-value Radiation Radiation N 949 (61.8%) 587 (38.2%) Age 70 (62, 76) 67 (60, 73) < Female 47.0% 41.6% Academic Center 30.9% 19.6% < Tumor Size > 5.0 cm 19.0% 27.5% < Clinical Stage II 20.4% 37.5% < Pathologic Stage II 36.4% 61.4% < Adjuvant Chemotherapy 27.3% 57.1% <

19 Variable No Adjuvant Adjuvant p-value Radiation Radiation N 949 (61.8%) 587 (38.2%) Age 70 (62, 76) 67 (60, 73) < Female 47.0% 41.6% Academic Center 30.9% 19.6% < Tumor Size > 5.0 cm 19.0% 27.5% < Clinical Stage II 20.4% 37.5% < Pathologic Stage II 36.4% 61.4% < Adjuvant Chemotherapy 27.3% 57.1% <

20 Variable No Adjuvant Adjuvant p-value Radiation Radiation N 949 (61.8%) 587 (38.2%) Age 70 (62, 76) 67 (60, 73) < Female 47.0% 41.6% Academic Center 30.9% 19.6% < Tumor Size > 5.0 cm 19.0% 27.5% < Clinical Stage II 20.4% 37.5% < Pathologic Stage II 36.4% 61.4% < Adjuvant Chemotherapy 27.3% 57.1% <

21 Variable No Adjuvant Adjuvant p-value Radiation Radiation N 949 (61.8%) 587 (38.2%) Age 70 (62, 76) 67 (60, 73) < Female 47.0% 41.6% Academic Center 30.9% 19.6% < Tumor Size > 5.0 cm 19.0% 27.5% < Clinical Stage II 20.4% 37.5% < Pathologic Stage II 36.4% 61.4% < Adjuvant Chemotherapy 27.3% 57.1% < No significant differences in insurance status, or Charlson/Deyo Comorbidity Index. 13

22 No Adjuvant Radiation Adjuvant Radiation P = Adjusted HR: 1.08 (95% CI: 0.88, 1.32) Covariates included in adjustment: age, sex, race, insurance status, Charlson/Deyo comorbidity index, pathologic grade, pathologic stage.

23 Variable Pneumonectomy Lobectomy p-value N Age 68 (59.2, 74) 67 (60, 74) 0.85 Female 42.4% 42.2% 0.99 Charlson/Deyo Comorbidity Index % 57.8% % 31.6% % 10.7% Tumor Size > 5.0 cm 21.8% 21.8% 0.99 Pathologic Stage II 57.6% 59.1%

24 Pneumonectomy Lobectomy w/xrt 16

25 Pneumonectomy Pneumonectomy vs Lobectomy HR: 0.96, 95% CI: 0.77, 1.20 Lobectomy w/xrt 16

26 Pneumonectomy Pneumonectomy vs Lobectomy HR: 0.73, 95% CI: 0.60, 0.89 Lobectomy w/xrt 16

27 Pneumonectomy 45.3% Lobectomy w/xrt 33.7% Pneumonectomy vs Lobectomy 5-Year: HR: 0.50, 95% CI: 0.38,

28 Limitations Potential for unobserved confounding. Details of treatment decisions regarding adjuvant therapy and deferring re-resection not available. Radiation therapy for other indications. Limited ability to assess the impact of adjuvant chemotherapy. 18

29 Summary Lobectomy for Stage I or II NSCLC is associated with a 4% positive margin rate. Positive margins are associated with reduced survival. Adjuvant Radiation therapy is not associated with a significant survival benefit. Re-resection, when feasible, may be a superior treatment option. 17