adjuvant radiation is not associated with improved survival in patients with positive margins...

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

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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.

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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

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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.

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Methods

Inclusion Criteria:• Lobectomy or Pneumonectomy for Clinical Stage I

or II NSCLC from 1998-2006.

Exclusion Criteria:• Unknown follow-up.• Known neoadjuvant therapy.• Patient receiving a lobectomy who died within 30

days of surgery.

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Lobectomy for Stage I or II NSCLC

Negative Margins Positive Margins

Included: -R1 Disease -R2 Disease -Positive Margins NOS

Methods

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Lobectomy for Stage I or II NSCLC

Negative Margins Positive Margins

Methods

Adjuvant Radiation

No Adjuvant Radiation

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Lobectomy for Stage I or II NSCLC

Negative Margins Positive Margins

Adjuvant Radiation

No Adjuvant Radiation

Adjuvant Radiation Pneumonectomy

Propensity Match

Methods

Results

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VariableNegative Margins Positive Margins P-value

N 48051 (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% < 0.01

Results

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VariableNegative Margins Positive Margins P-value

N 48051 (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% < 0.01

Results

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VariableNegative Margins Positive Margins P-value

N 48051 (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% < 0.01

Results

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VariableNegative Margins Positive Margins P-value

N 48051 (96.1%) 1959 (3.9%)Tumor Size > 5.0 cm 11.8% 21.7% < 0.01Clinical Stage II 10.5% 28.7% <0.01

Results

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VariableNegative Margins Positive Margins P-value

N 48051 (96.1%) 1959 (3.9%)Tumor Size > 5.0 cm 11.8% 21.7% < 0.01Clinical Stage II 10.5% 28.7% <0.01

Results

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VariableNegative Margins Positive Margins P-value

N 48051 (96.1%) 1959 (3.9%)Tumor Size > 5.0 cm 11.8% 21.7% < 0.01Clinical Stage II 10.5% 28.7% <0.01

Results

Negative Margin

34.5%

P < 0.001

57.2%

Positive Margin

Adjusted HR: 1.46 (95% CI: 1.33, 1.60)

Covariates included in adjustment: age, sex, race, insurance status, Charlson/Deyo comorbidity index, pathologic grade, pathologic stage.

Results

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Variable No Adjuvant Radiation

Adjuvant Radiation p-value

N 949 (61.8%) 587 (38.2%)Age 70 (62, 76) 67 (60, 73) < 0.001Female 47.0% 41.6% 0.043Academic Center 30.9% 19.6% < 0.001Tumor Size > 5.0 cm 19.0% 27.5% < 0.001Clinical Stage II 20.4% 37.5% < 0.001Pathologic Stage II 36.4% 61.4% < 0.001Adjuvant Chemotherapy 27.3% 57.1% < 0.001

Results

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Variable No Adjuvant Radiation

Adjuvant Radiation p-value

N 949 (61.8%) 587 (38.2%)Age 70 (62, 76) 67 (60, 73) < 0.001Female 47.0% 41.6% 0.043Academic Center 30.9% 19.6% < 0.001Tumor Size > 5.0 cm 19.0% 27.5% < 0.001Clinical Stage II 20.4% 37.5% < 0.001Pathologic Stage II 36.4% 61.4% < 0.001Adjuvant Chemotherapy 27.3% 57.1% < 0.001

Results

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Variable No Adjuvant Radiation

Adjuvant Radiation p-value

N 949 (61.8%) 587 (38.2%)Age 70 (62, 76) 67 (60, 73) < 0.001Female 47.0% 41.6% 0.043Academic Center 30.9% 19.6% < 0.001Tumor Size > 5.0 cm 19.0% 27.5% < 0.001Clinical Stage II 20.4% 37.5% < 0.001Pathologic Stage II 36.4% 61.4% < 0.001Adjuvant Chemotherapy 27.3% 57.1% < 0.001

Results

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Variable No Adjuvant Radiation

Adjuvant Radiation p-value

N 949 (61.8%) 587 (38.2%)Age 70 (62, 76) 67 (60, 73) < 0.001Female 47.0% 41.6% 0.043Academic Center 30.9% 19.6% < 0.001Tumor Size > 5.0 cm 19.0% 27.5% < 0.001Clinical Stage II 20.4% 37.5% < 0.001Pathologic Stage II 36.4% 61.4% < 0.001Adjuvant Chemotherapy 27.3% 57.1% < 0.001

Results

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Variable No Adjuvant Radiation

Adjuvant Radiation p-value

N 949 (61.8%) 587 (38.2%)Age 70 (62, 76) 67 (60, 73) < 0.001Female 47.0% 41.6% 0.043Academic Center 30.9% 19.6% < 0.001Tumor Size > 5.0 cm 19.0% 27.5% < 0.001Clinical Stage II 20.4% 37.5% < 0.001Pathologic Stage II 36.4% 61.4% < 0.001Adjuvant Chemotherapy 27.3% 57.1% < 0.001

Results

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Variable No Adjuvant Radiation

Adjuvant Radiation p-value

N 949 (61.8%) 587 (38.2%)Age 70 (62, 76) 67 (60, 73) < 0.001Female 47.0% 41.6% 0.043Academic Center 30.9% 19.6% < 0.001Tumor Size > 5.0 cm 19.0% 27.5% < 0.001Clinical Stage II 20.4% 37.5% < 0.001Pathologic Stage II 36.4% 61.4% < 0.001Adjuvant Chemotherapy 27.3% 57.1% < 0.001

No significant differences in insurance status, or Charlson/Deyo Comorbidity Index.

Results

No Adjuvant Radiation

P = 0.009

Adjuvant Radiation

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.

Results

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Variable Pneumonectomy Lobectomy p-value

N 450 225

Age 68 (59.2, 74) 67 (60, 74) 0.85

Female 42.4% 42.2% 0.99

Charlson/Deyo Comorbidity Index

0.96

0 56.9% 57.8%  

1 32.7% 31.6%  

2 10.4% 10.7%  

Tumor Size > 5.0 cm 21.8% 21.8% 0.99

Pathologic Stage II 57.6% 59.1% 0.79

Results

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Pneumonectomy

Lobectomy w/XRT

Results

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Pneumonectomy

Lobectomy w/XRT

Pneumonectomy vs LobectomyHR: 0.96, 95% CI: 0.77, 1.20

Results

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Pneumonectomy

Lobectomy w/XRTPneumonectomy vs LobectomyHR: 0.73, 95% CI: 0.60, 0.89

Results

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Pneumonectomy

Lobectomy w/XRT

Pneumonectomy vs Lobectomy5-Year: HR: 0.50, 95% CI: 0.38, 0.66

45.3%

33.7%

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.

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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.

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