Impact of brachytherapy on local recurrence rates after sublobar resection: results from ACOSOG Z4032 (Alliance), a phase III randomized trial for high-risk operable non-small-cell lung cancer

Abstract

Purpose: A major concern with sublobar resection (SR) for non-small-cell lung cancer (NSCLC) is high local recurrence (LR). Adjuvant brachytherapy may reduce LR This multicenter randomized trial compares SR to SR with brachytherapy (SRB).

Patients and methods: High-risk operable patients with NSCLC ≤ 3 cm were randomly assigned to SR or SRB. The primary end point was time to LR, where LR included recurrence at the staple line (local progression), in the primary tumor lobe away from the staple line, and in ipsilateral hilar nodes. The trial was designed to have a 90% power to detect a hazard ratio (HR) of 0.315 in favor of SRB, using a one-sided type I error rate of 0.05 with a sample size of 100 eligible patients in each arm.

Results: Two hundred twenty-four patients were randomly assigned; 222 patients were evaluable for intent-to-treat analysis. Median age was 71 years (range, 49 to 87 years). No differences were found in baseline characteristics. Median follow-up time was 4.38 years (range, 0.04 to 5.59 years). There was no difference in time to LR (HR, 1.01; 95% CI, 0.51 to 1.98; log-rank P = .98) or in the types of LR. Local progression occurred in only 17 (7.7%) of 222 patients. In patients with potentially compromised margins (margin < 1 cm, margin-to-tumor ratio < 1, positive staple line cytology, wedge resection, nodule size > 2.0 cm), SRB did not reduce LR, although trends favored the SRB arm. This was most marked in 14 patients with positive staple line cytology (HR, 0.22; P = .24). Three-year overall survival rates were similar for patients in the SR (71%) and SRB (71%) arms (P = .97).

Conclusion: Brachytherapy did not reduce LR after SR. This finding may have been related to closer attention to parenchymal margins by surgeons participating in this study.

Trial registration: ClinicalTrials.gov NCT00107172.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

© 2014 by American Society of Clinical Oncology.

Figures

Fig 1.

CONSORT diagram. CT, computed tomography; IRB, institutional review board; NSCLC, non–small-cell lung cancer.

Fig 2.

Pattern of local recurrence and cumulative incidence graph by arm for local recurrence with death or regional or distant recurrence as competing events in the intent-to-treat cohort. AnyLR, any local recurrence; LProgStpLine, local progression at staple line; LRAwayStpLine, lobar recurrence away from the staple line; N1R, nodal (N1) recurrence; SR, sublobar resection; SRB, sublobar resection with brachytherapy.

Fig 3.

Kaplan-Meier curves for overall survival in the intention-to-treat cohort. NR, not reached; SR, sublobar resection; SRB, sublobar resection with brachytherapy.

Fig A1.

Cumulative incidence graph by arm for local recurrence or death with regional or distant recurrence as competing events in the intention-to-treat cohort. NR, not reached; SR, sublobar resection; SRB, sublobar resection with brachytherapy.

Fig A2.

Pattern of local recurrence and cumulative incidence graph by arm for local recurrence with death or regional or distant recurrence as competing events in the per-protocol cohort. AnyLR, any local recurrence; LProgStpLine, local progression at staple line; LRAwayStpLine, lobar recurrence away from the staple line; N1R, nodal (N1) recurrence; SR, sublobar resection; SRB, sublobar resection with brachytherapy.

Fig A3.

Cumulative incidence graph by arm for local recurrence or death with regional or distant recurrence as competing events in the per-protocol cohort. NR, not reached; SR, sublobar resection; SRB, sublobar resection with brachytherapy.

Fig A4.

Kaplan-Meier curves for overall survival in the per-protocol cohort. NR, not reached; SR, sublobar resection; SRB, sublobar resection with brachytherapy.