Seven statistical models showed that both screening mammography and treatment have helped reduce the rate of death from breast cancer in the United States.
Summary
Background
The standard of care for operable, stage I, non-small-cell lung cancer (NSCLC) is lobectomy with mediastinal lymph node dissection or sampling. Stereotactic ablative radiotherapy (SABR) for inoperable stage I NSCLC has shown promising results, but two independent, randomised, phase 3 trials of SABR in patients with operable stage I NSCLC (STARS and ROSEL) closed early due to slow accrual. We aimed to assess overall survival for SABR versus surgery by pooling data from these trials.
Methods
Eligible patients in the STARS and ROSEL studies were those with clinical T1–2a (<4 cm), N0M0, operable NSCLC. Patients were randomly assigned in a 1:1 ratio to SABR or lobectomy with mediastinal lymph node dissection or sampling. We did a pooled analysis in the intention-to-treat population using overall survival as the primary endpoint. Both trials are registered with ClinicalTrials.gov (STARS: NCT00840749; ROSEL: NCT00687986).
Findings
58 patients were enrolled and randomly assigned (31 to SABR and 27 to surgery). Median follow-up was 40.2 months (IQR 23.0–47.3) for the SABR group and 35.4 months (18.9–40.7) for the surgery group. Six patients in the surgery group died compared with one patient in the SABR group. Estimated overall survival at 3 years was 95% (95% CI 85–100) in the SABR group compared with 79% (64–97) in the surgery group (hazard ratio [HR] 0.14 [95% CI 0.017–1.190], log-rank p=0.037). Recurrence-free survival at 3 years was 86% (95% CI 74–100) in the SABR group and 80% (65–97) in the surgery group (HR 0.69 [95% CI 0.21–2.29], log-rank p=0.54). In the surgery group, one patient had regional nodal recurrence and two had distant metastases; in the SABR group, one patient had local recurrence, four had regional nodal recurrence, and one had distant metastases. Three (10%) patients in the SABR group had grade 3 treatment-related adverse events (three [10%] chest wall pain, two [6%] dyspnoea or cough, and one [3%] fatigue and rib fracture). No patients given SABR had grade 4 events or treatment-related death. In the surgery group, one (4%) patient died of surgical complications and 12 (44%) patients had grade 3–4 treatment-related adverse events. Grade 3 events occurring in more than one patient in the surgery group were dyspnoea (four [15%] patients), chest pain (four [15%] patients), and lung infections (two [7%]).
Interpretation
SABR could be an option for treating operable stage I NSCLC. Because of the small patient sample size and short follow-up, additional randomised studies comparing SABR with surgery in operable patients are warranted.
Funding
Accuray Inc, Netherlands Organisation for Health Research and Development, NCI Cancer Center Support, NCI Clinical and Translational Science Award.
Bach reported that he has received speaking fees from Genentech. Dr. Detterbeck reported that he was reimbursed for travel costs associated with his work on the Oncimmune advisory board, and has participated without compensation in a symposium on CT screening sponsored by Covidien. Dr.Berry reported that he is co-owner of Berry Consultants LLC which designs adaptive clinical trials for pharmaceutical companies, medical device companies and NIH cooperative groups. To the best of his knowledge none of these parties have any interest in lung cancer screening. Dr. Gould reported that he receives grant support from the National Cancer Institute. Dr. Jett reported that he has grants pending for work related to screening and early detection of lung cancer with Oncimmune and Isense. Dr. Sabichi reported her membership on the National Cancer Institute's PDQ Prevention and Screening Editorial Board and her possession of a pending patent for a test for the detection of bladder cancer. Dr. Wood reported his participation in the development of the National Comprehensive Cancer Network's clinical practice guidelines for lung cancer screening in his role as Chair of the NCCN Lung Cancer Screening Panel.
Dose density improves clinical outcomes significantly, despite the lower than expected number of events at this time. Sequential chemotherapy is as effective as concurrent chemotherapy.
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