Risk factors associated with brain metastases in ECOG-ACRIN E1505, a phase III randomized trial of adjuvant chemotherapy with or without bevacizumab for patients with completely resected stage IB (>/= 4 cm) - IIIA non-small cell lung cancer (NSCLC).

8539 Background: ECOG-ACRIN E1505 was a phase III randomized trial of adjuvant chemotherapy with or without bevacizumab for patients with completely-resected Stage IB (>4CM) – IIIA non-small cell lung cancer. Prior studies have shown that the risk of brain recurrence in patients after definitive surgical resection is approximately 10%; however, covariates associated with development of brain recurrence have varied across these studies. We sought to estimate the incidence of and risk factors for brain recurrence. Methods: Among the 1501 patients enrolled to ECOG-ACRIN E1505, 121 patients developed brain metastases as their first site of recurrence and are the subject of this investigation. All 1501 patients underwent a pneumonectomy (N = 192) or (bi)lobectomy and had an R0 resection. The cumulative incidence of brain recurrence was estimated after adjusting for recurrence at other sites and death as competing events. A multivariable regression model was fitted using the methodology of Fine and Gray to evaluate the effect of covariates on the subdistribution of brain recurrence. Results: With a median follow-up of 50.3 months, a total of 121 brain metastases had been reported as the first site of recurrence. The incidence of brain recurrence at 12 months post-randomization was 3.7% (95% CI: 2.8% – 4.7%), and it increased to 8.5% (95% CI: 7.0% - 10.0%) at 3 years, and to 9.9% (95% CI: 8.0% - 11.7%) at 6 years. Risk factors for brain metastases included pneumonectomy(HR=1.8; p=0.01), and nonsquamous histology(HR=2.04; p=0.003), but bevacizumab(HR=0.64; p=0.02) was associated with potentially protective effect. Conclusions: The cumulative incidence of brain recurrence increased over time to 9.9% at 6 years in this population of patients with surgically-resected non-small cell lung cancer. Treatment, tumor histology, and type of resection appear to be associated with the risk of brain recurrence. Clinical trial information: NCT00324805.