Patterns of regional failure in stage III non-small cell lung cancer treated with neoadjuvant chemoradiation therapy and resection

Purpose: Treatment of locally advanced non-small cell lung cancer (LA-NSCLC) involves definitive chemoradiation therapy (CRT) or neoadjuvant CRT and resection, but radiation treatment volumes remain in question. With CRT, involved-field radiation therapy (IFRT) is replacing elective nodal irradiation, reducing toxicity, and allowing dose escalation. However, prior reports of IFRT describe failures only after radical CRT; with improved local control after resection, IFRT may lead to more regional recurrences. Our objective is to evaluate pattern-of-failure in patients with LA-NSCLC treated with split-course IFRT, chemotherapy, and subsequent surgery. Methods and Materials: Patients treated between December 2004 and 2010 were included. Imaging scans demonstrating failure were fused into the radiation therapy planning computed tomography, and recurrent nodes were contoured to determine pattern-of-failure (involved versus elective nodal failure [INF vs ENF]). Locoregional progression-free survival and distant metastasis-free survival were calculated using Kaplan-Meier methodology. The cumulative incidence of regional recurrence (CIRR) was determined with death as a competing risk. Results: Forty-five patients met inclusion criteria, and patients with RR had a lower rate of pN0 than those without RR (20% vs 60%, P = .02). With a median follow-up of 2.9 years, median survival was not reached, and 3-year locoregional progression-free survival and distant metastasis-free survival were 53% and 35%, respectively. Two and 3-year CIRR were 25% and 33%, respectively. There were no local failures. Thirteen (29%) patients had RR, 8 with INF only and 5 with ENF alone or both, totaling 27 recurrences. Only 2 (4%) ENF occurred without INF, both with distant metastasis, and no elective node was the first and only site of failure. Conclusions: Our data suggest that IFRT does not compromise regional control in the neoadjuvant management of LA-NSCLC. Tailoring nodal volumes may improve treatment-related morbidity and allow for dose intensification of involved nodes. Further research is necessary to improve regional and distant control.