Patterns of Failure According to Tumor Histology and Treatment Schedule in Patients with Locally Advanced Inoperable Non-Small Cell Lung Cancer: Secondary Analysis of NRG Oncology RTOG 9410

Background and Purpose: This secondary analysis of RTOG 9410 compared three chemoradiation treatment strategies for inoperable stage II-III non-small cell lung cancer) was done to clarify patterns of failure by treatment and histology.

Methods and Materials: 577 patients were treated with either sequential cisplatin based chemotherapy followed by radiation 63 Gy ,50 days later [n=195] or one of two forms of concurrent cisplatin based chemo-radiation 63 Gy in once-daily fractions, [n=195], or 69.6 Gy in twice-daily fractions; [n=187]. Outcomes were time to progression and components of initial failure, i.e., in the primary tumor, in-field with out-of-field nodes, distant metastases, and their relative prevalence by treatment and histology.

Results: Overall progression rates were 75.9% in the sequential group, 72.8% in the once-daily concurrent group, and 65.2% in the twice-daily concurrent group (in all, 65.1% for squamous tumors vs. 75.4% for nonsquamous). Time to any progression including infield was significantly shorter by sequential compared by twice-daily therapy regardless of histology; time to infield progression also differed in squamous tumors (shorter for by once-daily compared by twice-daily) and nonsquamous tumors (sequential was shorter than concurrent groups. The most prevalent initial sites of failure were distant metastases outside the brain and primary tumor.

Conclusions: Concurrent therapy produced longer infield failures than sequential therapy; that infield recurrence in squamous was significantly prolonged by twice daily concurrent treatment. Once-daily concurrent therapy showed that more distant (non-brain) metastases from non squamous tumors suggest that histology should be considered in the choice of therapy for non-small cell lung cancer.

Keywords: locally advanced NSCLC; squamous lung cancer; non squamous lung cancer; sequential chemoradiation therapy, concurrent chemoradiation therapy; progression-free survival.