1094 - Risk Classifier for Treatment of Stage III Non-Small Cell Lung Cancer Using Competing Event Regression: Ancillary Analysis of RTOG 0617
Presenter(s)
R. Morse1, A. A. Weiner2, Y. Cao1, R. Prabhakar3, G. N. Gan4, K. Reddy1, A. Amini5, C. Hu6, J. D. Bradley7, and L. K. Mell8; 1Department of Radiation Oncology, University of Kansas Medical Center, Kansas City, KS, 2Department of Radiation Oncology, University of North Carolina, Chapel Hill, NC, 3UC San Diego School of Medicine, La Jolla, CA, United States, 4University of Kansas Cancer Center, Kansas City, KS, 5Department of Radiation Oncology, City of Hope National Medical Center, Duarte, CA, 6Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 7Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 8Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA
Purpose/Objective(s):
Systemic therapy has continued to expand options for non-small cell lung cancer (NSCLC) patients in the neoadjuvant and adjuvant settings. Optimal selection of patients most likely to benefit from intensified local and systemic therapy with chemoradiation (CRT) is unknown. We sought to create a novel risk classifier (omega score) to identify subgroups most likely to benefit.Materials/Methods:
Ancillary analysis of 465 patients with inoperable stage III NSCLC enrolled on RTOG 0617 for the systemic therapy endpoint accessed via Project DataSphere. Patients received CRT randomized to standard dose (60 Gy) vs high-dose radiation (74 Gy) with or without cetuximab. We used generalized competing event (GCE) regression to identify patients’ risk for lung cancer recurrence (LCR) relative to competing mortality (CM) (omega ratio), as a function of baseline characteristics. The linear predictor was used to create a continuous classifier (omega score) ranging from 0 to 1. Higher omega scores indicate greater proportion of overall progression free survival (PFS) event risk attributable to LCR (vs CM).Results:
Median follow up time was 21 months (range 0.33-55 months). On multivariable GCE analyses, higher relative risk of LCR vs. CM was associated with female gender (relative hazard ratio (rHR) 2.21), adenocarcinoma histology (rHR 1.83), stage IIIB disease (rHR 1.91) and lung V5 (rHR 1.51). Lower relative risk of LCR vs. CM was associated with increasing age (rHR 0.59), IMRT technique (rHR 0.36), and heart V5 (rHR 0.59) (all p<0.05). The median omega score was 0.83 (range 0.42-0.99). When separated by tertile, the omega score classifier effectively stratified patients according to 2-year LCR vs CM: top tertile (72% vs 5%), middle tertile (55% vs 13%), and bottom tertile (52% vs 24%). Outcomes among the highest omega score tertile (>0.88) vs bottom two tertiles showed similar 2-year PFS (23% vs 28%, HR 0.98, 95% CI, 0.79-1.23) despite higher 2-year LCR (72% vs 54%, HR 1.47, 95% CI, 1.16-1.86) and lower 2-year CM (5% vs 18%, HR 0.25, 95% CI, 0.12-0.53). Higher omega score was associated with an increased relative hazard for LCR vs CM whether treated as binary (rHR 2.05, 95% CI, 1.42-2.98) or a continuous score (rHR 2.10, 95% CI, 1.61-2.73).Conclusion:
This is the first study to use prospective data to develop a relative event risk-based classifier for inoperable stage III NSCLC patients treated with CRT. This omega score may be useful for identifying patients who selectively benefit from intensified local and systemic therapy.