Chemoradiation in Elderly Patients With Stage III NSCLC Improves Overall Survival
Elderly patients with stage III non–small cell lung cancer (NSCLC) showed improved overall survival when treated with chemoradiation compared to definitive radiation alone, according to findings published by Miller et al in the Journal of Thoracic Oncology.
NSCLC constitutes between 80%–85% of all lung cancers, and more than 30% of those are diagnosed with stage III disease over the age of 65. Despite this large population, elderly patients are often excluded or underrepresented in clinical trials, resulting in limited treatment options for this population of patients. Given that NSCLC is a heterogeneous disease requiring a multidisciplinary treatment approach, and the limited treatment data available in this population, the optimal treatment strategy for stage III NSCLC in the elderly needs to be further explored.
Study Details
A group of investigators at The Ohio State University conducted a retrospective study to compare the effectiveness of radiation alone vs chemoradiation in elderly patients ≥ 70 years old with stage III NSCLC not treated surgically. Patients ≥ 70 years old with stage III NSCLC not surgically treated from 2003–2014 were selected from the National Cancer Database. Patients were divided into two cohorts: patients treated with definitive radiation, and patients treated with definitive chemoradiation. The chemoradiation patients were considered to have received concurrent chemoradiation if chemotherapy was delivered within 30 days prior to or after initiation of radiation, while sequential chemoradiation was defined as radiation delivered > 30 days after initiation of chemotherapy. The overall survival between treatment groups was compared using the Kaplan-Meier method and Cox proportional hazards regression before and after propensity score matching to reduce potential selection bias.
Study Findings
The study identified 5,023 elderly patients treated with definitive radiation and 18,206 patients treated with chemoradiation. Univariate analysis revealed that younger age; male sex; white race; higher income; stage IIIB disease; increased distance from the treating hospital; and a Charlson-Deyo score < 1 were associated with higher odds of receiving chemoradiation. These covariates were used to calculate propensity scores.
Treatment with chemoradiation was associated with improved overall survival compared to radiation before propensity score matching (hazard ratio [HR] = 0.66, 95% confidence interval [CI] = 0.64–0.68, P < .0001) and after propensity score matching (HR = 0.91, 95% CI = 0.85–0.96, P = .002). After propensity score matching, treatment with chemoradiation corresponded to a 33% reduction in the risk of death (HR = 0.67, 95% CI = 0.64–0.70, P < .001). The benefit of chemoradiation was greater for elderly patients treated with multi-agent chemotherapy (HR = 0.64, 95% CI = 0.61–0.67, P < .001) compared with single-agent chemotherapy (HR = 0.83, 95% CI = 0.75–0.92, P < .001). Finally, patients treated with chemoradiation were further subdivided into those treated with concurrent vs sequential chemoradiation with 15,840 treated with concurrent chemoradiation and 2,366 treated with sequential chemoradiation. Treatment with sequential chemoradiation corresponded to a 9% reduction in the risk of death (HR = 0.91, 95% CI = 0.85–0.96, P = .002).
The authors commented that, “Treatment of the elderly with locally advanced NSCLC is challenging and, with an aging population, will remain an issue for the U.S. health-care system for the foreseeable future. To our knowledge, our study represents the largest reported cohort of elderly stage III NSCLC patients not treated surgically. We found that [chemoradiation] is superior to definitive [radiation] in elderly patients with stage III NSCLC not treated surgically. We also found that in patients that receive [chemoradiation], sequential chemotherapy and [radiation] resulted in improved [overall survival] compared to concurrent [chemoradiation]. Treatment of the elderly with stage III NSCLC should involve a multidisciplinary discussion. All patients not eligible for surgery should first be considered for [chemoradiation], with either concurrent or sequential [radiation]. Based on our findings, multi-agent chemotherapy is preferred over single-agent regimens in suitable patients. When multi-agent chemotherapy is not feasible, a single-agent regimen is supported by our results. When chemotherapy is contraindicated or not recommended, then definitive [radiation] alone should be considered.”
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