Adding chemotherapy to radiation improves survival in older lung cancer patients

Robyn Boyle, RPh, for MDLinx | May 30, 2018

According to a study published in the Journal of Thoracic Oncology, combined radiation and chemotherapy resulted in improved overall survival (OS) in older patients with non-small cell lung cancer (NSCLC) when compared to radiation alone. In addition, sequential therapy performed better than concurrent treatment.


“Definitive CRT is superior to definitive RT in elderly patients with stage III NSCLC not treated surgically,” wrote the authors.

Studies evaluating chemotherapy in older patients with NSCLC are limited, and results are conflicting. Eric D. Miller MD, PhD, and colleagues from The Ohio State University in Columbus, OH, compared chemoradiation therapy (CRT) and radiation therapy (RT) alone in elderly patients (≥ 70 years old) with stage III cancer not treated surgically.

Patients were identified using the National Cancer Database (NCDB), a nationwide hospital-based database representing more than 70% of newly diagnosed cancer cases in the US. Two cohorts were evaluated: 5,023 patients treated with RT and 18,206 patients treated with CRT.

In addition, CRT was further classified as concurrent CRT (CCRT) if radiation and chemotherapy started within 30 days of each other, or sequential CRT (SCRT) if radiation started > 30 days after chemotherapy. The OS between treatment groups was compared using propensity score matching (PSM) to reduce potential selection bias.

Most baseline covariates were dichotomized: gender (male vs female), race (white vs nonwhite), median annual income (≥ $48,000 vs < $48,000), primary insurance payer (private vs non-private), location (metropolitan vs urban/rural), facility type (academic vs community), chemotherapy agents used (multi-agent vs single-agent regimens), clinical stage group (IIIB vs IIIA), and Charlson-Deyo score (no comorbities vs ≥ 1 comorbidity).

Patient age and distance to the nearest facility were analyzed as continuous variables.

The primary objective of the study was to evaluate OS in elderly patients treated with CRT vs RT alone. In addition, the impact of the number of chemotherapy agents used (multi-agent CRT vs RT alone, single-agent CRT vs RT, and multi-agent CRT vs single-agent CRT) was assessed. Additional analysis included comparison of OS in CRT treated with CCRT vs with SCRT.

The median radiation dose in the CRT and RT groups was similar—64.8 Gy for each. Patients were treated with a median of 34 fractions in the CRT group and 33 fractions in the RT group. Patients in the CRT group were more likely to have stage IIIB disease, but they were less likely to have comorbidities, and they were younger when compared with patients in the RT group (P < 0.001 for each).

Most patients in the CRT group received multi-agent chemotherapy (86%) and most were treated with CCRT (87%). The median time from the start of chemotherapy to radiation in the SCRT group was 82 days.

Factors independently associated with improved OS included younger age, female sex, nonwhite race, treatment at an academic facility, higher income, living in a metropolitan county, stage IIIA vs stage IIIB disease, closer distance to the treatment hospital, Charlson-Deyo score < 1, longer time to start of RT, and CRT vs RT alone.

In a matched cohort using PSM, CRT had a survival advantage over RT alone, with median OS times of 17.2 months and 12.2 months, respectively (P < 0.001). After adjustment for confounders, CRT corresponded to a 33% reduction in the risk for death (hazard ratio [HR]: 0.67, P < 0.001).

The benefit of CRT was greater for elderly patients treated with multi-agent (HR: 0.64, P < 0.001) than for those treated with single-agent chemotherapy (HR: 0.83, P < 0.001). Multi-agent chemotherapy resulted in a 21% decrease in the HR for death compared with that for patients treated with single-agent chemotherapy (HR: 0.79, P < 0.001).

Based on the timing of initiation of radiation and chemotherapy, patients were further subdivided into those treated with CCRT or SCRT. The median OS was significantly higher in patients treated with SCRT than in those treated with CCRT: 20.0 months vs 17.8 months, (P < 0.001).

The authors noted that using the NCDB limited the study. It is a retrospective database with inherent weaknesses, such as incomplete data, selection bias, and unmeasured confounders. The NCDB does not capture performance status or details of chemotherapy, such as specific agents used, duration, or cycles delivered. Moreover, data are not available regarding toxicity, quality of life, and cause of death.

The investigators acknowledge many factors need to be considered when making treatment decisions for elderly patients with stage III NSCLC; however, they suggested that CRT with either concurrent of sequential radiation might be an option in patients who are not eligible for surgery.

“Definitive CRT is superior to definitive RT in elderly patients with stage III NSCLC not treated surgically,” concluded the authors.

They added: “Patients who received CRT, sequential chemotherapy, and RT resulted in better OS than in those who received CCRT.”

To read more about this study, click here.