Sequencing of Postoperative Radiotherapy and Chemotherapy for Locally Advanced or Incompletely Resected Non–Small-Cell Lung Cancer

Abstract

Purpose Although several feasibility studies have demonstrated the safety of adjuvant concurrent chemoradiotherapy (CRT) for locally advanced or incompletely resected non-small-cell lung cancer (NSCLC), it remains uncertain whether this approach is superior to sequential chemotherapy followed by postoperative radiotherapy (C→PORT). We sought to determine the most effective treatment sequence. Patients and Methods Using the National Cancer Database, we selected two cohorts of patients with nonmetastatic NSCLC who had received at least a lobectomy followed by multiagent chemotherapy and radiotherapy; cohort one included patients with R0 resection and pN2 disease, whereas cohort two included patients with R1-2 resection regardless of nodal status. Overall survival (OS) was examined using a propensity score-matched analysis with a shared frailty Cox regression. Results A total of 747 patients in cohort one and 277 patients in cohort two were included, with a median follow-up of 32.8 and 27.9 months, respectively. The median OS was 58.8 months for patients who received C→PORT versus 40.4 months for patients who received CRT in cohort one (log-rank P < .001). For cohort two, the median OS was 42.6 months for patients who received C→PORT versus 38.5 months for patients who received CRT (log-rank P = .42). After propensity score matching, C→PORT remained associated with improved OS compared with CRT in cohort one (hazard ratio, 1.35; P = .019), and there was no statistical difference in OS between the sequencing groups for cohort two (hazard ratio, 1.35; P = .19). Conclusion Patients with NSCLC who undergo R0 resection and are found to have pN2 disease have improved outcomes when adjuvant chemotherapy is administered before, rather than concurrently with, radiotherapy. For patients with positive margins after surgery, there is not a clear association between treatment sequencing and survival.

Postoperative radiotherapy is effective in improving survival of patients with stage pIII-N2 non-small-cell lung Cancer after pneumonectomy

“…Radiation esophagitis was another common side effect of radiotherapy. However, large-scaled analysis showed that the rate of ≥grade 3 radiation esophagitis was only 4% in NSCLC patients after postoperative chemotherapy and radiotherapy [19]. Although there were nearly 1/3 of patients suffering grade 2 radiation esophagitis in our study, no severe radiation esophagitis was noted, which may be related to the precise techniques and careful protection of normal tissue in radiotherapy after pneumonectomy.…”

The Incidence of Node-Positive Non-small-Cell Lung Cancer Undergoing Sublobar Resection and the Role of Radiation in Its Management

“…Indeed, one recent retrospective series noted that node stage was related to distal recurrence and OS, but not local recurrence (32). In regard to positive margins, radiation therapy has been suggested to improve OS whether it is given concurrently or after chemotherapy (33,34). Of interest, a recent randomized phase II study assessed the benefits of postoperative concurrent chemo/radiation vs. postoperative chemotherapy only in patients undergoing complete resection [>90% (bi)lobectomy] of N2 involved NSCLC and noted no OS or disease-free survival benefit to radiation therapy (35).…”

Post-operative radiation therapy in locally advanced non-small cell lung cancer and the impact of sequential versus concurrent chemotherapy

“…To address this uncertainty, Francis et al, in the Journal of Clinical Oncology, investigated the optimal sequencing of postoperative radiotherapy and chemotherapy for locally advanced or incompletely resected NSCLC (19). In this study, the investigators leveraged the NCDB, a large hospital based observational cohort consisting of approximately 70% of newly diagnosed cases of cancer in the United States.…”