Association of Chemoradiotherapy With Outcomes Among Patients With Stage I to II vs Stage III Small Cell Lung Cancer: Secondary Analysis of a Randomized Clinical Trial

Ahmed Salem, Hitesh Mistry, Matthew Hatton, Imogen Locke, Isabelle Monnet, Fiona Blackhall, Corinne Faivre-Finn, Ahmed Salem, Hitesh Mistry, Matthew Hatton, Imogen Locke, Isabelle Monnet, Fiona Blackhall, Corinne Faivre-Finn

Abstract

Importance: There is limited evidence to guide stage I to II small cell lung cancer (SCLC) treatment.

Objective: To examine the characteristics and outcomes among patients with stage I to II SCLC treated with modern chemoradiotherapy.

Design, setting, and participants: In this post hoc secondary analysis of the Concurrent Once-Daily vs Twice-Daily Radiotherapy Trial (CONVERT), a multicenter phase 3 trial conducted in patients with limited-stage SCLC from April 7, 2008, to November 29, 2013, patients with TNM stage I to II SCLC were compared with those with stage III disease. Data analysis was performed from November 1, 2017, to February 28, 2018.

Interventions: In CONVERT, patients were randomized to receive twice-daily (45 Gy in 30 fractions) or once-daily (66 Gy in 33 fractions) chemoradiotherapy. Prophylactic cranial irradiation (PCI) was offered, if indicated.

Main outcomes and measures: The primary trial end point was overall survival (OS). TNM staging information was collected prospectively; this was an unplanned analysis because stratification was not performed according to TNM stage.

Results: A total of 509 (277 [54.4%] men; mean [SD] age, 61.5 [8.3] years) of 543 patients (93.7%) with TNM staging information were eligible for this subgroup analysis, and 86 of the 509 (16.9%) had TNM stage I to II disease. The median gross tumor volume was smaller in patients with stage I to II disease (38.4 cm3; range, 2.2-593.0 cm3) compared with patients with stage III disease (93 cm3; range, 0.5-513.4 cm3) (P < .001). No other significant differences were found in baseline and treatment characteristics and chemoradiotherapy adherence between the 2 groups or the number of patients with stage I to II disease (78 [90.7%]) and stage III disease (346 [81.8%]) who received PCI (P = .10). Patients with stage I to II disease achieved longer OS (median, 50 months [95% CI, 38 to not reached months] vs 25 months [95% CI, 21-29 months]; hazard ratio, 0.60 [95% CI, 0.44-0.83]; P = .001) compared with patients with stage III disease. In patients with stage I to II disease, no significant survival difference was found between the trial arms (median, 39 months in the once-daily arm vs 72 months in the twice-daily arm; P = .38). Apart from lower incidence of acute esophagitis in patients with stage I to II disease compared with patients with stage III disease (grade ≥3, 9 [11.3%] vs 82 [21.1%]; P < .001), the incidences of acute and late toxic effects were not significantly different.

Conclusions and relevance: Patients with stage I to II SCLC in CONVERT achieved long-term survival with acceptable toxic effects after chemoradiotherapy and PCI. This study suggests that patients with stage I to II small cell lung cancer treated with modern chemoradiotherapy have better outcomes compared with patients with stage III disease, providing information that practitioners can potentially give their patients to aid clinical decisions.

Trial registration: ClinicalTrials.gov identifier: NCT00433563.

Conflict of interest statement

Conflict of Interest Disclosures: Drs Faivre-Finn and Blackhall reported receiving grants from Cancer Research UK during the conduct of this study. No other disclosures were reported.

Figures

Figure.. Overall Survival and Local and Metastatic…
Figure.. Overall Survival and Local and Metastatic Progression-Free Survival in the 2 Groups
Data represent patients treated with both once-daily and twice-daily radiotherapy. HR indicates hazard ratio.

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