Excessive esophageal toxicity in patients with locally advanced non-small cell lung cancer treated with concurrent hypofractionated chemoradiotherapy and 3-weekly platinum doublet chemotherapy

Abstract

Introduction: Concurrent chemoradiation followed by immunotherapy is the standard of care for patients with stage III non-small cell lung cancer (NSCLC). Prior to the introduction of adjuvant immunotherapy, we treated patients with stage III NSCLC with concurrent platinum doublet chemotherapy and 66 Gy in 24 fractions. We determined the toxicity of this treatment. Methods: A retrospective observational study was performed in a cohort of patients with stage III NSCLC, <70 years old, and WHO performance score 0–1. Patients were treated with concurrent platinum doublet chemotherapy and 66 Gy in 24 fractions. All patients were staged with a PET-scan and brain MRI-scan. Toxicity was scored using the common criteria for adverse events (CTCAE v4.03). Results: Between 2012 and 2017, 41 patients were treated with mildly hypofractionated radiotherapy and platinum doublet chemotherapy. The median follow-up was 4.7 years. The median age was 57 and 58% of patients were male. The majority of patients had stage IIIB disease (68%). The median total Gross Tumor Volume (GTV) was 104 cc (range: 15–367 cc). The median lymph node GTV was 59 cc (10–341 cc). Five patients died: four due to an esophagus perforation or fistula, and one due to pulmonary bleeding. Grade ≥ 3 esophageal toxicity occurred in 16 patients. Five patients had late grade ≥ 3 esophageal toxicity (12%). The median overall survival was 19 months. Conclusion: Toxicity was unexpectedly high in patients with stage III NSCLC (WHO 0–1) after concurrent platinum doublet chemotherapy and 66 Gy in 24 fractions.

Keywords

• Non-small cell lung cancer (NSCLC)
• Concurrent chemoradiation
• Hypofractionation
• Platinum doublet chemotherapy
• Esophageal toxicity