Hypo-Fractionated Radiotherapy With Concurrent Chemotherapy (HFRT-CHT) for Locoregional Recurrence of Non-Small Cell Lung Cancer After Complete Resection: A Prospective, Single-Arm, Phase II Study (GASTO1017).

PURPOSE/OBJECTIVE(S) Postoperative locoregional recurrence (LRR) of non-small cell lung cancer (NSCLC) is common. We aimed to explore the efficacy and toxicities of split-course hypo-fractionated radiotherapy with concurrent chemotherapy (HFRT-CHT) with intensity modulated radiotherapy (IMRT) technique in this subgroup of patients. MATERIALS/METHODS NSCLC patients were eligible if confirmed as LRR disease without distant metastasis after complete resection. HFRT-CHT using IMRT technique was administered with 51 Gy in 17 fractions or 40 Gy in 10 fractions as the first course followed by a 3-week break. Patients with no disease progression and no persistent ≥grade 2 toxicities had the second course of 15 Gy in 5 fractions or 28 Gy in 7 fractions as a boost. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS) and objective response rate (ORR). RESULTS Fifty-eight patients were enrolled, and 49 patients (84.5%) completed the whole split-course HFRT-CHT protocol as scheduled. With a median follow-up of 23.9 months for all, the 2-year and 3-year PFS rate was 59.7% and 46.4%, the 2-year and 3-year OS rate was 72.5% and 52.2%, respectively. The ORR rate was 77.6% (45/58) after the first course of HFRT-CHT, and 95.9% (47/49) after the whole course protocol. Grade 3 acute pneumonitis and esophagitis occurred in 2 (3.4%) and 7 (12.1%) patients, and one case (1.7%) of fatal pneumonitis was reported. Grade ≥3 leucopenia, neutropenia, anemia and thrombocytopenia occurred in 3 (5.2%), 2 (3.4%), 1 (1.7%) and 3 (5.2%) patients, respectively. Exploratory subgroup analysis showed that performance status (PS) (PS 0 vs. 1: 2-year PFS, 88.1% vs. 46.9%, P = 0.001; 2-year OS, 100% vs. 59.4%, P < 0.001), recurrence site (single vs. multiple: 2-year PFS, 93.8% vs. 47.4%, P = 0.008; 2-year OS, 100% vs. 63.0%, P = 0.001), and gross tumor volume (GTV) (< 50cm3 vs. ≥50cm3: 2-year PFS, 70.6% vs. 46.2%, P = 0.024; 2-year OS, 85.6% vs. 57.4%, P = 0.034) were significantly associated with PFS and OS. CONCLUSION Split-course HFRT-CHT with IMRT technique achieved promising disease control and satisfactory survival with moderate toxicities in postoperative LRR NSCLC patients. Good PS, a single recurrence site and GTV < 50cm3 tended to have prolonged PFS and OS. Early detection and diagnosis of LRR may improve the efficacy of this treatment regimen. Postoperative LRR deserved a second attempt of cure.