Hypofractionated Radiation Therapy Combined With Weekly Chemotherapy in Patients With Unresectable or Recurrent Thymic Epithelial Tumor: A Prospective, Single-Arm Phase 2 Study (GASTO-1042).

PURPOSE: This prospective phase 2 study aimed to evaluate the efficacy and safety of hypofractionated radiation therapy (HRT) combined with concurrent weekly chemotherapy in patients with unresectable or recurrent thymic epithelial tumors (TETs). METHODS AND MATERIALS: Patients with unresectable or recurrent intrathoracic TETs that could be encompassed within the radiation fields were enrolled. HRT using intensity modulated radiation therapy (IMRT) technique was administered with 3 different levels of radiation doses (51 Gy/17 fractions (fx), 48 Gy/12 fx, and 45 Gy/9 fx; biologically effective dose of 66.3-67.5Gy), combined with weekly docetaxel (25 mg/m2) and nedaplatin (25 mg/m2). Weekly thymosin α1 (1.6 mg) was administered from the start to 2 months after radiation therapy. The objective response rate (ORR), progression-free survival (PFS), overall survival (OS), health-related quality of life (QOL), and toxicity were recorded. RESULTS: Fifty eligible patients enrolled from August 1, 2018, to July 1, 2020, were analyzed. Most patients (82.0%) had stage IVB tumors. Patients had IMRT-HRT (36-51 Gy in 9-17 fx, median biologically effective dose of 67.2 Gy) and concurrent weekly docetaxel/nedaplatin (2-4 cycles). During a median follow-up of 25.0 months (14.0-40.0), the ORR was 83.7%, the 2-year PFS was 59.1%, and the 2-year OS was 90.0%. There was 1 (2.0%) in-field recurrence while 19 (38.0%) patients developed out-of-field recurrence. Grade 3 pneumonitis was observed in 1 patient (2.0%). The ORR, 2-year PFS, 2-year OS, and toxicity were similar among 3 dose levels. Fourteen (28.0%) patients had 2 to 4 courses of radiation therapy because of recurrent diseases. Only 1 suffered from grade 1 pulmonary fibrosis during follow-up. Most patients (88%) maintained a stable QOL within 1 year after radiation therapy. CONCLUSIONS: IMRT-HRT and concurrent weekly docetaxel/nedaplatin was effective and well tolerated in unresectable or recurrent TETs. Considering the common out-of-field recurrence, this combined regimen could be an option for repeated radiation therapy. Thymosin α1 might help lower the incidence of pneumonitis and maintain the QOL.