Proton Beam Re-Irradiation for In-Field Recurrent Non-Small Cell Lung Cancer after Radiotherapy

Purpose/Objective(s)To investigate the safety and effectiveness of re-irradiation with proton beam therapy (PBT) for recurrent non-small cell lung cancer (NSCLC), we retrospectively reviewed clinical outcomes.Materials/MethodsFrom April 2009 to July 2021, 26 patients (23 males and 3 females) who were re-irradiated using PBT for recurrence in the irradiation field after radiotherapy for NSCLC, average age 70 years (range 38-88 years), PS 0, 1, 2 = 10, 14, 2 were enrolled in this study. The histology was squamous cell carcinoma in 9 patients, adenocarcinoma in 13, and NSCLC in 4, and all 10 tested for EGFR were negative. The initial treatment was a combination of lung resection and radiation in 4 patients (photon 3, PBT 1), and the remaining were chemoradiotherapy in 6 or radiotherapy alone in 16 (photon 4, PBT 18). The re-irradiation site was peripheral lung field in 22 patients, hilar in 7, and mediastinum in 2. The median tumor diameter was 33.5 mm (12-74 mm), and the clinical re-stage according to the UICC 8th classification was 1, 1, 1, 6, 1, 3, 13, 1 for Stage IA2, IA3, IB, IIA, IIB, IIIA, IIIB, respectively. Beam modulation for PBT was a passive method, with a median re-irradiation dose of 70.4 Gy (RBE) / 32 fr (36-80 Gy (RBE)/10-37 fr). Chemotherapy was used in 7 patients (27%). The overall survival rate (OS), median survival time (MST), local control rate (LC), and recurrence-free survival rate (RFS) were calculated by the Kaplan-Meier method starting from the re-irradiation start date, and the Log-rank test was performed to compare each factor. CTCAE ver5.0 was used to evaluate adverse events.ResultsThe median follow-up time was 23.5 months (3-148 months), and the median period from initial to re-irradiation was 16.5 months (5-60 months). Median initial dose was 66 Gy (RBE)/ 27.5 fr (40-85 Gy (RBE)/4-40 fr), median equivalent dose in 2Gy fraction (EQD2) for initial irradiation was 86.4 Gy (RBE) (40-99 Gy (RBE)), and median total EQD2 dose (combined dose of initial and re-irradiation) was 160.4Gy (RBE) (111.6-190.5 Gy (RBE)). Local recurrence was confirmed in 5 patients, regional recurrence in 2, and distant recurrence in 10, and 16 patients died (11 with disease (1 of them was Grade 5), 5 with other diseases). One, 2, 3, 5-year OS; LC; RFS was 84.4%, 61.3%, 47.2%, 27%; 100%, 82.6%, 63.0%, 63.0%; 82.0%, 47.9%, 35.9%, 29.9%, respectively. MST was 18 months. The prognosis for hilar recurrence was statistically significant poor in MST 15 months compared with the mediastinum in 74 months or peripheral lung field in 43 months (p = 0.007). Late adverse events were Grade 2 rib fracture in 1, Grade 2, 3 brachial plexus disorder in 1 each, Grade 2, 3 subcutaneous tissue disorder in 2, 1, Grade 2 pneumonitis in 4, and Grade 5 bronchial fistula in 1 with hilar recurrence.ConclusionProton beam re-irradiation for the NSCLC patients with local recurrence in the previous irradiation field can be a worthwhile salvage treatment. There is a room for further study on re-irradiation for hilar recurrence.