BackgroundTo evaluate the safety and efficacy of particle therapy (PT) using pencil beam scanning (PBS) technique for early stage non-small cell lung cancer (NSCLC).MethodsFrom 08/2014 to 03/2018, 31 consecutive patients with sum of the longest diameters of primary tumor and hilar lymph node <5cm, N0-1, M0 NSCLC treated with PT were retrospectively analyzed. Gating/active breathing control techniques were used to control tumor motion in 20 and 7 patients. PBS-based proton radiotherapy (PRT) or carbon ion radiotherapy (CIRT) plans were designed via Syngo (R) planningsystem. PRT, PRT+CIRT boost, and CIRT were used in 6, 6 and 19 patients, respectively. Prescriptions were categorized to 3 levels: 5-7.5 GyE * 8-10 Fx, 4-5 GyE * 15-16 Fx and 2.25-3.5 GyE * 20-31 Fx.ResultsThirty-one patients (20 males and 11 females) with a median age of 71 (50-80) years were enrolled with a median follow-up time of 12.1 (2.9-45.2) months. Fourteen were adenocarcinomas, 7 squamous cell carcinomas, 4 non-specified NSCLC and 6 had no histological diagnosis (4/6 had previous resected lung cancer). The median tumor size was 3.1 (1.1-4.7) cm. No grade 4-5 toxicities were observed. One patient experienced grade 3 (per the Common Terminology Criteria for Adverse Events version 4.03) radiation-induced lung injury (RILI) at 6.7months from radiation started. Grade 2 acute toxicities included hematological toxicities (5 cases), RILI (2), plural pain (1) and dermatitis (1). Grade 2 late toxicities included RILI (3) and asymptomatic rib fracture (1). Three patients had progressed disease at 4.0 similar to 10.6months after the initiation of PT. One experienced local failure withsimultaneous distant failure and died of brain metastasis at 10.8months; one developed regional and distant failure and died of lung infection at 8.7months; the other experienced isolated distant failure only and his disease was well controlled after salvage systemic therapy. The estimated rates of progression-free survival, local control, cause-specific survival and overall survival at 1, 2years were 85.5% and 85.5%, 95.2% and 95.2%, 95.0% and 95.0%, 90.7% and 90.7%, respectively.ConclusionsPBS-based PT appears safe and effective for early stage NSCLC. Further follow-up and investigation is warranted.Trial registrationISRCTN, ISRCTN78973763. Registered 14 August 2018- Retrospectively registered, http://www.isrctn.com/ISRCTN78973763.