Early stage non-small cell lung cancer treated with pencil beam scanning particle therapy: retrospective analysis of early results on safety and efficacy

Abstract

Background: To evaluate the safety and efficacy of particle therapy (PT) using pencil beam scanning (PBS) technique for early stage non-small cell lung cancer (NSCLC).

Methods: From 08/2014 to 03/2018, 31 consecutive patients with sum of the longest diameters of primary tumor and hilar lymph node < 5 cm, 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® planning system. 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.

Results: Thirty-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 6.7 months 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 4.0~10.6 months after the initiation of PT. One experienced local failure with simultaneous distant failure and died of brain metastasis at 10.8 months; one developed regional and distant failure and died of lung infection at 8.7 months; 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, 2 years were 85.5% and 85.5%, 95.2% and 95.2%, 95.0% and 95.0%, 90.7% and 90.7%, respectively.

Conclusions: PBS-based PT appears safe and effective for early stage NSCLC. Further follow-up and investigation is warranted.

Trial registration: ISRCTN, ISRCTN78973763. Registered 14 August 2018- Retrospectively registered, http://www.isrctn.com/ISRCTN78973763 .

Keywords: Carbon ion; Early stage non-small cell lung cancer; Particle therapy; Pencil beam scanning; Proton; Radiotherapy.

Fig. 1

Typical dose distribution of CIRT (pencial beam scannning) (a) vs. X-ray based radiation therapy (RapidARC®) (b). CIRT significantly reduced the doses to the contralateral lung, heart, spinal cord, and the volume of low-dose area as compared to X-ray based arc therapy

Fig. 2

The estimated curves of local control and various survival rates. Panel a shows that of progression-free survival (PFS), panel b local control (LC), panel c cause-specific survival (CSS), and panel d overall survival (OS)