Carbon Ion Radiotherapy in Hypo-Fractionation Regimen and Single Dose for Stage I Non-small-Cell Lung Cancer

Abstract

It has been more than one decade since we started carbon ion radiation therapy (CIRT) for non-small-cell lung cancer (NSCLC) in November 1994. From 1994 to 1999, we conducted a phase I/II clinical trial for stage I NSCLC with CIRT and demonstrated an optimal dose of 90 GyE in 18 fractions over 6 weeks and 72 GyE in 9 fractions over 3 weeks for achieving more than 90% local control with minimal pulmonary damage. In the following phase II study from 1999 to 2003, the total dose was fixed at 72 GyE in 9 fractions over 3 weeks and at 52.8 GyE for stage IA and at 60 GyE for stage 1B in 4 fractions over 1 week. Targets were irradiated from four oblique directions. A respiratory-gated irradiation system was used for all irradiation sessions. On these two phase II schedules combined, the 5-year local control rate for 131 primary tumors of 129 patients was 91.5%. The local control rate for T1 and T2 tumors was 96.3 and 84.7%, respectively. While there was significant difference in control rate between T1 and T2, there was no significant difference in histology between squamous and non-squamous type. The 5-year cause-specific survival rate of the patients was 67.0% (IA: 84.4, IB: 43.7), and their overall survival was 45.3% (IA: 53.9, 1B: 34.2). No adverse effects greater than grade III occurred in the lung. In this way, the treatment period and fractionation were shortened and lessened from 18 fractions over 6 weeks to 9 fractions over 3 weeks and further to 4 fractions over one week. Finally it reached a single dose. Since 2003, 210 patients have already been treated with CIRT in single dose increasing 28, 32, 34, 36, 38, 40, 42, 44, 46, and 48 GyE. Compared with the previous fractionation regimen, CIRT in single-dose is demonstrating low morbidity and high QOL. The 5-year local control rate of 131 tumors with doses more than 36 GyE was higher than 80%. The 5-year cause-specific and overall survival rate of 131 patients were 1.5 and 52.6%, respectively. Of the whole evaluate, we will finally recommend that CIRT in single dose is the best for the treatment of the peripheral type of stage I NSCLC.