Bayesian randomized trial comparing intensity-modulated radiation therapy versus passively scattered proton therapy for locally advanced non–small-cell lung cancer

Liao and colleagues assessed rates of and time to treatment failure (TF) (due either to grade ≥3 radiation pneumonitis [RP] or local recurrence [LR] within 12 months) in a phase 2 Bayesian randomized trial of intensity-modulated radiotherapy (IMRT) versus 3-dimensional proton therapy (3DPT), both with concurrent chemotherapy, for locally advanced non–small-cell lung cancer (NSCLC).¹ The purpose of the study is to determine if 3DPT will reduce irradiated lung volume and reduce the incidence of RP, and whether 3DPT is able to achieve the same local control as IMRT with the same biological effective radiation dose. Pairs of IMRT and 3DPT plans were created for each patient. Patients were eligible for randomization only if both plans satisfied normal tissue constraints at the same radiation dose. Patients not eligible for randomization (NR) were treated with the modality producing the better plan. Of 274 enrolled patients, 181 were randomly allocated to IMRT (n = 105) or 3DPT (n = 76), and 106 received NR-IMRT (n = 70) or NR-3DPT (n = 36). TF rates at 12 months were 20.7% in all, 15.6% in IMRT, and 24.6% in 3DPT groups; corresponding median times to TF were 10.5 months in all, in IMRT, and 3DPT groups. RP rates were 8.7% in all, 7.2% in IMRT, and 11.0% in 3DPT groups. The median times to RP were 4.3, 4.5, and 4.0 months in all patients, in IMRT, and in 3DPT groups, respectively. The incidence of LR was 23.5%, 22.8%, and 24.6% in all patients, in IMRT, and in 3DPT groups, respectively. The median times to LR were 13.0, 12.7, and 13.4 months in all patients, in IMRT, and in 3DPT groups, respectively. Overall survival was 29.3 months in patients receiving IMRT and 26.1 months in those receiving 3DPT (P = 0.27). Among NR patients, the IMRT group was younger (P = 0.013) and had higher-stage disease (P = 0.071); lung V_20-40 was significantly lower in NR-3DPT patients, but was not different at other dose levels. The TF rates and time to TF were no different for NR-IMRT versus NR-3DPT. The authors concluded that there was significant heart sparing with 3DPT compared with IMRT, but there was no difference in RP or local TF when pretreatment comparative IMRT and 3DPT plans met the standard dose constraints for the same prescribed dose.

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1. Liao ZX, et al. ASCO 2016. Abstract 8500.