Proton Beam Therapy versus Photon Radiotherapy for Stage I Non-Small Cell Lung Cancer

Abstract

Proton beam therapy (PBT) and photon radiotherapy for stage I non-small cell lung cancer (NSCLC) were compared in terms of clinical outcomes and dosimetry. Data were obtained from patients who underwent PBT or photon radiotherapy at two institutions-the only two facilities where PBT is available in the Republic of Korea. Multivariate Cox proportional hazards models and propensity score-matched analyses were used to compare local progression-free survival (PFS) and overall survival (OS). Survival and radiation exposure to the lungs were compared in the matched population. Of 289 patients included in the analyses, 112 and 177 underwent PBT and photon radiotherapy, respectively. With a median follow-up duration of 27 months, the 2-year local PFS and OS rates were 94.0% and 83.0%, respectively. In the multivariate analysis, a biologically effective dose (BED₁₀, using α/β = 10 Gy) of ≥125 cobalt gray equivalents was significantly associated with improved local PFS and OS. In the matched analyses, the local PFS and OS did not differ between groups. However, PBT showed significantly lower lung and heart radiation exposure in the mean dose, V5, and V10 than photon radiotherapy. PBT significantly reduced radiation exposure to the heart and lungs without worsening disease control in stage I NSCLC patients.

Keywords: dosimetric comparison; hypofractionated radiotherapy; non-small cell lung cancer; proton beam therapy; stereotactic ablative radiotherapy; stereotactic body radiotherapy.

Figure 1

Kaplan–Meier plot of local progression-free survival, progression-free survival, and overall survival rates for all patients over 48 months (A). Kaplan–Meier plot of local progression-free survival (B), progression-free survival (C), and overall survival rates (D) for matched patients according to radiotherapy techniques over 48 months. PFS, progression-free survival; OS, overall survival.

Figure 2

Forest plots of Cox proportional hazards regression model. Local progression-free survival (A). Overall survival (B). * <0.05; ** <0.01.

Figure 3

Radiation dose–response analysis. The blue line indicates the predicted local control rate determined by a generalized linear model according to the biologically equivalent dose using α/β = 10 Gy (BED₁₀). The red circles indicate estimated local control rates for groups by radiation dose categories. The radiation dose categories were BED₁₀ of 75–90 (n = 45), 90–110 (n = 23), 110–130 (n = 61), and 130–150 CGE (n = 160). The estimated local control rates for these categories were 86.7%, 82.6%, 93.4%, and 97.5%, respectively.

Figure 4

Box plot of mean radiation doses to the lung (A) and heart (B). Box plot of distributions of dose–volume indices for the lung (C) and heart (D). Whiskers indicate 1.5 times the interquartile range above and below the mean; dots represent individual observation. CGE, cobalt gray equivalent; ns, non-significant; ** <0.01; *** <0.001; **** <0.0001.