For patients with unresectable locally advanced non-small cell lung cancer (NSCLC), concurrent chemoradiotherapy (CRT) is the standard of care. However, CRT may be difficult to tolerate, particularly for patients with comorbidities and suboptimal performance status. The use of proton beam therapy (PBT) is an attractive approach that may lessen the unwanted toxic effects of conventional photon-based radiotherapy (eg, severe pneumonitis and esophagitis) and increase on-target effects.
Five-year follow-up results from an open-label, prospective, single-arm phase II trial that included 64 patients with unresectable stage IIIA/B NSCLC treated with concurrent PBT (74 Gy) and carboplatin/paclitaxel chemotherapy demonstrated that this combination was safe and associated with a median overall survival (OS) of 26.5 months and corresponding 5-year OS of 29%. Median progression-free survival (PFS) was 12.9 months, with a 5-year PFS of 22%. Distant recurrences occurred more frequently than locoregional. In a multivariate analysis, poor OS was independently associated with 4 factors: Karnofsky performance status 70%, stage IIIB, tumor location in left lung or right lower lobe, and pretreatment tumor size of greater than 7 cm
The adverse event profile of PBT was generally of a low grade and manageable. Acute toxic effects of note included grade 2 and 3 esophagitis (28% and 8%), grade 2 pneumonitis (2%), cardiac arrhythmia (3%), and ischemia (3%). Late toxic effects were uncommon, with grade 2 and 3 pneumonitis (16% and 12%) being the most common.
The investigators concluded that these results indicate the potential of concurrent chemotherapy and high-dose PBT as a treatment option for locally advanced NSCLC and support further investigation in multi-institutional prospective trials. Further studies should confirm the efficacy and safety of this approach compared to conventional radiotherapy techniques (eg, three-dimensional conformal radiotherapy and intensity-modulated radiation therapy), examine the role of dose escalation in this population, and determine the cost-effectiveness of these approaches. In an accompanying editorial, Charles Thomas Jr, MD (Oregon Health Sciences University, Portland, Oregon), commented on the difficulty in carrying out well-designed, prospective clinical trials on PBT and the need to further explore the safety and efficacy of this treatment approach. He added that the ongoing NRG/RTOG protocol 1308 will compare PBT to photon-based radiotherapy in NSCLC to determine the benefits of each approach.