Concurrent Chemotherapy, High-Dose Proton Beam Radiotherapy Show Promise in Advanced Lung Cancer

High-dose proton beam radiotherapy (PBT) combined with concurrent chemotherapy may be a viable option for patients with unresectable advanced non-small cell lung cancer (NSCLC), a new study suggests.

Although research has shown the potential for PBT to reduce toxic adverse events in locally advanced NSCLC, long-term prospective data has been lacking.

In a study published in JAMA Oncology, investigators sought to report the final 5-year results of a prospective study evaluating concurrent chemotherapy and high-dose PBT to treat unresectable stage 3 NSCLC.

The investigators enrolled and analyzed 64 patients in the open-label, single-group assignment study. The median follow-up was 27.3 months for all patients and 79.6 months for survivors.

Study interventions included concurrent chemotherapy with carboplatin-paclitaxel and passively scattered PBT in all patients.

The primary outcomes and measures were overall survival (OS), progression-free survival (PFS), actuarial distant metastasis, and locoregional recurrence. Treatment failure patterns were categorized as local/regional or distant.

At the last follow-up, the results of the study showed 17 of 64 participants were still alive, with a median OS of 26.5 months and a 5-year PFS of 22%.

Overall, 39 patients relapsed in a total of 50 sites that were local, regional, or distant. Treatment failures were mostly distant, accounting for 48% of the study participants. Almost all distant treatment failures were not accompanied by local or regional relapses, according to the study. Additionally, the rates of crude local and regional recurrences were found to be low.

The 5-year actuarial distant metastasis and locoregional recurrence were 54% and 28%, respectively. The management was found to be efficacious with promising rates of grade 3 and above toxic effects compared with historical photon therapy data, according to the authors.

“In light of encouraging previous data, it is imperative to provide long-term prospective experiences for the safety and efficacy of PBT as part of combined-modality management for locally advanced NSCLC,” the authors wrote. “… We demonstrate that concurrent PBT and chemotherapy was safe and efficacious from the long-term perspective, and hence justifies further prospective investigation.”

Limitations to the study included the use of non-standardized induction and/or adjuvant chemotherapy, heterogeneity in the population regarding other salient clinical factors, and applicability based on the unresolved issues regarding RTOG 0617 trial data.

“Altogether, with median follow-up of 79.6 months for alive patients, we observed encouraging clinical outcomes and low rates of toxic effects in both the acute and late settings, comparing favorably with historical data using photon-based therapy, particularly regarding toxic effects,” the authors concluded. “These results have implications for ongoing issues regarding the role of dose escalation in this population, further optimization of proton therapy such as IMPT, and cost effectiveness.”