Proton Therapy Reirradiation in Recurrent Head and Neck Squamous Cell Carcinoma

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In a single-institution retrospective cohort study reported in JAMA Network Open, Lee et al found that proton therapy reirradiation (PT-ReRT) may be associated with improved survival in patients with recurrent head and neck squamous cell carcinoma, with a fractionated regimen being associated with better outcomes than a quad shot regimen. However, the study authors noted, “toxic effects [from PT-ReRT] may be substantial.”

Study Details

The study included 242 patients with recurrent head and neck cancer treated with PT-ReRT from January 2013 to December 2020 at Memorial Sloan Kettering Cancer Center. The median interval between radiation courses was 22 months (range = 1–669 months). A total of 154 patients received fractionated radiation and 88 received a quad shot regimen. Median PT-ReRT doses were 70 cobalt gray equivalents (CGE) for the fractionated cohort (n = 154) and 44.4 CGE for the quad shot cohort (n = 88). Outcomes were measured from the start of PT-ReRT. Patients in the quad shot cohort were more likely to have unresectable disease (88.6% vs 42.9% in the fractionated cohort).

Key Findings

Median follow-up was 12.0 months (range = 5.8–26.0 months) for all patients and 24.5 months (range = 13.8–37.8 months) for surviving patients.

On Kaplan-Meier analysis, rates of local control, locoregional control, and overall survival were all significantly better in the fractionated cohort vs the quad shot cohort. At 1 and 2 years, local control rates were 71.8% vs 61.6% and 63.0% vs 52.2%, respectively. At 1 year, locoregional control rates were 62.0% vs 58.5% and 1-year overall survival was 66.6% vs 28.5%. No difference in distant metastatic control was observed.

On multivariate analysis, higher PT-ReRT dose (hazard ratio [HR] = 0.97, 95% confidence interval [CI] = 0.95–1.00,  P = .01) and receipt of salvage surgery (HR = 0.40, 95% CI = 0.22–0.74, P = .003) were significantly associated with improved local control; Karnofsky performance score of ≥ 70 (HR = 0.50, 95% CI = 0.25–0.99, P = .046) and receipt of salvage surgery (HR = 0.57, 95% CI = 0.39–0.84, P = .005) were associated with improved overall survival; and quad shot vs fractionated regimen was associated with worse overall survival (HR= 1.97, 95% CI = 1.36–2.86, P < .001).

Among all patients, early toxicity included 73 grade 3 events and 6 grade 4 events. Late toxicity included 79 grade 3 events, 4 grade 4 events, and 5 grade 5 events.

The investigators concluded, “The findings of this cohort study suggest that, compared with previous reports with photon-based reirradiation, patients are living longer with aggressive PT-ReRT; however, surviving patients remain at risk of early and late complications.”

Nancy Y. Lee, MD, of the Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, is the corresponding author for the JAMA Network Open article.

Disclosure: The study was supported by a grant from the National Cancer Institute. For full disclosures of the study authors, visit

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