Outcomes of Patients Treated with Re-Irradiation for Recurrent Head and Neck Cancer Using Pencil Beam Scanning Proton Therapy

Abstract

Re-irradiation (re-RT) for recurrent head and neck cancer (HNC) after prior HNC radiation therapy (RT) is clinically challenging given prior radiation of nearby organs at risk (OARs). We describe clinical outcomes and toxicity of pencil beam scanning proton therapy (PBS-PT) for recurrent HNC. We performed a retrospective analysis of recurrent HNC patients treated at a single institution with PBS-PT. Baseline demographic, disease and treatment characteristics were recorded. Local control (LC), locoregional control (LRC), progression free survival (PFS), distant metastasis free survival (DMFS), and overall survival (OS) were estimated using the Kaplan-Meier method. UVA was completed using logistic regression, and MVA was performed using a backward elimination model. We also report acute and late grade 3+ toxicity outcomes, graded per CTCAE v5.0. A total of 89 patients treated with PBS-PT for recurrent HNC between 2016 and 2022 were included. Primary sites included oropharynx (30.0%), oral cavity (22.5%), sinonasal cavity (15.7%), larynx (12.4%) and nasopharynx (6.7%). The most common tumor histology was SCC (73.0%). Median time to re-RT was 47 months. Median dose of PBS-PT was 60 Gy (range: 40-72) with 50.6% receiving BID treatment. Median GTV volume was 30cc (range 4.8-1083cc). 24% of patients received concurrent systemic therapy (46% cytotoxic, 4.5% immunotherapy). Median follow-up after PBS-PT was 8 months (range: 0-71), and median OS was 13 months (95% CI: 9.3-16.7). The median PFS and DMFS were 7 months (95% CI 5.0-9.0) and 9 months (95% CI 5.3-12.7) respectively. The 1- and 2-year LC rates were 80.8% (95% CI: 70.8-90.8) and 66.2% (95% CI: 50.7-81.7). The 1- and 2-year DMFS were 41.0% (95% CI: 30.0-52.0) and 26.3% (95% CI: 15.7-36.9). On UVA and MVA, smaller GTV volume was associated with improved OS (HR 1.002, p = .004), DMFS (HR 1.002, p = 0.004) and PFS (HR 1.002, p = 0.014). In addition, shorter time to re-RT was associated with worse LRC (HR 1.003, p = 0.002), and higher KPS was associated with improved PFS (HR 0.57, p = 0.04). There were 31 acute grade 3 toxicity events (21 patients), the most common being odynophagia (9.0%) followed mucositis (5.6%), dehydration and dermatitis (both 4.5%). One patient had grade 4 toxicity, laryngeal edema requiring intubation 40 days after completion of re-RT. One patient had acute grade 5 toxicity, an oropharyngeal bleed 74 days after completion of re-RT. There were 35 late toxicity events (n = 27), the most common being dysphagia (n = 7, 7.9%). One patient suffered late grade 5 osteoradionecrosis, which resulted in sepsis. PBS-PT for recurrent HNC results in effective disease control and favorable toxicity. Patients with smaller GTV volume appear to have improved OS, PFS and DMFS, and may be better candidates. Those with shorter time to re-RT also have worse LRC. However, distant failure (DF) comprises a major failure pattern, and biomarkers to identify patients at risk for DF may improve clinical decision making.