Proton therapy re-irradiation outcomes and genomic landscape of patients with recurrent head and neck cancer

• Published in: Oral oncology Vol. 154; p. 106875
• Main Authors: Krc, Rebecca, Mendes, William, Molitoris, Jason, Ferris, Matthew, Song, Yang, Shetty, Amol, Mehra, Ranee, Papadimitriou, John C., Hatten, Kyle, Taylor, Rodney, Wolf, Jeffrey, Sun, Kai, Bentzen, Soren, Regine, William, Tran, Phuoc, Witek, Matthew
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2024
• Subjects: Adult; Aged; Aged, 80 and over; Female; Genomics; Genomics - methods; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - radiotherapy; Humans; Male; Middle Aged; Mutation; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - radiotherapy; Pencil beam scanning; Proton therapy; Proton Therapy - adverse effects; Proton Therapy - methods; Re-Irradiation - methods; Recurrent head and neck cancer; Retrospective Studies; Toxicity; Treatment Outcome; Recurrent head and neck cancer; Proton therapy; Pencil beam scanning; Toxicity; Genomics
• DOI: 10.1016/j.oraloncology.2024.106875
• ISSN: 1368-8375

•Re-irradiation (re-RT) for recurrent head and neck cancer (rHNC) is clinically challenging.•Methods to better select patients for re-RT is of paramount importance.•Proton therapy re-RT of rHNC affords good local control and an acceptable toxicity profile.•Distant failures are common, and are associated with TP53, NOTCH4, and ARID1B somatic mutations.•Validation may provide rationale for inclusion of genomic alterations in the decision process. Re-irradiation (re-RT) for recurrent head and neck cancer (rHNC) is challenging. We describe clinical outcomes and toxicity of proton therapy (PT) for recurrent HNC, and report genomic alterations associated with patterns of failure. We performed a retrospective analysis of rHNC patients treated with PT. Outcomes were estimated using the Kaplan-Meier method. Univariate (UVA) and multivariate analyses (MVA) were performed to assess multiple patient factors. Next-generation sequencing and genomic analyses were performed on available samples. Eighty-nine patients treated with PBS-PT for rHNC with a median follow-up of 12 mo (0–71 mo) were included. The 1- and 2-y local control (LC) rates were 80.8 % (95 % CI: 70.8–90.8) and 66.2 % (95 % CI: 50.7–81.7), and 1- and 2-y distant metastasis-free survival (DMFS) were 41.0 % (95 % CI: 30.0–52.0) and 26.3 % (95 % CI: 15.7–36.9). The median overall survival (OS) was 13 mo (95 % CI: 9.3–16.7). On UVA and MVA, smaller gross tumor volume (GTV) was associated with improved OS (HR 1.002, P = 0.004), DMFS (HR 1.002, P = 0.004), and PFS (HR 1.002, P = 0.014). There were 35 late Gr3 + toxicity events (30.3 %). Patients with higher candidate gene-specific mutation burden (genes with [OR] > 2, P < 0.05) had inferior PFS. TP53, NOTCH4, and ARID1B mutations were associated with inferior DMFS (OR > 2, P < 0.05). PBS-PT is effective at achieving LC for rHNC with favorable toxicity. Distant metastases are common, and associated with TP53, NOTCH4, and ARID1B mutations. Inclusion of genomic alterations in the clinical decision process may be warranted.