Carbon-Ion Radiotherapy for Head and Neck Mucosal Melanoma: preliminary clinical outcomes and the MedAustron approach for reporting RBE weighted dose with two models

Ankita Nachankar, Maciej Pelak, Mansure Schafasand, Giovanna Martino, Slavisa Tubin, Eugen Hug, Antonio Carlino, Carola Lütgendorf-Caucig, Markus Stock, Piero Fossati

Research output: Journal article (peer-reviewed)Journal article

Abstract

Purpose: Head and neck mucosal melanomas (HNMMs) are aggressive, radiotherapy-resistant cancers. Previous JCROS studies demonstrated improved local control with carbon-ion radiotherapy (CIRT). This study evaluates early outcomes of CIRT for HNMM using the European and Japanese relative biological effectiveness (RBE)-adapted dose prescriptions. Materials and Methods: Between November 2019 and April 2023, 14 HNMM patients received CIRT treatment. Postoperative CIRT for R2 resection: 9 cases; biopsies only: 5 cases. Immune checkpoint inhibitors used as primary treatment: 6 cases; salvage: 8 cases. CIRT delivered in DRBE dose of 68.8 (64.5-68.8) Gy (RBE)/16 fractions, optimized with the local effect model I (LEM-I, European) for RBE-weighted dose, recalculated using the modified-microdosimetric kinetic model (mMKM, Japanese). Results: HNMM tumor and nodal stages: cT3: 2 (14%), cT4: 12 (86%), cN1: 1 (7%). The median follow-up was 22 months (range, 4-54). The 2-year local recurrence-free survival, regional recurrence-free survival, overall survival, and distant metastasis-free survival were 100%, 89% (CI, 71-100), 64% (CI, 44-95), and 43% (CI, 22-84), respectively. The median relative volumetric tumor regression at 3, 6, and 12 months post-CIRT was 40%, 63%, and 72%, respectively. CIRT-associated late toxicities were G3 mucositis: 2 (14%) and G3 anosmia: 1 (7%). The immune checkpoint inhibition-related late toxicities were G2 hypophysitis: 1 (11%) and G3 peripheral neuropathy: 1 (11%). The average attainable DRBE coverage for 95% of high-dose clinical target volume was 63.2 ± 6 Gy (RBE) (LEM-I) and 57.4 ± 5 Gy (RBE) (mMKM). The LETd distribution in high-dose clinical target volume was satisfactory, LETd50% (median) = 57.3 ± 6 keV/µm and LETd98% (near minimum) = 46.5 ± 6.1 keV/µm. Conclusion: Bi-RBE model (LEM-I, mMKM) optimized CIRT protocol improved dose comparability of plans between different systems. It also improved intratumoral LETd distribution and resulted in rapid tumor regression, favorable toxicity profile, and excellent early loco-regional control. It provides a promising alternative to surgery, though distant metastasis remains the key prognostic factor.

Original languageEnglish
Article number100738
Pages (from-to)100738
JournalInternational Journal of Particle Therapy
Volume15
DOIs
Publication statusAccepted/In press - 01 Jan 2025

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