TY - JOUR
T1 - Carbon-Ion Radiotherapy for Head and Neck Mucosal Melanoma: preliminary clinical outcomes and the MedAustron approach for reporting RBE weighted dose with two models
AU - Nachankar, Ankita
AU - Pelak, Maciej
AU - Schafasand, Mansure
AU - Martino, Giovanna
AU - Tubin, Slavisa
AU - Hug, Eugen
AU - Carlino, Antonio
AU - Lütgendorf-Caucig, Carola
AU - Stock, Markus
AU - Fossati, Piero
N1 - Publisher Copyright:
© 2025 The Authors
PY - 2025/1/1
Y1 - 2025/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85214890427&partnerID=8YFLogxK
U2 - 10.1016/j.ijpt.2025.100738
DO - 10.1016/j.ijpt.2025.100738
M3 - Journal article
SN - 2331-5180
VL - 15
SP - 100738
JO - International Journal of Particle Therapy
JF - International Journal of Particle Therapy
M1 - 100738
ER -