Nachankar Ankita, Pelak Maciej, Schafasand Mansure, Martino Giovanna, Tubin Slavisa, Hug Eugen, Carlino Antonio, Lütgendorf-Caucig Carola, Stock Markus, Fossati Piero
ACMIT Gmbh, Wiener Neustadt, Austria.
Department of Radiation Oncology, MedAustron Ion Therapy Center, Wiener Neustadt, Austria.
Int J Part Ther. 2025 Jan 9;15:100738. doi: 10.1016/j.ijpt.2025.100738. eCollection 2025 Mar.
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.
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 D 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).
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 D 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, LETd (median) = 57.3 ± 6 keV/µm and LETd (near minimum) = 46.5 ± 6.1 keV/µm.
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.
头颈部黏膜黑色素瘤（HNMMs）是侵袭性、放疗抵抗性癌症。先前的日本放射肿瘤学会（JCROS）研究表明，碳离子放疗（CIRT）可改善局部控制。本研究使用欧洲和日本相对生物效应（RBE）适应性剂量处方评估CIRT治疗HNMM的早期疗效。
2019年11月至2023年4月，14例HNMM患者接受了CIRT治疗。R2切除术后CIRT：9例；仅活检：5例。作为一线治疗使用免疫检查点抑制剂：6例；挽救性治疗：8例。CIRT以68.8（64.5 - 68.8）Gy（RBE）/16分次的D剂量给予，使用局部效应模型I（LEM-I，欧洲）优化RBE加权剂量，使用改良微剂量动力学模型（mMKM，日本）重新计算。
HNMM肿瘤和淋巴结分期：cT3：2例（14%），cT4：12例（86%），cN1：1例（7%）。中位随访时间为22个月（范围4 - 54个月）。2年局部无复发生存率、区域无复发生存率、总生存率和远处转移无复发生存率分别为100%、89%（CI，71 - 100）、64%（CI，44 - 95）和43%（CI，22 - 84）。CIRT后3、6和12个月的中位相对肿瘤体积退缩分别为40%、63%和72%。CIRT相关的晚期毒性为3级黏膜炎：2例（14%）和3级嗅觉丧失：1例（7%）。免疫检查点抑制相关的晚期毒性为2级垂体炎：1例（11%）和3级周围神经病变：1例（11%）。95%高剂量临床靶体积的平均可达到D覆盖剂量为63.2 ± 6 Gy（RBE）（LEM-I）和57.4 ± 5 Gy（RBE）（mMKM）。高剂量临床靶体积内的线性能量传递剂量（LETd）分布令人满意，LETd（中位数）= 57.3 ± 6 keV/µm，LETd（接近最小值）= 46.5 ± 6.1 keV/µm。
双RBE模型（LEM-I，mMKM）优化的CIRT方案提高了不同系统间计划的剂量可比性。它还改善了肿瘤内LETd分布，导致肿瘤快速退缩、毒性特征良好以及早期局部区域控制优异。尽管远处转移仍然是关键的预后因素，但它为手术提供了一个有前景的替代方案。
