局部复发仍然是 III-IV 期非转移性头颈癌 (HNC) 的主要原因，在高 18F-FDG-PET 信号总肿瘤体积内具有复发倾向区域。我们通过比较适应性 18F-FDG-PET-voxel-，研究了该子体积内的剂量递增与 3 阶段治疗适应相结合是否可以在同等或最小化辐射诱导毒性的情况下增加局部（LC）和区域（RC）控制。基于强度的数字剂量绘制 (A-DPBN) 与非适应性标准调强放射治疗 (S-IMRT)。这项两中心随机对照 II 期试验分配 (1:1) 患者接受 A- DPBN 或 S-IMRT（/-化疗）。资格：口腔、口/咽或喉部非转移性HNC，需要放（化疗）治疗； T1-4N0-3（例外：T1-2N0 声门）； KPS≥70； ≥18 岁并知情同意。1 年 LC 和 RC。 A-DPBN 的剂量处方同时分两步调整至绝对剂量体积限制（≤1.75cm3 可以接受 >84Gy 和标准化等有效剂量 >96Gy），作为 4/7 A-DPBN 后研究过程中的安全措施患者出现 ≥G3 粘膜溃疡。95 名患者被随机分组​​（A-DPBN：47；S-IMRT：48）。中位随访时间为 31 个月（IQR：14-48 个月）； 29 名患者死亡（其中 17 名患者因癌症进展）。与 S-IMRT 相比，A-DPBN 的 LC 效果更好，1 年和 2 年 LC 分别为 91% 和 88% vs. 78% 和 75%（风险比，3.13；95% 置信区间，1.13-8.71； p=0.021）。各组之间的 RC 和总生存率具有可比性，总体等级 (G) ≥3 的晚期毒性也具有可比性（36% 与 20%，p=0.1）。在活跃吸烟者（29% vs. 3%，p=0.005）和饮酒者（33% vs. 13%，p=0.02）中观察到更多≥G3晚期粘膜溃疡，与治疗组无关。同样，在 A-DPBN 组中，诊断时吸烟的患者明显更多出现≥G3（46% vs. 12%，p=0.005）和≥G4（29% vs. 8%，p=0.048）粘膜溃疡。 G5 粘膜毒性后发生一次动脉爆裂。与 S-IMRT 相比，A-DPBN 为 HNC 带来了优越的 1 年和 2 年 LC。这支持多中心 III 期试验的进一步探索。然而，为此类试验招募大量患者样本将具有挑战性，因为人们担心在持续吸烟者中增加剂量时与晚期粘膜溃疡的关联。版权所有 © 2024。由爱思唯尔公司出版。

Local recurrence remains the main cause of death in stage III-IV non-metastatic head-and-neck cancer (HNC) with relapse-prone regions within high 18F-FDG-PET-signal gross tumor volume. We investigated if dose-escalation within this subvolume combined with a 3-phase treatment-adaptation could increase local (LC) and regional (RC) control at equal or minimized radiation-induced toxicity, by comparing adaptive 18F-FDG-PET-voxel-intensity-based dose-painting-by-numbers (A-DPBN) with non-adaptive standard intensity-modulated radiotherapy (S-IMRT).This two-center randomized controlled phase II trial assigned (1:1) patients to receive A-DPBN or S-IMRT (+/-chemotherapy). Eligibility: non-metastatic HNC of oral cavity, oro-/hypopharynx or larynx, needing radio(chemo)therapy; T1-4N0-3 (exception: T1-2N0 glottic); KPS≥70; ≥18 years and informed consent.1-year LC and RC. The dose prescription for A-DPBN was intercurrently adapted in two steps to an absolute dose-volume limit (≤1.75cm3 can receive >84Gy and normalized isoeffective dose >96Gy) as a safety measure during the study course after 4/7 A-DPBN patients developed ≥G3 mucosal ulcers.Ninety-five patients were randomized (A-DPBN: 47; S-IMRT: 48). Median follow-up amounts 31 months (IQR: 14-48 months); 29 patients died (17 of cancer progression). A-DPBN results in superior LC compared to S-IMRT with 1- and 2-year LC of 91% and 88% vs. 78% and 75%, respectively (hazard ratio, 3.13; 95% confidence interval, 1.13-8.71; p=0.021). RC and overall survival are comparable between arms, as is overall grade (G) ≥3 late toxicity (36% vs. 20%, p=0.1). More ≥G3 late mucosal ulcers are observed in active smokers (29% vs. 3%, p=0.005) and alcohol users (33% vs. 13%, p=0.02), independent of treatment arm. Similarly, in the A-DPBN arm, significantly more patients that smoked at diagnosis developed ≥G3 (46% vs. 12%, p=0.005) and ≥G4 (29% vs. 8%, p=0.048) mucosal ulcers. One arterial blowout occurred following a G5 mucosal toxicity.A-DPBN resulted in superior 1- and 2-year LC for HNC compared to S-IMRT. This supports further exploration in multicenter phase III trials. It will however be challenging to recruit a substantial patient sample for such trials as concerns have arisen on the association of late mucosal ulcers when escalating the dose in continuing smokers.Copyright © 2024. Published by Elsevier Inc.