我们确定了通过图像引导适应性放射治疗 (IGART) 根治性治疗肌肉浸润性膀胱癌 (MIBC) 的最大耐受肿瘤聚焦剂量 (MTD) 和长期临床结果。 59 名 T2-T4aN0M0 单灶尿路上皮 MIBC 患者适合每日根治性放射治疗的患者被前瞻性地招募到伦理批准的方案中（XX）。未受累膀胱 (PTVbladder) 计划分 32 次接受 52Gy (f)。膀胱肿瘤 (PTVtumour) 计划指定的剂量水平为 68、70、72 或 74Gy。如果违反危及器官 (OAR) 剂量限制，则 PTVtumour 计划为 64Gy。剂量水平分配是通过对之前招募的所有患者进行同时毒性评估来确定的。使用CTCAE v3.0评估急性毒性；使用 RTOG 标准评估晚期毒性。 MTD 被预定义为最高剂量水平，估计概率 ≤ 15% ≥G3 晚期毒性，观察率 <50% 急性 G3 和 <10% 急性 G4 毒性。26 名患者被分配至 68Gy，其中 6 名计划接受治疗至 64Gy； 29名患者被分配至70Gy，其中1名患者计划接受68Gy，2名患者被分配并计划接受72Gy；没有患者被分配到 74Gy。 3名患者没有按计划完成治疗，其中只有1名患者因发生剂量限制性毒性而停止治疗。 MTD为70Gy。急性泌尿生殖系统 (GU) 和胃肠道 (GI) G3 急性毒性分别见于 19% 和 7% 的患者。未发现 4 级 GU 或 GI 毒性。晚期毒性（任何）G3 和 G4 分别见于 14% 和 2% 的患者。 5 年总生存率为 58%（95% CI 44-71%）。膀胱保留率为 89%（95% CI，88% 至 96%），其中 6 名患者未保留天然膀胱功能。使用 IGART 将膀胱肿瘤聚焦剂量递增至 70Gy 是可行的，且毒性可接受。该剂量水平已在 II 期随机对照试验 (XXXXX) 中进行了评估。版权所有 © 2024。由 Elsevier Inc. 出版。

We determine the maximum tolerated tumour focused dose (MTD) for the radical treatment of muscle invasive bladder cancer (MIBC) enabled by image guided adaptive radiotherapy (IGART) and long-term clinical outcomes.Fifty-nine patients with T2-T4aN0M0 unifocal urothelial MIBC suitable for daily radical radiotherapy were recruited prospectively to an ethics approved protocol (XX). The uninvolved bladder (PTVbladder) was planned to 52Gy in 32 fractions (f). The bladder tumour (PTVtumour) was planned to an assigned dose level of 68, 70, 72, or 74Gy. If organ at risk (OAR) dose constraints were violated, then PTVtumour was planned to 64Gy. Dose level allocation was determined by concurrent toxicity assessment of all previous patients recruited. Acute toxicity was evaluated using CTCAE v3.0; late toxicity was evaluated using RTOG criteria. The MTD was predefined as the highest dose level with estimated probability of ≤ 15% ≥G3 late toxicity and observed rate <50% acute G3 and <10% acute G4 toxicity.Twenty-six patients were assigned to 68Gy, of whom 6 were planned to 64Gy; 29 patients were assigned to 70Gy of whom 1 was planned to 68Gy, 2 patients were assigned and planned to 72Gy; no patients were assigned to 74Gy. Three patients did not complete treatment as planned, of whom only 1 patient stopped treatment because dose limiting toxicity occurred. The MTD was 70Gy. Acute genitourinary (GU) and gastrointestinal (GI) G3 acute toxicity was seen in 19% and 7% patients respectively. No grade 4 GU or GI toxicity was seen. Late toxicity (any) G3 and G4 was seen in 14% and 2% patients respectively. The 5-year overall survival was 58% (95% CI 44-71%). The bladder preservation rate was 89% (95% CI, 88 to 96%) with 6 patients not retaining native bladder function.Bladder tumour focused dose escalation to 70Gy using IGART is feasible with acceptable toxicity. This dose level has been evaluated in a phase II randomised control trial (XXXXX).Copyright © 2024. Published by Elsevier Inc.