Hafeez Shaista, Warren-Oseni Karole, Jones Kelly, Mohammed Kabir, El-Ghzal Amir, Dearnaley David, Harris Victoria, Khan Atia, Kumar Pardeep, Lalondrelle Susan, McDonald Fiona, Tan Melissa, Thomas Karen, Thompson Alan, McNair Helen A, Hansen Vibeke N, Huddart Robert A
The Institute of Cancer Research, London, United Kingdom; The Royal Marsden NHS Foundation Trust, London, United Kingdom.
The Institute of Cancer Research, London, United Kingdom; The Royal Marsden NHS Foundation Trust, London, United Kingdom.
Int J Radiat Oncol Biol Phys. 2025 Jan 1;121(1):165-175. doi: 10.1016/j.ijrobp.2024.07.2317. Epub 2024 Jul 26.
We determine the maximum tolerated tumor-focused dose (MTD) for the radical treatment of muscle invasive bladder cancer enabled by image guided adaptive radiation therapy and long-term clinical outcomes.
Fifty-nine patients with T2 to T4aN0M0 unifocal urothelial muscle invasive bladder cancer suitable for daily radical radiation therapy were recruited prospectively to an ethics-approved protocol (NCT01124682). The uninvolved bladder (PTV) was planned to 52 Gy in 32 fractions. The bladder tumor (PTV) was planned to an assigned dose level of 68, 70, 72, or 74 Gy. If organ at risk dose constraints were violated, then PTV was planned to 64 Gy. Dose level allocation was determined by concurrent toxicity assessment of all previous patients recruited. Acute toxicity was evaluated using Common Terminology Criteria for Adverse Events v3.0; late toxicity was evaluated using Radiation Therapy Oncology Group criteria. The MTD was predefined as the highest dose level with an estimated probability of ≤ 15% ≥ G3 late toxicity and an observed rate of <50% acute G3 and <10% acute G4 toxicity.
Twenty-six patients were assigned to 68 Gy, of whom 6 were planned to 64 Gy; 29 patients were assigned to 70 Gy of whom 1 was planned to 68 Gy, 2 patients were assigned and planned to 72 Gy; no patients were assigned to 74 Gy. Three patients did not complete the treatment as planned, of whom only 1 patient stopped treatment because dose-limiting toxicity occurred. The MTD was 70 Gy. Acute genito-urinary and gastro-intestinal G3 acute toxicity was seen in 19% and 7% of patients, respectively. No acute G4 genito-urinary or gastro-intestinal toxicity was seen. Late toxicity (any) G3 and G4 was seen in 14% and 2% of patients, respectively. The 5-year overall survival was 58% (95% CI, 44%-71%). The bladder preservation rate was 89% (95% CI, 88%-96%) with 6 patients not retaining native bladder function.
Bladder tumor-focused dose escalation to 70 Gy using image guided adaptive radiation therapy is feasible with acceptable toxicity. This dose level has been evaluated in a phase II randomized control trial (RAIDER NCT02447549).
我们确定通过图像引导的自适应放射治疗实现的肌肉浸润性膀胱癌根治性治疗的最大耐受肿瘤聚焦剂量（MTD）以及长期临床结果。
前瞻性招募了59例适合每日根治性放射治疗的T2至T4aN0M0单灶性尿路上皮肌肉浸润性膀胱癌患者，纳入一项经伦理批准的方案（NCT01124682）。未受累膀胱（计划靶体积）计划接受32次分割照射，总剂量52 Gy。膀胱肿瘤（计划靶体积）计划接受68、70、72或74 Gy的指定剂量水平照射。如果危及器官的剂量限制被违反，则计划靶体积计划接受64 Gy照射。剂量水平分配由所有先前招募患者的同步毒性评估确定。使用不良事件通用术语标准v3.0评估急性毒性；使用放射治疗肿瘤学组标准评估晚期毒性。MTD预先定义为估计≥3级晚期毒性概率≤15%且观察到的3级急性毒性发生率<50%和4级急性毒性发生率<10%的最高剂量水平。
26例患者被分配至68 Gy组，其中6例计划接受64 Gy照射；29例患者被分配至70 Gy组，其中1例计划接受68 Gy照射，2例被分配并计划接受72 Gy照射；无患者被分配至74 Gy组。3例患者未按计划完成治疗，其中仅1例患者因出现剂量限制性毒性而停止治疗。MTD为70 Gy。分别有19%和7%的患者出现泌尿生殖系统和胃肠道3级急性毒性。未观察到泌尿生殖系统或胃肠道4级急性毒性。分别有14%和2%的患者出现3级和4级晚期毒性（任何）。5年总生存率为58%（95%置信区间，44%-71%）。膀胱保留率为89%（95%置信区间，88%-96%），6例患者未保留膀胱功能。
使用图像引导的自适应放射治疗将膀胱肿瘤聚焦剂量提高至70 Gy是可行的，毒性可接受。该剂量水平已在一项II期随机对照试验（RAIDER NCT02447549）中进行评估。
