Aims

To determine the relationship between local relapse following radical radiotherapy for muscle-invasive bladder cancer (MIBC) and radiation dose.

Materials and methods

Patients with T2-4N0-3M0 MIBC were recruited to a phase II study assessing the feasibility of intensity-modulated radiotherapy to the bladder and pelvic lymph nodes. Patients were planned to receive 64 Gy/32 fractions to the bladder tumour, 60 Gy/32 fractions to the involved pelvic nodes and 52 Gy/32 fractions to the uninvolved bladder and pelvic nodes. Pre-treatment set-up was informed by cone-beam CT. For patients who experienced local relapse, cystoscopy and imaging (CT/MRI) was used to reconstruct the relapse gross tumour volume (GTV_relapse) on the original planning CT . GTV_relapse D98% and D95% was determined by co-registering the relapse image to the planning CT utilising deformable image registration (DIR) and rigid image registration (RIR). Failure was classified into five types based on spatial and dosimetric criteria as follows: A (central high-dose failure), B (peripheral high-dose failure), C (central elective dose failure), D (peripheral elective dose failure) and E (extraneous dose failure).

Results

Between June 2009 and November 2012, 38 patients were recruited. Following treatment, 18/38 (47%) patients experienced local relapse within the bladder. The median time to local relapse was 9.0 months (95% confidence interval 6.3–11.7). Seventeen of 18 patients were evaluable based on the availability of cross-sectional relapse imaging. A significant difference between DIR and RIR methods was seen. With the DIR approach, the median GTV_relapse D98% and D95% was 97% and 98% of prescribed dose, respectively. Eleven of 17 (65%) patients experienced type A failure and 6/17 (35%) patients type B failure. No patients had type C, D or E failure. MIBC failure occurred in 10/17 (59%) relapsed patients; of those, 7/11 (64%) had type A failure and 3/6 (50%) had type B failure. Non-MIBC failure occurred in 7/17 (41%) patients; 4/11 (36%) with type A failure and 3/6 (50%) with type B failure.

Conclusion

Relapse following radiotherapy occurred within close proximity to the original bladder tumour volume and within the planned high-dose region, suggesting possible biological causes for failure. We advise caution when considering margin reduction for future reduced high-dose radiation volume or partial bladder radiotherapy protocols.

中文翻译：

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根据剂量绘制膀胱放射治疗后的局部衰竭

 目标

确定肌层浸润性膀胱癌（MIBC）根治性放射治疗后局部复发与放射剂量之间的关系。

 材料和方法

T2-4N0-3M0 MIBC 患者被招募参加一项 II 期研究，评估膀胱和盆腔淋巴结调强放射治疗的可行性。患者计划对膀胱肿瘤接受 64 Gy/32 分次照射，对受累盆腔结节接受 60 Gy/32 分次照射，对未受累膀胱和盆腔结节接受 52 Gy/32 分次照射。通过锥束 CT 告知治疗前的设置。对于局部复发的患者，采用膀胱镜检查和影像学（CT/MRI）在原计划CT上重建复发肉眼肿瘤体积（GTV_复发）。 GTV_复发D98% 和 D95% 是通过利用变形图像配准 (DIR) 和刚性图像配准 (RIR) 将复发图像共同配准到计划 CT 来确定的。根据空间和剂量标准将失败分为以下五种类型：A（中心高剂量失败）、B（外周高剂量失败）、C（中心选择性剂量失败）、D（外周选择性剂量失败）和E （外部剂量失败）。

 结果

2009年6月至2012年11月期间，招募了38名患者。治疗后，18/38 (47%) 的患者出现膀胱内局部复发。局部复发的中位时间为 9.0 个月（95% 置信区间 6.3-11.7）。 18 名患者中的 17 名可根据横截面复发成像的可用性进行评估。 DIR 和 RIR 方法之间存在显着差异。采用 DIR 方法，中位 GTV_复发D98% 和 D95% 分别为处方剂量的 97% 和 98%。 17 名患者中的 11 名 (65%) 经历了 A 型失败，6/17 (35%) 名患者经历了 B 型失败。没有患者出现 C、D 或 E 型失败。 MIBC 失败发生在 10/17 (59%) 的复发患者中；其中，7/11 (64%) 存在 A 型故障，3/6 (50%) 存在 B 型故障。 7/17 (41%) 患者发生非 MIBC 失败； 4/11 (36%) 发生 A 类故障，3/6 (50%) 发生 B 类故障。

 结论

放疗后的复发发生在非常接近原始膀胱肿瘤体积和计划的高剂量区域内，这表明失败可能有生物学原因。我们建议在考虑减少未来高剂量辐射量或部分膀胱放疗方案的余量时谨慎行事。