University Hospital Tübingen, Department of Radiation Oncology, Germany; German Cancer Research Center (DKFZ) Heidelberg and German Consortium for Translational Cancer Research (DKTK), Partner Site Tübingen, Germany.
University Hospital Tübingen, Department of Radiation Oncology, Germany.
Radiother Oncol. 2021 Jun;159:155-160. doi: 10.1016/j.radonc.2021.03.011. Epub 2021 Mar 17.
The goal of the present study was to investigate the effect of deep regional hyperthermia on early and long-term oncological outcomes in the context of preoperative radiochemotherapy in rectal cancer.
In this prospective phase II trial, patients with locally advanced rectal cancer were treated with 5-fluorouracil based preoperative radiochemotherapy with 50.4 Gy in 28 fractions. Deep regional hyperthermia was scheduled twice weekly. Pathological tumor regression was scored according to the Dworak regression system. The primary endpoint was pathological complete response (pCR). Further endpoints were local control (LC), distant control (DC), disease-free survival (DFS) and overall survival (OS). Hyperthermia was defined as feasible if 70% of patients received at least eight treatments. Quality of life was assessed at follow-up by the EORTC-QLQ-C30 and QLQ-CR29 questionnaires. Time to event data was analyzed according to Kaplan-Meier based on first-events. The study was registered on clinicaltrials.gov (NCT02353858).
From 2012 until 2017, 78 patients were recruited. Median follow-up was 54 months. Based on magnetic resonance imaging, the mesorectal fascia was involved or threatened in 60% of the patients. Compliance with radiotherapy was 99%, 91% received both cycles of chemotherapy and 77% had eight or more hyperthermia treatments. Median time from the end of radiotherapy to surgery was 6.7 weeks. A pathological complete response was reported in 14% of the patients, 50% had either Dworak 4 (complete regression) or Dworak 3 regression (scattered tumor cells only). Three year estimates for OS, DFS, LC and DC were 94%, 81%, 96% and 87%. Patients with higher hyperthermia related cumulative temperatures showed stronger tumor regression. Global health status based on EORTC-QLQ-C30 was comparable with data from the general population.
Deep regional hyperthermia was feasible, did not compromise standard treatments and resulted in promising long-term oncological outcomes and QoL.
本研究旨在探讨在直肠癌术前放化疗的背景下，深部区域热疗对早期和长期肿瘤学结果的影响。
在这项前瞻性 II 期试验中，局部进展期直肠癌患者接受 5-氟尿嘧啶为基础的术前放化疗，总剂量为 50.4 Gy，共 28 个分次。深部区域热疗每周进行 2 次。根据 Dworak 回归系统对肿瘤组织学消退进行评分。主要终点为病理完全缓解（pCR）。进一步的终点包括局部控制（LC）、远处控制（DC）、无病生存（DFS）和总生存（OS）。如果 70%的患者接受了至少 8 次治疗，则将深部区域热疗定义为可行。在随访时通过 EORTC-QLQ-C30 和 QLQ-CR29 问卷评估生活质量。根据 Kaplan-Meier 进行时间事件数据分析，以首次事件为基础。该研究在 clinicaltrials.gov 上注册（NCT02353858）。
从 2012 年到 2017 年，共招募了 78 例患者。中位随访时间为 54 个月。根据磁共振成像，60%的患者直肠系膜筋膜受累或受侵犯。放疗的依从性为 99%，91%的患者接受了 2 个周期的化疗，77%的患者接受了 8 次或更多的深部区域热疗。从放疗结束到手术的中位时间为 6.7 周。14%的患者报告了病理完全缓解，50%的患者 Dworak 4 级（完全消退）或 Dworak 3 级（仅散在肿瘤细胞）。3 年 OS、DFS、LC 和 DC 的估计值分别为 94%、81%、96%和 87%。接受更高深部区域热疗相关累积温度的患者表现出更强的肿瘤消退。基于 EORTC-QLQ-C30 的全球健康状况与一般人群的数据相当。
深部区域热疗是可行的，不会影响标准治疗，并且带来了有希望的长期肿瘤学结果和生活质量。
