Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
Department of Radiology, Wrexham Maelor Hospital, Wrexham, UK.
BMJ Open. 2022 Apr 28;12(4):e049119. doi: 10.1136/bmjopen-2021-049119.
The standard of care for patients with localised rectal cancer is radical surgery, often combined with preoperative neoadjuvant (chemo)radiotherapy. While oncologically effective, this treatment strategy is associated with operative mortality risks, significant morbidity and stoma formation. An alternative approach is chemoradiotherapy to try to achieve a sustained clinical complete response (cCR). This non-surgical management can be attractive, particularly for patients at high risk of surgical complications. Modern radiotherapy techniques allow increased treatment conformality, enabling increased radiation dose to the tumour while reducing dose to normal tissue. The objective of this trial is to assess if radiotherapy dose escalation increases the cCR rate, with acceptable toxicity, for treatment of patients with early rectal cancer unsuitable for radical surgery.
APHRODITE (A Phase II trial of Higher RadiOtherapy Dose In The Eradication of early rectal cancer) is a multicentre, open-label randomised controlled phase II trial aiming to recruit 104 participants from 10 to 12 UK sites. Participants will be allocated with a 2:1 ratio of intervention:control. The intervention is escalated dose radiotherapy (62 Gy to primary tumour, 50.4 Gy to surrounding mesorectum in 28 fractions) using simultaneous integrated boost. The control arm will receive 50.4 Gy to the primary tumour and surrounding mesorectum. Both arms will use intensity-modulated radiotherapy and daily image guidance, combined with concurrent chemotherapy (capecitabine, 5-fluorouracil/leucovorin or omitted). The primary endpoint is the proportion of participants with cCR at 6 months after start of treatment. Secondary outcomes include early and late toxicities, time to stoma formation, overall survival and patient-reported outcomes (European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires QLQ-C30 and QLQ-CR29, low anterior resection syndrome (LARS) questionnaire).
The trial obtained ethical approval from North West Greater Manchester East Research Ethics Committee (reference number 19/NW/0565) and is funded by Yorkshire Cancer Research. The final trial results will be published in peer-reviewed journals and adhere to International Committee of Medical Journal Editors guidelines.
ISRCTN16158514.
局部直肠癌患者的标准治疗方法是根治性手术，通常结合术前新辅助（化疗）放疗。虽然在肿瘤学上有效，但这种治疗策略与手术死亡率风险、显著发病率和造口形成相关。另一种方法是化疗放疗，试图达到持续的临床完全缓解（cCR）。这种非手术治疗方法可能具有吸引力，特别是对于手术并发症风险高的患者。现代放疗技术允许增加治疗适形性，从而增加肿瘤的辐射剂量，同时减少对正常组织的剂量。本试验的目的是评估增加放疗剂量是否能提高不适合根治性手术的早期直肠癌患者的 cCR 率，同时具有可接受的毒性。
APHRODITE（早期直肠癌根治性放疗中更高放疗剂量的 II 期试验）是一项多中心、开放性随机对照 II 期试验，旨在从英国 10-12 个地点招募 104 名参与者。参与者将以 2:1 的比例随机分配干预组和对照组。干预措施是采用同步整合升压的方式进行递增剂量放疗（原发性肿瘤 62Gy，周围直肠系膜 50.4Gy，共 28 个分次）。对照组将接受原发性肿瘤和周围直肠系膜 50.4Gy 的照射。两组均将使用调强放疗和每日图像引导，结合同期化疗（卡培他滨、5-氟尿嘧啶/亚叶酸或省略）。主要终点是治疗开始后 6 个月时 cCR 的参与者比例。次要结局包括早期和晚期毒性、造口形成时间、总生存和患者报告的结局（欧洲癌症研究与治疗组织（EORTC）生活质量问卷 QLQ-C30 和 QLQ-CR29、低位前切除术综合征（LARS）问卷）。
该试验获得了西北大曼彻斯特东研究伦理委员会（参考号 19/NW/0565）的伦理批准，并由约克郡癌症研究资助。最终试验结果将发表在同行评议的期刊上，并遵守国际医学期刊编辑委员会的指南。
ISRCTN16158514。
