Harris Dean A, Thorne Kymberley, Hutchings Hayley, Islam Saiful, Holland Gail, Hatcher Olivia, Gwynne Sarah, Jenkins Ian, Coyne Peter, Duff Michael, Feldman Melanie, Winter Des C, Gollins Simon, Quirke Phil, West Nick, Brown Gina, Fitzsimmons Deborah, Brown Alan, Beynon John
Department of Colorectal Surgery, Singleton Hospital, Swansea, UK.
Swansea Trials Unit, Swansea University, Swansea, UK.
BMJ Open. 2016 Nov 21;6(11):e012496. doi: 10.1136/bmjopen-2016-012496.
There are 11 500 rectal cancers diagnosed annually in the UK. Although surgery remains the primary treatment, there is evidence that preoperative radiotherapy (RT) improves local recurrence rates. High-quality surgery in rectal cancer is equally important in minimising local recurrence. Advances in MRI-guided prediction of resection margin status and improvements in abdominoperineal excision of the rectum (APER) technique supports a reassessment of the contribution of preoperative RT. A more selective approach to RT may be appropriate given the associated toxicity.
This trial will explore the feasibility of a definitive trial evaluating the omission of RT in resectable low rectal cancer requiring APER. It will test the feasibility of randomising patients to (1) standard care (neoadjuvant long course RT±chemotherapy and APER, or (2) APER surgery alone for cT2/T3ab N0/1 low rectal cancer with clear predicted resection margins on MRI. RT schedule will be 45 Gy over 5 weeks as current standard, with restaging and surgery after 8-12 weeks. Recruitment will be for 24 months with a minimum 12-month follow-up.
Objectives include testing the ability to recruit, consent and retain patients, to quantify the number of patients eligible for a definitive trial and to test feasibility of outcomes measures. These include locoregional recurrence rates, distance to circumferential resection margin, toxicity and surgical complications including perineal wound healing, quality of life and economic analysis. The quality of MRI staging, RT delivery and surgical specimen quality will be closely monitored.
The trial is approved by the Regional Ethics Committee and Health Research Authority (HRA) or equivalent. Written informed consent will be obtained. Serious adverse events will be reported to Swansea Trials Unit (STU), the ethics committee and trial sites. Trial results will be submitted for peer review publication and to trial participants.
ISRCTN02406823.
英国每年有11500例直肠癌被诊断出来。虽然手术仍然是主要治疗方法，但有证据表明术前放疗（RT）可提高局部复发率。直肠癌的高质量手术对于将局部复发降至最低同样重要。MRI引导下对切缘状态预测的进展以及直肠腹会阴切除术（APER）技术的改进支持对术前放疗的作用进行重新评估。鉴于相关毒性，采用更具选择性的放疗方法可能是合适的。
本试验将探索一项确定性试验的可行性，该试验评估在需要进行APER的可切除低位直肠癌中省略放疗的情况。它将测试将患者随机分为两组的可行性：（1）标准治疗（新辅助长程放疗±化疗及APER），或（2）对于MRI显示预测切缘清晰的cT2/T3ab N0/1低位直肠癌仅进行APER手术。放疗方案将按照当前标准在5周内给予45 Gy，8 - 12周后进行重新分期和手术。招募期为24个月，至少随访12个月。
目标包括测试招募、征得患者同意并留住患者的能力，量化适合确定性试验的患者数量，以及测试结果测量的可行性。这些包括局部区域复发率、到环周切缘的距离、毒性和手术并发症，包括会阴伤口愈合、生活质量和经济分析。将密切监测MRI分期质量、放疗实施情况和手术标本质量。
该试验已获得地区伦理委员会和健康研究管理局（HRA）或同等机构的批准。将获得书面知情同意书。严重不良事件将报告给斯旺西试验单位（STU）、伦理委员会和试验地点。试验结果将提交同行评审发表并告知试验参与者。
ISRCTN02406823
