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背景和目的经腹会阴联合直肠癌切除术是T_2或T_3远端直肠癌的标准治疗方法 ,但这个手术切除范围广泛且毁损性大,因此研究者们一直致力于寻找其他可以替代的治疗方案。本研究是前瞻性观察试验,旨在评估使用高剂量放疗联合同期化疗和后续的观察等待治疗能否作为低位直肠癌的非手术治疗措施。方法本研究的对象为T_2或T_3、N_0~N_1、直肠下6 cm的原发性可切除的腺癌患者。患者接受为期6周的放化疗治疗,具体方案为60Gy分30次照射肿瘤,50G分30次照射淋巴结区域,另外增加5Gy作为直肠腔内近距离放疗,放疗的同时口服300 mg/m~2剂量的替加氟。在治疗开始前、治疗过程中(第2、4、6周)及6周治疗结束后均进行内镜及肿瘤穿刺检查。我们把肿瘤临床完全缓解、肿瘤穿刺部位阴性、6周治疗结束后CT及MRI提示无淋巴结或远处转移的患者分配到观察等待组,把其他所有患者分配到标准手术组。观察等待组的患者使用内镜及选择性部位穿刺密切随访,若发现局部复发则给予手术切除。本研究的主要终点是分配到观察组1年后的局部肿瘤复发率。本研究已在ClinicalT rials.gov注册,试验号为NCT00952926,研究对象入组已结束,但针对次要终点的随访仍在继续。结果本研究自2009年10月20日至2013年12月23日共纳入55名患者。患者从荷兰3个手术中心招募,继而统一在一个三级肿瘤中心(Vejle Hospital,Vejle,Denmark)接受治疗。55名患者中有51名符合纳入标准,其中40名患者为临床完全缓解并分配到观察等待组。观察等待组患者出现局部复发的中位随访时间为23.9个月(IQR:15.3~31.0)。1年的局部复发率为15.5%(95%CI:3.3~26.3)。治疗过程中最常见的急性3级不良反应是腹泻,51名患者中有4名(8%)患者出现腹泻。观察等待组患者的括约肌功能是极好的,1年内25名患者中有18名,2年内16名患者中有11名没有报告过大便失禁,而且在所有时间点里,Jorge-Wexner评分的中位数为0(IQR:0~0)。最常见的远期毒性反应是直肠黏膜出血,1年内30名患者中有2名,2年内17名患者有1名报告了3级出血事件。整个研究过程中没有出现意料以外的严重不良反应或治疗相关的死亡。结论高剂量放化疗及观察等待可能作为需行经腹会阴切除术的远端直肠癌患者的安全替代治疗方法。
Background and Objective Transabdominal perineal resection of the rectum resection is the standard treatment for T 2 or T 3 distal colorectal cancer. However, due to its wide range of surgical resections and its devastating effects, researchers have been searching for alternative therapies. This study is a prospective observational study to evaluate whether non-surgical treatment of low rectal cancer can be assessed using high-dose radiotherapy combined with concurrent chemotherapy and follow-up observation. Methods The subjects were T_2 or T_3, N_0 ~ N_1, patients with primary resectable adenocarcinoma of 6 cm under the rectum. Patients received 6 weeks of radiotherapy and chemotherapy treatment, the specific program for the 60Gy 30 times the irradiation of tumor, 50G 30 times irradiation lymph node area, an additional 5Gy as rectal cavity brachytherapy, radiotherapy at the same time oral dose of 300 mg / m ~ 2 Tegafur. Before the start of treatment, the course of treatment (2, 4, 6 weeks) and 6 weeks after the end of treatment were examined by endoscopy and tumor puncture. We completely rehabilitated the tumor and had a negative tumor puncture site. After 6 weeks of treatment, patients with no lymph node or distant metastasis were assigned to the observation waiting group by CT and MRI, and all other patients were assigned to the standard surgery group. Observed waiting group patients with endoscopic and selective site puncture close follow-up, if found to local recurrence was given surgical resection. The primary endpoint of this study was the local tumor recurrence rate 1 year after assignment to the observation group. This study has been registered with ClinicalTrials.gov, with trial number NCT00952926, and the study population was completed, but follow-up to the secondary endpoint is continuing. Results The study enrolled 55 patients from October 20, 2009 to December 23, 2013. Patients were recruited from three surgical centers in the Netherlands and subsequently treated in a unified tertiary tumor center (Vejle Hospital, Vejle, Denmark). Fifty-five of 51 patients met the inclusion criteria, 40 of whom were clinically complete and assigned to the observation-waiting group. The median follow-up time for observation of local recurrence in the waiting group was 23.9 months (IQR: 15.3 to 31.0). The 1-year local recurrence rate was 15.5% (95% CI: 3.3-26.3). The most common acute grade 3 adverse reaction during treatment was diarrhea, with 4 (51%) of 51 patients having diarrhea. The sphincter function observed in the waiting group was excellent, with 18 of 25 patients within 1 year and 11 of 16 patients not reporting fecal incontinence within 2 years, and at all time points in the Jorge-Wexner score The number of bits is 0 (IQR: 0 ~ 0). The most common long-term toxicities were rectal mucosal bleeding, 2 of 30 patients in 1 year, and 1 in 17 patients in 2 years reporting grade 3 bleeding. No unexpected serious adverse events or treatment-related deaths occurred during the entire study. Conclusions High-dose chemoradiotherapy and observation waiting may serve as a safe and alternative treatment for patients with distal rectal cancer requiring perineal resection of the peritoneum.