Balch C M, Durant J R, Bartolucci A A
Ann Surg. 1983 Aug;198(2):164-7. doi: 10.1097/00000658-198308000-00009.
Quality control involving surgical treatment in multi-institutional cancer trials is important because the results of postoperative adjuvant therapy might be obscured by inadequate surgery or pathologic examination of the specimen. In 1975, the Southeastern Cancer Study Group (SEG) initiated a randomized clinical trial of adjuvant immunotherapy (Corynebacterium parvum vs. bacillus Calmette-Guerin) in melanoma patients with nodal metastases. During the course of reviewing the results several years later, 20 of 136 patients (15%) entered into this study were judged as surgically ineligible. The reasons were: 1) biopsy of a metastatic node only without any subsequent regional lymph node dissection (12 patients), 2) partial lymph node dissection (six patients), or 3) too few nodes surgically removed or pathologically identified in the specimen (six patients). All 20 patients were entered into the study by medical oncologists. Thirteen of these 20 surgically ineligible patients have relapsed so far; many were taken off the study as "immunotherapy failures," when, in fact, they were surgical failures. Compared to the 116 surgically eligible patients, the 20 ineligible patients had a shorter median survival (4 months vs. 25 months) and a lower 1-year disease-free survival rate (36% vs. 62%, p = 0.01). The two groups were balanced equally with respect to prognostic factors. Because of these findings, minimum surgical and pathologic guidelines were established for each adjuvant therapy protocol in the SEG. Surgical quality control was reviewed by a surgeon in each institution prior to randomization and again by a surgical investigator centrally. Pathologic criteria were also defined more precisely. The problems with surgically ineligible patients have since been virtually eliminated. Quality control measures for surgical patients entered into cooperative group trials is an essential part of the protocol design and data review. In order to evaluate properly the impact of adjuvant therapy, each clinical trial must comprise a uniform group of surgically treated patients.
在多机构癌症试验中，涉及手术治疗的质量控制至关重要，因为术后辅助治疗的结果可能会因手术操作不当或标本病理检查不充分而受到影响。1975年，东南癌症研究组（SEG）启动了一项针对有淋巴结转移的黑色素瘤患者的辅助免疫治疗随机临床试验（微小棒状杆菌与卡介苗）。几年后在审查结果的过程中，该研究纳入的136例患者中有20例（15%）被判定为手术不符合要求。原因如下：1）仅对转移淋巴结进行活检，随后未进行任何区域淋巴结清扫（12例患者）；2）部分淋巴结清扫（6例患者）；3）手术切除或标本中病理鉴定的淋巴结过少（6例患者）。这20例患者均由肿瘤内科医生纳入研究。到目前为止，这20例手术不符合要求的患者中有13例复发；许多患者被作为“免疫治疗失败”退出研究，而实际上他们是手术失败。与116例手术符合要求的患者相比，这20例不符合要求的患者中位生存期较短（4个月对25个月），1年无病生存率较低（36%对62%，p = 0.01）。两组在预后因素方面均衡。基于这些发现，SEG为每个辅助治疗方案制定了最低手术和病理指南。在随机分组前，各机构的一名外科医生对手术质量控制进行审查，随后由一名外科研究者进行集中审查。病理标准也得到了更精确的定义。此后，手术不符合要求的患者问题几乎得到消除。纳入合作组试验的手术患者的质量控制措施是方案设计和数据审查的重要组成部分。为了正确评估辅助治疗的效果，每项临床试验必须包括一组经过统一手术治疗的患者。
