毛晓韵 金锋 中国医科大学附属第一医院乳腺外科

　　SUPERMO（乳腺癌乳房切除术后放疗选择性应用的临床试验）是一项III期的多中心随机对照临床试验，其用于评估中危可手术乳腺癌患者行全乳房切除术后胸壁辅助放疗的作用。这项临床试验由英国爱丁堡大学发起，16个国家共1688位乳腺癌患者入组。其将入组患者中危因素定义为如下：1)T1-2pN1M0患者；2)T2pN0病理组织学分级III级或/和淋巴管侵犯阳性患者；3)T3pN0患者。

　　目前SUPERMO试验的病理质控报告指出，研究中心的两位病理医师对参与此项临床试验患者乳腺癌原发灶及淋巴结切片进行病理复审，单盲阅片以得出关于肿瘤类型、组织学分级和淋巴结转移情况与入组时分中心一致的结论。在此项临床试验中，两个大的分中心英国和冰岛共入组此研究85%的患者（英国入组患者占75%，冰岛入组患者占10%），不同国家的分中心在组织学III级和淋巴管侵犯阳性患者占入组患者的比率无明显统计学差异，其中1215位为淋巴结转移阳性，414位为淋巴结转移阴性的乳腺癌患者。82.0%（1369例）的入组患者参与了此次病理复审，其中963位为淋巴结转移阳性，406位为淋巴结转移阴性的乳腺癌患者。其中104例淋巴结转移阴性患者在分中心不满足中危因素的组织学分级或淋巴管侵犯要求归为非中危因素组，但在此次病理复检中在组织学分级或淋巴管侵犯方面满足了中危因素，拟将其归为中危因素组。考虑到入组的严谨性，研究组让病理医生对此部分病例再次进行在线病理评估并得出一致性结论后，这个数由104例减少到70例。

　　来自最大的英国分中心数据表明，41.2％患者存在淋巴结侵犯阳性和54.6%患者组织学分级为III级，而研究组复审数据表明15.1%患者存在淋巴结侵犯阳性和42.4%患者组织学分级为III级，分中心的这两组数据与研究组复审的数据存在明显统计学差异（均P≤0.0001）。在此项临床试验中组织学分级和淋巴管侵犯的准确评估非常重要，其关系到病例的入组，对SUPERMO临床实验结果有举足重轻的影响。

　　SUPERMO临床试验旨在评估中危的可手术乳腺癌患者术后行胸壁辅助放疗的必要性，此试验的结果对于我们未来对肿物为T2且无淋巴结转移的患者是否进行放疗有重要意义，其在实验设计时认为病理组织学分级III级和淋巴管侵犯阳性是预后差、需要放疗的危险因素，将来病理组织学分级和淋巴管侵犯也许会像淋巴结转移一样作为评估患者预后和指导治疗的重要因素，但现阶段来说一致的评估标准和客观的准确评估是重点，研究者也推荐病理切片扫描技术的大规模应用，这对组织学分级和淋巴管侵犯的准确病理评估是大有裨益的。

　　金锋 教授，主任医师  博士研究生导师

　　中国医科大学附属一院乳腺外科主任

　　中国临床肿瘤学会（CSCO）执行委员

　　中国抗癌协会乳腺专业委员会常务委员

　　中国老年学学会乳腺癌分委会副主任委员

　　中华医学会肿瘤学分会乳腺癌学组委员

　　中国医师学会乳腺癌专业委员会常委

　　辽宁省抗癌协会理事

　　辽宁医学会肿瘤分会副主任委员

　　辽宁医学会外科分会乳腺外科学组组长

　研究摘要

The SUPREMO Trial – Pathology quality assurance of a large phase 3 randomised international clinical trial

Poster Spotlight: J. Thomas (United Kingdom)

Background: SUPREMO is a phase 3 randomised trial evaluating radiotherapy post-mastectomy for intermediate risk breast cancer accruing 1688 patients from 16 countries between 2006 and 2013. It was coordinated by the Scottish Clinical Trials Unit， Edinburgh. Intermediate risk was defined as either node-positive disease of any grade in tumours≤5cm diameter (T1 or T2)， or T2 node-negative tumours that were either grade3 and/or showed lymphatic invasion， or T3N0 tumours， independent of pathological features. Central pathology review was carried out for quality assurance. We report the results of this review.

Methods: The two reviewing pathologists were sent a single H&E section and were blinded to the original reported pathology and all patient-related data including nodal status. The review comprised tumour type， histological grade and lymphatic invasion. The slides from potentially ineligible patients by central review were scanned and reviewed online together by the two pathologists and a consensus reached. A subset of 25 of these cases was double-reported independently by the pathologists as an additional comparison.

Results: The two major contributors to the trial were the UK (75%) and the Netherlands (10%). There were no significant differences in the overall reporting profiles (grading and lymphatic invasion) of different countries. There were 1215 node-positive patients and 414 node-negative patients. 1369 (82.0%) of cases were reviewed and the pathologists reviewed 406 and 963 cases respectively. Of the node-negative cases 104 (25.1%) would have been deemed ineligible by initial central review by virtue of grade and/or lymphatic invasion status. Following online consensus review this figure fell to 70 cases (16.9%). The reviewing pathologists show similar reporting profiles with no evidence of case selection bias. There is a striking difference in lymphatic invasion rates (41.2%v 15.1% (UK);  P≤0.0001) and proportions of grade 3 carcinomas (54.6%v 42.4% (UK);  P≤0.0001) on comparing local reporting with central review. There was no significant difference in the locally reported lymphatic invasion rate in the node-negative and node-positive groups (38.2%v 39.6%;  P=0.76) whereas the reviewing pathologists found significant differences between these groups (10.3%v 16.9%; P=0.003).

Conclusions: These data have important implications for the interpretation of outcomes from this clinical trial and the design of future trials and how they are powered. If critical pathology criteria are determinants for trial-entry serious consideration needs to be given to up-front central pathology review. The use of slide scanning technology can facilitate such QA exercises. The lack of difference in pathology reporting profiles in different countries lends encouragement to mounting international trials in the future.