Detection of residual disease after neoadjuvant chemoradiotherapy for oesophageal cancer (preSANO): a prospective multicentre, diagnostic cohort study
Detection of residual disease after neoadjuvant chemoradiotherapy for oesophageal cancer (preSANO): a prospective multicentre, diagnostic cohort study
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DOI：
10.1016/s1470-2045(18)30201-8
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发表时间：
2018-07-01
期刊：
影响因子：
51.1
通讯作者：
van Lanschot, J. Jan B.
中科院分区：
文献类型：
--
作者：
Noordman, Bo Jan;Spaander, Manon C. W.;van Lanschot, J. Jan B.
背景食道癌新辅助放化疗后，约有一半的鳞癌患者和四分之一的腺癌患者手术前原发灶病理完全缓解。因此，对于对新辅助治疗有足够反应的患者，应该重新考虑新辅助化疗后标准食道切除术的必要性。在这项研究中，我们旨在建立不同诊断方法检测新辅助放化疗后残留疾病的准确性，以及用于临床疗效评估的诊断技术的最佳组合。方法在荷兰的6个中心进行前瞻性的多中心诊断队列研究。符合条件的患者年龄为18岁或以上，有组织学证实的可切除的食管鳞癌或腺癌或食管胃交界处的鳞癌或腺癌，并符合条件接受新辅助放化疗(每周5个周期的卡铂[曲线下面积每分钟2毫克/毫升]加紫杉醇[50毫克/米(2)体表面积]联合放射治疗，共23次)，然后进行食道切除术。新辅助化疗结束后4-6周，患者接受食管胃十二指肠镜活检和超声内窥镜检查，测量最大肿瘤厚度。经组织学证实为局部残留病变或未通过内窥镜检查且无远处转移的患者立即行手术切除。对其余患者进行第二次临床疗效评估(PET-CT、食道胃十二指肠镜活检、超声内窥镜测量最大肿瘤厚度和可疑淋巴结细针抽吸)，在新辅助放化疗完成12-14周后进行手术。主要终点是临床反应评估期间的临床反应与切除标本的最终病理反应之间的相关性，如在临床反应评估期间遗漏的肿瘤退化等级(TRG)3级或4级(切除标本中残留肿瘤的10%)的比例所示。这项研究在荷兰试验登记处(NTR4834)注册，并已完成。2013年7月22日至2016年12月28日的研究结果包括219名患者，其中207人进入分析。26个TRG3或TRG4肿瘤中有8个(31%[95%可信区间17-50])被常规活检和细针吸取的内窥镜检查漏诊。41个TRG3或TRG4肿瘤中有4个(10%[95%可信区间4~23])因咬合活检和细针抽吸而漏诊。39例患者中有11例(28%[95%可信区间17~44])超声内窥镜检查漏诊了TRG3或TRG4残留肿瘤。PET-CT漏诊了41个TRG3或TRG4肿瘤中的6个(15%[95%可信区间7~28])。在190例患者(1例鳞癌，17例腺癌)中，PET-CT检出18例(9%)经组织学证实的间歇性远处转移。食道癌新辅助放化疗后的解释、临床反应的超声内窥镜检查、咬合活检和可疑淋巴结的细针抽吸足以检测局部区域残留病变，而PET-CT用于间歇性转移的检测。目前正在第3阶段随机对照试验(SANO试验；荷兰试验登记NTR6803)中对这种诊断模式组合的积极监测进行评估。版权所有(C)2018爱思唯尔有限公司。保留所有权利。
Background After neoadjuvant chemoradiotherapy for oesophageal cancer, roughly half of the patients with squamous cell carcinoma and a quarter of those with adenocarcinoma have a pathological complete response of the primary tumour before surgery. Thus, the necessity of standard oesophagectomy after neoadjuvant chemoradiotherapy should be reconsidered for patients who respond sufficiently to neoadjuvant treatment. In this study, we aimed to establish the accuracy of detection of residual disease after neoadjuvant chemoradiotherapy with different diagnostic approaches, and the optimal combination of diagnostic techniques for clinical response evaluations.Methods The preSANO trial was a prospective, multicentre, diagnostic cohort study at six centres in the Netherlands. Eligible patients were aged 18 years or older, had histologically proven, resectable, squamous cell carcinoma or adenocarcinoma of the oesophagus or oesophagogastric junction, and were eligible for potential curative therapy with neoadjuvant chemoradiotherapy (five weekly cycles of carboplatin [area under the curve 2 mg/mL per min] plus paclitaxel [50 mg/m(2) of body-surface area] combined with 41.4 Gy radiotherapy in 23 fractions) followed by oesophagectomy. 4-6 weeks after completion of neoadjuvant chemoradiotherapy, patients had oesophagogastroduodenoscopy with biopsies and endoscopic ultrasonography with measurement of maximum tumour thickness. Patients with histologically proven locoregional residual disease or no-pass during endoscopy and without distant metastases underwent immediate surgical resection. In the remaining patients a second clinical response evaluation was done (PET-CT, oesophagogastroduodenoscopy with biopsies, endoscopic ultrasonography with measurement of maximum tumour thickness, and fine-needle aspiration of suspicious lymph nodes), followed by surgery 12-14 weeks after completion of neoadjuvant chemoradiotherapy. The primary endpoint was the correlation between clinical response during clinical response evaluations and the final pathological response in resection specimens, as shown by the proportion of tumour regression grade (TRG) 3 or 4 (>10% residual carcinoma in the resection specimen) residual tumours that was missed during clinical response evaluations. This study was registered with the Netherlands Trial Register (NTR4834), and has been completed.Findings Between July 22, 2013, and Dec 28, 2016, 219 patients were included, 207 of whom were included in the analyses. Eight of 26 TRG3 or TRG4 tumours (31% [95% CI 17-50]) were missed by endoscopy with regular biopsies and fine-needle aspiration. Four of 41 TRG3 or TRG4 tumours (10% [95% CI 4-23]) were missed with bite-on-bite biopsies and fine-needle aspiration. Endoscopic ultrasonography with maximum tumour thickness measurement missed TRG3 or TRG4 residual tumours in 11 of 39 patients (28% [95% CI 17-44]). PET-CT missed six of 41 TRG3 or TRG4 tumours (15% [95% CI 7-28]). PET-CT detected interval distant histologically proven metastases in 18 (9%) of 190 patients (one squamous cell carcinoma, 17 adenocarcinomas).Interpretation After neoadjuvant chemoradiotherapy for oesophageal cancer, clinical response evaluation with endoscopic ultrasonography, bite-on-bite biopsies, and fine-needle aspiration of suspicious lymph nodes was adequate for detection of locoregional residual disease, with PET-CT for detection of interval metastases. Active surveillance with this combination of diagnostic modalities is now being assessed in a phase 3 randomised controlled trial (SANO trial; Netherlands Trial Register NTR6803). Copyright (c) 2018 Elsevier Ltd. All rights reserved.