Huang Ming-Yii, Lee Hsin-Hua, Huang Ching-Wen, Huang Chun-Ming, Ma Cheng-Jen, Yin Tzu-Chieh, Tsai Hsiang-Lin, Chai Chee-Yin, Chen Yi-Ting, Wang Jaw-Yuan
Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C.
Department of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C.
Oncol Lett. 2020 Nov;20(5):212. doi: 10.3892/ol.2020.12075. Epub 2020 Sep 8.
Colorectal cancer (CRC) of the clinical tumor stage T4b (cT4b) refers to advanced tumors with direct invasion of adjacent structures and the tumors are considered unresectable. Despite advancements in aggressive surgery and combination chemotherapy, the prognosis of cT4b CRC remains poor. Optimizing the therapeutic sequence administered to patients with cT4b CRC to improve clinical outcomes is crucial. In the present study, patients with unresectable cT4b and nodal stage N1-2 CRC were investigated at a single institution. A total of 20 consecutive patients were treated with pre-operative concurrent chemoradiation by using 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX) since February 2015 and were regularly followed up until March 2020. Due to their poor response to concurrent chemoradiation (CCRT) with FOLFOX, the chemotherapy regimen was changed to irinotecan plus 5-fluorouracil/leucovorin (FOLFIRI) as the second-line neoadjuvant treatment. Genetic alterations, such as microsatellite instability (MSI), were documented, and the expression levels of excision repair cross-complementing group 1 (ERCC1) and ERCC2 were examined. Of the 20 patients, the tumors of 14 patients (70%) became resectable after FOLFIRI administration. The median duration between the last date of radiotherapy and surgery was 32.7 weeks (range, 10.1-59.3 weeks). Of note, 4 of the 14 patients with resectable tumors (28.6%) achieved a pathologic complete response. The median overall survival and progression-free survival were 27.5 months (range, 12-39 months) and 27.5 months (range, 8-39 months), respectively. The cancerous specimens of all of the patients (100%) exhibited ERCC2 overexpression and 18 specimens (90%) had ERCC1 overexpression. Only one tumor (5%) exhibited high MSI. The present study indicated that ERCC overexpression associated with the poor response of FOLFOX-based CCRT and FOLFIRI after FOLFOX-based CCRT failure may have a potential role in conversion to resectable tumors by neoadjuvant treatment in cT4b CRC. However, a further prospective study with more patients is required to improve the precision of the conclusions.
临床肿瘤分期为T4b（cT4b）的结直肠癌是指已侵犯相邻结构的晚期肿瘤，被认为无法切除。尽管在积极手术和联合化疗方面取得了进展，但cT4b期结直肠癌的预后仍然很差。优化给予cT4b期结直肠癌患者的治疗顺序以改善临床结局至关重要。在本研究中，在单一机构对无法切除的cT4b且淋巴结分期为N1-2的结直肠癌患者进行了调查。自2015年2月起，共有20例连续患者接受了术前同步放化疗，采用5-氟尿嘧啶/亚叶酸钙/奥沙利铂（FOLFOX）方案，并定期随访至2020年3月。由于他们对FOLFOX同步放化疗（CCRT）反应不佳，化疗方案改为伊立替康联合5-氟尿嘧啶/亚叶酸钙（FOLFIRI）作为二线新辅助治疗。记录了微卫星不稳定性（MSI）等基因改变，并检测了切除修复交叉互补组1（ERCC1）和ERCC2的表达水平。在这20例患者中，14例患者（70%）的肿瘤在给予FOLFIRI后变得可切除。放疗最后一天与手术之间的中位时间为32.7周（范围为10.1-59.3周）。值得注意的是，14例可切除肿瘤患者中有4例（28.6%）达到了病理完全缓解。中位总生存期和无进展生存期分别为27.5个月（范围为12-39个月）和27.5个月（范围为8-39个月）。所有患者（100%）的癌组织标本均表现出ERCC2过表达，18例标本（90%）有ERCC1过表达。只有1例肿瘤（5%）表现为高度MSI。本研究表明，基于FOLFOX的CCRT反应不佳以及基于FOLFOX的CCRT失败后FOLFIRI反应不佳与ERCC过表达相关，这可能在cT4b期结直肠癌新辅助治疗转化为可切除肿瘤方面具有潜在作用。然而，需要进一步开展有更多患者参与的前瞻性研究以提高结论的准确性。
