Suzuki Koichi, Muto Yuta, Ichida Kosuke, Fukui Taro, Takayama Yuji, Kakizawa Nao, Kato Takaharu, Hasegawa Fumi, Watanabe Fumiaki, Kaneda Yuji, Kikukawa Rina, Saito Masaaki, Tsujinaka Shingo, Futsuhara Kazushige, Takata Osamu, Noda Hiroshi, Miyakura Yasuyuki, Kiyozaki Hirokazu, Konishi Fumio, Rikiyama Toshiki
Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan.
Department of Surgery, Nerima-Hikarigaoka Hospital, Tokyo 179-0072, Japan.
Oncol Lett. 2017 Aug;14(2):1491-1499. doi: 10.3892/ol.2017.6338. Epub 2017 Jun 7.
Morphological response is considered an improved surrogate to the Response Evaluation Criteria in Solid Tumors (RECIST) model with regard to predicting the prognosis for patients with colorectal liver metastases. However, its use as a decision-making tool for surgical intervention has not been examined. The present study assessed the morphological response in 50 patients who underwent chemotherapy with or without bevacizumab for initially un-resectable colorectal liver metastases. Changes in tumor morphology between heterogeneous with uncertain borders and homogeneous with clear borders were defined as an optimal response (OR). Patients were also assessed as having an incomplete response (IR), and an absence of marked changes was assessed as no response (NR). No significant difference was observed in progression-free survival (PFS) between complete response/partial response (CR/PR) and stable disease/progressive disease (SD/PD), according to RECIST. By contrast, PFS for OR/IR patients was significantly improved compared with that for NR patients (13.2 vs. 8.7 months; P=0.0426). Exclusion of PD enhanced the difference in PFS between OR/IR and NR patients (15.1 vs. 9.3 months; P<0.0001), whereas no difference was observed between CR/PR and SD. The rate of OR and IR in patients treated with bevacizumab was 47.4% (9/19), but only 19.4% (6/31) for patients that were not administered bevacizumab. Comparison of the survival curves between OR/IR and NR patients revealed similar survival rates at 6 months after chemotherapy, but the groups exhibited different survival rates subsequent to this period of time. Patients showing OR/IR within 6 months appeared to be oncologically stable and could be considered as candidates for surgical intervention, including rescue liver resection. Comparing the pathological and morphological features of the tumor with representative optimal response, living tumor cells were revealed to be distributed within the area of vascular reconstruction induced by bevacizumab, resulting in a predictive value for prognosis in the patients treated with bevacizumab. The present findings provided the evidence for physicians to consider patients with previously un-resectable metastatic colorectal cancer as candidates for surgical treatment. Morphological response is a useful decision-making tool for evaluating these patients for rescue liver resection following chemotherapy.
在预测结直肠癌肝转移患者的预后方面,形态学反应被认为是比实体瘤疗效评价标准(RECIST)模型更好的替代指标。然而,其作为手术干预决策工具的应用尚未得到检验。本研究评估了50例接受化疗(联合或不联合贝伐单抗)治疗初始不可切除的结直肠癌肝转移患者的形态学反应。肿瘤形态从不规则边界的异质性变为边界清晰的同质性被定义为最佳反应(OR)。患者也被评估为有不完全反应(IR),无明显变化被评估为无反应(NR)。根据RECIST标准,完全缓解/部分缓解(CR/PR)组与疾病稳定/疾病进展(SD/PD)组的无进展生存期(PFS)无显著差异。相比之下,OR/IR患者的PFS较NR患者显著改善(13.2个月对8.7个月;P = 0.0426)。排除疾病进展(PD)增强了OR/IR和NR患者之间PFS的差异(15.1个月对9.3个月;P < 0.0001),而CR/PR和SD之间无差异。接受贝伐单抗治疗的患者中OR和IR的发生率为47.4%(9/19),但未接受贝伐单抗治疗的患者中仅为19.4%(6/31)。OR/IR和NR患者生存曲线的比较显示,化疗后6个月时生存率相似,但在此时间段之后两组的生存率不同。在6个月内显示OR/IR的患者似乎肿瘤学稳定,可以被视为包括挽救性肝切除在内的手术干预候选者。将肿瘤的病理和形态学特征与代表性的最佳反应进行比较,发现存活的肿瘤细胞分布在贝伐单抗诱导的血管重建区域内,从而对接受贝伐单抗治疗的患者的预后具有预测价值。本研究结果为医生将先前不可切除的转移性结直肠癌患者视为手术治疗候选者提供了证据。形态学反应是评估这些患者化疗后进行挽救性肝切除的有用决策工具。