Department of Medical Oncology, University of Health Sciences, Okmeydani Training and Research Hospital, Istanbul, Turkey.
Department of Medical Oncology, Faculty of Medicine, Medipol University, Istanbul, Turkey.
Colorectal Dis. 2021 Jan;23(1):206-212. doi: 10.1111/codi.15389. Epub 2020 Oct 20.
The aim was to investigate the RAS discordance between initial and recurrent metastasectomy specimens in metastatic colorectal cancer (mCRC) patients treated with chemotherapy (CT) plus biological agents in a first-line setting.
Patients who had been treated with CT plus bevacizumab or cetuximab or panitumumab followed by R0 resection for potentially resectable colorectal cancer liver metastases were scanned. Among these, patients who developed resectable new metastases after a disease-free interval longer than 6 months were included in the study. We compared the RAS mutation status between the first biopsy and the second metastasectomy specimen.
A total of 82 mCRC patients treated with CT plus biological agents in a first-line setting were included in the study. The first biopsy assessment showed wild-type RAS tumours in 39 (47.6%) patients and mutant RAS tumours in 43 (52.4%) patients. The mean time for new operable liver metastasis after R0 resection was 15.5 months. In the second metastasectomy specimens, the numbers of wild-type and mutant RAS tumours were 30 (36.6%) and 52 (63.4%), respectively. The comparison with the first biopsy specimens showed RAS status conversions in 17 (20.7%) patients. Univariate comparison between patients with and without RAS status conversion revealed that grade, pathological T stage, wild-type RAS tumour and longer biological agent use time in the first-line treatment were significant factors for RAS conversion.
Our results suggest that re-biopsy is needed for an optimal second-line treatment decision in mCRC patients regardless of backbone biological agent, especially in patients with wild-type RAS mCRC.
本研究旨在探讨一线化疗（CT）联合生物制剂治疗转移性结直肠癌（mCRC）患者中，初始和复发性转移灶标本间 RAS 不一致的情况。
对接受 CT 联合贝伐珠单抗或西妥昔单抗或帕尼单抗治疗后行潜在可切除结直肠癌肝转移灶 R0 切除的患者进行扫描。在这些患者中，无疾病间隔时间超过 6 个月后出现可切除新转移灶的患者被纳入研究。我们比较了首次活检和第二次转移灶标本的 RAS 突变状态。
本研究共纳入 82 例一线接受 CT 联合生物制剂治疗的 mCRC 患者。首次活检评估显示，39 例（47.6%）患者为野生型 RAS 肿瘤，43 例（52.4%）患者为突变型 RAS 肿瘤。R0 切除后新可切除肝转移的平均时间为 15.5 个月。在第二次转移灶标本中，野生型和突变型 RAS 肿瘤的数量分别为 30 例（36.6%）和 52 例（63.4%）。与首次活检标本比较，17 例（20.7%）患者的 RAS 状态发生转换。单因素比较显示，RAS 状态转换与患者的肿瘤分级、病理 T 分期、野生型 RAS 肿瘤和一线治疗中生物制剂使用时间较长有关。
无论主要的生物制剂如何，我们的结果表明，mCRC 患者在进行二线治疗决策时需要重新活检，特别是在野生型 RAS mCRC 患者中。
