Advanced colorectal cancer subtypes (aCRCS) help select oxaliplatin-based or irinotecan-based therapy for colorectal cancer.
Advanced colorectal cancer subtypes (aCRCS) help select oxaliplatin-based or irinotecan-based therapy for colorectal cancer.
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DOI：
10.1111/cas.14841
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发表时间：
2021-04
期刊：
影响因子：
5.7
通讯作者：
Ishioka C
中科院分区：
文献类型：
--
作者：
Takahashi S;Sakamoto Y;Denda T;Takashima A;Komatsu Y;Nakamura M;Ohori H;Yamaguchi T;Kobayashi Y;Baba H;Kotake M;Amagai K;Kondo H;Shimada K;Sato A;Yuki S;Okita A;Ouchi K;Komine K;Watanabe M;Morita S;Ishioka C
奥沙利铂（OX）和伊立替康（IRI）是转移性结直肠癌（mCRC）一线治疗的关键药物。然而，尚未确定生物标志物来决定最初使用哪种药物。在 TRICOLORE 试验的这项转化研究 (TR) 中，对晚期结直肠癌亚型 (aCRCS) 进行了分析，将其作为选择 OX 或 IRI 的潜在生物标志物。我们从 TRICOLORE 试验中注册的 487 名患者收集了 335 份（68.8%）福尔马林固定石蜡包埋 (FFPE) 原发性肿瘤标本，并对 CRC 相关基因进行了直接测序和免疫组织化学染色、全面的基因表达分析和全基因组甲基化分析。在 BRAF 野生型 (WT)、PTEN 阳性和 aCRCS A1 患者中，IRI 组的无进展生存期 (PFS) 显着优于 OX 组。分子因素中，aCRCS仅与OX组和IRI组的PFS相关。在 aCRCS A1 + B1 中，IRI 组的 PFS 显着优于 OX 组（风险比 [HR] = 0.58；95% 置信区间 [CI] = 0.41‐0.82；P = .0023）。相比之下，在 aCRCS B2 中，OX 组的 PFS 优于 IRI 组，尽管这没有统计学意义（HR = 1.66；95% CI = 0.94‐2.96；P = .083）。近一半的 mCRC 患者（46.8%，aCRCS A1+B1）对 IRI 反应良好，而只有约 18.5%（aCRCS B2）的 mCRC 患者对 OX 反应良好。总之，aCRCS 可能是基于 OX 和基于 IRI 的治疗临床结果的预测因素。从TRICOLORE试验的转化研究来看，晚期结直肠癌亚型（aCRCS）可以帮助选择基于奥沙利铂或伊立替康的一线治疗转移性结直肠癌。
Oxaliplatin (OX) and irinotecan (IRI) are used as key drugs for the first‐line treatment of metastatic colorectal cancer (mCRC). However, no biomarkers have been identified to decide which of the drugs is initially used. In this translational research (TR) of the TRICOLORE trial, the advanced colorectal cancer subtype (aCRCS) was analyzed as a potential biomarker for the selection of OX or IRI. We collected 335 (68.8%) formalin‐fixed, paraffin‐embedded (FFPE) primary tumor specimens from 487 patients registered in the TRICOLORE trial and performed direct sequencing and immunohistochemical staining of CRC‐related genes, comprehensive gene‐expression analysis, and genome‐wide methylation analysis. The progression‐free survival (PFS) of the IRI group was significantly better compared with the OX group in BRAF wild‐type (WT), PTEN‐positive, and aCRCS A1 patients. Among the molecular factors, aCRCS were only associated with the PFS of OX and IRI groups. The PFS of the IRI group was significantly better compared with the OX group in aCRCS A1 + B1 (hazard ratio [HR] = 0.58; 95% confidence interval [CI] = 0.41‐0.82; P = .0023). In contrast, the OX group had better PFS compared with the IRI group in aCRCS B2, although this was not statistically significant (HR = 1.66; 95% CI = 0.94‐2.96; P = .083). Nearly half of patients with mCRC (46.8%, aCRCS A1 + B1) respond well to IRI, while only about 18.5% (aCRCS B2) of patients with mCRC responded well to OX. In conclusion, the aCRCS might be a predictive factor for the clinical outcomes of OX‐based and IRI‐based therapies. From translational research of TRICOLORE trail, the advanced colorectal cancer subtypes (aCRCS) can help to select oxaliplatin‐based or irinotecan‐based therapy for first‐line metastatic colorectal cancer treatment.
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影响因子：
3.3
作者：
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通讯作者：
Ishioka, Chikashi
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Okita A;Takahashi S;Ouchi K;Inoue M;Watanabe M;Endo M;Honda H;Yamada Y;Ishioka C
通讯作者：
Ishioka C
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通讯作者：
Heinemann, Volker
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