Intrahepatic Cholangiocarcinoma: Recurrence Patterns, Genomics, and Survival.

IF 4.7 2区医学 Q1 ONCOLOGY

JCO precision oncology Pub Date : 2025-10-01 Epub Date: 2025-10-23 DOI:10.1200/PO-25-00402

Pratik Chandra, Yi Song, Esther Drill, Alice C Wei, Nancy Kemeny, Andrea Cercek, Louise Connell, James Harding, Ghassan Abou-Alfa, Wungki Park, T Peter Kingham, Kevin Soares, Vinod Balachandran, Jeffrey Drebin, Michael D'Angelica, Eileen O'Reilly, Bas Groot Koerkamp, William R Jarnagin

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Abstract

Purpose: The impact of first recurrence site on outcome after resection of intrahepatic cholangiocarcinoma (IHC) is ill-defined, as are the genomic underpinnings of recurrence and outcomes.

Methods: Resected patients with IHC at two institutions with genomic data were included. Sites of first recurrence (SOFR) were classified as liver only (LO), extrahepatic (EH) only, or simultaneous liver and extrahepatic (SIM). Overall survival (OS) was calculated from the time of recurrence.

Results: Between 1993 and 2021, 318 patients met inclusion criteria; 232 (73%) recurred. SOFR were LO = 93 (40%), EH = 80 (34%), and SIM = 59 (26%). Median OS from recurrence was similar in the LO (33 [26, 42] months) and EH groups (33 [23, 46] months) but much lower in SIM (12 [9.8, 18] months; P < .001). Moderate/poor tumor differentiation, lymphovascular invasion, N1 disease, perineural invasion, and time to recurrence (all P < .05) were associated with SIM; only positive resection margin predicted LO (P = .007). No individual genomic or pathway alterations predicted SOFR; however, for all recurrers, TP53mut (n = 51, 22%; hazard ratio [HR], 2.0 [1.4 to 2.9]; P = .002), CDKN2Adel (n = 34, 15%; HR, 3.4 [95% CI, 2.2 to 5.3]; P < .001), CDKN2B (n = 25, 11%; HR, 3.2 [95% CI, 2.0 to 5.0]; P < .001), and KRASmut (n = 25, 11%; HR, 2.5 [95% CI, 1.6 to 4.0]; P = .002) were associated with worse OS. On multivariable analysis, SIM (HR, 2.5 [95% CI, 1.7 to 3.5]; P < .001), N1 status (HR, 1.8 [95% CI, 1.2 to 2.6]; P = .004), and alterations in the high-risk genotype (TP53mut, CDKN2Adel or KRASmut; n = 84, 36%; HR, 2.4 [95% CI, 1.7 to 3.3]; P < .001) were independent predictors of poor OS.

Conclusion: Recurrence after resection of IHC is common, and the liver was the most common site (66%). Clinicopathologic and genomic factors had limited ability to predict SOFR. Although LO and EH were associated with similar OS, SIM recurrences had dramatically worse OS. Adjuvant strategies targeting liver recurrence may improve outcomes after resection of IHC.

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肝内胆管癌：复发模式、基因组学和生存。

目的：肝内胆管癌（IHC）切除术后首次复发部位对预后的影响尚不明确，复发和预后的基因组基础也是如此。方法：纳入两家机构有基因组数据的IHC切除患者。首次复发部位（SOFR）分为仅肝（LO）、仅肝外（EH）或同时肝和肝外（SIM）。总生存期（OS）以复发时间计算。结果：1993年至2021年间，318例患者符合纳入标准；232例（73%）复发。SOFR为LO = 93 (40%), EH = 80 (34%), SIM = 59（26%）。LO组（33[26,42]个月）和EH组（33[23,46]个月）复发的中位OS相似，但SIM组（12[9.8,18]个月，P < 0.001）的中位OS较低。中度/低度肿瘤分化、淋巴血管浸润、N1病、神经周围浸润、复发时间与SIM相关（均P < 0.05）；只有阳性切缘预测LO （P = 0.007）。没有个体基因组或通路改变预测SOFR；然而，对于所有的复发者，TP53mut （n = 51, 22%；危险比[HR]， 2.0[1.4至2.9];P = 0.002）、CDKN2Adel （n = 34, 15%；危险比3.4 [95% CI， 2.2至5.3];P < 0.001）、CDKN2B （n = 25, 11%；危险比3.2 [95% CI， 2.0至5.0];P < 0.001）和KRASmut （n = 25, 11%；危险比2.5 [95% CI， 1.6至4.0];P = 0.002）与较差的OS相关。在多变量分析中，SIM （HR, 2.5 [95% CI, 1.7 ~ 3.5], P < 0.001）、N1状态（HR, 1.8 [95% CI, 1.2 ~ 2.6], P = 0.004）和高危基因型（TP53mut、CDKN2Adel或KRASmut， n = 84, 36%； HR, 2.4 [95% CI, 1.7 ~ 3.3], P < 0.001）的改变是不良OS的独立预测因子。结论：免疫组化术后复发率较高，以肝脏为最常见部位（66%）。临床病理和基因组因素预测SOFR的能力有限。虽然LO和EH与相似的OS相关，但SIM复发的OS明显更差。针对肝脏复发的辅助策略可能改善免疫组化切除术后的预后。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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