Transplantation for Peri-Hilar and Intrahepatic Cholangiocarcinoma With mTOR Immunosuppression

IF 0.8 4区医学 Q4 IMMUNOLOGY

Transplantation proceedings Pub Date : 2025-02-12 DOI:10.1016/j.transproceed.2025.02.001

Samar Semaan , Ashton A. Connor , Ashish Saharia , Sudha Kodali , Ahmed Elaileh , Khush Patel , Nadine Soliman , Tamneet Basra , David W. Victor III , Caroline J. Simon , Yee Lee Cheah , Mark J. Hobeika , Constance M. Mobley , Sadhna Dhingra , Mary R. Schwartz , Anaum Maqsood , Kirk Heyne , Maen Abdelrahim , Xian C. Li , Milind Javle , R. Mark Ghobrial

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引用次数: 0

Abstract

Background

Cholangiocarcinoma (CCA) has rising incidence and mortality rates. Outcomes from combination systemic, loco-regional therapy (LRT) and liver transplantation (LT) are improving, but more granular data are needed to inform evidence-based management, including patient selection and immunosuppression.

Methods

Patients with peri-hilar (PH) and intrahepatic (IH) CCA who underwent LT at a single center between January 2008 and February 2023 were reviewed retrospectively. Primary outcomes were overall survival (OS) and recurrence-free survival (RFS) with significance determined by Cox proportional hazards model.

Results

During the study period, 53 patients underwent LT for either PH (n = 27), or IH (26). Cohort had mean age 58.5 years old (IQR, 47.0-63.0), body mass index (BMI) 25.9 (IQR, 22.9-30.0) kg/m², and mean biologic MELD 9 (IQR, 7-17). Most frequent etiology was PSC (n = 12, 22.6%). Forty-nine patients (92.5%) received neoadjuvant therapy, including systemic (n = 48, 90.6%) and locoregional therapy (LRT) (n = 22, 41.5%), to which PH tumors were both most and least responsive (P = .03). On explant pathology, tumor were a median size of 3.5 cm and lympho-vascular invasion (LVI) was present in 13 (24.5%) cases. Median follow-up post-transplant was 910 days (IQR, 407-1509). Probabilities of OS and RFS at 3-years post-LT were 69.2% (95% CI, 56.9%-84.2%) and 57.4% (95% CI, 43.7%-75.4%). In multivariable analysis, OS was associated with tumor type and LVI, and RFS with age, BMI, PSC and LRT. After a median post-LT period of 38 days (IQR, 27-79.5), 39 (71.7%) patients started mTOR inhibition with lowered tacrolimus goal. Cox proportional hazard model showed significant association of OS with mTOR inhibition, though this was not validated by a time-dependent co-variate approach.

Conclusions

In this single center cohort of CCA, post-LT outcomes were significantly greater for patients with IH tumors and no LVI. Immunosuppression with mTOR inhibition was not consistently associated with outcomes.

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肝门周围和肝内胆管癌移植伴mTOR免疫抑制。

背景：胆管癌（CCA）的发病率和死亡率都在上升。全身、局部、区域联合治疗（LRT）和肝移植（LT）的结果正在改善，但需要更细致的数据来为循证管理提供信息，包括患者选择和免疫抑制。方法：回顾性分析2008年1月至2023年2月在单一中心行肝门周围（PH）和肝内（IH） CCA的患者。主要结局为总生存期（OS）和无复发生存期（RFS），通过Cox比例风险模型确定其显著性。结果：在研究期间，53例患者因PH （n = 27）或IH（26）接受了肝移植。队列平均年龄58.5岁（IQR, 47.0 ~ 63.0），体重指数（BMI） 25.9 (IQR, 22.9 ~ 30.0) kg/m2，平均生物MELD 9 （IQR, 7 ~ 17）。最常见的病因是PSC （n = 12, 22.6%）。49例患者（92.5%）接受了新辅助治疗，包括全身治疗（n = 48, 90.6%）和局部治疗（n = 22, 41.5%），其中PH肿瘤对新辅助治疗的反应最多，对新辅助治疗的反应最少（P = 0.03）。外植体病理显示，肿瘤中位大小为3.5 cm， 13例（24.5%）存在淋巴血管浸润（LVI）。移植后中位随访时间为910天（IQR, 407-1509）。术后3年的OS和RFS概率分别为69.2% （95% CI, 56.9%-84.2%）和57.4% （95% CI, 43.7%-75.4%）。在多变量分析中，OS与肿瘤类型和LVI相关，RFS与年龄、BMI、PSC和LRT相关。中位lt后38天（IQR, 27-79.5）， 39例（71.7%）患者开始mTOR抑制，他克莫司目标降低。Cox比例风险模型显示OS与mTOR抑制显著相关，尽管这没有通过时间相关的协变量方法得到验证。结论：在CCA的单中心队列中，IH肿瘤和无LVI患者的lt后预后显著更高。免疫抑制与mTOR抑制并不总是与结果相关。

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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来源期刊

Transplantation proceedings 医学-免疫学

CiteScore

1.70

自引率

0.00%

发文量

502

审稿时长

60 days

期刊介绍： Transplantation Proceedings publishes several different categories of manuscripts, all of which undergo extensive peer review by recognized authorities in the field prior to their acceptance for publication. The first type of manuscripts consists of sets of papers providing an in-depth expression of the current state of the art in various rapidly developing components of world transplantation biology and medicine. These manuscripts emanate from congresses of the affiliated transplantation societies, from Symposia sponsored by the Societies, as well as special Conferences and Workshops covering related topics. Transplantation Proceedings also publishes several special sections including publication of Clinical Transplantation Proceedings, being rapid original contributions of preclinical and clinical experiences. These manuscripts undergo review by members of the Editorial Board. Original basic or clinical science articles, clinical trials and case studies can be submitted to the journal?s open access companion title Transplantation Reports.