First-line chemotherapy with selective internal radiation therapy for intrahepatic cholangiocarcinoma: The French ACABi GERCOR PRONOBIL cohort

IF 9.5 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

JHEP Reports Pub Date : 2025-02-01 DOI:10.1016/j.jhepr.2024.101279

Nicolas Adamus , Julien Edeline , Julie Henriques , Nadim Fares , Thierry Lecomte , Anthony Turpin , Dewi Vernerey , Mathilde Vincens , Brice Chanez , David Tougeron , Christophe Tournigand , Eric Assenat , Matthieu Delaye , Sylvain Manfredi , Olivier Bouché , Nicolas Williet , Angelique Vienot , Lorraine Blaise , Léo Mas , Cindy Neuzillet , Gaël S. Roth

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引用次数: 0

Abstract

Background & Aims

Selective internal radiation therapy (SIRT) is a promising option for liver-only unresectable intrahepatic cholangiocarcinoma (iCCA). The Real-SIRTCCA study retrospectively assessed the benefit of adding SIRT to chemotherapy in this setting within the French nationwide observational cohort ACABi-GERCOR-PRONOBIL.

Methods

Inclusion criteria were advanced iCCA with limited or no extrahepatic disease, treated with first-line gemcitabine plus platinum chemotherapy +/- concurrent SIRT. All patients treated with chemotherapy and concurrent SIRT were included. To ensure groups’ similarity, a rigorous selection was applied to the chemo-only group, with exclusion of patients with liver involvement >50% and extrahepatic metastases. The primary outcome was progression-free survival (PFS). Secondary outcomes were overall survival (OS), objective response rate (ORR) and tumor resection rate. Propensity score and inverse probability of treatment weighting (IPTW) propensity approaches were used to address confounding factors between groups.

Results

Between July 2007 and December 2023, 277 patients met the Real-SIRTCCA inclusion criteria, with 88 in the chemo-SIRT group and 189 in chemo-only group. Chemo-SIRT was associated with longer PFS (median = 10.8 vs. 5.5 months, hazard ratio [HR] 0.54, 95% CI 0.41-0.71, p <0.0001), a trend for longer OS (median = 22.5 vs. 15.1 months, HR 0.76, 95% CI 0.57-1.01), higher ORR (58.3% vs. 28.5%, odds ratio [OR] 3.51, 95% CI 2.03-6.09, p <0.0001), and resection rate (18.7% vs. 8.8%, p = 0.0279) compared to chemo-alone. After IPTW, the superiority of chemo-SIRT was confirmed with better PFS (HR 0.55, 95% CI 0.45-0.66, p <0,0001), OS (HR 0.70, 95% CI 0.58-0.85, p = 0.0004), ORR (OR 3.17, 95% CI 2.18-4.49, p <0.0001) and resection rate (OR 2.94, 95% CI 1.71-5.03, p <0.0001).

Conclusions

Adding SIRT to first-line chemotherapy significantly improved survival outcomes, ORR, and secondary tumor resection rates in locally advanced iCCA. Prospective randomized data are needed to confirm these results.

Impact and implications:

Herein, we report the results of the Real-SIRTCCA study, comparing the efficacy of the gemcitabine-platinum systemic first-line chemotherapy with or without selective internal radiation therapy (SIRT) in 277 patients with locally advanced intrahepatic cholangiocarcinoma within the cohort ACABi-PRONOBIL. An improvement of progression-free survival, overall survival, tumor response and secondary surgical resection rate was observed in favor of chemo-SIRT, before adjustment and after inverse probability of treatment weighting propensity score analyses. Even though prospective randomized data would be needed to confirm these findings, we believe that this study constitutes new evidence of the potential benefit of combining SIRT with chemotherapy. The safety and efficacy of this strategy whether as a bridge to intent-to-cure strategies or in a palliative setting, should encourage its adoption in a larger panel of clinical centers, or at very least, prompt clinicians to refer their patients to centers where SIRT is performed.

Clinical trial number

NCT04935853.

Abstract Image

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肝内胆管癌的一线化疗与选择性内放疗：法国ACABi GERCOR PRONOBIL队列

背景与目的：选择性内放射治疗（SIRT）是治疗仅肝不可切除的肝内胆管癌（iCCA）的一种很有前途的选择。Real-SIRTCCA研究在法国全国范围的观察性队列ACABi-GERCOR-PRONOBIL中回顾性评估了在化疗中加入SIRT的益处。方法：纳入标准为晚期iCCA伴有有限或无肝外疾病，接受一线吉西他滨加铂化疗+/-同期SIRT治疗。所有接受化疗和同期SIRT治疗的患者均被纳入研究。为了确保各组的相似性，对仅化疗组进行了严格的选择，排除了肝脏受损伤50%和肝外转移的患者。主要终点为无进展生存期（PFS）。次要结果为总生存期（OS）、客观有效率（ORR）和肿瘤切除率。倾向得分和治疗加权逆概率（IPTW）倾向方法用于处理组间的混杂因素。结果：2007年7月至2023年12月，277例患者符合Real-SIRTCCA纳入标准，其中化疗- sirrt组88例，单纯化疗组189例。与单独化疗相比，化疗- sirt与更长的PFS（中位数= 10.8 vs. 5.5个月，风险比[HR] 0.54, 95% CI 0.41-0.71, p 0.0001）、更长的OS（中位数= 22.5 vs. 15.1个月，HR 0.76, 95% CI 0.57-1.01）、更高的ORR （58.3% vs. 28.5%，优势比[OR] 3.51, 95% CI 2.03-6.09, p 0.0001）和切除率（18.7% vs. 8.8%, p = 0.0279）相关。IPTW后，化疗- sirt的优势被证实为更好的PFS (HR 0.55, 95% CI 0.45-0.66, p 0.0001), OS (HR 0.70, 95% CI 0.58-0.85, p = 0.0004), ORR （OR 3.17, 95% CI 2.18-4.49, p 0.0001）和切除率（OR 2.94, 95% CI 1.71-5.03, p 0.0001）。结论：在一线化疗中加入SIRT可显著改善局部晚期iCCA的生存结局、ORR和继发肿瘤切除率。需要前瞻性随机数据来证实这些结果。影响和意义：在此，我们报告了Real-SIRTCCA研究的结果，比较了在ACABi-PRONOBIL队列中277例局部晚期肝内胆管癌患者中，吉西他滨-铂全身一线化疗联合或不联合选择性内放疗（SIRT）的疗效。在调整前和治疗加权倾向评分逆概率分析后，观察到化疗- sirt在无进展生存期、总生存期、肿瘤反应和二次手术切除率方面的改善。尽管需要前瞻性随机数据来证实这些发现，但我们相信这项研究构成了SIRT联合化疗潜在益处的新证据。该策略的安全性和有效性，无论是作为意向治疗策略的桥梁，还是在姑息治疗环境中，都应该鼓励更多的临床中心采用该策略，或者至少促使临床医生将患者转介到进行SIRT的中心。临床试验号：NCT04935853。

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来源期刊

JHEP Reports GASTROENTEROLOGY & HEPATOLOGY-

CiteScore

12.40

自引率

2.40%

发文量

161

审稿时长

36 days

期刊介绍： JHEP Reports is an open access journal that is affiliated with the European Association for the Study of the Liver (EASL). It serves as a companion journal to the highly respected Journal of Hepatology. The primary objective of JHEP Reports is to publish original papers and reviews that contribute to the advancement of knowledge in the field of liver diseases. The journal covers a wide range of topics, including basic, translational, and clinical research. It also focuses on global issues in hepatology, with particular emphasis on areas such as clinical trials, novel diagnostics, precision medicine and therapeutics, cancer research, cellular and molecular studies, artificial intelligence, microbiome research, epidemiology, and cutting-edge technologies. In summary, JHEP Reports is dedicated to promoting scientific discoveries and innovations in liver diseases through the publication of high-quality research papers and reviews covering various aspects of hepatology.