Yuta Maruki, Yasushi Yatabe, Chiharu Mizoguchi, Kathleen Yasmin de Almeida, Aumkhae Sookprasert, Charuwan Akewanlop, Ming-Huang Chen, Ekaphop Sirachainan, Dao Van Tu, Rozita Abdul Malik, Chaiyut Charoentum, Hwoei Fen Soo Hoo, Suhana Yusak, Tsung-Hao Liu, Rangasamy Ramachandran, Patrapim Sunpaweravong, Pei Jye Voon, Najihah Abu Bakar, Junki Mizusawa, Hitomi Sumiyoshi Okuma, Kenichi Nakamura, Chigusa Morizane, Takuji Okusaka
{"title":"FGFR2在年轻肝内和肝门周围胆管癌患者中的融合或重排：来自泛亚研究的关键遗传学见解","authors":"Yuta Maruki, Yasushi Yatabe, Chiharu Mizoguchi, Kathleen Yasmin de Almeida, Aumkhae Sookprasert, Charuwan Akewanlop, Ming-Huang Chen, Ekaphop Sirachainan, Dao Van Tu, Rozita Abdul Malik, Chaiyut Charoentum, Hwoei Fen Soo Hoo, Suhana Yusak, Tsung-Hao Liu, Rangasamy Ramachandran, Patrapim Sunpaweravong, Pei Jye Voon, Najihah Abu Bakar, Junki Mizusawa, Hitomi Sumiyoshi Okuma, Kenichi Nakamura, Chigusa Morizane, Takuji Okusaka","doi":"10.1111/hepr.70031","DOIUrl":null,"url":null,"abstract":"<p><strong>Aim: </strong>Biliary tract cancers, including intrahepatic cholangiocarcinoma (ICC), are aggressive with limited treatment options and poor prognosis. Recent trials (TOPAZ-1, Keynote-966) showed improved survival with ICIs plus gemcitabine and cisplatin. Targeted therapies, including FGFR inhibitors, are promising for cholangiocarcinoma patients with FGFR2 gene fusions or rearrangements, although few reports exist on FGFR2 positivity and clinical data in Asia. This study aims to address this gap by evaluating FGFR2 fusions or rearrangements in intrahepatic and perihilar cholangiocarcinoma patients across Asia, providing insights into their clinical significance and potential therapeutic implications.</p><p><strong>Methods: </strong>This multicenter study evaluated the frequency of FGFR2 rearrangements and fusion genes in ICC and perihilar cholangiocarcinoma across Asia (Thailand, Malaysia, Vietnam, and Taiwan) using fluorescence in situ hybridization (FISH) and comprehensive genomic profiling with the Todai OncoPanel2 (TOP2).</p><p><strong>Results: </strong>Of 113 patients, 102 were eligible; FGFR2 rearrangements/fusions were found in 3.9% (4 cases) by FISH, all of which were also confirmed by the TOP2 panel, consistent with the Japanese PRELUDE study. Younger age was significantly associated with FGFR2 positivity (34.5 ± 3.17 vs. 62.69 ± 1.04; p = 0.0003), whereas no correlation was observed with hepatitis infection, alcohol use, or smoking history. Genomic profiling identified frequent mutations in TP53, KRAS, and ARID1A with notable regional variability. Patients treated with ICIs showed significantly longer progression-free survival compared to other therapies: ICI + cytotoxic (348 days, 95% CI: 0-897), platinum-based + GEM (240 days, 95% CI: 197-282), and other treatments (168 days, 95% CI: 11-325; p = 0.017).</p><p><strong>Conclusion: </strong>The FGFR2 positivity rate in Asia is slightly lower but consistent with Japanese reports and is more common in younger patients with ICC. Distinct genetic alterations may characterize Asian populations.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"FGFR2 Fusions or Rearrangements in Young Intrahepatic and Perihilar Cholangiocarcinoma Patients: Key Genetic Insights From a Pan-Asian Study.\",\"authors\":\"Yuta Maruki, Yasushi Yatabe, Chiharu Mizoguchi, Kathleen Yasmin de Almeida, Aumkhae Sookprasert, Charuwan Akewanlop, Ming-Huang Chen, Ekaphop Sirachainan, Dao Van Tu, Rozita Abdul Malik, Chaiyut Charoentum, Hwoei Fen Soo Hoo, Suhana Yusak, Tsung-Hao Liu, Rangasamy Ramachandran, Patrapim Sunpaweravong, Pei Jye Voon, Najihah Abu Bakar, Junki Mizusawa, Hitomi Sumiyoshi Okuma, Kenichi Nakamura, Chigusa Morizane, Takuji Okusaka\",\"doi\":\"10.1111/hepr.70031\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aim: </strong>Biliary tract cancers, including intrahepatic cholangiocarcinoma (ICC), are aggressive with limited treatment options and poor prognosis. Recent trials (TOPAZ-1, Keynote-966) showed improved survival with ICIs plus gemcitabine and cisplatin. Targeted therapies, including FGFR inhibitors, are promising for cholangiocarcinoma patients with FGFR2 gene fusions or rearrangements, although few reports exist on FGFR2 positivity and clinical data in Asia. This study aims to address this gap by evaluating FGFR2 fusions or rearrangements in intrahepatic and perihilar cholangiocarcinoma patients across Asia, providing insights into their clinical significance and potential therapeutic implications.</p><p><strong>Methods: </strong>This multicenter study evaluated the frequency of FGFR2 rearrangements and fusion genes in ICC and perihilar cholangiocarcinoma across Asia (Thailand, Malaysia, Vietnam, and Taiwan) using fluorescence in situ hybridization (FISH) and comprehensive genomic profiling with the Todai OncoPanel2 (TOP2).</p><p><strong>Results: </strong>Of 113 patients, 102 were eligible; FGFR2 rearrangements/fusions were found in 3.9% (4 cases) by FISH, all of which were also confirmed by the TOP2 panel, consistent with the Japanese PRELUDE study. Younger age was significantly associated with FGFR2 positivity (34.5 ± 3.17 vs. 62.69 ± 1.04; p = 0.0003), whereas no correlation was observed with hepatitis infection, alcohol use, or smoking history. Genomic profiling identified frequent mutations in TP53, KRAS, and ARID1A with notable regional variability. Patients treated with ICIs showed significantly longer progression-free survival compared to other therapies: ICI + cytotoxic (348 days, 95% CI: 0-897), platinum-based + GEM (240 days, 95% CI: 197-282), and other treatments (168 days, 95% CI: 11-325; p = 0.017).</p><p><strong>Conclusion: </strong>The FGFR2 positivity rate in Asia is slightly lower but consistent with Japanese reports and is more common in younger patients with ICC. 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引用次数: 0
摘要
目的：胆道肿瘤，包括肝内胆管癌（ICC），具有侵袭性，治疗方案有限，预后差。最近的试验（TOPAZ-1, Keynote-966）显示ICIs联合吉西他滨和顺铂可改善生存率。包括FGFR抑制剂在内的靶向治疗对于FGFR2基因融合或重排的胆管癌患者是有希望的，尽管在亚洲很少有关于FGFR2阳性和临床数据的报道。本研究旨在通过评估亚洲肝内和肝门周围胆管癌患者的FGFR2融合或重排来解决这一差距，为其临床意义和潜在的治疗意义提供见解。方法：这项多中心研究利用荧光原位杂交（FISH）和Todai OncoPanel2 （TOP2）的全面基因组图谱分析，评估了亚洲（泰国、马来西亚、越南和台湾）ICC和肝门周围胆管癌中FGFR2重排和融合基因的频率。结果：113例患者中，102例符合条件；FISH发现FGFR2重排/融合占3.9%（4例），所有这些也被TOP2小组证实，与日本PRELUDE研究一致。年龄较小与FGFR2阳性显著相关（34.5±3.17 vs 62.69±1.04;p = 0.0003），而与肝炎感染、饮酒或吸烟史无相关性。基因组分析鉴定了TP53、KRAS和ARID1A的频繁突变，具有显著的区域差异。与其他治疗方法相比，接受ICIs治疗的患者显示出更长的无进展生存期：ICI +细胞毒（348天，95% CI: 0-897），铂基+ GEM（240天，95% CI: 197-282）和其他治疗（168天，95% CI: 11-325; p = 0.017）。结论：亚洲的FGFR2阳性率略低，但与日本的报道一致，并且在年轻的ICC患者中更为常见。不同的基因改变可能是亚洲人群的特征。
FGFR2 Fusions or Rearrangements in Young Intrahepatic and Perihilar Cholangiocarcinoma Patients: Key Genetic Insights From a Pan-Asian Study.
Aim: Biliary tract cancers, including intrahepatic cholangiocarcinoma (ICC), are aggressive with limited treatment options and poor prognosis. Recent trials (TOPAZ-1, Keynote-966) showed improved survival with ICIs plus gemcitabine and cisplatin. Targeted therapies, including FGFR inhibitors, are promising for cholangiocarcinoma patients with FGFR2 gene fusions or rearrangements, although few reports exist on FGFR2 positivity and clinical data in Asia. This study aims to address this gap by evaluating FGFR2 fusions or rearrangements in intrahepatic and perihilar cholangiocarcinoma patients across Asia, providing insights into their clinical significance and potential therapeutic implications.
Methods: This multicenter study evaluated the frequency of FGFR2 rearrangements and fusion genes in ICC and perihilar cholangiocarcinoma across Asia (Thailand, Malaysia, Vietnam, and Taiwan) using fluorescence in situ hybridization (FISH) and comprehensive genomic profiling with the Todai OncoPanel2 (TOP2).
Results: Of 113 patients, 102 were eligible; FGFR2 rearrangements/fusions were found in 3.9% (4 cases) by FISH, all of which were also confirmed by the TOP2 panel, consistent with the Japanese PRELUDE study. Younger age was significantly associated with FGFR2 positivity (34.5 ± 3.17 vs. 62.69 ± 1.04; p = 0.0003), whereas no correlation was observed with hepatitis infection, alcohol use, or smoking history. Genomic profiling identified frequent mutations in TP53, KRAS, and ARID1A with notable regional variability. Patients treated with ICIs showed significantly longer progression-free survival compared to other therapies: ICI + cytotoxic (348 days, 95% CI: 0-897), platinum-based + GEM (240 days, 95% CI: 197-282), and other treatments (168 days, 95% CI: 11-325; p = 0.017).
Conclusion: The FGFR2 positivity rate in Asia is slightly lower but consistent with Japanese reports and is more common in younger patients with ICC. Distinct genetic alterations may characterize Asian populations.
期刊介绍：
Hepatology Research (formerly International Hepatology Communications) is the official journal of the Japan Society of Hepatology, and publishes original articles, reviews and short comunications dealing with hepatology. Reviews or mini-reviews are especially welcomed from those areas within hepatology undergoing rapid changes. Short communications should contain concise definitive information.
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