Predictive marker for response to trifluridine/tipiracil plus bevacizumab in metastatic colorectal cancer patients
Abstract Objective Trifluridine/tipiracil (FTD/TPI) is one of the options for late-line treatment of colorectal cancer (CRC). However, the specific patient populations that would particularly benefit from it remain unclear. This study attempted to identify predictive markers of chemotherapy efficacy...
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BMC
2025-01-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-024-13370-8 |
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| author | Toshiaki Takahashi Kunitoshi Shigeyasu Yoshitaka Kondo Sho Takeda Hibiki Umeda Kazuya Moriwake Masashi Kayano Yuya Sakurai Shunsuke Nakamura Masafumi Takahashi Kaori Nitta Kazuhiro Yoshida Yuki Matsumi Hiroyuki Michiue Hideki Yamamoto Hiroyuki Kishimoto Fuminori Teraishi Ryohei Shoji Nobuhiko Kanaya Hajime Kashima Yoshihiko Kakiuchi Shinji Kuroda Shunsuke Kagawa Toshiyoshi Fujiwara |
| author_facet | Toshiaki Takahashi Kunitoshi Shigeyasu Yoshitaka Kondo Sho Takeda Hibiki Umeda Kazuya Moriwake Masashi Kayano Yuya Sakurai Shunsuke Nakamura Masafumi Takahashi Kaori Nitta Kazuhiro Yoshida Yuki Matsumi Hiroyuki Michiue Hideki Yamamoto Hiroyuki Kishimoto Fuminori Teraishi Ryohei Shoji Nobuhiko Kanaya Hajime Kashima Yoshihiko Kakiuchi Shinji Kuroda Shunsuke Kagawa Toshiyoshi Fujiwara |
| author_sort | Toshiaki Takahashi |
| collection | DOAJ |
| description | Abstract Objective Trifluridine/tipiracil (FTD/TPI) is one of the options for late-line treatment of colorectal cancer (CRC). However, the specific patient populations that would particularly benefit from it remain unclear. This study attempted to identify predictive markers of chemotherapy efficacy with trifluridine/tipiracil (FTD/TPI), focusing on the RNA-editing enzyme adenosine deaminase acting on RNA 1 (ADAR1) expression and neutrophil–lymphocyte ratio (NLR). Methods To assess the effectiveness of FTD/TPI in CRC patients, we retrospectively analyzed 72 CRC patients at Okayama University Hospital from 2014 to 2022. Results Adding bevacizumab to FTD/TPI resulted in a more prolonged progression-free survival (PFS), consistent with the SUNLIGHT study findings (p = 0.0028). Among the participants, those with a high NLR had a shorter PFS (p = 0.0395). Moreover, high ADAR1 expression was associated with longer PFS (p = 0.0151). In multivariate analysis, low ADAR1 (HR = 3.43, p = 0.01) and absence of bevacizumab (HR = 4.25, p = 0.01) were identified as factors shortening PFS. The high ADAR1 group demonstrated fewer cases of progressive disease and a higher proportion of stable disease than the low ADAR1 group (p = 0.0288). Low NLR and high ADAR1 were predictive markers of prolonged PFS in the bevacizumab-treated group (p = 0.0036). Conclusion Low NLR and high ADAR1 were predictive markers for a positive response to the FTD/TPI plus bevacizumab regimen associated with prolonged PFS. The FTD/TPI plus bevacizumab regimen should be proactively implemented in the low NLR and high ADAR1 subgroups. |
| format | Article |
| id | doaj-art-97f5a73df1374d969304c9486e5ecbc6 |
| institution | Kabale University |
| issn | 1471-2407 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj-art-97f5a73df1374d969304c9486e5ecbc62025-01-05T12:33:04ZengBMCBMC Cancer1471-24072025-01-0125111010.1186/s12885-024-13370-8Predictive marker for response to trifluridine/tipiracil plus bevacizumab in metastatic colorectal cancer patientsToshiaki Takahashi0Kunitoshi Shigeyasu1Yoshitaka Kondo2Sho Takeda3Hibiki Umeda4Kazuya Moriwake5Masashi Kayano6Yuya Sakurai7Shunsuke Nakamura8Masafumi Takahashi9Kaori Nitta10Kazuhiro Yoshida11Yuki Matsumi12Hiroyuki Michiue13Hideki Yamamoto14Hiroyuki Kishimoto15Fuminori Teraishi16Ryohei Shoji17Nobuhiko Kanaya18Hajime Kashima19Yoshihiko Kakiuchi20Shinji Kuroda21Shunsuke Kagawa22Toshiyoshi Fujiwara23Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNeutron Therapy Research Center, Okayama UniversityDepartment of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesAbstract Objective Trifluridine/tipiracil (FTD/TPI) is one of the options for late-line treatment of colorectal cancer (CRC). However, the specific patient populations that would particularly benefit from it remain unclear. This study attempted to identify predictive markers of chemotherapy efficacy with trifluridine/tipiracil (FTD/TPI), focusing on the RNA-editing enzyme adenosine deaminase acting on RNA 1 (ADAR1) expression and neutrophil–lymphocyte ratio (NLR). Methods To assess the effectiveness of FTD/TPI in CRC patients, we retrospectively analyzed 72 CRC patients at Okayama University Hospital from 2014 to 2022. Results Adding bevacizumab to FTD/TPI resulted in a more prolonged progression-free survival (PFS), consistent with the SUNLIGHT study findings (p = 0.0028). Among the participants, those with a high NLR had a shorter PFS (p = 0.0395). Moreover, high ADAR1 expression was associated with longer PFS (p = 0.0151). In multivariate analysis, low ADAR1 (HR = 3.43, p = 0.01) and absence of bevacizumab (HR = 4.25, p = 0.01) were identified as factors shortening PFS. The high ADAR1 group demonstrated fewer cases of progressive disease and a higher proportion of stable disease than the low ADAR1 group (p = 0.0288). Low NLR and high ADAR1 were predictive markers of prolonged PFS in the bevacizumab-treated group (p = 0.0036). Conclusion Low NLR and high ADAR1 were predictive markers for a positive response to the FTD/TPI plus bevacizumab regimen associated with prolonged PFS. The FTD/TPI plus bevacizumab regimen should be proactively implemented in the low NLR and high ADAR1 subgroups.https://doi.org/10.1186/s12885-024-13370-8ADAR1Colorectal cancerBiomarkerTrifluridine/tipiracil |
| spellingShingle | Toshiaki Takahashi Kunitoshi Shigeyasu Yoshitaka Kondo Sho Takeda Hibiki Umeda Kazuya Moriwake Masashi Kayano Yuya Sakurai Shunsuke Nakamura Masafumi Takahashi Kaori Nitta Kazuhiro Yoshida Yuki Matsumi Hiroyuki Michiue Hideki Yamamoto Hiroyuki Kishimoto Fuminori Teraishi Ryohei Shoji Nobuhiko Kanaya Hajime Kashima Yoshihiko Kakiuchi Shinji Kuroda Shunsuke Kagawa Toshiyoshi Fujiwara Predictive marker for response to trifluridine/tipiracil plus bevacizumab in metastatic colorectal cancer patients BMC Cancer ADAR1 Colorectal cancer Biomarker Trifluridine/tipiracil |
| title | Predictive marker for response to trifluridine/tipiracil plus bevacizumab in metastatic colorectal cancer patients |
| title_full | Predictive marker for response to trifluridine/tipiracil plus bevacizumab in metastatic colorectal cancer patients |
| title_fullStr | Predictive marker for response to trifluridine/tipiracil plus bevacizumab in metastatic colorectal cancer patients |
| title_full_unstemmed | Predictive marker for response to trifluridine/tipiracil plus bevacizumab in metastatic colorectal cancer patients |
| title_short | Predictive marker for response to trifluridine/tipiracil plus bevacizumab in metastatic colorectal cancer patients |
| title_sort | predictive marker for response to trifluridine tipiracil plus bevacizumab in metastatic colorectal cancer patients |
| topic | ADAR1 Colorectal cancer Biomarker Trifluridine/tipiracil |
| url | https://doi.org/10.1186/s12885-024-13370-8 |
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