Effect of immune checkpoint inhibitor time-of-day infusion on survival in advanced biliary tract cancer: a propensity score-matched analysis
BackgroundCircadian rhythms in the immune system and anti-tumor responses are underexplored in cancer immunotherapy. Despite the success of immune checkpoint inhibitors (ICIs) in treating advanced biliary tract cancers (BTCs), not all patients benefit. This study examined whether the timing of ICI a...
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Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1512972/full |
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| author | Yichen Zheng Fanfan Shi Lingqi Sun Jiamin Guo Tonghui Ren Ji Ma |
| author_facet | Yichen Zheng Fanfan Shi Lingqi Sun Jiamin Guo Tonghui Ren Ji Ma |
| author_sort | Yichen Zheng |
| collection | DOAJ |
| description | BackgroundCircadian rhythms in the immune system and anti-tumor responses are underexplored in cancer immunotherapy. Despite the success of immune checkpoint inhibitors (ICIs) in treating advanced biliary tract cancers (BTCs), not all patients benefit. This study examined whether the timing of ICI administration affects outcomes in advanced BTC patients.MethodsWe included advanced BTC patients from West China Hospital of Sichuan University who received ≥2 ICI treatments from October 2019 to September 2023, with follow-up until May 2024. Primary outcome was overall survival (OS), with secondary outcomes including progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). Propensity score matching (1:2 ratio, caliper width 0.1) mitigated confounding factors. Cox proportional hazards regression analyzed the impact of ICI timing (post-16:30) on OS and PFS. Chi-square test assessed ORR and AE differences.ResultsAmong 221 patients, 51 received ≥20% of ICIs after 16:30; 170 received <20%. Post-matching, 49 late-infusion patients had significantly shorter OS (median 10.1 vs. 14.5 months, HR=1.80, P=0.012) compared to 90 early-infusion patients. Pre-matching, late-infusion patients also had shorter OS (median 9.8 vs. 13.7 months, HR=1.68, P=0.010) and PFS (median 4.9 vs. 8.1 months, HR=1.62, P=0.006). Multivariate analysis confirmed these results. No significant differences were found in ORR (χ^2 = 1.53, P=0.215) or AEs (all P>0.050). Sensitivity analyses supported these findings.ConclusionTiming of ICI administration affects efficacy in advanced BTC, with pre-16:30 infusions linked to better survival. Larger, prospective studies are needed to validate these results. |
| format | Article |
| id | doaj-art-0e1e0f08a70f4897a32f5fd90d0526fd |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-0e1e0f08a70f4897a32f5fd90d0526fd2025-08-20T02:48:54ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-12-011510.3389/fimmu.2024.15129721512972Effect of immune checkpoint inhibitor time-of-day infusion on survival in advanced biliary tract cancer: a propensity score-matched analysisYichen Zheng0Fanfan Shi1Lingqi Sun2Jiamin Guo3Tonghui Ren4Ji Ma5Department of Medical Oncology, Cancer Center and Laboratory of Molecular Targeted Therapy in Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Clinical Research and Management, Center of Biostatistics, Design, Measurement and Evaluation (CBDME), West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaSleep Medicine Center, Mental Health Center, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Medical Oncology, Cancer Center and Laboratory of Molecular Targeted Therapy in Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Medical Oncology, Cancer Center and Laboratory of Molecular Targeted Therapy in Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Medical Oncology, Cancer Center and Laboratory of Molecular Targeted Therapy in Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaBackgroundCircadian rhythms in the immune system and anti-tumor responses are underexplored in cancer immunotherapy. Despite the success of immune checkpoint inhibitors (ICIs) in treating advanced biliary tract cancers (BTCs), not all patients benefit. This study examined whether the timing of ICI administration affects outcomes in advanced BTC patients.MethodsWe included advanced BTC patients from West China Hospital of Sichuan University who received ≥2 ICI treatments from October 2019 to September 2023, with follow-up until May 2024. Primary outcome was overall survival (OS), with secondary outcomes including progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). Propensity score matching (1:2 ratio, caliper width 0.1) mitigated confounding factors. Cox proportional hazards regression analyzed the impact of ICI timing (post-16:30) on OS and PFS. Chi-square test assessed ORR and AE differences.ResultsAmong 221 patients, 51 received ≥20% of ICIs after 16:30; 170 received <20%. Post-matching, 49 late-infusion patients had significantly shorter OS (median 10.1 vs. 14.5 months, HR=1.80, P=0.012) compared to 90 early-infusion patients. Pre-matching, late-infusion patients also had shorter OS (median 9.8 vs. 13.7 months, HR=1.68, P=0.010) and PFS (median 4.9 vs. 8.1 months, HR=1.62, P=0.006). Multivariate analysis confirmed these results. No significant differences were found in ORR (χ^2 = 1.53, P=0.215) or AEs (all P>0.050). Sensitivity analyses supported these findings.ConclusionTiming of ICI administration affects efficacy in advanced BTC, with pre-16:30 infusions linked to better survival. Larger, prospective studies are needed to validate these results.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1512972/fullimmune checkpoint inhibitorbiliary tract cancerchronotherapycircadianpropensity score-matched analysis |
| spellingShingle | Yichen Zheng Fanfan Shi Lingqi Sun Jiamin Guo Tonghui Ren Ji Ma Effect of immune checkpoint inhibitor time-of-day infusion on survival in advanced biliary tract cancer: a propensity score-matched analysis Frontiers in Immunology immune checkpoint inhibitor biliary tract cancer chronotherapy circadian propensity score-matched analysis |
| title | Effect of immune checkpoint inhibitor time-of-day infusion on survival in advanced biliary tract cancer: a propensity score-matched analysis |
| title_full | Effect of immune checkpoint inhibitor time-of-day infusion on survival in advanced biliary tract cancer: a propensity score-matched analysis |
| title_fullStr | Effect of immune checkpoint inhibitor time-of-day infusion on survival in advanced biliary tract cancer: a propensity score-matched analysis |
| title_full_unstemmed | Effect of immune checkpoint inhibitor time-of-day infusion on survival in advanced biliary tract cancer: a propensity score-matched analysis |
| title_short | Effect of immune checkpoint inhibitor time-of-day infusion on survival in advanced biliary tract cancer: a propensity score-matched analysis |
| title_sort | effect of immune checkpoint inhibitor time of day infusion on survival in advanced biliary tract cancer a propensity score matched analysis |
| topic | immune checkpoint inhibitor biliary tract cancer chronotherapy circadian propensity score-matched analysis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1512972/full |
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