Pub Date : 2025-01-01Epub Date: 2024-11-14DOI: 10.1016/j.ejca.2024.115125
K Sarti, V Boige, G M Camilleri, M Ducreux, A Boilève
{"title":"Defying the odds: Outstanding survival in lung-only pancreatic cancer treated by Trifluridine-Tipiracil.","authors":"K Sarti, V Boige, G M Camilleri, M Ducreux, A Boilève","doi":"10.1016/j.ejca.2024.115125","DOIUrl":"10.1016/j.ejca.2024.115125","url":null,"abstract":"","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":" ","pages":"115125"},"PeriodicalIF":7.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2024-11-30DOI: 10.1016/j.ejca.2024.115154
De-Shen Wang, William Pat Fong, Lei Wen, Yan-Yu Cai, Chao Ren, Xiao-Jun Wu, Tian-Qi Zhang, Fei Cao, Meng-Xuan Zuo, Bin-Kui Li, Yun Zheng, Li-Ren Li, Gong Chen, Pei-Rong Ding, Zhen-Hai Lu, Rong-Xin Zhang, Yun-Fei Yuan, Zhi-Zhong Pan, Yu-Hong Li
Background: Hepatic artery infusion (HAI) chemotherapy, particularly with floxuridine (FUDR), has previously shown effectiveness in improving recurrence-free survival (RFS) in colorectal cancer (CRC) patients with colorectal liver metastases (CRLM). Nonetheless, its adjuvant use alongside modern systemic chemotherapy remains unevaluated.
Patients and methods: The HARVEST trial is an open-label, randomized, controlled study conducted from May 2018 to August 2021. CRC patients with resectable primary tumors and CRLM were recruited and randomized to receive standard systemic chemotherapy only (non-HAI group) or in combination with HAI-FUDR (HAI group). However, due to a FUDR manufacturing shortage, the study was terminated early after enrolling 92 patients. The primary endpoint was the 3-year RFS rate, with secondary endpoints including overall survival (OS), liver-specific RFS, and adverse events.
Results: Of the 92 randomized patients, 77 were included in the modified intention-to-treat analysis. Three-year RFS rates were comparable between the HAI (N = 38) and non-HAI (N = 39) groups (31.4 % vs. 34.4 %; P = 0.28). However, improved 1-year RFS and a longer expected five-year OS were observed in the HAI group. While exploratory subgroup analysis suggested potential RFS benefits for patients with multiple liver metastases, RAS/BRAF mutations, and positive postoperative ctDNA methylation, multivariable analysis did not identify these as independent factors. Safety analysis showed comparable chemotherapy-related adverse events, except for a higher occurrence of ALT elevation in the HAI group.
Conclusions: While our study showed no significant difference in three-year RFS, adjuvant chemotherapy intensification with HAI-FUDR is feasible and may offer early benefits in RFS and long-term OS. Nonetheless, a larger sample size is needed for validation and identifying which patient subgroup might benefit from this regimen.
{"title":"Safety and efficacy of adjuvant FOLFOX/FOLFIRI with versus without hepatic arterial infusion of floxuridine in patients following colorectal cancer liver metastasectomy (HARVEST trial): A randomized controlled trial.","authors":"De-Shen Wang, William Pat Fong, Lei Wen, Yan-Yu Cai, Chao Ren, Xiao-Jun Wu, Tian-Qi Zhang, Fei Cao, Meng-Xuan Zuo, Bin-Kui Li, Yun Zheng, Li-Ren Li, Gong Chen, Pei-Rong Ding, Zhen-Hai Lu, Rong-Xin Zhang, Yun-Fei Yuan, Zhi-Zhong Pan, Yu-Hong Li","doi":"10.1016/j.ejca.2024.115154","DOIUrl":"10.1016/j.ejca.2024.115154","url":null,"abstract":"<p><strong>Background: </strong>Hepatic artery infusion (HAI) chemotherapy, particularly with floxuridine (FUDR), has previously shown effectiveness in improving recurrence-free survival (RFS) in colorectal cancer (CRC) patients with colorectal liver metastases (CRLM). Nonetheless, its adjuvant use alongside modern systemic chemotherapy remains unevaluated.</p><p><strong>Patients and methods: </strong>The HARVEST trial is an open-label, randomized, controlled study conducted from May 2018 to August 2021. CRC patients with resectable primary tumors and CRLM were recruited and randomized to receive standard systemic chemotherapy only (non-HAI group) or in combination with HAI-FUDR (HAI group). However, due to a FUDR manufacturing shortage, the study was terminated early after enrolling 92 patients. The primary endpoint was the 3-year RFS rate, with secondary endpoints including overall survival (OS), liver-specific RFS, and adverse events.</p><p><strong>Results: </strong>Of the 92 randomized patients, 77 were included in the modified intention-to-treat analysis. Three-year RFS rates were comparable between the HAI (N = 38) and non-HAI (N = 39) groups (31.4 % vs. 34.4 %; P = 0.28). However, improved 1-year RFS and a longer expected five-year OS were observed in the HAI group. While exploratory subgroup analysis suggested potential RFS benefits for patients with multiple liver metastases, RAS/BRAF mutations, and positive postoperative ctDNA methylation, multivariable analysis did not identify these as independent factors. Safety analysis showed comparable chemotherapy-related adverse events, except for a higher occurrence of ALT elevation in the HAI group.</p><p><strong>Conclusions: </strong>While our study showed no significant difference in three-year RFS, adjuvant chemotherapy intensification with HAI-FUDR is feasible and may offer early benefits in RFS and long-term OS. Nonetheless, a larger sample size is needed for validation and identifying which patient subgroup might benefit from this regimen.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov: NCT03500874.</p>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"214 ","pages":"115154"},"PeriodicalIF":7.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-26DOI: 10.1016/j.ejca.2024.115192
Natalie Dennis, Kyle Dunton, Christopher Livings, Nataliya Bogoeva, Siobhan Bourke, Yemi Oluboyede, Erika Hamilton, Hiroji Iwata, Javier Cortés
Objective: DESTINY-Breast03, a randomised, phase 3 trial, evaluated trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients with human epidermal growth factor receptor (HER2)-positive unresectable and/or metastatic breast cancer who progressed on or after treatment with trastuzumab and a taxane. At the current data cut off overall survival analysis, T-DXd demonstrated a substantial improvement in overall survival over T-DM1. This secondary analysis use of DESTINY-Breast03 aimed to further evaluate the treatment differences using quality-adjusted survival time without symptoms or toxicity (Q-TWiST) methods.
Methods: Patients' survival data was divided into three health states: time spent with grade 3-4 adverse events (TOX), time without adverse events before disease progression (TWiST), and time from disease progression to death (PROG). Mean health state duration was weighted by patients' mean utility score in each health state based on the EQ-5D-5L questionnaire and summed to obtain the Q-TWiST value. A threshold utility analysis was also conducted using a range of hypothetical utility scores to assess the impact on Q-TWiST values obtained.
Results: T-DXd was associated with a substantial and clinically important improvement in Q-TWiST compared to T-DM1 (mean difference = 3.80 months, 95 % CI: [1.91, 5.62], nominal P-value <0.001; relative gain = 11.64 %). The robustness of the results was supported by threshold utility analysis.
Conclusion: T-DXd produced a substantial improvement in quality-adjusted time without symptoms or toxicity when accounting for time on treatment exposure compared to T-DM1. Consequently, T-DXd is shown to improve both length and quality of life.
{"title":"Quality-adjusted time without symptoms or toxicity analysis of trastuzumab deruxtecan versus trastuzumab emtansine in HER2- positive metastatic breast cancer patients based on secondary use of the DESTINY-Breast03 trial.","authors":"Natalie Dennis, Kyle Dunton, Christopher Livings, Nataliya Bogoeva, Siobhan Bourke, Yemi Oluboyede, Erika Hamilton, Hiroji Iwata, Javier Cortés","doi":"10.1016/j.ejca.2024.115192","DOIUrl":"https://doi.org/10.1016/j.ejca.2024.115192","url":null,"abstract":"<p><strong>Objective: </strong>DESTINY-Breast03, a randomised, phase 3 trial, evaluated trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients with human epidermal growth factor receptor (HER2)-positive unresectable and/or metastatic breast cancer who progressed on or after treatment with trastuzumab and a taxane. At the current data cut off overall survival analysis, T-DXd demonstrated a substantial improvement in overall survival over T-DM1. This secondary analysis use of DESTINY-Breast03 aimed to further evaluate the treatment differences using quality-adjusted survival time without symptoms or toxicity (Q-TWiST) methods.</p><p><strong>Methods: </strong>Patients' survival data was divided into three health states: time spent with grade 3-4 adverse events (TOX), time without adverse events before disease progression (TWiST), and time from disease progression to death (PROG). Mean health state duration was weighted by patients' mean utility score in each health state based on the EQ-5D-5L questionnaire and summed to obtain the Q-TWiST value. A threshold utility analysis was also conducted using a range of hypothetical utility scores to assess the impact on Q-TWiST values obtained.</p><p><strong>Results: </strong>T-DXd was associated with a substantial and clinically important improvement in Q-TWiST compared to T-DM1 (mean difference = 3.80 months, 95 % CI: [1.91, 5.62], nominal P-value <0.001; relative gain = 11.64 %). The robustness of the results was supported by threshold utility analysis.</p><p><strong>Conclusion: </strong>T-DXd produced a substantial improvement in quality-adjusted time without symptoms or toxicity when accounting for time on treatment exposure compared to T-DM1. Consequently, T-DXd is shown to improve both length and quality of life.</p>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"217 ","pages":"115192"},"PeriodicalIF":7.6,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cancer immunotherapy, including immune checkpoint inhibitors, chimeric antigen receptor T-cell therapy and bispecific antibodies, has led to major improvements in the treatment of a wide range of hematologic malignancies and solid tumors. However, age-mediated immune system modifications, known as immunosenescence, may preclude its efficacy in elderly patients. In this review, we assessed the efficacy of these different cancer immunotherapies in elderly patients compared to young patients to revisit the concept of immunosenescence from a therapeutic perspective.
{"title":"Cancer immunotherapy in elderly patients: The concept of immune senescence challenged by clinical experience","authors":"Mathilde Guégan , Malvina Bichon , Nathalie Chaput , Roch Houot , Jean Lemoine","doi":"10.1016/j.ejca.2024.115145","DOIUrl":"10.1016/j.ejca.2024.115145","url":null,"abstract":"<div><div>Cancer immunotherapy, including immune checkpoint inhibitors, chimeric antigen receptor T-cell therapy and bispecific antibodies, has led to major improvements in the treatment of a wide range of hematologic malignancies and solid tumors. However, age-mediated immune system modifications, known as immunosenescence, may preclude its efficacy in elderly patients. In this review, we assessed the efficacy of these different cancer immunotherapies in elderly patients compared to young patients to revisit the concept of immunosenescence from a therapeutic perspective.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"214 ","pages":"Article 115145"},"PeriodicalIF":7.6,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142744513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-22DOI: 10.1016/j.ejca.2024.115144
Pieternella Johanna Lugtenburg, Peter de Nully Brown, Bronno van der Holt, Eva de Jongh, Josée M. Zijlstra
{"title":"Rituximab maintenance for patients with diffuse large B-cell lymphoma in first complete remission: Long-term results of the HOVON-84 randomized phase III study by the HOVON and the Nordic Lymphoma Group (clinical trial number: NTR1014)","authors":"Pieternella Johanna Lugtenburg, Peter de Nully Brown, Bronno van der Holt, Eva de Jongh, Josée M. Zijlstra","doi":"10.1016/j.ejca.2024.115144","DOIUrl":"10.1016/j.ejca.2024.115144","url":null,"abstract":"","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"214 ","pages":"Article 115144"},"PeriodicalIF":7.6,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142744514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-22DOI: 10.1016/j.ejca.2024.115143
A. Benarfa, S. Ingen-Housz-Oro, E. Durot, M. Beylot-Barry, A. Pham-Ledard
{"title":"Cutaneous relapses location in diffuse large B-cell lymphoma leg type after first line immunochemotherapy","authors":"A. Benarfa, S. Ingen-Housz-Oro, E. Durot, M. Beylot-Barry, A. Pham-Ledard","doi":"10.1016/j.ejca.2024.115143","DOIUrl":"10.1016/j.ejca.2024.115143","url":null,"abstract":"","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"214 ","pages":"Article 115143"},"PeriodicalIF":7.6,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-20DOI: 10.1016/j.ejca.2024.115137
Julie F.M. Geerts , Marieke Pape , Pauline A.J. Vissers , Rob H.A. Verhoeven , Bianca Mostert , Bas P.L. Wijnhoven , Camiel Rosman , Irene E.G. van Hellemond , Grard A.P. Nieuwenhuijzen , Hanneke W.M. van Laarhoven
Background
The FLOT4 trial demonstrated superior survival of perioperative chemotherapy with 5-fluorouracil, oxaliplatin, and docetaxel (FLOT) compared to anthracycline triplets for resectable gastric cancer. These results were presented at the American Society of Clinical Oncology (ASCO) congress in June 2017 and published in April 2019. However, adoption of novel treatments in clinical practice often encounters delays. This study assesses the patterns of perioperative chemotherapy utilization and FLOT uptake in clinical practice within the Netherlands.
Materials and methods
A retrospective cohort study was conducted with resectable gastric cancer patients (cT1–4a,XcNallcM0) between 2015–2020 from the Netherlands Cancer Registry. Descriptive statistics, Cochran-Armitage tests, Fisher's exact or unpaired T-tests, and Jonckheere-Terpstra tests were used to analyze chemotherapy trends and FLOT uptake across hospitals.
Results
Among 3290 included patients, 42.9 % received neoadjuvant treatment. In 2015, 43.6 % of patients received perioperative chemotherapy versus 43.5 % in 2020 (p = 0.63). 40 out of 62 hospitals (64.5 %) adopted FLOT between the ASCO presentation and the full publication. FLOT increased from 42.9 % before publication to 86.8 % after publication (p < 0.0001), while anthracycline triplet use decreased to 0.9 % (p < 0.0001). Higher hospital volume was associated with fewer days to adoption (p = 0.04) but not with adoption of FLOT before publication (p = 0.14).
Conclusion
Timing of FLOT adoption varied among Dutch hospitals, leading to unequal patient access to effective treatments. Establishing (inter)national guidelines on provisional treatment adjustment pending publication is crucial to reduce variation in access. Moreover, rapid publication of final trial results is imperative to reduce variation in practice and ensure fair patient treatment.
{"title":"Patient access to perioperative chemotherapy with fluorouracil, leucovorin, oxaliplatin and docetaxel in patients with resectable gastric cancer in the Netherlands","authors":"Julie F.M. Geerts , Marieke Pape , Pauline A.J. Vissers , Rob H.A. Verhoeven , Bianca Mostert , Bas P.L. Wijnhoven , Camiel Rosman , Irene E.G. van Hellemond , Grard A.P. Nieuwenhuijzen , Hanneke W.M. van Laarhoven","doi":"10.1016/j.ejca.2024.115137","DOIUrl":"10.1016/j.ejca.2024.115137","url":null,"abstract":"<div><h3>Background</h3><div>The FLOT4 trial demonstrated superior survival of perioperative chemotherapy with 5-fluorouracil, oxaliplatin, and docetaxel (FLOT) compared to anthracycline triplets for resectable gastric cancer. These results were presented at the American Society of Clinical Oncology (ASCO) congress in June 2017 and published in April 2019. However, adoption of novel treatments in clinical practice often encounters delays. This study assesses the patterns of perioperative chemotherapy utilization and FLOT uptake in clinical practice within the Netherlands.</div></div><div><h3>Materials and methods</h3><div>A retrospective cohort study was conducted with resectable gastric cancer patients (cT<sub>1–4a,X</sub>cN<sub>all</sub>cM<sub>0</sub>) between 2015–2020 from the Netherlands Cancer Registry. Descriptive statistics, Cochran-Armitage tests, Fisher's exact or unpaired T-tests, and Jonckheere-Terpstra tests were used to analyze chemotherapy trends and FLOT uptake across hospitals.</div></div><div><h3>Results</h3><div>Among 3290 included patients, 42.9 % received neoadjuvant treatment. In 2015, 43.6 % of patients received perioperative chemotherapy versus 43.5 % in 2020 (p = 0.63). 40 out of 62 hospitals (64.5 %) adopted FLOT between the ASCO presentation and the full publication. FLOT increased from 42.9 % before publication to 86.8 % after publication (p < 0.0001), while anthracycline triplet use decreased to 0.9 % (p < 0.0001). Higher hospital volume was associated with fewer days to adoption (p = 0.04) but not with adoption of FLOT before publication (p = 0.14).</div></div><div><h3>Conclusion</h3><div>Timing of FLOT adoption varied among Dutch hospitals, leading to unequal patient access to effective treatments. Establishing (inter)national guidelines on provisional treatment adjustment pending publication is crucial to reduce variation in access. Moreover, rapid publication of final trial results is imperative to reduce variation in practice and ensure fair patient treatment.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"214 ","pages":"Article 115137"},"PeriodicalIF":7.6,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-20DOI: 10.1016/j.ejca.2024.115138
Alice Blandino , Dominique Scherer , Felix Boekstegers , Trine B. Rounge , Hilde Langseth , Stephanie Roessler , Kristian Hveem , Hermann Brenner , Sonali Pechlivanis , Melanie Waldenberger , Justo Lorenzo Bermejo
Gallbladder cancer (GBC) is an aggressive disease with limited treatment options but high prevention potential. GBC tumours take 10–20 years to develop, a timeframe that holds potential for early detection. MicroRNAs (miRNAs) play a central role in abnormal cell processes, and circulating miRNAs may constitute valuable biomarkers of early disease. We used microarray data to pre-select differentially expressed miRNAs in formalin-fixed paraffin-embedded (FFPE) gallbladder tissue samples (GBC n = 40, normal n = 8). We then applied small-RNA sequencing to screen for miRNA expression differences in serum samples from three European prospective cohorts (n = 37 GBC case-control pairs), and validated the most promising candidates in three independent cohorts (n = 36 GBC case- control pairs). Statistical analyses included robust linear regression, pathway and meta-analysis, and examination of expression correlation between miRNAs and target genes. MiR-4533 and miR-671–5p were overexpressed in GBC tissue and serum samples, and meta-analysis confirmed the overexpression of miR-4533 in GBC serum samples from the prospective cohorts (p-value = 4.1×10-4), especially in individuals of female sex, under 63.5 years, or with a BMI below 26.2 kg/m2. Pathway and correlation analyses revealed that miR-4533 targets SIPA1L2 in the Rap1 signalling pathway, and SIPA1L2 was downregulated in GBC serum samples. Our study highlights the advantage of integrating small-RNA sequencing results from different types of samples and independent datasets, and the need for international research collaborations to identify and validate biomarkers for secondary prevention of rare tumours such as GBC. The function of miR-4533 and its interaction with SIPA1L2 in GBC development need to be further investigated.
{"title":"Small-RNA sequencing reveals potential serum biomarkers for gallbladder cancer: Results from a three-stage collaborative study of large European prospective cohorts","authors":"Alice Blandino , Dominique Scherer , Felix Boekstegers , Trine B. Rounge , Hilde Langseth , Stephanie Roessler , Kristian Hveem , Hermann Brenner , Sonali Pechlivanis , Melanie Waldenberger , Justo Lorenzo Bermejo","doi":"10.1016/j.ejca.2024.115138","DOIUrl":"10.1016/j.ejca.2024.115138","url":null,"abstract":"<div><div>Gallbladder cancer (GBC) is an aggressive disease with limited treatment options but high prevention potential. GBC tumours take 10–20 years to develop, a timeframe that holds potential for early detection. MicroRNAs (miRNAs) play a central role in abnormal cell processes, and circulating miRNAs may constitute valuable biomarkers of early disease. We used microarray data to pre-select differentially expressed miRNAs in formalin-fixed paraffin-embedded (FFPE) gallbladder tissue samples (GBC n = 40, normal n = 8). We then applied small-RNA sequencing to screen for miRNA expression differences in serum samples from three European prospective cohorts (n = 37 GBC case-control pairs), and validated the most promising candidates in three independent cohorts (n = 36 GBC case- control pairs). Statistical analyses included robust linear regression, pathway and meta-analysis, and examination of expression correlation between miRNAs and target genes. MiR-4533 and miR-671–5p were overexpressed in GBC tissue and serum samples, and meta-analysis confirmed the overexpression of miR-4533 in GBC serum samples from the prospective cohorts (p-value = 4.1×10<sup>-4</sup>), especially in individuals of female sex, under 63.5 years, or with a BMI below 26.2 kg/m<sup>2</sup>. Pathway and correlation analyses revealed that miR-4533 targets <em>SIPA1L2</em> in the Rap1 signalling pathway, and <em>SIPA1L2</em> was downregulated in GBC serum samples. Our study highlights the advantage of integrating small-RNA sequencing results from different types of samples and independent datasets, and the need for international research collaborations to identify and validate biomarkers for secondary prevention of rare tumours such as GBC. The function of miR-4533 and its interaction with <em>SIPA1L2</em> in GBC development need to be further investigated.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"214 ","pages":"Article 115138"},"PeriodicalIF":7.6,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-19DOI: 10.1016/j.ejca.2024.115140
Cecilia Radkiewicz , Jonas F. Ludvigsson , Ernesto Sparrelid , Louise Emilsson
Aim
The purpose of this nationwide registry-based cohort study was to outline pancreatic cancer risk after benign gallbladder disease (GBD). Anatomically adjacent cancers were investigated to address incidental findings.
Methods
We included all Swedes aged 20–79 years with histologically confirmed GBD (cholecystitis and/or cholecystectomy) in 1992–2016 and five matched non-exposed population comparators. Follow-up started one month after GBD and incidence rates (IR) and hazard ratios (HR) with 95 % confidence intervals (CI) up to 15 years after GBD were estimated using Poisson and Cox regression, respectively. Fully adjusted models included sex, age, year, education, type 2 diabetes, obesity, smoking-, and alcohol-related disorders. Analyses were stratified by follow-up and flexible parametric models applied to assess time-varying effects. Interaction models were used to identify patient groups at risk.
Results
680 and 1890 incident pancreatic cancers were detected over 15 years in 130907 GBD exposed and 571618 non-exposed, respectively. An excess pancreatic cancer risk was mainly seen within the first 2 years; IR: 84 [95 % CI 73,95] versus 31 [95 % CI 27,34] per 100000 person-years corresponding to an HR of 2.74 [95 % CI 2.31,3.25]. The same pattern was noted for duodenal cancer while primary liver cancer risk was elevated across follow-up. An initial extrahepatic biliary cancer risk elevation shifted to a reduction over time. The 2-year pancreatic cancer risk was augmented in younger (age 20–49) individuals, HR 7.64 [95 % CI 3.73,15.65].
Conclusion
Our findings urge more studies on the clinical follow-up the first years after cholecystitis to detect early pancreatic cancer.
{"title":"Panacreatic cancer risk after benign gallbladder disease: A Swedish population-based cohort study","authors":"Cecilia Radkiewicz , Jonas F. Ludvigsson , Ernesto Sparrelid , Louise Emilsson","doi":"10.1016/j.ejca.2024.115140","DOIUrl":"10.1016/j.ejca.2024.115140","url":null,"abstract":"<div><h3>Aim</h3><div>The purpose of this nationwide registry-based cohort study was to outline pancreatic cancer risk after benign gallbladder disease (GBD). Anatomically adjacent cancers were investigated to address incidental findings.</div></div><div><h3>Methods</h3><div>We included all Swedes aged 20–79 years with histologically confirmed GBD (cholecystitis and/or cholecystectomy) in 1992–2016 and five matched non-exposed population comparators. Follow-up started one month after GBD and incidence rates (IR) and hazard ratios (HR) with 95 % confidence intervals (CI) up to 15 years after GBD were estimated using Poisson and Cox regression, respectively. Fully adjusted models included sex, age, year, education, type 2 diabetes, obesity, smoking-, and alcohol-related disorders. Analyses were stratified by follow-up and flexible parametric models applied to assess time-varying effects. Interaction models were used to identify patient groups at risk.</div></div><div><h3>Results</h3><div>680 and 1890 incident pancreatic cancers were detected over 15 years in 130907 GBD exposed and 571618 non-exposed, respectively. An excess pancreatic cancer risk was mainly seen within the first 2 years; IR: 84 [95 % CI 73,95] versus 31 [95 % CI 27,34] per 100000 person-years corresponding to an HR of 2.74 [95 % CI 2.31,3.25]. The same pattern was noted for duodenal cancer while primary liver cancer risk was elevated across follow-up. An initial extrahepatic biliary cancer risk elevation shifted to a reduction over time. The 2-year pancreatic cancer risk was augmented in younger (age 20–49) individuals, HR 7.64 [95 % CI 3.73,15.65].</div></div><div><h3>Conclusion</h3><div>Our findings urge more studies on the clinical follow-up the first years after cholecystitis to detect early pancreatic cancer.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"214 ","pages":"Article 115140"},"PeriodicalIF":7.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fluoropyrimidine remains the key agent of adjuvant chemotherapy for stage III colorectal cancer (CRC). Western studies have shown that female sex is a favorable prognostic factor after surgery, but it is also a risk factor for adverse events (AEs) during adjuvant chemotherapy with fluoropyrimidine. However, little is known about whether sex differences in treatment outcomes exist in this setting in the Asian population.
Methods
Patients with stage III CRC who received adjuvant fluoropyrimidine monotherapy in 4 randomized controlled trials were analyzed. Incidences of AEs and survival outcomes were compared between female and male patients.
Results
A total of 3170 patients (female, 1516; male, 1654) were included in this analysis. Compared with males, females were less likely to have a relative dose intensity (≥90 %: female 59.1 % vs. male 67.6 %), with a higher proportion of requiring dose reduction (28.8 % vs. 20.4 %) and a lower proportion of completing adjuvant chemotherapy (77.0 % vs. 81.7 %). Multivariable analyses demonstrated that female sex was associated with a higher incidence of grade 3–4 AEs (odds ratio 1.80 [95 % CI 1.51–2.14]). Female sex was identified as a favorable prognostic factor for overall survival (hazard ratio [HR]: 0.80 [0.65–0.97]) and relapse-free survival (HR: 0.73 [0.63–0.85]) in multivariable analyses. Female patients had fewer time-to recurrence (TTR) events than male patients (5-year TTR: 17.7 % vs. 22.3 %).
Conclusion
Sex had implications for the development of AEs and survival outcomes of Japanese patients with stage III CRC who received adjuvant fluoropyrimidine monotherapy.
背景：氟嘧啶仍是 III 期结直肠癌（CRC）辅助化疗的主要药物。西方研究表明，女性性别是手术后的有利预后因素，但也是氟嘧啶辅助化疗期间不良事件（AEs）的风险因素。然而，在亚洲人群中，治疗结果是否存在性别差异却鲜为人知：方法：分析了在 4 项随机对照试验中接受氟嘧啶单药辅助化疗的 III 期 CRC 患者。方法：分析在 4 项随机对照试验中接受氟嘧啶单药辅助治疗的 III 期 CRC 患者，比较女性和男性患者的 AEs 发生率和生存结果：共有 3170 例患者（女性 1516 例，男性 1654 例）被纳入本次分析。与男性相比，女性的相对剂量强度（≥90%：女性59.1%对男性67.6%）更低，需要减少剂量的比例更高（28.8%对20.4%），完成辅助化疗的比例更低（77.0%对81.7%）。多变量分析表明，女性与较高的3-4级AE发生率相关（几率比1.80 [95 % CI 1.51-2.14]）。在多变量分析中，女性性别被确定为总生存期（危险比 [HR]：0.80 [0.65-0.97]）和无复发生存期（HR：0.73 [0.63-0.85]）的有利预后因素。女性患者的复发时间（TTR）少于男性患者（5年TTR：17.7%对22.3%）：性别对接受氟嘧啶单药辅助治疗的日本 III 期 CRC 患者的 AEs 发生和生存结果有影响。
{"title":"Sex differences in toxicities and survival outcomes among Japanese patients with Stage III colorectal cancer receiving adjuvant fluoropyrimidine monotherapy: A pooled analysis of 4 randomized controlled trials (JCOG2310A)","authors":"Hidekazu Hirano , Kozo Kataoka , Toshifumi Yamaguchi , Anna Dorothea Wagner , Yasuhiro Shimada , Masafumi Inomata , Tetsuya Hamaguchi , Yasumasa Takii , Junki Mizusawa , Yusuke Sano , Akio Shiomi , Manabu Shiozawa , Masayuki Ohue , Tomohiro Adachi , Hideki Ueno , Satoshi Ikeda , Koji Komori , Shunsuke Tsukamoto , Atsuo Takashima , Yukihide Kanemitsu","doi":"10.1016/j.ejca.2024.115139","DOIUrl":"10.1016/j.ejca.2024.115139","url":null,"abstract":"<div><h3>Background</h3><div>Fluoropyrimidine remains the key agent of adjuvant chemotherapy for stage III colorectal cancer (CRC). Western studies have shown that female sex is a favorable prognostic factor after surgery, but it is also a risk factor for adverse events (AEs) during adjuvant chemotherapy with fluoropyrimidine. However, little is known about whether sex differences in treatment outcomes exist in this setting in the Asian population.</div></div><div><h3>Methods</h3><div>Patients with stage III CRC who received adjuvant fluoropyrimidine monotherapy in 4 randomized controlled trials were analyzed. Incidences of AEs and survival outcomes were compared between female and male patients.</div></div><div><h3>Results</h3><div>A total of 3170 patients (female, 1516; male, 1654) were included in this analysis. Compared with males, females were less likely to have a relative dose intensity (≥90 %: female 59.1 % vs. male 67.6 %), with a higher proportion of requiring dose reduction (28.8 % vs. 20.4 %) and a lower proportion of completing adjuvant chemotherapy (77.0 % vs. 81.7 %). Multivariable analyses demonstrated that female sex was associated with a higher incidence of grade 3–4 AEs (odds ratio 1.80 [95 % CI 1.51–2.14]). Female sex was identified as a favorable prognostic factor for overall survival (hazard ratio [HR]: 0.80 [0.65–0.97]) and relapse-free survival (HR: 0.73 [0.63–0.85]) in multivariable analyses. Female patients had fewer time-to recurrence (TTR) events than male patients (5-year TTR: 17.7 % vs. 22.3 %).</div></div><div><h3>Conclusion</h3><div>Sex had implications for the development of AEs and survival outcomes of Japanese patients with stage III CRC who received adjuvant fluoropyrimidine monotherapy.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"214 ","pages":"Article 115139"},"PeriodicalIF":7.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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