Rebecca Landy, Gregory W Haber, Barry I Graubard, Carole Fakhry, Nicole G Campos, Emily A Burger, Li C Cheung, Hormuzd A Katki, Maura L Gillison, Anil K Chaturvedi
Background We estimated the impact of screening on morbidity and mortality of HPV16-positive oropharyngeal cancer among US men aged 45-79 years. Methods We developed an individual-level, state-transition natural history microsimulation model to estimate the impact of screening using oral HPV16 detection, HPV16-E6 antibody detection, and transcervical-ultrasound of neck/oropharynx. We compared clinical detection to counterfactual screen detection for cancer stage, single- vs multiple-modality treatment, and survival. Screening scenarios encompassed four progression speeds across cancer stages (very-slow, slow, fast, and very-fast) and four screening frequencies. Results Among US men aged 45-79 years in 2021 (N = 54,881,311), 163,958 clinically diagnosed HPV-positive oropharyngeal cancers and 32,009 deaths would occur through age 84 in the absence of screening. Assuming very-fast progression, 4%, 20%, 31%, and 60% of these cancers would be detected by one-off, 5-yearly, 3-yearly, and annual screening. Annual screening (very-fast progression) could reduce the number of cancers diagnosed at advanced stages (AJCC 7, Stages III/IV: 90.0% with no screening vs 59.1%) and treated by multiple-modalities (80.6% with no screening vs 50.6%). Cancer mortality would also be reduced by 36.2%, with a gain of 106,000 life-years. Annual screening would have a number needed to screen (NNS) of 561 per screen-detected cancer, 1,118 per additional cancer treated by single-modality, 4,740 per death prevented, and 520 per life-year gained; such high NNS reflect potential inefficiency of population-level screening. Conclusions If proven efficacious in randomized trials and cost-effective, screening for HPV-positive oropharyngeal cancers could provide considerable population-level reductions in advanced stage cancers, treatment-related morbidities, and mortality.
{"title":"Impact of screening for HPV-positive oropharyngeal cancers: a microsimulation-based modeling study","authors":"Rebecca Landy, Gregory W Haber, Barry I Graubard, Carole Fakhry, Nicole G Campos, Emily A Burger, Li C Cheung, Hormuzd A Katki, Maura L Gillison, Anil K Chaturvedi","doi":"10.1093/jnci/djaf033","DOIUrl":"https://doi.org/10.1093/jnci/djaf033","url":null,"abstract":"Background We estimated the impact of screening on morbidity and mortality of HPV16-positive oropharyngeal cancer among US men aged 45-79 years. Methods We developed an individual-level, state-transition natural history microsimulation model to estimate the impact of screening using oral HPV16 detection, HPV16-E6 antibody detection, and transcervical-ultrasound of neck/oropharynx. We compared clinical detection to counterfactual screen detection for cancer stage, single- vs multiple-modality treatment, and survival. Screening scenarios encompassed four progression speeds across cancer stages (very-slow, slow, fast, and very-fast) and four screening frequencies. Results Among US men aged 45-79 years in 2021 (N = 54,881,311), 163,958 clinically diagnosed HPV-positive oropharyngeal cancers and 32,009 deaths would occur through age 84 in the absence of screening. Assuming very-fast progression, 4%, 20%, 31%, and 60% of these cancers would be detected by one-off, 5-yearly, 3-yearly, and annual screening. Annual screening (very-fast progression) could reduce the number of cancers diagnosed at advanced stages (AJCC 7, Stages III/IV: 90.0% with no screening vs 59.1%) and treated by multiple-modalities (80.6% with no screening vs 50.6%). Cancer mortality would also be reduced by 36.2%, with a gain of 106,000 life-years. Annual screening would have a number needed to screen (NNS) of 561 per screen-detected cancer, 1,118 per additional cancer treated by single-modality, 4,740 per death prevented, and 520 per life-year gained; such high NNS reflect potential inefficiency of population-level screening. Conclusions If proven efficacious in randomized trials and cost-effective, screening for HPV-positive oropharyngeal cancers could provide considerable population-level reductions in advanced stage cancers, treatment-related morbidities, and mortality.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143258399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Luca Arecco, Eva Blondeaux, Marco Bruzzone, Grazia Arpino, Carmine De Angelis, Michelino De Laurentiis, Roberta Caputo, Alessandra Fabi, Valeria Sanna, Stefania Gori, Fabio Puglisi, Luca Boni, Simone Nardin, Irene Giannubilo, Marta Perachino, Roberto Borea, Elisa Agostinetto, Evandro de Azambuja, Matteo Lambertini, Lucia Del Mastro
Background The monarchE and NATALEE trials employed different high-risk inclusion criteria. Main objective is to assess prognostic differences based on their inclusion criteria. Methods Patients with hormone receptor-positive/HER2-negative early breast cancer enrolled in the phase III MIG1, GIM2, and GIM3 trials were categorized as high-risk cohort (HRC) and low-risk cohort (LRC) according to the inclusion criteria of monarchE and NATALEE trials. Subsequently, they were further classified in three different cohorts concordant LRC (low-risk for both trials), discordant risk cohort (high-risk for only one trial), and concordant HRC (high-risk for both trials). Main outcomes were disease-free survival (DFS) and overall survival (OS). Results Among 4,795 patients included, 1,343 (28.0%) and 2,689 (56.1%) were classified as HRC according to the monarchE and NATALEE, respectively.
{"title":"Prognostic implications of risk definitions from the monarchE and NATALEE trials","authors":"Luca Arecco, Eva Blondeaux, Marco Bruzzone, Grazia Arpino, Carmine De Angelis, Michelino De Laurentiis, Roberta Caputo, Alessandra Fabi, Valeria Sanna, Stefania Gori, Fabio Puglisi, Luca Boni, Simone Nardin, Irene Giannubilo, Marta Perachino, Roberto Borea, Elisa Agostinetto, Evandro de Azambuja, Matteo Lambertini, Lucia Del Mastro","doi":"10.1093/jnci/djaf031","DOIUrl":"https://doi.org/10.1093/jnci/djaf031","url":null,"abstract":"Background The monarchE and NATALEE trials employed different high-risk inclusion criteria. Main objective is to assess prognostic differences based on their inclusion criteria. Methods Patients with hormone receptor-positive/HER2-negative early breast cancer enrolled in the phase III MIG1, GIM2, and GIM3 trials were categorized as high-risk cohort (HRC) and low-risk cohort (LRC) according to the inclusion criteria of monarchE and NATALEE trials. Subsequently, they were further classified in three different cohorts concordant LRC (low-risk for both trials), discordant risk cohort (high-risk for only one trial), and concordant HRC (high-risk for both trials). Main outcomes were disease-free survival (DFS) and overall survival (OS). Results Among 4,795 patients included, 1,343 (28.0%) and 2,689 (56.1%) were classified as HRC according to the monarchE and NATALEE, respectively.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We would like to thank Dr Oleribe for their interest in the study, “Predicting Persistent Opioid Use, Abuse, and Toxicity Among Cancer Survivors”. In the critical appraisal, the author concludes that there is an increased rate of persistent opioid use among Black veterans because the proportion of veterans with persistent opioid use who were Black was higher than the proportion of African American veterans on a census bureau report of veterans. While we appreciate the author’s investigation into potential racial disparities in adverse opioid outcomes, we do not agree with their methodology and do not believe the data supports their conclusion.
{"title":"Response to Oleribe","authors":"Paul Riviere, James D Murphy, Lucas K Vitzthum","doi":"10.1093/jnci/djaf020","DOIUrl":"https://doi.org/10.1093/jnci/djaf020","url":null,"abstract":"We would like to thank Dr Oleribe for their interest in the study, “Predicting Persistent Opioid Use, Abuse, and Toxicity Among Cancer Survivors”. In the critical appraisal, the author concludes that there is an increased rate of persistent opioid use among Black veterans because the proportion of veterans with persistent opioid use who were Black was higher than the proportion of African American veterans on a census bureau report of veterans. While we appreciate the author’s investigation into potential racial disparities in adverse opioid outcomes, we do not agree with their methodology and do not believe the data supports their conclusion.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"121 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143072485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maureen E Canavan, Sarah Westvold, Valerie Csik, Jeffrey Franks, Gabrielle Rocque, Cary P Gross, Kerin B Adelson
It has long been assumed that academic oncology practices are disadvantaged in value-based payment programs, due to patient complexity and research costs. This assumption not been tested. The Oncology Care Model (OCM) was a Medicare alternative payment model, which sought to curb costs while improving care. We assessed the impact of clinical trial (CT) participation on two outcomes: 1. cost and 2. practice performance among three participating NCI designated cancer centers using a random effects meta-analysis. The mean total Medicare cost per episode was $42,225 for CT episodes and $34,937 for non-CT episodes. Despite higher total costs, CT episodes were more likely to be under spending targets than non-CT episodes (odds ratio 0.37 (CI 0.25, 0.48). Drug costs in CT episodes were lower than in non-CT episodes, although this was only statistically significant at the largest volume practice. In conclusion, CTs may offer an advantage in value-based programs.
{"title":"The association between clinical trial participation, drug costs, and performance in the Oncology Care Model (OCM)","authors":"Maureen E Canavan, Sarah Westvold, Valerie Csik, Jeffrey Franks, Gabrielle Rocque, Cary P Gross, Kerin B Adelson","doi":"10.1093/jnci/djaf008","DOIUrl":"https://doi.org/10.1093/jnci/djaf008","url":null,"abstract":"It has long been assumed that academic oncology practices are disadvantaged in value-based payment programs, due to patient complexity and research costs. This assumption not been tested. The Oncology Care Model (OCM) was a Medicare alternative payment model, which sought to curb costs while improving care. We assessed the impact of clinical trial (CT) participation on two outcomes: 1. cost and 2. practice performance among three participating NCI designated cancer centers using a random effects meta-analysis. The mean total Medicare cost per episode was $42,225 for CT episodes and $34,937 for non-CT episodes. Despite higher total costs, CT episodes were more likely to be under spending targets than non-CT episodes (odds ratio 0.37 (CI 0.25, 0.48). Drug costs in CT episodes were lower than in non-CT episodes, although this was only statistically significant at the largest volume practice. In conclusion, CTs may offer an advantage in value-based programs.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ioannis Zerdes, Panagiotis Filis, Georgios Fountoukidis, Ali Inan El-Naggar, Foteini Kalofonou, Antonio D’Alessio, Athanasios Pouptsis, Theodoros Foukakis, George Pentheroudakis, Johan Ahlgren, Daniel Smith, Antonios Valachis
Background Although precision oncology has rapidly been developed in recent years, its real-world impact and challenges in healthcare implementation remain underexplored. Through a meta-analysis of real-world evidence (RWE), we aimed at investigating the applicability and clinical impact of comprehensive cancer genome profiling (CGP) in cancer patients with metastatic solid tumors. Methods We systematically searched Medline, Embase, and Web of Science for RWE studies on CGP and matched therapies in metastatic solid tumors (publication period: 2012—2023). Pooled proportions of actionable genomic alterations, patients treated with matched targeted therapies, treatment, and survival outcomes were calculated. Data from Swedish cancer registries were used as a case-study for nationwide CGP implementation. Results Out of the 7218 identified studies, 144 were included in our analysis. 59.8% of CGP-tested patients had actionable genomic alterations, with 15.6% (95% Confidence Interval (CI) 13.4-18.2%) of them having received targeted therapy. Objective response was seen in 23.9% (95% CI 20.8-27.3%). Overall, CGP-guided treatment was correlated with prolonged progression-free survival (pooled Hazard Ratio (HR) = 0.63; 95% CI, 0.56-0.70; 18 studies) and overall survival (pooled HR = 0.60; 95% CI, 0.51-0.70; 21 studies) when compared to conventional treatment. Meta-regression time projections analyses showed that these rates will steadily increase by 2030. Conclusions Pooled analyses of RWE studies indicate that approximately one-fourth of the patients receiving CGP-matched treatment have an objective response. By utilizing meta-regression projections, our nationwide cancer registry case-study offers insights into the potential of precision oncology for patients with metastatic cancer and to inform future healthcare strategies.
尽管近年来精确肿瘤学发展迅速，但其在医疗保健实施中的现实影响和挑战仍未得到充分探讨。通过真实世界证据（RWE）的荟萃分析，我们旨在探讨综合癌症基因组谱（CGP）在转移性实体瘤癌症患者中的适用性和临床影响。方法我们系统地检索Medline、Embase和Web of Science关于转移性实体瘤中CGP和匹配疗法的RWE研究（发表期：2012-2023）。计算可操作的基因组改变、接受匹配靶向治疗的患者、治疗和生存结果的合并比例。来自瑞典癌症登记处的数据被用作全国CGP实施的案例研究。结果在7218项确定的研究中，144项纳入我们的分析。59.8%的cgp检测患者有可操作的基因组改变，其中15.6%（95%置信区间（CI） 13.4-18.2%）的患者接受了靶向治疗。客观缓解率为23.9% （95% CI 20.8-27.3%）。总体而言，cgp引导治疗与延长无进展生存期相关(合并风险比(HR) = 0.63；95% ci, 0.56-0.70；18项研究)和总生存率(合并HR = 0.60；95% ci, 0.51-0.70；21项研究)，与常规治疗相比。元回归时间预测分析表明，到2030年，这些比率将稳步上升。RWE研究的汇总分析表明，大约四分之一接受cgp匹配治疗的患者有客观反应。通过利用meta回归预测，我们的全国癌症登记案例研究为转移性癌症患者提供了精确肿瘤学潜力的见解，并为未来的医疗保健策略提供了信息。
{"title":"Comprehensive Genome Profiling for Treatment Decisions in Patients with Metastatic Tumors: Real-World Evidence Meta-Analysis and Registry Data Implementation","authors":"Ioannis Zerdes, Panagiotis Filis, Georgios Fountoukidis, Ali Inan El-Naggar, Foteini Kalofonou, Antonio D’Alessio, Athanasios Pouptsis, Theodoros Foukakis, George Pentheroudakis, Johan Ahlgren, Daniel Smith, Antonios Valachis","doi":"10.1093/jnci/djaf015","DOIUrl":"https://doi.org/10.1093/jnci/djaf015","url":null,"abstract":"Background Although precision oncology has rapidly been developed in recent years, its real-world impact and challenges in healthcare implementation remain underexplored. Through a meta-analysis of real-world evidence (RWE), we aimed at investigating the applicability and clinical impact of comprehensive cancer genome profiling (CGP) in cancer patients with metastatic solid tumors. Methods We systematically searched Medline, Embase, and Web of Science for RWE studies on CGP and matched therapies in metastatic solid tumors (publication period: 2012—2023). Pooled proportions of actionable genomic alterations, patients treated with matched targeted therapies, treatment, and survival outcomes were calculated. Data from Swedish cancer registries were used as a case-study for nationwide CGP implementation. Results Out of the 7218 identified studies, 144 were included in our analysis. 59.8% of CGP-tested patients had actionable genomic alterations, with 15.6% (95% Confidence Interval (CI) 13.4-18.2%) of them having received targeted therapy. Objective response was seen in 23.9% (95% CI 20.8-27.3%). Overall, CGP-guided treatment was correlated with prolonged progression-free survival (pooled Hazard Ratio (HR) = 0.63; 95% CI, 0.56-0.70; 18 studies) and overall survival (pooled HR = 0.60; 95% CI, 0.51-0.70; 21 studies) when compared to conventional treatment. Meta-regression time projections analyses showed that these rates will steadily increase by 2030. Conclusions Pooled analyses of RWE studies indicate that approximately one-fourth of the patients receiving CGP-matched treatment have an objective response. By utilizing meta-regression projections, our nationwide cancer registry case-study offers insights into the potential of precision oncology for patients with metastatic cancer and to inform future healthcare strategies.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nobuhiko Kanaya, Waleed Seddiq, Kok-Siong Chen, Yoshinori Kajiwara, Lucia Moreno Lama, Paulo Borges, Shinji Kuroda, Hiroaki Wakimoto, Khalid Shah
Background Immune-checkpoint inhibitors have shown clinical benefit in non-small cell lung cancer (NSCLC) derived brain metastasis (BM), however, their efficacy in lung to leptomeningeal brain metastasis (LLBM) remains poor. Methods A paired matched RNA expression dataset of patients with NSCLCs and BMs was analyzed to idenfiy BM specific suppressive tumor microenvironment (TME) features. Next, we created immune-competent LLBM mouse models that mimic clinical LLBM. We evaluated the efficacy of intrathecal (IT) delivery of allogeneic stem cells (SCs) engineered to release single-chain variable fragment anti-PD-1 (scFvPD-1). To enhance tumor cell killing and subsequent modulation of the immune TME, we explored the therapeutic activity of dual SCs releasing oncolytic herpes simplex virus (oHSV) and scFvPD-1 and profiled immune and metabolic consequences. Results RNA sequencing analysis of primary NSCLCs and BMs revealed an immune-suppressive TME with reduced immune cells and increased PD-1+ T cells in BMs. We showed significantly decreased immune cells and increased PD-1+ T cells in the TME of LLBM compared to primary NSCLC tumors in LLBM mouse tumor models. Next, we showed that locoregional IT treatment with SC releasing scFvPD-1, but not conventional systemic injection of anti-PD-1 antibody, suppressed tumor growth and improved survival in our immune-competent LLBM models. Furthermore, dual SCs releasing oHSV and scFvPD-1 (SC-oHSV/scFvPD-1) enhanced therapeutic outcomes by inducing oHSV-mediated immunogenic cell death, activating anti-tumor T cell signaling, and disrupting oxidative phosphorylation, which sensitized tumors to cisplatin. Conclusion Locoregional delivery of SC-oHSV/scFvPD-1 effectively targets the immune-suppressive TME in LLBM, providing a promising strategy for treating LLBM.
{"title":"Engineered allogeneic stem cells orchestrate T lymphocyte driven immunotherapy in immunosuppressive leptomeningeal brain metastasis","authors":"Nobuhiko Kanaya, Waleed Seddiq, Kok-Siong Chen, Yoshinori Kajiwara, Lucia Moreno Lama, Paulo Borges, Shinji Kuroda, Hiroaki Wakimoto, Khalid Shah","doi":"10.1093/jnci/djaf006","DOIUrl":"https://doi.org/10.1093/jnci/djaf006","url":null,"abstract":"Background Immune-checkpoint inhibitors have shown clinical benefit in non-small cell lung cancer (NSCLC) derived brain metastasis (BM), however, their efficacy in lung to leptomeningeal brain metastasis (LLBM) remains poor. Methods A paired matched RNA expression dataset of patients with NSCLCs and BMs was analyzed to idenfiy BM specific suppressive tumor microenvironment (TME) features. Next, we created immune-competent LLBM mouse models that mimic clinical LLBM. We evaluated the efficacy of intrathecal (IT) delivery of allogeneic stem cells (SCs) engineered to release single-chain variable fragment anti-PD-1 (scFvPD-1). To enhance tumor cell killing and subsequent modulation of the immune TME, we explored the therapeutic activity of dual SCs releasing oncolytic herpes simplex virus (oHSV) and scFvPD-1 and profiled immune and metabolic consequences. Results RNA sequencing analysis of primary NSCLCs and BMs revealed an immune-suppressive TME with reduced immune cells and increased PD-1+ T cells in BMs. We showed significantly decreased immune cells and increased PD-1+ T cells in the TME of LLBM compared to primary NSCLC tumors in LLBM mouse tumor models. Next, we showed that locoregional IT treatment with SC releasing scFvPD-1, but not conventional systemic injection of anti-PD-1 antibody, suppressed tumor growth and improved survival in our immune-competent LLBM models. Furthermore, dual SCs releasing oHSV and scFvPD-1 (SC-oHSV/scFvPD-1) enhanced therapeutic outcomes by inducing oHSV-mediated immunogenic cell death, activating anti-tumor T cell signaling, and disrupting oxidative phosphorylation, which sensitized tumors to cisplatin. Conclusion Locoregional delivery of SC-oHSV/scFvPD-1 effectively targets the immune-suppressive TME in LLBM, providing a promising strategy for treating LLBM.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"105 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BACKGROUNDRecent decades have witnessed tangible improvements in childhood cancer survival. However, the prognosis for children with congenital heart disease (CHD), the most prevalent birth defect, remains unclear. Due to improved survival of CHD and childhood cancer, evaluating outcomes within this intersection is important for clinical practice. We aimed to assess mortality post-cancer diagnosis among children with CHD.METHODSWe conducted a study on the population of Denmark and Sweden, born 1970-2014, with a cancer diagnosis before age 20 in the national cancer registers (end of follow-up 2015; n = 20,665). CHD diagnoses (n = 397) and recorded deaths were retrieved from national health registers. We evaluated the effect of CHD on five-year mortality post-cancer diagnosis fitting Cox proportional hazards regression.RESULTSWhen excluding children with Down syndrome, children with CHD had a higher five-year mortality post-cancer diagnosis compared to children without (HR 1.48, 95% CI 1.18-1.86). This was particularly notable in children with lymphoma (HR 2.17, 95% CI 1.11-4.25) and neuroblastoma (HR 2.39, 95% CI 1.11-5.15). In more recent decades (post-1990), children with CHD had similar five-year mortality as their counterparts without, except for children diagnosed with lymphoma, where mortality remained elevated (HR 3.37, 95% CI 1.65-6.89).CONCLUSIONSIn this large, register-based cohort study, children with CHD fared worse post-cancer diagnosis-particularly lymphoma and neuroblastoma. While a more positive trend emerged in recent years, lymphoma-related mortality remained disproportionately high among children with CHD, underscoring the need for continued research and interventions to improve outcomes for this vulnerable group.
背景近几十年来，儿童癌症存活率有了明显提高。然而，先天性心脏病（CHD）是最常见的出生缺陷，患有先天性心脏病的儿童的预后仍不明确。由于先天性心脏病和儿童癌症的存活率有所提高，评估这两种疾病的预后对临床实践非常重要。我们的研究对象是丹麦和瑞典1970-2014年出生的人群，他们在全国癌症登记中被诊断出20岁以前患有癌症（2015年随访结束；n = 20,665）。心脏病诊断（n = 397）和记录的死亡病例均来自国家健康登记册。结果当排除患有唐氏综合征的儿童时，与未患有唐氏综合征的儿童相比，患有先天性心脏病的儿童在癌症确诊后的五年死亡率更高（HR 1.48，95% CI 1.18-1.86）。这在淋巴瘤（HR 2.17，95% CI 1.11-4.25）和神经母细胞瘤（HR 2.39，95% CI 1.11-5.15）患儿中尤为明显。结论在这项基于登记的大型队列研究中，患有先天性心脏病的儿童在癌症确诊后的情况较差，尤其是淋巴瘤和神经母细胞瘤。虽然近年来出现了更积极的趋势，但患有先天性心脏病的儿童中与淋巴瘤相关的死亡率仍然过高，这说明有必要继续开展研究并采取干预措施，以改善这一弱势群体的预后。
{"title":"Mortality after cancer diagnosis among children with congenital heart disease in Denmark and Sweden.","authors":"Christina-Evmorfia Kampitsi,Line Kenborg,Hanna Mogensen,Olof Broberg,Ingrid Glimelius,Friederike Erdmann,Jeanette Falck Winther,Maria Feychting,Giorgio Tettamanti","doi":"10.1093/jnci/djaf010","DOIUrl":"https://doi.org/10.1093/jnci/djaf010","url":null,"abstract":"BACKGROUNDRecent decades have witnessed tangible improvements in childhood cancer survival. However, the prognosis for children with congenital heart disease (CHD), the most prevalent birth defect, remains unclear. Due to improved survival of CHD and childhood cancer, evaluating outcomes within this intersection is important for clinical practice. We aimed to assess mortality post-cancer diagnosis among children with CHD.METHODSWe conducted a study on the population of Denmark and Sweden, born 1970-2014, with a cancer diagnosis before age 20 in the national cancer registers (end of follow-up 2015; n = 20,665). CHD diagnoses (n = 397) and recorded deaths were retrieved from national health registers. We evaluated the effect of CHD on five-year mortality post-cancer diagnosis fitting Cox proportional hazards regression.RESULTSWhen excluding children with Down syndrome, children with CHD had a higher five-year mortality post-cancer diagnosis compared to children without (HR 1.48, 95% CI 1.18-1.86). This was particularly notable in children with lymphoma (HR 2.17, 95% CI 1.11-4.25) and neuroblastoma (HR 2.39, 95% CI 1.11-5.15). In more recent decades (post-1990), children with CHD had similar five-year mortality as their counterparts without, except for children diagnosed with lymphoma, where mortality remained elevated (HR 3.37, 95% CI 1.65-6.89).CONCLUSIONSIn this large, register-based cohort study, children with CHD fared worse post-cancer diagnosis-particularly lymphoma and neuroblastoma. While a more positive trend emerged in recent years, lymphoma-related mortality remained disproportionately high among children with CHD, underscoring the need for continued research and interventions to improve outcomes for this vulnerable group.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pietro Scilipoti, Hans Garmo, Rolf Gedeborg, David Robinson, Pär Stattin, Marcus Westerberg
Background There has been a wide range in incidence of prostate-specific antigen (PSA) persistence and relapse after radical prostatectomy (RP) for prostate cancer (PCa). We aimed to describe incidence and prognostic implications of PSA persistence and relapse. Methods Register-based cohort study in Sweden of men diagnosed with PCa between 2007 and 2020 who underwent RP. Risks were estimated using competing risk cumulative incidence curves. Treatment after persistence or relapse and risk of PCa death and other causes were stratified according to persistence, European Association of Urology relapse risk groups, time to relapse, and life expectancy based on age and comorbidities. Results Among 10,700 men, the 10-year risk of PSA persistence or relapse after RP was 34% (95% CI, 32-35%). Within 12 months of persistence/relapse, 75% of men with persistence, high-risk relapse or early relapse (<2 years) received treatment. The 10-year risk of PCa death ranged from 12% for men with persistence to 2% in men with low-risk relapse, while death from other causes ranged from 11% to 16%. Risk of PCa death was 8.5% after early relapse (<2 years) and 1.4% after late relapse (>5 years). Conclusions This population-based study estimated that one third of men would have PSA persistence or relapse within 10 years from RP. There was a wide range in risk of death from PCa according to cancer characteristics and time to relapse. Risk of death from other causes was substantial. These factors, along with life expectancy, should inform treatment decisions for men with persistence or relapse.
{"title":"Incidence and prognostic implications of PSA persistence and relapse after radical prostatectomy. Population-based study","authors":"Pietro Scilipoti, Hans Garmo, Rolf Gedeborg, David Robinson, Pär Stattin, Marcus Westerberg","doi":"10.1093/jnci/djaf012","DOIUrl":"https://doi.org/10.1093/jnci/djaf012","url":null,"abstract":"Background There has been a wide range in incidence of prostate-specific antigen (PSA) persistence and relapse after radical prostatectomy (RP) for prostate cancer (PCa). We aimed to describe incidence and prognostic implications of PSA persistence and relapse. Methods Register-based cohort study in Sweden of men diagnosed with PCa between 2007 and 2020 who underwent RP. Risks were estimated using competing risk cumulative incidence curves. Treatment after persistence or relapse and risk of PCa death and other causes were stratified according to persistence, European Association of Urology relapse risk groups, time to relapse, and life expectancy based on age and comorbidities. Results Among 10,700 men, the 10-year risk of PSA persistence or relapse after RP was 34% (95% CI, 32-35%). Within 12 months of persistence/relapse, 75% of men with persistence, high-risk relapse or early relapse (&lt;2 years) received treatment. The 10-year risk of PCa death ranged from 12% for men with persistence to 2% in men with low-risk relapse, while death from other causes ranged from 11% to 16%. Risk of PCa death was 8.5% after early relapse (&lt;2 years) and 1.4% after late relapse (&gt;5 years). Conclusions This population-based study estimated that one third of men would have PSA persistence or relapse within 10 years from RP. There was a wide range in risk of death from PCa according to cancer characteristics and time to relapse. Risk of death from other causes was substantial. These factors, along with life expectancy, should inform treatment decisions for men with persistence or relapse.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"55 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Karen M Tuesley, Katrina Spilsbury, Sallie-Anne Pearson, Peter Donovan, Andreas Obermair, Michael D Coory, Sitwat Ali, Nirmala Pandeya, Louise Stewart, Susan J Jordan, Penelope M Webb
Background Use of long-acting, reversible contraceptives has increased over the past 20 years, but an understanding of how they could influence cancer risk is limited. Methods We conducted a nested case-control study among a national cohort of Australian women (n = 176 601 diagnosed with cancer between 2004 and 2013; 882 999 matched control individuals) to investigate the associations between the levonorgestrel intrauterine system, etonogestrel implants, depot-medroxyprogesterone acetate and cancer risk and compared these results with the oral contraceptive pill. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI). Results Levonorgestrel intrauterine system and etonogestrel implant use was associated with breast cancer risk (OR = 1.26, 95% CI = 1.21 to 1.31, and OR = 1.24, 95% CI = 1.17 to 1.32, respectively), but depot-medroxyprogesterone acetate was not, except when used for 5 or more years (OR = 1.23, 95% CI = 0.95 to 1.59). Reduced risks were seen for levonorgestrel intrauterine system (≥1 years of use) in endometrial cancer (OR = 0.80, 95% CI = 0.65 to 0.99), ovarian cancer (OR = 0.71, 95% CI = 0.57 to 0.88), and cervical cancer (OR = 0.62, 95% CI = 0.51 to 0.75); for etonogestrel implant in endometrial cancer (OR = 0.21, 95% CI = 0.13 to 0.34) and ovarian cancer (OR = 0.76, 95% CI = 0.57 to 1.02); and for depot-medroxyprogesterone acetate in endometrial cancer (OR = 0.21, 95% CI = 0.13 to 0.34). Although levonorgestrel intrauterine system, etonogestrel implant and depot-medroxyprogesterone acetate were all associated with increased cancer risk overall, for etonogestrel implant, the risk returned to baseline after cessation, similar to the oral contraceptive pill. We were unable to adjust for all potential confounders, but sensitivity analyses suggested that adjusting for parity, smoking, and obesity would not have materially changed our findings. Conclusion Long-acting, reversible contraceptives have similar cancer associations to the oral contraceptive pill (reduced endometrial and ovarian cancer risks and short-term increased breast cancer risk). This information may be helpful to women and their physicians when discussing contraception options.
背景 过去20年来，长效、可逆避孕药的使用有所增加，但人们对它们如何影响癌症风险的了解却很有限。方法 我们对澳大利亚全国妇女队列（n = 176 601，2004-2013年间确诊为癌症；882 999名匹配对照个体）进行了一项巢式病例对照研究，以调查左炔诺孕酮宫内避孕系统、依托诺孕酮植入剂、醋酸去甲羟孕酮与癌症风险之间的关系，并将这些结果与口服避孕药进行比较。我们使用条件逻辑回归法估算了几率比（OR）和 95% 的置信区间（CI）。结果 使用左炔诺孕酮宫内避孕系统和伊托诺孕酮植入剂与乳腺癌风险有关（OR = 1.26，95% CI = 1.21 至 1.31；OR = 1.24，95% CI = 1.17 至 1.32），但醋酸去甲羟孕酮与乳腺癌风险无关，使用 5 年或 5 年以上者除外（OR = 1.23，95% CI = 0.95 至 1.59）。左炔诺孕酮宫内避孕系统（使用≥1 年）在子宫内膜癌（OR = 0.80，95% CI = 0.65 至 0.99）、卵巢癌（OR = 0.71，95% CI = 0.57 至 0.88）和宫颈癌（OR = 0.62，95% CI = 0.51 至 0.75）方面的风险降低；依托孕酮宫内避孕系统（使用≥1 年）在子宫内膜癌（OR = 0.80，95% CI = 0.65 至 0.99）、卵巢癌（OR = 0.71，95% CI = 0.57 至 0.88）和宫颈癌（OR = 0.62，95% CI = 0.51 至 0.75）方面的风险降低。75）；子宫内膜癌（OR = 0.21，95% CI = 0.13 至 0.34）和卵巢癌（OR = 0.76，95% CI = 0.57 至 1.02）中的依托孕烯植入物；子宫内膜癌（OR = 0.21，95% CI = 0.13 至 0.34）中的醋酸去甲羟孕酮（OR = 0.21，95% CI = 0.13 至 0.34）。虽然左炔诺孕酮宫内避孕系统、依托诺孕酮植入剂和醋酸去甲羟孕酮总体上都与癌症风险增加有关，但就依托诺孕酮植入剂而言，停药后风险恢复到基线，与口服避孕药类似。我们无法对所有潜在的混杂因素进行调整，但敏感性分析表明，对奇偶性、吸烟和肥胖进行调整不会对我们的研究结果产生实质性的改变。结论 长效、可逆避孕药与口服避孕药的癌症相关性相似（子宫内膜癌和卵巢癌风险降低，乳腺癌风险短期内增加）。这些信息可能会对妇女及其医生讨论避孕选择时有所帮助。
{"title":"Long-acting, progestin-based contraceptives and risk of breast, gynecological, and other cancers","authors":"Karen M Tuesley, Katrina Spilsbury, Sallie-Anne Pearson, Peter Donovan, Andreas Obermair, Michael D Coory, Sitwat Ali, Nirmala Pandeya, Louise Stewart, Susan J Jordan, Penelope M Webb","doi":"10.1093/jnci/djae282","DOIUrl":"https://doi.org/10.1093/jnci/djae282","url":null,"abstract":"Background Use of long-acting, reversible contraceptives has increased over the past 20 years, but an understanding of how they could influence cancer risk is limited. Methods We conducted a nested case-control study among a national cohort of Australian women (n = 176 601 diagnosed with cancer between 2004 and 2013; 882 999 matched control individuals) to investigate the associations between the levonorgestrel intrauterine system, etonogestrel implants, depot-medroxyprogesterone acetate and cancer risk and compared these results with the oral contraceptive pill. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI). Results Levonorgestrel intrauterine system and etonogestrel implant use was associated with breast cancer risk (OR = 1.26, 95% CI = 1.21 to 1.31, and OR = 1.24, 95% CI = 1.17 to 1.32, respectively), but depot-medroxyprogesterone acetate was not, except when used for 5 or more years (OR = 1.23, 95% CI = 0.95 to 1.59). Reduced risks were seen for levonorgestrel intrauterine system (≥1 years of use) in endometrial cancer (OR = 0.80, 95% CI = 0.65 to 0.99), ovarian cancer (OR = 0.71, 95% CI = 0.57 to 0.88), and cervical cancer (OR = 0.62, 95% CI = 0.51 to 0.75); for etonogestrel implant in endometrial cancer (OR = 0.21, 95% CI = 0.13 to 0.34) and ovarian cancer (OR = 0.76, 95% CI = 0.57 to 1.02); and for depot-medroxyprogesterone acetate in endometrial cancer (OR = 0.21, 95% CI = 0.13 to 0.34). Although levonorgestrel intrauterine system, etonogestrel implant and depot-medroxyprogesterone acetate were all associated with increased cancer risk overall, for etonogestrel implant, the risk returned to baseline after cessation, similar to the oral contraceptive pill. We were unable to adjust for all potential confounders, but sensitivity analyses suggested that adjusting for parity, smoking, and obesity would not have materially changed our findings. Conclusion Long-acting, reversible contraceptives have similar cancer associations to the oral contraceptive pill (reduced endometrial and ovarian cancer risks and short-term increased breast cancer risk). This information may be helpful to women and their physicians when discussing contraception options.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gonçalo Forjaz, Betsy Kohler, Michel P Coleman, Eva Steliarova-Foucher, Serban Negoita, Jaime M Guidry Auvil, Fernanda Silva Michels, Johanna Goderre, Charles Wiggins, Eric B Durbin, Gijs Geleijnse, Marie-Charlotte Henrion, Candice Altmayer, Thomas Dubois, Lynne Penberthy
Childhood cancers are a heterogeneous group of rare diseases, accounting for less than 2% of all cancers diagnosed worldwide. Most countries, therefore, do not have enough cases to provide robust information on epidemiology, treatment, and late effects, especially for rarer types of cancer. Thus, only through a concerted effort to share data internationally will we be able to answer research questions that could not otherwise be answered. With this goal in mind, the U.S. National Cancer Institute and the French National Cancer Institute co-sponsored the Paris Conference for an International Childhood Cancer Data Partnership in November 2023. This meeting convened more than 200 participants from 17 countries to address complex challenges in pediatric cancer research and data sharing. This Commentary delves into some key topics discussed during the Paris Conference and describes pilots that will help move this international effort forward. Main topics presented include: 1) the wide variation in interpreting the European Union's General Data Protection Regulation among Member States; 2) obstacles with transferring personal health data outside of the European Union; 3) standardization and harmonization, including common data models; and 4) novel approaches to data sharing such as federated querying and federated learning. We finally provide a brief description of three ongoing pilot projects. The International Childhood Cancer Data Partnership is the first step in developing a process to better support pediatric cancer research internationally through combining data from multiple countries.
{"title":"Making the Case for an International Childhood Cancer Data Partnership","authors":"Gonçalo Forjaz, Betsy Kohler, Michel P Coleman, Eva Steliarova-Foucher, Serban Negoita, Jaime M Guidry Auvil, Fernanda Silva Michels, Johanna Goderre, Charles Wiggins, Eric B Durbin, Gijs Geleijnse, Marie-Charlotte Henrion, Candice Altmayer, Thomas Dubois, Lynne Penberthy","doi":"10.1093/jnci/djaf003","DOIUrl":"https://doi.org/10.1093/jnci/djaf003","url":null,"abstract":"Childhood cancers are a heterogeneous group of rare diseases, accounting for less than 2% of all cancers diagnosed worldwide. Most countries, therefore, do not have enough cases to provide robust information on epidemiology, treatment, and late effects, especially for rarer types of cancer. Thus, only through a concerted effort to share data internationally will we be able to answer research questions that could not otherwise be answered. With this goal in mind, the U.S. National Cancer Institute and the French National Cancer Institute co-sponsored the Paris Conference for an International Childhood Cancer Data Partnership in November 2023. This meeting convened more than 200 participants from 17 countries to address complex challenges in pediatric cancer research and data sharing. This Commentary delves into some key topics discussed during the Paris Conference and describes pilots that will help move this international effort forward. Main topics presented include: 1) the wide variation in interpreting the European Union's General Data Protection Regulation among Member States; 2) obstacles with transferring personal health data outside of the European Union; 3) standardization and harmonization, including common data models; and 4) novel approaches to data sharing such as federated querying and federated learning. We finally provide a brief description of three ongoing pilot projects. The International Childhood Cancer Data Partnership is the first step in developing a process to better support pediatric cancer research internationally through combining data from multiple countries.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"47 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：