Masood Moghul, Amina Tran, Fionnuala Croft, Netty Kinsella, Clare Peckitt, Declan Cahill, Nicholas D James
Early diagnosis remains a major limitation of cancer outcomes with ethnicity and deprivation being determinants of inequalities that impact outcomes. Prostate cancer suffers from lower incidence rates and higher mortality rates in the most deprived versus the least deprived groups. We developed the 'Man Van' to enable high-risk male patients' from deprived communities and ethnic minorities increased access to health care to address these health inequalities. Between December 2021 and December 2022 the Man Van project was piloted in eight different locations chosen using geospatial targeting based on ethnic minority populations and deprivation scores. The primary outcome measures were the prevalence of prostate cancer and other health conditions. 810 men were recruited to be seen at our Man Van clinics with 610 men attending. 48% of attendees were non-White including 30% of men who were Black. 420 men had PSA tests performed with a median PSA of 1 μg/L. 15 prostate cancers were diagnosed (3.6%; 95% CI 2.0-5.9) with 10 of these being clinically significant disease. Black men were more likely to be diagnosed compared to white men: 7.1% versus 1.8% (p < .05). The Man Van project is a novel approach to tackling health inequalities combining awareness raising, improved access to healthcare as well as ease of follow-up. Comparatively high levels of prostate cancers were diagnosed at early stages and high levels of other health conditions were found which could improve the economic value of the service.
{"title":"The Man Van: A pilot study of using mobile targeted case-finding to address health inequalities in prostate cancer.","authors":"Masood Moghul, Amina Tran, Fionnuala Croft, Netty Kinsella, Clare Peckitt, Declan Cahill, Nicholas D James","doi":"10.1002/ijc.35169","DOIUrl":"https://doi.org/10.1002/ijc.35169","url":null,"abstract":"<p><p>Early diagnosis remains a major limitation of cancer outcomes with ethnicity and deprivation being determinants of inequalities that impact outcomes. Prostate cancer suffers from lower incidence rates and higher mortality rates in the most deprived versus the least deprived groups. We developed the 'Man Van' to enable high-risk male patients' from deprived communities and ethnic minorities increased access to health care to address these health inequalities. Between December 2021 and December 2022 the Man Van project was piloted in eight different locations chosen using geospatial targeting based on ethnic minority populations and deprivation scores. The primary outcome measures were the prevalence of prostate cancer and other health conditions. 810 men were recruited to be seen at our Man Van clinics with 610 men attending. 48% of attendees were non-White including 30% of men who were Black. 420 men had PSA tests performed with a median PSA of 1 μg/L. 15 prostate cancers were diagnosed (3.6%; 95% CI 2.0-5.9) with 10 of these being clinically significant disease. Black men were more likely to be diagnosed compared to white men: 7.1% versus 1.8% (p < .05). The Man Van project is a novel approach to tackling health inequalities combining awareness raising, improved access to healthcare as well as ease of follow-up. Comparatively high levels of prostate cancers were diagnosed at early stages and high levels of other health conditions were found which could improve the economic value of the service.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Accelerated biological aging may be associated with increased risk of esophageal adenocarcinoma (EAC). However, its relationship with genetic variation, and its effect on improving risk population stratification, remains unknown. We performed an exposome association study to determine potential associated factors associated with EAC. To quantify biological age and its difference from chronological age, we calculated the BioAge10 and Biological Age Acceleration (BioAgeAccel) based on chronological age and nine biomarkers. Multivariable Cox regression models for 362,310 participants from the UK Biobank with a median follow-up of 13.70 years were performed. We established a weighted polygenic risk score (wPRS) associated with EAC, to assess joint and interaction effects with BioAgeAccel. Four indicators were used to evaluate their interaction effects, and we fitted curves to evaluate the risk stratification ability of BioAgeAccel. Compared with biologically younger participants, those older had higher risk of EAC, with adjusted HR of 1.79 (95%CI: 1.52-2.10). Compared with low wPRS and biologically younger group, the high wPRS and biologically older group had a 4.30-fold increase in HR (95% CI: 2.78-6.66), at meanwhile, 1.15-fold relative excess risk was detected (95% CI: 0.30-2.75), and 22% of the overall EAC risk was attributable to the interactive effects (95% CI: 12%-31%). The 10-year absolute incidence risk indicates that biologically older individuals should begin screening procedures 4.18 years in advance, while youngers can postpone screening by 4.96 years, compared with general population. BioAgeAccel interacted positively with genetic variation and increased risk of EAC, it could serve as a novel indicator for predicting incidence.
{"title":"Impact of accelerated biological aging and genetic variation on esophageal adenocarcinoma: Joint and interaction effect in a prospective cohort.","authors":"Renjia Zhao, Huangbo Yuan, Shuaizhou Chen, Kelin Xu, Tiejun Zhang, Zhenqiu Liu, Yanfeng Jiang, Chen Suo, Xingdong Chen","doi":"10.1002/ijc.35161","DOIUrl":"https://doi.org/10.1002/ijc.35161","url":null,"abstract":"<p><p>Accelerated biological aging may be associated with increased risk of esophageal adenocarcinoma (EAC). However, its relationship with genetic variation, and its effect on improving risk population stratification, remains unknown. We performed an exposome association study to determine potential associated factors associated with EAC. To quantify biological age and its difference from chronological age, we calculated the BioAge10 and Biological Age Acceleration (BioAgeAccel) based on chronological age and nine biomarkers. Multivariable Cox regression models for 362,310 participants from the UK Biobank with a median follow-up of 13.70 years were performed. We established a weighted polygenic risk score (wPRS) associated with EAC, to assess joint and interaction effects with BioAgeAccel. Four indicators were used to evaluate their interaction effects, and we fitted curves to evaluate the risk stratification ability of BioAgeAccel. Compared with biologically younger participants, those older had higher risk of EAC, with adjusted HR of 1.79 (95%CI: 1.52-2.10). Compared with low wPRS and biologically younger group, the high wPRS and biologically older group had a 4.30-fold increase in HR (95% CI: 2.78-6.66), at meanwhile, 1.15-fold relative excess risk was detected (95% CI: 0.30-2.75), and 22% of the overall EAC risk was attributable to the interactive effects (95% CI: 12%-31%). The 10-year absolute incidence risk indicates that biologically older individuals should begin screening procedures 4.18 years in advance, while youngers can postpone screening by 4.96 years, compared with general population. BioAgeAccel interacted positively with genetic variation and increased risk of EAC, it could serve as a novel indicator for predicting incidence.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fredrik Mertens, Jakob Hofvander, Nils Mandahl, Felix Mitelman
Chromosomal aneuploidy, that is, numerical chromosome aberrations, is one of the molecular hallmarks of cancer. However, when neoplasms are studied with sequencing- and array-based approaches, chromosome numbers and ploidy states are typically inferred from bulk DNA data. Furthermore, published molecular estimates of neoplasia-associated aneuploidy often also include genomic imbalances resulting from various types of structural rearrangement, which likely result from other mechanisms than numerical chromosome aberrations. We thus analyzed chromosome numbers using single-cell cytogenetic data from 83,862 tumors, and show that both benign and malignant tumors are highly heterogeneous with regard to deviations from the normal, diploid state. Focusing on the chromosome numbers in 112 specific tumor types, defined by both exact morphologic diagnosis and organ location and from which data from ≥50 cases were available, we found two major clusters: one predominated by near-diploid neoplasms and one by neoplasms with extensive aneuploidy and one or more whole genome doublings. The former cluster included most benign solid tumors, myeloid neoplasms, and malignant gene fusion-associated solid tumors, whereas the latter was predominated by malignant solid tumors and lymphomas. For 16 malignant tumor types, the distribution of chromosome numbers could be compared to TCGA ploidy level data. Cytogenetic and molecular data correlated well, but the former indicates a higher level of clonal heterogeneity. The results presented here suggest shared pathogenetic mechanisms in certain tumor types and provide a reference for molecular analyses.
染色体非整倍体,即染色体数目畸变,是癌症的分子特征之一。然而,在使用基于测序和阵列的方法研究肿瘤时,染色体数目和倍性状态通常是通过大量 DNA 数据推断出来的。此外,已发表的肿瘤相关非整倍体的分子估计通常还包括各种结构重排导致的基因组失衡,而这些失衡可能是由染色体数目畸变以外的其他机制导致的。因此,我们利用来自 83,862 例肿瘤的单细胞细胞遗传学数据分析了染色体数目,结果显示良性肿瘤和恶性肿瘤在偏离正常二倍体状态方面存在高度异质性。我们重点研究了112种特定肿瘤类型的染色体数目,这些肿瘤类型由确切的形态学诊断和器官位置定义,并且有≥50个病例的数据可用,我们发现了两大类肿瘤:一类以接近二倍体的肿瘤为主,另一类以具有广泛非整倍体和一个或多个全基因组加倍的肿瘤为主。前者包括大多数良性实体瘤、骨髓肿瘤和恶性基因融合相关实体瘤,后者则以恶性实体瘤和淋巴瘤为主。对于 16 种恶性肿瘤类型,染色体数目的分布可与 TCGA 倍性水平数据进行比较。细胞遗传学数据与分子数据相关性良好,但前者表明克隆异质性更高。本文介绍的结果表明某些肿瘤类型具有共同的致病机制,并为分子分析提供了参考。
{"title":"Aneuploidy in neoplasia: Single-cell data on 83,862 tumors.","authors":"Fredrik Mertens, Jakob Hofvander, Nils Mandahl, Felix Mitelman","doi":"10.1002/ijc.35163","DOIUrl":"https://doi.org/10.1002/ijc.35163","url":null,"abstract":"<p><p>Chromosomal aneuploidy, that is, numerical chromosome aberrations, is one of the molecular hallmarks of cancer. However, when neoplasms are studied with sequencing- and array-based approaches, chromosome numbers and ploidy states are typically inferred from bulk DNA data. Furthermore, published molecular estimates of neoplasia-associated aneuploidy often also include genomic imbalances resulting from various types of structural rearrangement, which likely result from other mechanisms than numerical chromosome aberrations. We thus analyzed chromosome numbers using single-cell cytogenetic data from 83,862 tumors, and show that both benign and malignant tumors are highly heterogeneous with regard to deviations from the normal, diploid state. Focusing on the chromosome numbers in 112 specific tumor types, defined by both exact morphologic diagnosis and organ location and from which data from ≥50 cases were available, we found two major clusters: one predominated by near-diploid neoplasms and one by neoplasms with extensive aneuploidy and one or more whole genome doublings. The former cluster included most benign solid tumors, myeloid neoplasms, and malignant gene fusion-associated solid tumors, whereas the latter was predominated by malignant solid tumors and lymphomas. For 16 malignant tumor types, the distribution of chromosome numbers could be compared to TCGA ploidy level data. Cytogenetic and molecular data correlated well, but the former indicates a higher level of clonal heterogeneity. The results presented here suggest shared pathogenetic mechanisms in certain tumor types and provide a reference for molecular analyses.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bryan A Bassig, Xiao-Ou Shu, Melissa C Friesen, Roel Vermeulen, Mark P Purdue, Bu-Tian Ji, Gong Yang, Jason Y Y Wong, Nathan Appel, Wei Hu, Yu-Tang Gao, Wei Zheng, Nathaniel Rothman, Qing Lan
The carcinogenicity of benzene was reevaluated by the International Agency for Research on Cancer in 2017, with the Working Group reaffirming positive yet inconclusive associations with non-Hodgkin lymphoma (NHL). To extend our previous observation of a significant exposure-response for cumulative occupational benzene exposure and NHL risk among Chinese women in a population-based cohort in Shanghai, we extended follow-up of this cohort and pooled the data with a similarly designed population-based cohort of men in Shanghai. Cumulative exposure estimates were derived for 134,449 participants in the pooled analysis by combining ordinal job-exposure matrix intensity ratings with quantitative benzene measurements from an inspection database of Shanghai factories. Associations between benzene exposure metrics and NHL (n = 363 cases including multiple myeloma [MM]) were assessed using Cox proportional hazard models. Ever occupational exposure to benzene in the pooled population was associated with NHL risk (HR = 1.5, 95% CI = 1.2-2.0), and exposure-response relationships were observed for increasing duration (ptrend = .003) and cumulative exposure (ptrend = .003). Associations with ever exposure, duration, and cumulative exposure were similar for NHL with and without MM in the case definition, including lifetime cumulative exposures in the highest quartile (HR = 1.6, 95% CI = 1.1-2.4 with MM included; HR = 1.7, 95% CI = 1.1-2.7 with MM excluded). An elevated risk of the chronic lymphocytic leukemia subtype was suggested in the pooled analyses (HR for ever vs. never exposure = 2.3, 95% CI = 0.9-5.6). These observations provide additional support for a plausible association between occupational benzene exposure and risk of NHL.
国际癌症研究机构于 2017 年对苯的致癌性进行了重新评估,工作组重申苯与非霍奇金淋巴瘤(NHL)之间存在积极但尚无定论的关联。为了扩展我们之前在上海一个基于人群的队列中观察到的中国女性累积职业苯暴露与 NHL 风险之间存在显著的暴露反应,我们延长了对该队列的随访,并将数据与设计类似的上海男性人群队列进行了汇总。通过将工作暴露矩阵强度等级序数与上海工厂检测数据库中的苯定量测量值相结合,得出了汇总分析中 134,449 名参与者的累积暴露估计值。采用 Cox 比例危险模型评估了苯暴露指标与 NHL(n = 363 例,包括多发性骨髓瘤 [MM])之间的关系。汇总人群中的苯职业暴露与 NHL 风险相关(HR = 1.5,95% CI = 1.2-2.0),暴露-反应关系随着持续时间(ptrend = .003)和累积暴露(ptrend = .003)的增加而增加。在病例定义中,有 MM 和没有 MM 的 NHL 与曾经暴露、持续时间和累积暴露的关系相似,包括最高四分位数的终生累积暴露(包括 MM 时,HR = 1.6,95% CI = 1.1-2.4;不包括 MM 时,HR = 1.7,95% CI = 1.1-2.7)。汇总分析表明,慢性淋巴细胞白血病亚型的风险升高(曾经接触与从未接触的 HR = 2.3,95% CI = 0.9-5.6)。这些观察结果进一步证实了职业苯暴露与 NHL 风险之间存在合理的联系。
{"title":"Occupational exposure to benzene and risk of non-Hodgkin lymphoma in an extended follow-up of two population-based prospective cohorts of Chinese men and women.","authors":"Bryan A Bassig, Xiao-Ou Shu, Melissa C Friesen, Roel Vermeulen, Mark P Purdue, Bu-Tian Ji, Gong Yang, Jason Y Y Wong, Nathan Appel, Wei Hu, Yu-Tang Gao, Wei Zheng, Nathaniel Rothman, Qing Lan","doi":"10.1002/ijc.35095","DOIUrl":"https://doi.org/10.1002/ijc.35095","url":null,"abstract":"<p><p>The carcinogenicity of benzene was reevaluated by the International Agency for Research on Cancer in 2017, with the Working Group reaffirming positive yet inconclusive associations with non-Hodgkin lymphoma (NHL). To extend our previous observation of a significant exposure-response for cumulative occupational benzene exposure and NHL risk among Chinese women in a population-based cohort in Shanghai, we extended follow-up of this cohort and pooled the data with a similarly designed population-based cohort of men in Shanghai. Cumulative exposure estimates were derived for 134,449 participants in the pooled analysis by combining ordinal job-exposure matrix intensity ratings with quantitative benzene measurements from an inspection database of Shanghai factories. Associations between benzene exposure metrics and NHL (n = 363 cases including multiple myeloma [MM]) were assessed using Cox proportional hazard models. Ever occupational exposure to benzene in the pooled population was associated with NHL risk (HR = 1.5, 95% CI = 1.2-2.0), and exposure-response relationships were observed for increasing duration (p<sub>trend</sub> = .003) and cumulative exposure (p<sub>trend</sub> = .003). Associations with ever exposure, duration, and cumulative exposure were similar for NHL with and without MM in the case definition, including lifetime cumulative exposures in the highest quartile (HR = 1.6, 95% CI = 1.1-2.4 with MM included; HR = 1.7, 95% CI = 1.1-2.7 with MM excluded). An elevated risk of the chronic lymphocytic leukemia subtype was suggested in the pooled analyses (HR for ever vs. never exposure = 2.3, 95% CI = 0.9-5.6). These observations provide additional support for a plausible association between occupational benzene exposure and risk of NHL.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dieter Mainka, Nathalie Bauer, Lutz Dietze, Sonja Lehnert, Johanna Krandick, Daniel Himmelreich, Hassan Jomaa, Maximilian Zimmermann, Peter Borchmann, Swetlana Herbrandt, Achim Rothe
Cancer patients are at a higher risk to develop severe COVID-19 symptoms after SARS-CoV-2 infection compared to the general population and regularly show an impaired immune response to SARS-CoV-2 vaccination. In our oncological center, 357 patients with hematological and oncological diseases were monitored for neutralizing antibodies from October 2021 over 12 months. All patients had received three anti-SARS-CoV-2 vaccinations with an mRNA-(Comirnaty/BionTech or Spikevax/Moderna) or a vector vaccine (Vakzevria/AstraZeneca or JCOVDEN/Johnson&Johnson). Neutralizing anti-SARS-CoV-2 IgG antibodies in the patients' sera were detected within 3 months before, 3-10 weeks and 5-7 months after the booster vaccination (third vaccination). 112 patients developed a breakthrough SARS-CoV-2 infection during the observation period. High anti-SARS-Cov-2 antibody levels before infection significantly protected against symptomatic Covid-19 disease (p = .003). The median antibody titer in patients with asymptomatic Covid-19 disease was 2080 BAU/ml (binding antibody units per Milliliter) and 765 BAU/ml in symptomatic patients. 98% of the solid tumor patients reached seroconversion after the booster vaccination in comparison to 79% of the hematological patients. High antibody titers of >2080 BAU/ml after the booster vaccination were detected in 61% of the oncological and 34.8% of the hematological patients. 7-10 months after the booster vaccination, the anti-SARS-CoV-2 antibody titer declined to an average of 849 BAU/ml. Considering the heterogenous humoral immune response of cancer patients observed in this study, an individual vaccination strategy based on regular measurement of anti-SARS-CoV-2 antibody levels should be considered in contrast to fixed vaccination intervals.
{"title":"Humoral immune response as an indicator for protection against Covid-19 after anti-SARS-COV2-booster vaccination in hematological and oncological patients.","authors":"Dieter Mainka, Nathalie Bauer, Lutz Dietze, Sonja Lehnert, Johanna Krandick, Daniel Himmelreich, Hassan Jomaa, Maximilian Zimmermann, Peter Borchmann, Swetlana Herbrandt, Achim Rothe","doi":"10.1002/ijc.35162","DOIUrl":"https://doi.org/10.1002/ijc.35162","url":null,"abstract":"<p><p>Cancer patients are at a higher risk to develop severe COVID-19 symptoms after SARS-CoV-2 infection compared to the general population and regularly show an impaired immune response to SARS-CoV-2 vaccination. In our oncological center, 357 patients with hematological and oncological diseases were monitored for neutralizing antibodies from October 2021 over 12 months. All patients had received three anti-SARS-CoV-2 vaccinations with an mRNA-(Comirnaty/BionTech or Spikevax/Moderna) or a vector vaccine (Vakzevria/AstraZeneca or JCOVDEN/Johnson&Johnson). Neutralizing anti-SARS-CoV-2 IgG antibodies in the patients' sera were detected within 3 months before, 3-10 weeks and 5-7 months after the booster vaccination (third vaccination). 112 patients developed a breakthrough SARS-CoV-2 infection during the observation period. High anti-SARS-Cov-2 antibody levels before infection significantly protected against symptomatic Covid-19 disease (p = .003). The median antibody titer in patients with asymptomatic Covid-19 disease was 2080 BAU/ml (binding antibody units per Milliliter) and 765 BAU/ml in symptomatic patients. 98% of the solid tumor patients reached seroconversion after the booster vaccination in comparison to 79% of the hematological patients. High antibody titers of >2080 BAU/ml after the booster vaccination were detected in 61% of the oncological and 34.8% of the hematological patients. 7-10 months after the booster vaccination, the anti-SARS-CoV-2 antibody titer declined to an average of 849 BAU/ml. Considering the heterogenous humoral immune response of cancer patients observed in this study, an individual vaccination strategy based on regular measurement of anti-SARS-CoV-2 antibody levels should be considered in contrast to fixed vaccination intervals.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Renhua Na, Susan J Jordan, Anna DeFazio, Merran Williams, Karen Livingstone, Andreas Obermair, Michael Friedlander, Peter Grant, Penelope M Webb
Menopausal hormone therapy (MHT) use before ovarian cancer diagnosis has been associated with improved survival but whether the association varies by type and duration of use is inconclusive; data on MHT use after treatment, particularly the effect on health-related quality of life (HRQOL), are scarce. We investigated survival in women with ovarian cancer according to MHT use before and after diagnosis, and post-treatment MHT use and its association with HRQOL in a prospective nationwide cohort in Australia. We used Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) and propensity scores to reduce confounding by indication. Among 690 women who were peri-/postmenopausal at diagnosis, pre-diagnosis MHT use was associated with a significant 26% improvement in ovarian cancer-specific survival; with a slightly stronger association for high-grade serous carcinoma (HGSC, HR = 0.69, 95%CI 0.54-0.87). The associations did not differ by recency or duration of use. Among women with HGSC who were pre-/perimenopausal or aged ≤55 years at diagnosis (n = 259), MHT use after treatment was not associated with a difference in survival (HR = 1.04, 95%CI 0.48-2.22). Compared to non-users, women who started MHT after treatment reported poorer overall HRQOL before starting MHT and this difference was still seen 1-3 months after starting MHT. In conclusion, pre-diagnosis MHT use was associated with improved survival, particularly in HGSC. Among women ≤55 years, use of MHT following treatment was not associated with poorer survival for HGSC. Further large-scale studies are needed to understand menopause-specific HRQOL issues in ovarian cancer.
{"title":"Use of menopausal hormone therapy before and after diagnosis and ovarian cancer survival-A prospective cohort study in Australia.","authors":"Renhua Na, Susan J Jordan, Anna DeFazio, Merran Williams, Karen Livingstone, Andreas Obermair, Michael Friedlander, Peter Grant, Penelope M Webb","doi":"10.1002/ijc.35154","DOIUrl":"https://doi.org/10.1002/ijc.35154","url":null,"abstract":"<p><p>Menopausal hormone therapy (MHT) use before ovarian cancer diagnosis has been associated with improved survival but whether the association varies by type and duration of use is inconclusive; data on MHT use after treatment, particularly the effect on health-related quality of life (HRQOL), are scarce. We investigated survival in women with ovarian cancer according to MHT use before and after diagnosis, and post-treatment MHT use and its association with HRQOL in a prospective nationwide cohort in Australia. We used Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) and propensity scores to reduce confounding by indication. Among 690 women who were peri-/postmenopausal at diagnosis, pre-diagnosis MHT use was associated with a significant 26% improvement in ovarian cancer-specific survival; with a slightly stronger association for high-grade serous carcinoma (HGSC, HR = 0.69, 95%CI 0.54-0.87). The associations did not differ by recency or duration of use. Among women with HGSC who were pre-/perimenopausal or aged ≤55 years at diagnosis (n = 259), MHT use after treatment was not associated with a difference in survival (HR = 1.04, 95%CI 0.48-2.22). Compared to non-users, women who started MHT after treatment reported poorer overall HRQOL before starting MHT and this difference was still seen 1-3 months after starting MHT. In conclusion, pre-diagnosis MHT use was associated with improved survival, particularly in HGSC. Among women ≤55 years, use of MHT following treatment was not associated with poorer survival for HGSC. Further large-scale studies are needed to understand menopause-specific HRQOL issues in ovarian cancer.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immune checkpoint inhibitor (ICI)-induced adverse events due to excessive immune stimulation are problematic in immunotherapy. The activation of viral infection triggered by ICI-induced dysregulated immunity has been proposed; however, this association remains inconsistent. This study investigated the association between ICI administration and cytomegalovirus (CMV) infections, a pathogen linked to immune abnormalities and reactivation, using the Food and Drug Administration Adverse Event Reporting System. We used the crude data set and immunocompromise-free data set from the fourth quarter of 2012 to 2023. The disproportionality between CMV infection and ICI was analyzed using reporting odds ratio (ROR) and information component (IC) methodologies. Disproportionality between ipilimumab and nivolumab combination case and CMV infection was observed in the crude (ROR: 2.83, 95% confidence interval [CI]: 2.32-3.47; IC: 1.48, 95% CI: 1.14-1.73) and immunocompromise-free data set (ROR: 1.76, 95% CI: 1.33-2.33; IC: 0.80, 95% CI: 0.33-1.14), whereas disproportionality between other ICI and CMV infection was not observed in the immunocompromise-free data set. Multiple sensitivity analyses and time-scan analysis also revealed the consistent disproportionality between ipilimumab and nivolumab combination cases and CMV infection, regardless of the host's immune status. While further research is warranted to validate our findings, these results highlight new insights into ICI-induced viral infections and suggest the importance of considering the possibility of CMV infections during ipilimumab and nivolumab combination therapy, regardless of the host's immune status.
{"title":"Association between immune checkpoint inhibitor and cytomegalovirus infection: A pharmacovigilance study based on the adverse event reporting system.","authors":"Naoto Okada, Tomoyuki Yanagi, Takaaki Sasaki, Miho Tamura, Masakazu Ozaki, Atsuyuki Saisyo, Takashi Kitahara","doi":"10.1002/ijc.35155","DOIUrl":"https://doi.org/10.1002/ijc.35155","url":null,"abstract":"<p><p>Immune checkpoint inhibitor (ICI)-induced adverse events due to excessive immune stimulation are problematic in immunotherapy. The activation of viral infection triggered by ICI-induced dysregulated immunity has been proposed; however, this association remains inconsistent. This study investigated the association between ICI administration and cytomegalovirus (CMV) infections, a pathogen linked to immune abnormalities and reactivation, using the Food and Drug Administration Adverse Event Reporting System. We used the crude data set and immunocompromise-free data set from the fourth quarter of 2012 to 2023. The disproportionality between CMV infection and ICI was analyzed using reporting odds ratio (ROR) and information component (IC) methodologies. Disproportionality between ipilimumab and nivolumab combination case and CMV infection was observed in the crude (ROR: 2.83, 95% confidence interval [CI]: 2.32-3.47; IC: 1.48, 95% CI: 1.14-1.73) and immunocompromise-free data set (ROR: 1.76, 95% CI: 1.33-2.33; IC: 0.80, 95% CI: 0.33-1.14), whereas disproportionality between other ICI and CMV infection was not observed in the immunocompromise-free data set. Multiple sensitivity analyses and time-scan analysis also revealed the consistent disproportionality between ipilimumab and nivolumab combination cases and CMV infection, regardless of the host's immune status. While further research is warranted to validate our findings, these results highlight new insights into ICI-induced viral infections and suggest the importance of considering the possibility of CMV infections during ipilimumab and nivolumab combination therapy, regardless of the host's immune status.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Florian Janke, Florian Stritzke, Katharina Dvornikovich, Henrik Franke, Arlou Kristina Angeles, Anja Lisa Riediger, Simon Ogrodnik, Sabrina Gerhardt, Sebastian Regnery, Philipp Schröter, Lukas Bauer, Katharina Weusthof, Magdalena Görtz, Semi Harrabi, Klaus Herfarth, Christian Neelsen, Daniel Paech, Heinz-Peter Schlemmer, Amir Abdollahi, Sebastian Adeberg, Jürgen Debus, Holger Sültmann, Thomas Held
Local recurrence after radiotherapy is common in locally advanced head and neck cancer (HNC) patients. Re-irradiation can improve local disease control, but disease progression remains frequent. Hence, predictive biomarkers are needed to adapt treatment intensity to the patient's individual risk. We quantified circulating tumor DNA (ctDNA) in sequential plasma samples and correlated ctDNA levels with disease outcome. Ninety four longitudinal plasma samples from 16 locally advanced HNC patients and 57 healthy donors were collected at re-radiotherapy baseline, after 5 and 10 radiation fractions, at irradiation end, and at routine follow-up visits. Plasma DNA was subjected to low coverage whole genome sequencing for copy number variation (CNV) profiling to quantify ctDNA burden. CNV-based ctDNA burden was detected in 8/16 patients and 25/94 plasma samples. Ten additional ctDNA-positive samples were identified by tracking patient-specific CNVs found in earlier sequential plasma samples. ctDNA-positivity after 5 and 10 radiation fractions (both: log-rank, p = .050) as well as at the end of irradiation correlated with short progression-free survival (log-rank, p = .006). Moreover, a pronounced decrease of ctDNA toward re-radiotherapy termination was associated with worse treatment outcome (log-rank, p = .005). Dynamic ctDNA tracking in serial plasma beyond re-radiotherapy reflected treatment response and imminent disease progression. In five patients, molecular progression was detected prior to tumor progression based on clinical imaging. Our findings emphasize that quantifying ctDNA during re-radiotherapy may contribute to disease monitoring and personalization of adjuvant treatment, follow-up intervals, and dose prescription.
{"title":"Early circulating tumor DNA changes predict outcomes in head and neck cancer patients under re-radiotherapy.","authors":"Florian Janke, Florian Stritzke, Katharina Dvornikovich, Henrik Franke, Arlou Kristina Angeles, Anja Lisa Riediger, Simon Ogrodnik, Sabrina Gerhardt, Sebastian Regnery, Philipp Schröter, Lukas Bauer, Katharina Weusthof, Magdalena Görtz, Semi Harrabi, Klaus Herfarth, Christian Neelsen, Daniel Paech, Heinz-Peter Schlemmer, Amir Abdollahi, Sebastian Adeberg, Jürgen Debus, Holger Sültmann, Thomas Held","doi":"10.1002/ijc.35152","DOIUrl":"https://doi.org/10.1002/ijc.35152","url":null,"abstract":"<p><p>Local recurrence after radiotherapy is common in locally advanced head and neck cancer (HNC) patients. Re-irradiation can improve local disease control, but disease progression remains frequent. Hence, predictive biomarkers are needed to adapt treatment intensity to the patient's individual risk. We quantified circulating tumor DNA (ctDNA) in sequential plasma samples and correlated ctDNA levels with disease outcome. Ninety four longitudinal plasma samples from 16 locally advanced HNC patients and 57 healthy donors were collected at re-radiotherapy baseline, after 5 and 10 radiation fractions, at irradiation end, and at routine follow-up visits. Plasma DNA was subjected to low coverage whole genome sequencing for copy number variation (CNV) profiling to quantify ctDNA burden. CNV-based ctDNA burden was detected in 8/16 patients and 25/94 plasma samples. Ten additional ctDNA-positive samples were identified by tracking patient-specific CNVs found in earlier sequential plasma samples. ctDNA-positivity after 5 and 10 radiation fractions (both: log-rank, p = .050) as well as at the end of irradiation correlated with short progression-free survival (log-rank, p = .006). Moreover, a pronounced decrease of ctDNA toward re-radiotherapy termination was associated with worse treatment outcome (log-rank, p = .005). Dynamic ctDNA tracking in serial plasma beyond re-radiotherapy reflected treatment response and imminent disease progression. In five patients, molecular progression was detected prior to tumor progression based on clinical imaging. Our findings emphasize that quantifying ctDNA during re-radiotherapy may contribute to disease monitoring and personalization of adjuvant treatment, follow-up intervals, and dose prescription.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Expression of Concern: A small molecule, LLL12 inhibits constitutive STAT3 and IL-6-induced STAT3 signaling and exhibits potent growth suppressive activity in human multiple myeloma cells.","authors":"","doi":"10.1002/ijc.35160","DOIUrl":"https://doi.org/10.1002/ijc.35160","url":null,"abstract":"","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142085877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Different endogenous and exogenous mutational processes cause specific patterns of somatic mutations and mutational signatures. Although their biological research has been intensive, there are only rare studies assessing the possible prognostic role of mutational signatures. We used data from The Cancer Genome Atlas to study the associations between the activity of the mutational signatures and four survival endpoints in 18 types of malignancies. We further explored the prognostic differences according to, for example, the HPV status in head and neck squamous cell carcinomas and smoking status in lung cancers. The predictive power of the signatures over time was evaluated with a dynamic area under the curve model, and the links between mutational signature activities and differences in gene expression patterns were analyzed. In 12 of 18 studied cancer types, we identified at least one mutational signature whose activity predicted survival outcomes after adjusting for the established prognostic factors. For example, overall survival was associated with the activity of mutational signatures in nine cancer types and disease-specific survival in seven cancer types. The clock-like signatures SBS5 and SBS40 were most commonly associated with survival endpoints. The genes of the myosin binding protein and melanoma antigen families were among the most substantially dysregulated genes between the signatures of low and high activity. The differences in gene expression also revealed various enriched pathways. Based on these data, specific mutational signatures associate with the gene expression and have the potential to serve as strong prognostic factors in several cancer types.
{"title":"Mutational signatures and their association with cancer survival and gene expression in multiple cancer types.","authors":"Peeter Karihtala, Outi Kilpivaara, Katja Porvari","doi":"10.1002/ijc.35148","DOIUrl":"https://doi.org/10.1002/ijc.35148","url":null,"abstract":"<p><p>Different endogenous and exogenous mutational processes cause specific patterns of somatic mutations and mutational signatures. Although their biological research has been intensive, there are only rare studies assessing the possible prognostic role of mutational signatures. We used data from The Cancer Genome Atlas to study the associations between the activity of the mutational signatures and four survival endpoints in 18 types of malignancies. We further explored the prognostic differences according to, for example, the HPV status in head and neck squamous cell carcinomas and smoking status in lung cancers. The predictive power of the signatures over time was evaluated with a dynamic area under the curve model, and the links between mutational signature activities and differences in gene expression patterns were analyzed. In 12 of 18 studied cancer types, we identified at least one mutational signature whose activity predicted survival outcomes after adjusting for the established prognostic factors. For example, overall survival was associated with the activity of mutational signatures in nine cancer types and disease-specific survival in seven cancer types. The clock-like signatures SBS5 and SBS40 were most commonly associated with survival endpoints. The genes of the myosin binding protein and melanoma antigen families were among the most substantially dysregulated genes between the signatures of low and high activity. The differences in gene expression also revealed various enriched pathways. Based on these data, specific mutational signatures associate with the gene expression and have the potential to serve as strong prognostic factors in several cancer types.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}