Pub Date : 2024-12-01Epub Date: 2024-08-07DOI: 10.1002/ijc.35115
Maki Inoue-Choi, Neal D Freedman, Arash Etemadi, Maryam Hashemian, Paul Brennan, Gholamreza Roshandel, Hossein Poustchi, Paolo Boffetta, Farin Kamangar, Taghi Amiriani, Alireza Norouzi, Sandy Dawsey, Reza Malekzadeh, Christian C Abnet
Incidence of esophageal and gastric cancer has been linked to low B-vitamin status. We conducted matched nested case-control studies of incident esophageal squamous cell carcinoma (ESCC; 340 case-control pairs) and gastric cancer (GC; 352 case-control pairs) within the Golestan Cohort Study. The primary exposure was plasma biomarkers: riboflavin and flavin mononucleotide (FMN) (vitamin B2), pyridoxal phosphate (PLP) (B6), cobalamin (B12), para-aminobenzoylglutamate (pABG) (folate), and total homocysteine (tHcy); and indicators for deficiency: 3-hydroxykyurenine-ratio (HK-r for vitamin B6) and methylmalonic acid (MMA for B12). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression adjusting for matching factors and potential confounders. High proportions of participants had low B-vitamin and high tHcy levels. None of the measured vitamin B levels was associated with the risk of ESCC and GC, but elevated level of MMA was marginally associated with ESCC (OR = 1.42, 95% CI = 0.99-2.04) and associated with GC (OR = 1.53, 95% CI = 1.05-2.22). Risk of GC was higher for the highest versus lowest quartile of HK-r (OR = 1.95, 95%CI = 1.19-3.21) and for elevated versus non-elevated HK-r level (OR = 1.59, 95% CI = 1.13-2.25). Risk of ESCC (OR = 2.81, 95% CI = 1.54-5.13) and gastric cancer (OR = 2.09, 95%CI = 1.17-3.73) was higher for the highest versus lowest quartile of tHcy. In conclusion, insufficient vitamin B12 was associated with higher risk of ESCC and GC, and insufficient vitamin B6 status was associated with higher risk of GC in this population with prevalent low plasma B-vitamin status. Higher level of tHcy, a global indicator of OCM function, was associated with higher risk of ESCC and GC.
食管癌和胃癌的发病率与维生素 B 含量低有关。我们在戈勒斯坦队列研究(Golestan Cohort Study)中对食管鳞状细胞癌(ESCC,340 对病例对照)和胃癌(GC,352 对病例对照)的发病率进行了匹配巢式病例对照研究。主要暴露指标是血浆生物标志物:核黄素和黄素单核苷酸 (FMN)(维生素 B2)、磷酸吡哆醛 (PLP)(维生素 B6)、钴胺素 (B12)、对氨基苯甲酰谷氨酸 (pABG) (叶酸)和同型半胱氨酸总量 (tHcy);以及缺乏指标:3-羟基尿氨酸比率 (HK-r for vitamin B6) 和甲基丙二酸 (MMA for B12)。我们采用条件逻辑回归法估算了几率比(OR)和 95% 置信区间(CI),并对匹配因素和潜在混杂因素进行了调整。参与者中维生素 B 含量低和 tHcy 含量高的比例较高。测得的维生素 B 水平均与 ESCC 和 GC 风险无关,但 MMA 水平升高与 ESCC 略有相关(OR = 1.42,95% CI = 0.99-2.04),与 GC 相关(OR = 1.53,95% CI = 1.05-2.22)。HK-r最高四分位数相对于最低四分位数(OR = 1.95,95%CI = 1.19-3.21),以及HK-r水平升高相对于未升高(OR = 1.59,95%CI = 1.13-2.25),患GC的风险更高。tHcy最高四分位数与最低四分位数相比,ESCC(OR = 2.81,95% CI = 1.54-5.13)和胃癌(OR = 2.09,95% CI = 1.17-3.73)风险更高。总之,在血浆 B 族维生素含量普遍较低的人群中,维生素 B12 不足与 ESCC 和 GC 风险较高有关,维生素 B6 不足与 GC 风险较高有关。作为 OCM 功能的总体指标,tHcy 水平越高,罹患 ESCC 和 GC 的风险越高。
{"title":"One-carbon metabolism biomarkers and upper gastrointestinal cancer in the Golestan Cohort Study.","authors":"Maki Inoue-Choi, Neal D Freedman, Arash Etemadi, Maryam Hashemian, Paul Brennan, Gholamreza Roshandel, Hossein Poustchi, Paolo Boffetta, Farin Kamangar, Taghi Amiriani, Alireza Norouzi, Sandy Dawsey, Reza Malekzadeh, Christian C Abnet","doi":"10.1002/ijc.35115","DOIUrl":"10.1002/ijc.35115","url":null,"abstract":"<p><p>Incidence of esophageal and gastric cancer has been linked to low B-vitamin status. We conducted matched nested case-control studies of incident esophageal squamous cell carcinoma (ESCC; 340 case-control pairs) and gastric cancer (GC; 352 case-control pairs) within the Golestan Cohort Study. The primary exposure was plasma biomarkers: riboflavin and flavin mononucleotide (FMN) (vitamin B2), pyridoxal phosphate (PLP) (B6), cobalamin (B12), para-aminobenzoylglutamate (pABG) (folate), and total homocysteine (tHcy); and indicators for deficiency: 3-hydroxykyurenine-ratio (HK-r for vitamin B6) and methylmalonic acid (MMA for B12). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression adjusting for matching factors and potential confounders. High proportions of participants had low B-vitamin and high tHcy levels. None of the measured vitamin B levels was associated with the risk of ESCC and GC, but elevated level of MMA was marginally associated with ESCC (OR = 1.42, 95% CI = 0.99-2.04) and associated with GC (OR = 1.53, 95% CI = 1.05-2.22). Risk of GC was higher for the highest versus lowest quartile of HK-r (OR = 1.95, 95%CI = 1.19-3.21) and for elevated versus non-elevated HK-r level (OR = 1.59, 95% CI = 1.13-2.25). Risk of ESCC (OR = 2.81, 95% CI = 1.54-5.13) and gastric cancer (OR = 2.09, 95%CI = 1.17-3.73) was higher for the highest versus lowest quartile of tHcy. In conclusion, insufficient vitamin B12 was associated with higher risk of ESCC and GC, and insufficient vitamin B6 status was associated with higher risk of GC in this population with prevalent low plasma B-vitamin status. Higher level of tHcy, a global indicator of OCM function, was associated with higher risk of ESCC and GC.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Currently, conventional immunotherapies for the treatment of non-small cell lung cancer (NSCLC) have low response rates and benefit only a minority of patients, particularly those with advanced disease, so novel therapeutic strategies are urgent deeded. Therapeutic cancer vaccines, a form of active immunotherapy, harness potential to activate the adaptive immune system against tumor cells via antigen cross-presentation. Cancer vaccines can establish enduring immune memory and guard against recurrences. Vaccine-induced tumor cell death prompts antigen epitope spreading, activating functional T cells and thereby sustaining a cancer-immunity cycle. The success of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rendered cancer vaccines a promising avenue, especially when combined with immunotherapy or chemoradiotherapy for NSCLC. This review delves into the intricate antitumor immune mechanisms underlying therapeutic cancer vaccines, enumerates the tumor antigen spectrum of NSCLC, discusses different cancer vaccines progress and summarizes relevant clinical trials. Additionally, we analyze the combination strategies, current limitations, and future prospects of cancer vaccines in NSCLC treatment, aiming to offer fresh insights for their clinical application in managing NSCLC. Overall, cancer vaccines offer promising potential for NSCLC treatment, particularly combining with chemoradiotherapy or immunotherapy could further improve survival in advanced patients. Exploring inhaled vaccines or prophylactic vaccines represents a crucial research avenue.
{"title":"The current therapeutic cancer vaccines landscape in non-small cell lung cancer.","authors":"Shaoyi Chen, Sida Cheng, Jingsheng Cai, Zheng Liu, Haoran Li, Peiyu Wang, Yun Li, Fan Yang, Kezhong Chen, Mantang Qiu","doi":"10.1002/ijc.35088","DOIUrl":"10.1002/ijc.35088","url":null,"abstract":"<p><p>Currently, conventional immunotherapies for the treatment of non-small cell lung cancer (NSCLC) have low response rates and benefit only a minority of patients, particularly those with advanced disease, so novel therapeutic strategies are urgent deeded. Therapeutic cancer vaccines, a form of active immunotherapy, harness potential to activate the adaptive immune system against tumor cells via antigen cross-presentation. Cancer vaccines can establish enduring immune memory and guard against recurrences. Vaccine-induced tumor cell death prompts antigen epitope spreading, activating functional T cells and thereby sustaining a cancer-immunity cycle. The success of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rendered cancer vaccines a promising avenue, especially when combined with immunotherapy or chemoradiotherapy for NSCLC. This review delves into the intricate antitumor immune mechanisms underlying therapeutic cancer vaccines, enumerates the tumor antigen spectrum of NSCLC, discusses different cancer vaccines progress and summarizes relevant clinical trials. Additionally, we analyze the combination strategies, current limitations, and future prospects of cancer vaccines in NSCLC treatment, aiming to offer fresh insights for their clinical application in managing NSCLC. Overall, cancer vaccines offer promising potential for NSCLC treatment, particularly combining with chemoradiotherapy or immunotherapy could further improve survival in advanced patients. Exploring inhaled vaccines or prophylactic vaccines represents a crucial research avenue.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896178","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}
Pub Date : 2024-12-01Epub Date: 2024-08-11DOI: 10.1002/ijc.35128
Yanxia Guo, Yujie Sun, Zhongying Li, Chaohui Zuo, Xiaoqing Liu, Yu Chen, Zhen Xun, Jinling Liu, Yang Mei, Jung-Joon Min, Min Wen, Jin Hai Zheng, Wenzhi Tan
Bacteria are ideal anticancer agents and carriers due to their unique capabilities that are convenient in genetic manipulation, tumor-specific targeting, and deep-tissue penetration. However, the specific molecular mechanisms of bacteria-mediated cancer therapy (BMCT) have not been clarified. In this study, we found that TLR4 signaling pathway is critical for Salmonella-mediated tumor targeting, tumor suppression, and liver and spleen protection. TLR4 knockout in mice decreased the levels of cytokines and chemokines, such as S100a8, S100a9, TNF-α, and IL-1β, in tumor microenvironments (TMEs) after Salmonella treatment, which inhibited tumor cell death and nutrient release, led to reduced bacterial contents in tumors and attenuated antitumor efficacy in a negative feedback manner. Importantly, we found that S100a8 and S100a9 played a leading role in Salmonella-mediated cancer therapy (SMCT). The antitumor efficacy was abrogated and liver damage was prominent when blocked with a specific inhibitor. These findings elucidated the mechanism of Salmonella-mediated tumor targeting, suppression, and host antibacterial defense, providing insights into clinical cancer therapeutics.
{"title":"S100a8/a9 regulated by LPS/TLR4 axis plays an important role in Salmonella-based tumor therapy and host defense.","authors":"Yanxia Guo, Yujie Sun, Zhongying Li, Chaohui Zuo, Xiaoqing Liu, Yu Chen, Zhen Xun, Jinling Liu, Yang Mei, Jung-Joon Min, Min Wen, Jin Hai Zheng, Wenzhi Tan","doi":"10.1002/ijc.35128","DOIUrl":"10.1002/ijc.35128","url":null,"abstract":"<p><p>Bacteria are ideal anticancer agents and carriers due to their unique capabilities that are convenient in genetic manipulation, tumor-specific targeting, and deep-tissue penetration. However, the specific molecular mechanisms of bacteria-mediated cancer therapy (BMCT) have not been clarified. In this study, we found that TLR4 signaling pathway is critical for Salmonella-mediated tumor targeting, tumor suppression, and liver and spleen protection. TLR4 knockout in mice decreased the levels of cytokines and chemokines, such as S100a8, S100a9, TNF-α, and IL-1β, in tumor microenvironments (TMEs) after Salmonella treatment, which inhibited tumor cell death and nutrient release, led to reduced bacterial contents in tumors and attenuated antitumor efficacy in a negative feedback manner. Importantly, we found that S100a8 and S100a9 played a leading role in Salmonella-mediated cancer therapy (SMCT). The antitumor efficacy was abrogated and liver damage was prominent when blocked with a specific inhibitor. These findings elucidated the mechanism of Salmonella-mediated tumor targeting, suppression, and host antibacterial defense, providing insights into clinical cancer therapeutics.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141915605","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}
Pub Date : 2024-12-01Epub Date: 2024-08-15DOI: 10.1002/ijc.35134
Jesús Duque-Afonso, Pia Veratti, Usama-Ur Rehman, Heike Herzog, Jan Mitschke, Gabriele Greve, Julian Eble, Bettina Berberich, Johanna Thomas, Milena Pantic, Miguel Waterhouse, Gaia Gentile, Olaf Heidenreich, Cornelius Miething, Michael Lübbert
Aberrant gene expression patterns in acute myeloid leukemia (AML) with balanced chromosomal translocations are often associated with dysregulation of epigenetic modifiers. The AML1/ETO (RUNX1/MTG8) fusion protein, caused by the translocation (8;21)(q22;q22), leads to the epigenetic repression of its target genes. We aimed in this work to identify critical epigenetic modifiers, on which AML1/ETO-positive AML cells depend on for proliferation and survival using shRNA library screens and global transcriptomics approaches. Using shRNA library screens, we identified 41 commonly depleted genes in two AML1/ETO-positive cell lines Kasumi-1 and SKNO-1. We validated, genetically and pharmacologically, DNMT1 and ATR using several AML1/ETO-positive and negative cell lines. We also demonstrated in vivo differentiation of myeloblasts after treatment with the DNMT1 inhibitor decitabine in a patient with an AML1/ETO-positive AML. Bioinformatic analysis of global transcriptomics after AML1/ETO induction in 9/14/18-U937 cells identified 973 differentially expressed genes (DEGs). Three genes (PARP2, PRKCD, and SMARCA4) were both downregulated after AML1/ETO induction, and identified in shRNA screens. In conclusion, using unbiased shRNA library screens and global transcriptomics, we have identified several driver epigenetic regulators for proliferation in AML1/ETO-positive AML. DNMT1 and ATR were validated and are susceptible to pharmacological inhibition by small molecules showing promising preclinical and clinical efficacy.
{"title":"Identification of epigenetic modifiers essential for growth and survival of AML1/ETO-positive leukemia.","authors":"Jesús Duque-Afonso, Pia Veratti, Usama-Ur Rehman, Heike Herzog, Jan Mitschke, Gabriele Greve, Julian Eble, Bettina Berberich, Johanna Thomas, Milena Pantic, Miguel Waterhouse, Gaia Gentile, Olaf Heidenreich, Cornelius Miething, Michael Lübbert","doi":"10.1002/ijc.35134","DOIUrl":"10.1002/ijc.35134","url":null,"abstract":"<p><p>Aberrant gene expression patterns in acute myeloid leukemia (AML) with balanced chromosomal translocations are often associated with dysregulation of epigenetic modifiers. The AML1/ETO (RUNX1/MTG8) fusion protein, caused by the translocation (8;21)(q22;q22), leads to the epigenetic repression of its target genes. We aimed in this work to identify critical epigenetic modifiers, on which AML1/ETO-positive AML cells depend on for proliferation and survival using shRNA library screens and global transcriptomics approaches. Using shRNA library screens, we identified 41 commonly depleted genes in two AML1/ETO-positive cell lines Kasumi-1 and SKNO-1. We validated, genetically and pharmacologically, DNMT1 and ATR using several AML1/ETO-positive and negative cell lines. We also demonstrated in vivo differentiation of myeloblasts after treatment with the DNMT1 inhibitor decitabine in a patient with an AML1/ETO-positive AML. Bioinformatic analysis of global transcriptomics after AML1/ETO induction in 9/14/18-U937 cells identified 973 differentially expressed genes (DEGs). Three genes (PARP2, PRKCD, and SMARCA4) were both downregulated after AML1/ETO induction, and identified in shRNA screens. In conclusion, using unbiased shRNA library screens and global transcriptomics, we have identified several driver epigenetic regulators for proliferation in AML1/ETO-positive AML. DNMT1 and ATR were validated and are susceptible to pharmacological inhibition by small molecules showing promising preclinical and clinical efficacy.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141986929","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}
Pub Date : 2024-12-01Epub Date: 2024-08-19DOI: 10.1002/ijc.35110
Sujay Kalathoor, Sanam Ghazi, Beryl Otieno, Melissa A Babcook, Sunnia Chen, Neha Nidhi, Junu Bae, Jovan Pierre-Charles, Khadijah Breathett, Sula Mazimba, Amber Johnson, LaPrincess Brewer, Selma Mohammed, Rebecca R Carter, Janice M Bonsu, Mussammat Ferdousi, Onaopepo Kola-Kehinde, Eric McLaughlin, Jonathan Brammer, Patrick Ruz, Sarah Khan, Bismarck Odei, Darrion Mitchell, Lai Wei, Prem Patel, Electra D Paskett, Daniel Addison
Contemporary anticancer therapies frequently have different efficacy and side effects in men and women. Yet, whether women are well-represented in pivotal trials supporting contemporary anticancer drugs is unknown. Leveraging the Drugs@FDA database, clinicaltrials.gov, MEDLINE, and publicly available FDA-drug-reviews, we identified all pivotal (phase II and III) non-sex specific trials supporting FDA-approval of anticancer drugs (1998-2018). Observed-enrollment-rates were compared to expected-population-rates derived from concurrent US-National-Cancer-Institute's Surveillance-Epidemiology-and-End-Results (SEER) reported rates and US-Census databases. Primary outcome was the proportional representation of women across trials, evaluated by a participation-to-prevalence ratio (PPR), according to cancer type. Secondary outcome was the report of any sex-specific analysis of efficacy and/or safety, irrespective of treatment-arm. Overall, there were 148 trials, enrolling 60,216 participants (60.5 ± 4.0 years, 40.7% female, 79.1% biologic, targeted, or immune-based therapies) evaluating 99 drugs. Sex was reported in 146 (98.6%) trials, wherein 40.7% (24,538) were women, compared to 59.3% (35,678) men (p < .01). Altogether, women were under-represented in 66.9% trials compared to the proportional incidence of cancers by respective disease type; weight-average PPR of 0.91 (relative difference: -9.1%, p < .01). Women were most under-represented in gastric (PPR = 0.63), liver (PPR = 0.71), and lung (PPR = .81) cancer trials. Sex-based safety data was reported in 4.0% trials. There was no association between adequate female enrollment and drug efficacy (HR: 0.616 vs. 0.613, p = .96). Over time, there was no difference in the percentage of women recruited into clinical trials. Among pivotal clinical trials supporting contemporary FDA-approved cancer drugs, women were frequently under-represented and sex-specific-efficacy and safety-outcomes were commonly not reported.
当代抗癌疗法对男性和女性的疗效和副作用往往不同。然而,在支持当代抗癌药物的关键性试验中,女性是否具有充分的代表性还不得而知。利用 Drugs@FDA 数据库、clinicaltrials.gov、MEDLINE 和公开的 FDA 药物评论,我们确定了所有支持 FDA 批准抗癌药物的关键性(II 期和 III 期)非性别特定试验(1998-2018 年)。我们将观察到的注册率与同时从美国国家癌症研究所的 "监测-流行病学-最终结果"(SEER)报告率和美国人口普查数据库中得出的预期人口比例进行了比较。主要结果是根据癌症类型,通过参与率与患病率之比(PPR)评估女性在各项试验中的比例。次要结果是对疗效和/或安全性的性别特异性分析报告,与治疗臂无关。总体而言,共有 148 项试验,60216 名参与者(60.5 ± 4.0 岁,40.7% 为女性,79.1% 为生物、靶向或免疫疗法)参与了 99 种药物的评估。146项(98.6%)试验报告了性别,其中女性占40.7%(24,538人),男性占59.3%(35,678人)(p
{"title":"Representation of women in clinical trials supporting FDA-approval of contemporary cancer therapies.","authors":"Sujay Kalathoor, Sanam Ghazi, Beryl Otieno, Melissa A Babcook, Sunnia Chen, Neha Nidhi, Junu Bae, Jovan Pierre-Charles, Khadijah Breathett, Sula Mazimba, Amber Johnson, LaPrincess Brewer, Selma Mohammed, Rebecca R Carter, Janice M Bonsu, Mussammat Ferdousi, Onaopepo Kola-Kehinde, Eric McLaughlin, Jonathan Brammer, Patrick Ruz, Sarah Khan, Bismarck Odei, Darrion Mitchell, Lai Wei, Prem Patel, Electra D Paskett, Daniel Addison","doi":"10.1002/ijc.35110","DOIUrl":"10.1002/ijc.35110","url":null,"abstract":"<p><p>Contemporary anticancer therapies frequently have different efficacy and side effects in men and women. Yet, whether women are well-represented in pivotal trials supporting contemporary anticancer drugs is unknown. Leveraging the Drugs@FDA database, clinicaltrials.gov, MEDLINE, and publicly available FDA-drug-reviews, we identified all pivotal (phase II and III) non-sex specific trials supporting FDA-approval of anticancer drugs (1998-2018). Observed-enrollment-rates were compared to expected-population-rates derived from concurrent US-National-Cancer-Institute's Surveillance-Epidemiology-and-End-Results (SEER) reported rates and US-Census databases. Primary outcome was the proportional representation of women across trials, evaluated by a participation-to-prevalence ratio (PPR), according to cancer type. Secondary outcome was the report of any sex-specific analysis of efficacy and/or safety, irrespective of treatment-arm. Overall, there were 148 trials, enrolling 60,216 participants (60.5 ± 4.0 years, 40.7% female, 79.1% biologic, targeted, or immune-based therapies) evaluating 99 drugs. Sex was reported in 146 (98.6%) trials, wherein 40.7% (24,538) were women, compared to 59.3% (35,678) men (p < .01). Altogether, women were under-represented in 66.9% trials compared to the proportional incidence of cancers by respective disease type; weight-average PPR of 0.91 (relative difference: -9.1%, p < .01). Women were most under-represented in gastric (PPR = 0.63), liver (PPR = 0.71), and lung (PPR = .81) cancer trials. Sex-based safety data was reported in 4.0% trials. There was no association between adequate female enrollment and drug efficacy (HR: 0.616 vs. 0.613, p = .96). Over time, there was no difference in the percentage of women recruited into clinical trials. Among pivotal clinical trials supporting contemporary FDA-approved cancer drugs, women were frequently under-represented and sex-specific-efficacy and safety-outcomes were commonly not reported.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999069","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}
Pub Date : 2024-12-01Epub Date: 2024-08-23DOI: 10.1002/ijc.35146
Methmi M Perera, Amelia K Smit, Andrea L Smith, Bruna Gallo, Ivy Tan, David Espinoza, Bela I Laginha, Pascale Guitera, Linda K Martin, Anne E Cust
Population-wide skin cancer screening is not currently recommended in most countries. Instead, most clinical guidelines incorporate risk-based recommendations for skin checks, despite limited evidence around implementation and adherence to recommendations in practice. We aimed to determine adherence to personal risk-tailored melanoma skin check schedules and explore reasons influencing adherence. Patients (with/without a previous melanoma) attending tertiary dermatology clinics at the Melanoma Institute Australia, Sydney, Australia, were invited to complete a melanoma risk assessment questionnaire via iPad and provided with personal risk information alongside a risk-tailored skin check schedule. Data were collected from the risk tool, clinician-recorded data on schedule deviations, and appointment booking system. Post-consultation, we conducted semi-structured interviews with patients and clinic staff. We used a convergent segregated mixed methods approach for analysis. Interviews were audio recorded, transcribed and data were analysed thematically. Participant data were analysed from clinic records (n = 247) and interviews (n = 29 patients, 11 staff). Overall, there was 62% adherence to risk-tailored skin check schedules. In cases of non-adherence, skin checks tended to occur more frequently than recommended. Decisions to deviate were similarly influenced by patients (44%) and clinicians (56%). Themes driving non-adherence among patients included anxiety and wanting autonomy around decision-making, and among clinicians included concerns around specific lesions and risk estimate accuracy. There was moderate adherence to a clinical service program of personal risk-tailored skin check recommendations. Further adherence may be gained by incorporating strategies to identify and assist patients with high levels of anxiety and supporting clinicians to communicate risk-based recommendations with patients.
{"title":"Adherence to melanoma screening and surveillance skin check schedules tailored to personal risk.","authors":"Methmi M Perera, Amelia K Smit, Andrea L Smith, Bruna Gallo, Ivy Tan, David Espinoza, Bela I Laginha, Pascale Guitera, Linda K Martin, Anne E Cust","doi":"10.1002/ijc.35146","DOIUrl":"10.1002/ijc.35146","url":null,"abstract":"<p><p>Population-wide skin cancer screening is not currently recommended in most countries. Instead, most clinical guidelines incorporate risk-based recommendations for skin checks, despite limited evidence around implementation and adherence to recommendations in practice. We aimed to determine adherence to personal risk-tailored melanoma skin check schedules and explore reasons influencing adherence. Patients (with/without a previous melanoma) attending tertiary dermatology clinics at the Melanoma Institute Australia, Sydney, Australia, were invited to complete a melanoma risk assessment questionnaire via iPad and provided with personal risk information alongside a risk-tailored skin check schedule. Data were collected from the risk tool, clinician-recorded data on schedule deviations, and appointment booking system. Post-consultation, we conducted semi-structured interviews with patients and clinic staff. We used a convergent segregated mixed methods approach for analysis. Interviews were audio recorded, transcribed and data were analysed thematically. Participant data were analysed from clinic records (n = 247) and interviews (n = 29 patients, 11 staff). Overall, there was 62% adherence to risk-tailored skin check schedules. In cases of non-adherence, skin checks tended to occur more frequently than recommended. Decisions to deviate were similarly influenced by patients (44%) and clinicians (56%). Themes driving non-adherence among patients included anxiety and wanting autonomy around decision-making, and among clinicians included concerns around specific lesions and risk estimate accuracy. There was moderate adherence to a clinical service program of personal risk-tailored skin check recommendations. Further adherence may be gained by incorporating strategies to identify and assist patients with high levels of anxiety and supporting clinicians to communicate risk-based recommendations with patients.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034663","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}
Pub Date : 2024-12-01Epub Date: 2024-07-18DOI: 10.1002/ijc.35094
Mathias Meyer, Hideki Ota, Christina Messiou, Charlotte Benson, Thomas Henzler, Sarah A Mattonen, Daniele Marin, Anna Bartsch, Stefan O Schoenberg, Richard F Riedel, Peter Hohenberger
The purpose of this study was to determine if dual-energy CT (DECT) vital iodine tumor burden (ViTB), a direct assessment of tumor vascularity, allows reliable response assessment in patients with GIST compared to established CT criteria such as RECIST1.1 and modified Choi (mChoi). From 03/2014 to 12/2019, 138 patients (64 years [32-94 years]) with biopsy proven GIST were entered in this prospective, multi-center trial. All patients were treated with tyrosine kinase inhibitors (TKI) and underwent pre-treatment and follow-up DECT examinations for a minimum of 24 months. Response assessment was performed according to RECIST1.1, mChoi, vascular tumor burden (VTB) and DECT ViTB. A change in therapy management could be because of imaging (RECIST1.1 or mChoi) and/or clinical progression. The DECT ViTB criteria had the highest discrimination ability for progression-free survival (PFS) of all criteria in both first line and second line and thereafter treatment, and was significantly superior to RECIST1.1 and mChoi (p < .034). Both, the mChoi and DECT ViTB criteria demonstrated a significantly early median time-to-progression (both delta 2.5 months; both p < .036). Multivariable analysis revealed 6 variables associated with shorter overall survival: secondary mutation (HR = 4.62), polymetastatic disease (HR = 3.02), metastatic second line and thereafter treatment (HR = 2.33), shorter PFS determined by the DECT ViTB criteria (HR = 1.72), multiple organ metastases (HR = 1.51) and lower age (HR = 1.04). DECT ViTB is a reliable response criteria and provides additional value for assessing TKI treatment in GIST patients. A significant superior response discrimination ability for median PFS was observed, including non-responders at first follow-up and patients developing resistance while on therapy.
{"title":"Prospective evaluation of quantitative response parameter in patients with Gastrointestinal Stroma Tumor undergoing tyrosine kinase inhibitor therapy-Impact on clinical outcome.","authors":"Mathias Meyer, Hideki Ota, Christina Messiou, Charlotte Benson, Thomas Henzler, Sarah A Mattonen, Daniele Marin, Anna Bartsch, Stefan O Schoenberg, Richard F Riedel, Peter Hohenberger","doi":"10.1002/ijc.35094","DOIUrl":"10.1002/ijc.35094","url":null,"abstract":"<p><p>The purpose of this study was to determine if dual-energy CT (DECT) vital iodine tumor burden (ViTB), a direct assessment of tumor vascularity, allows reliable response assessment in patients with GIST compared to established CT criteria such as RECIST1.1 and modified Choi (mChoi). From 03/2014 to 12/2019, 138 patients (64 years [32-94 years]) with biopsy proven GIST were entered in this prospective, multi-center trial. All patients were treated with tyrosine kinase inhibitors (TKI) and underwent pre-treatment and follow-up DECT examinations for a minimum of 24 months. Response assessment was performed according to RECIST1.1, mChoi, vascular tumor burden (VTB) and DECT ViTB. A change in therapy management could be because of imaging (RECIST1.1 or mChoi) and/or clinical progression. The DECT ViTB criteria had the highest discrimination ability for progression-free survival (PFS) of all criteria in both first line and second line and thereafter treatment, and was significantly superior to RECIST1.1 and mChoi (p < .034). Both, the mChoi and DECT ViTB criteria demonstrated a significantly early median time-to-progression (both delta 2.5 months; both p < .036). Multivariable analysis revealed 6 variables associated with shorter overall survival: secondary mutation (HR = 4.62), polymetastatic disease (HR = 3.02), metastatic second line and thereafter treatment (HR = 2.33), shorter PFS determined by the DECT ViTB criteria (HR = 1.72), multiple organ metastases (HR = 1.51) and lower age (HR = 1.04). DECT ViTB is a reliable response criteria and provides additional value for assessing TKI treatment in GIST patients. A significant superior response discrimination ability for median PFS was observed, including non-responders at first follow-up and patients developing resistance while on therapy.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632157","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}
Pub Date : 2024-12-01Epub Date: 2024-07-22DOI: 10.1002/ijc.35102
Su-Ran Li, Zhi-Zhong Wu, Hai-Jun Yu, Zhi-Jun Sun
Immunotherapy, especially immune checkpoint blockade therapy, represents a major milestone in the history of cancer therapy. However, the current response rate to immunotherapy among cancer patients must be improved; thus, new strategies for sensitizing patients to immunotherapy are urgently needed. Erythroid progenitor cells (EPCs), a population of immature erythroid cells, exert potent immunosuppressive functions. As a newly recognized immunosuppressive population, EPCs have not yet been effectively targeted. In this review, we summarize the immunoregulatory mechanisms of EPCs, especially for CD45+ EPCs. Moreover, in view of the regulatory effects of EPCs on the tumor microenvironment, we propose the concept of EPC-immunity, present existing strategies for targeting EPCs, and discuss the challenges encountered in both basic research and clinical applications. In particular, the impact of existing cancer treatments on EPCs is discussed, laying the foundation for combination therapies. The aim of this review is to provide new avenues for improving the efficacy of cancer immunotherapy by targeting EPCs.
{"title":"Targeting erythroid progenitor cells for cancer immunotherapy.","authors":"Su-Ran Li, Zhi-Zhong Wu, Hai-Jun Yu, Zhi-Jun Sun","doi":"10.1002/ijc.35102","DOIUrl":"10.1002/ijc.35102","url":null,"abstract":"<p><p>Immunotherapy, especially immune checkpoint blockade therapy, represents a major milestone in the history of cancer therapy. However, the current response rate to immunotherapy among cancer patients must be improved; thus, new strategies for sensitizing patients to immunotherapy are urgently needed. Erythroid progenitor cells (EPCs), a population of immature erythroid cells, exert potent immunosuppressive functions. As a newly recognized immunosuppressive population, EPCs have not yet been effectively targeted. In this review, we summarize the immunoregulatory mechanisms of EPCs, especially for CD45<sup>+</sup> EPCs. Moreover, in view of the regulatory effects of EPCs on the tumor microenvironment, we propose the concept of EPC-immunity, present existing strategies for targeting EPCs, and discuss the challenges encountered in both basic research and clinical applications. In particular, the impact of existing cancer treatments on EPCs is discussed, laying the foundation for combination therapies. The aim of this review is to provide new avenues for improving the efficacy of cancer immunotherapy by targeting EPCs.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747041","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}
Pub Date : 2024-12-01Epub Date: 2024-08-28DOI: 10.1002/ijc.35151
Retraction: B. Pan , H. Ren , Y. Ma , D. Liu , B. Yu , L. Ji , L. Pan , J. Li , L. Yang , X. Lv , X. Shen , B. Chen , Y. Zhang , B. Willard , Y. He , and L. Zheng , "High-Density Lipoprotein of Patients with Type 2 Diabetes Mellitus Elevates the Capability of Promoting Migration and Invasion of Breast Cancer Cells," International Journal of Cancer 131, no. 1 (2012): 70-82. https://doi.org/10.1002/ijc.26341. The above article, published online on 29 April 2011, in Wiley Online Library (wileyonlinelibrary.com), and has been retracted by agreement between the journal Editor-in-Chief, Prof. Christoph Plass; the Union for International Cancer Control; and John Wiley and Sons Ltd. A third party reported that they had detected image similarities between figures 3B and 3F. The publisher requested original raw data and images for all Western Blot figures included in the published article, and in response the authors shared what they reported as raw images. A detailed investigation by the editors revealed additional irregularities in the raw data, including the discovery that the data for the Akt and p-Akt bands in Figure 5A had been manipulated between the original images and those presented in the published article. The retraction has been agreed to as the results presented in the article can no longer be considered reliable. The authors disagree with the retraction.
Retraction:B. Pan , H. Ren , Y. Ma , D. Liu , B. Yu , L. Ji , L. Pan , J. Li , L. Yang , X. Lv , X. Shen , B. Chen , Y. Zhang , B. Willard , Y. He , and L. Zheng , "High-Density Lipoprotein of Patients with Type 2 Diabetes Mellitus Elevates the Capability of Promoting Migration and Invasion of Breast Cancer Cells," International Journal of Cancer 131, no:70-82. https://doi.org/10.1002/ijc.26341.上述文章于 2011 年 4 月 29 日在线发表于 Wiley Online Library (wileyonlinelibrary.com),经期刊主编 Christoph Plass 教授、国际癌症控制联盟和 John Wiley and Sons Ltd.协商后已撤回。第三方报告称,他们发现图 3B 和图 3F 的图像相似。出版商要求提供已发表文章中所有 Western Blot 图的原始数据和图像,作为回应,作者分享了他们报告的原始图像。编辑进行了详细调查,发现原始数据中还有更多不规范之处,包括发现图5A中Akt和p-Akt条带的数据在原始图像和发表文章中的图像之间进行了篡改。由于文章中的结果不再可靠,因此同意撤回。作者不同意撤稿。
{"title":"RETRACTION: High-density lipoprotein of patients with type 2 diabetes mellitus elevates the capability of promoting migration and invasion of breast cancer cells.","authors":"","doi":"10.1002/ijc.35151","DOIUrl":"10.1002/ijc.35151","url":null,"abstract":"<p><p>Retraction: B. Pan , H. Ren , Y. Ma , D. Liu , B. Yu , L. Ji , L. Pan , J. Li , L. Yang , X. Lv , X. Shen , B. Chen , Y. Zhang , B. Willard , Y. He , and L. Zheng , \"High-Density Lipoprotein of Patients with Type 2 Diabetes Mellitus Elevates the Capability of Promoting Migration and Invasion of Breast Cancer Cells,\" International Journal of Cancer 131, no. 1 (2012): 70-82. https://doi.org/10.1002/ijc.26341. The above article, published online on 29 April 2011, in Wiley Online Library (wileyonlinelibrary.com), and has been retracted by agreement between the journal Editor-in-Chief, Prof. Christoph Plass; the Union for International Cancer Control; and John Wiley and Sons Ltd. A third party reported that they had detected image similarities between figures 3B and 3F. The publisher requested original raw data and images for all Western Blot figures included in the published article, and in response the authors shared what they reported as raw images. A detailed investigation by the editors revealed additional irregularities in the raw data, including the discovery that the data for the Akt and p-Akt bands in Figure 5A had been manipulated between the original images and those presented in the published article. The retraction has been agreed to as the results presented in the article can no longer be considered reliable. The authors disagree with the retraction.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078627","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}
Daniela Doege, Julien Frick, Rachel D Eckford, Lena Koch-Gallenkamp, Michael Schlander, Volker Arndt
Treatment modifications and contact restrictions were common during the COVID-19 pandemic and can be stressors for mental health. There is a lack of studies assessing pandemic-related risk factors for anxiety and depression of cancer patients and survivors systematically in multifactorial models. A total of 2391 participants, mean age 65.5 years, ≤5 years post-diagnosis of either lung, prostate, breast, colorectal cancer, or leukemia/lymphoma, were recruited in 2021 via the Baden-Württemberg Cancer Registry, Germany. Sociodemographic information, pandemic-related treatment modifications, contact restrictions, and anxiety/depression (Hospital Anxiety and Depression Scale, HADS) were assessed via self-administered questionnaire. Clinical information (diagnosis, stage, and treatment information) was obtained from the cancer registry. Overall, 22% of participants reported oncological care modifications due to COVID-19, mostly in follow-up care and rehabilitation. Modifications of active cancer treatment were reported by 5.8%. Among those, 50.5% had subclinical anxiety and 55.4% subclinical depression (vs. 37.4% and 45.4%, respectively, for unchanged active treatment). Age <60 years, female sex, lung cancer, low income, and contact restrictions to peer support groups or physicians were identified as independent risk factors for anxiety. Risk factors for depression were lung cancer (both sexes), leukemia/lymphoma (females), recurrence or palliative treatment, living alone, low income, and contact restrictions to relatives, physicians, or caregivers. The study demonstrates that changes in active cancer treatment and contact restrictions are associated with impaired mental well-being. The psychological consequences of treatment changes and the importance for cancer patients to maintain regular contact with their physicians should be considered in future responses to threats to public health.
{"title":"Anxiety and depression in cancer patients and survivors in the context of restrictions in contact and oncological care during the COVID-19 pandemic.","authors":"Daniela Doege, Julien Frick, Rachel D Eckford, Lena Koch-Gallenkamp, Michael Schlander, Volker Arndt","doi":"10.1002/ijc.35204","DOIUrl":"https://doi.org/10.1002/ijc.35204","url":null,"abstract":"<p><p>Treatment modifications and contact restrictions were common during the COVID-19 pandemic and can be stressors for mental health. There is a lack of studies assessing pandemic-related risk factors for anxiety and depression of cancer patients and survivors systematically in multifactorial models. A total of 2391 participants, mean age 65.5 years, ≤5 years post-diagnosis of either lung, prostate, breast, colorectal cancer, or leukemia/lymphoma, were recruited in 2021 via the Baden-Württemberg Cancer Registry, Germany. Sociodemographic information, pandemic-related treatment modifications, contact restrictions, and anxiety/depression (Hospital Anxiety and Depression Scale, HADS) were assessed via self-administered questionnaire. Clinical information (diagnosis, stage, and treatment information) was obtained from the cancer registry. Overall, 22% of participants reported oncological care modifications due to COVID-19, mostly in follow-up care and rehabilitation. Modifications of active cancer treatment were reported by 5.8%. Among those, 50.5% had subclinical anxiety and 55.4% subclinical depression (vs. 37.4% and 45.4%, respectively, for unchanged active treatment). Age <60 years, female sex, lung cancer, low income, and contact restrictions to peer support groups or physicians were identified as independent risk factors for anxiety. Risk factors for depression were lung cancer (both sexes), leukemia/lymphoma (females), recurrence or palliative treatment, living alone, low income, and contact restrictions to relatives, physicians, or caregivers. The study demonstrates that changes in active cancer treatment and contact restrictions are associated with impaired mental well-being. The psychological consequences of treatment changes and the importance for cancer patients to maintain regular contact with their physicians should be considered in future responses to threats to public health.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142363622","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}