Robert T Galvin, Yan Chen, Yan Yuan, Tabitha Cooney, Rebecca Howell, Susan Smith, Michael A Arnold, Miriam Conces, Wendy Leisenring, Gregory T Armstrong, Joseph P Neglia, Lucie M Turcotte
PURPOSE It is not known whether temporal changes in childhood cancer therapy have reduced risk of subsequent malignant neoplasms (SMNs) of the central nervous system (CNS), a frequently fatal late effect of cancer therapy. METHODS Five-year survivors of primary childhood cancers diagnosed between 1970-1999 in the Childhood Cancer Survivor Study with a subsequent CNS SMN were identified. Cumulative incidence rates and standardized incidence ratios (SIR) were compared among survivors diagnosed between 1970-1979 (N = 6223), 1980-1989 (N = 9680), and 1990–1999 (N = 8999). Multivariable models assessed risk factors for CNS SMN. RESULTS 157 CNS SMNs (1970s, 52; 1980s, 63; 1990s, 42) were identified, excluding meningiomas, which were most often malignant gliomas. The proportion of survivors receiving any cranial radiotherapy (CRT) exposure was reduced over time (1970s 77.0%, 1980s 54.3%, 1990s 33.9%), while the proportion receiving >35Gy CRT showed a smaller reduction (11.4%, 10.8%, and 8.5%, respectively). Twenty-year cumulative incidence (95% CI) and SIR (95% CI) for CNS SMN by treatment decade were 0.32% (0.18-0.46%) and 6.6 (5.0–8.7); 0.55% (0.41-0.70%) and 8.3 (6.6-10.4); and 0.43% (0.31-0.55%) and 9.2 (7.0–12.0), respectively, with no statistically significant decreases between eras. Multivariable analyses showed increased risk for CRT dose levels >10Gy and for primary diagnoses of medulloblastoma/PNET (HR 18.7, 9.2-37.9) and astrocytoma (HR 10.1, 5.3-19.5). Three-year cumulative incidence of death after CNS SMN, by treatment decade, were 76%, 74%, and 73%, respectively. CONCLUSION CNS SMN incidence has not decreased despite fewer survivors exposed to CNS-directed radiotherapy. CNS SMNs remain a substantial source of mortality for affected patients.
{"title":"Temporal Trends of Subsequent CNS Malignancies Among Survivors of Childhood Cancer","authors":"Robert T Galvin, Yan Chen, Yan Yuan, Tabitha Cooney, Rebecca Howell, Susan Smith, Michael A Arnold, Miriam Conces, Wendy Leisenring, Gregory T Armstrong, Joseph P Neglia, Lucie M Turcotte","doi":"10.1093/jnci/djaf005","DOIUrl":"https://doi.org/10.1093/jnci/djaf005","url":null,"abstract":"PURPOSE It is not known whether temporal changes in childhood cancer therapy have reduced risk of subsequent malignant neoplasms (SMNs) of the central nervous system (CNS), a frequently fatal late effect of cancer therapy. METHODS Five-year survivors of primary childhood cancers diagnosed between 1970-1999 in the Childhood Cancer Survivor Study with a subsequent CNS SMN were identified. Cumulative incidence rates and standardized incidence ratios (SIR) were compared among survivors diagnosed between 1970-1979 (N = 6223), 1980-1989 (N = 9680), and 1990–1999 (N = 8999). Multivariable models assessed risk factors for CNS SMN. RESULTS 157 CNS SMNs (1970s, 52; 1980s, 63; 1990s, 42) were identified, excluding meningiomas, which were most often malignant gliomas. The proportion of survivors receiving any cranial radiotherapy (CRT) exposure was reduced over time (1970s 77.0%, 1980s 54.3%, 1990s 33.9%), while the proportion receiving >35Gy CRT showed a smaller reduction (11.4%, 10.8%, and 8.5%, respectively). Twenty-year cumulative incidence (95% CI) and SIR (95% CI) for CNS SMN by treatment decade were 0.32% (0.18-0.46%) and 6.6 (5.0–8.7); 0.55% (0.41-0.70%) and 8.3 (6.6-10.4); and 0.43% (0.31-0.55%) and 9.2 (7.0–12.0), respectively, with no statistically significant decreases between eras. Multivariable analyses showed increased risk for CRT dose levels >10Gy and for primary diagnoses of medulloblastoma/PNET (HR 18.7, 9.2-37.9) and astrocytoma (HR 10.1, 5.3-19.5). Three-year cumulative incidence of death after CNS SMN, by treatment decade, were 76%, 74%, and 73%, respectively. CONCLUSION CNS SMN incidence has not decreased despite fewer survivors exposed to CNS-directed radiotherapy. CNS SMNs remain a substantial source of mortality for affected patients.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"83 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142939660","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}
Emily A Burger, Erik E L Jansen, Daniël de Bondt, James Killen, Jennifer C Spencer, Mary Caroline Regan, Megan A Smith, Stephen Sy, Karen Canfell, Inge M C M de Kok, Jane J Kim, Jan A C Hontelez
Population-level estimates in timeframes for reaching cervical cancer (CC) elimination (ie, <4 cases per 100,000 women) in the United States may mask potential disparities in achieving elimination among sub-populations. We used three independent Cancer Intervention and Surveillance Modeling Network (CISNET) models to estimate differences in the time to CC elimination across seven strata of correlated screening and human papillomavirus vaccination uptake, based on national survey data. Compared to the average population, elimination was achieved ≥22 years earlier for the high-uptake strata and ≥27 years later for the most extreme low-uptake strata. Accounting for correlated uptake impacted the population average timeframe by ≤ 1 year. Consequently, national average elimination timeframes mask substantial disparities in reaching elimination among sub-populations. Addressing inequalities in CC control could shorten elimination timeframes and would ensure more equitable elimination across populations. Furthermore, country-level elimination monitoring could be supplemented by monitoring progress in sub-populations.
{"title":"Disparities in cervical cancer elimination timeframes in the United States: a comparative modeling study","authors":"Emily A Burger, Erik E L Jansen, Daniël de Bondt, James Killen, Jennifer C Spencer, Mary Caroline Regan, Megan A Smith, Stephen Sy, Karen Canfell, Inge M C M de Kok, Jane J Kim, Jan A C Hontelez","doi":"10.1093/jnci/djae319","DOIUrl":"https://doi.org/10.1093/jnci/djae319","url":null,"abstract":"Population-level estimates in timeframes for reaching cervical cancer (CC) elimination (ie, &lt;4 cases per 100,000 women) in the United States may mask potential disparities in achieving elimination among sub-populations. We used three independent Cancer Intervention and Surveillance Modeling Network (CISNET) models to estimate differences in the time to CC elimination across seven strata of correlated screening and human papillomavirus vaccination uptake, based on national survey data. Compared to the average population, elimination was achieved ≥22 years earlier for the high-uptake strata and ≥27 years later for the most extreme low-uptake strata. Accounting for correlated uptake impacted the population average timeframe by ≤ 1 year. Consequently, national average elimination timeframes mask substantial disparities in reaching elimination among sub-populations. Addressing inequalities in CC control could shorten elimination timeframes and would ensure more equitable elimination across populations. Furthermore, country-level elimination monitoring could be supplemented by monitoring progress in sub-populations.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142962794","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}
Caitlin C Murphy, Jennifer S Wang, Andrea C Betts, Philip J Lupo, L Aubree Shay, Marlyn A Allicock, Caroline L Kirk, Sandi L Pruitt
Background Few studies have examined childbirth and adverse perinatal outcomes among male adolescents and young adults with cancer (AYAs, diagnosed at age 15-39 years). We conducted a population-based assessment of these outcomes in a large, diverse sample. Methods Male AYAs diagnosed between January 1, 1995 and December 31, 2015 were identified using the Texas Cancer Registry and linked to live birth certificates and the Texas Birth Defects Registry through December 31, 2016. Cumulative incidence of live birth after diagnosis was estimated. Log binomial regression models were used to estimate prevalence of preterm birth (<37 weeks), low birth weight (<2,500 grams), small for gestational age (<10th percentile), and any birth defect among liveborn offspring of male AYAs compared to age- and race/ethnicity-matched men without cancer. Results We identified 42,896 male AYAs, among whom germ cell cancers (20.0%) were the most common. There were 9,686 live births to 6,833 male AYAs after diagnosis. Cumulative incidence of live birth was 18.0% (95% CI 17.6, 18.4) at ten years after diagnosis. Ten-year cumulative incidence differed by cancer type (p < .01) and was highest for thyroid (27.6%, 95% CI 25.4, 29.9) but lowest for gastrointestinal (9.6%, 95% CI 8.1, 10.6) cancer. Prevalence of preterm birth (8.9 vs. 8.0%, p = .02) and low birth weight (6.0 vs. 5.3%, p = .02) was higher for liveborn offspring of male AYAs compared to men without cancer. There was no difference in prevalence of birth defects (4.9 vs. 4.8%, p = .64). Conclusions Our findings underscore the continued importance of reproductive counseling for AYAs.
背景：很少有研究调查患有癌症的男性青少年和年轻成人（AYAs，在15-39岁诊断）的分娩和不良围产期结局。我们在一个大的、多样化的样本中对这些结果进行了基于人群的评估。方法使用德克萨斯州癌症登记处识别1995年1月1日至2015年12月31日诊断的男性aya，并将其与2016年12月31日的活产出生证和德克萨斯州出生缺陷登记处联系起来。估计诊断后活产的累积发生率。使用对数二项回归模型来估计早产（37周）、低出生体重（2500克）、胎龄小（10个百分位数）以及与年龄和种族/民族匹配的未患癌症男性的活产后代的任何出生缺陷的患病率。结果共发现42,896例男性aya，其中生殖细胞癌（20.0%）最为常见。确诊后6833名男性AYAs有9686名活产。诊断后10年的累计活产发生率为18.0% （95% CI 17.6, 18.4）。不同癌症类型的十年累积发病率不同(p <；.01)，甲状腺癌发生率最高（27.6%,95% CI 25.4, 29.9），胃肠道癌发生率最低（9.6%,95% CI 8.1, 10.6）。与没有癌症的男性相比，AYAs男性活产后代的早产患病率（8.9比8.0%,p = 0.02）和低出生体重（6.0比5.3%,p = 0.02）更高。出生缺陷患病率无差异（4.9 vs 4.8%, p = 0.64）。结论：我们的研究结果强调了对青少年青少年进行生殖咨询的持续重要性。
{"title":"Childbirth after cancer among 42,896 male adolescents and young adults: a population-based study","authors":"Caitlin C Murphy, Jennifer S Wang, Andrea C Betts, Philip J Lupo, L Aubree Shay, Marlyn A Allicock, Caroline L Kirk, Sandi L Pruitt","doi":"10.1093/jnci/djae347","DOIUrl":"https://doi.org/10.1093/jnci/djae347","url":null,"abstract":"Background Few studies have examined childbirth and adverse perinatal outcomes among male adolescents and young adults with cancer (AYAs, diagnosed at age 15-39 years). We conducted a population-based assessment of these outcomes in a large, diverse sample. Methods Male AYAs diagnosed between January 1, 1995 and December 31, 2015 were identified using the Texas Cancer Registry and linked to live birth certificates and the Texas Birth Defects Registry through December 31, 2016. Cumulative incidence of live birth after diagnosis was estimated. Log binomial regression models were used to estimate prevalence of preterm birth (&lt;37 weeks), low birth weight (&lt;2,500 grams), small for gestational age (&lt;10th percentile), and any birth defect among liveborn offspring of male AYAs compared to age- and race/ethnicity-matched men without cancer. Results We identified 42,896 male AYAs, among whom germ cell cancers (20.0%) were the most common. There were 9,686 live births to 6,833 male AYAs after diagnosis. Cumulative incidence of live birth was 18.0% (95% CI 17.6, 18.4) at ten years after diagnosis. Ten-year cumulative incidence differed by cancer type (p &lt; .01) and was highest for thyroid (27.6%, 95% CI 25.4, 29.9) but lowest for gastrointestinal (9.6%, 95% CI 8.1, 10.6) cancer. Prevalence of preterm birth (8.9 vs. 8.0%, p = .02) and low birth weight (6.0 vs. 5.3%, p = .02) was higher for liveborn offspring of male AYAs compared to men without cancer. There was no difference in prevalence of birth defects (4.9 vs. 4.8%, p = .64). Conclusions Our findings underscore the continued importance of reproductive counseling for AYAs.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"116 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924963","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}
Austin R Waters, Stephanie B Wheeler, Jeremey Fine, Christabel K Cheung, Kelly R Tan, Donald L Rosenstein, Mya L Roberson, Erin E Kent
Background lesbian, gay, bisexual, transgender, queer, or another non-heterosexual or cisgender identity (LGBTQ+) cancer survivors experience high financial hardship. However, structural drivers of inequities do not impact all LGBTQ+ individuals equally. Using All of Us data, we conducted an intersectional analysis of behavioral financial hardship among LGBTQ+ cancer survivors. Methods LGBTQ+ inequities in behavioral financial hardship (ie, cost-related foregone care, delayed care, and medication alterations) and non-cost-related delayed care were estimated using All of Us Data. Multivariable logit models were used to generate predicted probabilities, average marginal effects (AME), and 95% confidence intervals. Models were then used to estimate inequities when disaggregating LGBTQ+ status and combing LGBTQ+ status with age, race, ethnicity, and treatment status. Results This analysis included N = 36,217 cancer survivors (6.6%, n = 2,399 LGBTQ+). In multivariable models, LGBTQ+ identity was associated with higher probabilities of and significant AME for all types of behavioral financial hardship (foregone care 31.1% vs. 19.4%; delayed care 22.6% vs. 15.6%; medication alterations 19.2% vs. 11.9%) and non-cost delayed care (14.3% vs. 7.2%). Within the disaggregated analysis, cisgender bisexual and another/multiple orientation women and gender minority survivors had the highest predicted probabilities of all outcomes. In intersectional analyses, survivors who were aged 18-39 and LGBTQ+, Black and LGBTQ+, or Hispanic/Latine and LGBTQ+ had the highest predicted probabilities of all outcomes. Conclusions LGBTQ+ cancer survivors experience significantly more behavioral financial hardship and non-cost-related delayed care then non-LGBTQ+ cancer survivors. Interventions at the individual, system, and policy level are needed to address LGBTQ+ inequities in financial hardship.
女同性恋、男同性恋、双性恋、变性人、酷儿或其他非异性恋或顺性身份（LGBTQ+）的癌症幸存者经历了很高的经济困难。然而，不平等的结构性驱动因素并没有平等地影响所有LGBTQ+个人。使用All of Us的数据，我们对LGBTQ+癌症幸存者的行为经济困难进行了交叉分析。方法使用All of Us数据对LGBTQ+在行为经济困难（即与费用相关的放弃治疗、延迟治疗和药物变更）和非与费用相关的延迟治疗方面的不平等进行评估。多变量logit模型用于生成预测概率、平均边际效应（AME）和95%置信区间。然后，将LGBTQ+地位与年龄、种族、民族和待遇状况结合起来，使用模型来估计不平等现象。结果N = 36217例癌症幸存者（6.6%,N = 2399例LGBTQ+）。在多变量模型中，LGBTQ+身份与所有类型的行为经济困难的更高概率和显著AME相关(放弃护理31.1%对19.4%；延迟护理22.6% vs. 15.6%；药物改变（19.2%对11.9%）和非成本延迟护理（14.3%对7.2%）。在分类分析中，顺性双性恋和其他/多重取向的女性和少数性别幸存者在所有结果中的预测概率最高。在交叉分析中，18-39岁的幸存者和LGBTQ+、黑人和LGBTQ+、西班牙裔/拉丁裔和LGBTQ+的所有结果的预测概率最高。结论与非LGBTQ癌症幸存者相比，LGBTQ+癌症幸存者经历了更多的行为经济困难和非成本相关的延迟护理。需要在个人、制度和政策层面进行干预，以解决LGBTQ+群体在经济困难方面的不平等问题。
{"title":"An Intersectional Analysis of Behavioral Financial Hardship and Healthcare Utilization among LGBTQ+ Cancer Survivors","authors":"Austin R Waters, Stephanie B Wheeler, Jeremey Fine, Christabel K Cheung, Kelly R Tan, Donald L Rosenstein, Mya L Roberson, Erin E Kent","doi":"10.1093/jnci/djae350","DOIUrl":"https://doi.org/10.1093/jnci/djae350","url":null,"abstract":"Background lesbian, gay, bisexual, transgender, queer, or another non-heterosexual or cisgender identity (LGBTQ+) cancer survivors experience high financial hardship. However, structural drivers of inequities do not impact all LGBTQ+ individuals equally. Using All of Us data, we conducted an intersectional analysis of behavioral financial hardship among LGBTQ+ cancer survivors. Methods LGBTQ+ inequities in behavioral financial hardship (ie, cost-related foregone care, delayed care, and medication alterations) and non-cost-related delayed care were estimated using All of Us Data. Multivariable logit models were used to generate predicted probabilities, average marginal effects (AME), and 95% confidence intervals. Models were then used to estimate inequities when disaggregating LGBTQ+ status and combing LGBTQ+ status with age, race, ethnicity, and treatment status. Results This analysis included N = 36,217 cancer survivors (6.6%, n = 2,399 LGBTQ+). In multivariable models, LGBTQ+ identity was associated with higher probabilities of and significant AME for all types of behavioral financial hardship (foregone care 31.1% vs. 19.4%; delayed care 22.6% vs. 15.6%; medication alterations 19.2% vs. 11.9%) and non-cost delayed care (14.3% vs. 7.2%). Within the disaggregated analysis, cisgender bisexual and another/multiple orientation women and gender minority survivors had the highest predicted probabilities of all outcomes. In intersectional analyses, survivors who were aged 18-39 and LGBTQ+, Black and LGBTQ+, or Hispanic/Latine and LGBTQ+ had the highest predicted probabilities of all outcomes. Conclusions LGBTQ+ cancer survivors experience significantly more behavioral financial hardship and non-cost-related delayed care then non-LGBTQ+ cancer survivors. Interventions at the individual, system, and policy level are needed to address LGBTQ+ inequities in financial hardship.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142917832","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}
Andrea L Roberts, Mary K Townsend, Lori B Chibnik, Laura D Kubzansky, Shelley S Tworoger
Objective Several studies have suggested that depression may be associated with increased risk of ovarian cancer. Less is known about whether timing matters regarding when depression occurs. To provide evidence for an etiologically relevant exposure period, we examined depression occurring during the time in which precursor lesions develop and progress to invasive carcinoma with risk of developing ovarian cancer. Methods Using data from two prospective cohorts (1992-2015), we divided follow-up into consecutive two-year periods for analytic purposes, referred to as “cancer ascertainment periods.” We estimated associations of depression in the 10 years before each cancer ascertainment period with incident cancer, using Cox proportional hazards models. Next, we estimated associations of depression occurring up to 18 years before each ascertainment period, in two-year increments, with incident cancer. We adjusted for demographic, health, and behavioral factors. All tests of statistical significance were 2-sided, with a p-value threshold of < 0.05. Results Depression occurring in the 10 prior years was associated with 30% greater risk of cancer (hazard ratio (HR)=1.30, 95% confidence interval (CI)=1.15-1.46). Associations were similar in fully adjusted models (HR = 1.27). Depression occurring in the 14 years before ascertainment was associated with elevated risk, although only estimates for depression 0-2, 6-8, and 8-10 years before ascertainment reached statistical significance (HR range, 1.20-1.36). Conclusion Depression occurring up to 14 years before cancer ascertainment was associated with greater cancer risk. This is the time of precursor progression to invasive ovarian carcinoma, suggesting depression may be an ovarian cancer promoting agent.
{"title":"Timing of depression in relation to risk of ovarian cancer","authors":"Andrea L Roberts, Mary K Townsend, Lori B Chibnik, Laura D Kubzansky, Shelley S Tworoger","doi":"10.1093/jnci/djae348","DOIUrl":"https://doi.org/10.1093/jnci/djae348","url":null,"abstract":"Objective Several studies have suggested that depression may be associated with increased risk of ovarian cancer. Less is known about whether timing matters regarding when depression occurs. To provide evidence for an etiologically relevant exposure period, we examined depression occurring during the time in which precursor lesions develop and progress to invasive carcinoma with risk of developing ovarian cancer. Methods Using data from two prospective cohorts (1992-2015), we divided follow-up into consecutive two-year periods for analytic purposes, referred to as “cancer ascertainment periods.” We estimated associations of depression in the 10 years before each cancer ascertainment period with incident cancer, using Cox proportional hazards models. Next, we estimated associations of depression occurring up to 18 years before each ascertainment period, in two-year increments, with incident cancer. We adjusted for demographic, health, and behavioral factors. All tests of statistical significance were 2-sided, with a p-value threshold of &lt; 0.05. Results Depression occurring in the 10 prior years was associated with 30% greater risk of cancer (hazard ratio (HR)=1.30, 95% confidence interval (CI)=1.15-1.46). Associations were similar in fully adjusted models (HR = 1.27). Depression occurring in the 14 years before ascertainment was associated with elevated risk, although only estimates for depression 0-2, 6-8, and 8-10 years before ascertainment reached statistical significance (HR range, 1.20-1.36). Conclusion Depression occurring up to 14 years before cancer ascertainment was associated with greater cancer risk. This is the time of precursor progression to invasive ovarian carcinoma, suggesting depression may be an ovarian cancer promoting agent.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142917407","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}
{"title":"Correction to: Delta-Like Ligand 4-Notch Blockade and Tumor Radiation Response.","authors":"","doi":"10.1093/jnci/djae337","DOIUrl":"https://doi.org/10.1093/jnci/djae337","url":null,"abstract":"","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"70 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887557","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}
Ann Oluloro, Elizabeth M Swisher, Heidi J Gray, Barbara Goff, Kemi M Doll
Background Racial and ethnic minorities remain underrepresented in gynecologic cancer clinical trials despite disproportionately worse oncologic outcomes. Research shows differential racial enrollment patterns due to comorbidity-based exclusion criteria (CEC). Our objective was to evaluate contemporary trends in CECs among NCI-sponsored gynecologic cancer clinical trials and protocol adherence to broadened eligibility criteria guidelines as an assessment of equitable enrollment access. Methods The ClinicalTrials.gov registry was queried for NCI-sponsored gynecologic cancer clinical trials (1994-2021). Study characteristics and CECs were abstracted from protocols. Descriptive statistics and temporal trends were calculated using chi-square testing with STATA v17 software. Results Among 279 clinical trials identified, 65% completed enrollment, 53% were Phase II, and 48% focused on ovarian cancer. Pharmaceutical agents (85%) were the primary therapeutic interventions. Several inequitably restrictive exclusion criteria increased over time such as hepatitis infection (17% in 1994-2000 vs 49% in 2015-2021, p < .001) and cardiovascular disease (47% in 1994-2000 vs 66% in 2015-2021, p = .002). A previously rare exclusion, “mental illness/social situations,” dramatically increased from 5% to 51% (p < .001) over three decades. Adherence to broadened eligibility criteria recommendations was mixed. Renal function, cardiovascular disease, and performance status criteria were not broadened but HIV, prior/concurrent malignancies, and brain metastasis criteria were. Conclusions Some, but not all, of the known restrictive CECs have increased in gynecologic cancer clinical trial design, despite calls for improving racial and ethnic minority representation. While exclusion criteria are critical for trial safety, they must be carefully considered given the differential racial impact on eligibility.
种族和少数民族在妇科癌症临床试验中的代表性仍然不足，尽管肿瘤预后不成比例地差。研究表明，由于基于合并症的排除标准（CEC），不同种族的入学模式存在差异。我们的目的是评估nci赞助的妇科癌症临床试验中CECs的当代趋势，以及扩大资格标准指南的协议遵守情况，以评估公平的入组机会。方法查询ClinicalTrials.gov注册中心1994-2021年nci赞助的妇科癌症临床试验。从方案中提取研究特征和CECs。描述性统计和时间趋势采用STATA v17软件卡方检验计算。结果在279项临床试验中，65%完成入组，53%为II期，48%为卵巢癌。药物（85%）是主要的治疗干预措施。一些不公平的限制性排除标准随着时间的推移而增加，例如肝炎感染（1994-2000年为17%，2015-2021年为49%）。.001)和心血管疾病（1994-2000年47% vs 2015-2021年66%，p = .002）。以前很少被排除在外的“精神疾病/社会状况”从5%急剧增加到51% (p <；.001)。对扩大资格标准建议的遵守情况参差不齐。肾功能、心血管疾病和运动状态标准没有扩大，但艾滋病毒、既往/并发恶性肿瘤和脑转移标准扩大了。结论：尽管人们呼吁提高少数种族和少数民族的代表性，但在妇科癌症临床试验设计中，一些（但不是全部）已知的限制性CECs有所增加。虽然排除标准对试验安全至关重要，但考虑到种族对资格的不同影响，必须仔细考虑排除标准。
{"title":"Gynecologic cancer clinical trial eligibility criteria as a marker for equitable clinical trial access","authors":"Ann Oluloro, Elizabeth M Swisher, Heidi J Gray, Barbara Goff, Kemi M Doll","doi":"10.1093/jnci/djae338","DOIUrl":"https://doi.org/10.1093/jnci/djae338","url":null,"abstract":"Background Racial and ethnic minorities remain underrepresented in gynecologic cancer clinical trials despite disproportionately worse oncologic outcomes. Research shows differential racial enrollment patterns due to comorbidity-based exclusion criteria (CEC). Our objective was to evaluate contemporary trends in CECs among NCI-sponsored gynecologic cancer clinical trials and protocol adherence to broadened eligibility criteria guidelines as an assessment of equitable enrollment access. Methods The ClinicalTrials.gov registry was queried for NCI-sponsored gynecologic cancer clinical trials (1994-2021). Study characteristics and CECs were abstracted from protocols. Descriptive statistics and temporal trends were calculated using chi-square testing with STATA v17 software. Results Among 279 clinical trials identified, 65% completed enrollment, 53% were Phase II, and 48% focused on ovarian cancer. Pharmaceutical agents (85%) were the primary therapeutic interventions. Several inequitably restrictive exclusion criteria increased over time such as hepatitis infection (17% in 1994-2000 vs 49% in 2015-2021, p &lt; .001) and cardiovascular disease (47% in 1994-2000 vs 66% in 2015-2021, p = .002). A previously rare exclusion, “mental illness/social situations,” dramatically increased from 5% to 51% (p &lt; .001) over three decades. Adherence to broadened eligibility criteria recommendations was mixed. Renal function, cardiovascular disease, and performance status criteria were not broadened but HIV, prior/concurrent malignancies, and brain metastasis criteria were. Conclusions Some, but not all, of the known restrictive CECs have increased in gynecologic cancer clinical trial design, despite calls for improving racial and ethnic minority representation. While exclusion criteria are critical for trial safety, they must be carefully considered given the differential racial impact on eligibility.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"86 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142858417","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}
Xinyi Li, Jinhee Hur, Yin Zhang, Mingyang Song, Stephanie A Smith-Warner, Liming Liang, Kenneth J Mukamal, Eric B Rimm, Edward L Giovannucci
Background Association between light to moderate alcohol consumption and colorectal cancer (CRC) incidence remains understudied, especially regarding drinking pattern, beverage type and temporal aspects. Methods Hazard ratios (HRs) and 95% confidence intervals (CIs) for time to CRC diagnosis were estimated among 137,710 participants. Estimates based on remote (eg, >10 years before follow-up) and recent (eg, the preceding 10 years before follow-up) alcohol intake, using different cutoffs (eg, 8, 10, 12 years, etc) and mutual adjustment, enabled separating independent effects and investigating time lag of alcohol-CRC association. Results 3,599 CRC cases were documented over three decades. Light to moderate drinking was associated with an increased CRC risk only in men: HR (95% CI) for 5-14.9 and 15-29.9 vs 0 g/day of alcohol intake was 1.19 (1.01, 1.41) and 1.38 (1.13, 1.67). In women, that for 0.1-4.9 and 5-14.9 vs 0 g/day of alcohol was 1.07 (0.96, 1.20) and 1.05 (0.91, 1.20). Drinkers with both high drinking frequency and daily intake had the highest CRC risk, suggesting total alcohol intake was the critical factor. We estimated the time lag between alcohol consumption and CRC occurrence to be 8 to 12 years. Former drinkers did not experience a significant reduction in CRC risk even after 10 years of quitting or reducing consumption. Conclusions Based on two cohorts of health professionals, our findings suggest that the increased risk of CRC associated with alcohol intake is mainly driven by total quantity and remote intake. Former drinkers did not experience an immediate reduction in CRC risk after quitting or reducing consumption.
{"title":"Drinking pattern and time lag of alcohol consumption with colorectal cancer risk in US men and women","authors":"Xinyi Li, Jinhee Hur, Yin Zhang, Mingyang Song, Stephanie A Smith-Warner, Liming Liang, Kenneth J Mukamal, Eric B Rimm, Edward L Giovannucci","doi":"10.1093/jnci/djae330","DOIUrl":"https://doi.org/10.1093/jnci/djae330","url":null,"abstract":"Background Association between light to moderate alcohol consumption and colorectal cancer (CRC) incidence remains understudied, especially regarding drinking pattern, beverage type and temporal aspects. Methods Hazard ratios (HRs) and 95% confidence intervals (CIs) for time to CRC diagnosis were estimated among 137,710 participants. Estimates based on remote (eg, &gt;10 years before follow-up) and recent (eg, the preceding 10 years before follow-up) alcohol intake, using different cutoffs (eg, 8, 10, 12 years, etc) and mutual adjustment, enabled separating independent effects and investigating time lag of alcohol-CRC association. Results 3,599 CRC cases were documented over three decades. Light to moderate drinking was associated with an increased CRC risk only in men: HR (95% CI) for 5-14.9 and 15-29.9 vs 0 g/day of alcohol intake was 1.19 (1.01, 1.41) and 1.38 (1.13, 1.67). In women, that for 0.1-4.9 and 5-14.9 vs 0 g/day of alcohol was 1.07 (0.96, 1.20) and 1.05 (0.91, 1.20). Drinkers with both high drinking frequency and daily intake had the highest CRC risk, suggesting total alcohol intake was the critical factor. We estimated the time lag between alcohol consumption and CRC occurrence to be 8 to 12 years. Former drinkers did not experience a significant reduction in CRC risk even after 10 years of quitting or reducing consumption. Conclusions Based on two cohorts of health professionals, our findings suggest that the increased risk of CRC associated with alcohol intake is mainly driven by total quantity and remote intake. Former drinkers did not experience an immediate reduction in CRC risk after quitting or reducing consumption.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"58 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841556","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}
Suhair Lolas-Hamameh, Sari Lieberman, Alaa Sarahneh, Tom Walsh, Ming K Lee, Suleyman Gulsuner, Grace Rabie, Rachel Beeri, Amal Aburayyan, Jessica B Mandell, Hila Fridman, Galit Lazer-Derbeko, Tehila Klopstock, Orit Freireich, Amnon Lahad, Mary-Claire King, Ephrat Levy-Lahad, Moien N Kanaan
Pathogenic TP53 germline variants cause young-onset breast cancer and other cancers of the Li-Fraumeni syndrome (LFS) spectrum, but the clinical consequences of partial-loss-of function TP53 variants are incompletely understood. In the consecutive cohort of Palestinian breast cancer patients of the Middle East Breast Cancer Study (MEBCS), breast cancer risk among TP53 p. R181C heterozygotes was 50% by age 50 y and 81% by age 80 y. In contrast, prevalence of pediatric cancers in the MEBCS was similar among first degree relatives of TP53 p. R181C carriers (3/519 = 0.0058) and first degree relatives of MEBCS patients with no pathogenic germline variant in any known breast cancer gene (7/1082 = 0.0065; OR = 0.90, 95%CI [0.23,3.49], Fisher P = .90 (2-tailed)). This result suggests that in families harboring this TP53 allele, genetic testing in children is unwarranted, and screening children for LFS tumors is unnecessary. More generally, some TP53 missense alleles can predispose to very high risk of breast cancer without pleiotropic effects.
致病性TP53种系变异可导致年轻发病的乳腺癌和其他Li-Fraumeni综合征（LFS）谱系的癌症，但TP53变异部分功能丧失的临床后果尚不完全清楚。连续队列的中东巴勒斯坦乳腺癌患者乳腺癌研究(MEBCS), TP53 p . R181C杂合的罹患乳腺癌的风险为50%按年龄50到80岁y y和81%。相比之下,小儿癌症患病率在MEBCS相似TP53的一级亲属中p。R181C运营商(3/519 = 0.0058)和MEBCS患者的一级亲属中没有致病性生殖系在任何已知的乳腺癌基因变体(7/1082 = 0.0065;OR = 0.90, 95%CI [0.23,3.49], Fisher P = 0.90（双尾）)。这一结果表明，在携带TP53等位基因的家庭中，没有必要对儿童进行基因检测，也没有必要对儿童进行LFS肿瘤筛查。更普遍的是，一些TP53错义等位基因可以使乳腺癌的风险非常高，但没有多效性效应。
{"title":"TP53 missense allele predisposing to high risk of breast cancer but not pediatric cancers","authors":"Suhair Lolas-Hamameh, Sari Lieberman, Alaa Sarahneh, Tom Walsh, Ming K Lee, Suleyman Gulsuner, Grace Rabie, Rachel Beeri, Amal Aburayyan, Jessica B Mandell, Hila Fridman, Galit Lazer-Derbeko, Tehila Klopstock, Orit Freireich, Amnon Lahad, Mary-Claire King, Ephrat Levy-Lahad, Moien N Kanaan","doi":"10.1093/jnci/djae334","DOIUrl":"https://doi.org/10.1093/jnci/djae334","url":null,"abstract":"Pathogenic TP53 germline variants cause young-onset breast cancer and other cancers of the Li-Fraumeni syndrome (LFS) spectrum, but the clinical consequences of partial-loss-of function TP53 variants are incompletely understood. In the consecutive cohort of Palestinian breast cancer patients of the Middle East Breast Cancer Study (MEBCS), breast cancer risk among TP53 p. R181C heterozygotes was 50% by age 50 y and 81% by age 80 y. In contrast, prevalence of pediatric cancers in the MEBCS was similar among first degree relatives of TP53 p. R181C carriers (3/519 = 0.0058) and first degree relatives of MEBCS patients with no pathogenic germline variant in any known breast cancer gene (7/1082 = 0.0065; OR = 0.90, 95%CI [0.23,3.49], Fisher P = .90 (2-tailed)). This result suggests that in families harboring this TP53 allele, genetic testing in children is unwarranted, and screening children for LFS tumors is unnecessary. More generally, some TP53 missense alleles can predispose to very high risk of breast cancer without pleiotropic effects.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823185","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}
Heidi Moseson, Sachiko Ragosta, Anu Manchikanti Gómez, Jae Corman, Jay Zussman, Bori Lesser-Lee, Sydney Reese, India Rose Carter-Bolick, Juno Obedin-Maliver
Objectives To evaluate the acceptability and performance of an organ inventory as an alternative to asking about gender and/or sex assigned at birth in cancer screening. Methods We fielded an online, self-administered survey to a convenience sample of English- or Spanish-speaking transgender and gender-diverse (TGD), intersex, and cisgender people (>/=15 years) in the US. The survey contained an organ inventory developed with community input and questions regarding acceptability. The primary outcome was organ inventory acceptability by the four-item Acceptability of Intervention Measure (AIM). Additional outcomes included inter-method screening agreement between the organ inventory, gender, and sex assigned at birth. Results In 2022, 333 eligible individuals completed the survey; 44.4% cisgender, 34.2% TGD, and 14.1% intersex. Overall, participants rated the organ inventory as acceptable (median AIM score = 18/20, IQR: 16-20). Most (73%) found it easy to understand, and comfortable to complete (65%). Cancer screening eligibility varied based on the method used; relying solely on gender or sex data would have missed some eligible participants that the organ inventory identified. Conclusions Using an organ inventory as an alternative to gender or sex-based screening questions was acceptable, and has implications for addressing cancer screening disparities.
{"title":"Acceptability of an organ inventory for cancer screening across gender identity and intersex status","authors":"Heidi Moseson, Sachiko Ragosta, Anu Manchikanti Gómez, Jae Corman, Jay Zussman, Bori Lesser-Lee, Sydney Reese, India Rose Carter-Bolick, Juno Obedin-Maliver","doi":"10.1093/jnci/djae336","DOIUrl":"https://doi.org/10.1093/jnci/djae336","url":null,"abstract":"Objectives To evaluate the acceptability and performance of an organ inventory as an alternative to asking about gender and/or sex assigned at birth in cancer screening. Methods We fielded an online, self-administered survey to a convenience sample of English- or Spanish-speaking transgender and gender-diverse (TGD), intersex, and cisgender people (&gt;/=15 years) in the US. The survey contained an organ inventory developed with community input and questions regarding acceptability. The primary outcome was organ inventory acceptability by the four-item Acceptability of Intervention Measure (AIM). Additional outcomes included inter-method screening agreement between the organ inventory, gender, and sex assigned at birth. Results In 2022, 333 eligible individuals completed the survey; 44.4% cisgender, 34.2% TGD, and 14.1% intersex. Overall, participants rated the organ inventory as acceptable (median AIM score = 18/20, IQR: 16-20). Most (73%) found it easy to understand, and comfortable to complete (65%). Cancer screening eligibility varied based on the method used; relying solely on gender or sex data would have missed some eligible participants that the organ inventory identified. Conclusions Using an organ inventory as an alternative to gender or sex-based screening questions was acceptable, and has implications for addressing cancer screening disparities.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"146 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820868","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}
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