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Costs of care during chimeric antigen receptor T-cell therapy in relapsed or refractory B-cell lymphomas. 嵌合抗原受体 T 细胞疗法治疗复发/难治性 B 细胞淋巴瘤的护理成本。
IF 3.4 Q2 ONCOLOGY Pub Date : 2024-07-01 DOI: 10.1093/jncics/pkae059
Mengyang Di, Kunal C Potnis, Jessica B Long, Iris Isufi, Francine Foss, Stuart Seropian, Cary P Gross, Scott F Huntington

High upfront cost may be a barrier to adopting chimeric antigen receptor T-cell (CAR-T) therapy for relapsed or refractory B-cell lymphoma. Data on the real-world costs are limited. Using the Blue Cross Blue Shield Axis database, we evaluated 271 commercially insured patients who received CAR-T therapy for B-cell lymphoma (median age = 58 years; men = 68%; diffuse large B-cell lymphoma = 87%; inpatient CAR-T therapy = 85%). Our peri-CAR-T period of interest was from 41 days before to 154 days after CAR-T therapy index divided into seven 28-day intervals. Median total costs were $608 100 (interquartile range, IQR = $534 100-$732 800); 8.5% of patients had total costs exceeding $1 million. The median cost of CAR-T therapy products was $402 500, and the median out-of-pocket copayment was $510. Monthly costs were highest during the month of CAR-T therapy administration (median = $521 500), with median costs below $25 000 in all other 28-day intervals. Costs of CAR-T therapy use were substantial, largely driven by product acquisition. Future studies should examine the relationship between costs, access, and financial outcomes.

高昂的前期费用可能会阻碍采用嵌合抗原受体 T 细胞疗法(CAR-T)治疗复发/难治性 B 细胞淋巴瘤(BCL)。有关真实世界成本的数据十分有限。利用蓝十字蓝盾轴数据库,我们对 271 名接受 CAR-T 治疗 BCL 的商业保险患者进行了评估(中位年龄:58 岁,男性:68%,弥漫性大 BCL:87%,住院 CAR-T:85%)。我们关注的围 CAR-T 期包括从 CAR-T 指数开始的 -41 天到 + 154 天,分为 7 个 28 天的间隔期。总费用中位数为 608,100 美元(四分位间范围:534,100 美元-732,800 美元);8.5% 的患者总费用超过 1,000,000 美元。CAR-T 产品的费用中位数为 402,500 美元,自付部分的费用中位数为 510 美元。在使用 CAR-T 的当月,每月费用最高(中位数:521,500 美元),中位数费用如下
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引用次数: 0
Advancing clinical trial equity through integration of telehealth and decentralized treatment. 通过整合远程医疗和分散治疗促进临床试验公平。
IF 3.4 Q2 ONCOLOGY Pub Date : 2024-07-01 DOI: 10.1093/jncics/pkae050
Eleanor Brown, George Albert Fisher, Andrew Shelton, Daniel T Chang, Erqi Pollom

Innovative strategies to increase clinical trial accessibility and equity are needed. We conducted a retrospective review of a phase II investigator-initiated trial to determine whether the modification of clinical trial design to decentralize study treatment can improve trial accessibility among underrepresented groups. Sociodemographic characteristics, including area deprivation indices, as well as study site travel distance, time, and costs were compared between enrolled participants who received chemotherapy locally and participants who did not. Participants who received chemotherapy locally lived substantially farther from the study site (median = 95.90 vs 25.20 miles, P = .004), faced a greater time burden traveling to the study site (median = 115.00 vs 34.00 minutes, P = .002), and had higher travel-related costs for a single trip to the study site (median = $62.81 vs $16.51, P = .004). This study highlights opportunities for alleviating financial and time burdens associated with clinical trial participation, promoting equity in clinical research. Trial Registration: ClinicalTrials.gov identifier: NCT04380337.

我们需要创新的策略来提高临床试验的可及性和公平性。我们对一项由研究者发起的 II 期试验进行了回顾性研究,以确定修改临床试验设计以分散研究治疗是否能提高代表性不足群体的试验可及性。研究人员比较了在当地接受化疗的参与者与不在当地接受化疗的参与者的社会人口学特征,包括地区剥夺指数以及研究地点的旅行距离、时间和费用。在当地接受化疗的参与者居住地距离研究地点明显较远(中位数为 95.90 英里 vs 25.20 英里,p = .004),前往研究地点的时间负担较重(中位数为 115.00 分钟 vs 34.00 分钟,p = .002),前往研究地点的单次旅行相关费用较高(中位数为 62.81 美元 vs 16.51 美元,p = .004)。本研究强调了减轻与参与临床试验相关的经济和时间毒性的机会,促进了临床研究的公平性。
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引用次数: 0
Social networks, social determinants, and mortality: Western New York Exposures and Breast Cancer study. 社会网络、社会决定因素和死亡率:纽约西部暴露与乳腺癌 (WEB) 研究》。
IF 3.4 Q2 ONCOLOGY Pub Date : 2024-07-01 DOI: 10.1093/jncics/pkae057
Shipra Gandhi, Jing Nie, Maurizio Trevisan, Kristopher Attwood, Jo L Freudenheim

Background: There are few studies of social support and other social determinants of health after breast cancer diagnosis and their associations with mortality; results have been inconclusive. Further, it is not known if observed associations are specific to women with breast cancer diagnosis or if associations would be similar among healthy women.

Methods: Women with incident, pathologically confirmed invasive breast cancer, stage I-IV (n = 1012), and healthy frequency age-matched participants (n = 2036) answered a social support questionnaire in prospective follow-up of a population-based case-control study, the Western New York Exposures and Breast Cancer Study. At interview, all participants were aged 35-79 years and resident of 2 counties in Western New York State. Mortality status was ascertained from the National Death Index. Participants were queried regarding the number of their close friends, frequency of seeing them, household size, household income, and marital status. Hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer-specific mortality (breast cancer women only) and all-cause mortality were estimated.

Results: Lower household income was associated with higher all-cause mortality among women diagnosed with breast cancer (HR = 2.48, 95% CI = 1.24 to 4.97) and similarly among the healthy women (HR = 2.63, 95% CI = 1.25 to 5.53). Number and frequency of seeing friends, marital status, and household size were not associated with mortality, either among breast cancer patients or among healthy women.

Conclusion: Among those diagnosed with breast cancer and healthy women, lower income was associated with more than twice the mortality. Marital status, household size, and number or frequency of meeting friends were not associated with survival.

背景:关于乳腺癌(BC)确诊后的社会支持和其他决定健康的社会因素及其与死亡率的关系的研究很少;结果也不确定。此外,尚不清楚所观察到的关联是否仅针对确诊为乳腺癌的女性,或者是否与健康女性的关联相似:方法:在一项基于人群的病例对照研究 "纽约西部暴露与乳腺癌(WEB)研究 "的前瞻性随访中,患有经病理证实的浸润性乳腺癌 I-IV 期的女性(n = 1012)和年龄匹配的健康频率对照组(n = 2036)回答了一份社会支持问卷。受访时,所有参与者的年龄都在 35-79 岁之间,居住在纽约州西部的两个县。死亡状况由国家死亡指数确定。研究人员询问了参与者密友的数量、与密友见面的频率、家庭规模、家庭收入和婚姻状况。结果发现,家庭收入越低,全因死亡率越高:结果:家庭收入越低,确诊为乳腺癌的妇女的全因死亡率越高(HR 2.48,95% CI,1.24-4.97),健康妇女的全因死亡率也较高(HR 2.63,95% CI,1.25-5.53)。无论是在 BC 患者中还是在健康女性中,与朋友见面的次数和频率、婚姻状况和家庭规模都与死亡率无关:结论:在确诊为乳腺癌的患者和健康女性中,收入越低,死亡率越高。婚姻状况、家庭规模、与朋友见面的次数或频率与存活率无关。
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引用次数: 0
Neighborhood-level social determinants of health burden among adolescent and young adult cancer patients and impact on overall survival. 青少年癌症患者健康负担的邻里层面社会决定因素及其对总生存期的影响。
IF 3.4 Q2 ONCOLOGY Pub Date : 2024-07-01 DOI: 10.1093/jncics/pkae062
Elizabeth R Rodriguez, Tori Tonn, Midhat Jafry, Sairah Ahmed, Branko Cuglievan, J Andrew Livingston, Christopher R Flowers, Gregory J Aune, Karen H Albritton, Michael E Roth, Qian Xiao, Michelle A T Hildebrandt

Background: Neighborhood socioeconomic deprivation has been linked to adverse health outcomes, yet it is unclear whether neighborhood-level social determinants of health (SDOH) measures affect overall survival in adolescent and young adult patients with cancer.

Methods: This study used a diverse cohort of adolescent and young adult patients with cancer (N = 10 261) seen at MD Anderson Cancer Center. Zip codes were linked to Area Deprivation Index (ADI) values, a validated neighborhood-level SDOH measure, with higher ADI values representing worse SDOH.

Results: ADI was statistically significantly worse (P < .050) for Black (61.7) and Hispanic (65.3) patients than for White patients (51.2). Analysis of ADI by cancer type showed statistically significant differences, mainly driven by worse ADI in patients with cervical cancer (62.3) than with other cancers. In multivariable models including sex, age at diagnosis, cancer diagnosis, and race and ethnicity, risk of shorter survival for people residing in neighborhoods with the least favorable ADI quartile was greater than for individuals in the most favorable ADI quartile (hazard ratio = 1.09, 95% confidence interval = 1.00 to 1.19, P = .043).

Conclusion: Adolescent and young adult patients with cancer and the worst ADI values experienced a nearly 10% increase in risk of dying than patients with more favorable ADI values. This effect was strongest among White adolescent and young adult survivors. Although the magnitude of the effect of ADI on survival was moderate, the presence of a relationship between neighborhood-level SDOH and survival among patients who received care at a tertiary cancer center suggests that ADI is a meaningful predictor of survival. These findings provide intriguing evidence for potential interventions aimed at supporting adolescent and young adult patients with cancer from disadvantaged neighborhoods.

目的:邻里社会经济贫困与不良健康结果有关,但邻里层面的健康社会决定因素(SDOH)措施是否会影响青少年和年轻成人癌症患者的总体生存率尚不清楚:本研究使用了在 MD 安德森癌症中心就诊的不同青少年和青年癌症患者队列(N = 10,261)。邮政编码与地区贫困指数(ADI)值相关联,ADI是一种经过验证的邻里层面SDOH测量方法,ADI越高代表SDOH越差:结果:ADI 明显更差(P与 ADI 值较高的患者相比,ADI 值最差的青壮年癌症患者的死亡风险增加了近 10%,这种影响在白人青壮年幸存者中最为明显。虽然 ADI 对存活率的影响程度不大,但在三级癌症中心接受治疗的患者中,邻里层面的 SDOH 与存活率之间存在关系,这表明 ADI 是一个有意义的存活率预测指标。这些发现为旨在支持来自弱势社区的青少年癌症患者的潜在干预措施提供了耐人寻味的证据。
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引用次数: 0
Perspectives of pediatric oncologists on referral for CAR-T therapy: a mixed methods pilot study. 儿科肿瘤专家对 CAR-T 疗法转诊的看法:一项混合方法试点研究。
IF 3.4 Q2 ONCOLOGY Pub Date : 2024-07-01 DOI: 10.1093/jncics/pkae063
Anurekha G Hall, Devan M Duenas, Jenna Voutsinas, Qian Wu, Adam J Lamble, Elizabeth Gruber, Benjamin Wilfond, Julie R Park, Anurag K Agrawal, Jonathan M Marron

Background: Receipt of chimeric antigen receptor T-cell (CAR-T) therapy at an institution different from the primary oncologist's institution is a complex, multistep process. Referral by oncologists plays an important role in the process but may be susceptible to bias.

Methods: Oncologists who previously referred patients for CAR-T therapy at 5 pediatric hospitals were sent surveys by email exploring their CAR-T referral practices. Descriptive statistics were generated, and multivariate analyses examined associations among oncologist characteristics, familiarity with CAR-T therapy, and referral practices. We conducted semistructured interviews with a subset of participants and used thematic analysis to code transcripts.

Results: Sixty-eight oncologists completed the survey; 77% expressed being "very familiar" with CAR-T therapy. Hispanic oncologists and oncologists at institutions with 50 or fewer new diagnoses per year were more likely to identify as less familiar with CAR-T therapy (odds ratio [OR] = 64.3, 95% confidence interval [CI] = 2.45 to 10 452.50, P = .04 and OR = 24.5, 95% CI = 3.3 to 317.3, P = .005, respectively). In total, 38% of respondents considered nonclinical features (compliance, social support, resources, insurance, language, education, and race or ethnicity) influential in referral decisions. Oncologists who were Hispanic and oncologists who had been practicing for 20 or more years were more likely to consider these features significantly influential (OR = 14.52, 95% CI = 1.49 to 358.66, P = .04 and OR = 6.76, 95% CI = 1.18 to 50.5, P = .04). Nine oncologists completed in-depth interviews; common themes included barriers and concerns regarding CAR-T therapy referral, the value of an established relationship with a CAR-T therapy center, and poor communication after CAR-T therapy.

Conclusions: Nearly 40% of oncologists consider nonclinical features significantly influential when deciding to refer patients for CAR-T therapy, raising concern for bias in the referral process. Establishing formal partnerships with CAR-T therapy centers may help address physician barriers in referral.

背景:在不同机构接受 CAR-T 治疗是一个复杂、多步骤的过程:在不同机构接受 CAR-T 治疗是一个复杂、多步骤的过程;肿瘤学家的转诊在这一过程中起着重要作用,但可能容易出现偏差:通过电子邮件向曾为五家儿科医院的 CAR-T 患者转诊的肿瘤学家发送调查问卷,探讨他们的 CAR-T 转诊做法。我们进行了描述性统计,并通过多变量分析研究了肿瘤学家的特征、对 CAR-T 的熟悉程度和转诊实践之间的关联。我们对部分参与者进行了半结构化访谈,并使用主题分析法对记录誊本进行编码:68名肿瘤学家完成了调查,其中77%(n = 44)的人表示 "非常熟悉 "CAR-T。西班牙裔肿瘤学家和每年新诊断病例少于 50 例的机构的肿瘤学家更有可能认为自己对 CAR-T 不太熟悉(OR 64.3 (CI:2.45-10452.5),p = 0.04 和 OR 24.5 (CI:3.3-317.3),p = 0.005)。38%的人认为非临床特征(依从性、社会支持、资源、保险、语言、教育、种族或民族)对转诊决定有影响。西班牙裔肿瘤学家和从业 20 年以上的肿瘤学家更有可能认为这些特征具有重大影响(OR 14.52 (CI:1.49-358.66),p = 0.04 和 OR 6.76 (CI:1.18-50.5),p = 0.04)。九名肿瘤学家完成了深度访谈;共同主题包括 CAR-T 转诊的障碍和顾虑、与 CAR-T 中心建立关系的价值以及 CAR-T 后沟通不畅:近 40% 的肿瘤学家认为,在决定是否将患者转诊接受 CAR-T 治疗时,非临床特征会产生重大影响,这引起了人们对转诊过程中存在偏见的担忧。与CAR-T中心建立正式的合作关系可能有助于解决医生在转诊过程中遇到的障碍。
{"title":"Perspectives of pediatric oncologists on referral for CAR-T therapy: a mixed methods pilot study.","authors":"Anurekha G Hall, Devan M Duenas, Jenna Voutsinas, Qian Wu, Adam J Lamble, Elizabeth Gruber, Benjamin Wilfond, Julie R Park, Anurag K Agrawal, Jonathan M Marron","doi":"10.1093/jncics/pkae063","DOIUrl":"10.1093/jncics/pkae063","url":null,"abstract":"<p><strong>Background: </strong>Receipt of chimeric antigen receptor T-cell (CAR-T) therapy at an institution different from the primary oncologist's institution is a complex, multistep process. Referral by oncologists plays an important role in the process but may be susceptible to bias.</p><p><strong>Methods: </strong>Oncologists who previously referred patients for CAR-T therapy at 5 pediatric hospitals were sent surveys by email exploring their CAR-T referral practices. Descriptive statistics were generated, and multivariate analyses examined associations among oncologist characteristics, familiarity with CAR-T therapy, and referral practices. We conducted semistructured interviews with a subset of participants and used thematic analysis to code transcripts.</p><p><strong>Results: </strong>Sixty-eight oncologists completed the survey; 77% expressed being \"very familiar\" with CAR-T therapy. Hispanic oncologists and oncologists at institutions with 50 or fewer new diagnoses per year were more likely to identify as less familiar with CAR-T therapy (odds ratio [OR] = 64.3, 95% confidence interval [CI] = 2.45 to 10 452.50, P = .04 and OR = 24.5, 95% CI = 3.3 to 317.3, P = .005, respectively). In total, 38% of respondents considered nonclinical features (compliance, social support, resources, insurance, language, education, and race or ethnicity) influential in referral decisions. Oncologists who were Hispanic and oncologists who had been practicing for 20 or more years were more likely to consider these features significantly influential (OR = 14.52, 95% CI = 1.49 to 358.66, P = .04 and OR = 6.76, 95% CI = 1.18 to 50.5, P = .04). Nine oncologists completed in-depth interviews; common themes included barriers and concerns regarding CAR-T therapy referral, the value of an established relationship with a CAR-T therapy center, and poor communication after CAR-T therapy.</p><p><strong>Conclusions: </strong>Nearly 40% of oncologists consider nonclinical features significantly influential when deciding to refer patients for CAR-T therapy, raising concern for bias in the referral process. Establishing formal partnerships with CAR-T therapy centers may help address physician barriers in referral.</p>","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Travel-time barriers to specialized cancer care for adolescents and young adults with acute lymphoblastic leukemia. 患有急性白血病的青少年接受专门癌症治疗的旅行时间障碍。
IF 3.4 Q2 ONCOLOGY Pub Date : 2024-07-01 DOI: 10.1093/jncics/pkae046
Helen M Parsons, Lori S Muffly, Ariadna Garcia, Amy Zhang, Kate Miller, David Van Riper, Kate Knowles, Theresa H Keegan

Background: Prior studies demonstrate that 20%-50% of adolescents and young adults (age 15-39 years) with acute lymphoblastic leukemia (ALL) receive care at specialty cancer centers, yet a survival benefit has been observed for patients at these sites. Our objective was to identify patients at risk of severe geographic barriers to specialty cancer center-level care.

Methods: We used data from the North American Association of Central Cancer Registries Cancer in North America database to identify adolescent and young adult ALL patients diagnosed between 2004 and 2016 across 43 US states. We calculated driving distance and travel time from counties where participants lived to the closest specialty cancer center sites. We then used multivariable logistic regression models to examine the relationship between sociodemographic characteristics of counties where adolescent and young adult ALL patients resided and the need to travel more than 1 hour to obtain care at a specialty cancer center.

Results: Among 11 813 adolescent and young adult ALL patients, 43.4% were aged 25-39 years, 65.5% were male, 32.9% were Hispanic, and 28.7% had public insurance. We found 23.6% of adolescent and young adult ALL patients from 60.8% of included US counties would be required to travel more than 1 hour one way to access a specialty cancer center. Multivariable models demonstrate that patients living in counties that are nonmetropolitan, with lower levels of educational attainment, with higher income inequality, with lower internet access, located in primary care physician shortage areas, and with fewer hospitals providing chemotherapy services are more likely to travel more than 1 hour to access a specialty cancer center.

Conclusions: Substantial travel-related barriers exist to accessing care at specialty cancer centers across the United States, particularly for patients living in areas with greater concentrations of historically marginalized communities.

背景:先前的研究表明,20%-50%的急性淋巴细胞白血病(ALL)青少年和年轻成人(AYA,15-39 岁)在专科癌症中心(SCC)接受治疗;然而,在这些地方观察到的患者生存率显著提高。我们的目标是确定哪些患者有可能因严重的地理障碍而无法接受 SCC 级别的治疗:我们利用北美中央癌症登记协会(North American Association of Central Cancer Registries)的北美癌症数据库(Cancer in North America)中的数据,识别了 2004-2016 年间在美国 43 个州确诊的青壮年 ALL 患者。我们计算了从参与者居住的县到最近的 SCC 机构的车程和旅行时间。然后,我们使用多变量逻辑回归模型研究了AYA ALL患者所在县的社会人口学特征与前往SCC接受治疗所需时间大于1小时之间的关系:在11813名AYA ALL患者中,43.4%为25-39岁,65.5%为男性,32.9%为西班牙裔,28.7%有公共保险。我们发现,在美国60.8%的县中,有23.6%的AYA ALL患者需要单程旅行1小时以上才能到达SCC。多变量模型表明,生活在非大都市、教育程度较低、收入不平等程度较高、互联网接入较低、位于初级保健医生短缺地区以及提供化疗服务的医院较少的地区的患者更有可能需要旅行超过1小时才能接受SCC治疗:结论:在全美范围内,患者在接受 SCC 治疗时存在大量与旅行相关的障碍,尤其是对于生活在历史上被边缘化社区较为集中的地区的患者而言。
{"title":"Travel-time barriers to specialized cancer care for adolescents and young adults with acute lymphoblastic leukemia.","authors":"Helen M Parsons, Lori S Muffly, Ariadna Garcia, Amy Zhang, Kate Miller, David Van Riper, Kate Knowles, Theresa H Keegan","doi":"10.1093/jncics/pkae046","DOIUrl":"10.1093/jncics/pkae046","url":null,"abstract":"<p><strong>Background: </strong>Prior studies demonstrate that 20%-50% of adolescents and young adults (age 15-39 years) with acute lymphoblastic leukemia (ALL) receive care at specialty cancer centers, yet a survival benefit has been observed for patients at these sites. Our objective was to identify patients at risk of severe geographic barriers to specialty cancer center-level care.</p><p><strong>Methods: </strong>We used data from the North American Association of Central Cancer Registries Cancer in North America database to identify adolescent and young adult ALL patients diagnosed between 2004 and 2016 across 43 US states. We calculated driving distance and travel time from counties where participants lived to the closest specialty cancer center sites. We then used multivariable logistic regression models to examine the relationship between sociodemographic characteristics of counties where adolescent and young adult ALL patients resided and the need to travel more than 1 hour to obtain care at a specialty cancer center.</p><p><strong>Results: </strong>Among 11 813 adolescent and young adult ALL patients, 43.4% were aged 25-39 years, 65.5% were male, 32.9% were Hispanic, and 28.7% had public insurance. We found 23.6% of adolescent and young adult ALL patients from 60.8% of included US counties would be required to travel more than 1 hour one way to access a specialty cancer center. Multivariable models demonstrate that patients living in counties that are nonmetropolitan, with lower levels of educational attainment, with higher income inequality, with lower internet access, located in primary care physician shortage areas, and with fewer hospitals providing chemotherapy services are more likely to travel more than 1 hour to access a specialty cancer center.</p><p><strong>Conclusions: </strong>Substantial travel-related barriers exist to accessing care at specialty cancer centers across the United States, particularly for patients living in areas with greater concentrations of historically marginalized communities.</p>","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11229987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The genomic landscape of breast and non-breast cancers from individuals with germline CHEK2 deficiency. CHEK2基因缺陷患者的乳腺癌和非乳腺癌基因组图谱。
IF 3.4 Q2 ONCOLOGY Pub Date : 2024-07-01 DOI: 10.1093/jncics/pkae044
Snežana Hinić, Rachel S van der Post, Lilian Vreede, Janneke Schuurs-Hoeijmakers, Saskia Koene, Erik A M Jansen, Franziska Bervoets-Metge, Arjen R Mensenkamp, Nicoline Hoogerbrugge, Marjolijn J L Ligtenberg, Richarda M de Voer

CHEK2 is considered to be involved in homologous recombination repair (HRR). Individuals who have germline pathogenic variants (gPVs) in CHEK2 are at increased risk to develop breast cancer and likely other primary cancers. PARP inhibitors (PARPi) have been shown to be effective in the treatment of cancers that present with HRR deficiency-for example, caused by inactivation of BRCA1/2. However, clinical trials have shown little to no efficacy of PARPi in patients with CHEK2 gPVs. Here, we show that both breast and non-breast cancers from individuals who have biallelic gPVs in CHEK2 (germline CHEK2 deficiency) do not present with molecular profiles that fit with HRR deficiency. This finding provides a likely explanation why PARPi therapy is not successful in the treatment of CHEK2-deficient cancers.

CHEK2 被认为参与了同源重组修复(HRR)。CHEK2中存在种系致病变异(gPV)的人罹患乳腺癌和其他原发性癌症的风险会增加。PARP 抑制剂(PARPi)已被证明能有效治疗 HRR 缺失的癌症,例如由 BRCA1/2 失活引起的癌症。然而,临床试验表明,PARPi 对 CHEK2 gPV 患者几乎没有疗效。在这里,我们发现,CHEK2 双拷贝 gPV(种系 CHEK2 缺失)患者的乳腺癌和非乳腺癌的分子特征都不符合 HRR 缺失的特征。这一发现很可能解释了为什么PARPi疗法不能成功治疗CHEK2缺陷型癌症。
{"title":"The genomic landscape of breast and non-breast cancers from individuals with germline CHEK2 deficiency.","authors":"Snežana Hinić, Rachel S van der Post, Lilian Vreede, Janneke Schuurs-Hoeijmakers, Saskia Koene, Erik A M Jansen, Franziska Bervoets-Metge, Arjen R Mensenkamp, Nicoline Hoogerbrugge, Marjolijn J L Ligtenberg, Richarda M de Voer","doi":"10.1093/jncics/pkae044","DOIUrl":"10.1093/jncics/pkae044","url":null,"abstract":"<p><p>CHEK2 is considered to be involved in homologous recombination repair (HRR). Individuals who have germline pathogenic variants (gPVs) in CHEK2 are at increased risk to develop breast cancer and likely other primary cancers. PARP inhibitors (PARPi) have been shown to be effective in the treatment of cancers that present with HRR deficiency-for example, caused by inactivation of BRCA1/2. However, clinical trials have shown little to no efficacy of PARPi in patients with CHEK2 gPVs. Here, we show that both breast and non-breast cancers from individuals who have biallelic gPVs in CHEK2 (germline CHEK2 deficiency) do not present with molecular profiles that fit with HRR deficiency. This finding provides a likely explanation why PARPi therapy is not successful in the treatment of CHEK2-deficient cancers.</p>","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11216722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141288093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Rethinking the use of germline CHEK2 mutation as a marker for PARP inhibitor sensitivity. 重新思考使用种系CHEK2突变作为PARP抑制剂敏感性的标记。
IF 3.4 Q2 ONCOLOGY Pub Date : 2024-07-01 DOI: 10.1093/jncics/pkae045
Thomas J Hayman
{"title":"Rethinking the use of germline CHEK2 mutation as a marker for PARP inhibitor sensitivity.","authors":"Thomas J Hayman","doi":"10.1093/jncics/pkae045","DOIUrl":"10.1093/jncics/pkae045","url":null,"abstract":"","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11216723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unmet needs in people with high-grade glioma: defining criteria for stepped care intervention. 高级别胶质瘤患者未满足的需求:确定阶梯护理干预的标准。
IF 3.4 Q2 ONCOLOGY Pub Date : 2024-07-01 DOI: 10.1093/jncics/pkae034
Mona M Faris, Haryana M Dhillon, Rachel Campbell, Georgia K B Halkett, Annie Miller, Raymond J Chan, Helen M Haydon, Ursula M Sansom-Daly, Eng-Siew Koh, Tamara Ownsworth, Anna K Nowak, Brian Kelly, Robyn Leonard, Kerryn E Pike, Dianne M Legge, Mark B Pinkham, Meera R Agar, Joanne Shaw

Background: We aimed to define levels of unmet supportive care needs in people with primary brain tumor and to reach expert consensus on feasibility of addressing patients' needs in clinical practice.

Methods: We conducted secondary analysis of a prospective cohort study of people diagnosed with high-grade glioma (n = 116) who completed the Supportive Care Needs Survey-Short Form during adjuvant chemoradiation therapy. Participants were allocated to 1 of 3 categories: no need ("no need" for help on all items), low need ("low need" for help on at least 1 item, but no "moderate" or "high" need), or moderate/high need (at least 1 "moderate" or "high" need indicated). Clinical capacity to respond to the proportion of patients needing to be prioritized was assessed.

Results: Overall, 13% (n = 5) were categorized as no need, 23% (n = 27) low need, and 64% (n = 74) moderate/high need. At least 1 moderate/high need was reported in the physical and daily living domain (42%) and the psychological (34%) domain. In recognition of health system capacity, the moderate/high need category was modified to distinguish between moderate need ("moderate" need indicated for at least 1 item but "high" need was not selected for any item) and high need (at least 1 "high" need indicated). Results revealed 24% (n = 28) moderate need and 40% (n = 46) high need. Those categorized as high need indicated needing assistance navigating the health system and information.

Conclusions: Using four step allocations resulted in 40% of patients indicating high need. Categories may facilitate appropriate triaging and guide stepped models of healthcare delivery.

背景我们旨在确定原发性脑肿瘤患者未得到满足的支持性护理需求水平,并就临床实践中满足患者需求的可行性达成专家共识:我们对一项前瞻性队列研究进行了二次分析,研究对象是在辅助化疗放疗期间完成支持性护理需求调查-SF34的高级别胶质瘤患者(n = 116)。参与者被分为三类:无需求(在所有项目上均 "无需求")、低需求(在至少一个项目上 "低需求",但无 "中度 "或 "高度 "需求)或中度/高度需求(至少有一项 "中度 "或 "高度 "需求)。对需要优先处理的患者比例的临床应对能力进行了评估:总体而言,13% 的患者(5 人)被归类为无需求,23% 的患者(27 人)为低需求,64% 的患者(74 人)为中度/高度需求。在身体和日常生活领域(42%)和心理领域(34%)至少有一项中度/高度需求。考虑到医疗系统的能力,对中度/高度需求类别进行了修改,以区分:中度需求(至少有一个项目显示 "中度 "需求,但任何项目均未选择 "高度 "需求)和高度需求(至少有一个项目显示 "高度 "需求)。结果显示,24%(n = 28)为中度需求,40%(n = 46)为高度需求。被归类为高需求的人表示需要在医疗系统和信息方面得到帮助:结论:使用四步分配法后,40% 的患者表示有较高需求。分类可促进适当的分流,并指导分步医疗服务模式。
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引用次数: 0
Effects of vitamin D supplementation on a deep learning-based mammographic evaluation in SWOG S0812. 补充维生素 D 对 SWOG S0812 中基于深度学习的乳房 X 线照相术评估的影响。
IF 3.4 Q2 ONCOLOGY Pub Date : 2024-07-01 DOI: 10.1093/jncics/pkae042
Julia E McGuinness, Garnet L Anderson, Simukayi Mutasa, Dawn L Hershman, Mary Beth Terry, Parisa Tehranifar, Danika L Lew, Monica Yee, Eric A Brown, Sebastien S Kairouz, Nafisa Kuwajerwala, Therese B Bevers, John E Doster, Corrine Zarwan, Laura Kruper, Lori M Minasian, Leslie Ford, Banu Arun, Marian L Neuhouser, Gary E Goodman, Powel H Brown, Richard Ha, Katherine D Crew

Deep learning-based mammographic evaluations could noninvasively assess response to breast cancer chemoprevention. We evaluated change in a convolutional neural network-based breast cancer risk model applied to mammograms among women enrolled in SWOG S0812, which randomly assigned 208 premenopausal high-risk women to receive oral vitamin D3 20 000 IU weekly or placebo for 12 months. We applied the convolutional neural network model to mammograms collected at baseline (n = 109), 12 months (n = 97), and 24 months (n = 67) and compared changes in convolutional neural network-based risk score between treatment groups. Change in convolutional neural network-based risk score was not statistically significantly different between vitamin D and placebo groups at 12 months (0.005 vs 0.002, P = .875) or at 24 months (0.020 vs 0.001, P = .563). The findings are consistent with the primary analysis of S0812, which did not demonstrate statistically significant changes in mammographic density with vitamin D supplementation compared with placebo. There is an ongoing need to evaluate biomarkers of response to novel breast cancer chemopreventive agents.

基于深度学习的乳房 X 线照片评估可以无创评估对乳腺癌(BC)化学预防的反应。我们评估了基于卷积神经网络(CNN)的乳腺癌风险模型的变化,该模型适用于参加 SWOG S0812 研究的妇女的乳房 X 光照片,该研究将 208 名绝经前高危妇女随机分为每周口服维生素 D3 20,000IU 或安慰剂 12 个月。我们将 CNN 模型应用于基线(109 人)、12 个月(97 人)和 24 个月(67 人)收集的乳房 X 光照片,并比较了不同治疗组 CNN 风险评分的变化。在12个月和24个月时,维生素D组和安慰剂组的CNN评分变化均无明显差异(0.005 vs. 0.002,p = 0.875),也无明显差异(0.020 vs. 0.001,p = 0.563)。这些研究结果与 S0812 的主要分析结果一致,即与安慰剂相比,维生素 D 补充剂未显示出 MD 的显著变化。目前需要对新型 BC 化学预防药物反应的生物标志物进行评估。
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