Pub Date : 2024-11-10Epub Date: 2024-08-05DOI: 10.1200/JCO.24.00081
Ethan B Ludmir, Alexander D Sherry, Bryan M Fellman, Suyu Liu, Tharakeswara Bathala, Cara Haymaker, Marina N Medina-Rosales, Alexandre Reuben, Emma B Holliday, Grace L Smith, Sonal S Noticewala, Sarah Nicholas, Tracy R Price, Rachael M Martin-Paulpeter, Luis A Perles, Sunyoung S Lee, Michael S Lee, Brandon G Smaglo, Ryan W Huey, Jason Willis, Dan Zhao, Lorenzo Cohen, Cullen M Taniguchi, Eugene J Koay, Matthew H G Katz, Robert A Wolff, Prajnan Das, Shubham Pant, Albert C Koong, Chad Tang
Purpose: The EXTEND trial tested the hypothesis that adding comprehensive metastasis-directed therapy (MDT) to chemotherapy would improve progression-free survival (PFS) over chemotherapy alone among patients with oligometastatic pancreatic ductal adenocarcinoma (PDAC).
Methods: EXTEND (ClinicalTrials.gov identifier: NCT03599765) is a multicenter, phase II basket trial randomly assigning patients with ≤five metastases 1:1 to MDT plus systemic therapy versus systemic therapy. Disease progression was defined by radiologic criteria (RECIST v1.1), clinical progression, or death. The primary end point was PFS in the per-protocol population, evaluated after all patients achieved at least 6 months of follow-up. Exploratory end points included systemic immune response measures.
Results: Between March 19, 2019, and February 13, 2023, 41 patients were randomly assigned and 40 were eligible for the primary analysis of PFS (19 patients in the MDT arm; 21 patients in the control arm). At a median follow-up time of 17 months, the median PFS time was 10.3 months (95% CI, 4.6 to 14.0) in the MDT arm versus 2.5 months (95% CI, 1.7 to 5.1) in the control arm. PFS was significantly improved by the addition of MDT to systemic therapy (P = .030 for stratified log-rank test) with a hazard ratio of 0.43 (95% CI, 0.20 to 0.94). No grade ≥3 or greater adverse events related to MDT were observed. Systemic immune activation events were associated with MDT and correlated with improved PFS.
Conclusion: This study supports the addition of MDT to systemic therapy for patients with oligometastatic PDAC. Induction of systemic immunity is a possible mechanism of benefit. These results warrant confirmatory trials to refine treatment strategy and provide external validation.
{"title":"Addition of Metastasis-Directed Therapy to Systemic Therapy for Oligometastatic Pancreatic Ductal Adenocarcinoma (EXTEND): A Multicenter, Randomized Phase II Trial.","authors":"Ethan B Ludmir, Alexander D Sherry, Bryan M Fellman, Suyu Liu, Tharakeswara Bathala, Cara Haymaker, Marina N Medina-Rosales, Alexandre Reuben, Emma B Holliday, Grace L Smith, Sonal S Noticewala, Sarah Nicholas, Tracy R Price, Rachael M Martin-Paulpeter, Luis A Perles, Sunyoung S Lee, Michael S Lee, Brandon G Smaglo, Ryan W Huey, Jason Willis, Dan Zhao, Lorenzo Cohen, Cullen M Taniguchi, Eugene J Koay, Matthew H G Katz, Robert A Wolff, Prajnan Das, Shubham Pant, Albert C Koong, Chad Tang","doi":"10.1200/JCO.24.00081","DOIUrl":"10.1200/JCO.24.00081","url":null,"abstract":"<p><strong>Purpose: </strong>The EXTEND trial tested the hypothesis that adding comprehensive metastasis-directed therapy (MDT) to chemotherapy would improve progression-free survival (PFS) over chemotherapy alone among patients with oligometastatic pancreatic ductal adenocarcinoma (PDAC).</p><p><strong>Methods: </strong>EXTEND (ClinicalTrials.gov identifier: NCT03599765) is a multicenter, phase II basket trial randomly assigning patients with ≤five metastases 1:1 to MDT plus systemic therapy versus systemic therapy. Disease progression was defined by radiologic criteria (RECIST v1.1), clinical progression, or death. The primary end point was PFS in the per-protocol population, evaluated after all patients achieved at least 6 months of follow-up. Exploratory end points included systemic immune response measures.</p><p><strong>Results: </strong>Between March 19, 2019, and February 13, 2023, 41 patients were randomly assigned and 40 were eligible for the primary analysis of PFS (19 patients in the MDT arm; 21 patients in the control arm). At a median follow-up time of 17 months, the median PFS time was 10.3 months (95% CI, 4.6 to 14.0) in the MDT arm versus 2.5 months (95% CI, 1.7 to 5.1) in the control arm. PFS was significantly improved by the addition of MDT to systemic therapy (<i>P</i> = .030 for stratified log-rank test) with a hazard ratio of 0.43 (95% CI, 0.20 to 0.94). No grade ≥3 or greater adverse events related to MDT were observed. Systemic immune activation events were associated with MDT and correlated with improved PFS.</p><p><strong>Conclusion: </strong>This study supports the addition of MDT to systemic therapy for patients with oligometastatic PDAC. Induction of systemic immunity is a possible mechanism of benefit. These results warrant confirmatory trials to refine treatment strategy and provide external validation.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-10Epub Date: 2024-09-17DOI: 10.1200/JCO-24-01200
Jaleh Fallah, Flora Mulkey, Mallorie H Fiero, Haley Gittleman, Chi Song, Jeevan Puthiamadathil, Anup Amatya, Sundeep Agrawal, Paz Vellanki, Daniel L Suzman, Harpreet Singh, Laleh Amiri-Kordestani, Pallavi Mishra-Kalyani, Richard Pazdur, Paul G Kluetz
FDA Oncology Center's @Falleh_Fallah and colleagues discuss loss of equipoise and other trial conduct challenges in an era of breakthrough therapies - via @JCO_ASCO.
FDA 肿瘤中心的 @Falleh_Fallah 及其同事讨论了突破性疗法时代的平衡损失和其他试验行为挑战 - via @JCO_ASCO。
{"title":"Equipoise Lost? Trial Conduct Challenges in an Era of Breakthrough Therapies.","authors":"Jaleh Fallah, Flora Mulkey, Mallorie H Fiero, Haley Gittleman, Chi Song, Jeevan Puthiamadathil, Anup Amatya, Sundeep Agrawal, Paz Vellanki, Daniel L Suzman, Harpreet Singh, Laleh Amiri-Kordestani, Pallavi Mishra-Kalyani, Richard Pazdur, Paul G Kluetz","doi":"10.1200/JCO-24-01200","DOIUrl":"10.1200/JCO-24-01200","url":null,"abstract":"<p><p>FDA Oncology Center's @Falleh_Fallah and colleagues discuss loss of equipoise and other trial conduct challenges in an era of breakthrough therapies - via @JCO_ASCO.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-10Epub Date: 2024-08-06DOI: 10.1200/JCO.23.02483
Katherine E Reeder-Hayes, Bradford E Jackson, Tzy-Mey Kuo, Chris D Baggett, Juan Yanguela, Matthew R LeBlanc, Mya L Roberson, Stephanie B Wheeler
Purpose: Structural racism (SR) is a potential driver of health disparities, but research quantifying its impacts on cancer outcomes has been limited. We aimed to develop a multidimensional county-level SR measure and to examine the association of SR with breast cancer (BC) treatment delays among Black and White patients.
Methods: The cohort included 32,095 individuals from the North Carolina Central Cancer Registry with stage I to III BC diagnosed between 2004 and 2017 and linked to multipayer insurance claims from the Cancer Information and Population Health Resource. County-level data were drawn from multiple public sources aggregated in the Robert Wood Johnson County Health Rankings database. Racial gaps in eight social determinants across five domains were quantified at the county level and ranked on a 0-100 minimum-maximum scale. Domain scores were averaged to create a SR Composite Index (SRCI) score. We used multilevel logistic regression with random intercepts and multiple cross-level interaction terms to evaluate the association between county-level SRCI and patient-level treatment delays, adjusting for patient-level characteristics and stratified by race.
Results: The SRCI score ranged from 21 to 75 with a median (IQR) of 39.0 (31.8, 45.7). For Black patients, a 10-unit increase in SRCI score was associated with increased odds of delay (Adjusted odds ratios [aOR], 1.25; 95% confidence limits [CL], 1.08 to 1.45). No such association was found for White patients (OR, 1.05; 95% CL, 0.97 to 1.15).
Conclusion: Area-level SR measured by a composite index is associated with higher odds of BC treatment delays among Black, but not White patients. Increasing county-level SR is associated with increasing Black-White disparities in treatment delay. Further research is needed to refine the measurement of SR and to examine its association with other cancer care disparities.
目的:结构性种族主义(SR)是健康差异的潜在驱动因素,但量化其对癌症结果影响的研究却很有限。我们旨在开发一种多维度的县级 SR 测量方法,并研究黑人和白人患者中 SR 与乳腺癌(BC)治疗延迟的关系:研究队列包括北卡罗来纳州中央癌症登记处的 32,095 名患者,他们在 2004 年至 2017 年期间确诊为 I 期至 III 期乳腺癌,并与癌症信息和人口健康资源的多方保险索赔相关联。县级数据来自罗伯特-伍德-约翰逊县健康排名数据库汇总的多个公共来源。在县一级对五个领域中八个社会决定因素的种族差距进行了量化,并按 0-100 最小值-最大值进行排序。各领域得分取平均值,得出 SR 综合指数 (SRCI) 分值。我们使用带有随机截距和多个跨级别交互项的多级别逻辑回归来评估县级 SRCI 与患者级别治疗延迟之间的关联,同时对患者级别特征进行调整并按种族进行分层:SRCI得分介于21到75之间,中位数(IQR)为39.0(31.8,45.7)。对于黑人患者,SRCI 分数每增加 10 个单位,延迟的几率就会增加(调整后的几率比 [aOR],1.25;95% 置信区间 [CL],1.08 至 1.45)。白人患者没有发现这种关联(OR,1.05;95% CL,0.97 至 1.15):结论:以综合指数衡量的地区级SR与黑人而非白人患者出现BC治疗延迟的几率较高有关。县级 SR 的增加与黑人和白人治疗延迟差异的增加有关。还需要进一步研究来完善SR的测量方法,并检查其与其他癌症治疗差异的关联。
{"title":"Structural Racism and Treatment Delay Among Black and White Patients With Breast Cancer.","authors":"Katherine E Reeder-Hayes, Bradford E Jackson, Tzy-Mey Kuo, Chris D Baggett, Juan Yanguela, Matthew R LeBlanc, Mya L Roberson, Stephanie B Wheeler","doi":"10.1200/JCO.23.02483","DOIUrl":"10.1200/JCO.23.02483","url":null,"abstract":"<p><strong>Purpose: </strong>Structural racism (SR) is a potential driver of health disparities, but research quantifying its impacts on cancer outcomes has been limited. We aimed to develop a multidimensional county-level SR measure and to examine the association of SR with breast cancer (BC) treatment delays among Black and White patients.</p><p><strong>Methods: </strong>The cohort included 32,095 individuals from the North Carolina Central Cancer Registry with stage I to III BC diagnosed between 2004 and 2017 and linked to multipayer insurance claims from the Cancer Information and Population Health Resource. County-level data were drawn from multiple public sources aggregated in the Robert Wood Johnson County Health Rankings database. Racial gaps in eight social determinants across five domains were quantified at the county level and ranked on a 0-100 minimum-maximum scale. Domain scores were averaged to create a SR Composite Index (SRCI) score. We used multilevel logistic regression with random intercepts and multiple cross-level interaction terms to evaluate the association between county-level SRCI and patient-level treatment delays, adjusting for patient-level characteristics and stratified by race.</p><p><strong>Results: </strong>The SRCI score ranged from 21 to 75 with a median (IQR) of 39.0 (31.8, 45.7). For Black patients, a 10-unit increase in SRCI score was associated with increased odds of delay (Adjusted odds ratios [aOR], 1.25; 95% confidence limits [CL], 1.08 to 1.45). No such association was found for White patients (OR, 1.05; 95% CL, 0.97 to 1.15).</p><p><strong>Conclusion: </strong>Area-level SR measured by a composite index is associated with higher odds of BC treatment delays among Black, but not White patients. Increasing county-level SR is associated with increasing Black-White disparities in treatment delay. Further research is needed to refine the measurement of SR and to examine its association with other cancer care disparities.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-10Epub Date: 2024-10-04DOI: 10.1200/JCO-24-02083
{"title":"Erratum: CML and the WHO: Why?","authors":"","doi":"10.1200/JCO-24-02083","DOIUrl":"10.1200/JCO-24-02083","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-10Epub Date: 2024-07-22DOI: 10.1200/JCO.24.00152
Hari T Vigneswaran, Martin Eklund, Andrea Discacciati, Tobias Nordström, Rebecca A Hubbard, Nathan Perlis, Michael R Abern, Daniel M Moreira, Scott Eggener, Paul Yonover, Alexander K Chow, Kara Watts, Michael A Liss, Gregory R Thoreson, Andre L Abreu, Geoffrey A Sonn, Thorgerdur Palsdottir, Anna Plym, Fredrik Wiklund, Henrik Grönberg, Adam B Murphy
Purpose: Asian, Black, and Hispanic men are underrepresented in prostate cancer (PCa) clinical trials. Few novel prostate cancer biomarkers have been validated in diverse cohorts. We aimed to determine if Stockholm3 can improve prostate cancer detection in a diverse cohort.
Methods: An observational prospective multicentered (17 sites) clinical trial (2019-2023), supplemented by prospectively recruited participants (2008-2020) in a urology clinic setting included men with suspicion of PCa and underwent prostate biopsy. Before biopsy, sample was collected for measurement of the Stockholm3 risk score. Parameters include prostate-specific antigen (PSA), free PSA, KLK2, GDF15, PSP94, germline risk (single-nucleotide polymorphisms), age, family history, and previous negative biopsy. The primary endpoint was detection of International Society of Urological Pathology (ISUP) Grade ≥2 cancer (clinically significant PCa, csPC). The two primary aims were to (1) demonstrate noninferior sensitivity (0.8 lower bound 95% CI noninferiority margin) in detecting csPC using Stockholm3 compared with PSA (relative sensitivity) and (2) demonstrate superior specificity by reducing biopsies with benign results or low-grade cancers (relative specificity).
Results: A total of 2,129 biopsied participants were included: Asian (16%, 350), Black or African American (Black; 24%, 505), Hispanic or Latino and White (Hispanic; 14%, 305), and non-Hispanic or non-Latino and White (White; 46%, 969). Overall, Stockholm3 showed noninferior sensitivity compared with PSA ≥4 ng/mL (relative sensitivity: 0.95 [95% CI, 0.92 to 0.99]) and nearly three times higher specificity (relative specificity: 2.91 [95% CI, 2.63 to 3.22]). Results were consistent across racial and ethnic subgroups: noninferior sensitivity (0.91-0.98) and superior specificity (2.51-4.70). Compared with PSA, Stockholm3 could reduce benign and ISUP 1 biopsies by 45% overall and between 42% and 52% across racial and ethnic subgroups.
Conclusion: In a substantially diverse population, Stockholm3 significantly reduces unnecessary prostate biopsies while maintaining a similar sensitivity to PSA in detecting csPC.
{"title":"Stockholm3 in a Multiethnic Cohort for Prostate Cancer Detection (SEPTA): A Prospective Multicentered Trial.","authors":"Hari T Vigneswaran, Martin Eklund, Andrea Discacciati, Tobias Nordström, Rebecca A Hubbard, Nathan Perlis, Michael R Abern, Daniel M Moreira, Scott Eggener, Paul Yonover, Alexander K Chow, Kara Watts, Michael A Liss, Gregory R Thoreson, Andre L Abreu, Geoffrey A Sonn, Thorgerdur Palsdottir, Anna Plym, Fredrik Wiklund, Henrik Grönberg, Adam B Murphy","doi":"10.1200/JCO.24.00152","DOIUrl":"10.1200/JCO.24.00152","url":null,"abstract":"<p><strong>Purpose: </strong>Asian, Black, and Hispanic men are underrepresented in prostate cancer (PCa) clinical trials. Few novel prostate cancer biomarkers have been validated in diverse cohorts. We aimed to determine if Stockholm3 can improve prostate cancer detection in a diverse cohort.</p><p><strong>Methods: </strong>An observational prospective multicentered (17 sites) clinical trial (2019-2023), supplemented by prospectively recruited participants (2008-2020) in a urology clinic setting included men with suspicion of PCa and underwent prostate biopsy. Before biopsy, sample was collected for measurement of the Stockholm3 risk score. Parameters include prostate-specific antigen (PSA), free PSA, KLK2, GDF15, PSP94, germline risk (single-nucleotide polymorphisms), age, family history, and previous negative biopsy. The primary endpoint was detection of International Society of Urological Pathology (ISUP) Grade ≥2 cancer (clinically significant PCa, csPC). The two primary aims were to (1) demonstrate noninferior sensitivity (0.8 lower bound 95% CI noninferiority margin) in detecting csPC using Stockholm3 compared with PSA (relative sensitivity) and (2) demonstrate superior specificity by reducing biopsies with benign results or low-grade cancers (relative specificity).</p><p><strong>Results: </strong>A total of 2,129 biopsied participants were included: Asian (16%, 350), Black or African American (Black; 24%, 505), Hispanic or Latino and White (Hispanic; 14%, 305), and non-Hispanic or non-Latino and White (White; 46%, 969). Overall, Stockholm3 showed noninferior sensitivity compared with PSA ≥4 ng/mL (relative sensitivity: 0.95 [95% CI, 0.92 to 0.99]) and nearly three times higher specificity (relative specificity: 2.91 [95% CI, 2.63 to 3.22]). Results were consistent across racial and ethnic subgroups: noninferior sensitivity (0.91-0.98) and superior specificity (2.51-4.70). Compared with PSA, Stockholm3 could reduce benign and ISUP 1 biopsies by 45% overall and between 42% and 52% across racial and ethnic subgroups.</p><p><strong>Conclusion: </strong>In a substantially diverse population, Stockholm3 significantly reduces unnecessary prostate biopsies while maintaining a similar sensitivity to PSA in detecting csPC.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-10Epub Date: 2024-07-26DOI: 10.1200/JCO.22.02819
Bhavika K Patel, Molly B Carnahan, Donald Northfelt, Karen Anderson, Gina L Mazza, Victor J Pizzitola, Marina E Giurescu, Roxanne Lorans, William G Eversman, Richard E Sharpe, Laura K Harper, Heidi Apsey, Patricia Cronin, Juliana Kling, Brenda Ernst, Jennifer Palmieri, Jessica Fraker, Lida Mina, Felipe Batalini, Barbara Pockaj
Purpose: Contrast-enhanced mammography (CEM) and magnetic resonance imaging (MRI) have shown similar diagnostic performance in detection of breast cancer. Limited CEM data are available for high-risk breast cancer screening. The purpose of the study was to prospectively investigate the efficacy of supplemental screening CEM in elevated risk patients.
Materials and methods: A prospective, single-institution, institutional review board-approved observational study was conducted in asymptomatic elevated risk women age 35 years or older who had a negative conventional two-dimensional digital breast tomosynthesis screening mammography (MG) and no additional supplemental screening within the prior 12 months.
Results: Four hundred sixty women were enrolled from February 2019 to April 2021. The median age was 56.8 (range, 35.0-79.2) years; 408 of 460 (88.7%) were mammographically dense. Biopsy revealed benign changes in 22 women (22/37, 59%), high-risk lesions in four women (4/37, 11%), and breast cancer in 11 women (11/37, 30%). Fourteen cancers (10 invasive, tumor size range 4-15 mm, median 9 mm) were diagnosed in 11 women. The overall supplemental cancer detection rate was 23.9 per 1,000 patients, 95% CI (12.0 to 42.4). All cancers were grade 1 or 2, ER+ ERBB2-, and node negative. CEM imaging screening offered high specificity (0.875 [95% CI, 0.844 to 0.906]), high NPV (0.998 [95% CI, 0.993 to 1.000), moderate PPV1 (0.164 [95% CI, 0.076 to 0.253), moderate PPV3 (0.275 [95% CI, 0.137 to 0.413]), and high sensitivity (0.917 [95% CI, 0.760 to 1.000]). At least 1 year of imaging follow-up was available on all patients, and one interval cancer was detected on breast MRI 4 months after negative screening CEM.
Conclusion: A pilot trial demonstrates a supplemental cancer detection rate of 23.9 per 1,000 in women at an elevated risk for breast cancer. Larger, multi-institutional, multiyear CEM trials in patients at elevated risk are needed for validation.
目的:对比增强乳腺 X 光造影术(CEM)和磁共振成像(MRI)在检测乳腺癌方面显示出相似的诊断性能。用于高危乳腺癌筛查的 CEM 数据有限。本研究旨在前瞻性地调查高危患者补充筛查 CEM 的疗效:这项前瞻性、单一机构、机构审查委员会批准的观察性研究针对35岁或35岁以上、常规二维数字乳腺断层合成筛查乳腺X线摄影(MG)呈阴性且在之前12个月内未进行额外补充筛查的无症状高危女性:从 2019 年 2 月到 2021 年 4 月,共有 4600 名妇女参加了此次筛查。中位年龄为 56.8 岁(35.0-79.2 岁);460 名女性中有 408 名(88.7%)乳腺组织致密。活检结果显示,22 名女性(22/37,59%)为良性病变,4 名女性(4/37,11%)为高危病变,11 名女性(11/37,30%)为乳腺癌。11 名妇女中确诊了 14 例癌症(10 例为浸润性,肿瘤大小范围为 4-15 毫米,中位数为 9 毫米)。癌症总补充检测率为每千名患者 23.9 例,95% CI (12.0 至 42.4)。所有癌症均为 1 级或 2 级、ER+ ERBB2-、结节阴性。CEM成像筛查具有高特异性(0.875 [95% CI, 0.844 to 0.906])、高NPV(0.998 [95% CI, 0.993 to 1.000])、中度PPV1(0.164 [95% CI, 0.076 to 0.253])、中度PPV3(0.275 [95% CI, 0.137 to 0.413])和高灵敏度(0.917 [95% CI, 0.760 to 1.000])。所有患者都接受了至少一年的影像学随访,其中一名患者在CEM筛查阴性后4个月通过乳腺核磁共振检查发现了间期癌:一项试点试验表明,在乳腺癌风险较高的妇女中,癌症补充检测率为 23.9‰。需要对高危患者进行更大规模、多机构、多年期的 CEM 试验,以进行验证。
{"title":"Prospective Study of Supplemental Screening With Contrast-Enhanced Mammography in Women With Elevated Risk of Breast Cancer: Results of the Prevalence Round.","authors":"Bhavika K Patel, Molly B Carnahan, Donald Northfelt, Karen Anderson, Gina L Mazza, Victor J Pizzitola, Marina E Giurescu, Roxanne Lorans, William G Eversman, Richard E Sharpe, Laura K Harper, Heidi Apsey, Patricia Cronin, Juliana Kling, Brenda Ernst, Jennifer Palmieri, Jessica Fraker, Lida Mina, Felipe Batalini, Barbara Pockaj","doi":"10.1200/JCO.22.02819","DOIUrl":"10.1200/JCO.22.02819","url":null,"abstract":"<p><strong>Purpose: </strong>Contrast-enhanced mammography (CEM) and magnetic resonance imaging (MRI) have shown similar diagnostic performance in detection of breast cancer. Limited CEM data are available for high-risk breast cancer screening. The purpose of the study was to prospectively investigate the efficacy of supplemental screening CEM in elevated risk patients.</p><p><strong>Materials and methods: </strong>A prospective, single-institution, institutional review board-approved observational study was conducted in asymptomatic elevated risk women age 35 years or older who had a negative conventional two-dimensional digital breast tomosynthesis screening mammography (MG) and no additional supplemental screening within the prior 12 months.</p><p><strong>Results: </strong>Four hundred sixty women were enrolled from February 2019 to April 2021. The median age was 56.8 (range, 35.0-79.2) years; 408 of 460 (88.7%) were mammographically dense. Biopsy revealed benign changes in 22 women (22/37, 59%), high-risk lesions in four women (4/37, 11%), and breast cancer in 11 women (11/37, 30%). Fourteen cancers (10 invasive, tumor size range 4-15 mm, median 9 mm) were diagnosed in 11 women. The overall supplemental cancer detection rate was 23.9 per 1,000 patients, 95% CI (12.0 to 42.4). All cancers were grade 1 or 2, ER+ ERBB2-, and node negative. CEM imaging screening offered high specificity (0.875 [95% CI, 0.844 to 0.906]), high NPV (0.998 [95% CI, 0.993 to 1.000), moderate PPV1 (0.164 [95% CI, 0.076 to 0.253), moderate PPV3 (0.275 [95% CI, 0.137 to 0.413]), and high sensitivity (0.917 [95% CI, 0.760 to 1.000]). At least 1 year of imaging follow-up was available on all patients, and one interval cancer was detected on breast MRI 4 months after negative screening CEM.</p><p><strong>Conclusion: </strong>A pilot trial demonstrates a supplemental cancer detection rate of 23.9 per 1,000 in women at an elevated risk for breast cancer. Larger, multi-institutional, multiyear CEM trials in patients at elevated risk are needed for validation.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141766151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-10Epub Date: 2024-09-13DOI: 10.1200/JCO.24.00554
Olivier Tournilhac, Bettina Altmann, Birte Friedrichs, Kamal Bouabdallah, Mathieu Leclerc, Guillaume Cartron, Pascal Turlure, Peter Reimer, Eva Wagner-Drouet, Laurence Sanhes, Roch Houot, Murielle Roussel, Frank Kroschinsky, Peter Dreger, Andreas Viardot, Laurence de Leval, Andreas Rosenwald, Philippe Gaulard, Gerald Wulf, Alban Villate, Christelle Latiere, Ahmet Elmaagacli, Bertram Glass, Viola Poeschel, Gandhi Damaj, David Sibon, Eric Durot, Karin Bilger, Anne Banos, Mathias Haenel, Martin Dreyling, Ulrich Keller, Mourad Tiab, Bernard Drenou, Jérome Cornillon, Stéphanie Nguyen, Marie Robin, Maike Nickelsen, Lorenz Trümper, Georg Lenz, Marita Ziepert, Norbert Schmitz
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Primary analysis of the phase III randomized AATT study showed that younger patients with peripheral T-cell lymphoma (PTCL) consolidated with autologous or allogeneic transplantation (alloSCT) had similar event-free survival (EFS) and overall survival (OS). Seven-year EFS of patients randomly assigned to alloSCT was 38% (95% CI, 25 to 52) compared with 34% (95% CI, 22 to 47) for patients randomly assigned to autologous transplantation of hematopoietic stem cells (autoSCT); OS was 55% (95% CI, 41 to 69) and 61% (95% CI, 47 to 74). Among patients undergoing alloSCT (n = 26) or autoSCT (n = 41) on study, the cumulative progression/relapse rate was 8% (95% CI, 0 to 19) and 55% (95% CI, 35 to 74). Nonrelapse mortality (NRM) was 31% (95% CI, 13 to 49) and 3% (95% CI, 0 to 8) after alloSCT and autoSCT, respectively. Fifteen of 30 patients with early progression and 11 of 20 patients with progression/relapse after autoSCT received alloSCT. Seven-year OS after salvage alloSCT was 61% (95% CI, 47 to 74); NRM was 23% (95% CI, 6 to 40). Long-term follow-up documents the strong graft versus lymphoma effect of alloSCT independent of the timing of transplantation. Survival of patients unable to undergo transplantation was dismal. AlloSCT is the treatment of choice for younger, transplant-eligible patients with relapsed/refractory PTCL. AlloSCT is currently not recommended as part of first-line consolidation.
{"title":"Long-Term Follow-Up of the Prospective Randomized AATT Study (Autologous or Allogeneic Transplantation in Patients With Peripheral T-Cell Lymphoma).","authors":"Olivier Tournilhac, Bettina Altmann, Birte Friedrichs, Kamal Bouabdallah, Mathieu Leclerc, Guillaume Cartron, Pascal Turlure, Peter Reimer, Eva Wagner-Drouet, Laurence Sanhes, Roch Houot, Murielle Roussel, Frank Kroschinsky, Peter Dreger, Andreas Viardot, Laurence de Leval, Andreas Rosenwald, Philippe Gaulard, Gerald Wulf, Alban Villate, Christelle Latiere, Ahmet Elmaagacli, Bertram Glass, Viola Poeschel, Gandhi Damaj, David Sibon, Eric Durot, Karin Bilger, Anne Banos, Mathias Haenel, Martin Dreyling, Ulrich Keller, Mourad Tiab, Bernard Drenou, Jérome Cornillon, Stéphanie Nguyen, Marie Robin, Maike Nickelsen, Lorenz Trümper, Georg Lenz, Marita Ziepert, Norbert Schmitz","doi":"10.1200/JCO.24.00554","DOIUrl":"10.1200/JCO.24.00554","url":null,"abstract":"<p><p><i>Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in</i> JCO <i>or elsewhere, for which the primary end point has already been reported.</i>Primary analysis of the phase III randomized AATT study showed that younger patients with peripheral T-cell lymphoma (PTCL) consolidated with autologous or allogeneic transplantation (alloSCT) had similar event-free survival (EFS) and overall survival (OS). Seven-year EFS of patients randomly assigned to alloSCT was 38% (95% CI, 25 to 52) compared with 34% (95% CI, 22 to 47) for patients randomly assigned to autologous transplantation of hematopoietic stem cells (autoSCT); OS was 55% (95% CI, 41 to 69) and 61% (95% CI, 47 to 74). Among patients undergoing alloSCT (n = 26) or autoSCT (n = 41) on study, the cumulative progression/relapse rate was 8% (95% CI, 0 to 19) and 55% (95% CI, 35 to 74). Nonrelapse mortality (NRM) was 31% (95% CI, 13 to 49) and 3% (95% CI, 0 to 8) after alloSCT and autoSCT, respectively. Fifteen of 30 patients with early progression and 11 of 20 patients with progression/relapse after autoSCT received alloSCT. Seven-year OS after salvage alloSCT was 61% (95% CI, 47 to 74); NRM was 23% (95% CI, 6 to 40). Long-term follow-up documents the strong graft versus lymphoma effect of alloSCT independent of the timing of transplantation. Survival of patients unable to undergo transplantation was dismal. AlloSCT is the treatment of choice for younger, transplant-eligible patients with relapsed/refractory PTCL. AlloSCT is currently not recommended as part of first-line consolidation.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-10Epub Date: 2024-09-17DOI: 10.1200/JCO.23.02311
Juliana M Torres, Michelle O Sodipo, Margaret F Hopkins, Paulette D Chandler, Erica T Warner
Purpose: Despite effective early-detection approaches and innovative treatments, Black women in the United States have higher breast cancer mortality rates compared with White women. The purpose of this systematic review and meta-analysis is to determine the extent of disparities in breast cancer survival between Black and White women according to tumor subtype.
Methods: A comprehensive database search was performed for full-text, English-language articles published from January 1, 2000, to December 31, 2022. Included studies compared survival between Black and White female patients with breast cancer within subtypes defined by hormone receptor and human epidermal growth factor receptor 2 (HER2)/neu (HER2; now known as ERBB2) status. Random-effects models were used to combine study-specific results and generate pooled relative risks (RRs) and 95% CIs for breast cancer-specific or overall survival (OS). A protocol for this review was registered in PROSPERO (CRD42021268212).
Results: Eighteen studies including 228,885 (34,262 Black; 182,466 White) patients with breast cancer were identified. Compared with White women, Black women had a higher risk of breast cancer death for all tumor subtypes. The summary risk of breast cancer death was 50% higher among hormone receptor-positive HER2-negative [HER2-] tumors (RR, 1.50 [95% CI, 1.30 to 1.72]), 34% higher for hormone receptor+/HER2+ (RR, 1.34 [95% CI, 1.10 to 1.64]), 20% higher for hormone receptor-negative (-)/HER2+ (RR, 1.29 [95% CI, 1.00 to 1.43]), and 17% higher among individuals with hormone receptor-/HER2- tumors (hazard ratio, 1.17; 95% CI, 1.10 to 1.25). Black women also had poorer OS than White women for all subtypes.
Conclusion: These results suggest there are both subtype-specific and subtype-independent mechanisms that contribute to disparities in breast cancer survival between Black and White women, which require multilevel interventions to address and achieve health equity.
{"title":"Racial Differences in Breast Cancer Survival Between Black and White Women According to Tumor Subtype: A Systematic Review and Meta-Analysis.","authors":"Juliana M Torres, Michelle O Sodipo, Margaret F Hopkins, Paulette D Chandler, Erica T Warner","doi":"10.1200/JCO.23.02311","DOIUrl":"10.1200/JCO.23.02311","url":null,"abstract":"<p><strong>Purpose: </strong>Despite effective early-detection approaches and innovative treatments, Black women in the United States have higher breast cancer mortality rates compared with White women. The purpose of this systematic review and meta-analysis is to determine the extent of disparities in breast cancer survival between Black and White women according to tumor subtype.</p><p><strong>Methods: </strong>A comprehensive database search was performed for full-text, English-language articles published from January 1, 2000, to December 31, 2022. Included studies compared survival between Black and White female patients with breast cancer within subtypes defined by hormone receptor and human epidermal growth factor receptor 2 (HER2)/neu (HER2; now known as ERBB2) status. Random-effects models were used to combine study-specific results and generate pooled relative risks (RRs) and 95% CIs for breast cancer-specific or overall survival (OS). A protocol for this review was registered in PROSPERO (CRD42021268212).</p><p><strong>Results: </strong>Eighteen studies including 228,885 (34,262 Black; 182,466 White) patients with breast cancer were identified. Compared with White women, Black women had a higher risk of breast cancer death for all tumor subtypes. The summary risk of breast cancer death was 50% higher among hormone receptor-positive HER2-negative [HER2-] tumors (RR, 1.50 [95% CI, 1.30 to 1.72]), 34% higher for hormone receptor+/HER2+ (RR, 1.34 [95% CI, 1.10 to 1.64]), 20% higher for hormone receptor-negative (-)/HER2+ (RR, 1.29 [95% CI, 1.00 to 1.43]), and 17% higher among individuals with hormone receptor-/HER2- tumors (hazard ratio, 1.17; 95% CI, 1.10 to 1.25). Black women also had poorer OS than White women for all subtypes.</p><p><strong>Conclusion: </strong>These results suggest there are both subtype-specific and subtype-independent mechanisms that contribute to disparities in breast cancer survival between Black and White women, which require multilevel interventions to address and achieve health equity.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-10Epub Date: 2024-08-02DOI: 10.1200/JCO-24-01365
Christopher A Barker, Sue S Yom
{"title":"Reply to M. Boileau et al.","authors":"Christopher A Barker, Sue S Yom","doi":"10.1200/JCO-24-01365","DOIUrl":"10.1200/JCO-24-01365","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-10Epub Date: 2024-10-10DOI: 10.1200/JCO-24-02040
{"title":"Erratum: Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase II Study of Onartuzumab Plus Bevacizumab Versus Placebo Plus Bevacizumab in Patients With Recurrent Glioblastoma: Efficacy, Safety, and Hepatocyte Growth Factor and O6-Methylguanine-DNA Methyltransferase Biomarker Analyses.","authors":"","doi":"10.1200/JCO-24-02040","DOIUrl":"10.1200/JCO-24-02040","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}