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Standardized Definitions for Efficacy End Points for Adjuvant Trials—The Updated STEEP Criteria 辅助试验疗效终点的标准化定义--最新的 STEEP 标准
IF 28.4 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-19 DOI: 10.1001/jamaoncol.2024.3888
Dominik Hlauschek, Christian Fesl, Michael Gnant
This Viewpoint discusses how the inclusion or exclusion of certain events in the standardization of clinical trial end points can affect the interpretation of results.
本视点讨论了在临床试验终点标准化中纳入或排除某些事件会如何影响结果的解释。
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引用次数: 0
Chimeric Antigen Receptor T Cells Targeting CD19 and GCC in Metastatic Colorectal Cancer 靶向 CD19 和 GCC 的嵌合抗原受体 T 细胞治疗转移性结直肠癌
IF 28.4 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-19 DOI: 10.1001/jamaoncol.2024.3891
Naifei Chen, Chengfei Pu, Lingling Zhao, Wei Li, Chang Wang, Ruihong Zhu, Tingting Liang, Chao Niu, Xi Huang, Haiyang Tang, Yizhuo Wang, Hang Yang, Beibei Jia, Xianyang Jiang, Guiting Han, Wensheng Wang, Dongqi Chen, Yiming Wang, Eric K. Rowinsky, Eugene Kennedy, Victor X. Lu, Guozhen Cui, Zhao Wu, Lei Xiao, Jiuwei Cui
ImportanceChimeric antigen receptor (CAR) T-cell therapy (CART) has transformed the treatment landscape of hematologic cancer, but has negligible effects for adult solid cancers. In this trial, an autologous CAR T-cell product demonstrated antitumor activity in heavily pretreated patients with metastatic colorectal cancer (mCRC).ObjectiveTo evaluate the safety and efficacy of guanylate cyclase-C (GCC19) CART in participants with metastatic colorectal cancer (mCRC).Design, Setting, and ParticipantsThis single-arm, nonrandomized, phase 1 trial was conducted at the First Hospital of Jilin University from December 3, 2020, to April 13, 2022. Data analysis was conducted from May 2022 to April 2024. Adults with relapsed and refractory mCRC expressing GCC were treated with GCC19CART, a mixture of autologous CAR T cells transduced with lentiviral vectors expressing genes that encode either CD-19 CAR or GCC CAR.Main Outcomes and MeasuresSafety and tolerability of CAR T-cell therapy targeting GCC in patients with mCRC without therapeutic options is capable of conferring a reasonable likeliness of clinical benefit. Other outcomes included objective response rate, progression-free survival, overall survival, and immune activation.ResultsOf 15 patients 9 (60%) were women, and the median (range) age was 44 (33-61) years. Treatment with GCC19CART was associated with the development of cytokine release syndrome and diarrhea in most patients, all of which were self-limited and manageable. The objective response rate was 40%, with a partial response in 2 of 8 and 4 of 7 patients treated with either 1 × 106 cells/kg or 2 × 106 cells/kg. Median overall survival was 22.8 months (95% CI, 13.4-26.1) at data cutoff; the median progress-free survival was 6.0 months in the high dose level group (95% CI, 3.0 to not available).Conclusions and RelevanceThe results of this nonrandomized clinical trial suggest that GCC19CART was safe and tolerable in heavily pretreated patients with mCRC and is the first CAR T-cell therapy known to produce objective clinical activity in refractory cancer. Given the paucity of effective therapeutics developed for colorectal cancer in recent decades, the observation that CD-19 CART target engagement can robustly induce GCC19CART target engagement sufficient to produce objective activity may serve as a foundation to develop effective cellular therapy in mCRC and other solid cancers.Trial RegistrationChinese Clinical Trial Registry: ChiCTR2000040645
重要性嵌合抗原受体(CAR)T 细胞疗法(CART)改变了血液肿瘤的治疗格局,但对成人实体瘤的疗效却微乎其微。在这项试验中,一种自体CAR T细胞产品在重度预处理的转移性结直肠癌(mCRC)患者中显示出抗肿瘤活性。目的评估鸟苷酸环化酶-C(GCC19)CART在转移性结直肠癌(mCRC)患者中的安全性和有效性。数据分析于 2022 年 5 月至 2024 年 4 月进行。表达GCC的复发性和难治性mCRC成人患者接受了GCC19CART治疗,这是一种用表达编码CD-19 CAR或GCC CAR基因的慢病毒载体转导的自体CAR T细胞混合物。主要结果和测量指标在没有治疗选择的mCRC患者中,靶向GCC的CAR T细胞疗法的安全性和耐受性能够带来合理的临床获益可能性。其他结果包括客观反应率、无进展生存期、总生存期和免疫激活。结果15名患者中有9名(60%)为女性,年龄中位数(范围)为44(33-61)岁。大多数患者在接受 GCC19CART 治疗后会出现细胞因子释放综合征和腹泻,但这些症状都是自限性的,可以控制。客观反应率为40%,在接受1×106细胞/千克或2×106细胞/千克治疗的8名患者中,有2人出现部分反应,7名患者中有4人出现部分反应。数据截止时,中位总生存期为22.8个月(95% CI,13.4-26.1个月);高剂量组的中位无进展生存期为6.0个月(95% CI,3.0-不可用)。结论与意义这项非随机临床试验的结果表明,GCC19CART在重度预处理的mCRC患者中是安全和可耐受的,是已知的首个能在难治性癌症中产生客观临床活性的CAR T细胞疗法。鉴于近几十年来针对结直肠癌开发的有效疗法很少,CD-19 CART靶点参与能强有力地诱导GCC19CART靶点参与,从而产生足够的客观活性,这一观察结果可能为开发针对mCRC和其他实体癌的有效细胞疗法奠定基础:中国临床试验注册中心
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引用次数: 0
Stereotactic vs Hypofractionated Radiotherapy for Inoperable Stage I Non–Small Cell Lung Cancer 无法手术的 I 期非小细胞肺癌的立体定向放疗与低分次放疗对比
IF 28.4 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-19 DOI: 10.1001/jamaoncol.2024.3089
Anand Swaminath, Sameer Parpia, Marcin Wierzbicki, Vijayananda Kundapur, Sergio Faria, Gordon S. Okawara, Theodoros K. Tsakiridis, Naseer Ahmed, Alexis Bujold, Khalid Hirmiz, Timothy Owen, Nelson Leong, Kevin Ramchandar, Edith Filion, Harold Lau, Zsolt Gabos, Robert Thompson, Brian Yaremko, Selma Mehiri, Alexander V. Louie, Kimmen Quan, Mark N. Levine, James R. Wright, Timothy J. Whelan
ImportanceStereotactic body radiotherapy (SBRT) is widely used for stage I medically inoperable non–small cell lung cancer (NSCLC), yet varied results from randomized clinical trials (RCTs) and concerns in treating centrally located tumors persist.ObjectiveTo examine whether SBRT would improve local control (LC) compared with hypofractionated conventional radiotherapy (CRT).Design, Setting, and ParticipantsThis phase 3 RCT was conducted in 16 Canadian centers. Patients with medically inoperable stage I (≤5 cm) NSCLC were randomized 2:1 to SBRT of 48 Gy in 4 fractions (peripheral NSCLC) or 60 Gy in 8 fractions (central NSCLC) vs CRT of 60 Gy in 15 fractions. Data were collected from May 2014 to January 2020, and data were analyzed from July 2022 to July 2023.InterventionsSBRT or CRT.Main Outcomes and MeasuresThe primary objective was to determine the effectiveness of SBRT compared with CRT based on LC at 3 years. Secondary outcomes included event-free survival, overall survival, and toxic effects. All radiation plans were subject to real-time/final review. Local failures were centrally adjudicated. The study was designed to detect a 3-year LC improvement of SBRT from 75% to 87.5%. The target sample size was 324 patients.ResultsOf 233 included patients, 119 (51.1%) were male, and the mean (SD) age was 75.4 (7.7) years; the median (IQR) follow-up was 36.1 (26.4-52.8) months. A total of 154 patients received SBRT and 79 received CRT. The 3-year LC was 87.6% (95% CI, 81.9%-93.4%) for SBRT and 81.2% (95% CI, 71.9%-90.5%) for CRT (hazard ratio [HR], 0.61; 95% CI, 0.31-1.20; P = .15). The HR was 1.02 (95% CI, 0.72-1.45; P = .87) for event-free survival and 1.18 (95% CI, 0.80-1.76; P = .40) for overall survival. Minimal acute toxic effects were observed. Among those randomized to SBRT, late grade 3 or 4 toxic effects occurred in 5 of 45 (11%) with central NSCLC and 2 of 109 (1.8%) with peripheral NSCLC; among those randomized to CRT, in 1 of 19 (5%) with central NSCLC and 1 of 60 (2%) with peripheral NSCLC. One patient who received SBRT for an ultracentral lesion (target overlapping proximal bronchus) experienced a possible treatment-related grade 5 event (hemoptysis).Conclusions and RelevanceThis RCT compared lung SBRT with hypofractionated CRT that included central/ultracentral tumors. No difference was detected in LC between groups. Severe toxic effects were limited, including patients with central tumors. The trial provides important prospective data evaluating SBRT; however, further research is necessary to determine if SBRT is more effective than CRT for peripheral and central NSCLC.Trial RegistrationClinicalTrials.gov Identifier: NCT03924869
重要性立体定向体放射治疗(SBRT)被广泛用于医学上无法手术的I期非小细胞肺癌(NSCLC),但随机临床试验(RCT)的结果不尽相同,治疗中心位置肿瘤的问题依然存在。目的研究与低分次常规放射治疗(CRT)相比,SBRT是否能改善局部控制(LC)。医学上无法手术的I期(≤5厘米)NSCLC患者按照2:1的比例随机接受48 Gy分4次(周边NSCLC)或60 Gy分8次(中心NSCLC)的SBRT与60 Gy分15次的CRT治疗。数据收集时间为2014年5月至2020年1月,数据分析时间为2022年7月至2023年7月。干预措施SBRT或CRT。主要结果和测量指标主要目的是根据3年后的LC确定SBRT与CRT相比的有效性。次要结果包括无事件生存期、总生存期和毒性反应。所有放射计划均接受实时/最终审查。局部失败由中央裁决。该研究旨在检测 SBRT 3 年生存率从 75% 提高到 87.5%。结果 在233例纳入患者中,119例(51.1%)为男性,平均(SD)年龄为75.4(7.7)岁;中位(IQR)随访时间为36.1(26.4-52.8)个月。共有154名患者接受了SBRT治疗,79名患者接受了CRT治疗。SBRT的3年生存率为87.6%(95% CI,81.9%-93.4%),CRT为81.2%(95% CI,71.9%-90.5%)(危险比[HR],0.61;95% CI,0.31-1.20;P = .15)。无事件生存率为 1.02 (95% CI, 0.72-1.45; P = .87),总生存率为 1.18 (95% CI, 0.80-1.76; P = .40)。急性毒性反应极小。在随机接受SBRT治疗的患者中,45例中心型NSCLC患者中有5例(11%)出现了晚期3级或4级毒性反应,109例外周型NSCLC患者中有2例(1.8%)出现了晚期3级或4级毒性反应;在随机接受CRT治疗的患者中,19例中心型NSCLC患者中有1例(5%)出现了晚期3级或4级毒性反应,60例外周型NSCLC患者中有1例(2%)出现了晚期3级或4级毒性反应。一名接受SBRT治疗超中心病灶(靶点与近端支气管重叠)的患者可能发生了治疗相关的5级事件(咯血)。两组患者的低密度脂蛋白血症无差异。严重毒性反应有限,包括中心性肿瘤患者。该试验提供了评估SBRT的重要前瞻性数据;但是,要确定SBRT是否比CRT对周围和中心NSCLC更有效,还需要进一步的研究:NCT03924869
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引用次数: 0
Molecular, Socioeconomic, and Clinical Factors Affecting Racial and Ethnic Disparities in Colorectal Cancer Survival. 影响结直肠癌种族和民族存活率差异的分子、社会经济和临床因素。
IF 28.4 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-12 DOI: 10.1001/jamaoncol.2024.3666
Mahmoud Yousef,Abdelrahman Yousef,Saikat Chowdhury,Mohammad M Fanaeian,Mark Knafl,Jennifer Peterson,Mohammad Zeineddine,Kristin Alfaro,Fadl Zeineddine,Drew Goldstein,Nicholas Hornstein,Arvind Dasari,Ryan Huey,Benny Johnson,Victoria Higbie,Alisha Bent,Bryan Kee,Michael Lee,Maria Pia Morelli,Van Karlyle Morris,Daniel Halperin,Michael J Overman,Christine Parseghian,Eduardo Vilar,Robert Wolff,Kanwal P Raghav,Michael G White,Abhineet Uppal,Ryan Sun,Wenyi Wang,Scott Kopetz,Jason Willis,John Paul Shen
ImportanceDisparity in overall survival (OS) and differences in the frequency of driver gene variants by race and ethnicity have been separately observed in patients with colorectal cancer; however, how these differences contribute to survival disparity is unknown.ObjectiveTo quantify the association of molecular, socioeconomic, and clinical covariates with racial and ethnic disparities in overall survival among patients with colorectal cancer.Design, Setting, and ParticipantsThis single-center cohort study was conducted at a tertiary-level cancer center using relevant data on all patients diagnosed with colorectal cancer from January 1, 1973, to March 1, 2023. The relative contribution of variables to the disparity was determined using mediation analysis with sequential multivariate Cox regression models.Main OutcomeOS, from diagnosis date and from start of first-line chemotherapy.ResultsThe study population of 47 178 patients (median [IQR] age, 57.0 [49-66] years; 20 465 [43.4%] females and 26 713 [56.6%] males; 3.0% Asian, 8.7% Black, 8.8% Hispanic, and 79.4% White individuals) had a median (IQR) follow-up from initial diagnosis of 124 (174) months and OS of 55 (145) months. Compared with White patients, Black patients had worse OS (hazard ratio [HR], 1.16; 95% CI, 1.09-1.24; P <.001), whereas Asian and Hispanic patients had better OS (HR, 0.66; 95% CI, 0.59-0.74; P <.001; and 0.86; 95% CI, 0.81-0.92; P <.001, respectively). When restricted to patients with metastatic disease, the greatest disparity was between Black patients compared with White patients (HR, 1.2; 95% CI, 1.06-1.37; P <.001). Evaluating changes in OS disparity over 20 years showed disparity decreasing among Asian, Hispanic, and White patients, but increasing between Black patients and White patients (HRs, 1.18; 95% CI, 1.07-1.31 for 2008-2012; 1.24, 95% CI, 1.08-1.42 for 2013-2017; and 1.50; 95% CI, 1.20-1.87 for 2018-2023). Survival outcomes for first-line chemotherapy were worse for Black patients compared with White patients (median OS, 18 vs 26 months; HR, 1.30; 95% CI, 1.01-1.70). Among 7628 patients who had clinical molecular testing, APC, KRAS, and PIK3CA showed higher variant frequency in Black patients (false discovery rate [FDR], 0.01; < 0.001; and 0.01, respectively), whereas BRAF and KIT were higher among White patients (FDR, 0.001 and 0.01). Mediation analysis identified neighborhood socioeconomic status as the greatest contributor to OS disparity (29%), followed by molecular characteristics (microsatellite instability status, KRAS variation and BRAF variation, 10%), and tumor sidedness (9%).ConclusionsThis single-center cohort study identified substantial OS disparity and differing frequencies of driver gene variations by race and ethnicity. Socioeconomic status had the largest contribution but accounted for less than one-third of the disparity, with substantial contribution from tumor molecular features. Further study of the associations of genetic ancestry and
重要性在结直肠癌患者中已分别观察到总生存期(OS)的差异以及不同种族和民族驱动基因变异频率的差异;然而,这些差异是如何导致生存期差异的尚不清楚。目的量化分子、社会经济和临床协变量与结直肠癌患者总生存期的种族和民族差异之间的关系。设计、设置和参与者这项单中心队列研究是在一家三级癌症中心进行的,使用了自 1973 年 1 月 1 日至 2023 年 3 月 1 日期间诊断为结直肠癌的所有患者的相关数据。主要结果OS、从诊断日期起和从开始一线化疗起。结果研究人群中有 47 178 名患者(中位数[IQR]年龄,57.0[49-66]岁;20 465[43.4%]名女性和26 713[56.6%]名男性;3.0%为亚裔、8.7%为黑人、8.8%为西班牙裔、79.4%为白人),自初次诊断起的中位(IQR)随访时间为124(174)个月,OS为55(145)个月。与白人患者相比,黑人患者的OS较差(危险比[HR],1.16;95% CI,1.09-1.24;P<.001),而亚裔和西班牙裔患者的OS较好(HR,分别为0.66;95% CI,0.59-0.74;P<.001;和0.86;95% CI,0.81-0.92;P<.001)。如果仅限于转移性疾病患者,黑人患者与白人患者之间的差异最大(HR,1.2;95% CI,1.06-1.37;P <.001)。评估20年间OS差异的变化显示,亚裔、西班牙裔和白人患者之间的差异在缩小,但黑人患者和白人患者之间的差异在扩大(2008-2012年的HR为1.18;95% CI为1.07-1.31;2013-2017年的HR为1.24,95% CI为1.08-1.42;2018-2023年的HR为1.50;95% CI为1.20-1.87)。与白人患者相比,黑人患者一线化疗的生存结果更差(中位OS,18个月 vs 26个月;HR,1.30;95% CI,1.01-1.70)。在接受临床分子检测的7628名患者中,黑人患者中APC、KRAS和PIK3CA的变异频率较高(假发现率[FDR]分别为0.01;<0.001;和0.01),而白人患者中BRAF和KIT的变异频率较高(FDR分别为0.001和0.01)。通过中介分析发现,邻里社会经济状况是导致OS差异的最大因素(29%),其次是分子特征(微卫星不稳定性状态、KRAS变异和BRAF变异,10%)和肿瘤侧位(9%)。社会经济状况的影响最大,但只占差距的不到三分之一,肿瘤分子特征的影响也很大。需要进一步研究遗传血统和结直肠癌分子发病机制与化疗反应之间的关联。
{"title":"Molecular, Socioeconomic, and Clinical Factors Affecting Racial and Ethnic Disparities in Colorectal Cancer Survival.","authors":"Mahmoud Yousef,Abdelrahman Yousef,Saikat Chowdhury,Mohammad M Fanaeian,Mark Knafl,Jennifer Peterson,Mohammad Zeineddine,Kristin Alfaro,Fadl Zeineddine,Drew Goldstein,Nicholas Hornstein,Arvind Dasari,Ryan Huey,Benny Johnson,Victoria Higbie,Alisha Bent,Bryan Kee,Michael Lee,Maria Pia Morelli,Van Karlyle Morris,Daniel Halperin,Michael J Overman,Christine Parseghian,Eduardo Vilar,Robert Wolff,Kanwal P Raghav,Michael G White,Abhineet Uppal,Ryan Sun,Wenyi Wang,Scott Kopetz,Jason Willis,John Paul Shen","doi":"10.1001/jamaoncol.2024.3666","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.3666","url":null,"abstract":"ImportanceDisparity in overall survival (OS) and differences in the frequency of driver gene variants by race and ethnicity have been separately observed in patients with colorectal cancer; however, how these differences contribute to survival disparity is unknown.ObjectiveTo quantify the association of molecular, socioeconomic, and clinical covariates with racial and ethnic disparities in overall survival among patients with colorectal cancer.Design, Setting, and ParticipantsThis single-center cohort study was conducted at a tertiary-level cancer center using relevant data on all patients diagnosed with colorectal cancer from January 1, 1973, to March 1, 2023. The relative contribution of variables to the disparity was determined using mediation analysis with sequential multivariate Cox regression models.Main OutcomeOS, from diagnosis date and from start of first-line chemotherapy.ResultsThe study population of 47 178 patients (median [IQR] age, 57.0 [49-66] years; 20 465 [43.4%] females and 26 713 [56.6%] males; 3.0% Asian, 8.7% Black, 8.8% Hispanic, and 79.4% White individuals) had a median (IQR) follow-up from initial diagnosis of 124 (174) months and OS of 55 (145) months. Compared with White patients, Black patients had worse OS (hazard ratio [HR], 1.16; 95% CI, 1.09-1.24; P &lt;.001), whereas Asian and Hispanic patients had better OS (HR, 0.66; 95% CI, 0.59-0.74; P &lt;.001; and 0.86; 95% CI, 0.81-0.92; P &lt;.001, respectively). When restricted to patients with metastatic disease, the greatest disparity was between Black patients compared with White patients (HR, 1.2; 95% CI, 1.06-1.37; P &lt;.001). Evaluating changes in OS disparity over 20 years showed disparity decreasing among Asian, Hispanic, and White patients, but increasing between Black patients and White patients (HRs, 1.18; 95% CI, 1.07-1.31 for 2008-2012; 1.24, 95% CI, 1.08-1.42 for 2013-2017; and 1.50; 95% CI, 1.20-1.87 for 2018-2023). Survival outcomes for first-line chemotherapy were worse for Black patients compared with White patients (median OS, 18 vs 26 months; HR, 1.30; 95% CI, 1.01-1.70). Among 7628 patients who had clinical molecular testing, APC, KRAS, and PIK3CA showed higher variant frequency in Black patients (false discovery rate [FDR], 0.01; &lt; 0.001; and 0.01, respectively), whereas BRAF and KIT were higher among White patients (FDR, 0.001 and 0.01). Mediation analysis identified neighborhood socioeconomic status as the greatest contributor to OS disparity (29%), followed by molecular characteristics (microsatellite instability status, KRAS variation and BRAF variation, 10%), and tumor sidedness (9%).ConclusionsThis single-center cohort study identified substantial OS disparity and differing frequencies of driver gene variations by race and ethnicity. Socioeconomic status had the largest contribution but accounted for less than one-third of the disparity, with substantial contribution from tumor molecular features. Further study of the associations of genetic ancestry and ","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":null,"pages":null},"PeriodicalIF":28.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174605","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}
引用次数: 0
Radiation-Associated Secondary Cancer in Patients With Breast Cancer Harboring TP53 Germline Variants. 携带 TP53 基因变异的乳腺癌患者中与辐射相关的继发性癌症
IF 28.4 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-12 DOI: 10.1001/jamaoncol.2024.3683
Gustav Y Cederquist,Lillian A Boe,Michael Walsh,Gary M Freedman,Kara N Maxwell,Neil Taunk,Lior Z Braunstein
{"title":"Radiation-Associated Secondary Cancer in Patients With Breast Cancer Harboring TP53 Germline Variants.","authors":"Gustav Y Cederquist,Lillian A Boe,Michael Walsh,Gary M Freedman,Kara N Maxwell,Neil Taunk,Lior Z Braunstein","doi":"10.1001/jamaoncol.2024.3683","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.3683","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":null,"pages":null},"PeriodicalIF":28.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174531","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}
引用次数: 0
Cervical Cancer Incidence in the US-Affiliated Pacific Islands. 隶属美国的太平洋岛屿的宫颈癌发病率。
IF 28.4 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-12 DOI: 10.1001/jamaoncol.2024.3675
Sameer V Gopalani,Jin Qin,Janos Baksa,Trevor D Thompson,Mona Saraiya,Virginia Senkomago,Paran Pordell,Youngju Jeong,Neal A Palafox,Martina Reichhardt,Lee E Buenconsejo-Lum
ImportanceThe World Health Organization has called for eliminating cervical cancer as a public health problem. Accurate and up-to-date estimates of population-based cervical cancer incidence are essential for monitoring progress toward elimination and informing local cancer control strategies, but these estimates are lacking for the US-Affiliated Pacific Islands (USAPI).ObjectiveTo calculate age-standardized incidence rates for cervical cancer in the 6 USAPI and compare these rates with rates in the US (50 states and the District of Columbia).Design, Setting, and ParticipantsThis cross-sectional study used population-based data from the Pacific Regional Central Cancer Registry for women aged 20 years or older who were diagnosed with invasive cervical cancer from January 1, 2007, to December 31, 2020. The registry comprises data on all cervical cancers from the USAPI, which include 3 US territories (American Samoa, Commonwealth of the Northern Mariana Islands, and Guam) and 3 freely associated states (Federated States of Micronesia [FSM], Republic of the Marshall Islands [RMI], and Republic of Palau). Data were analyzed from July 10, 2023, to November 28, 2023.Main Outcomes and MeasuresThe main outcome was age-standardized cervical cancer incidence rates, stratified by age, stage, and histologic code for the USAPI using population estimates from 3 different sources (US Census Bureau International Database, United Nations Population Division, and Pacific Data Hub). Rate ratios were calculated to compare incidence rates between the USAPI and the US.ResultsFrom 2007 to 2020, 409 cases of cervical cancer were diagnosed in the USAPI (median age at diagnosis, 46.0 years [25th-75th percentile, 39.0-55.0 years]), with an age-standardized incidence rate ranging from 21.7 (95% CI, 19.6-23.9) to 22.1 (95% CI, 20.0-24.4) per 100 000 women, depending on the population estimate. Incidence rates were highest in RMI, ranging from 58.1 (95% CI, 48.0-69.7) to 83.4 (95% CI, 68.3-101.0) per 100 000 women, followed by FSM, ranging from 28.7 (95% CI, 23.4-34.9) to 29.8 (95% CI, 24.3-36.3) per 100 000 women. Compared with the US, incidence rates were highest in RMI (rate ratio, 5.7 [95% CI, 4.7-6.8] to 8.2 [95% CI, 6.7-9.9]) and FSM (rate ratio; 2.8; 95% CI, 2.3-3.4). Of all cases in the USAPI, 213 (68.2%) were diagnosed at a late stage.Conclusions and RelevanceIn this cross-sectional study, cervical cancer remained a major public health issue in some USAPI, with RMI reporting the highest incidence rates. The findings suggest that improvements in human papillomavirus vaccination and cancer screening coverage through efforts tailored to the unique geographic, sociocultural, economic, and health care landscape of the USAPI may reduce the burden of cervical cancer.
重要性世界卫生组织呼吁消除宫颈癌这一公共卫生问题。准确和最新的宫颈癌发病率估计值对于监测消除宫颈癌的进展情况和为当地癌症控制策略提供信息至关重要,但美属太平洋岛屿(USAPI)却缺乏这些估计值。这项横断面研究使用了太平洋地区中央癌症登记处的人口数据,这些数据针对的是 2007 年 1 月 1 日至 2020 年 12 月 31 日期间被诊断出患有浸润性宫颈癌的 20 岁及以上女性。该登记处包括来自美国太平洋地区的所有宫颈癌数据,其中包括 3 个美国领地(美属萨摩亚、北马里亚纳群岛联邦和关岛)和 3 个自由联系州(密克罗尼西亚联邦、马绍尔群岛共和国和帕劳共和国)。主要结果和测量指标主要结果是年龄标准化的宫颈癌发病率,按年龄、分期和组织学代码进行分层,使用 3 个不同来源(美国人口普查局国际数据库、联合国人口司和太平洋数据中心)的人口估计值对美国亚太地区的宫颈癌发病率进行分析。结果从 2007 年到 2020 年,美国亚太地区共诊断出 409 例宫颈癌病例(诊断时的中位年龄为 46.0 岁 [第 25-75 百分位数,39.0-55.0 岁]),年龄标准化发病率为每 10 万名妇女中 21.7 例(95% CI,19.6-23.9 例)到 22.1 例(95% CI,20.0-24.4 例),具体取决于人口估计值。马绍尔群岛的发病率最高,每 100 000 名妇女中的发病率从 58.1(95% CI,48.0-69.7)到 83.4(95% CI,68.3-101.0)不等,其次是密克罗尼西亚联邦,每 100 000 名妇女中的发病率从 28.7(95% CI,23.4-34.9)到 29.8(95% CI,24.3-36.3)不等。与美国相比,RMI(比率比为 5.7 [95% CI, 4.7-6.8] 至 8.2 [95% CI, 6.7-9.9])和 FSM(比率比为 2.8; 95% CI, 2.3-3.4)的发病率最高。在美国亚太地区的所有病例中,有 213 例(68.2%)是在晚期确诊的。结论和相关性在这项横断面研究中,宫颈癌仍然是美国亚太地区一些国家的主要公共卫生问题,其中马绍尔群岛的发病率最高。研究结果表明,根据美国亚太地区独特的地理、社会文化、经济和医疗保健状况,提高人类乳头瘤病毒疫苗接种率和癌症筛查覆盖率,可以减轻宫颈癌的负担。
{"title":"Cervical Cancer Incidence in the US-Affiliated Pacific Islands.","authors":"Sameer V Gopalani,Jin Qin,Janos Baksa,Trevor D Thompson,Mona Saraiya,Virginia Senkomago,Paran Pordell,Youngju Jeong,Neal A Palafox,Martina Reichhardt,Lee E Buenconsejo-Lum","doi":"10.1001/jamaoncol.2024.3675","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.3675","url":null,"abstract":"ImportanceThe World Health Organization has called for eliminating cervical cancer as a public health problem. Accurate and up-to-date estimates of population-based cervical cancer incidence are essential for monitoring progress toward elimination and informing local cancer control strategies, but these estimates are lacking for the US-Affiliated Pacific Islands (USAPI).ObjectiveTo calculate age-standardized incidence rates for cervical cancer in the 6 USAPI and compare these rates with rates in the US (50 states and the District of Columbia).Design, Setting, and ParticipantsThis cross-sectional study used population-based data from the Pacific Regional Central Cancer Registry for women aged 20 years or older who were diagnosed with invasive cervical cancer from January 1, 2007, to December 31, 2020. The registry comprises data on all cervical cancers from the USAPI, which include 3 US territories (American Samoa, Commonwealth of the Northern Mariana Islands, and Guam) and 3 freely associated states (Federated States of Micronesia [FSM], Republic of the Marshall Islands [RMI], and Republic of Palau). Data were analyzed from July 10, 2023, to November 28, 2023.Main Outcomes and MeasuresThe main outcome was age-standardized cervical cancer incidence rates, stratified by age, stage, and histologic code for the USAPI using population estimates from 3 different sources (US Census Bureau International Database, United Nations Population Division, and Pacific Data Hub). Rate ratios were calculated to compare incidence rates between the USAPI and the US.ResultsFrom 2007 to 2020, 409 cases of cervical cancer were diagnosed in the USAPI (median age at diagnosis, 46.0 years [25th-75th percentile, 39.0-55.0 years]), with an age-standardized incidence rate ranging from 21.7 (95% CI, 19.6-23.9) to 22.1 (95% CI, 20.0-24.4) per 100 000 women, depending on the population estimate. Incidence rates were highest in RMI, ranging from 58.1 (95% CI, 48.0-69.7) to 83.4 (95% CI, 68.3-101.0) per 100 000 women, followed by FSM, ranging from 28.7 (95% CI, 23.4-34.9) to 29.8 (95% CI, 24.3-36.3) per 100 000 women. Compared with the US, incidence rates were highest in RMI (rate ratio, 5.7 [95% CI, 4.7-6.8] to 8.2 [95% CI, 6.7-9.9]) and FSM (rate ratio; 2.8; 95% CI, 2.3-3.4). Of all cases in the USAPI, 213 (68.2%) were diagnosed at a late stage.Conclusions and RelevanceIn this cross-sectional study, cervical cancer remained a major public health issue in some USAPI, with RMI reporting the highest incidence rates. The findings suggest that improvements in human papillomavirus vaccination and cancer screening coverage through efforts tailored to the unique geographic, sociocultural, economic, and health care landscape of the USAPI may reduce the burden of cervical cancer.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":null,"pages":null},"PeriodicalIF":28.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174532","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}
引用次数: 0
Accrual to Radiotherapy Trials in the US-Pitfalls and Potential Solutions. 美国放疗试验的累积--陷阱与潜在解决方案。
IF 28.4 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-12 DOI: 10.1001/jamaoncol.2024.3663
Nina N Sanford,William A Hall
{"title":"Accrual to Radiotherapy Trials in the US-Pitfalls and Potential Solutions.","authors":"Nina N Sanford,William A Hall","doi":"10.1001/jamaoncol.2024.3663","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.3663","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":null,"pages":null},"PeriodicalIF":28.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174624","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}
引用次数: 0
Heterogeneity of Residual Disease After Neoadjuvant Systemic Therapy in Breast Cancer: A Review. 乳腺癌新辅助系统疗法后残留疾病的异质性:综述。
IF 28.4 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-12 DOI: 10.1001/jamaoncol.2024.3679
Paolo Tarantino,Gabriel Hortobagyi,Sara M Tolaney,Elizabeth A Mittendorf
ImportanceOver the past 2 decades, systemic therapy for early-stage breast cancer has gradually moved from the adjuvant to the neoadjuvant setting. Administration of systemic therapy before surgery leads to potential improvements in surgical outcomes and allows for the assessment of the pathologic response to treatment. For patients with residual disease (RD), 3 adjuvant strategies have been shown to improve outcomes: (1) adjuvant trastuzumab emtansine for ERBB2-positive disease, (2) adjuvant capecitabine for triple-negative disease, and (3) adjuvant olaparib for patients with germline BRCA variants. Furthermore, studies are testing novel drugs in the postneoadjuvant setting. Given the potential to tailor adjuvant therapy based on the response to preoperative systemic therapy, recognizing the complexities of response to neoadjuvant therapy and moving beyond the binary paradigm of RD vs experiencing a pathologic complete response is becoming increasingly necessary.ObservationsNovel antibody-drug conjugates, anti-ERBB2 tyrosine kinase inhibitors, and immune checkpoint inhibitors are being evaluated as additional rescue options in phase 3 trials for patients with RD after neoadjuvant treatment. Concomitantly, the prognostic role of RD has been refined by the introduction of the residual cancer burden. In addition, the genomic landscape of RD has been found to be associated with long-term prognosis, as has the immune background of the disease evaluated via the presence of tumor-infiltrating lymphocytes. Lastly, the dynamics of circulating tumor DNA may allow for further improvement in prognostication by understanding which patients harbor detectable minimal RD.Conclusions and RelevanceEscalating adjuvant treatment has led to meaningful survival improvements among patients with breast cancer and RD after neoadjuvant therapy. Uncovering the anatomic and biological intricacies of RD will allow for increased precision in postneoadjuvant treatments, moving beyond the binary paradigm of RD vs pathologic complete response, toward more tailored rescue strategies in the adjuvant setting.
重要性在过去 20 年中,早期乳腺癌的全身治疗已逐渐从辅助治疗转向新辅助治疗。在手术前进行全身治疗有可能改善手术效果,并可评估病理对治疗的反应。对于有残留疾病(RD)的患者,有三种辅助治疗策略可改善预后:(1)针对ERBB2阳性疾病的辅助曲妥珠单抗;(2)针对三阴性疾病的辅助卡培他滨;以及(3)针对有种系BRCA变异的患者的辅助奥拉帕利。此外,还有研究正在对新辅助治疗后的新型药物进行测试。鉴于根据术前全身治疗反应定制辅助治疗的潜力,认识到新辅助治疗反应的复杂性并超越 RD 与病理完全反应的二元范式变得越来越有必要。观察结果新型抗体药物共轭物、抗 ERBB2 酪氨酸激酶抑制剂和免疫检查点抑制剂正被评估为新辅助治疗后 RD 患者 3 期试验中的额外挽救方案。与此同时,残留癌负担的引入也完善了 RD 的预后作用。此外,还发现 RD 的基因组结构与长期预后有关,通过肿瘤浸润淋巴细胞的存在评估疾病的免疫背景也与长期预后有关。最后,通过了解哪些患者体内存在可检测到的最小 RD,循环肿瘤 DNA 的动态变化可进一步改善预后。揭示 RD 在解剖学和生物学上的复杂性将有助于提高新辅助治疗后治疗的精确性,超越 RD 与病理完全反应的二元模式,在辅助治疗中采取更有针对性的挽救策略。
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引用次数: 0
Externally Controlled Studies Using Real-World Data in Patients With Hematological Cancers 使用血液肿瘤患者真实世界数据的外部对照研究
IF 28.4 1区 医学 Q1 ONCOLOGY Pub Date : 2024-08-29 DOI: 10.1001/jamaoncol.2024.3466
Sjoerd J. F. Hermans, Niek G. van der Maas, Yvette van Norden, Avinash G. Dinmohamed, Elizabeth Berkx, Peter C. Huijgens, Donna R. Rivera, R. Angelo de Claro, Francesco Pignatti, Jurjen Versluis, Jan J. Cornelissen
ImportanceThe use of real-world data (RWD) external control arms in prospective studies is increasing. The advantages, including the immediate availability of a control population, must be balanced with the requirements of meeting evidentiary standards.ObjectiveTo address the question of whether and to what extent the methods of RWD studies compare to standard methods used in randomized clinical trials.Evidence ReviewA systematic search across 4 electronic databases and Google Scholar was conducted from January 1, 2000, to October 23, 2023. Studies were included in the systematic review if they compared an intervention arm in a clinical trial to an RWD control arm in patients with hematological cancers and if they were published between 2000 and 2023.FindingsThirty-two prospective intervention studies incorporating external control data from RWD sources of patients with hematological cancers were identified. A total of 4306 patients from intervention arms and 10 594 from RWD control arms were included across all studies. Only 2 studies (6%) included prospectively collected RWD. The complete trial inclusion criteria were applied to the RWD cohort in 7 studies (22%). Four studies (13%) published the statistical analysis plan and prespecified use of RWD. A total of 23 studies (72%) applied matching algorithms for trial and RWD cohorts, including matching for demographic, disease, and/or therapy-related characteristics. The end point criteria were the same as the trial in 8 studies (25%). In contrast, 12 studies (38%) used different end points, and 12 (38%) did not provide an end point definition for the RWD. Twelve studies (38%) had a median follow-up difference of less than a year between arms. Eight studies (25%) reported toxic effect data for the trial arm, of which 5 studies reported toxic effect data for the RWD arm.Conclusions and RelevanceIn this systematic review, limitations were observed in the application of clinical trial eligibility criteria to RWD, statistical rigor and application of matching methods, the definition of end points, follow-up, and reporting of adverse events, which may challenge the conclusions reported in studies using RWD.
重要性在前瞻性研究中使用真实世界数据(RWD)外部对照臂的情况越来越多。证据综述 2000 年 1 月 1 日至 2023 年 10 月 23 日,对 4 个电子数据库和 Google Scholar 进行了系统检索。将血液肿瘤患者临床试验中的干预组与RWD对照组进行比较的研究,以及在2000年至2023年期间发表的研究均被纳入系统综述。所有研究共纳入了4306名干预组患者和10 594名RWD对照组患者。只有 2 项研究(6%)纳入了前瞻性收集的 RWD。7项研究(22%)对RWD队列采用了完整的试验纳入标准。有 4 项研究(13%)公布了统计分析计划,并预先指定使用 RWD。共有 23 项研究(72%)对试验队列和 RWD 队列采用了匹配算法,包括人口统计、疾病和/或治疗相关特征的匹配。有 8 项研究(25%)的终点标准与试验相同。相比之下,12 项研究(38%)采用了不同的终点,12 项研究(38%)没有提供 RWD 的终点定义。12项研究(38%)的两组随访时间中位数相差不到一年。8项研究(25%)报告了试验组的毒副作用数据,其中5项研究报告了RWD组的毒副作用数据。结论与相关性在本系统综述中,观察到RWD在临床试验资格标准的应用、统计学的严谨性和匹配方法的应用、终点的定义、随访和不良事件的报告等方面存在局限性,这可能会对使用RWD的研究报告的结论提出质疑。
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引用次数: 0
Caring for Your Heart During Cancer Treatment 癌症治疗期间的心脏护理
IF 28.4 1区 医学 Q1 ONCOLOGY Pub Date : 2024-08-29 DOI: 10.1001/jamaoncol.2024.3033
Manu Mysore, Dylan Singhi, Eric K. Singhi
This JAMA Oncology Patient Page describes cardio-oncology, a relatively new area in medicine that focuses on taking care of the heart while going through cancer treatments.
这篇《美国医学会肿瘤学杂志》的 "肿瘤患者页面 "介绍了心脏肿瘤学,这是一个相对较新的医学领域,其重点是在治疗癌症的同时保护心脏。
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引用次数: 0
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JAMA Oncology
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