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Phase II Trial of Enfortumab Vedotin in Patients With Previously Treated Advanced Head and Neck Cancer. Enfortumab Vedotin 用于曾接受过治疗的晚期头颈癌患者的 II 期试验。
IF 42.1 1区 医学 Q1 ONCOLOGY Pub Date : 2024-10-31 DOI: 10.1200/JCO.24.00646
Paul L Swiecicki, Emrullah Yilmaz, Ari Joseph Rosenberg, Takao Fujisawa, Justine Yang Bruce, Changting Meng, Michele Wozniak, Yongyun Zhao, Michael Mihm, Jason Kaplan, Seema Gorla, Jessica L Geiger

Purpose: Despite advances in immunotherapy, unresectable recurrent/metastatic head and neck cancer (HNC) carries a poor prognosis, and effective treatments are needed. As nectin-4 is widely expressed in HNC, enfortumab vedotin (EV), a nectin-4-directed antibody-drug conjugate, was explored in HNC in EV-202 (ClinicalTrials.gov identifier: NCT04225117).

Methods: This open-label, multicohort, phase II study evaluated intravenous EV 1.25 mg/kg on days 1, 8, and 15 of each 28-day cycle. In the HNC cohort, eligible patients had recurrent/metastatic HNC and had received platinum-based therapy for locally advanced/metastatic disease and a PD-1/PD-L1 inhibitor. The primary end point was investigator-assessed confirmed objective response rate (ORR) per RECIST version 1.1. Secondary end points were investigator-assessed duration of response (DOR), disease control rate (DCR), and progression-free survival (PFS); overall survival (OS); and safety.

Results: The primary analysis included 46 patients; all received EV (median follow-up, 9.3 months). Most patients (52.2%) had ≥3 previous lines of systemic therapy in the metastatic setting. Confirmed ORR was 23.9%, DCR was 56.5%, and median DOR was not reached (median DOR was 9.4 months at a later data cutoff [median follow-up, 11.3 months]). Median PFS and OS were 3.9 and 6.0 months, respectively. Treatment-related adverse events (TRAEs) occurring in >20% of patients were alopecia (28.3%), fatigue (26.1%), and peripheral sensory neuropathy (23.9%). Sixteen patients (34.8%) experienced grade ≥3 TRAEs; anemia and decreased neutrophil count occurred in ≥1 patient (both n = 2; 4.3%).

Conclusion: EV demonstrated antitumor activity in heavily pretreated HNC. Safety was consistent with the known safety profile of EV; no new safety signals were identified. These data support further evaluation of EV for advanced HNC not amenable to definitive local therapy.

目的:尽管免疫疗法取得了进展,但不可切除的复发/转移性头颈癌(HNC)预后较差,需要有效的治疗方法。由于Nectin-4在HNC中广泛表达,因此在EV-202(ClinicalTrials.gov标识符:NCT04225117)中探讨了恩福单抗韦多汀(EV)这种Nectin-4导向的抗体药物共轭物在HNC中的应用:这项开放标签、多队列的II期研究评估了静脉注射EV 1.25 mg/kg,每28天周期的第1、8和15天各注射1.25 mg/kg。在HNC队列中,符合条件的患者均为复发性/转移性HNC患者,并曾接受过铂类治疗局部晚期/转移性疾病和PD-1/PD-L1抑制剂。主要终点是根据 RECIST 1.1 版由研究者评估确认的客观反应率 (ORR)。次要终点为研究者评估的应答持续时间(DOR)、疾病控制率(DCR)和无进展生存期(PFS);总生存期(OS);以及安全性:主要分析包括 46 名患者;所有患者都接受了 EV 治疗(中位随访时间为 9.3 个月)。大多数患者(52.2%)既往接受过≥3种转移性全身治疗。确诊ORR为23.9%,DCR为56.5%,未达到中位DOR(后期数据截止时,中位DOR为9.4个月[中位随访11.3个月])。中位 PFS 和 OS 分别为 3.9 个月和 6.0 个月。超过20%的患者出现了治疗相关不良事件(TRAEs),包括脱发(28.3%)、疲劳(26.1%)和周围感觉神经病变(23.9%)。16名患者(34.8%)出现≥3级TRAEs;≥1名患者出现贫血和中性粒细胞计数减少(均为n = 2;4.3%):EV对重度预处理的HNC具有抗肿瘤活性。安全性与EV已知的安全性特征一致;未发现新的安全性信号。这些数据支持进一步评估EV对无法接受明确局部治疗的晚期HNC的治疗效果。
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引用次数: 0
Onvansertib in Combination With Chemotherapy and Bevacizumab in Second-Line Treatment of KRAS-Mutant Metastatic Colorectal Cancer: A Single-Arm, Phase II Trial. Onvansertib 联合化疗和贝伐单抗二线治疗 KRAS 突变转移性结直肠癌:单臂 II 期试验。
IF 42.1 1区 医学 Q1 ONCOLOGY Pub Date : 2024-10-30 DOI: 10.1200/JCO-24-01266
Daniel H Ahn, Maya Ridinger, Timothy L Cannon, Lawrence Mendelsohn, Jason S Starr, Joleen M Hubbard, Anup Kasi, Afsaneh Barzi, Errin Samuëlsz, Anju Karki, Ramanand A Subramanian, Divora Yemane, Roy Kim, Chu-Chiao Wu, Peter J P Croucher, Tod Smeal, Fairooz F Kabbinavar, Heinz-Josef Lenz

Purpose: This phase II study evaluated the efficacy and tolerability of onvansertib, a polo-like kinase 1 (PLK1) inhibitor, in combination with fluorouracil, leucovorin, and irinotecan (FOLFIRI) + bevacizumab for the second-line treatment of KRAS-mutant metastatic colorectal cancer (mCRC).

Patients and methods: This multicenter, open-label, single-arm study enrolled patients with KRAS-mutated mCRC previously treated with oxaliplatin and fluorouracil with or without bevacizumab. Patients received onvansertib (15 mg/m2 once daily on days 1-5 and 15-19 of a 28-day cycle) and FOLFIRI + bevacizumab (days 1 and 15). The primary end point was the objective response rate (ORR), and secondary endpoints included progression-free survival (PFS), duration of response (DOR), and tolerability. Translational and preclinical studies were conducted in KRAS-mutant CRC.

Results: Among the 53 patients treated, the confirmed ORR was 26.4% (95% CI, 15.3 to 40.3). The median DOR was 11.7 months (95% CI, 9.4 to not reached). Grade 3/4 adverse events were reported in 62% of patients. A post hoc analysis revealed that patients with no prior bevacizumab treatment had a significantly higher ORR and longer PFS compared with patients with prior bevacizumab treatment: ORR of 76.9% versus 10.0% (odds ratio of 30.0, P < .001) and median PFS of 14.9 months versus 6.6 months (hazard ratio of 0.16, P < .001). Our translational findings support that prior bevacizumab exposure contributes to onvansertib resistance. Preclinically, we showed that onvansertib inhibited the hypoxia pathway and exhibited robust antitumor activity in combination with bevacizumab through the inhibition of angiogenesis.

Conclusion: Onvansertib in combination with FOLFIRI + bevacizumab showed significant activity in the second-line treatment of patients with KRAS-mutant mCRC, particularly in patients with no prior bevacizumab treatment. These findings led to the evaluation of the combination in the first-line setting (ClinicalTrails.gov identifier: NCT06106308).

目的:这项II期研究评估了onvansertib(一种多聚样激酶1(PLK1)抑制剂)与氟尿嘧啶、亮菌素和伊立替康(FOLFIRI)+贝伐单抗联合用于KRAS突变转移性结直肠癌(mCRC)二线治疗的疗效和耐受性:这项多中心、开放标签、单臂研究招募了曾接受奥沙利铂和氟尿嘧啶联合或不联合贝伐珠单抗治疗的KRAS突变mCRC患者。患者接受安万斯替布(15 mg/m2,每天一次,28 天为一个周期,第 1-5 天和第 15-19 天)和 FOLFIRI + 贝伐珠单抗(第 1 天和第 15 天)治疗。主要终点是客观反应率(ORR),次要终点包括无进展生存期(PFS)、反应持续时间(DOR)和耐受性。在 KRAS 突变的 CRC 中进行了转化和临床前研究:在接受治疗的 53 名患者中,确诊 ORR 为 26.4%(95% CI,15.3 至 40.3)。中位DOR为11.7个月(95% CI,9.4至未达到)。62%的患者出现了3/4级不良反应。一项事后分析显示,与既往接受过贝伐珠单抗治疗的患者相比,既往未接受过贝伐珠单抗治疗的患者的ORR明显更高,PFS也更长:ORR为76.9%对10.0%(几率比为30.0,P < .001),中位PFS为14.9个月对6.6个月(危险比为0.16,P < .001)。我们的转化研究结果支持先前贝伐珠单抗暴露会导致昂万舍替耐药。临床前研究表明,onvansertib可抑制缺氧通路,并通过抑制血管生成与贝伐珠单抗联用显示出强大的抗肿瘤活性:结论:onvansertib联合FOLFIRI+贝伐珠单抗在KRAS突变mCRC患者的二线治疗中表现出显著的活性,尤其是在既往未接受过贝伐珠单抗治疗的患者中。这些研究结果促成了在一线治疗中对联合用药的评估(ClinicalTrails.gov 标识符:NCT06106308)。
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引用次数: 0
Second Primary Cancer Risks After Breast Cancer in BRCA1 and BRCA2 Pathogenic Variant Carriers. BRCA1 和 BRCA2 致病变异携带者患乳腺癌后的第二原发性癌症风险。
IF 42.1 1区 医学 Q1 ONCOLOGY Pub Date : 2024-10-29 DOI: 10.1200/JCO.24.01146
Isaac Allen, Hend Hassan, Yvonne Walburga, Catherine Huntley, Lucy Loong, Tameera Rahman, Sophie Allen, Alice Garrett, Bethany Torr, Andrew Bacon, Craig Knott, Sophie Jose, Sally Vernon, Margreet Lüchtenborg, Joanna Pethick, Francesco Santaniello, Shilpi Goel, Ying-Wen Wang, Katrina Lavelle, Fiona McRonald, Diana Eccles, Eva Morris, Steven Hardy, Clare Turnbull, Marc Tischkowitz, Paul Pharoah, Antonis C Antoniou

Purpose: Second primary cancer (SPC) risks after breast cancer (BC) in BRCA1/BRCA2 pathogenic variant (PV) carriers are uncertain. We estimated relative and absolute risks using a novel linkage of genetic testing data to population-scale National Disease Registration Service and Hospital Episode Statistics electronic health records.

Methods: We followed 25,811 females and 480 males diagnosed with BC and tested for germline BRCA1/BRCA2 PVs in NHS Clinical Genetics centers in England between 1995 and 2019 until SPC diagnosis, death, migration, contralateral breast/ovarian surgery plus 1 year, or the 31st of December 2020. We estimated standardized incidence ratios (SIRs) using English population incidences, hazard ratios (HRs) comparing carriers to noncarriers using Cox regression, and Kaplan-Meier 10-year cumulative risks.

Results: There were 1,840 BRCA1 and 1,750 BRCA2 female PV carriers. Compared with population incidences, BRCA1 carriers had elevated contralateral BC (CBC; SIR, 15.6 [95% CI, 11.8 to 20.2]), ovarian (SIR, 44.0 [95% CI, 31.4 to 59.9]), combined nonbreast/ovarian (SIR, 2.18 [95% CI, 1.59 to 2.92]), colorectal (SIR, 4.80 [95% CI, 2.62 to 8.05]), and endometrial (SIR, 2.92 [95% CI, 1.07 to 6.35]) SPC risks. BRCA2 carriers had elevated CBC (SIR, 7.70 [95% CI, 5.45 to 10.6]), ovarian (SIR, 16.8 [95% CI, 10.3 to 26.0]), pancreatic (SIR, 5.42 [95% CI, 2.09 to 12.5]), and combined nonbreast/ovarian (SIR, 1.68 [95% CI, 1.24 to 2.23]) SPC risks. Compared with females without BRCA1/BRCA2 PVs on testing, BRCA1 carriers had elevated CBC (HR, 3.60 [95% CI, 2.65 to 4.90]), ovarian (HR, 33.0 [95% CI, 19.1 to 57.1]), combined nonbreast/ovarian (HR, 1.45 [95% CI, 1.05 to 2.01]), and colorectal (HR, 2.93 [95% CI, 1.53 to 5.62]) SPC risks. BRCA2 carriers had elevated CBC (HR, 2.40 [95% CI, 1.70 to 3.40]), ovarian (HR, 12.0 [95% CI, 6.70 to 21.5]), and pancreatic (HR, 3.56 [95% CI, 1.34 to 9.48]) SPC risks. Ten-year cumulative CBC, ovarian, and combined nonbreast/ovarian cancer risks were 16%/6.3%/7.8% (BRCA1 carriers), 12%/3.0%/6.2% (BRCA2 carriers), and 3.6%/0.4%/4.9% (noncarriers). Male BRCA2 carriers had higher CBC (HR, 13.1 [95% CI, 1.19 to 146]) and prostate (HR, 5.61 [95% CI, 1.96 to 16.0]) SPC risks than noncarriers.

Conclusion: Survivors of BC carrying BRCA1 and BRCA2 PVs are at high SPC risk. They may benefit from enhanced surveillance and risk-reduction measures.

目的:BRCA1/BRCA2致病变异体(PV)携带者罹患乳腺癌(BC)后的第二原发性癌症(SPC)风险尚不确定。我们利用基因检测数据与人口规模的国家疾病登记服务和医院病历统计电子健康记录的新型关联,估算了相对风险和绝对风险:我们对 1995 年至 2019 年期间英国国家医疗服务系统(NHS)临床遗传学中心诊断为 BC 并进行了种系 BRCA1/BRCA2 PV 检测的 25811 名女性和 480 名男性进行了随访,直至 SPC 诊断、死亡、迁移、对侧乳房/卵巢手术加 1 年或 2020 年 12 月 31 日。我们利用英国人口发病率估算了标准化发病率(SIR),利用 Cox 回归估算了携带者与非携带者的危险比(HR),并估算了 Kaplan-Meier 10 年累积风险:共有 1,840 名 BRCA1 和 1,750 名 BRCA2 女性 PV 携带者。9])、合并非乳腺癌/卵巢癌(SIR,2.18 [95% CI,1.59 至 2.92])、结直肠癌(SIR,4.80 [95% CI,2.62 至 8.05])和子宫内膜癌(SIR,2.92 [95% CI,1.07 至 6.35])的 SPC 风险。BRCA2携带者的CBC(SIR,7.70 [95% CI,5.45至10.6])、卵巢(SIR,16.8 [95% CI,10.3至26.0])、胰腺(SIR,5.42 [95% CI,2.09至12.5])和非乳腺/卵巢联合(SIR,1.68 [95% CI,1.24至2.23])SPC风险升高。与检测时未发现 BRCA1/BRCA2 PV 的女性相比,BRCA1 携带者的 CBC(HR,3.60 [95% CI,2.65 至 4.90])、卵巢(HR,33.0 [95% CI,19.1 至 57.1])、合并非乳腺/卵巢(HR,1.45 [95% CI,1.05 至 2.01])和结直肠(HR,2.93 [95% CI,1.53 至 5.62])SPC 风险升高。BRCA2携带者的CBC(HR,2.40 [95% CI,1.70至3.40])、卵巢(HR,12.0 [95% CI,6.70至21.5])和胰腺(HR,3.56 [95% CI,1.34至9.48])SPC风险升高。CBC、卵巢癌和非乳腺癌/卵巢癌的十年累积风险分别为16%/6.3%/7.8%(BRCA1携带者)、12%/3.0%/6.2%(BRCA2携带者)和3.6%/0.4%/4.9%(非携带者)。男性 BRCA2 携带者的 CBC(HR,13.1 [95% CI,1.19 至 146])和前列腺(HR,5.61 [95% CI,1.96 至 16.0])SPC 风险高于非携带者:结论:携带 BRCA1 和 BRCA2 PV 的 BC 幸存者具有较高的 SPC 风险。结论:携带 BRCA1 和 BRCA2 PV 的 BC 幸存者具有较高的 SPC 风险,加强监测和降低风险的措施可使他们受益。
{"title":"Second Primary Cancer Risks After Breast Cancer in <i>BRCA1</i> and <i>BRCA2</i> Pathogenic Variant Carriers.","authors":"Isaac Allen, Hend Hassan, Yvonne Walburga, Catherine Huntley, Lucy Loong, Tameera Rahman, Sophie Allen, Alice Garrett, Bethany Torr, Andrew Bacon, Craig Knott, Sophie Jose, Sally Vernon, Margreet Lüchtenborg, Joanna Pethick, Francesco Santaniello, Shilpi Goel, Ying-Wen Wang, Katrina Lavelle, Fiona McRonald, Diana Eccles, Eva Morris, Steven Hardy, Clare Turnbull, Marc Tischkowitz, Paul Pharoah, Antonis C Antoniou","doi":"10.1200/JCO.24.01146","DOIUrl":"10.1200/JCO.24.01146","url":null,"abstract":"<p><strong>Purpose: </strong>Second primary cancer (SPC) risks after breast cancer (BC) in <i>BRCA1/BRCA2</i> pathogenic variant (PV) carriers are uncertain. We estimated relative and absolute risks using a novel linkage of genetic testing data to population-scale National Disease Registration Service and Hospital Episode Statistics electronic health records.</p><p><strong>Methods: </strong>We followed 25,811 females and 480 males diagnosed with BC and tested for germline <i>BRCA1/BRCA2</i> PVs in NHS Clinical Genetics centers in England between 1995 and 2019 until SPC diagnosis, death, migration, contralateral breast/ovarian surgery plus 1 year, or the 31st of December 2020. We estimated standardized incidence ratios (SIRs) using English population incidences, hazard ratios (HRs) comparing carriers to noncarriers using Cox regression, and Kaplan-Meier 10-year cumulative risks.</p><p><strong>Results: </strong>There were 1,840 <i>BRCA1</i> and 1,750 <i>BRCA2</i> female PV carriers. Compared with population incidences, <i>BRCA1</i> carriers had elevated contralateral BC (CBC; SIR, 15.6 [95% CI, 11.8 to 20.2]), ovarian (SIR, 44.0 [95% CI, 31.4 to 59.9]), combined nonbreast/ovarian (SIR, 2.18 [95% CI, 1.59 to 2.92]), colorectal (SIR, 4.80 [95% CI, 2.62 to 8.05]), and endometrial (SIR, 2.92 [95% CI, 1.07 to 6.35]) SPC risks. <i>BRCA2</i> carriers had elevated CBC (SIR, 7.70 [95% CI, 5.45 to 10.6]), ovarian (SIR, 16.8 [95% CI, 10.3 to 26.0]), pancreatic (SIR, 5.42 [95% CI, 2.09 to 12.5]), and combined nonbreast/ovarian (SIR, 1.68 [95% CI, 1.24 to 2.23]) SPC risks. Compared with females without <i>BRCA1/BRCA2</i> PVs on testing, <i>BRCA1</i> carriers had elevated CBC (HR, 3.60 [95% CI, 2.65 to 4.90]), ovarian (HR, 33.0 [95% CI, 19.1 to 57.1]), combined nonbreast/ovarian (HR, 1.45 [95% CI, 1.05 to 2.01]), and colorectal (HR, 2.93 [95% CI, 1.53 to 5.62]) SPC risks. <i>BRCA2</i> carriers had elevated CBC (HR, 2.40 [95% CI, 1.70 to 3.40]), ovarian (HR, 12.0 [95% CI, 6.70 to 21.5]), and pancreatic (HR, 3.56 [95% CI, 1.34 to 9.48]) SPC risks. Ten-year cumulative CBC, ovarian, and combined nonbreast/ovarian cancer risks were 16%/6.3%/7.8% (<i>BRCA1</i> carriers), 12%/3.0%/6.2% (<i>BRCA2</i> carriers), and 3.6%/0.4%/4.9% (noncarriers). Male <i>BRCA2</i> carriers had higher CBC (HR, 13.1 [95% CI, 1.19 to 146]) and prostate (HR, 5.61 [95% CI, 1.96 to 16.0]) SPC risks than noncarriers.</p><p><strong>Conclusion: </strong>Survivors of BC carrying <i>BRCA1</i> and <i>BRCA2</i> PVs are at high SPC risk. They may benefit from enhanced surveillance and risk-reduction measures.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2401146"},"PeriodicalIF":42.1,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7616773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545726","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}
引用次数: 0
Phase III Evaluation of Treatment Combinations in Three-Arm Trials. 三臂试验中治疗组合的 III 期评估。
IF 42.1 1区 医学 Q1 ONCOLOGY Pub Date : 2024-10-28 DOI: 10.1200/JCO-24-01476
Edward L Korn, Carmen J Allegra, Boris Freidlin

Phase III trials that randomly assign patients to a control treatment (C), an experimental treatment (A), or a combination treatment (AB) should be designed with the goal to recommend the best treatment: AB (if it is better than A and C), A (if it is better than C, and AB is not better than A), or C (if neither AB nor A is better than C). However, this goal can be challenging to achieve with statistical confidence. We performed a survey of cancer trials published in five journals from January 2018 to May 2024 to assess the trial designs being used in this setting and found that three quarters of them did not have a provision for a formal comparison of the AB treatment arm with the A treatment arm, a possible shortcoming. A limited simulation evaluates two analysis strategies that incorporate an AB versus A comparison and is used to formulate some recommendations for designing these types of trials.

随机分配患者接受对照治疗(C)、试验性治疗(A)或综合治疗(AB)的 III 期试验,应以推荐最佳治疗为目标:AB(如果它优于 A 和 C)、A(如果它优于 C,而 AB 不优于 A)或 C(如果 AB 和 A 都不优于 C)。然而,要在统计置信度上实现这一目标可能具有挑战性。我们对 2018 年 1 月至 2024 年 5 月期间在五种期刊上发表的癌症试验进行了调查,以评估在这种情况下使用的试验设计,结果发现四分之三的试验没有规定对 AB 治疗组和 A 治疗组进行正式比较,这可能是一个缺陷。通过有限的模拟,评估了纳入AB与A对比的两种分析策略,并以此为基础制定了设计此类试验的一些建议。
{"title":"Phase III Evaluation of Treatment Combinations in Three-Arm Trials.","authors":"Edward L Korn, Carmen J Allegra, Boris Freidlin","doi":"10.1200/JCO-24-01476","DOIUrl":"https://doi.org/10.1200/JCO-24-01476","url":null,"abstract":"<p><p>Phase III trials that randomly assign patients to a control treatment (C), an experimental treatment (A), or a combination treatment (AB) should be designed with the goal to recommend the best treatment: AB (if it is better than A and C), A (if it is better than C, and AB is not better than A), or C (if neither AB nor A is better than C). However, this goal can be challenging to achieve with statistical confidence. We performed a survey of cancer trials published in five journals from January 2018 to May 2024 to assess the trial designs being used in this setting and found that three quarters of them did not have a provision for a formal comparison of the AB treatment arm with the A treatment arm, a possible shortcoming. A limited simulation evaluates two analysis strategies that incorporate an AB versus A comparison and is used to formulate some recommendations for designing these types of trials.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2401476"},"PeriodicalIF":42.1,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522039","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
Oncology Care Model and Ripple Effects of Value-Based Care. 肿瘤护理模式和基于价值的护理的涟漪效应。
IF 42.1 1区 医学 Q1 ONCOLOGY Pub Date : 2024-10-28 DOI: 10.1200/JCO-24-01983
Gabriel A Brooks, Nancy L Keating
{"title":"Oncology Care Model and Ripple Effects of Value-Based Care.","authors":"Gabriel A Brooks, Nancy L Keating","doi":"10.1200/JCO-24-01983","DOIUrl":"https://doi.org/10.1200/JCO-24-01983","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2401983"},"PeriodicalIF":42.1,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522038","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
Reply to Y. Liang et al. 对 Y. Liang 等人的答复
IF 42.1 1区 医学 Q1 ONCOLOGY Pub Date : 2024-10-28 DOI: 10.1200/JCO-24-01794
Lukas Perkhofer, Thomas Seufferlein, Anna Melzer, Thomas J Ettrich
{"title":"Reply to Y. Liang et al.","authors":"Lukas Perkhofer, Thomas Seufferlein, Anna Melzer, Thomas J Ettrich","doi":"10.1200/JCO-24-01794","DOIUrl":"https://doi.org/10.1200/JCO-24-01794","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2401794"},"PeriodicalIF":42.1,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522040","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
Risks of Organ Preservation in Rectal Cancer: Data From Two International Registries on Rectal Cancer. 直肠癌保留器官的风险:来自两个国际直肠癌登记处的数据。
IF 42.1 1区 医学 Q1 ONCOLOGY Pub Date : 2024-10-28 DOI: 10.1200/JCO.24.00405
Laura M Fernandez, Guilherme P São Julião, Carlos Cerdan Santacruz, Andrew G Renehan, Oscar Cano-Valderrama, Geerard L Beets, Jose Azevedo, Blas F Lorente, Rocío S Rancaño, Sebastiano Biondo, Eloy Espin-Basany, Bruna B Vailati, Per J Nilsson, Anna Martling, Cornelis J H Van De Velde, Amjad Parvaiz, Angelita Habr-Gama, Rodrigo O Perez

Purpose: Organ preservation has become an attractive alternative to surgery (total mesorectal excision [TME]) among patients with rectal cancer after neoadjuvant therapy who achieve a clinical complete response (cCR). Nearly 30% of these patients will develop local regrowth (LR). Although salvage resection is frequently feasible, there may be an increased risk for development of subsequent distant metastases (DM). The aim of this study is to compare the risk of DM between patients with LR after Watch and Wait (WW) and patients with near-complete pathologic response (nPCR) managed by TME at the time of reassessment of response.

Methods: Data from patients enrolled in the International Watch & Wait Database (IWWD) with cCR managed by WW and subsequent LR were compared with patients managed by TME (with ≤10% cancer cells-nPCR) from the Spanish Rectal Cancer Project (VIKINGO project). The primary end point was DM-free survival at 3 years from decision to WW or TME. The secondary end point was possible risk factors associated with DM.

Results: Five hundred and eight patients with LR were compared with 893 patients with near-complete response after TME. Overall, DM rate was significantly higher among LRs (22.8% v 10.2%; P ≤ .001). Independent risk factors for DM included LR (v TME at reassessment; P = .001), ypT3-4 status (P = .016), and ypN+ status (P = .001) at the time of surgery. 3-year DM-free survival was significantly worse for patients with LR (75% v 87%; P = .001). When stratified for pathologic stage, patients with LR did significantly worse through all stages (P ≤ .009).

Conclusion: Patients with LR appear to have a higher risk for subsequent DM development than patients with nPCR managed by TME at restaging irrespective of final pathology. Leaving the primary undetectable tumor in situ until development of LR may result in worse oncologic outcomes.

目的:对于经过新辅助治疗并获得临床完全反应(cCR)的直肠癌患者来说,保留器官已成为手术(全直肠中胚层切除术 [TME])的一种有吸引力的替代方案。其中近 30% 的患者会出现局部再生(LR)。虽然挽救性切除术通常是可行的,但随后发生远处转移(DM)的风险可能会增加。本研究的目的是比较经过观察和等待(WW)后出现局部再生长(LR)的患者与在重新评估反应时接受TME治疗的近完全病理反应(nPCR)患者发生DM的风险:方法:比较了国际观察和等待数据库(IWWD)中登记的通过WW治疗的cCR患者的数据,以及西班牙直肠癌项目(VIKINGO项目)中通过TME治疗的患者的数据(癌细胞-nPCR≤10%)。主要终点是决定WW或TME后3年的无DM生存率。次要终点是与 DM 相关的可能风险因素:58名LR患者与893名TME后接近完全反应的患者进行了比较。总体而言,LR 患者的 DM 发生率明显更高(22.8% 对 10.2%;P ≤ .001)。DM的独立风险因素包括手术时的LR(v TME at reassessment; P = .001)、ypT3-4状态(P = .016)和ypN+状态(P = .001)。LR患者的3年无DM生存率明显较低(75% 对 87%; P = .001)。根据病理分期进行分层后,LR患者在所有分期中的表现都明显较差(P ≤ .009):结论:无论最终的病理结果如何,LR 患者在重新分期时发生 DM 的风险似乎高于接受 TME 治疗的 nPCR 患者。在出现LR之前,将原发的无法检测的肿瘤留在原位可能会导致更差的肿瘤治疗效果。
{"title":"Risks of Organ Preservation in Rectal Cancer: Data From Two International Registries on Rectal Cancer.","authors":"Laura M Fernandez, Guilherme P São Julião, Carlos Cerdan Santacruz, Andrew G Renehan, Oscar Cano-Valderrama, Geerard L Beets, Jose Azevedo, Blas F Lorente, Rocío S Rancaño, Sebastiano Biondo, Eloy Espin-Basany, Bruna B Vailati, Per J Nilsson, Anna Martling, Cornelis J H Van De Velde, Amjad Parvaiz, Angelita Habr-Gama, Rodrigo O Perez","doi":"10.1200/JCO.24.00405","DOIUrl":"https://doi.org/10.1200/JCO.24.00405","url":null,"abstract":"<p><strong>Purpose: </strong>Organ preservation has become an attractive alternative to surgery (total mesorectal excision [TME]) among patients with rectal cancer after neoadjuvant therapy who achieve a clinical complete response (cCR). Nearly 30% of these patients will develop local regrowth (LR). Although salvage resection is frequently feasible, there may be an increased risk for development of subsequent distant metastases (DM). The aim of this study is to compare the risk of DM between patients with LR after Watch and Wait (WW) and patients with near-complete pathologic response (nPCR) managed by TME at the time of reassessment of response.</p><p><strong>Methods: </strong>Data from patients enrolled in the International Watch & Wait Database (IWWD) with cCR managed by WW and subsequent LR were compared with patients managed by TME (with ≤10% cancer cells-nPCR) from the Spanish Rectal Cancer Project (VIKINGO project). The primary end point was DM-free survival at 3 years from decision to WW or TME. The secondary end point was possible risk factors associated with DM.</p><p><strong>Results: </strong>Five hundred and eight patients with LR were compared with 893 patients with near-complete response after TME. Overall, DM rate was significantly higher among LRs (22.8% <i>v</i> 10.2%; <i>P</i> ≤ .001). Independent risk factors for DM included LR (<i>v</i> TME at reassessment; <i>P</i> = .001), ypT3-4 status (<i>P</i> = .016), and ypN+ status (<i>P</i> = .001) at the time of surgery. 3-year DM-free survival was significantly worse for patients with LR (75% <i>v</i> 87%; <i>P</i> = .001). When stratified for pathologic stage, patients with LR did significantly worse through all stages (<i>P</i> ≤ .009).</p><p><strong>Conclusion: </strong>Patients with LR appear to have a higher risk for subsequent DM development than patients with nPCR managed by TME at restaging irrespective of final pathology. Leaving the primary undetectable tumor in situ until development of LR may result in worse oncologic outcomes.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2400405"},"PeriodicalIF":42.1,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522041","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
Growing Evidence for the Role of Air Pollution in Breast Cancer Development. 越来越多的证据表明空气污染在乳腺癌发病中的作用。
IF 42.1 1区 医学 Q1 ONCOLOGY Pub Date : 2024-10-28 DOI: 10.1200/JCO-24-01987
Alexandra J White
{"title":"Growing Evidence for the Role of Air Pollution in Breast Cancer Development.","authors":"Alexandra J White","doi":"10.1200/JCO-24-01987","DOIUrl":"https://doi.org/10.1200/JCO-24-01987","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2401987"},"PeriodicalIF":42.1,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522037","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
UGT1A1 Testing for the Risk of Nanoliposomal Irinotecan-Related Toxicity. 纳米脂质体伊立替康相关毒性风险的 UGT1A1 检测。
IF 42.1 1区 医学 Q1 ONCOLOGY Pub Date : 2024-10-28 DOI: 10.1200/JCO-24-01366
Yao Liang, Yuichi Ando
{"title":"<i>UGT1A1</i> Testing for the Risk of Nanoliposomal Irinotecan-Related Toxicity.","authors":"Yao Liang, Yuichi Ando","doi":"10.1200/JCO-24-01366","DOIUrl":"https://doi.org/10.1200/JCO-24-01366","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2401366"},"PeriodicalIF":42.1,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522036","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
Targeting DKK1 to Remodel the Tumor Microenvironment and Enhance Immune Checkpoint Blockade Therapy. 以 DKK1 为靶点重塑肿瘤微环境,加强免疫检查点阻断疗法。
IF 42.1 1区 医学 Q1 ONCOLOGY Pub Date : 2024-10-28 DOI: 10.1200/JCO-24-01619
Tao Shi, Jia Wei
{"title":"Targeting DKK1 to Remodel the Tumor Microenvironment and Enhance Immune Checkpoint Blockade Therapy.","authors":"Tao Shi, Jia Wei","doi":"10.1200/JCO-24-01619","DOIUrl":"https://doi.org/10.1200/JCO-24-01619","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2401619"},"PeriodicalIF":42.1,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522042","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
期刊
Journal of Clinical Oncology
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