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Race-specific temporal trends of HPV-related cancers in South Africa: An analysis of the South African National Cancer Registry, 2011-2022. 南非hpv相关癌症的种族特异性时间趋势:2011-2022年南非国家癌症登记处的分析
IF 4.7 2区 医学 Q1 ONCOLOGY Pub Date : 2025-12-31 DOI: 10.1002/ijc.70323
Adino T Tsegaye, Sizeka A Mashele, Jaimie Z Shing, Judith Mwansa-Kambafwile, Aimée R Kreimer, Carole Metekoua, Meredith S Shiels, Mazvita Muchengeti

Evaluating trends in HPV-related cancer rates by race is essential for identifying high-risk populations and improving prevention efforts. Using 2011-2022 South African National Cancer Registry data, we analyzed age-standardized incidence rates by race and sex across three periods (2011-2014, 2015-2018, 2019-2022) using linear regression. Significant increases were observed for oropharyngeal squamous cell carcinoma (SCC) among White females (p < .01), vulvar SCC among Asian (p < .01) and Black (p = .02) females, and anal SCC among Colored females and Black males (p < .01). Cervical carcinoma rates remained stable for most racial groups, except for the annual trends showing a 1.9% increase per year (95% CI = 1.0, 2.7) among White females. These findings suggest rising incidence rates for some HPV-related cancers across racial groups in South Africa. Further research is needed to explore the constellation of risk factors contributing to these trends and to guide targeted interventions.

按种族评估hpv相关癌症发病率的趋势对于确定高危人群和改进预防工作至关重要。使用2011-2022年南非国家癌症登记处的数据,我们使用线性回归分析了三个时期(2011-2014年、2015-2018年、2019-2022年)按种族和性别划分的年龄标准化发病率。在白人女性中,口咽鳞状细胞癌(SCC)的发病率显著增加
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引用次数: 0
Distribution and prognostic value of T-cells in primary colorectal cancer and adjacent non-tumor mucosa in stage IV versus stage I-III patients. IV期与I-III期患者原发性结直肠癌及邻近非肿瘤粘膜中t细胞的分布及预后价值
IF 4.7 2区 医学 Q1 ONCOLOGY Pub Date : 2025-12-30 DOI: 10.1002/ijc.70319
Esraa Ali, Wenjing Ye, Sergii Pavlov, Lenka Červenková, Filip Ambrozkiewicz, Ondřej Vyčítal, Petr Hošek, Ondřej Daum, Václav Liška, Kari Hemminki, Andriy Trailin

Analyzing T-cell subsets in and between primary colorectal cancer (pCRC) and adjacent non-tumor mucosa (NM) may reveal distinct prognostic value in stage IV versus stages I-III patients. Specimens of pCRC and NM were collected retrospectively from stage IV patients (n = 55) with synchronous liver metastases (LM), and stages I-III patients (n = 44) who developed metachronous LM. CD3+, CD8+, CD45RO+, CD4+, and Foxp3+ T-cells were quantified in NM and the tumor center (TC) of pCRC using immunohistochemistry. T-cell densities in NM and TC and their ratios (TC/NM) were tested as prognostic variables for overall survival (OS), along with Foxp3+/CD8+, Foxp3+/CD4+ and CD4+/CD8+ ratios. In stages I-III, associations with the time to occurrence of LM were also evaluated. In both groups, NM exhibited greater densities of CD3+, CD8+, CD45RO+, and CD4+ cells compared to TC, whereas Foxp3+ cells were more abundant in the TC. In stage IV, high densities of Foxp3+ cells, high Foxp3+/CD4+ and Foxp3+/CD8+ ratios in the NM, and high CD4+ cell densities in the TC were associated with longer OS. Stages I-III patients with a high CD4+/CD8+ ratio in the NM had longer OS, whereas a high Foxp3+/CD8+ ratio in the TC was associated with a shorter time to LM. We revealed a significant difference in the T-cell landscape between pCRC and adjacent NM with Foxp3+ cells predominating in the TC and other subsets in the NM. Assessing T-cells and their ratios in both regions may improve prediction of survival in CRC patients and the time to LM in stages I-III.

分析原发性结直肠癌(pCRC)和邻近非肿瘤粘膜(NM)内和之间的t细胞亚群可能揭示IV期和I-III期患者的不同预后价值。回顾性收集同步肝转移(LM)的IV期患者(n = 55)和发生异时性肝转移的I-III期患者(n = 44)的pCRC和NM标本。采用免疫组化方法定量检测NM及肿瘤中心(TC)的CD3+、CD8+、CD45RO+、CD4+、Foxp3+ t细胞。检测淋巴细胞和淋巴细胞的t细胞密度及其比值(TC/NM),以及Foxp3+/CD8+、Foxp3+/CD4+和CD4+/CD8+比值作为总生存期(OS)的预后变量。在I-III期,还评估了与LM发生时间的关系。在两组中,与TC相比,NM表现出更高的CD3+、CD8+、CD45RO+和CD4+细胞密度,而Foxp3+细胞在TC中更丰富。在IV期,高Foxp3+细胞密度、高Foxp3+/CD4+和高Foxp3+/CD8+比值在NM和高CD4+细胞密度在TC与较长的生存期相关。淋巴结中CD4+/CD8+比值较高的I-III期患者生存期较长,而淋巴结中Foxp3+/CD8+比值较高的患者生存期较短。我们揭示了pCRC和相邻NM之间t细胞景观的显著差异,Foxp3+细胞在TC和NM的其他亚群中占主导地位。评估t细胞及其在这两个区域的比例可能会提高对结直肠癌患者生存期的预测以及I-III期到晚期的时间。
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引用次数: 0
Prevalence, incidence, and dynamics of oral human papillomavirus infection among healthy individuals-A molecular epidemiology field study from India. 健康人群口腔人乳头瘤病毒感染的流行、发病率和动态——来自印度的分子流行病学现场研究。
IF 4.7 2区 医学 Q1 ONCOLOGY Pub Date : 2025-12-30 DOI: 10.1002/ijc.70298
Nandimandalam Venkata Vani, Rajendran Madhanagopal, Malliga J Subramanian, Shirley Sundersingh, Antony Xavier Helen, Balaiah Meenakumari, Deva Magendhra Rao, Trivadi Sundaram Ganesan, Rajaraman Swaminathan

Persistent infection with human papillomavirus (HPV) is associated with an increased risk of head and neck cancers (HNC), particularly oropharyngeal cancer. This longitudinal cohort study investigated the prevalence and dynamics of oral HPV infection among healthy adults in South India. A total of 5325 participants were enrolled, and demographic, behavioral, and oral gargle samples were collected. HPV deoxyribonucleic acid (DNA) was detected using nested PCR (PGMY/GP) and genotyped by Sanger sequencing. HPV16 messenger ribonucleic acid (mRNA) expression was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and validated using droplet digital polymerase chain reaction (ddPCR). Logistic regression analyses were performed to estimate odds ratios. At baseline, 5011 samples were analyzed; 274 (5.5%) were HPV-positive and 4737 were negative. Among 3792 initially HPV-negative participants followed up, 126 (3.3%) acquired new infections (median 8 months; range, 6-15 months). Of 274 baseline HPV-positive individuals, 241 were followed up: 24 (10%) showed persistence, while 217 (90%) cleared infection after a median of 9 months (range, 6-20 months). Sanger sequencing of 471 samples from prevalent and incident infections yielded 290 (61.6%) high-quality sequences; 284 (98%) were HPV16, with isolated detections of HPV18, HPV66, HPV70, and HPV89. Ten novel variants were identified-nine HPV16 and one HPV89-while remaining sequences aligned with established Indian cervical HPV lineages. None of the 176 HPV16 DNA-positive samples analyzed expressed mRNA by RT-PCR, confirmed in 136 samples using ddPCR. Oral HPV infection among healthy individuals in India appears predominantly transient. Long-term monitoring may elucidate the oncogenic potential of oral HPV in this population.

持续感染人乳头瘤病毒(HPV)与头颈癌(HNC),特别是口咽癌的风险增加有关。这项纵向队列研究调查了印度南部健康成年人口腔HPV感染的患病率和动态。共纳入5325名参与者,收集了人口统计学、行为学和口腔含漱液样本。采用巢式PCR (PGMY/GP)检测HPV脱氧核糖核酸(DNA), Sanger测序分型。采用逆转录聚合酶链式反应(RT-PCR)分析HPV16信使核糖核酸(mRNA)的表达,并采用液滴数字聚合酶链式反应(ddPCR)进行验证。采用Logistic回归分析估计优势比。在基线时,分析了5011份样本;hpv阳性274例(5.5%),阴性4737例。在3792名最初hpv阴性的随访参与者中,126名(3.3%)获得了新的感染(中位8个月,范围6-15个月)。在274名基线hpv阳性个体中,241人接受了随访:24人(10%)表现出持续性,而217人(90%)在中位9个月(范围6-20个月)后清除了感染。对来自流行感染和偶发感染的471个样本进行Sanger测序,获得290个(61.6%)高质量序列;HPV16检出284例(98%),HPV18、HPV66、HPV70、HPV89检出。发现了10个新的变异- 9个HPV16和1个hpv89 -而其余的序列与已建立的印度宫颈HPV谱系一致。RT-PCR分析的176份HPV16 dna阳性样本均未表达mRNA,而ddPCR分析的136份样本证实了这一点。在印度健康人群中,口腔HPV感染似乎主要是短暂的。长期监测可能阐明口腔HPV在这一人群中的致癌潜力。
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引用次数: 0
Patient- and caregiver-reported barriers to chemotherapy in nine sub-Saharan African countries: A cross-sectional survey among population-based registries. 9个撒哈拉以南非洲国家患者和护理人员报告的化疗障碍:基于人口登记的横断面调查。
IF 4.7 2区 医学 Q1 ONCOLOGY Pub Date : 2025-12-30 DOI: 10.1002/ijc.70309
Tamara König, Nikolaus Christian Simon Mezger, Ole Stoeter, Phoebe Mary Amulen, Margaret Borok, Gladys C Chesumbai, Moudiongui MBoungou Dimitry, Ima-Obong Ekanem, Adugna Fekadu, Bakarou Kamaté, William Muller, Alex Alain Kabena Nzambikolo, Abidemi Omonisi, Furaha Serventi, Markus Wallwiener, Biying Liu, Donald Maxwell Parkin, Pablo Sandro Carvalho Santos, Eva Johanna Kantelhardt, Eric Sven Kroeber

Chemotherapy is an essential component of cancer treatment, as outlined in the National Comprehensive Cancer Network (NCCN) guidelines for Sub-Saharan Africa (SSA). Lack of access to treatment is a key driver of impaired survival rates. This study assessed patient-perceived barriers to chemotherapy in SSA according to the five dimensions of access to care: availability, accessibility, accommodation, affordability, and acceptability. Telephone interviews were conducted with 553 randomly selected cancer patients (or caretakers), registered between 2018 and 2019 in 11 urban population-based cancer registries across nine countries in SSA. Malignancy types included breast, cervical, prostate, and colorectal cancer; non-Hodgkin lymphoma; and Kaposi sarcoma. Patients rated barriers using a 3-point Likert scale. Barriers to chemotherapy and their associations with patient characteristics were analysed using multivariate ordinal regression analysis. Major barriers included accessibility (cost of transport), affordability (cost of treatment, being absent from home), and acceptability (lack of knowledge/awareness and fear of treatment). Results varied between countries: affordability was especially severe in the Republic of Congo, while in Gabon, fear of treatment prevailed. Knowledge and awareness were particularly concerning in Ethiopia and Zimbabwe. A combined educational level and self-reported wealth variable, and national human development index (HDI) were consistently associated with reported barriers. Overall, 58.6% of participants received chemotherapy, while 13.2% were recommended chemotherapy but did not receive it. A higher HDI correlated with an increased probability of receiving treatment. A complex set of barriers influenced patients' non-receipt of treatment. Regionally adapted strategies, including psychosocial support, financial assistance for vulnerable groups, and education, are essential to improve treatment uptake in SSA.

正如撒哈拉以南非洲(SSA)国家综合癌症网络(NCCN)指南所概述的那样,化疗是癌症治疗的重要组成部分。缺乏获得治疗的机会是降低存活率的一个关键因素。本研究根据获得治疗的五个维度评估SSA患者对化疗的感知障碍:可用性、可及性、住宿、可负担性和可接受性。对随机选择的553名癌症患者(或护理人员)进行了电话采访,这些患者于2018年至2019年间在SSA 9个国家的11个城市人口癌症登记处登记。恶性肿瘤类型包括乳腺癌、宫颈癌、前列腺癌和结直肠癌;非霍奇金淋巴瘤;和卡波西肉瘤。患者使用3分李克特量表对障碍进行评分。使用多变量有序回归分析化疗障碍及其与患者特征的关系。主要障碍包括可及性(交通费用)、可负担性(治疗费用、不在家)和可接受性(缺乏知识/意识和对治疗的恐惧)。各国的结果各不相同:在刚果共和国,负担能力特别严重,而在加蓬,对治疗的恐惧普遍存在。在埃塞俄比亚和津巴布韦,知识和认识特别令人关切。综合教育水平和自我报告的财富变量以及国家人类发展指数(HDI)始终与报告的障碍相关。总体而言,58.6%的参与者接受了化疗,而13.2%的参与者被推荐化疗但没有接受化疗。较高的HDI与接受治疗的可能性增加相关。一系列复杂的障碍影响着患者不接受治疗。区域适应策略,包括社会心理支持、对弱势群体的财政援助和教育,对于提高SSA的治疗接受度至关重要。
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引用次数: 0
Integrating polygenic and methylation risk scores for pleural mesothelioma risk stratification. 胸膜间皮瘤风险分层的多基因和甲基化风险评分整合。
IF 4.7 2区 医学 Q1 ONCOLOGY Pub Date : 2025-12-30 DOI: 10.1002/ijc.70316
Khadija Sana Hafeez, Carla Debernardi, Alessandra Allione, Elton Jalis Herman, Simonetta Guarrera, Daniela Ferrante, Anna Aspesi, Marika Sculco, Marta La Vecchia, Carlotta Sacerdote, Federica Grosso, Christina M Lill, Giovanna Masala, Marcela Guevara, Matthias B Schulze, Salvatore Panico, Yaszan Asgari, Seehyun Park, Giovanna Tagliabue, Anne Tjønneland, Antonio Agudo, Elisabete Weiderpass, Corrado Magnani, Irma Dianzani, Paolo Vineis, Elisabetta Casalone, Giuseppe Matullo

Pleural mesothelioma (PM) is a lethal cancer primarily caused by asbestos exposure. Not all exposed individuals develop PM, suggesting the involvement of additional factors. This underscores the need for robust predictive models integrating biomarkers from multi-omic domains to improve risk stratification and early detection. We developed and evaluated polygenic risk scores (PRS) and methylation risk scores (MRS) using a retrospective case-control study (749 participants: 387 PM cases, 362 controls) and a nested case-control European Prospective Investigation into Cancer and Nutrition (EPIC)-Meso study (268 participants: 134 preclinical PM cases, 134 matched controls) within the EPIC cohort. Genome-wide association analyses in the retrospective case-control study identified PM-associated variants. The PRS (1123 SNPs with p < 0.001) in the retrospective training subset stratified disease risk in the test set (ORs 3.46-9.54 across top percentiles) and improved model discrimination (AUC = 0.75 vs. 0.71 in baseline model, p = 0.04). In EPIC-Meso, PRS performance was limited (AUC = 0.52). External validation in the UK-Biobank (UKBB) confirmed a modest but consistent association with PM-risk. A Meta-PRS derived from the UKBB-FinnGen meta-analysis replicated this trend in the full retrospective dataset, showing higher OR across top percentiles (2.5-12.3) and improved discrimination (AUC 0.74 vs. 0.72, p = 0.016). MRS, with 68 differentially methylated CpGs (effect-size >|0.10|, FDR p < 0.05) in the retrospective training set, increased the AUC from 0.66 to 0.85 (p < 0.001) in the test set and from 0.51 to 0.62 in EPIC-Meso. PRS was most predictive in low-exposure groups, while MRS remained robust across exposure levels. Combined PRS-MRS models improved discrimination. Integrating multi-omic biomarkers can enhance PM-risk stratification and support earlier, targeted interventions in high-risk asbestos-exposed groups.

胸膜间皮瘤(PM)是一种主要由石棉暴露引起的致命癌症。并非所有暴露的个体都会发展为PM,这表明还涉及其他因素。这强调了整合来自多组学域的生物标志物的强大预测模型的需求,以改善风险分层和早期检测。我们通过一项回顾性病例对照研究(749名参与者:387例PM病例,362例对照)和一项嵌套病例对照欧洲癌症与营养前瞻性调查(EPIC)-Meso研究(268名参与者:134例临床前PM病例,134例匹配对照),在EPIC队列中开发并评估了多基因风险评分(PRS)和甲基化风险评分(MRS)。在回顾性病例对照研究中,全基因组关联分析确定了pm相关变异。PRS (1123 snp)与p |0.10|, FDR p
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引用次数: 0
Conditional survival in glioblastoma: The evolution of prognostic factors over time. 胶质母细胞瘤的条件生存:预后因素随时间的演变。
IF 4.7 2区 医学 Q1 ONCOLOGY Pub Date : 2025-12-30 DOI: 10.1002/ijc.70285
Timothy Mueller, Flavio Vasella, Julia Velz, Stefanos Voglis, Kevin Akeret, Luis Padevit, Morton Schubert, Jonathan Weller, Sarah Brüningk, Elisabeth Rushing, Johannes Sarnthein, Dorothee Gramatzki, Levin Häni, Andreas Raabe, Anna M Zeitlberger, Oliver Bozinov, Emilie Le Rhun, Michael Weller, Luca Regli, Marian C Neidert

Conditional survival provides insights into the evolution of prognosis over time and reveals changing associations of prognostic factors during disease progression. Data on the temporal evolution of prognostic factors in glioblastoma remain scarce. We analyzed 315 patients with IDH-wildtype glioblastoma from a prospectively collected registry (01/2008-06/2017). Our primary outcome was 12-month conditional survival (CS), defined as the probability of surviving the next 12 months given survival for "s" months. This analysis was conducted at five landmarks (s = 0, 6, 12, 18, 24) for baseline prognostic factors, including tumor volume compartments. 12-month conditional survival estimates at s = 0, 6, 12, 18, and 24 months from diagnosis were 0.51 (95% CI 0.45-0.56), 0.46 (95% CI 0.39-0.52), 0.41 (95% CI 0.33-0.49), 0.43 (95% CI 0.33-0.52), and 0.56 (95% CI 0.42-0.67), respectively. At diagnosis (s = 0), 12-month survival estimates varied significantly with age >60 at diagnosis, preoperative tumor rim volume >20 cm3, absence of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, postoperative KPS ≥70, residual postoperative tumor >1 cm3, or biopsy only. Residual tumor volume mainly influences survival in the initial months following surgery, while MGMT promoter methylation and age remain significant predictors beyond this period. These findings may refine stratification strategies in recurrent glioblastoma trials.

条件生存提供了对预后随时间演变的见解,并揭示了疾病进展过程中预后因素的变化关联。关于胶质母细胞瘤预后因素的时间演变的数据仍然很少。我们分析了来自前瞻性登记的315例idh野生型胶质母细胞瘤患者(2008年1月- 2017年6月)。我们的主要终点是12个月的条件生存(CS),定义为在生存期为“s”个月的情况下,未来12个月存活的概率。该分析在5个里程碑(s = 0、6、12、18、24)进行,以确定包括肿瘤体积区室在内的基线预后因素。诊断后0、6、12、18和24个月的条件生存估计分别为0.51 (95% CI 0.45-0.56)、0.46 (95% CI 0.39-0.52)、0.41 (95% CI 0.33-0.49)、0.43 (95% CI 0.33-0.52)和0.56 (95% CI 0.42-0.67)。诊断时(s = 0),诊断时年龄bbb60,术前肿瘤边缘体积>20 cm3, o6 -甲基鸟嘌呤- dna甲基转移酶(MGMT)启动子甲基化缺失,术后KPS≥70,术后残留肿瘤>1 cm3,或仅活检,12个月生存率估计差异显著。残留肿瘤体积主要影响手术后最初几个月的生存,而MGMT启动子甲基化和年龄仍然是这一时期后的重要预测因素。这些发现可以完善复发性胶质母细胞瘤试验的分层策略。
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引用次数: 0
Surufatinib combined with sintilimab and IBI310 for the treatment of high-grade advanced-neuroendocrine neoplasms: A single arm, open-label, single-center, phase II study. 舒伐替尼联合辛替单和IBI310治疗高级别晚期神经内分泌肿瘤:单组、开放标签、单中心、II期研究
IF 4.7 2区 医学 Q1 ONCOLOGY Pub Date : 2025-12-29 DOI: 10.1002/ijc.70311
Panpan Zhang, Miao Zhang, Yakun Wang, Lin Shen, Ming Lu

This single-center, open-label, single-arm phase II trial (NCT05165407) aimed to evaluate the efficacy and safety of surufatinib (250 mg orally once daily) combined with sintilimab (200 mg intravenously every 3 weeks) and IBI310 (1 mg/kg intravenously every 6 weeks) in patients with advanced high-grade neuroendocrine neoplasms (HG-NENs). The primary endpoint was the objective response rate (ORR). Secondary endpoints included the disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. As of March 28, 2025, 24 patients with measurable baseline lesions and at least one post-treatment tumor assessment were included in the efficacy-evaluable analysis set. The ORR was 37.5% (95% confidence interval [CI]: 18.8-59.4); DCR, 79.2% (95% CI: 57.8-92.9); and median DoR, 14.8 months. Among 31 treated patients in the full analysis set population, the median PFS was 3.81 months (95% CI: 2.79-4.50), and the median OS was 13.44 months (95% CI: 10.28-not estimable). Subgroup analyses showed improved response in patients with the following characteristics: female sex, age <55 years, ECOG performance status of 1, received ≤1 prior treatment line, without liver metastases, and <2 metastatic sites. Treatment-related adverse events (TRAEs) occurred in 96.8% of patients; 45.2% experienced grade ≥3 TRAEs. Among them, 71.0% experienced TRAEs attributed to sintilimab/IBI310, and 87.1% to surufatinib. Serious adverse events occurred in 45.2% of patients. These findings suggest that surufatinib, IBI310, and sintilimab may offer clinical benefit with manageable toxicity in patients with advanced HG-NENs.

这项单中心、开放标签、单组II期试验(NCT05165407)旨在评估舒法替尼(250mg口服,每日1次)联合辛替单(200mg静脉注射,每3周)和IBI310 (1mg /kg静脉注射,每6周)治疗晚期高级别神经内分泌肿瘤(HG-NENs)患者的疗效和安全性。主要终点为客观缓解率(ORR)。次要终点包括疾病控制率(DCR)、反应持续时间(DoR)、无进展生存期(PFS)、总生存期(OS)和安全性。截至2025年3月28日,24例基线病变可测量且至少有一项治疗后肿瘤评估的患者被纳入疗效评估分析集。ORR为37.5%(95%可信区间[CI]: 18.8-59.4);Dcr, 79.2% (95% ci: 57.8-92.9);中位DoR为14.8个月。在全分析集人群中的31例治疗患者中,中位PFS为3.81个月(95% CI: 2.79-4.50),中位OS为13.44个月(95% CI: 10.28-不可估计)。亚组分析显示,具有以下特征的患者疗效改善:女性,年龄
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引用次数: 0
Accelerated approvals in oncology: Trial design strategies and insights driving successful regulatory outcomes across three decades. 肿瘤学加速审批:30年来推动成功监管结果的试验设计策略和见解
IF 4.7 2区 医学 Q1 ONCOLOGY Pub Date : 2025-12-29 DOI: 10.1002/ijc.70317
Rohini Sharma, Anamika Gulati, Kanwaljit Chopra

This descriptive analysis evaluates design strategies, regulatory outcomes, and temporal trends in oncology accelerated approvals (AAs) over three decades, comparing solid tumors with hematologic malignancies. We retrospectively reviewed publicly available U.S. Food and Drug Administration (FDA) data on oncology drugs granted AA between December 1992 and January 2025, focusing on those with completed post-approval assessments. Key measures included trial design, endpoints, conversion and withdrawal rates, and time to regulatory resolution. Of 204 AAs representing 204 drug-indication pairs (across 133 drugs), 138 had completed post-approval assessments; 77.5% converted to regular approval, 22.5% were withdrawn. Solid tumors accounted for 63% (87/138) of AAs, and had higher conversion rates to regular approvals compared to hematologic malignancies (82% vs. 71%, respectively). Withdrawals were more frequent in hematologic malignancies compared to solid tumors (29% vs. 18%, respectively). Orphan drug designation and post-approval label modifications were more common in hematologic malignancies than solid tumors (76% vs. 45%, and 18% vs. 11%, respectively). Randomized controlled trials (RCTs) drove most successful conversions (63%). Among 105 AA trials for solid tumors, overall response rate (ORR) was the primary endpoint in 74%, with progression-free survival (PFS) and overall survival (OS) in 13% and 9% AAs, respectively. Hematologic trials favored ORR (33%) and disease-specific endpoints. The most common AA → confirmatory pathway was ORR → PFS (46%). OS as a confirmatory endpoint after surrogate-based AA was linked to higher withdrawal rates, whereas consistent endpoints (e.g., OS → OS) had none. RCTs and aligned endpoints drive successful oncology AA conversions, while surrogate-confirmed OS often precedes withdrawal.

本描述性分析评估了三十年来肿瘤加速批准(AAs)的设计策略、监管结果和时间趋势,比较了实体瘤和血液恶性肿瘤。我们回顾性地回顾了1992年12月至2025年1月期间美国食品和药物管理局(FDA)公开获得的AA级肿瘤药物数据,重点关注那些已完成批准后评估的药物。关键措施包括试验设计、终点、转化率和退出率,以及监管决议的时间。在代表204个药物适应症对(133种药物)的204个asa中,138个完成了批准后评估;转为定期审批的占77.5%,撤销的占22.5%。实体肿瘤占全部批准的63%(87/138),与血液系统恶性肿瘤相比,实体肿瘤向常规批准的转换率更高(分别为82%和71%)。与实体肿瘤相比,血液恶性肿瘤的停药更为频繁(分别为29%和18%)。孤儿药指定和批准后标签修改在血液恶性肿瘤中比实体肿瘤更常见(分别为76%对45%,18%对11%)。随机对照试验(rct)推动了最成功的转化(63%)。在105项针对实体瘤的AA试验中,总缓解率(ORR)是主要终点,占74%,无进展生存期(PFS)和总生存期(OS)分别占13%和9%。血液学试验支持ORR(33%)和疾病特异性终点。最常见的AA→确认途径是ORR→PFS(46%)。在基于替代药物的AA后,作为验证终点的OS与更高的停药率有关,而一致终点(例如,OS→OS)则没有。随机对照试验和一致的终点驱动成功的肿瘤学AA转换,而替代证实的OS通常在停药之前。
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引用次数: 0
High potassium enhances the immunosuppressive function of myeloid-derived suppressor cells via Kir4.1-dependent metabolic reprogramming and promotes tumor immune escape. 高钾通过kir4.1依赖性代谢重编程增强髓源性抑制细胞的免疫抑制功能,促进肿瘤免疫逃逸。
IF 4.7 2区 医学 Q1 ONCOLOGY Pub Date : 2025-12-29 DOI: 10.1002/ijc.70313
Zhiqi Xie, Jiayi Liu, Ying Chen, Kexin Wang, Ziyi Hong, Yanjie Li, Luqiong Liang, Jinglu Bi, Yuanzhen Jin, Weida Shen, Masashi Tachibana, Zeren Shen, Jinjin Shao

Despite advances in cancer immunotherapy, low response rates remain a critical clinical challenge. Myeloid-derived suppressor cells (MDSCs) drive tumor immune evasion by directly suppressing antitumor immunity, positioning them as prime therapeutic targets to improve immunotherapy efficacy. While dysregulated ionic microenvironments, particularly elevated potassium, are emerging as broad-spectrum immunomodulators, the role of high potassium in regulating MDSC function remains poorly understood. Here, we demonstrate that elevated extracellular potassium reprograms MDSC differentiation toward an immunosuppressive phenotype via the activation of the inwardly rectifying potassium channel Kir4.1. Mechanistically, Kir4.1 triggers metabolic rewiring by upregulating fatty acid-binding protein 3, thereby enhancing fatty acid uptake and oxidation to fuel the production of immunosuppressive molecules. In preclinical models, pharmacological inhibition of Kir4.1 with VU0134992 reversed MDSC-mediated T cell suppression, remodeled the tumor microenvironment, and synergized with anti-PD-1 therapy to achieve superior antitumor responses. Clinically, elevated Kir4.1 expression in tumor-infiltrating MDSCs correlates with an adverse prognosis in patients with lung and gastric cancer. Our study establishes Kir4.1 as a critical metabolic regulator governing MDSC functionality and proposes targeting potassium signaling as a strategy to overcome resistance to cancer immunotherapies.

尽管癌症免疫治疗取得了进展,但低应答率仍然是一个关键的临床挑战。髓源性抑制细胞(Myeloid-derived suppressor cells, MDSCs)通过直接抑制抗肿瘤免疫来驱动肿瘤免疫逃避,使其成为提高免疫治疗效果的主要治疗靶点。虽然失调的离子微环境,特别是高钾,正在成为广谱免疫调节剂,但高钾在调节MDSC功能中的作用仍然知之甚少。在这里,我们证明了升高的细胞外钾通过激活内校正钾通道Kir4.1将MDSC分化重编程为免疫抑制表型。从机制上讲,Kir4.1通过上调脂肪酸结合蛋白3触发代谢重布线,从而增强脂肪酸的摄取和氧化,从而促进免疫抑制分子的产生。在临床前模型中,VU0134992对Kir4.1的药理学抑制逆转了mdsc介导的T细胞抑制,重塑了肿瘤微环境,并与抗pd -1治疗协同,实现了卓越的抗肿瘤反应。在临床上,肿瘤浸润性MDSCs中Kir4.1表达升高与肺癌和胃癌患者的不良预后相关。我们的研究确定Kir4.1是控制MDSC功能的关键代谢调节因子,并提出靶向钾信号作为克服癌症免疫疗法耐药的策略。
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引用次数: 0
Prior immunotherapy enhances survival outcomes of third-line apatinib treatment in advanced gastric cancer: A retrospective cohort study. 既往免疫治疗提高三线阿帕替尼治疗晚期胃癌的生存结果:一项回顾性队列研究。
IF 4.7 2区 医学 Q1 ONCOLOGY Pub Date : 2025-12-29 DOI: 10.1002/ijc.70322
Chongya Zhai, Minjie Ying, Xufei Wang, Zhen Liu, Yu Zheng

The impact of prior immune checkpoint inhibitor (ICI) therapy on subsequent antiangiogenic treatment efficacy in advanced gastric cancer remains unclear. We retrospectively analyzed 134 patients with advanced gastric cancer who received apatinib as third-line treatment between January 2018 and October 2023, comparing outcomes between those with (n = 66) and without (n = 68) prior ICI exposure. The ICI-pretreated group demonstrated significantly improved survival outcomes, with longer median progression-free survival (7.1 vs. 4.2 months; HR = 0.42, 95% CI: 0.24-0.75, p = .003) and overall survival (9.0 vs. 5.1 months; HR = 0.53, 95% CI: 0.31-0.91, p = .023) compared to the ICI-naive group. Disease control rate was also higher in ICI-pretreated patients (72.7% vs. 61.8%). Subgroup analyses revealed particularly pronounced survival benefits among male patients (HR = 0.30, 95% CI: 0.14-0.65), HER2-negative patients (HR = 0.35, 95% CI: 0.18-0.69), and those with liver metastases (HR = 0.33, 95% CI: 0.15-0.76, p = .009). Prior ICI therapy emerged as an independent favorable prognostic factor for survival in multivariate analysis. These findings suggest that prior ICI therapy may enhance the efficacy of subsequent third-line apatinib treatment in patients with advanced gastric cancer, providing important insights for optimizing treatment sequencing strategies in this setting.

既往免疫检查点抑制剂(ICI)治疗对晚期胃癌后续抗血管生成治疗效果的影响尚不清楚。我们回顾性分析了2018年1月至2023年10月期间接受阿帕替尼作为三线治疗的134例晚期胃癌患者,比较了有(n = 66)和没有(n = 68)既往ICI暴露的患者的结果。CI预处理组的生存结果显著改善,中位无进展生存期更长(7.1个月vs 4.2个月;HR = 0.42, 95% CI: 0.24-0.75, p =。003)和总生存期(9.0个月vs. 5.1个月;HR = 0.53, 95% CI: 0.31-0.91, p =。023)与ci幼稚组相比。ci预处理患者的疾病控制率也更高(72.7% vs. 61.8%)。亚组分析显示,男性患者(HR = 0.30, 95% CI: 0.14-0.65)、her2阴性患者(HR = 0.35, 95% CI: 0.18-0.69)和肝转移患者(HR = 0.33, 95% CI: 0.15-0.76, p = 0.009)的生存获益尤为显著。在多变量分析中,既往ICI治疗成为独立的有利预后因素。这些发现表明,先前的ICI治疗可能会提高晚期胃癌患者后续三线阿帕替尼治疗的疗效,为优化这种情况下的治疗顺序策略提供重要见解。
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引用次数: 0
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International Journal of Cancer
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