ovarian cancer

卵巢癌
  • 文章类型: Journal Article
    卵巢癌(OC),以其明显的异质性而闻名,尽管进行了广泛的研究,但长期以来一直回避统一的分类系统。这项研究整合了来自八个多中心队列的五个不同的多组数据集,应用十种聚类算法和九十九种机器学习模型的组合。这种方法使我们能够完善OC的分子亚型,导致了一种新颖的共识机器学习驱动签名(CMLS)的开发。我们的分析描绘了两种具有预后意义的癌症亚型(CS),每个都有独特的遗传和免疫特征。值得注意的是,CS1与不良预后相关。利用子类型分类器,我们确定了五个关键基因(CTHRC1,SPEF1,SCGB3A1,FOXJ1和C1orf194)有助于构建CMLS。高CMLS组患者预后较差,表现为“冷肿瘤”表型,指示富含MDSCs的免疫抑制微环境,CAF,和Tregs.有趣的是,该组还呈现较高水平的肿瘤突变负荷(TMB)和肿瘤新抗原负荷(TNB),与低CMLS对应物相比,与免疫疗法更有利的反应相关的因素。相比之下,低CMLS组,尽管还显示出“冷肿瘤”表型,显示良好的预后和对化疗的反应性增强。这项研究的发现强调了靶向免疫抑制细胞的潜力,特别是在高CMLS患者中,作为提高OC预后的战略方法。此外,重新定义的分子亚型和风险分层,通过复杂的多组学分析,提供了选择治疗剂的框架。
    Ovarian cancer (OC), known for its pronounced heterogeneity, has long evaded a unified classification system despite extensive research efforts. This study integrated five distinct multi-omics datasets from eight multicentric cohorts, applying a combination of ten clustering algorithms and ninety-nine machine learning models. This methodology has enabled us to refine the molecular subtyping of OC, leading to the development of a novel Consensus Machine Learning-driven Signature (CMLS). Our analysis delineated two prognostically significant cancer subtypes (CS), each marked by unique genetic and immunological signatures. Notably, CS1 is associated with an adverse prognosis. Leveraging a subtype classifier, we identified five key genes (CTHRC1, SPEF1, SCGB3A1, FOXJ1, and C1orf194) instrumental in constructing the CMLS. Patients classified within the high CMLS group exhibited a poorer prognosis and were characterized by a \"cold tumor\" phenotype, indicative of an immunosuppressive microenvironment rich in MDSCs, CAFs, and Tregs. Intriguingly, this group also presented higher levels of tumor mutation burden (TMB) and tumor neoantigen burden (TNB), factors that correlated with a more favorable response to immunotherapy compared to their low CMLS counterparts. In contrast, the low CMLS group, despite also displaying a \"cold tumor\" phenotype, showed a favorable prognosis and a heightened responsiveness to chemotherapy. This study\'s findings underscore the potential of targeting immune-suppressive cells, particularly in patients with high CMLS, as a strategic approach to enhance OC prognosis. Furthermore, the redefined molecular subtypes and risk stratification, achieved through sophisticated multi-omics analysis, provide a framework for the selection of therapeutic agents.
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  • 文章类型: Journal Article
    近年来,通过盆腔超声进行诊断成像在妇科癌症的诊断和分期中的作用呈指数增长。来自最近的前瞻性多中心研究的证据表明,妇科癌症的术前局部超声分期具有很高的准确性。因此,在许多领先的妇科肿瘤单位,在盆腔MRI旁边实施超声作为妇科癌症的一线成像方式。本文的工作是关于超声和其他成像方式在术前成像在妇科癌症中的作用的共识声明。遵循欧洲社会的指导方针。
    In recent years the role of diagnostic imaging by pelvic ultrasound in the diagnosis and staging of gynecological cancers has been growing exponentially. Evidence from recent prospective multicenter studies has demonstrated high accuracy for pre-operative locoregional ultrasound staging in gynecological cancers. Therefore, in many leading gynecologic oncology units, ultrasound is implemented next to pelvic MRI as the first-line imaging modality for gynecological cancer. The work herein is a consensus statement on the role of pre-operative imaging by ultrasound and other imaging modalities in gynecological cancer, following European Society guidelines.
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  • 文章类型: Practice Guideline
    欧洲妇科肿瘤学会,2022年6月15日至16日,欧洲肿瘤医学学会(ESMO)和欧洲病理学会在瓦伦西亚举行了关于卵巢癌的共识会议(CC),西班牙。CC小组包括44位卵巢癌和病理学管理专家,ESMO科学顾问和方法学家。目的是讨论新的或有争议的话题,并提出建议以改善和协调卵巢癌患者的管理。在四个主要主题下确定了18个问题供讨论:(i)病理学和分子生物学,(ii)妊娠早期疾病和盆腔肿块,(iii)晚期(包括老年/体弱患者)和(iv)复发性疾病。该小组分为四个工作组(WG),每个工作组都解决与上述四个主题之一有关的问题,基于他们的专业知识。相关科学文献已提前审查。工作组提出了建议,然后提交给整个小组进行进一步讨论和修改,然后再进行表决。这份手稿侧重于达成共识的建议声明,他们的投票结果和支持每一项建议的证据摘要。
    The European Society of Gynaecological Oncology, the European Society for Medical Oncology (ESMO) and the European Society of Pathology held a consensus conference (CC) on ovarian cancer on 15-16 June 2022 in Valencia, Spain. The CC panel included 44 experts in the management of ovarian cancer and pathology, an ESMO scientific advisor and a methodologist. The aim was to discuss new or contentious topics and develop recommendations to improve and harmonise the management of patients with ovarian cancer. Eighteen questions were identified for discussion under four main topics: (i) pathology and molecular biology, (ii) early-stage disease and pelvic mass in pregnancy, (iii) advanced stage (including older/frail patients) and (iv) recurrent disease. The panel was divided into four working groups (WGs) to each address questions relating to one of the four topics outlined above, based on their expertise. Relevant scientific literature was reviewed in advance. Recommendations were developed by the WGs and then presented to the entire panel for further discussion and amendment before voting. This manuscript focuses on the recommendation statements that reached a consensus, their voting results and a summary of evidence supporting each recommendation.
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  • 文章类型: Journal Article
    暂无摘要。
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  • 文章类型: Journal Article
    与高级别浆液性癌相比,低级别卵巢或腹膜浆液性癌是一种不太常见的上皮性卵巢癌类型,对化疗不敏感,影响年轻女性,他们中的许多人忍受了多年无效的治疗和生活质量差。这种疾病的发病机制及其管理仍未完全了解。然而,该疾病的分子表征的最新进展以及在低级别浆液性癌中具有活性的新型靶向治疗的鉴定为改善预后提供了希望。更新临床医生最近的科学和临床试验进展,并讨论与低级别浆液性癌诊断和治疗相关的未解决的问题,一个专家小组于2022年10月召开了一次研讨会,以制定一份关于病理学的共识文件,翻译研究,流行病学和风险,临床管理,和正在进行的研究。此外,讨论了患者的观点。该专家小组在本共识文件中提出的建议将指导从业人员在所有情况下对低级别浆液性癌妇女的临床管理,并讨论改善研究和患者护理的未来机会。
    Compared with high-grade serous carcinoma, low-grade serous carcinoma of the ovary or peritoneum is a less frequent epithelial ovarian cancer type that is poorly sensitive to chemotherapy and affects younger women, many of whom endure years of ineffective treatments and poor quality of life. The pathogenesis of this disease and its management remain incompletely understood. However, recent advances in the molecular characterization of the disease and identification of novel targeted therapies with activity in low-grade serous carcinoma offer the promise of improved outcomes. To update clinicians regarding recent scientific and clinical trial advancements and discuss unanswered questions related to low-grade serous carcinoma diagnosis and treatment, a panel of experts convened for a workshop in October 2022 to develop a consensus document addressing pathology, translational research, epidemiology and risk, clinical management, and ongoing research. In addition, the patient perspective was discussed. The recommendations developed by this expert panel-presented in this consensus document-will guide practitioners in all settings regarding the clinical management of women with low-grade serous carcinoma and discuss future opportunities to improve research and patient care.
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  • 文章类型: Journal Article
    在35至45岁之间,对患有卵巢癌的高遗传风险妇女进行降低风险的输卵管卵巢切除术(RRSO)。虽然有可能挽救生命,RRSO可能会引起对生活质量产生负面影响并损害长期健康的症状。RRSO后的临床护理通常是次优的。本范围审查描述了RRSO如何影响短期和长期健康,并为从术前咨询到长期疾病预防的护理提供了基于证据的国际共识建议。这包括激素和非激素治疗血管舒缩症状的疗效和安全性,睡眠障碍和性功能障碍以及预防骨骼和心血管疾病的有效方法。
    Women at high inherited risk of ovarian cancer are offered risk-reducing salpingo-oophorectomy (RRSO) from age 35 to 45 years. Although potentially life-saving, RRSO may induce symptoms that negatively affect quality of life and impair long-term health. Clinical care following RRSO is often suboptimal. This scoping review describes how RRSO affects short- and long-term health and provides evidence-based international consensus recommendations for care from preoperative counselling to long-term disease prevention. This includes the efficacy and safety of hormonal and non-hormonal treatments for vasomotor symptoms, sleep disturbance and sexual dysfunction and effective approaches to prevent bone and cardiovascular disease.
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  • 文章类型: Journal Article
    Background: Ovarian malignant tumours are rarely diagnosed in adolescents but may have a significant impact on their survival, future fertility and quality of life. The management of such cases is rather complex and requires expertise and careful planning according to scarce existing evidence and recommendations. Objective: The aim of this study was to review and compare recommendations from published guidelines regarding the diagnosis, prognosis and treatment of malignant ovarian tumours in adolescents. Evidence acquisition: A comparative descriptive/narrative review of guidelines issued by L\'Observatoire des Tumeurs Malignes Rares Gynécologiques, the British Society for Paediatric & Adolescent Gynaecology, the European Society for Medical Oncology, the European Society of Gynecological Oncology-European Society for Paediatric Oncology and the European Cooperative Study Group for Pediatric Rare Tumors was conducted. Results: All guidelines recommend a thorough diagnostic work-up, consisting of both imaging tests and serum tumour marker measurement, as well as the use of immunohistochemical methods to confirm the diagnosis and complete surgical staging prior to constructing the treatment plan. There is a lack of recommendations regarding the assessment of prognostic factors, with only one guideline providing detailed information. Treatment strategies, as suggested by the majority of guidelines and with only a few discrepancies between them, should include both surgery and adjuvant therapies, mainly chemotherapy, with great emphasis on fertility preservation when it is considered oncologically safe and on the significance of regular and long-term follow-up. Conclusions: There is a significant degree of agreement among recommendations of existing guidelines. The reported differences, although limited, highlight the need for the adoption of an international consensus in order to further improve the management of adolescent ovarian cancer.
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  • 文章类型: Systematic Review
    目的:在癌症诊断前通过基因检测确定有遗传综合征风险的人可以积极降低癌症负担的发病率和死亡率。使用健康公平的框架,这项研究描述了出版和参考BRCA1/2基因检测指南(GTG)的全球格局。
    方法:本研究采用了系统的文献检索,辅以国际妇科癌症协会(IGCS)非正式调查,并与MyriadGenetics记录交叉引用,为了确定已发布的GTG,他们的原籍国,以及引用它们的国家。
    结果:在1011种确定的出版物中,166符合纳入标准,从中确定了46条独特的指南,由18个国家和两个地区(欧洲和英国)出版。来自美国的作者占GTG出版物的63%。系统制图审查显示,34个国家公布和/或引用了指南,IGCS调查显示另外22个国家,与MyriadGenetics的协调揭示了两个国家的更多信息和一个国家的主要信息。在评估的57个国家中,33%的人发布了自己的指南和来自其他国家/地区的参考指南。5%的人发布了自己的指南,但没有引用其他国家/地区。61%的人只引用了另一个国家/地区的指南。195个国家中的138个国家没有数据,不成比例地来自非洲,中东,东欧,和东南亚。
    结论:GTG的出版物和引用存在全球地理差异,在已发表的文献中非常重视北美和欧洲的指导方针。这些差异凸显了需要统一的BRCAGTG来改善全球卫生公平性。
    Identification of persons at risk for hereditary syndromes through genetic testing prior to cancer diagnosis may proactively reduce the cancer burden morbidity and mortality. Using a framework of health equity, this study characterizes the global landscape of publication and reference to BRCA1/2 genetic testing guidelines (GTG).
    This study used a systematic literature search supplemented by an International Gynecologic Cancer Society (IGCS) informal survey and cross referenced with Myriad Genetics records, to identify published GTG, their country of origin, and countries referencing them.
    Of 1011 identified publications, 166 met the inclusion criteria, from which 46 unique guidelines were identified, published by 18 countries and two regions (Europe and the UK). Authorship from the USA accounted for 63% of publications on GTG. Systematic mapping reviews revealed 34 countries with published and/or referenced guidelines, the IGCS survey revealed 22 additional countries, and coordination with Myriad Genetics revealed additional information for two countries and primary information for one country. Of the 57 countries evaluated, 33% published their own guidelines and reference guidelines from another country/region, 5% published their own guidelines without referencing another country/region, and 61% only referenced a guideline from another country/region. No data were available for 138 of 195 countries, disproportionately from Africa, the Middle East, Eastern Europe, and Southeast Asia.
    Global geographic disparities in the publication and referencing of GTG exist, with a large emphasis on North American and European guidelines in the published literature. These disparities highlight a need for uniform BRCA GTG to improve global health equity.
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  • 文章类型: Journal Article
    在接受卵巢癌(OC)的指南一致治疗时存在种族差异。然而,很少有研究评估医疗保健服务(HCA)的各个维度是如何导致这些差异的。
    我们分析了来自非西班牙裔(NH)-布莱克的数据,西班牙裔,从SEER-Medicare数据库中诊断出2008年至2015年患有OC的NH-White患者,并将HCA维度定义为可负担性,可用性,和可访问性,用因子分析创建的总分衡量。根据卵巢癌NCCN指南定义了指南一致的OC手术和化疗。使用多变量调整的改良Poisson回归模型来评估与HCA相关的指南一致治疗的相对风险(RR)。
    研究队列包括5,632名患者:6%NH-Black,6%的西班牙裔,88%的NH-White。只有23.8%的NH-White患者接受了指南一致的手术和完整的化疗周期,而NH-Black患者为14.2%。更高的负担能力(RR,1.05;95%CI,1.01-1.08)和可用性(RR,1.06;95%CI,1.02-1.10)与接受指南一致的手术有关,而较高的负担能力与开始全身治疗相关(风险比,1.09;95%CI,1.05-1.13)。在调整了所有3个HCA评分以及人口统计学和临床特征后,NH-Black患者比NH-White患者开始全身治疗的可能性较小(风险比,0.86;95%CI,0.75-0.99)。
    多个HCA维度可预测是否接受与指南一致的治疗,但不能完全解释OC患者的种族差异。可接受性和适应性是两个额外的HCA维度,这对于解决这些差异可能至关重要。
    Racial disparities exist in receipt of guideline-concordant treatment of ovarian cancer (OC). However, few studies have evaluated how various dimensions of healthcare access (HCA) contribute to these disparities.
    We analyzed data from non-Hispanic (NH)-Black, Hispanic, and NH-White patients with OC diagnosed in 2008 to 2015 from the SEER-Medicare database and defined HCA dimensions as affordability, availability, and accessibility, measured as aggregate scores created with factor analysis. Receipt of guideline-concordant OC surgery and chemotherapy was defined based on the NCCN Guidelines for Ovarian Cancer. Multivariable-adjusted modified Poisson regression models were used to assess the relative risk (RR) for guideline-concordant treatment in relation to HCA.
    The study cohort included 5,632 patients: 6% NH-Black, 6% Hispanic, and 88% NH-White. Only 23.8% of NH-White patients received guideline-concordant surgery and the full cycles of chemotherapy versus 14.2% of NH-Black patients. Higher affordability (RR, 1.05; 95% CI, 1.01-1.08) and availability (RR, 1.06; 95% CI, 1.02-1.10) were associated with receipt of guideline-concordant surgery, whereas higher affordability was associated with initiation of systemic therapy (hazard ratio, 1.09; 95% CI, 1.05-1.13). After adjusting for all 3 HCA scores and demographic and clinical characteristics, NH-Black patients remained less likely than NH-White patients to initiate systemic therapy (hazard ratio, 0.86; 95% CI, 0.75-0.99).
    Multiple HCA dimensions predict receipt of guideline-concordant treatment but do not fully explain racial disparities among patients with OC. Acceptability and accommodation are 2 additional HCA dimensions which may be critical to addressing these disparities.
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  • 文章类型: Journal Article
    目的:先前的研究表明,临床早期卵巢癌患者对手术分期指南的依从性较低。这项研究的目的是确定手术分期的指南依从性,并显示研究人群中每个手术项目的分布。此外,我们研究了荷兰是否存在完整手术分期的区域差异.
    方法:纳入2015年1月1日至2019年12月31日在荷兰妇科肿瘤审核中注册的卵巢癌患者和手术分期。根据荷兰循证指南定义完整的手术分期。对手术项目进行排序和说明。漏斗图中显示了八个区域癌症网络的完整手术分期变化。在三个妇科肿瘤中心对注册数据进行了手动验证。
    结果:604例患者接受了手术分期,365(60%)接受了不完整的分期程序,295人(81%)登记为早期疾病(国际妇产科联合会I-IIA),在这些患者中,115(39%)接受辅助化疗。与完整分期组的患者相比,手术分期不完整的患者使用微创技术(腹腔镜或机器人)进行手术的频率更高(p<0.001)。细胞学/腹水采样是最常见的缺乏因素(29%)。对三个妇科肿瘤中心的数据进行手动验证,确定了分期不完整的原因,最常见的是“围手术期发现”,例如肿瘤和腹膜之间的致密粘连,符合晚期疾病(≥IIA)。完整手术分期的区域差异显示两个区域在置信区间之外(12.5%和25.5%,平均40%)。
    结论:分期指南的依从性低于预期,数据的验证为导致手术分期不完整的原因提供了更多的见解。此外,这项分析表明,手术分期存在区域差异,这是改善和协调全国这些患者分期程序的起点。
    Previous studies have shown low adherence to surgical staging guidelines in patients with clinical early-stage ovarian carcinoma. The aim of this study was to identify guideline adherence for surgical staging and to show the distribution of each surgical item within the study population. In addition, we examined whether regional variation in the Netherlands exists for complete surgical staging.
    Patients with ovarian cancer and surgical staging registered in the Dutch Gynecological Oncology Audit between January 1, 2015 and December 31, 2019 in the Netherlands were included. Complete surgical staging was defined according to the Dutch evidence-based guideline. Surgical items were ranked and illustrated. Variation in complete surgical staging for eight regional cancer networks was shown in funnel plots. Manual validation of registered data was performed in three gynecological oncology centers.
    604 patients underwent surgical staging, 365 (60%) underwent an incomplete staging procedure, 295 (81%) were registered with early-stage disease (International Federation of Gynecology and Obstetrics I-IIA) and, of these patients, 115 (39%) received adjuvant chemotherapy. Patients with incomplete surgical staging were operated more often with minimal invasive techniques (laparoscopy or robot) compared with patients in the complete staging group (p<0.001). Sampling of cytology/ascites was the most frequently lacking factor (29%). Manual validation of data in three gynecological oncology centers identified reasons for incomplete staging, the most common being \'perioperative findings\' such as dense adhesions between tumor and peritoneum, consistent with advanced stage disease (≥IIA). Regional variation for complete surgical staging showed two regions performing outside the confidence intervals (12.5% and 25.5%, mean 40%).
    Guideline adherence for staging was lower than expected and validation of data gave additional insights into the reasons that were contributing to incomplete surgical staging. Moreover, this analysis showed that regional variation for surgical staging exists, which forms a starting point to improve and harmonize staging procedures for these patients nationwide.
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