Gynecologic oncology最新文献_第3页

ATR inhibition increases reliance on PARP-mediated DNA repair revealing an improved therapeutic strategy for cervical cancer ATR 抑制增加了对 PARP 介导的 DNA 修复的依赖，揭示了一种更好的宫颈癌治疗策略。

IF 4.5 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Gynecologic oncology

Pub Date : 2024-10-19 DOI: 10.1016/j.ygyno.2024.10.009

Objective

Cervical cancer results from persistent infection with high-risk human papillomavirus (HR-HPV) and the expression of E6 and E7 oncoproteins. E6 and E7 compromise the activity of p53 and Rb, the G1-S cell cycle checkpoint, and ATM-mediated DNA damage repair (DDR), which in turn increases reliance on ATR- and PARP-mediated DDR at the G2 cell cycle checkpoint. This study aimed to determine the effects of an ATR inhibitor (ATRi, AZD6738) and a PARP-inhibitor (PARPi, AZD2281) on HR-HPV+ cervical cancer cell lines.

Methods

The effects of ATRi and PARPi, alone and in combination, on metabolic viability, cell cycle arrest, apoptosis, and DDR pathways in cervical cancer cell lines were evaluated in vitro, and the in vivo tumor response was evaluated using a xenograft model.

Results

Cervical cancer cells were sensitive to ATRi and PARPi monotherapy. The combination therapy was only synergistic in reducing metabolic viability when exposed to ATRi first, followed by PARPi, owing to ATRi-mediated upregulation of PARP expression. Combination of ATRi and PARPi induced G2 cell cycle arrest and apoptosis. PARPi induced DNA damage and γH2AX phosphorylation, which was further increased by ATRi treatment. However, PARPi-induced Rad51 foci formation was reduced by ATRi treatment, suggesting the inhibition of homologous recombination repair. ATRi significantly reduced cervical cancer xenograft tumor growth and was not affected by simultaneous PARPi treatment at the doses studied.

Conclusions

Our findings show that ATRi increased reliance on PARP for metabolic viability, the combination of ATRi and PARPi induced synthetic lethality in cervical cancer in vitro, and reduced tumor burden in vivo.

目的：宫颈癌源于高危人类乳头瘤病毒（HR-HPV）的持续感染以及 E6 和 E7 肿瘤蛋白的表达。E6 和 E7 会损害 p53 和 Rb、G1-S 细胞周期检查点以及 ATM 介导的 DNA 损伤修复（DDR）的活性，进而增加 G2 细胞周期检查点对 ATR 和 PARP 介导的 DDR 的依赖。本研究旨在确定ATR抑制剂（ATRi，AZD6738）和PARP抑制剂（PARPi，AZD2281）对HR-HPV+宫颈癌细胞系的影响：方法：在体外评估 ATRi 和 PARPi 单独或联合使用对宫颈癌细胞株代谢活力、细胞周期停滞、细胞凋亡和 DDR 通路的影响，并使用异种移植模型评估体内肿瘤反应：结果：宫颈癌细胞对 ATRi 和 PARPi 单药治疗敏感。结果表明：宫颈癌细胞对 ATRi 和 PARPi 单药治疗均敏感，但由于 ATRi 介导的 PARP 表达上调，联合治疗在降低代谢活力方面只有先暴露于 ATRi 后暴露于 PARPi 的协同作用。ATRi 和 PARPi 联合使用可诱导 G2 细胞周期停滞和细胞凋亡。PARPi 可诱导 DNA 损伤和 γH2AX 磷酸化，而 ATRi 可进一步提高这种磷酸化。然而，PARPi诱导的Rad51病灶形成在ATRi处理后减少，这表明同源重组修复受到了抑制。ATRi能明显降低宫颈癌异种移植瘤的生长，在研究剂量下，ATRi不受同时PARPi治疗的影响：我们的研究结果表明，ATRi 增加了对 PARP 代谢活力的依赖，ATRi 和 PARPi 的联合应用在体外诱导了宫颈癌的合成致死率，并减少了体内的肿瘤负荷。

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引用次数: 0

Mild symptoms matter: Results from a prospective, longitudinal study on the relationship between symptoms, lymphedema and health-related outcomes post-gynecological cancer 轻微症状很重要：妇科癌症术后症状、淋巴水肿和健康相关结果之间关系的前瞻性纵向研究结果

IF 4.5 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Gynecologic oncology

Pub Date : 2024-10-18 DOI: 10.1016/j.ygyno.2024.10.011

Objectives

To describe lower-limb symptoms pre- through to 2-years post-surgery following newly diagnosed gynecological cancer; to explore relationships between lower-limb symptoms, lower-limb lymphedema, body image, quality of life, anxiety and depression; and to determine whether lower-limb symptoms predict lower-limb lymphedema.

Methods

Fourteen lower-limb symptoms, lymphedema, body image, anxiety, depression, and quality of life were prospectively collected in 408 women with gynecological cancer pre-surgery, and at 6-, 12-, and 24-months post-surgery. Point prevalence and cumulative incidence were calculated for symptoms. Cross-sectional relationships were explored between symptoms, lower-limb lymphedema and health-related outcomes at all timepoints, while regression analyses were used to assess the predictive relationships between lower-limb symptoms at 6-months post-surgery, and lymphedema at 12- and 24-months post-surgery.

Results

Participants were on average 59 (SD: 11) years of age, and 58 %, 28 %, 9 % and 5 % were diagnosed with endometrial, ovarian, cervical, and vulvar/vaginal cancer, respectively. Prevalence of any given lower limb symptom among all cancer types ranged between 11 and 59 %, with the most prevalent symptoms being pain, stiffness, and aching (prevalence >40 % across all time-points). The presence of symptoms was associated with higher anxiety and depression, poorer overall quality of life and body image (p < 0.01). Compared to those without symptoms, one or more lower limb symptoms of at least mild severity increased the odds of developing lymphedema up to 24 months post-surgery (OR > 1.3).

Conclusions

Self-reported symptoms are associated with adverse health-related outcomes. Assessment and management of symptoms, irrespective of symptom severity, has potential for improving health outcomes, including lymphedema, in those following gynecological cancer.

目的描述新确诊妇科癌症术前至术后两年的下肢症状；探讨下肢症状、下肢淋巴水肿、身体形象、生活质量、焦虑和抑郁之间的关系；确定下肢症状是否可预测下肢淋巴水肿。方法前瞻性地收集了 408 名妇科癌症妇女在手术前、手术后 6 个月、12 个月和 24 个月时的 14 种下肢症状、淋巴水肿、身体形象、焦虑、抑郁和生活质量。计算了症状的点流行率和累积发生率。研究人员探讨了所有时间点的症状、下肢淋巴水肿和健康相关结果之间的横断面关系，并使用回归分析评估了手术后 6 个月的下肢症状与手术后 12 个月和 24 个月的淋巴水肿之间的预测关系。结果参与者的平均年龄为59岁（标准差：11岁），被诊断患有子宫内膜癌、卵巢癌、宫颈癌和外阴/阴道癌的比例分别为58%、28%、9%和5%。在所有癌症类型中，任何一种下肢症状的发病率在11%到59%之间，最常见的症状是疼痛、僵硬和酸痛（在所有时间点的发病率为40%）。出现症状与较高的焦虑和抑郁、较差的整体生活质量和身体形象有关（p <0.01）。与无症状者相比，一种或多种至少轻度的下肢症状会增加术后 24 个月内发生淋巴水肿的几率（OR > 1.3）。无论症状严重程度如何，对症状进行评估和管理都有可能改善妇科癌症患者的健康状况，包括淋巴水肿。

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引用次数: 0

Less is more? Comparison between genomic profiling and immunohistochemistry-based models in endometrial cancer molecular classification: A multicenter, retrospective, propensity-matched survival analysis. 少即是多？在子宫内膜癌分子分类中比较基因组剖析和免疫组化模型：多中心、回顾性、倾向匹配生存分析。

IF 4.5 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Gynecologic oncology

Pub Date : 2024-10-17 DOI: 10.1016/j.ygyno.2024.10.010

Emanuele Perrone, Ilaria Capasso, Diana Giannarelli, Rita Trozzi, Luigi Congedo, Elisa Ervas, Vincenzo Tarantino, Giovanni Esposito, Luca Palmieri, Arianna Guaita, Anne-Sophie van Rompuy, Giulia Scaglione, Gian Franco Zannoni, Giovanni Scambia, Frédéric Amant, Francesco Fanfani

Background: Genomic profiling-based model (GP-M) is the gold-standard for endometrial cancer (EC) molecular classification, but several issues related to the availability of genomic sequencing in low-income settings remain and health disparities in the management are increasing. This study aims to investigate the non-inferiority of the immunohistochemistry-alone model in classifying ECs compared to the standard genomic profiling-based model in terms of oncologic outcomes.

Methods: All preoperative uterine-confined ECs undergoing surgical staging were retrospectively included. Patients classified by IHC-M were stratified into: MMR-proficient (MMRp), p53 wild type (p53wt) and estrogen receptor (ER) positive, 2) MMRp, p53wt and ER-negative, 3) MMRd, and 4) p53abn. A case-control comparison was performed between the IHC-M and GP-M cohorts. Then, a propensity-matched analysis was performed: ECs classified by IHC-M were matched in a 3:1 ratio with patients classified by GP-M.

Results: 1587 patients with EC were included. The Kaplan-Meier survival curves for disease-free survival and overall survival demonstrated that the two models performed similarly in risk-stratifying the study population (p < 0.0001). Moreover, the AUC-ROC showed overlapping results: 0.77 (0.66-0.87) for IHC-M and 0.72 (0.63-0.81) for GP-M, indicating that both models were able to successfully identify patients at high-risk and low-risk of disease recurrence/progression.

Conclusion: The IHC-M showed overlapping classification performance compared to the GP-M in terms of oncologic outcomes. This study may lay the basis to further investigate the real-life clinical impact of POLE sequencing in molecular classification and the potential stand-alone prognostic role of ER status for further allocation of EC patients into risk classes.

背景：基于基因组图谱的模型（GP-M）是子宫内膜癌（EC）分子分类的黄金标准，但在低收入环境中，与基因组测序可用性相关的几个问题依然存在，而且管理中的健康差异正在增加。本研究旨在探讨免疫组化单独模式与基于基因组图谱的标准模式相比，在对子宫内膜癌进行分类时在肿瘤治疗效果方面的非劣效性：方法：回顾性纳入所有术前接受手术分期的子宫内膜癌患者。根据 IHC-M 对患者进行分层：MMRp、p53野生型（p53wt）和雌激素受体（ER）阳性；2）MMRp、p53wt和ER阴性；3）MMRd；4）p53abn。IHC-M和GP-M队列之间进行了病例对照比较。然后，进行倾向匹配分析：根据IHC-M分类的EC患者与根据GP-M分类的患者按3:1的比例进行匹配：结果：共纳入1587名EC患者。无病生存期和总生存期的 Kaplan-Meier 生存曲线显示，这两种模型在对研究人群进行风险分级时表现相似（p 结论：IHC-M 与 GP-M 的分级结果存在重叠：与 GP-M 相比，IHC-M 在肿瘤结果方面显示出重叠的分类性能。本研究可为进一步研究 POLE 测序在分子分级中的实际临床影响，以及ER 状态在进一步将 EC 患者划分为不同风险等级时的潜在独立预后作用奠定基础。

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引用次数: 0

Surgery after upfront chemoradiation in locally advanced squamous cell vulvar cancer: Analysis of postoperative outcomes and survival 局部晚期鳞状细胞外阴癌前期化疗后的手术治疗：术后疗效和生存率分析

IF 4.5 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Gynecologic oncology

Pub Date : 2024-10-16 DOI: 10.1016/j.ygyno.2024.10.005

Objective

The aim of the study was to assess the survival rates and surgery-related toxicity in patients with locally advanced squamous cell vulvar cancer (LAVC) managed by upfront chemoradiation (CRT) with/without following by surgery.

CRT is the primary treatment for patients with unresectable locally advanced squamous cell vulvar carcinoma (LAVC), followed by surgery in case of residual tumor.

Methods

Patients with AJCC stage II-IV squamous cell vulvar carcinoma referred to Gynecologic Oncology Unit at Fondazione Policlinico Universitario Agostino Gemelli I.R.C.C.S. from January 2016 to February 2023, managed by upfront CRT, were included.

Results

63 patients were included, 21 (33 %) had complete response (cCR) to CRT, 26 (41 %) had partial response (cPR), 1 (2 %) stable disease (cSD), 15 (24 %) had disease progression (cPD).

In the whole population, cPR/SD and cPD were associated with reduced PFS (p < 0.001) and overall survival (OS) (p < 0.001), p16 expression was associated with improved PFS (p < 0.001) and OS (p = 0.001).

Among patients with clinical residual disease after CRT, 23 patients undergoing surgery experienced improved PFS (p = 0.003) and OS (p = 0.003) compared to those receiving other treatments.

Eight (35 %) patients experienced severe (grade ≥ III) postoperative complications; vulvar and groin wound dehiscence/infection were the most common complications; one (4 %) patient died in the postoperative. Patients with pathological residual disease experienced worse PFS (p = 0.013) and OS (p = 0.034).

Conclusions

Clinical response to CRT and p16 expression strongly predict survival in LAVC. Surgery for residual disease might be associated with improved survival but is burdened by high rates of complications. Pathologic residual disease correlates with high recurrence rates and poor survival.

目的该研究旨在评估局部晚期鳞状细胞外阴癌（LAVC）患者接受前期化疗（CRT）并/不接受手术治疗后的生存率和手术相关毒性。CRT是不可切除的局部晚期鳞状细胞外阴癌（LAVC）患者的主要治疗方法，如有残余肿瘤，则进行手术治疗。方法纳入2016年1月至2023年2月期间转诊至Fondazione Policlinico Universitario Agostino Gemelli I.R.C.C.S.妇科肿瘤科并接受前期CRT治疗的AJCC II-IV期鳞状细胞外阴癌患者。结果63名患者中，21人（33%）对CRT有完全反应（cCR），26人（41%）有部分反应（cPR），1人（2%）病情稳定（cSD），15人（24%）病情进展（cPD）。在整个人群中，cPR/SD 和 cPD 与缩短的 PFS（p < 0.001）和总生存期（OS）（p < 0.001）有关，p16 表达与改善的 PFS（p < 0.001）和 OS（p = 0.001）有关。在CRT后有临床残留疾病的患者中，与接受其他治疗的患者相比，23例接受手术治疗的患者的PFS（p = 0.003）和OS（p = 0.003）均有所改善。8例（35%）患者出现严重的术后并发症（等级≥ III）；外阴和腹股沟伤口裂开/感染是最常见的并发症；1例（4%）患者在术后死亡。有病理残留疾病的患者PFS（p = 0.013）和OS（p = 0.034）均较差。对残留疾病进行手术治疗可能会提高生存率，但并发症发生率较高。病理残留疾病与高复发率和低生存率相关。

{"title":"Surgery after upfront chemoradiation in locally advanced squamous cell vulvar cancer: Analysis of postoperative outcomes and survival","authors":"","doi":"10.1016/j.ygyno.2024.10.005","DOIUrl":"10.1016/j.ygyno.2024.10.005","url":null,"abstract":"<div><h3>Objective</h3><div>The aim of the study was to assess the survival rates and surgery-related toxicity in patients with locally advanced squamous cell vulvar cancer (LAVC) managed by upfront chemoradiation (CRT) with/without following by surgery.</div><div>CRT is the primary treatment for patients with unresectable locally advanced squamous cell vulvar carcinoma (LAVC), followed by surgery in case of residual tumor.</div></div><div><h3>Methods</h3><div>Patients with AJCC stage II-IV squamous cell vulvar carcinoma referred to Gynecologic Oncology Unit at Fondazione Policlinico Universitario Agostino Gemelli I.R.C.C.S. from January 2016 to February 2023, managed by upfront CRT, were included.</div></div><div><h3>Results</h3><div>63 patients were included, 21 (33 %) had complete response (cCR) to CRT, 26 (41 %) had partial response (cPR), 1 (2 %) stable disease (cSD), 15 (24 %) had disease progression (cPD).</div><div>In the whole population, cPR/SD and cPD were associated with reduced PFS (<em>p</em> < 0.001) and overall survival (OS) (p < 0.001), p16 expression was associated with improved PFS (p < 0.001) and OS (<em>p</em> = 0.001).</div><div>Among patients with clinical residual disease after CRT, 23 patients undergoing surgery experienced improved PFS (<em>p</em> = 0.003) and OS (p = 0.003) compared to those receiving other treatments.</div><div>Eight (35 %) patients experienced severe (grade ≥ III) postoperative complications; vulvar and groin wound dehiscence/infection were the most common complications; one (4 %) patient died in the postoperative. Patients with pathological residual disease experienced worse PFS (<em>p</em> = 0.013) and OS (<em>p</em> = 0.034).</div></div><div><h3>Conclusions</h3><div>Clinical response to CRT and p16 expression strongly predict survival in LAVC. Surgery for residual disease might be associated with improved survival but is burdened by high rates of complications. Pathologic residual disease correlates with high recurrence rates and poor survival.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Immunological impact of intraperitoneal and intravenous chemotherapy in ovarian cancer, translational analyses of the Phase 3 iPocc trial 腹腔化疗和静脉化疗对卵巢癌免疫学的影响：iPocc 3 期试验的转化分析

IF 4.5 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Gynecologic oncology

Pub Date : 2024-10-15 DOI: 10.1016/j.ygyno.2024.09.023

Background

The iPocc trial, a randomized, global phase 3 study that compared intraperitoneal (IP) and intravenous (IV) carboplatin with dose-dense paclitaxel chemotherapy in epithelial ovarian cancer (EOC) patients, demonstrated improved progression-free survival in patients who received IP chemotherapy. The present study aimed to investigate the role of preexisting tumor immunity in the clinical outcomes of patients receiving IP chemotherapy.

Methods

This study involved analyzing patient data from the iPocc trial, selectively of those whose tumor specimens were preserved at the time of primary surgery. A total of 116 cases ((IP; n = 59), (IV; n = 57)) were subjected to microarray analysis. Single-sample gene set enrichment analyses were performed to evaluate the tumor immune microenvironment.

Results

Patients with enhanced tumor infiltration of T cells, natural killer (NK) cells, and cytotoxic lymphocytes in the IP group had a longer overall survival (OS) than those in the IV group, but not in the group with low infiltration. IP therapy improved the OS of patients with high expression of immune-related genes such as CD8A and FOXP3. In patients' subdivided into “immune Hot” and “immune Cold” groups based on hierarchical clustering analysis using four parameters representing “Innate immunity,” “T cells,” “IFNG response” and “Inhibitory molecules,” IP therapy significantly improved prognosis in the “immune Hot” group, but not in the “immune Cold” group compared to that of IV therapy.

Conclusions

IP chemotherapy enhances the survival rates of patients with EOC with an immune-Hot phenotype in the tumor microenvironment prior to treatment.

(Japan Registry of Clinical Trials number, jRCTs031180141.)

背景iPocc试验是一项随机、全球性的三期研究，比较了上皮性卵巢癌（EOC）患者腹腔注射（IP）和静脉注射（IV）卡铂与剂量密集型紫杉醇化疗，结果显示接受IP化疗的患者无进展生存期有所改善。本研究旨在探讨肿瘤免疫在接受 IP 化疗患者临床预后中的作用。方法本研究分析了 iPocc 试验中的患者数据，选择性地分析了那些在初次手术时保留了肿瘤标本的患者。共对 116 个病例（（IP；n = 59），（IV；n = 57））进行了芯片分析。结果IP组肿瘤浸润T细胞、自然杀伤（NK）细胞和细胞毒性淋巴细胞增多的患者的总生存期（OS）长于IV组，但浸润较少的患者的总生存期不长。IP疗法改善了CD8A和FOXP3等免疫相关基因高表达患者的OS。根据代表 "先天免疫"、"T 细胞"、"IFNG 反应 "和 "抑制分子 "的四个参数进行分层聚类分析，将患者细分为 "免疫热 "组和 "免疫冷 "组，与静脉注射疗法相比，IP 疗法显著改善了 "免疫热 "组的预后，而 "免疫冷 "组的预后则没有改善。结论IP化疗可提高治疗前肿瘤微环境中存在免疫热表型的EOC患者的生存率。

{"title":"Immunological impact of intraperitoneal and intravenous chemotherapy in ovarian cancer, translational analyses of the Phase 3 iPocc trial","authors":"","doi":"10.1016/j.ygyno.2024.09.023","DOIUrl":"10.1016/j.ygyno.2024.09.023","url":null,"abstract":"<div><h3>Background</h3><div>The iPocc trial, a randomized, global phase 3 study that compared intraperitoneal (IP) and intravenous (IV) carboplatin with dose-dense paclitaxel chemotherapy in epithelial ovarian cancer (EOC) patients, demonstrated improved progression-free survival in patients who received IP chemotherapy. The present study aimed to investigate the role of preexisting tumor immunity in the clinical outcomes of patients receiving IP chemotherapy.</div></div><div><h3>Methods</h3><div>This study involved analyzing patient data from the iPocc trial, selectively of those whose tumor specimens were preserved at the time of primary surgery. A total of 116 cases ((IP; <em>n</em> = 59), (IV; <em>n</em> = 57)) were subjected to microarray analysis. Single-sample gene set enrichment analyses were performed to evaluate the tumor immune microenvironment.</div></div><div><h3>Results</h3><div>Patients with enhanced tumor infiltration of T cells, natural killer (NK) cells, and cytotoxic lymphocytes in the IP group had a longer overall survival (OS) than those in the IV group, but not in the group with low infiltration. IP therapy improved the OS of patients with high expression of immune-related genes such as CD8A and FOXP3. In patients' subdivided into “immune Hot” and “immune Cold” groups based on hierarchical clustering analysis using four parameters representing “Innate immunity,” “T cells,” “IFNG response” and “Inhibitory molecules,” IP therapy significantly improved prognosis in the “immune Hot” group, but not in the “immune Cold” group compared to that of IV therapy.</div></div><div><h3>Conclusions</h3><div>IP chemotherapy enhances the survival rates of patients with EOC with an immune-Hot phenotype in the tumor microenvironment prior to treatment.</div><div>(Japan Registry of Clinical Trials number, jRCTs031180141.)</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Comparative analysis of hormonal therapy in low-grade endometrial stromal sarcoma: A retrospective study 低级别子宫内膜间质肉瘤激素疗法的比较分析：回顾性研究

IF 4.5 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Gynecologic oncology

Pub Date : 2024-10-12 DOI: 10.1016/j.ygyno.2024.10.008

Objective

To evaluate the disease course of patients with low grade endometrial stromal sarcoma (LG-ESS) and compare oncologic outcomes associated with hormonal therapy in primary and recurrent disease.

Methods

This is a retrospective study of patients with LG-ESS who underwent active treatment between January 2000 and July 2023. Recurrence-free survival (RFS) and overall survival (OS) were estimated using the Kaplan-Meier product-limit estimator and modeled via Cox proportional hazards regression.

Results

A total of 221 patients were included; 58 % of patients (91/157) were stage I, 12 % (19/157) stage II, 13 % (20/157) stage III, and 17 % (27/157) stage IV. Surgery was the primary treatment for 98 % (213/218). Only 79 patients received hormonal adjuvant therapy, 58 % (46/79) Megace, 24 % (19/79) Letrozole, and 18 % (14/79) received other hormonal therapy. There was no significant difference in RFS (p = 0.159) and OS (p = 0.167) between patients receiving Megace versus Letrozole as adjuvant therapy. At first recurrence, patients given Megace had a similar RFS to those on Letrozole (p = 0.302), but a better OS (27 vs 10 months, p = 0.018). Negative status of estrogen, smooth muscle actin, and desmin were associated with lower RFS (p = 0.039, p = 0.002, and p = 0.015, respectively) and OS (p = 0.008, p = 0.012, and p = 0.013, respectively). Lymphovascular invasion was associated with lower RFS (p = 0.033), and negative status of progesterone was associated with lower OS (p = 0.003).

Conclusion

There was no difference in oncologic outcomes between Megace and Letrozole in patients who received adjuvant therapy for LG-ESS. Megace may have potential survival advantage in recurrent disease. Further study is warranted to determine the most effective agents and their sequence in the treatment of LG-ESS.

目的评估低级别子宫内膜间质肉瘤（LG-ESS）患者的病程，并比较原发性和复发性疾病中与激素治疗相关的肿瘤学结果。方法这是对2000年1月至2023年7月期间接受积极治疗的LG-ESS患者进行的一项回顾性研究。结果共纳入221例患者，其中58%（91/157）为I期，12%（19/157）为II期，13%（20/157）为III期，17%（27/157）为IV期。98%的患者（213/218）以手术为主要治疗手段。只有79名患者接受了激素辅助治疗，其中58%（46/79）接受了美加净治疗，24%（19/79）接受了来曲唑治疗，18%（14/79）接受了其他激素治疗。接受美加净与来曲唑辅助治疗的患者在RFS（P = 0.159）和OS（P = 0.167）方面没有明显差异。首次复发时，接受 Megace 治疗的患者的 RFS 与来曲唑治疗的患者相似（p = 0.302），但 OS 更好（27 个月对 10 个月，p = 0.018）。雌激素、平滑肌肌动蛋白和desmin阴性与较低的RFS（分别为p = 0.039、p = 0.002和p = 0.015）和OS（分别为p = 0.008、p = 0.012和p = 0.013）相关。淋巴管侵犯与较低的RFS相关（p = 0.033），孕酮阴性与较低的OS相关（p = 0.003）。对于复发性疾病，Megace可能具有潜在的生存优势。需要进一步研究确定治疗LG-ESS最有效的药物及其使用顺序。

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引用次数: 0

LGBTQIA+ populations still neglected in trials and their health needs 女同性恋、男同性恋、双性恋、变性人和两性人群体及其健康需求仍被忽视。

IF 4.5 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Gynecologic oncology

Pub Date : 2024-10-10 DOI: 10.1016/j.ygyno.2024.10.002

引用次数: 0

Tirzepatide as an innovative treatment strategy in a pre-clinical model of obesity-driven endometrial cancer 在肥胖驱动的子宫内膜癌临床前模型中将替扎帕肽作为一种创新治疗策略。

IF 4.5 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Gynecologic oncology

Pub Date : 2024-10-10 DOI: 10.1016/j.ygyno.2024.10.004

Objective

Interventions that combat obesity and its associated metabolic perturbations may decrease incidence and improve outcomes of endometrial cancer (EC). Potential options for weight loss include pharmacotherapeutic interventions such as tirzepatide, a dual-acting glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP) receptor agonist. Given this, we explored the anti-obesity and anti-tumorigenic effects of tirzepatide in our pre-clinical mouse model of endometrioid EC.

Methods

Starting at 4 weeks of age, Lkb1^fl/flp53^fl/fl mice were fed a low-fat diet vs a high-fat diet to generate a lean or obese phenotype. Nine weeks after induction of EC, obese and lean mice were randomized to receive tirzepatide for 4 weeks. Body and tumor weights, tumor transcriptomic and metabolomic profiles, and serum metabolic markers and chemokines were assessed.

Results

Both obese and lean mice began to lose body weight after 2 weeks of tirzepatide treatment, ultimately achieving a significant weight loss of 20.1 % in obese mice and 16.8 % in lean mice. Tirzepatide improved obesity-induced serum adiponectin, leptin, GIP, and C-reactive protein levels. Furthermore, tirzepatide relative to vehicle, effectively reduced tumor growth in obese and lean mice, inhibited the ErbB signaling and glycolysis/gluconeogenesis in tumors of obese mice, and increased O-linked glycosylation biosynthesis and phospholipase D signaling in tumors of lean mice.

Conclusion

Tirzepatide decreased both mouse weight and tumor growth via effects on metabolic and immune pathways in the EC tumors that differed between obese and lean mice. This novel weight loss treatment deserves further evaluation as an innovative strategy in the management of EC.

目的：针对肥胖及其相关代谢紊乱的干预措施可降低子宫内膜癌（EC）的发病率并改善其预后。减肥的潜在选择包括药物治疗干预，如替泽帕特，一种双效胰高血糖素样肽 1（GLP-1）和胃抑制多肽（GIP）受体激动剂。有鉴于此，我们在子宫内膜样癌小鼠临床前模型中探索了替哌肽的抗肥胖和抗肿瘤作用：方法：从4周龄开始，给Lkb1fl/flp53fl/fl小鼠喂食低脂饮食和高脂饮食，以产生瘦或肥胖表型。诱导 EC 9 周后，肥胖和瘦小鼠随机接受替扎帕肽治疗 4 周。对体重和肿瘤重量、肿瘤转录组和代谢组概况、血清代谢标记物和趋化因子进行了评估：结果：肥胖小鼠和瘦小鼠在接受替扎帕肽治疗 2 周后体重都开始下降，最终肥胖小鼠体重显著下降 20.1%，瘦小鼠体重显著下降 16.8%。替扎帕肽改善了肥胖引起的血清脂肪连素、瘦素、GIP 和 C 反应蛋白水平。此外，相对于药物，替西帕肽能有效减少肥胖和瘦小鼠的肿瘤生长，抑制肥胖小鼠肿瘤中的ErbB信号传导和糖酵解/糖元生成，增加瘦小鼠肿瘤中的O-连接糖基化生物合成和磷脂酶D信号传导：结论：替唑帕肽通过影响肥胖小鼠和瘦小鼠EC肿瘤中的代谢和免疫途径，降低了小鼠体重和肿瘤生长。这种新颖的减肥治疗方法值得进一步评估，因为它是治疗欧共体肿瘤的一种创新策略。

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引用次数: 0

Prediction of non-resectability in tubo-ovarian cancer patients using Peritoneal Cancer Index – A prospective multicentric study using imaging (ISAAC study) 利用腹膜癌指数预测输卵管卵巢癌患者的不可切除性--一项利用成像技术进行的前瞻性多中心研究（ISAAC 研究）。

IF 4.5 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Gynecologic oncology

Pub Date : 2024-10-10 DOI: 10.1016/j.ygyno.2024.10.003

Background

The aim was to evaluate the performance of the Peritoneal Cancer Index (PCI) using imaging (ultrasound, contrast-enhanced computed tomography (CT), and whole-body diffusion-weighted magnetic resonance imaging (WB-DWI/MRI) in assessing peritoneal carcinomatosis and predicting non-resectability in tubo-ovarian carcinoma patients.

Methods

This was a prospective multicenter observational study. We considered all patients with suspected primary ovarian/tubal/peritoneal cancer who underwent preoperative ultrasound, CT, and WB-DWI/MRI (if available). The optimal cut off value for assessing the performance of the methods in predicting non-resectability was identified at the point at which the sensitivity and specificity were most similar. The reference standard to predict non-resectability was surgical outcome in terms of residual disease >1 cm or surgery not feasible. Agreement between imaging methods and surgical exploration in assessing sites included in the PCI score was evaluated using the Intraclass Correlation Coefficient (ICC).

Results

242 patients were included from January 2020 until November 2022. The optimal PCI cut-off for predicting non-resectability for surgical exploration was >12, which achieved the best AUC of 0.87, followed by ultrasound with a cut-off of >10 and AUC of 0.81, WB-DWI/MRI with a cut-off of >12 and AUC of 0.81, and CT with a cut-off of >11 and AUC of 0.74. Using ICC, ultrasound had very high agreement (0.94) with surgical PCI, while CT and WB-DWI/MRI had high agreement (0.86 and 0.87, respectively).

Conclusion

Ultrasound performed by an expert operator had the best agreement with surgical findings compared to WB-DWI/MRI and CT in assessing radiological PCI. In predicting non-resectability, ultrasound was non-inferior to CT, while its non-inferiority to WB-DWI/MRI was not demonstrated.

研究背景目的是评估腹膜癌指数（PCI）使用影像学（超声波、对比增强计算机断层扫描（CT）和全身弥散加权磁共振成像（WB-DWI/MRI））评估腹膜癌肿和预测输卵管卵巢癌患者不可切除性的性能：这是一项前瞻性多中心观察研究。我们考虑了所有疑似原发性卵巢癌/输卵管癌/腹膜癌患者，他们都接受了术前超声波、CT 和 WB-DWI/MRI（如果有的话）检查。评估各种方法预测不可切除性的性能的最佳临界值是灵敏度和特异性最接近的点。预测不可切除性的参考标准是残留病灶大于 1 厘米或手术不可行的手术结果。使用类内相关系数（ICC）评估了成像方法和手术探查在评估PCI评分所含部位方面的一致性。结果：从2020年1月到2022年11月，共纳入242例患者。预测手术探查不可切除性的最佳PCI临界值为>12，其最佳AUC为0.87；其次是超声，临界值为>10，AUC为0.81；WB-DWI/MRI，临界值为>12，AUC为0.81；CT，临界值为>11，AUC为0.74。使用ICC，超声与外科PCI的一致性非常高（0.94），而CT和WB-DWI/MRI的一致性也很高（分别为0.86和0.87）：结论：在评估放射学PCI方面，与WB-DWI/MRI和CT相比，由专家操作员进行的超声与手术结果的一致性最好。在预测不可切除性方面，超声并不优于 CT，而其不优于 WB-DWI/MRI 的优势并未得到证实。

{"title":"Prediction of non-resectability in tubo-ovarian cancer patients using Peritoneal Cancer Index – A prospective multicentric study using imaging (ISAAC study)","authors":"","doi":"10.1016/j.ygyno.2024.10.003","DOIUrl":"10.1016/j.ygyno.2024.10.003","url":null,"abstract":"<div><h3>Background</h3><div>The aim was to evaluate the performance of the Peritoneal Cancer Index (PCI) using imaging (ultrasound, contrast-enhanced computed tomography (CT), and whole-body diffusion-weighted magnetic resonance imaging (WB-DWI/MRI) in assessing peritoneal carcinomatosis and predicting non-resectability in tubo-ovarian carcinoma patients.</div></div><div><h3>Methods</h3><div>This was a prospective multicenter observational study. We considered all patients with suspected primary ovarian/tubal/peritoneal cancer who underwent preoperative ultrasound, CT, and WB-DWI/MRI (if available). The optimal cut off value for assessing the performance of the methods in predicting non-resectability was identified at the point at which the sensitivity and specificity were most similar. The reference standard to predict non-resectability was surgical outcome in terms of residual disease >1 cm or surgery not feasible. Agreement between imaging methods and surgical exploration in assessing sites included in the PCI score was evaluated using the Intraclass Correlation Coefficient (ICC).</div></div><div><h3>Results</h3><div>242 patients were included from January 2020 until November 2022. The optimal PCI cut-off for predicting non-resectability for surgical exploration was >12, which achieved the best AUC of 0.87, followed by ultrasound with a cut-off of >10 and AUC of 0.81, WB-DWI/MRI with a cut-off of >12 and AUC of 0.81, and CT with a cut-off of >11 and AUC of 0.74. Using ICC, ultrasound had very high agreement (0.94) with surgical PCI, while CT and WB-DWI/MRI had high agreement (0.86 and 0.87, respectively).</div></div><div><h3>Conclusion</h3><div>Ultrasound performed by an expert operator had the best agreement with surgical findings compared to WB-DWI/MRI and CT in assessing radiological PCI. In predicting non-resectability, ultrasound was non-inferior to CT, while its non-inferiority to WB-DWI/MRI was not demonstrated.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Finding a needle in the haystack: Identifying risk of MDS/AML after PARP inhibitor treatment 大海捞针：识别 PARP 抑制剂治疗后发生 MDS/AML 的风险

IF 4.5 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Gynecologic oncology

Pub Date : 2024-10-09 DOI: 10.1016/j.ygyno.2024.07.070

引用次数: 0