المؤلفون: Huayi Li, Zikun Peng, Jianqing Zhu, Weidong Zhao, Yi Huang, Ruifang An, Hong Zheng, Pengpeng Qu, Li Wang, Qi Zhou, Danbo Wang, Ge Lou, Jing Wang, Ke Wang, Beihua Kong, Xing Xie, Rutie Yin, John Low, Abdul Malik Rozita, Lim Chun Sen, Yong Chee Meng, Kho Swee Kiong, Jihong Liu, Zhiqing Liang, Weiguo Lv, Yaping Zhu, Weiguo Hu, Wei Sun, Jingya Su, Qiqi Wang, Rongyu Zang, Ding Ma, Qinglei Gao

المصدر: BMC Medicine, Vol 22, Iss 1, Pp 1-13 (2024)

مصطلحات موضوعية: Platinum-sensitive relapsed ovarian cancer, Olaparib, PD-L1 expression, BRCA1/2, PARP inhibitors, Homologous recombination deficiency, Medicine

الوصف: Abstract Background The prospective phase III multi-centre L-MOCA trial (NCT03534453) has demonstrated the encouraging efficacy and manageable safety profile of olaparib maintenance therapy in the Asian (mainly Chinese) patients with platinum-sensitive relapsed ovarian cancer (PSROC). In this study, we report the preplanned exploratory biomarker analysis of the L-MOCA trial, which investigated the effects of homologous recombination deficiency (HRD) and programmed cell death ligand 1 (PD-L1) expression on olaparib efficacy. Methods HRD status was determined using the ACTHRD assay, an enrichment-based targeted next-generation sequencing assay. PD-L1 expression was assessed by SP263 immunohistochemistry assay. PD-L1 expression positivity was defined by the PD-L1 expression on ≥ 1% of immune cells. Kaplan–Meier method was utilised to analyse progression-free survival (PFS). Results This exploratory biomarker analysis included 225 patients and tested HRD status [N = 190; positive, N = 125 (65.8%)], PD-L1 expression [N = 196; positive, N = 56 (28.6%)], and BRCA1/2 mutation status (N = 219). The HRD-positive patients displayed greater median PFS than the HRD-negative patients [17.9 months (95% CI: 14.5–22.1) versus 9.2 months (95% CI: 7.5–13.8)]. PD-L1 was predominantly expressed on immune cells. Positive PD-L1 expression on immune cells was associated with shortened median PFS in the patients with germline BRCA1/2 mutations [14.5 months (95% CI: 7.4–18.2) versus 22.2 months (95% CI: 18.3–NA)]. Conversely, positive PD-L1 expression on immune cells was associated with prolonged median PFS in the patients with wild-type BRCA1/2 [20.9 months (95% CI: 13.9–NA) versus 8.3 months (95% CI: 6.7–13.8)]. Conclusions HRD remained an effective biomarker for enhanced olaparib efficacy in the Asian patients with PSROC. Positive PD-L1 expression was associated with decreased olaparib efficacy in the patients with germline BRCA1/2 mutations but associated with improved olaparib efficacy in the patients with wild-type BRCA1/2. Trial registration NCT03534453. Registered at May 23, 2018.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1741-7015Test

الوصول الحر: https://doaj.org/article/f5e3af1247dd40f9aa8344da62322e0aTest

المؤلفون: Lilit Harutyunyan, Evelina Manvelyan, Nune Karapetyan, Samvel Bardakhchyan, Aram Jilavyan, Gevorg Tamamyan, Armen Avagyan, Liana Safaryan, Davit Zohrabyan, Narine Movsisyan, Anna Avinyan, Arevik Galoyan, Mariam Sargsyan, Martin Harutyunyan, Hasmik Nersoyan, Arevik Stepanyan, Armenuhi Galstyan, Samvel Danielyan, Armen Muradyan, Gagik Jilavyan

المصدر: Current Oncology, Vol 31, Iss 3, Pp 1323-1334 (2024)

مصطلحات موضوعية: recurrent ovarian cancer, platinum-sensitive relapse, platinum-resistant relapse, platinum-refractory relapse, targeted therapy, chemotherapy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Background: Annually, approximately 200 new ovarian cancer cases are diagnosed in Armenia, which is considered an upper-middle-income country. This study aimed to summarize the survival outcomes of patients with relapsed ovarian cancer in Armenia based on the type of recurrence, risk factors, and choice of systemic treatment. Methods: This retrospective case-control study included 228 patients with relapsed ovarian cancer from three different institutions. Results: The median age of the patients was 55. The median follow-up times from relapse and primary diagnosis were 21 and 48 months, respectively. The incidence of platinum-sensitive relapse was 81.6% (186), while platinum-resistant relapse was observed in only 18.4% (42) of patients. The median post-progression survival of the platinum-sensitive group compared to the platinum-resistant group was 54 vs. 25 months (p < 0.001), respectively, while the median survival after relapse was 25 vs. 13 months, respectively; three- and five-year post-progression survival rates in these groups were 31.2% vs. 23.8%, and 15.1% vs. 9.5%, respectively (p = 0.113). Conclusions: Overall, despite new therapeutic approaches, ovarian cancer continues to be one of the deadly malignant diseases affecting women, especially in developing countries with a lack of resources, where chemotherapy remains the primary available systemic treatment for the majority of patients. Low survival rates demonstrate the urgent need for more research focused on this group of patients with poor outcomes.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1718-7729/31/3/100Test; https://doaj.org/toc/1198-0052Test; https://doaj.org/toc/1718-7729Test

الوصول الحر: https://doaj.org/article/786ec4df7f0149208daeb599b2e0349eTest

المؤلفون: Yana Ma, Jiale Liu, Ning Li, Hualei Bu, Yongwen Huang, Chengjuan Jin, Hao Wen, Shuai Feng, Hui Zhang, Xiaorong Yang, Beihua Kong, Lingying Wu, Kun Song

المصدر: Journal of Ovarian Research, Vol 16, Iss 1, Pp 1-9 (2023)

مصطلحات موضوعية: PARPi monotherapy, Platinum-sensitive recurrence, BRCA1/2 mutation, Post-recurrence survival, Gynecology and obstetrics, RG1-991

الوصف: Abstract Background The therapeutic effect of poly (ADP-ribose) polymerase inhibitors (PARPi) monotherapy compared with platinum-based chemotherapy, and the impact to subsequent platinum-based chemotherapy after PARPi resistance were inconclusive in breast cancer susceptibility genes (BRCA)1/2-mutated ovarian cancer patients with secondary platinum-sensitive relapse. Methods BRCA1/2-mutated patients with secondary platinum-sensitive relapse included in this study did not receive any maintenance regimen after first- and second-line platinum-based chemotherapy, and the secondary platinum-free interval (PFI) was more than 6 months. Patients in study group were treated with PARPi monotherapy until disease progression, and patients in control group were treated with platinum-based chemotherapy without restriction. Progression-free survival (PFS) was defined as the time from third-line therapy to disease progression or death, PFS2 was defined as the time from platinum-based chemotherapy after PARPi resistance to next subsequent therapy or death. Post-recurrence survival (PRS) refers to the survival time after secondary platinum-sensitive relapse. Results A total of 119 patients were retrospectively analyzed, including 71 (59.7%) in study group and 48 (40.3%) in control group. The objective response rate (ORR: 77.5% vs. 80.0%, p=0.766) and PFS (median: 11.2 vs. 11.0 months, p=0.962) were comparable. The benefit of subsequent platinum-based chemotherapy after PARPi resistance was more pronounced in patients with PARPi treatment for more than 12 months (median PFS2: 8.6 vs. 4.3 months, p=0.040). PARPi monotherapy had no adverse effect on PRS compared with platinum-based chemotherapy (median PRS:41.2 vs. 42.8 months, p=0.323). Compared to patients in control group who had never received PARPi, PARPi monotherapy (median PRS: 41.2 vs. 33.7 months, p=0.019) and post-line treatment with PARPi in the control group (median PRS: 48.1 vs. 33.7 months, p=0.002) could prolong PRS for patients with secondary platinum-sensitive relapse. Conclusions PARPi monotherapy was similar to platinum-based chemotherapy for BRCA1/2-mutated ovarian cancer patients with secondary platinum-sensitive recurrence, and could improve prognosis.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1757-2215Test

الوصول الحر: https://doaj.org/article/8e7ef6a125174ca0be522d3c813836b7Test

المؤلفون: Jinghong Chen, Mengpei Zhang, Kemin Li, Yuanqiong Duan, Xiaojuan Lin, Lan Zhong, Qintong Li, Rutie Yin

المصدر: Frontiers in Oncology, Vol 13 (2024)

مصطلحات موضوعية: PARP inhibitor, platinum-sensitive recurrent ovarian cancer, real-world study, progression-free survival, safety, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: ObjectiveThe aim of this study is to assess the efficacy and safety of poly (ADP-ribose) polymerase inhibitor (PARPi) as a maintenance therapy for patients with platinum-sensitive recurrent epithelial ovarian cancer (PSROC) at the largest center of gynecologic oncology in Western China.Patients and methodsThe efficacy of PARPi was evaluated by progression-free survival (PFS) and overall survival (OS) in this real-world single-center retrospective cohort study conducted at West China Second University Hospital. The safety of PARPi was assessed using Common Terminology Criteria for Adverse Events Version 5.0.ResultsIn this study, we included a total of 75 eligible patients, of which 54 (72.0%) received olaparib and 21 (28.0%) received niraparib. Among these patients, 24 (32.0%) had breast cancer susceptibility gene (BRCA) mutations, 27 (36.0%) achieved complete response after their last platinum-based therapy, and 22 (29.3%) had previously received ≥3rd-line chemotherapy. The median progression-free survival (mPFS) was 19.1 months (95% CI 8.5-29.7), and the median overall survival (mOS) had not been reached. Log-rank analysis revealed that age (0.05). The most common grade≥3 adverse events in the olaparib group were anemia, thrombocytopenia, and leukopenia, while in the niraparib group, they were anemia and thrombocytopenia.ConclusionThis study confirmed that olaparib and niraparib are effective and tolerate for PSROC in real-world settings. At the follow-up endpoint, no independent prognostic factor associated with prolonged PFS was identified.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fonc.2023.1300199/fullTest; https://doaj.org/toc/2234-943XTest

الوصول الحر: https://doaj.org/article/cc7ff35485b7413c99e47c41146ab30eTest

المؤلفون: Kemin Li, Rutie Yin

المصدر: Frontiers in Immunology, Vol 15 (2024)

مصطلحات موضوعية: high-grade serous adenocarcinoma of the ovary, platinum allergy, platinum desensitization therapy, platinum-sensitive recurrence, prognosis, Immunologic diseases. Allergy, RC581-607

الوصف: BackgroundTo examine the value of five-step platinum desensitization therapy in epithelial ovarian cancerMethodsA retrospective study was conducted on the high-grade serous adenocarcinoma of the ovary (HGSAO) patients who developed a platinum allergy during treatment and received desensitization therapy between January, 2016 and December, 2020. The logistic-regression was adopted to analyze the relationship between platinum desensitization therapy and prognosis in HGSAO patients.Results92 HGSAO patients were included in the study. Among these, 35 patients (38.0%) experienced mild allergic reactions, 51 (55.4%) experienced moderate allergic reactions, and 6 (6.5%) experienced severe allergic reactions. The desensitization therapy was successful in 86 patients (93.5%). Six patients had desensitization failure, of which five experienced severe allergic reactions during desensitization. The logistic-regression analysis revealed no significant correlation between platinum desensitization therapy and progression-free survival (PFS) or overall survival (OS) of patients (P < 0.05). However, the subgroup analysis demonstrated that the success or failure of platinum desensitization therapy significantly impacted the OS of patients who were platinum-sensitive recurrence. The patients who had successful desensitization therapy had a superior OS.ConclusionFive-step platinum desensitization therapy has potential application value in patients who were platinum-sensitive recurrence after first-line treatment but may bear the risk of severe allergic reactions.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2024.1346464/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/2eb60a9d49144dd9ba433d9f9370e295Test

المؤلفون: Rakhimov Nodir Makhammatkulovich, Shakhanova Shakhnoza Shavkatovna, Abdurakhmonov Jurabek Amrilloevich, Talibova Nilufar Aktamovna, Sulimova Olga Gennadievna

مصطلحات موضوعية: ovarian cancer, lymph node dissection, cytoreduction, metastasis, platinum-sensitive and platinum-resistant recurrence

الوصف: Ovarian cancer (OC) remains the leading cause of death from gynecological cancer. The initial treatment for IC-IV stages of OC includes surgical cytoreduction followed by platinum-containing chemotherapy. The best outcomes are observed in patients, in whom complete cytoreduction has been achieved. Despite this fact, most patients develop relapses and the 5-year survival rate is about 30 %. The frequency of lymph node involvement in patients with recurrent OC is not reliably known; isolated lymph node recurrence is reported to occur in 5–32 % of patients. To date, the problem regarding the extent of lymph node dissection in treatment of OC recurrence is still unsolved. In our paper we review the available data concerning the role of secondary cytoreductive surgery for isolated lymph node recurrence of ovarian cancer. Isolated lymph node recurrence of ovarian cancer may indicate a more favorable prognosis and has a less aggressive pattern of OC relapse. The role of secondary cytoreduction in this context is ...

العلاقة: https://dx.doi.org/10.5281/zenodo.10963163Test

الإتاحة: https://doi.org/10.5281/zenodo.1096316210.5281/zenodo.10963163Test

المؤلفون: Meteran, Hanieh, Knudsen, Anja &Ør, Jørgensen, Trine Lembrecht, Nielsen, Dorte, Herrstedt, Jørn

المصدر: Meteran , H , Knudsen , A Ø , Jørgensen , T L , Nielsen , D & Herrstedt , J 2024 , ' Carboplatin plus Paclitaxel in Combination with the Histone Deacetylate Inhibitor, Vorinostat, in Patients with Recurrent Platinum-Sensitive Ovarian Cancer ' , Journal of Clinical Medicine , vol. 13 , no. 3 , 897 . https://doi.org/10.3390/jcm13030897Test

مصطلحات موضوعية: histone deacetylase inhibitor, ovarian cancer, platinum-sensitive recurrence, vorinostat

الوصف: Background: This phase II study evaluated the efficacy and safety of the histone deacetylase (HDAC) inhibitor, vorinostat, administered in combination with paclitaxel and carboplatin in patients with platinum sensitive recurrent ovarian cancer. Methods: Women with recurrent platinum-sensitive ovarian, peritoneal, or Fallopian tube carcinoma, a performance status of 0–2, and good overall organ function were eligible. Patients received 6 courses of paclitaxel (175 mg/m 2 ) and carboplatin area under the curve (AUC) of 5.0 mg/mL/min administered via intravenous infusion on day 1 of a 3-week schedule. In addition, patients received vorinostat 400 mg orally once daily on days −4 through 10 of Cycle 1 and days 1 through 14 of each subsequent treatment cycle. The primary endpoints were progression-free survival (PFS) and adverse events. The secondary endpoints were the objective response rate and overall survival. Results: Fifty-five patients were included. CR was obtained in 14 patients (26.4%) and PR in 19 patients (35.8%), resulting in an ORR of 62.2%. Twenty patients (37.7%) had SD. The median duration of response (DoR) was 12.6 (range 6–128) months. The median PFS was 11.6 months (95% CI, 10.3–18.0; p < 0.001). Median OS was 40.6 months (95% Cl, 25.1–56.1). The most common treatment-related adverse events (all grades) were fatigue, anemia, thrombocytopenia, neutropenia, anorexia, nausea, pain, sensory neuropathy, myalgia, stomatitis and diarrhea. Conclusions: Vorinostat combined with carboplatin plus paclitaxel was tolerable and generated significant responses including a long median overall survival in recurrent platinum-sensitive ovarian cancer.

وصف الملف: application/pdf

العلاقة: https://portal.findresearcher.sdu.dk/da/publications/84e285ba-e92e-41ab-8b4f-0b5dc758bbfaTest

الإتاحة: https://doi.org/10.3390/jcm13030897Test
https://portal.findresearcher.sdu.dk/da/publications/84e285ba-e92e-41ab-8b4f-0b5dc758bbfaTest
https://findresearcher.sdu.dk/ws/files/256050698/jcm-13-00897-v2.pdfTest

المؤلفون: Yen-Fu Chen, Shih-Tien Hsu, Sheau-Feng Hwang, Lou Sun, Chih-Ku Liu, Yu-Hsiang Shih, Ting-Fang Lu, Jun-Sing Wang, Chien-Hsing Lu

المصدر: Journal of Clinical Medicine, Vol 13, Iss 2, p 566 (2024)

مصطلحات موضوعية: recurrent ovarian cancer, platinum-sensitive ovarian cancer, epithelial ovarian cancer, chemotherapy, maintenance therapy, Medicine

الوصف: (1) Background: Our aim was to evaluate the efficacy and adverse effects of maintenance chemotherapy in platinum-sensitive recurrent epithelial ovarian cancer after second-line chemotherapy. (2) Methods: A total of 72 patients from a single institute who had been diagnosed with platinum-sensitive recurrent ovarian cancer and had experienced either complete or partial response after six cycles of second-line chemotherapy were divided into a standard group ( n = 31) with six cycles or a maintenance group ( n = 41) with more than six cycles. We then compared patient characteristics and survival outcomes between these two groups. (3) Results: In all patients, after primary management for the first recurrence, the maintenance group showed worse survival outcomes. Patients who had not undergone either surgery or radiotherapy were divided into complete response and partial response groups after six cycles of chemotherapy. In patients with partial response, maintenance chemotherapy led to a significant improvement in PFS (median, 3.6 vs. 6.7 months, p = 0.007), but no significant change in in OS. The median cycle number of maintenance chemotherapy was four. (4) Conclusions: Maintenance chemotherapy may still play an important role in patients with platinum-sensitive recurrent ovarian cancer, particularly in selected patient groups.

العلاقة: https://www.mdpi.com/2077-0383/13/2/566Test; https://doaj.org/toc/2077-0383Test; https://doaj.org/article/e01e372e1fd94a91a59dbc4365be623dTest

الإتاحة: https://doi.org/10.3390/jcm13020566Test
https://doaj.org/article/e01e372e1fd94a91a59dbc4365be623dTest

المؤلفون: Jiao Liu, Yaoyao Liu, Chunjiao Yang, Jingjing Liu, Jiaxin Hao

المصدر: Translational Oncology, Vol 37, Iss , Pp 101762- (2023)

مصطلحات موضوعية: Ovarian cancer, Platinum-sensitive, Prognostic model, Chemo drug, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Background: Ovarian cancer (OC) is one of the most lethal gynecological malignancies. This study aimed to identify biomarkers that were sensitive to platinum-based chemotherapeutic agents and can be used in immunotherapy and explore the importance of their mechanisms of action. Methods: RNA-seq profiles and clinicopathological data for OC samples were obtained from The Cancer Genome Atlas (TCGA) and cBioPortal platform, respectively. Platinum-sensitive and platinum-resistant OC samples in the TCGA cohort were selected based on the clinical information. RNA-seq data for 70 OC samples withSingle-sample gene set enrichment analysis (ssGSEA) and unsupervised clustering were used to classify OC patients from the TCGA cohort into clusters with different proportions of infiltrating immune cells. ESTIMATE analysis was used to assess the immune landscape among clusters. Differential expression, univariate Cox regression, and LASSO regression analyses were performed to construct prognostic model. Spearman correlation analysis was conducted to investigate the correlations among immune checkpoint inhibitors (ICIs) and risk score, half-maximal drug inhibitory concentration (IC50) and risk score. Results: Using ssGSEA and unsupervised clustering, OC samples were divided into two clusters with different immune cell infiltration. Then, 1715 differentially expressed immune-related genes (DEIRGs) were identified between two clusters, 984 differentially expressed platinum-sensitive related genes (DEPSRGs) between 149 platinum-sensitive and 63 platinum-resistant OC samples were identified, and 5384 differentially expressed genes (DEGs) between 380 OC and 194 normal samples were detected from the TCGA cohort. Six biomarkers (GMPPB, SRPK1, STC1, PRSS16, HPDL, and SPTSSB) were detected to establish a prognostic model. The OC patients in the TCGA cohort were classified into high- and low-risk groups. The receive operating characteristic (ROC) curve was plotted and demonstrated that the prognostic model performed well with the area under ROC curve (AUC) greater than 0.6. The expressions of 5 ICIs, including CD200, TNFRSF18, CD160, CD200R1, and CD274 (PD-L1), were significantly different between two risk groups, and the risk score was significant negative associated with CTLA4, TNFRSF4, TNFRSF18, and CD274. Moreover, there were significant differences in IC50 of 10 chemo drugs between two risk groups, patients in the high-risk group could be more resistant to po0tinib, dasatinib, and neratinib. Conclusion: In summary, this study constructed a novel prognostic model based on six prognostic biomarkers, including GMPPB, SRPK1, STC1, PRSS16, HPDL, and SPTSSB, which can be utilized for predicting the prognosis of OC patients. These biomarkers were the potential therapeutic targets.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S1936523323001481Test; https://doaj.org/toc/1936-5233Test

الوصول الحر: https://doaj.org/article/7eb04faaf7094c549bfd535e43022afcTest

المؤلفون: Hanieh Meteran, Anja Ør Knudsen, Trine Lembrecht Jørgensen, Dorte Nielsen, Jørn Herrstedt

المصدر: Journal of Clinical Medicine, Vol 13, Iss 3, p 897 (2024)

مصطلحات موضوعية: ovarian cancer, platinum-sensitive recurrence, histone deacetylase inhibitor, vorinostat, Medicine

الوصف: Background: This phase II study evaluated the efficacy and safety of the histone deacetylase (HDAC) inhibitor, vorinostat, administered in combination with paclitaxel and carboplatin in patients with platinum sensitive recurrent ovarian cancer. Methods: Women with recurrent platinum-sensitive ovarian, peritoneal, or Fallopian tube carcinoma, a performance status of 0–2, and good overall organ function were eligible. Patients received 6 courses of paclitaxel (175 mg/m2) and carboplatin area under the curve (AUC) of 5.0 mg/mL/min administered via intravenous infusion on day 1 of a 3-week schedule. In addition, patients received vorinostat 400 mg orally once daily on days −4 through 10 of Cycle 1 and days 1 through 14 of each subsequent treatment cycle. The primary endpoints were progression-free survival (PFS) and adverse events. The secondary endpoints were the objective response rate and overall survival. Results: Fifty-five patients were included. CR was obtained in 14 patients (26.4%) and PR in 19 patients (35.8%), resulting in an ORR of 62.2%. Twenty patients (37.7%) had SD. The median duration of response (DoR) was 12.6 (range 6–128) months. The median PFS was 11.6 months (95% CI, 10.3–18.0; p < 0.001). Median OS was 40.6 months (95% Cl, 25.1–56.1). The most common treatment-related adverse events (all grades) were fatigue, anemia, thrombocytopenia, neutropenia, anorexia, nausea, pain, sensory neuropathy, myalgia, stomatitis and diarrhea. Conclusions: Vorinostat combined with carboplatin plus paclitaxel was tolerable and generated significant responses including a long median overall survival in recurrent platinum-sensitive ovarian cancer.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2077-0383/13/3/897Test; https://doaj.org/toc/2077-0383Test

الوصول الحر: https://doaj.org/article/b16797c7e0f8462f9dff526026ace7c1Test