Abstract:Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer mortality among women. Two-thirds of patients present at advanced stage at diagnosis, and the estimated 5 year survival rate is 20–40%. This heterogeneous group of malignancies has distinguishable etiology and molecular biology. Initially, single-gene sequencing was performed to identify germline DNA variations associated with EOC. However, hereditary EOC syndrome can be explained by germline pathogenic variants (gPVs) in several genes. In th… Show more
“…In addition, the efficacy of chemotherapy for FIGO stage IC and advanced patients is controversial. Long-term chemotherapy can cause irreversible and severe toxicity resulting from the cumulative dose effect [ 18 ]. Hence, the present study was designed to build a more comprehensive prognostic model and to consider the effect of chemotherapy in different stages.…”
Section: Discussionmentioning
confidence: 99%
“…This finding suggests that surgery is sufficient for indolent early-stage cancer, and that chemotherapy can impair quality of life by serious adverse effects. Several single-nucleotide polymorphisms could be used to identify patients who are more likely to experience cisplatin-related toxicities [ 18 ]. Interestingly, even stage IA patients can experience relapse after administration of chemotherapy [ 36 ].…”
Background
We developed a nomogram for prognostic prediction of overall survival (OS) in postoperative ovarian sex cord-stromal tumor (SCST) patients and discuss the effect of chemotherapy at various FIGO stages.
Material/Methods
SCST patients after surgery from 2004 to 2015 were enrolled from the Surveillance, Epidemiology and End-Results (SEER) database, matched into pairs by propensity score matching (PSM), and divided into a training set and a validation set. Univariate and multivariate Cox analyses were conducted to identify significant variables for the development of the nomogram. The nomogram model was validated by concordance index (C-index), receiver operating characteristics (ROCs) curve, calibration plot, and decision curve analysis (DCA). Survival curves showed the integrative ability of prognostic prediction and the efficacy of chemotherapy.
Results
A total of 913 SCST patients were initially enrolled, and after PSM, 506 patients were included. Age, marital status, CA125 levels, tumor size, FIGO stage, grade, and chemotherapy were indicators for building the OS nomogram. The C-index was 0.850 in the training set and 0.786 in the validation set. Calibration plots were satisfactory and the nomogram had relatively better clinical utility than FIGO stage. The survival analysis showed that the low-risk group had generally longer survival than the high-risk group based on the prognostic score, and chemotherapy had an overall reverse effect on OS.
Conclusions
The nomogram model displays the potential to provide individualized prognosis probability of SCSTs and to aid in clinical decision-making. The unfavorable results of chemotherapy in all stages shows the need for further exploration.
“…In addition, the efficacy of chemotherapy for FIGO stage IC and advanced patients is controversial. Long-term chemotherapy can cause irreversible and severe toxicity resulting from the cumulative dose effect [ 18 ]. Hence, the present study was designed to build a more comprehensive prognostic model and to consider the effect of chemotherapy in different stages.…”
Section: Discussionmentioning
confidence: 99%
“…This finding suggests that surgery is sufficient for indolent early-stage cancer, and that chemotherapy can impair quality of life by serious adverse effects. Several single-nucleotide polymorphisms could be used to identify patients who are more likely to experience cisplatin-related toxicities [ 18 ]. Interestingly, even stage IA patients can experience relapse after administration of chemotherapy [ 36 ].…”
Background
We developed a nomogram for prognostic prediction of overall survival (OS) in postoperative ovarian sex cord-stromal tumor (SCST) patients and discuss the effect of chemotherapy at various FIGO stages.
Material/Methods
SCST patients after surgery from 2004 to 2015 were enrolled from the Surveillance, Epidemiology and End-Results (SEER) database, matched into pairs by propensity score matching (PSM), and divided into a training set and a validation set. Univariate and multivariate Cox analyses were conducted to identify significant variables for the development of the nomogram. The nomogram model was validated by concordance index (C-index), receiver operating characteristics (ROCs) curve, calibration plot, and decision curve analysis (DCA). Survival curves showed the integrative ability of prognostic prediction and the efficacy of chemotherapy.
Results
A total of 913 SCST patients were initially enrolled, and after PSM, 506 patients were included. Age, marital status, CA125 levels, tumor size, FIGO stage, grade, and chemotherapy were indicators for building the OS nomogram. The C-index was 0.850 in the training set and 0.786 in the validation set. Calibration plots were satisfactory and the nomogram had relatively better clinical utility than FIGO stage. The survival analysis showed that the low-risk group had generally longer survival than the high-risk group based on the prognostic score, and chemotherapy had an overall reverse effect on OS.
Conclusions
The nomogram model displays the potential to provide individualized prognosis probability of SCSTs and to aid in clinical decision-making. The unfavorable results of chemotherapy in all stages shows the need for further exploration.
“…Opportunities for further exploration of CHK inhibitors in HGSOC arise from the observation that CHK1 inhibition is synergistic with inhibition of mitotic kinase AURKA. 42 The CHK1 inhibitor LY2603618 and the AURKA inhibitor alisertib exhibited synergistic effects in vitro in ovarian cancer cell lines, producing cell cycle arrest and inducing apoptosis. 43 WEE1 kinase and related kinase PKMYT1 phosphorylate kinase CDK1 preventing the formation of the complex with cyclin B and preventing CDK1 activation which pushes the cell through the G2 phase into mitosis.…”
High-grade serous ovarian carcinoma (HGSOC) is the most common type of ovarian cancer and the most lethal gynecologic malignancy due to advanced stage at presentation. Recent years have witnessed progress in the therapy of HGSOC with the introduction of PARP (poly-adenosine diphosphate ribose polymerase) inhibitors and the anti-angiogenic monoclonal antibody bevacizumab to the backbone of chemotherapy or as maintenance therapy after chemotherapy. The improved molecular understanding of ovarian cancer pathogenesis, which has brought these therapies into the clinic, aspires to extend the boundaries of therapies through elucidation of other molecular aspects of ovarian carcinogenesis. This accumulating knowledge has started to be translated to additional targeted therapies that are in various stages of development. These include inhibitors of the function of other proteins involved in homologous recombination deficiency (HRD), such as WEE1 kinase, ATM/ATR kinases and CDK12 inhibitors. Despite disappointing results with immune checkpoint inhibitors monotherapy, harnessing the immune system in HGSOC with combination therapies that promote antigen production and immune cell activation is an avenue being explored. This paper examines arising HGSOC therapies based on molecular understanding of pathogenesis.
“…Therefore, personalised molecular therapeutic strategies (antiestrogens, HER2 targeted therapies, RAS/RAF inhibitors, KRAS inhibitors, P53 reactivators, PI3-kinase inhibitors, …) will become crucial in the future as an alternative/complement to conventional chemotherapy [2,10]. These last years, in ovarian carcinomas associated with BRCA1/2 mutations, poly (ADP-ribose) polymerase inhibitors (PARP inhibitors) (olaparib, niraparib, veliparib, …) demonstrated evident improvements in progressionfree survival [16][17][18]. Nevertheless, BRCA 1 or 2 mutations or homologous recombinant deficiency are not associated with mucinous carcinomas [2].…”
Primary ovarian intestinal-type mucinous carcinomas associated with mature teratoma are rare and represent less than 3% of all primary ovarian neoplasms. The molecular profile of these tumors is still controversial. We report here the first case of mucinous ovarian tumor in which mutation of the PIK3CA and P53 genes could be demonstrated by the next generation sequencing technique without KRAS mutation or HER2 amplification. Our data suggest that these mucinous carcinoma variants probably present an extremely complex molecular biology profile that should be known in the future to stratify therapeutic outcomes and potential targeted therapies, particularly in recurrent disease.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.