Genomic instability (GI) score post-neoadjuvant chemotherapy (NACT) to predict overall survival (OS) in high grade ovarian cancer (HGSOC).

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 5573-5573
Author(s):  
Aurelie Auguste ◽  
Elena Cojocaru ◽  
Soizick Mesnage ◽  
Audrey Le Formal ◽  
Romy chen-Min-Tao ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Genomic Instability ◽  
High Grade

Histopathologic response to neoadjuvant chemotherapy as a prognostic biomarker in tubo-ovarian high-grade serous carcinoma: updated Chemotherapy Response Score (CRS) results

2019 ◽  
Vol 29 (2) ◽  
pp. 353-356 ◽  
Author(s):  
Steffen Böhm ◽  
Nhu Le ◽  
Michelle Lockley ◽  
Elly Brockbank ◽  
Asma Faruqi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
European Society ◽  
Prognostic Biomarker ◽  
Serous Carcinoma ◽  
Chemotherapy Response ◽  
High Grade ◽  
Cancer Management

ObjectiveThe Chemotherapy Response Scoring (CRS) system was developed to enable reproducible reporting of histologic tumor response in interval debulking specimens following neoadjuvant chemotherapy in advanced stage tubo-ovarian high-grade serous carcinoma. This prognostic biomarker has been included in ovarian cancer pathology reporting guidelines (International Collaboration on Cancer Reporting, College of American Pathologists) and in the upcoming European Society for Medical Oncology-European Society of Gynaecological Oncology (ESMO-ESGO) guidelines for ovarian cancer management. We present follow-up data on the CRS validation initiatives and suggest research with novel therapeutic agents incorporating this biomarker.MethodsThe cohort on whom CRS was originally developed was analyzed after an extended follow-up of an additional 36 months. The CRS histopathologic scoring system was applied to omental sections obtained at interval surgery from all 80 patients. Progression-free and overall survival were re-calculated.ResultsAfter a median follow-up of 4.3 years the CRS score predicted progression-free survival with an HR of 0.39 (95% CI 0.21 to 0.70), p = 0.002 adjusted for age, stage, and debulking status (median 1.08 vs 2.27 years for CRS1/2 vs CRS3). CRS was also predictive of overall survival with an HR of 0.17 (95% CI 0.07 to 0.44), p = 0.0002 adjusted for age, stage, and debulking status (median 2.55 vs 5.47 years for CRS1/2 vs CRS3).ConclusionCRS3 is a reproducible prognostic biomarker for improved progression-free and overall survival in stage 3C or 4 tubo-ovarian high-grade serous carcinoma after neoadjuvant chemotherapy. The score, obtained at interval debulking surgery, can help facilitate research and biomarker driven first-line treatment of patients with advanced ovarian cancer.

scholarly journals Trace Amine-Associated Receptor 1 (TAAR1) Is a Positive Prognosticator for Epithelial Ovarian Cancer

2021 ◽  
Vol 22 (16) ◽  
pp. 8479
Author(s):  
Tilman L. R. Vogelsang ◽  
Aurelia Vattai ◽  
Elisa Schmoeckel ◽  
Till Kaltofen ◽  
Anca Chelariu-Raicu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Epithelial Ovarian Cancer ◽  
Tnm Classification ◽  
Rank Correlation ◽  
University Hospital ◽  
Cancer Tissue ◽  
Low Grade ◽  
High Grade ◽  
Trace Amine

Trace amine-associated receptor 1 (TAAR1) is a Gαs- protein coupled receptor that plays an important role in the regulation of the immune system and neurotransmission in the CNS. In ovarian cancer cell lines, stimulation of TAAR1 via 3-iodothyronamine (T1AM) reduces cell viability and induces cell death and DNA damage. Aim of this study was to evaluate the prognostic value of TAAR1 on overall survival of ovarian carcinoma patients and the correlation of TAAR1 expression with clinical parameters. Ovarian cancer tissue of n = 156 patients who were diagnosed with epithelial ovarian cancer (serous, n = 110 (high-grade, n = 80; low-grade, n = 24; unknown, n = 6); clear cell, n = 12; endometrioid, n = 21; mucinous, n = 13), and who underwent surgery at the Department of Obstetrics and Gynecology, University Hospital of the Ludwig-Maximilians University Munich, Germany between 1990 and 2002, were analyzed. The tissue was stained immunohistochemically with anti-TAAR1 and evaluated with the semiquantitative immunoreactive score (IRS). TAAR1 expression was correlated with grading, FIGO and TNM-classification, and analyzed via the Spearman’s rank correlation coefficient. Further statistical analysis was obtained using nonparametric Kruskal-Wallis rank-sum test and Mann-Whitney-U-test. This study shows that high TAAR1 expression is a positive prognosticator for overall survival in ovarian cancer patients and is significantly enhanced in low-grade serous carcinomas compared to high-grade serous carcinomas. The influence of TAAR1 as a positive prognosticator on overall survival indicates a potential prognostic relevance of signal transduction of thyroid hormone derivatives in epithelial ovarian cancer. Further studies are required to evaluate TAAR1 and its role in the development of ovarian cancer.

Genomic profiling of the residual disease of advanced high‐grade serous ovarian cancer after neoadjuvant chemotherapy

2019 ◽  
Vol 146 (7) ◽  
pp. 1851-1861 ◽  
Author(s):  
Yong J. Lee ◽  
Dachan Kim ◽  
Jung E. Shim ◽  
Su‐Jin Bae ◽  
Yu‐Jin Jung ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Residual Disease ◽  
Genomic Profiling ◽  
High Grade ◽  
Serous Ovarian Cancer

scholarly journals The FIGO Stage IVA Versus IVB of Ovarian Cancer: Prognostic Value and Predictive Value for Neoadjuvant Chemotherapy

2018 ◽  
Vol 28 (3) ◽  
pp. 453-458 ◽  
Author(s):  
Parvin Tajik ◽  
Roelien van de Vrie ◽  
Mohammad H. Zafarmand ◽  
Corneel Coens ◽  
Marrije R. Buist ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Epithelial Ovarian Cancer ◽  
Prognostic Value ◽  
Median Overall Survival ◽  
Stage Iv ◽  
Figo Stage ◽  
Figo Staging ◽  
Stage Ivb

ObjectiveThe revised version of the International Federation of Gynaecology and Obstetrics (FIGO) staging system (2014) for epithelial ovarian cancer includes a number of changes. One of these is the division of stage IV into 2 subgroups. Data on the prognostic and predictive significance of this classification are scarce. The effect of neoadjuvant chemotherapy (NACT) versus primary debulking surgery (PDS) in relation to the subclassification of FIGO stage IV is also unknown.MethodsWe used data of the EORTC 55971 trial, in which 670 patients with previous stage IIIC or IV epithelial ovarian cancer were randomly assigned to PDS or NACT; 160 patients had previous stage IV. Information on previous FIGO staging and presence of pleural effusion with positive cytology were used to classify tumors as either stage IVA or IVB. We tested the association between stage IVA/IVB and survival to evaluate the prognostic value and interactions between stage, treatment, and survival to evaluate the predictive performance.ResultsAmong the 160 participants with previous stage IV disease, 103 (64%) were categorized as stage IVA and 57 (36%) as stage IVB tumors. Median overall survival was 24 months in FIGO stage IVA and 31 months in stage IVB patients (P = 0.044). Stage IVB patients treated with NACT had 9 months longer median overall survival compared with IVB patients undergoing PDS (P = 0.025), whereas in IVA patients, no significant difference was observed (24 vs 26 months, P = 0.48).ConclusionsThe reclassification of FIGO stage IV into stage IVA or IVB was not prognostic as expected. Compared with stage IVA patients, stage IVB patients have a better overall survival and may benefit more from NACT.

TRUST: Trial of Radical Upfront Surgical Therapy in advanced ovarian cancer (ENGOT ov33/AGO‐OVAR OP7)

2019 ◽  
Vol 29 (8) ◽  
pp. 1327-1331 ◽  
Author(s):  
Alexander Reuss ◽  
Andreas du Bois ◽  
Philipp Harter ◽  
Christina Fotopoulou ◽  
Jalid Sehouli ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Cytoreductive Surgery ◽  
Advanced Ovarian Cancer ◽  
Figo Stage ◽  
Complete Resection ◽  
Peritoneal Carcinoma ◽  
Exclusion Criteria ◽  
Platinum Based Chemotherapy

BackgroundPrimary cytoreductive surgery followed by chemotherapy has been considered standard management for patients with advanced ovarian cancer over decades. An alternative approach of interval debulking surgery following neoadjuvant chemotherapy was subsequently reported by two randomized phase III trials (EORTC‐GCG, CHORUS), which were criticized owing to important limitations, especially regarding the rate of complete resection.Primary ObjectiveTo clarify the optimal timing of surgical therapy in advanced ovarian cancer.Study HypothesisPrimary cytoreductive surgery is superior to interval cytoreductive surgery following neoadjuvant chemotherapy for overall survival in patients with advanced ovarian cancer.Trial DesignTRUST is an international open, randomized, controlled multi-center trial investigating overall survival after primary cytoreductive surgery versus neoadjuvant chemotherapy and subsequent interval cytoreductive surgery in patients with FIGO stage IIIB–IVB ovarian, tubal, and peritoneal carcinoma. To guarantee adequate surgical quality, participating centers need to fulfill specific quality assurance criteria (eg, ≥50% complete resection rate in upfront surgery for FIGO IIIB–IVB patients, ≥36 debulking-surgeries/year) and agree to independent audits by TRUST quality committee delegates. Patients in the primary cytoreductive surgery arm undergo surgery followed by 6 cycles of platinum-based chemotherapy, whereas patients in the interval cytoreductive surgery arm undergo 3 cycles of neoadjuvant chemotherapy after histologic confirmation of the disease, followed by interval cytoreductive surgery and subsequently, 3 cycles of platinum-based chemotherapy. The intention of surgery for both groups is complete tumor resection according to guideline recommendations.Major Inclusion/Exclusion CriteriaMajor inclusion criteria are suspected or histologically confirmed, newly diagnosed invasive epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinoma FIGO stage IIIB–IVB (IV only if resectable metastasis). Major exclusion criteria are non-epithelial ovarian malignancies and borderline tumors; prior chemotherapy for ovarian cancer; or abdominal/pelvic radiotherapy.Primary EndpointOverall survival.Sample Size772 patients.Estimated Dates for Completing Accrual and Presenting ResultsAccrual completion approximately mid-2019, results are expected after 5 years' follow-up in 2024.Trial RegistrationNCT02828618.

scholarly journals KLF7: a new candidate biomarker and therapeutic target for high-grade serous ovarian cancer

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Marta De Donato ◽  
Gabriele Babini ◽  
Simona Mozzetti ◽  
Marianna Buttarelli ◽  
Alessandra Ciucci ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Prognostic Marker ◽  
Late Stage ◽  
Therapeutic Target ◽  
Family Members ◽  
High Grade ◽  
Serous Ovarian Cancer

Abstract Background In spite of great progress in the surgical and clinical management, until now no significant improvement in overall survival of High-Grade Serous Ovarian Cancer (HGSOC) patients has been achieved. Important aspects for disease control remain unresolved, including unclear pathogenesis, high heterogeneity and relapse resistance after chemotherapy. Therefore, further research on molecular mechanisms involved in cancer progression are needed to find new targets for disease management. The Krüppel-like factors (KLFs) are a family of transcriptional regulators controlling several basic cellular processes, including proliferation, differentiation and migration. They have been shown to play a role in various cancer-relevant processes, in a context-dependent way. Methods To investigate a possible role of KLF family members as prognostic biomarkers, we carried out a bioinformatic meta-analysis of ovarian transcriptome datasets in different cohorts of late-stage HGSOC patients. In vitro cellular models of HGSOC were used for functional studies exploring the role of KLF7 in disease development and progression. Finally, molecular modelling and virtual screening were performed to identify putative KLF7 inhibitors. Results Bioinformatic analysis highlighted KLF7 as the most significant prognostic gene, among the 17 family members. Univariate and multivariate analyses identified KLF7 as an unfavourable prognostic marker for overall survival in late-stage TCGA-OV and GSE26712 HGSOC cohorts. Functional in vitro studies demonstrated that KLF7 can play a role as oncogene, driving tumour growth and dissemination. Mechanistic targets of KLF7 included genes involved in epithelial to mesenchymal transition, and in maintaining pluripotency and self-renewal characteristics of cancer stem cells. Finally, in silico analysis provided reliable information for drug-target interaction prediction. Conclusions Results from the present study provide the first evidence for an oncogenic role of KLF7 in HGSOC, suggesting it as a promising prognostic marker and therapeutic target.

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