SOX2 is a promising predictor of relapse and death in advanced stage high-grade serous ovarian cancer patients with residual disease after debulking surgery

The aim of this study is to evaluate the effects on survival outcomes of the disease burden before interval debulking surgery (IDS), surgical complexity, and residual disease after IDS in advanced-stage ovarian cancer treated with neoadjuvant chemotherapy (NAC). We reviewed the data of 268 epithelial ovarian cancer patients who had received three or four cycles of NAC and undergone optimal resections through IDS. The Kaplan–Meier method and Cox regression analysis were used to assess the effects of disease burden (peritoneal cancer index (PCI)), degree of complexity of surgery (surgical complexity score/s (SCS)), and extent of residual disease. In no residual disease (R0) patients, those with intermediate/high SCS had shorter progression-free survival (PFS; p = 0.001) and overall survival (OS; p = 0.001) than patients with low SCS. An analysis of a subset of patients with R0 and low PCIs showed those with intermediate/high SCS had worse PFS and OS than patients with low SCS (p = 0.049) and OS (p = 0.037). In multivariate analysis, patients with R0 as a result of intermediate/high SCS fared worse than patients whose R0 was achieved by low SCS (PFS hazard ratio (HR) 1.80, 95% CI 1.05–3.10; OS HR 5.59, 95% CI 1.70–18.39). High PCIs at the time of IDS, high SCS, and residual disease signal poor prognoses for patients treated with NAC.

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A Comparison of Survival Outcomes in Advanced Serous Ovarian Cancer Patients Treated With Primary Debulking Surgery Versus Neoadjuvant Chemotherapy

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000946 ◽

2017 ◽

Vol 27 (4) ◽

pp. 668-674 ◽

Cited By ~ 18

Author(s):

Taymaa May ◽

Robyn Comeau ◽

Ping Sun ◽

Joanne Kotsopoulos ◽

Steven A. Narod ◽

...

Keyword(s):

Ovarian Cancer ◽

Overall Survival ◽

Neoadjuvant Chemotherapy ◽

Cancer Patients ◽

Residual Disease ◽

Survival Outcomes ◽

Serous Ovarian Cancer ◽

Debulking Surgery ◽

Cancer Specific Survival ◽

Primary Debulking Surgery

ObjectiveThe management of women with advanced-stage serous ovarian cancer includes a combination of surgery and chemotherapy. The choice of treatment with primary debulking surgery or neoadjuvant chemotherapy varies by institution. The objective of this study was to report 5-year survival outcomes for ovarian cancer patients treated at a single institution with primary debulking surgery or neoadjuvant chemotherapy.MethodsThis study included a retrospective chart review of 303 patients with stage IIIC or IV serous ovarian carcinoma diagnosed in Calgary, Canada. The patients were categorized into 1 of the 2 treatment arms: primary debulking surgery or neoadjuvant chemotherapy. The 5-year ovarian cancer–specific survival rates were estimated using Kaplan-Meier curves.ResultsAmong the 303 eligible patients, 142 patients (47%) underwent primary debulking surgery, and 161 patients (53%) were treated with neoadjuvant chemotherapy. Five-year survival was better for patients undergoing primary debulking surgery (39%) than for patients who received neoadjuvant chemotherapy (27%; P = 0.02). Women with no residual disease experienced better overall survival than those with any residual disease (47% vs. 26%, respectively; P = 0.0002). This difference was significant for those who had primary debulking surgery (P = 0.0004) but not for the patients who received neoadjuvant chemotherapy (P = 0.09). Women who received intraperitoneal chemotherapy had better overall survival as compared with patients who received intravenous chemotherapy (44% vs 30%, respectively; P = 0.002).ConclusionsOur findings suggest that among women with no residual disease, survival is better among those who undergo primary debulking surgery than treatment with neoadjuvant chemotherapy. The latter should be reserved for women who are deemed not to be candidates for primary debulking surgery.

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Management of the Elderly Patients with High-Grade Serous Ovarian Cancer in the REAL-WORLD Setting

Current Oncology ◽

10.3390/curroncol28020110 ◽

2021 ◽

Vol 28 (2) ◽

pp. 1143-1152

Author(s):

Michalis Liontos ◽

Alkistis Papatheodoridi ◽

Angeliki Andrikopoulou ◽

Nikolaos Thomakos ◽

Dimitrios Haidopoulos ◽

...

Keyword(s):

Ovarian Cancer ◽

Overall Survival ◽

Elderly Patients ◽

Cancer Patients ◽

Progression Free Survival ◽

Optimal Treatment ◽

High Grade ◽

Serous Ovarian Cancer ◽

Debulking Surgery ◽

Free Survival

Treatment of elderly patients with neoplasia is challenging. Age is a known prognostic factor in ovarian cancer but the optimal treatment of elderly patients has not been determined. We undertook a retrospective analysis to determine clinical practice in advanced-stage ovarian cancer patients older than 70 years of age. Methods: Medical records of women with high-grade serous ovarian cancer, stage III and IV were retrospectively analyzed. Results: A total of 735 patients were identified with a median age of 61.5 years. 22.4% among them were older than 70 years of age at diagnosis. First-line Progression-Free Survival (PFS) and Overall Survival (OS) were significantly worse in elderly patients in comparison to the younger ones [mPFS 11.3 months vs. 14.8 months, (p < 0.001) and mOS 30.2 months vs. 45.6 months (p < 0.001)]. However, elderly patients were characterized by worse ECOG-Performance Status and they were more frequently treated with Neoadjuvant Chemotherapy followed by Interval Debulking Surgery, while often they were more frequently denied debulking surgery compared to patients under 70 years of age. Moreover, elderly patients received more frequently monotherapy with platinum as frontline treatment. In contrast, there was no significant difference in the outcome of the debulking surgery in comparison to the younger patients or the frequency that gBRCA test was performed. Age over 70 years did not retain its significance for either Progression-Free Survival or Overall Survival when adjusted for all other reported prognostic factors. Conclusions: Elderly ovarian cancer patients have a worse prognosis. Comprehensive geriatric assessment should be performed for the optimal treatment of these patients.

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Cell-free tumor DNA in peri-operative blood samples from advanced high-grade serous ovarian cancer patients with and without complete resection.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.5555 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 5555-5555 ◽

Cited By ~ 1

Author(s):

Florian Heitz ◽

Sotirios Lakis ◽

Philipp Harter ◽

Jalid Sehouli ◽

Jatin Talwar ◽

...

Keyword(s):

Ovarian Cancer ◽

Residual Disease ◽

Complete Resection ◽

High Grade ◽

Serous Ovarian Cancer ◽

Debulking Surgery ◽

Tp53 Mutations ◽

Post Surgery ◽

Tumor Dna

5555 Background: Surgical outcome is an important prognostic factor in advanced high-grade serous ovarian cancer (HGOC). Intra-operative determination of residual disease may be prone to subjective bias. Methods: We prospectively collected and analyzed tumor tissue and plasma from 21 pts with FIGO IIIC-IV HGOC. All tumor specimen showed loss of TP53 in immunohistochemistry. Tumor DNA from tissue and peri-operative cell-free DNA at baseline (BL) and at d(ays) 1, d4 and d10 were subjected to comprehensive hybrid-capture based next-generation sequencing (NEO New Oncology GmbH, Cologne, Germany). Results: The initial cohort comprised 10 pts without (TR>0) and 11 pts with complete resection TR0, with a total of 43 somatic genomic alterations. TP53 was mutated in 20/21 (95.2%) of tissue samples and in 15/21 (71.4%) corresponding plasma samples at BL. Therefore, TP53 mutations were used as a molecular marker of circulating tumor DNA levels post-surgery. In the remaining 5 BL cases the TP53 mutations were either not present in plasma (N= 3) or rested below the detection limit (N= 2). In d1, d4 and d10 post-surgical samples, the sample specific TP53 mutations were detected in 12 out of 15, 10 out of 14 and in 7 out of 13 cases, respectively. TP53variant allele frequency (VAF) did not differ among TR0 and TR>0 at BL (mean= 1.91 versus 1.73, Mann-Whitney test p = 0.86) whereas it was significantly lower for TR0 at d1 (mean= 0.06 versus 2,06; p value= 0.002), d4 (mean= 0.07 versus 1.8; p= 0.04) and d10 (mean VAF= 0 versus 1.04; p= 0.008). Five out of 9 TR>0 cases showed at least one increase in VAF between d0 and any additional time-point. In 8 out of 9 mutations remained detectable at d10 (VAF: 0.076 – 3.26). By contrast, TR0 cases showed consistent reduction in VAF throughout the follow-up period which maximized at d10. Conclusions: Liquid biopsycan efficiently detect somatic mutations in the cfDNA of pts with HGOC following debulking surgery. Variation of the TP53 VAF in sequential post-surgical samples appears to be restricted to TR>0 cases, whereas in TR0 pts VAF progressively decreases. Liquid biopsy may hold promise as a tool for the objective determination of residual disease after debulking surgery.

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SHOULD AROMATASE INHIBITORS BE USED AS MAINTENANCE TREATMENT IN HIGH-GRADE SEROUS OVARIAN CANCER PATIENTS?

10.26226/morressier.599bdc7ad462b80296ca1822 ◽

2017 ◽

Author(s):

Alexandra Maria Knipprath-Mészáros

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Aromatase Inhibitors ◽

Maintenance Treatment ◽

High Grade ◽

Serous Ovarian Cancer

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Molecular predictors of the outcome of paclitaxel plus carboplatin neoadjuvant therapy in high-grade serous ovarian cancer patients

Cancer Chemotherapy and Pharmacology ◽

10.1007/s00280-021-04301-6 ◽

2021 ◽

Author(s):

Anna P. Sokolenko ◽

Tatiana V. Gorodnova ◽

Ilya V. Bizin ◽

Ekaterina Sh. Kuligina ◽

Khristina B. Kotiv ◽

...

Keyword(s):

Ovarian Cancer ◽

Neoadjuvant Therapy ◽

Cancer Patients ◽

High Grade ◽

Serous Ovarian Cancer

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

International Journal of Cancer ◽

10.1002/ijc.32729 ◽

2019 ◽

Vol 146 (7) ◽

pp. 1851-1861 ◽

Cited By ~ 2

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

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Role of discoidin domain receptor 2 (DDR2) and microRNA-182 in survival of women with high-grade serous ovarian cancer

Tumor Biology ◽

10.1177/1010428318823988 ◽

2019 ◽

Vol 41 (1) ◽

pp. 101042831882398

Author(s):

Susana Ramalho ◽

Liliana AL De Angelo Andrade ◽

Cássio Cardoso Filho ◽

Rodrigo de Andrade Natal ◽

Marina Pavanello ◽

...

Keyword(s):

Ovarian Cancer ◽

Residual Disease ◽

Figo Stage ◽

Stage I ◽

High Grade ◽

Serous Ovarian Cancer ◽

Discoidin Domain Receptor ◽

Post Surgery ◽

Platinum Based Chemotherapy ◽

Discoidin Domain Receptor 2

The objective of this study is to evaluate the relationship between discoidin domain receptor 2 (DDR2) and miR-182 expression with response to platinum-based chemotherapy and survival in women with high-grade serous ovarian cancer (HGSOC). We evaluated 78 women with HGSOC stages I-IV, diagnosed between 1996 and 2013, and followed up until 2016. DDR2 expression was assessed using immunohistochemistry on tissue microarray slides. The microRNAs were evaluated by qRT-PCR. DDR2 expression was high in 11 (14.1%) women. PFS was significantly lower in women with FIGO stage I/II – versus III/IV, post-surgery residual disease and high expression of DDR2. Women with postsurgery residual disease, FIGO stage I/II – versus III/IV and DDR2 expression had worse OS, but only post-surgery residual disease remained an independent prognostic factor for worse OS in multivariable analysis. miR-182 expression levels were significantly lower in patients harboring tumors with higher expression of DDR2 (p < 0.001). In this relatively large cohort of women with HSGOC, higher DDR2 expression was associated with lower miR-182 levels and worse PFS, suggesting that these molecules may be associated with mechanisms of HGSOC progression.

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