Microscopic Peritoneal Residual Disease after Complete Macroscopic Cytoreductive Surgery for Advanced High Grade Serous Ovarian Cancer

Background: Epithelial ovarian cancers (EOC) are usually diagnosed at an advanced stage and managed by complete macroscopic cytoreductive surgery (CRS) and systemic chemotherapy. Peritoneal recurrence occurs in 60% of patients and may be due to microscopic peritoneal metastases (mPM) which are neither eradicated by surgery nor controlled by systemic chemotherapy. The aim of this study was to assess and quantify the prevalence of residual mPM after complete macroscopic CRS in patients with advanced high-grade serous ovarian cancer (HGSOC). Methods: A prospective study conducted between 1 June 2018 and 10 July 2019 in a single referent center accredited by the European Society of Gynecological Oncology for advanced EOC management. Consecutive patients presenting with advanced HGSOC and eligible for complete macroscopic CRS were included. Up to 13 peritoneal biopsies were taken from macroscopically healthy peritoneum at the end of CRS and examined for the presence of mPM. A mathematical model was designed to determine the probability of presenting at least one mPM after CRS. Results: 26 patients were included and 26.9% presented mPM. There were no differences in characteristics between patients with or without identified mPM. After mathematical analysis, the probability that mPM remained after complete macroscopic CRS in patients with EOC was 98.14%. Conclusion: Microscopic PM is systematically present after complete macroscopic CRS for EOC and could be a relevant therapeutic target. Adjuvant locoregional strategies to conventional surgery may improve survival by achieving microscopic CRS.

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

Molecular & Cellular Oncology ◽

10.1080/23723556.2020.1805094 ◽

2020 ◽

Vol 7 (6) ◽

pp. 1805094

Author(s):

Maria Bååth ◽

Sofia Westbom-Fremer ◽

Laura Martin de la Fuente ◽

Anna Ebbesson ◽

Juliette Davis ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Residual Disease ◽

High Grade ◽

Advanced Stage ◽

Serous Ovarian Cancer ◽

Debulking Surgery

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Paraneoplastic Cerebellar Ataxia Can Affect Prognosis in High-Grade Serous Ovarian Cancer: A Case Report

Case Reports in Oncology ◽

10.1159/000509029 ◽

2020 ◽

Vol 13 (2) ◽

pp. 1006-1012

Author(s):

Aikaterini Liapi ◽

Apostolos Sarivalasis

Keyword(s):

Ovarian Cancer ◽

Cerebellar Ataxia ◽

Systemic Treatment ◽

Residual Disease ◽

Oncological Outcome ◽

Favorable Effect ◽

High Grade ◽

Serous Ovarian Cancer ◽

Oncological Treatment ◽

Transient Improvement

The reported case is a 61-year-old woman, admitted for gradual onset of gait disturbances and dysphonia. The serum immunological panel revealed anti-Yo autoantibodies, suggestive of a paraneoplastic syndrome (PNS). A PET-CT revealed a suspicious left ovarian mass with retroperitoneal nodal involvement, and the histological assessment of surgical samples confirmed a FIGO IIIC high-grade serous ovarian cancer (HGSOC). Deemed inoperable at first, the patient was treated by carboplatin and paclitaxel chemotherapy, after which she refused surgical debulking. At the end of her systemic treatment, the patient only experienced a transient improvement of the cerebellar ataxia. Despite the suboptimal oncological treatment, the patient still presents stable disease and is free of progression 7 years from her diagnosis. This case study illustrates the favorable effect of PNS occurrence on oncological outcome in a patient with advanced HGSOC. The absence of recurrence despite the presence of residual disease after the systemic treatment is unusual and could be related to the PNS.

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The rate and role of diaphragmatic peritonectomy in optimal cytoreduction in patients with advanced stage ovarian cancer: a prospective study of 100 patients

Acta medica Lituanica ◽

10.6001/actamedica.v21i1.2882 ◽

2014 ◽

Vol 21 (1) ◽

pp. 1-7

Author(s):

Tomas Lūža ◽

Agnė Ožalinskaitė ◽

Vilius Rudaitis

Keyword(s):

Ovarian Cancer ◽

Confidence Interval ◽

Cytoreductive Surgery ◽

Residual Disease ◽

Advanced Ovarian Cancer ◽

Optimal Cytoreduction ◽

Entire Cohort ◽

Kaplan Meier ◽

Upper Abdominal ◽

A Prospective Study

Background. Diaphragmatic peritoneal metastasis by advanced epithelial ovarian cancer is a very common holdback precluding optimal cytoreduction. The aim of this study was to determine the rate of diaphragmatic peritonectomy during optimal cytoreductive surgery and its role in postoperative morbidity and survival in patients with advanced ovarian cancer. Materials and methods. 100 consecutive patients with advanced epithelial ovarian cancer underwent cytoreductive surgery and were followed up prospectively (January 2009 – March 2014). Characteristics of surgery, rate of diaphragmatic peritonectomy and post operative complications were assessed. The Kaplan-Meier method was used for survival analysis. Results. The median age of the entire cohort at the time of primary cytoreduction was 58.5 years (23–83). Optimal cytoreduction was achieved in 73 cases out of 100 patients. From 73 patients in 30 cases (41.1%) upper abdominal procedures, specifically diaphragmatic peritonectomy, was performed to achieve the main goal of cytoreduction – no visible or palbable disease at the end of cytoreduction. Non-optimal cytoreduction was achieved in 27 cases. According to the Clavien-Dindo complication grading system grade I and grade II complications occurred more often in patients that underwent diaphragmatic surgery. The median overall survival from the time of diagnosis to the last follow-up or death was 28 months (range 0–63 months). The factors associated with the longest survival after primary cytoreductive surgery were the disease free interval from the primary cytoreduction of more than 19 months (n = 51) versus less than 19 months (n = 49) (95% confidence interval, 51.7–59.5; P = 0.013) and no visible or palpable residual disease at the end of cytoreduction (n = 73) versus visible or palpable residual disease (n = 27) (95% confidence interval, 52.7–61.2; P = 0.03). Conclusions. Based on our prospective analysis of advanced ovarian cancer patients, diaphragmatic peritonectomy is feasible and safe, ensures better rates of optimal cytoreduction and should not be an obstacle towards better survival.

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Integrated Molecular Profiling Studies to Characterize the Cellular Origins of High-Grade Serous Ovarian Cancer

10.1101/330597 ◽

2018 ◽

Cited By ~ 9

Author(s):

Kate Lawrenson ◽

Marcos A.S. Fonseca ◽

Felipe Segato ◽

Janet M. Lee ◽

Rosario I. Corona ◽

...

Keyword(s):

Ovarian Cancer ◽

Epithelial Cells ◽

Tumor Development ◽

Molecular Profiling ◽

High Grade ◽

Serous Ovarian Cancer ◽

Cell Of Origin ◽

Ovarian Cancers ◽

Integrative Analyses ◽

Ovarian Surface Epithelial

AbstractHistorically, high-grade serous ovarian cancers (HGSOCs) were thought to arise from ovarian surface epithelial cells (OSECs) but recent data implicate fallopian tube secretory epithelial cells (FTSECs) as the major precursor. We performed transcriptomic and epigenomic profiling to characterize molecular similarities between OSECs, FTSECs and HGSOCs. Transcriptomic signatures of FTSECs were preserved in most HGSOCs reinforcing FTSECs as the predominant cell-of-origin; though an OSEC-like signature was associated with increased chemosensitivity (Padj= 0.03) and was enriched in proliferative-type tumors, suggesting a dualistic model for HGSOC origins. More super-enhancers (SEs) were shared between FTSECs and HGSOCs than between OSECS and HGSOCs (P< 2.2 × 10−16). SOX18, ELF3 and EHF transcription factors (TFs) coincided with HGSOC SEs and represent putative novel drivers of tumor development. Our integrative analyses support a predominantly fallopian origin for HGSOCs and indicate tumorigenesis may be driven by different TFs according to cell-of-origin.

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Odd-skipped related 2 (OSR2) is differentially expressed in high-grade serous ovarian cancers.

10.31219/osf.io/uwjt4 ◽

2020 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Ovarian Cancer ◽

Cell Fate ◽

Microarray Data ◽

Expression Profiles ◽

Gynecologic Cancer ◽

Differentially Expressed ◽

High Grade ◽

Serous Ovarian Cancer ◽

Primary Tumors ◽

Ovarian Cancers

Ovarian cancer is the most lethal gynecologic cancer (1). We sought to identify genes associated with high-grade serous ovarian cancer (HGSC) by comparing global gene expression profiles of normal ovary with that of primary tumors from women diagnosed with HGSC using published microarray data (2,3). We previously identified forkhead box L2 (4), (FOXL2) as among the genes whose expression was most different in HGSC ovarian tumors when compared to the ovary. Here, we find that potential FOXL2 transcriptional target (5,6) odd-skipped related gene OSR2 (7) is differentially expressed in high-grade serous ovarian cancer, and could be observed in independent tumor microarray data (2,3). These data reveal perturbed expression of a target gene of a key transcription factor and specifier of ovarian cell fate in high-grade serous ovarian cancers.

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