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

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.

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

Tumor Biology ◽  
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.

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

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

scholarly journals Validation analysis of the novel imaging-based prognostic radiomic signature in patients undergoing primary surgery for advanced high-grade serous ovarian cancer (HGSOC)

2021 ◽  
Author(s):  
Christina Fotopoulou ◽  
Andrea Rockall ◽  
Haonan Lu ◽  
Philippa Lee ◽  
Giacomo Avesani ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Residual Disease ◽  
Performance Status ◽  
Progression Free Survival ◽  
Treatment Quality ◽  
Disease Stage ◽  
Preoperative Imaging ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Primary Surgery

Abstract Background Predictive models based on radiomics features are novel, highly promising approaches for gynaecological oncology. Here, we wish to assess the prognostic value of the newly discovered Radiomic Prognostic Vector (RPV) in an independent cohort of high-grade serous ovarian cancer (HGSOC) patients, treated within a Centre of Excellence, thus avoiding any bias in treatment quality. Methods RPV was calculated using standardised algorithms following segmentation of routine preoperative imaging of patients (n = 323) who underwent upfront debulking surgery (01/2011-07/2018). RPV was correlated with operability, survival and adjusted for well-established prognostic factors (age, postoperative residual disease, stage), and compared to previous validation models. Results The distribution of low, medium and high RPV scores was 54.2% (n = 175), 33.4% (n = 108) and 12.4% (n = 40) across the cohort, respectively. High RPV scores independently associated with significantly worse progression-free survival (PFS) (HR = 1.69; 95% CI:1.06–2.71; P = 0.038), even after adjusting for stage, age, performance status and residual disease. Moreover, lower RPV was significantly associated with total macroscopic tumour clearance (OR = 2.02; 95% CI:1.56–2.62; P = 0.00647). Conclusions RPV was validated to independently identify those HGSOC patients who will not be operated tumour-free in an optimal setting, and those who will relapse early despite complete tumour clearance upfront. Further prospective, multicentre trials with a translational aspect are warranted for the incorporation of this radiomics approach into clinical routine.

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

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5555-5555 ◽  
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.

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

2020 ◽  
Vol 10 (1) ◽  
pp. 41
Author(s):  
Henri Azaïs ◽  
Anne-Sophie Vignion-Dewalle ◽  
Marine Carrier ◽  
Jeremy Augustin ◽  
Elisabeth Da Maïa ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cytoreductive Surgery ◽  
Systemic Chemotherapy ◽  
Residual Disease ◽  
Peritoneal Metastases ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Conventional Surgery ◽  
Ovarian Cancers ◽  
A Prospective Study

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.

scholarly journals Loss of LKB1-NUAK1 Signalling Enhances NF-κB Activity in a Spheroid Model of High-Grade Serous Ovarian Cancer

2021 ◽  
Author(s):  
Adrian Buensuceso ◽  
Jamie Lee Fritz ◽  
Olga Collins ◽  
Yudith Ramos Valdes ◽  
Gabriel E. DiMattia ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Survival ◽  
Residual Disease ◽  
Immunohistochemical Analysis ◽  
Signalling Pathways ◽  
Nuclear Staining ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Loss Of Function ◽  
Inflammatory Signalling

Abstract High-grade serous ovarian cancer (HGSOC) is an aggressive malignancy often diagnosed at an advanced stage. Although most HGSOC patients respond initially to debulking surgery combined with cytotoxic chemotherapy, many ultimately relapse with platinum-resistant disease. Thus, improving outcomes requires new ways of limiting metastasis and eradicating residual disease. We identified previously that Liver kinase B1 (LKB1) and its substrate NUAK1 are implicated in EOC spheroid cell viability and are required for efficient metastasis in orthotopic mouse models. Here, we sought to identify additional signalling pathways altered in EOC cells due to LKB1 or NUAK1 loss-of-function. Transcriptome analysis revealed that inflammatory signalling mediated by NF-κB transcription factors is hyperactive due to LKB1-NUAK1 loss in HGSOC cells and spheroids. Upregulated NF-κB signalling due to NUAK1 loss suppresses reactive oxygen species (ROS) production and sustains cell survival in spheroids. NF-κB signalling is also activated in HGSOC precursor fallopian tube secretory epithelial cell spheroids, and is further enhanced by NUAK1 loss. Finally, immunohistochemical analysis of OVCAR8 xenograft tumors lacking NUAK1 displayed increased RelB expression and nuclear staining. Our results support the idea that NUAK1 and NF-κB signalling pathways together regulate ROS and inflammatory signalling, supporting cell survival during each step of HGSOC pathogenesis. We propose that their combined inhibition may be efficacious as a novel therapeutic strategy for advanced HGSOC.

scholarly journals Molecular Biomarkers of Residual Disease after Surgical Debulking of High-Grade Serous Ovarian Cancer

2014 ◽  
Vol 20 (12) ◽  
pp. 3280-3288 ◽  
Author(s):  
Susan L. Tucker ◽  
Kshipra Gharpure ◽  
Shelley M. Herbrich ◽  
Anna K. Unruh ◽  
Alpa M. Nick ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Residual Disease ◽  
Molecular Biomarkers ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Surgical Debulking
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