Special Issue "Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment"

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: 31 December 2019.

Special Issue Editor

Dr. Edward J. Pavlik
E-Mail Website
Guest Editor
Director of Ovarian Screening Research in Gynecologic Oncology, University of Kentucky College of Medicine, Lexington, KY 40536-0298, USA
Interests: ovarian cancer; cancer screening; tumor imaging
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Ovarian cancer is deadly, claiming more women than all other gynecological malignancies combined. However, when detected at an early stage, ovarian cancer is highly curable. Consequently, screening efforts are likely to be the best way to detect early stage disease. The forthcoming Special Issue focuses on several key elements that are essential for an understanding of ovarian cancer, its characteristics, and risk factors that are relevant to screening for ovarian cancer. Invited topics that are:

  1. Risk factors for ovarian cancer.
  2. Markers and new genes associated with ovarian cancer.
  3. Ovarian cancer subtypes and their relatedness.
  4. Treatment related to high volume centers and National Comprehensive Cancer Network guidelines.
  5. Predictors of treatment responses.
  6. Treatment costs and effectiveness.
  7. Therapies and precision therapies for ovarian cancer.
  8. Vaccines and checkpoints in the immune therapy of ovarian cancer.
  9. Diagnostic tools: Strengths and limitations.
  10. International variations in ovarian cancer diagnosis and treatment.
  11. Determining ovarian cancer risk by tests for the general population.
  12. Mitigating risk of ovarian cancer surgically or medically.
  13. Screening trial design: Selection, make-up, execution, protocol driven aspects, age of participants, duration of screening, follow-up and events to be censored.
  14. Collateral affectors in screening: Perceptions of well-being and potential complications of treatment as confounders of compliance.
  15. Endpoints and efficacy: Early stage detection, disease specific survival, overall survival and avoidance of an ovarian cancer death as endpoints, with considerations of screen   performance and cost.
  16. Interpretation of ovarian screening trials. Comparisons between screening trials conducted in the United States, the United Kingdom and Japan are informative regarding the current status of ovarian screening.
Dr. Edward J. Pavlik
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Diagnostics is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • ovarian cancer
  • risk
  • treatment
  • detection
  • screening
  • trail design
  • treatment
  • collateral affectors
  • endpoints
  • costs
  • efficacy

Related Special Issue

Published Papers (9 papers)

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Research

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Open AccessArticle
Sarcopenic Factors May Have No Impact on Outcomes in Ovarian Cancer Patients
Diagnostics 2019, 9(4), 206; https://doi.org/10.3390/diagnostics9040206 - 28 Nov 2019
Abstract
Although the prognostic value of sarcopenic factors, such as loss of muscle mass and quality, have been widely reported in patients with cancer during the last decade, the value in those with ovarian cancer remains unclear. Therefore, this study evaluated the prognostic impact [...] Read more.
Although the prognostic value of sarcopenic factors, such as loss of muscle mass and quality, have been widely reported in patients with cancer during the last decade, the value in those with ovarian cancer remains unclear. Therefore, this study evaluated the prognostic impact of sarcopenic factors in patients with ovarian cancer. We retrospectively evaluated the data of 94 ovarian cancer patients who underwent surgery and chemotherapy at the Shimane University Hospital between March 2006 and 2013. Preoperative computed tomography scan at the level of the third lumbar vertebra was used to evaluate skeletal muscle volume and quality based on the skeletal muscle index (SMI) and intramuscular adipose tissue content (IMAC), respectively. The impact of preoperative SMI and IMAC on outcomes was subsequently investigated. Low SMI and high IMAC were not significantly associated with disease-free survival (p = 0.329 and p = 0.3370, respectively) or poor overall survival (p = 0.921 and p = 0.988, respectively). Neither preoperative low muscle volume nor low muscle quality was a poor prognostic factor in ovarian cancer. Full article
(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)
Open AccessCommunication
Overall Survival and Adjuvant Therapy in Women with Ovarian Carcinosarcoma: A Single-Institution Experience
Diagnostics 2019, 9(4), 200; https://doi.org/10.3390/diagnostics9040200 - 22 Nov 2019
Abstract
Background: Carcinosarcoma of the ovary (CSO) is a rare and aggressive variant of ovarian cancer. Due to the rare nature of the disease there is insufficient evidence to make recommendations regarding standard management and overall prognosis. Methods: An Institutional Review Board-approved study identified [...] Read more.
Background: Carcinosarcoma of the ovary (CSO) is a rare and aggressive variant of ovarian cancer. Due to the rare nature of the disease there is insufficient evidence to make recommendations regarding standard management and overall prognosis. Methods: An Institutional Review Board-approved study identified all our patients with CSO between January 2011 and May 2018. Demographic and outcome measures were abstracted from the medical records and tumor board files. Cox proportional hazard models, log rank tests, and comparisons of means were used to calculate significance (p < 0.05). Results: 27 women with CSO were identified. The median age at diagnosis was 65 years (range 48–91). Five women (18%) presented with early stage disease (Stage I or II) and 22 patients (82%) presented with late stage III or IV disease. Twenty patients (74%) received intravenous platinum-based combination chemotherapy. Seven patients did not receive chemotherapy during their treatment course. The median overall survival was 23 months (range 2–68 months). Overall survival was not significantly worsened by the stage of disease at diagnosis. There was no difference in survival based on the age at diagnosis, tobacco status or ethnicity (p > 0.05). Conclusion: This is one of the largest single institution experiences with CSO. The majority of our patients presented with advanced stage disease and received adjuvant platinum-based chemotherapy after cytoreductive surgery. The median overall survival of 23 months was not affected by the stage of the disease. The optimal management of this rare disease needs further study with collaborative, prospective multi-institutional trials. Full article
(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)
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Open AccessArticle
Ovarian Cancer Targeting Phage for In Vivo Near-Infrared Optical Imaging
Diagnostics 2019, 9(4), 183; https://doi.org/10.3390/diagnostics9040183 - 10 Nov 2019
Abstract
Ovarian cancer is often diagnosed at late stages due to current inadequate detection. Therefore, the development of new detection methods of ovarian cancer is needed. This may be achieved by phage nanoparticles that display targeting peptides for optical imaging. Here, two such phage [...] Read more.
Ovarian cancer is often diagnosed at late stages due to current inadequate detection. Therefore, the development of new detection methods of ovarian cancer is needed. This may be achieved by phage nanoparticles that display targeting peptides for optical imaging. Here, two such phage clones are reported. Ovarian cancer binding and specificity of phage clones (pJ18, pJ24) and peptides (J18, J24) were investigated using fluorescent microscopy and modified ELISA. Further, AF680-labeled phage particles were subjected to biodistribution and optical imaging studies in SKOV-3 xenografted mice. Fluorescent microscopy and ELISA of phage and peptides showed significantly increased binding to SKOV-3 cells compared to controls. Additionally, these studies revealed that J18 exhibits specificity for ovarian cancer SKOV-3 and OVCAR-3 cell lines. Further, peptides displayed increased SKOV-3 binding compared to N35 (non-relevant peptide) with EC50 values of 22.2 ± 10.6 μM and 29.0 ± 6.9 (mean ± SE), respectively. Biodistribution studies of AF680-labeled phage particles showed tumor uptake after 4 h and excretion through the reticuloendothelial system. Importantly, SKOV-3 tumors were easily localized by optical imaging after 2 h and 4 h and displayed good tumor-to-background contrast. The fluorescent tumor signal intensity was significantly higher for pJ18 compared to wild type (WT) after 2 h. Full article
(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)
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Open AccessArticle
BRCA1/2 Molecular Assay for Ovarian Cancer Patients: A Survey through Italian Departments of Oncology and Molecular and Genomic Diagnostic Laboratories
Diagnostics 2019, 9(4), 146; https://doi.org/10.3390/diagnostics9040146 - 09 Oct 2019
Abstract
In Italy, 5200 new ovarian cancers were diagnosed in 2018, highlighting an increasing need to test women for BRCA1/2. The number of labs offering this test is continuously increasing. The aim of this study was to show the results coming from the [...] Read more.
In Italy, 5200 new ovarian cancers were diagnosed in 2018, highlighting an increasing need to test women for BRCA1/2. The number of labs offering this test is continuously increasing. The aim of this study was to show the results coming from the intersociety survey coordinated by four different Clinical and Laboratory Italian Scientific Societies (AIOM, SIAPEC-IAP, SIBIOC, and SIGU). A multidisciplinary team belonging to the four scientific societies drew up two different questionnaires: One was targeted toward all Italian Departments of Medical Oncology, and the second toward laboratories of clinical molecular biology. This survey was implemented from September 2017 to March 2018. Seventy-seven out of 305 (25%) Departments of Medical Oncology filled our survey form. Indeed, 59 molecular laboratories were invited. A total of 41 laboratories (70%) filled in the questionnaire. From 2014 to 2017, 16 new molecular laboratories were activated. A total of 12,559 tests were performed in the year 2016, with a mean of 339 tests and a median of 254 tests per laboratory, showing a glimpse of an extreme low number of tests performed per year by some laboratories. In terms of the type and number of professionals involved in the pre- and post-test counseling, results among the onco-genetic team were heterogeneous. Our data show that the number of laboratories providing BRCA1/2 germline assays is significantly increased with further implementation of the somatic test coming soon. The harmonization of the complete laboratory diagnostic path should be encouraged, particularly in order to reduce the gap between laboratories with high and low throughput. Full article
(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)
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Open AccessArticle
Psychological Response to a False Positive Ovarian Cancer Screening Test Result: Distinct Distress Trajectories and Their Associated Characteristics
Diagnostics 2019, 9(4), 128; https://doi.org/10.3390/diagnostics9040128 - 25 Sep 2019
Abstract
Routine screening for ovarian cancer (OC) can yield an abnormal result later deemed benign. Such false positive (FP) results have been shown to trigger distress, which generally resolves over time. However, women might differ in the trajectory of the distress experience. Women participating [...] Read more.
Routine screening for ovarian cancer (OC) can yield an abnormal result later deemed benign. Such false positive (FP) results have been shown to trigger distress, which generally resolves over time. However, women might differ in the trajectory of the distress experience. Women participating in a routine OC screening program (n = 373) who received an abnormal screening result completed a baseline assessment prior to a follow-up screening test to clarify the nature of their abnormal result. All women were subsequently informed that no malignancy was present, and follow-up assessments were completed one and four months post-baseline. Demographic, clinical, dispositional (optimism, monitoring), and social environmental (social constraint, social support) variables were assessed at baseline. OC-specific distress was assessed at all three assessments. Trajectory analyses identified three distress trajectories differing in the baseline level of distress. A high decreasing trajectory, representing about 25% of women, was characterized by high levels of distress at baseline with distress declining over time, but still elevated at four-month follow-up. In contrast, a no distress trajectory group, representing about 30% of women, was characterized by essentially no distress at any time point. Principal risk factors for membership in the high decreasing trajectory group included a family history of OC, lower dispositional optimism, and greater social constraint. These risk factors could be used to target resources efficiently towards managing women at risk for potentially clinically-significant distress after receipt of an FP OC screening test. Full article
(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)
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Open AccessArticle
Mining Featured Biomarkers Linked with Epithelial Ovarian CancerBased on Bioinformatics
Diagnostics 2019, 9(2), 39; https://doi.org/10.3390/diagnostics9020039 - 09 Apr 2019
Abstract
Epithelial ovarian cancer (EOC) is the18th most common cancer worldwide and the 8th most common in women. The aim of this study was to diagnose the potential importance of, as well as novel genes linked with, EOC and to provide valid biological information [...] Read more.
Epithelial ovarian cancer (EOC) is the18th most common cancer worldwide and the 8th most common in women. The aim of this study was to diagnose the potential importance of, as well as novel genes linked with, EOC and to provide valid biological information for further research. The gene expression profiles of E-MTAB-3706 which contained four high-grade ovarian epithelial cancer samples, four normal fallopian tube samples and four normal ovarian epithelium samples were downloaded from the ArrayExpress database. Pathway enrichment and Gene Ontology (GO) enrichment analysis of differentially expressed genes (DEGs) were performed, and protein-protein interaction (PPI) network, microRNA-target gene regulatory network and TFs (transcription factors) -target gene regulatory network for up- and down-regulated were analyzed using Cytoscape. In total, 552 DEGs were found, including 276 up-regulated and 276 down-regulated DEGs. Pathway enrichment analysis demonstrated that most DEGs were significantly enriched in chemical carcinogenesis, urea cycle, cell adhesion molecules and creatine biosynthesis. GO enrichment analysis showed that most DEGs were significantly enriched in translation, nucleosome, extracellular matrix organization and extracellular matrix. From protein-protein interaction network (PPI) analysis, modules, microRNA-target gene regulatory network and TFs-target gene regulatory network for up- and down-regulated, and the top hub genes such as E2F4, SRPK2, A2M, CDH1, MAP1LC3A, UCHL1, HLA-C (major histocompatibility complex, class I, C), VAT1, ECM1 and SNRPN (small nuclear ribonucleoprotein polypeptide N) were associated in pathogenesis of EOC. The high expression levels of the hub genes such as CEBPD (CCAAT enhancer binding protein delta) and MID2 in stages 3 and 4 were validated in the TCGA (The Cancer Genome Atlas) database. CEBPD andMID2 were associated with the worst overall survival rates in EOC. In conclusion, the current study diagnosed DEGs between normal and EOC samples, which could improve our understanding of the molecular mechanisms in the progression of EOC. These new key biomarkers might be used as therapeutic targets for EOC. Full article
(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)
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Review

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Open AccessReview
Characteristics of in Vivo Model Systems for Ovarian Cancer Studies
Diagnostics 2019, 9(3), 120; https://doi.org/10.3390/diagnostics9030120 - 14 Sep 2019
Abstract
An understanding of the molecular pathogenesis and heterogeneity of ovarian cancer holds promise for the development of early detection strategies and novel, efficient therapies. In this review, we discuss the advantages and limitations of animal models available for basic and preclinical studies. The [...] Read more.
An understanding of the molecular pathogenesis and heterogeneity of ovarian cancer holds promise for the development of early detection strategies and novel, efficient therapies. In this review, we discuss the advantages and limitations of animal models available for basic and preclinical studies. The fruit fly model is suitable mainly for basic research on cellular migration, invasiveness, adhesion, and the epithelial-to-mesenchymal transition. Higher-animal models allow to recapitulate the architecture and microenvironment of the tumor. We discuss a syngeneic mice model and the patient derived xenograft model (PDX), both useful for preclinical studies. Conditional knock-in and knock-out methodology allows to manipulate selected genes at a given time and in a certain tissue. Such models have built our knowledge about tumor-initiating genetic events and cell-of-origin of ovarian cancers; it has been shown that high-grade serous ovarian cancer may be initiated in both the ovarian surface and tubal epithelium. It is postulated that clawed frog models could be developed, enabling studies on tumor immunity and anticancer immune response. In laying hen, ovarian cancer develops spontaneously, which provides the opportunity to study the genetic, biochemical, and environmental risk factors, as well as tumor initiation, progression, and histological origin; this model can also be used for drug testing. The chick embryo chorioallantoic membrane is another attractive model and allows the study of drug response. Full article
(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)
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Open AccessReview
Combined Strategies with Poly (ADP-Ribose) Polymerase (PARP) Inhibitors for the Treatment of Ovarian Cancer: A Literature Review
Diagnostics 2019, 9(3), 87; https://doi.org/10.3390/diagnostics9030087 - 01 Aug 2019
Cited by 4
Abstract
Poly (ADP-ribose) polymerase (PARP) inhibitors are the first clinically approved drugs designed to exploit synthetic lethality, and were first introduced as a cancer-targeting strategy in 2005. They have led to a major change in the treatment of advanced ovarian cancer, and altered the [...] Read more.
Poly (ADP-ribose) polymerase (PARP) inhibitors are the first clinically approved drugs designed to exploit synthetic lethality, and were first introduced as a cancer-targeting strategy in 2005. They have led to a major change in the treatment of advanced ovarian cancer, and altered the natural history of a disease with extreme genetic complexity and defective DNA repair via homologous recombination (HR) pathway. Furthermore, additional mechanisms apart from breast related cancer antigens 1 and 2 (BRCA1/2) mutations can also result in HR pathway alterations and consequently lead to a clinical benefit from PARP inhibitors. Novel combinations of PARP inhibitors with other anticancer therapies are challenging, and better understanding of PARP biology, DNA repair mechanisms, and PARP inhibitor mechanisms of action is crucial. It seems that PARP inhibitor and biologic agent combinations appear well tolerated and clinically effective in both BRCA-mutated and wild-type cancers. They target differing aberrant and exploitable pathways in ovarian cancer, and may induce greater DNA damage and HR deficiency. The input of immunotherapy in ovarian cancer is based on the observation that immunosuppressive microenvironments can affect tumour growth, metastasis, and even treatment resistance. Several biologic agents have been studied in combination with PARP inhibitors, including inhibitors of vascular endothelial growth factor (VEGF; bevacizumab, cediranib), and PD-1 or PD-L1 (durvalumab, pembrolizumab, nivolumab), anti-CTLA4 monoclonal antibodies (tremelimumab), mTOR-(vistusertib), AKT-(capivasertib), and PI3K inhibitors (buparlisib, alpelisib), as well as MEK 1/2, and WEE1 inhibitors (selumetinib and adavosertib, respectively). Olaparib and veliparib have also been combined with chemotherapy with the rationale of disrupting base excision repair via PARP inhibition. Olaparib has been investigated with carboplatin and paclitaxel, whereas veliparib has been tested additionally in combination with temozolomide vs. pegylated liposomal doxorubicin, as well as with oral cyclophosphamide, and topoisomerase inhibitors. However, overlapping myelosuppression observed with PARP inhibitor and chemotherapy combinations requires further investigation with dose escalation studies. In this review, we discuss multiple clinical trials that are underway examining the antitumor activity of such combination strategies. Full article
(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)
Open AccessReview
PARP Inhibitors in Ovarian Cancer: The Route to “Ithaca”
Diagnostics 2019, 9(2), 55; https://doi.org/10.3390/diagnostics9020055 - 18 May 2019
Cited by 5
Abstract
Poly (ADP-ribose) polymerase (PARP) inhibitors are a novel class of therapeutic agents that target tumors with deficiencies in the homologous recombination DNA repair pathway. Genomic instability characterizes high-grade serous ovarian cancer (HGSOC), with one half of all tumors displaying defects in the important [...] Read more.
Poly (ADP-ribose) polymerase (PARP) inhibitors are a novel class of therapeutic agents that target tumors with deficiencies in the homologous recombination DNA repair pathway. Genomic instability characterizes high-grade serous ovarian cancer (HGSOC), with one half of all tumors displaying defects in the important DNA repair pathway of homologous recombination. Early studies have shown significant efficacy for PARP inhibitors in patients with germline breast related cancer antigens 1 and 2 (BRCA1/2) mutations. It has also become evident that BRCA wild-type patients with other defects in the homologous recombination repair pathway benefit from this treatment. Companion homologous recombination deficiency (HRD) scores are being developed to guide the selection of patients that are most likely to benefit from PARP inhibition. The choice of which PARP inhibitor is mainly based upon the number of prior therapies and the presence of a BRCA mutation or HRD. The identification of patients most likely to benefit from PARP inhibitor therapy in view of HRD and other biomarker assessments is still challenging. The aim of this review is to describe the current evidence for PARP inhibitors in ovarian cancer, their mechanism of action, and the outstanding issues, including the rate of long-term toxicities and the evolution of resistance. Full article
(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)

Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Clinical utility of preoperative assessment of ovarian cancer cytoreduction
Authors: Ashley Moon, Pratistha Koirala, Vaagn Andikyan, and Linus Chuang

Title: International variations in ovarian cancer diagnosis and treatment
Authors: Brett M, Nelson G, Koebel M.

Title: Characteristics of in vivo model systems for ovarian cancer studies
Authors: Patrycja Tudrej, Katarzyna Aleksandra Kujawa, Alexander Jorge Cortez and Katarzyna Marta Lisowska
Abstract: Understanding of the molecular pathogenesis and heterogeneity of ovarian cancer hold promise for the development of early detection strategies and novel, efficient therapies. In this review, we discuss the advantages and limitations of animal models available for basic and preclinical studies. The fruit fly model is suitable mainly for basic research on cellular migration, invasiveness, adhesion, and the epithelial-to-mesenchymal transition. Higher-animal models allow to recapitulate architecture and microenvironment of the tumor. We discuss a syngeneic mice model and the patient derived xenograft model (PDX), both useful for preclinical studies. Conditional knock-in and knock-out methodology allows to manipulate selected genes at a given time and in a certain tissue. Such models have built our knowledge about tumor-initiating genetic events and cell-of-origin of ovarian cancers; it has been shown that high-grade serous ovarian cancer may be initiated both in the ovarian surface and tubal epithelium. In laying hen, ovarian cancer develops spontaneously, what gives the opportunity to study the genetic, biochemical and environmental risk factors, tumor initiation, progression and its histological origin; this model can also be used for drug testing. The chick embryo chorioallantoic membrane is another attractive model and allows to study drug response.

 

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