Ovarian Cancer Biomarkers in the COVID-19 Era.

Ovarian Cancer (OC) diagnosis is entrusted to CA125 and HE4. Since the latter has been found increased in COVID-19 patients, in this study, we aimed to evaluate the influence of SARS-CoV-2 infection on OC biomarkers. HE4 values above the cut-off were observed in 65% of OC patients and in 48% of SARS-CoV-2-positive patients (not oncologic patients), whereas CA125 values above the cut-off were observed in 71% of OC patients and in 11% of SARS-CoV-2 patients. Hence, by dividing the HE4 levels into quartiles, we can state that altered levels of HE4 in COVID-19 patients were mostly detectable in quartile I (151-300 pmol/L), while altered levels in OC patients were mostly clustered in quartile III (>600, pmol/L). In light of these observations, in order to better discriminate women with ovarian cancer versus those with COVID-19, we established a possible HE4 cut-off of 328 pmol/L by means of a ROC curve. These results demonstrate that the reliability of HE4 as a biomarker in ovarian cancer remains unchanged, despite COVID-19 interference; moreover, it is important for a proper diagnosis that whether the patient has a recent history of SARS-CoV-2 infection is determined.

A patient with advanced breast cancer and hyperthyroidism associated with struma ovarii.

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Application of machine learning techniques for predicting survival in ovarian cancer.

BACKGROUND: Ovarian cancer is the fifth leading cause of mortality among women in the United States. Ovarian cancer is also known as forgotten cancer or silent disease. The survival of ovarian cancer patients depends on several factors, including the treatment process and the prognosis. METHODS: The ovarian cancer patients' dataset is compiled from the Surveillance, Epidemiology, and End Results (SEER) database. With the help of a clinician, the dataset is curated, and the most relevant features are selected. Pearson's second coefficient of skewness test is used to evaluate the skewness of the dataset. Pearson correlation coefficient is also used to investigate the associations between features. Statistical test is utilized to evaluate the significance of the features. Six Machine Learning (ML) models, including K-Nearest Neighbors , Support Vector Machine (SVM), Decision Tree (DT), Random Forest (RF), Adaptive Boosting (AdaBoost), and Extreme Gradient Boosting (XGBoost), are implemented for survival prediction in both classification and regression approaches. An interpretable method, Shapley Additive Explanations (SHAP), is applied to clarify the decision-making process and determine the importance of each feature in prediction. Additionally, DTs of the RF model are displayed to show how the model predicts the survival intervals. RESULTS: Our results show that RF (Accuracy = 88.72%, AUC = 82.38%) and XGBoost (Root Mean Squad Error (RMSE)) = 20.61%, R2 = 0.4667) have the best performance for classification and regression approaches, respectively. Furthermore, using the SHAP method along with extracted DTs of the RF model, the most important features in the dataset are identified. Histologic type ICD-O-3, chemotherapy recode, year of diagnosis, age at diagnosis, tumor stage, and grade are the most important determinant factors in survival prediction. CONCLUSION: To the best of our knowledge, our study is the first study that develops various ML models to predict ovarian cancer patients' survival on the SEER database in both classification and regression approaches. These ML algorithms also achieve more accurate results and outperform statistical methods. Furthermore, our study is the first study to use the SHAP method to increase confidence and transparency of the proposed models' prediction for clinicians. Moreover, our developed models, as an automated auxiliary tool, can help clinicians to have a better understanding of the estimated survival as well as important features that affect survival.

Electronic patient-reported monitoring of symptoms during follow-up of ovarian cancer patients: a feasibility study.

BACKGROUND: Ovarian cancer patients require monitoring for relapse. Innovative follow-up methods are increasingly being explored. An electronic patient-reported outcome (ePRO) follow-up pathway was developed for women treated for ovarian cancer. This feasibility study explored patient acceptability and compliance. METHODS: A single-arm non-blinded prospective feasibility study was undertaken at two hospitals. Participants were women who had completed treatment for ovarian cancer whose clinician was happy for them to be monitored remotely. Automated 3-monthly reminders were sent to participants to complete an ePRO questionnaire and obtain blood tests. Participants were reviewed over the phone by their clinical nurse specialist instead of attending clinic-based follow-up. The primary outcome was compliance (expected ePRO completions/blood tests) across the 12-month study period. Secondary outcomes were recruitment, attrition, resource use, symptom severity/alerts and patient acceptability. RESULTS: Twenty-four women consented (50% consent rate), and 13 remained on study at 12 months. Seven women relapsed, 3 chose to withdraw, and 1 withdrew for other clinical reasons. ePRO compliance was high and consistent at 75-82%, although the two hospitals differed. Adherence to the clinical protocol was evident for blood tests and contacts with staff (fewer visits, more phonecalls compared to an earlier audit). End-of-study feedback indicated high patient satisfaction. CONCLUSIONS: Remote ePRO follow-up for ovarian cancer is feasible and acceptable to patients who are able and willing to participate. However, the low recruitment rate (ineligible + declined) indicate it is not suitable/acceptable to all patients immediately post-treatment. Further large-scale research and implementation work is required, especially in a post-COVID era. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02847715 (first registered 19/05/2016).

The utility of physical examination in ovarian cancer recurrence detection: a retrospective analysis informing virtual surveillance care.

OBJECTIVES: Given the recent rapid increase in telemedicine in the setting of the COVID-19 pandemic, we sought to investigate the utility of symptom review, CA125, and physical examination in the detection of ovarian cancer recurrence to determine the role of virtual surveillance care in the COVID-19 era. METHODS: This retrospective cohort study included patients diagnosed with ovarian cancer between 2013 and 2020 who achieved remission after primary treatment and then had recurrence while in a routine surveillance program. Modalities that detected recurrence including symptoms, CA125, physical examination, or 'other,' which was denoted if imaging was obtained for reasons other than suspected recurrence and recurrence was incidentally identified, were recorded. Descriptive statistics were performed to summarize the cohort. RESULTS: One hundred and nine patients met inclusion criteria. At time of recurrence, elevated CA125 was present in 97 (89.0%) patients, symptoms in 41 (37.6%), and abnormal physical exam findings in 27 (24.8%). Recurrence was incidentally found with imaging obtained for reasons other than suspicion of recurrence in six (5.5%) patients. Recurrence was suspected based on multiple modalities in 46 (42.2%) patients. Elevated CA125, symptoms, or both were present in 102 (93.6%) patients. Of patients with abnormal physical exam findings, 26 (96.3%) also had elevated CA125 or symptoms present. Recurrence was suspected based on physical exam findings alone in one (0.9%) patient. CONCLUSIONS: Over 90% of ovarian cancer recurrences were detected by rising CA125, symptoms, or both. Only one patient had recurrence detected by physical examination alone. Given that review of symptoms and CA125 can be conducted virtually, virtual visits may offer a reasonable alternative to in-person visits for ovarian cancer surveillance for patients who have pre-treatment elevated CA125.

The "collateral damage" of the war on COVID-19: impact of the pandemic on the care of epithelial ovarian cancer.

The covid-19 pandemic has impacted the management of non-covid-19 illnesses. Epithelial ovarian cancer (EOC) requires long-duration multidisciplinary treatment. Teleconsultation and shared care are suggested solutions to mitigate the consequences of the pandemic. However, these may be challenging to implement among patients who come from the lower economic strata. We report the disastrous impact of the pandemic on the care of EOC by comparing patients who were treated during the pandemic with those treated in the previous year. We collected the following data from newly diagnosed patients with EOC: time from diagnosis to treatment, time for completion of planned chemotherapy, and proportion of patients completing various components of therapy (surgery and chemotherapy). Patients treated between January 2019 and September 2019 (Group 1: Pre-covid) were compared with those treated between January 2020 and December 2020 (Group 2: During covid pandemic). A total of 82 patients were registered [Group 1: 43(51%) Group 2: 39(49)]. The median time from diagnosis to start of treatment was longer in group 2 when compared to group 1 [31(23-58) days versus 17(11-30) days (p = 0.03)]. The proportion of patients who had surgery in group 2 was lower in comparison to group 1 [33(77%) versus 21(54%) (p = 0.02)]. Proportion of patients who underwent neoadjuvant (NACT) and surgery were fewer in group 2 in comparison to group 1 [9(33%) versus 18(64%) p = 0.002]. Among patients planned for adjuvant chemotherapy, the median time from diagnosis to treatment was longer in group 2 [28(17-45) days, group 1 versus 49(26-78) days, group 2 (p = 0.04)]. The treatment of patients with EOC was adversely impacted due to the COVID-19 pandemic. There was a compromise in the proportion of patients completing planned therapy. Even among those who completed the treatment, there were considerable delays when compared with the pre-covid period. The impact of these compromises on the outcomes will be known with longer follow-up.

Trigeminal neuralgia leading to a diagnosis of ovarian cancer: a timely coincidence or a case of paraneoplastic syndrome?

A 51-year-old woman was referred to oral medicine with a 2-month history of progressive paraesthesia of the right lip, chin and oral mucosa. Examination revealed decreased sensation to the right dermatone of the inferior alveolar nerve and allodynia to light touch of the lower lip. An MRI of the head revealed bilateral cisternal trigeminal nerve pathological enhancement. While blood tests suggested a connective tissue disorder as the cause of the trigeminal neuralgia, a subsequent diagnosis of high-grade serous ovarian cancer gave a differential diagnosis of paraneoplastic syndrome.

Challenges and opportunities for ovarian cancer management in the epidemic of Covid-19: lessons learned from Wuhan, China.

China and the rest of the world are experiencing an outbreak of the 2019 novel coronavirus disease (COVID-19). Patients with cancer are more susceptible to viral infection and are more likely to develop severe complications, as compared to healthy individuals. The growing spread of COVID-19 presents challenges for the clinical care of patients with gynecological malignancies. Ovarian debulking surgery combined with the frequent need for chemotherapy is most likely why ovarian cancer was rated as the gynecologic cancer most affected by COVID-19. Therefore, ovarian cancer presents a particular challenging task. Concerning the ovarian cancer studies with confirmed COVID-19 reported from large-scale general hospitals in Wuhan, we hold that the treatment plan was adjusted appropriately and an individualized remedy was implemented. The recommendations discussed here were developed mainly based on the experience from Wuhan. We advise that the management strategy for ovarian cancer patients should be adjusted in the light of the local epidemic situation and formulated according to the pathological type, tumor stage and the current treatment phase. Online medical service is an effective and convenient communication platform during the pandemic.

BRCA testing delay during the COVID-19 pandemic: How to act?

Recently, our lab, part of a referral center in Italy, reported its experience regarding the execution of germline BRCA1/2 (gBRCA) testing during the first months of the coronavirus disease-2019 (COVID-19) pandemic, which highlights a substantial reduction (about 60%) compared with the first 2 months of the current year. This evidence appeared to be a lockdown effect due to extraordinary restriction measures to slow down the spread of SARS-CoV-2. In this study, we aimed to evaluate the overall effects of the ongoing pandemic on gBRCA testing in our institution and to understand how COVID-19 has influenced testing after the complete lockdown (March 8-May 5, 2020). Additionally, we compared this year's trend with trends of the last 3 years to better monitor gBRCA testing progress. This detailed analysis highlights two important findings: (1) gBRCA testing did not increase significantly after the lockdown period (May-October 2020) compared with the lockdown period (March-April 2020), emphasizing that even after the lockdown period testing remained low. (2) Comparing the total tests per year (January-October 2017, 2018, 2019, with 2020), the impact of COVID-19 on gBRCA testing is apparent, with similarities of trends registered in 2017. These evidences reveal a gBRCA testing delay for cancer patients and healthy patients at this moment, and the new era of gBRCA testing in the management of ovarian, breast, pancreas and prostate cancer patients has been seriously questioned due to the COVID-19 pandemic. As consequence, we underline that measures to guarantee oncogenetic testing (e.g., gBRCA testing) along with new diagnostic/clinic strategies are mandatory. For these reasons, several proposals are presented in this study.

Exploring the real-world effect of the SARS-CoV-2 pandemic on the molecular diagnostics for cancer patients and high-risk individuals.

Background: The SARS-CoV-2 pandemic introduced a global distraction effect in cancer patients' care. The aim of this study was to explore the effect of the pandemic on the largest molecular diagnostics center for cancer patients and high-risk individuals in Serbia.Research design and methods: EGFR, KRAS/NRAS, BRAF, and BRCA1/2 mutation testing were performed by qPCR and NGS. NGS was used for panel testing of hereditary breast/ovarian cancer and cancers associated with Lynch syndrome. The analytical output during the state of emergency (SoE) was compared to the period before and after the outbreak using one-way ANOVA. Statistical significance was set at p < 0.05.Results: A 38% reduction in the number of analysis was detected during the SoE. After the SoE, a 19% reduction was noted compared to SoE and 50% compared to the period before the SoE (p = 0.038). Three of the 48 scheduled appointments for pretest genetic counseling were carried out during the SoE, but the number of NGS tests increased by 50%.Conclusions: The SARS-CoV-2 pandemic had a profound negative effect on the diagnostic output of our centralized molecular diagnostics center. The only positive effect was shortening of waiting lists for hereditary cancer patients and high-risk individuals.

ESMO management and treatment adapted recommendations in the COVID-19 era: gynaecological malignancies.

The rapid spread of severe acute respiratory syndrome coronavirus 2 infection and its related disease (COVID-19) has required an immediate and coordinate healthcare response to face the worldwide emergency and define strategies to maintain the continuum of care for the non-COVID-19 diseases while protecting patients and healthcare providers. The dimension of the COVID-19 pandemic poses an unprecedented risk especially for the more vulnerable populations. To manage patients with cancer adequately, maintaining the highest quality of care, a definition of value-based priorities is necessary to define which interventions can be safely postponed without affecting patients' outcome. The European Society for Medical Oncology (ESMO) has endorsed a tiered approach across three different levels of priority (high, medium, low) incorporating information on the value-based prioritisation and clinical cogency of the interventions that can be applied for different disease sites. Patients with gynaecological cancer are at particular risk of COVID-19 complications because of their age and prevalence of comorbidities. The definition of priority level should be based on tumour stage and histology, cancer-related symptoms or complications, aim (curative vs palliative) and magnitude of benefit of the oncological intervention, patients' general condition and preferences. The decision-making process always needs to consider the disease-specific national and international guidelines and the local healthcare system and social resources, and a changing situation in relation to COVID-19 infection. These recommendations aim to provide guidance for the definition of deferrable and undeferrable interventions during the COVID-19 pandemic for ovarian, endometrial and cervical cancers within the context of the ESMO Clinical Practice Guidelines.

BRCA testing in a genomic diagnostics referral center during the COVID-19 pandemic.

The first person-to-person transmission of the 2019-novel coronavirus in Italy on 21 February 2020 led to an infection chain that represents one of the largest known COVID-19 outbreaks outside Asia. Hospitals have been forced to reorganized their units in response to prepare for an unforeseen healthcare emergency. In this context, our laboratory (Molecular and Genomic Diagnostics Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS) re-modulated its priorities by temporarily interrupting most of the molecular tests guaranteeing only those considered "urgent" and not postponable. In particular, this paper details changes regarding the execution of germline BRCA (gBRCA) testing in our laboratory. A substantial reduction in gBRCA testing (about 60%) compared to the first 2 months of the current year was registered, but the requests have not been reset. The requesting physicians were mainly gynaecologists and oncologists. These evidences further emphasize the new era of gBRCA testing in the management of cancer patients and confirms definitively the integration of gBRCA testing/Next Generation Sequencing (NGS) into clinical oncology. Finally, a re-organization of gBRCA testing in our Unit, mainly related to delayed and reduced arrival of tests was necessary, ensuring, however, a high-quality standard and reliability, mandatory for gBRCA testing in a clinical setting.