A Tale of Two Counties With the Same Telehealth Story: Experience with Cancer Genetics Testing During COVID-19 at a Community Hospital

Introduction: With the onset of the COVID-19 pandemic in 2020, the utilization of telemedicine now offered an alternative diagnostic and treatment resource to providers in many areas of medicine including oncology and cancer genetics. This care option paired with genetic testing labs' ability to send saliva-based DNA collection kits to patients, enabled our community hospital in Detroit to offer diagnostic testing without the patient coming to a healthcare setting for a host of reasons. Social determinants of health have been found to influence success with telehealth, and this study sought to analyze how successful telehealth cancer genetics care was throughout the Detroit Metro area. Methods: Patient demographics for in person visits six months before COVID were analyzed, and then compared with demographics of patients during the 2020-2021 pandemic period where visits were telehealth. Results: Pre-pandemic there were , 192 unique patients seen in person with the top three cities patients were from were Detroit (12.1%), Clinton Township (8.3%), and Saint Clair Shores (10.4%). During the pandemic, with telehealth as the major modality, the top three cities were Macomb (7.2%), Detroit (7%), and Clinton Township (7%). Detroit is in Wayne County, while St.Clair Shores and Clinton Township are in Macomb County. Per the US Census Bureau Macomb county has a median income of $64,641 and Wayne county has a median income of $49,359, and poverty level in Macomb county is 9.2% versus in Wayne the level is 20%. Conclusions: This paper outlines the challenges of initiating a telemedicine program in an urban community area and highlights the benefits of a concierge service in serving cancer patients who may have economic and historically poor perceived technologic abilities.

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.

Best original research presented at the 23rd European Congress on Gynaecological Oncology-Best of ESGO 2022.

Best of ESGO 2022 includes a selection of best original research presented during the 23rd European Congress on Gynaecological Oncology between October 27 and 30, 2022 in Berlin. Out of 1107 submitted abstracts, authors of studies which obtained the highest scores in a blinded review process were invited to present their results during four oral sessions, young investigators session, and oral poster sessions. By means of this publication, we aim to provide readers with an overview of the best quality research presented at the European Society of Gynaecological Oncology (ESGO) 2022.

Rising CA-125 (Cancer Antigen 125) Levels: Cancer Recurrence or a Vaccine Reaction?

Cancer antigen 125 (CA-125) is a transmembrane glycoprotein, and it is known to be an essential biomarker in detecting treatment response and recurrence of ovarian cancer. It may also be used in monitoring colorectal cancer. It tends to rise in states of inflammation. Recent studies have demonstrated a temporary rise in CA-125 levels and other cancer biomarkers in patients suffering from coronavirus disease 2019 (COVID-19) infection. However, in the following case report, we hope to shed light on a possible association between CA-125 levels and the COVID-19 mRNA vaccine. We present the case of a 79-year-old woman with moderately differentiated adenocarcinoma of the right adnexa, who had a transient increase in CA-125 levels after a period, during which she underwent treatment for COVID-19 infection and received the first dose of COVID-19 mRNA (Pfizer-BioNTech) vaccine with no evidence of disease progression on imaging.

Lesion-specific 3D-printed moulds for image-guided tissue multi-sampling of ovarian tumours: A prospective pilot study.

Background: High-Grade Serous Ovarian Carcinoma (HGSOC) is the most prevalent and lethal subtype of ovarian cancer, but has a paucity of clinically-actionable biomarkers due to high degrees of multi-level heterogeneity. Radiogenomics markers have the potential to improve prediction of patient outcome and treatment response, but require accurate multimodal spatial registration between radiological imaging and histopathological tissue samples. Previously published co-registration work has not taken into account the anatomical, biological and clinical diversity of ovarian tumours. Methods: In this work, we developed a research pathway and an automated computational pipeline to produce lesion-specific three-dimensional (3D) printed moulds based on preoperative cross-sectional CT or MRI of pelvic lesions. Moulds were designed to allow tumour slicing in the anatomical axial plane to facilitate detailed spatial correlation of imaging and tissue-derived data. Code and design adaptations were made following each pilot case through an iterative refinement process. Results: Five patients with confirmed or suspected HGSOC who underwent debulking surgery between April and December 2021 were included in this prospective study. Tumour moulds were designed and 3D-printed for seven pelvic lesions, covering a range of tumour volumes (7 to 133 cm3) and compositions (cystic and solid proportions). The pilot cases informed innovations to improve specimen and subsequent slice orientation, through the use of 3D-printed tumour replicas and incorporation of a slice orientation slit in the mould design, respectively. The overall research pathway was compatible with implementation within the clinically determined timeframe and treatment pathway for each case, involving multidisciplinary clinical professionals from Radiology, Surgery, Oncology and Histopathology Departments. Conclusions: We developed and refined a computational pipeline that can model lesion-specific 3D-printed moulds from preoperative imaging for a variety of pelvic tumours. This framework can be used to guide comprehensive multi-sampling of tumour resection specimens.

Rapid microRNA detection method based on DNA strand displacement for ovarian cancer cells.

The current cancer detection methods are heavily dependent on the component analysis of corresponding cancer antigens. There is a lack of effective and simple clinical methods of ovarian cancer screening, which hinders the early identification for ovarian cancer and its treatment. To develop a simple and rapid method for quantitative analysis of ovarian cancer, we developed a DNA strand displacement-based method and finished the rapid detection of miR-21 in ovarian cancer cells within 5 min by a one-step isothermal reaction. The fluorescence intensity trajectory had a good linear relationship with miR-21 concentrations in the range of 100 fM-100 nM, with a lower limit of 6.05 pM. This detection method is simple, faster, and accurate. Besides, it can be applied to detect the miRNA biomarkers of other cancers by changing the preset sequences of toehold.

Pancreatic Choristoma in Omentum in Advanced CA Ovary: A Clinical Puzzle.

Ectopic pancreatic tissue is called pancreatic choristoma or heterotopia of pancreas. It is a rare entity. We present a case of advanced Ca ovary with omental pancreatic choristoma.

In silico designed mRNA vaccines targeting CA-125 neoantigen in breast and ovarian cancer.

Somatic mutation-derived neoantigens are associated with patient survival in breast and ovarian cancer. These neoantigens are targets for cancer, as shown by the implementation of neoepitope peptides as cancer vaccines. The success of cost-effective multi-epitope mRNA vaccines against SARS-Cov-2 in the pandemic established a model for reverse vaccinology. In this study, we aimed to develop an in silico pipeline designing an mRNA vaccine of the CA-125 neoantigen against breast and ovarian cancer, respectively. Using immuno-bioinformatics tools, we predicted cytotoxic CD8+ T cell epitopes based on somatic mutation-driven neoantigens of CA-125 in breast or ovarian cancer, constructed a self-adjuvant mRNA vaccine with CD40L and MHC-I -targeting domain to enhance cross-presentation of neoepitopes by dendritic cells. With an in silico ImmSim algorithm, we estimated the immune responses post-immunization, showing IFN-γ and CD8+ T cell response. The strategy described in this study may be scaled up and implemented to design precision multi-epitope mRNA vaccines by targeting multiple neoantigens.

Longitudinal Modulation of Loco-Regional Immunity in Ovarian Cancer Patients Receiving Intraperitoneal Chemotherapy.

The immune tumor microenvironment (TME) of epithelial ovarian cancer (EOC) carries both effector and suppressive functions. To define immune correlates of chemotherapy-induced tumor involution, we performed longitudinal evaluation of biomarker expression on serial biological specimens collected during intraperitoneal (IP) platinum-based chemotherapy. Serial biological samples were collected at several time points during IP chemotherapy. RNA from IP fluid cells and tumor tissue was analyzed via NanoString. Meso Scale Discovery (MSD) multiplex assay and ELISA for MUC1 antibodies were performed on plasma and IP fluid. Differentially expressed genes in IP fluid demonstrate an upregulation of B cell function and activation of Th2 immune response along with dampening of Th1 immunity during chemotherapy. MSD analysis of IP fluid and gene expression analysis of tumor tissue revealed activation of Th2 immunity and the complement system. Anti-MUC1 antibodies were detected in IP fluid samples. IP fluid analysis in a secondary cohort also identified chemotherapy-induced B cell function genes. This study shows that serial IP fluid sampling is an effective method to capture changes in the immune TME during chemotherapy and reveals treatment induced changes in B cell function and Th2 immunity.

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.

Why women do not have surgical treatment for advanced stage ovarian cancer: cohort study from east London cancer centre

ObjectivesThe Ovarian Cancer Audit Feasibility Pilot found that nearly 40% of patients diagnosed with ovarian cancer in the United Kingdom did not have surgical treatment with a large degree of geographical variation, highlighting the need to look at these discrepancies within each cancer centre. This audit set out to identify women within Barts Health NHS Foundation Trust with stage 3 or 4 ovarian cancer who did not have surgical management, determine their demographics and the reasons for not having surgery.MethodsData was collected retrospectively from MDT proformas over a 5-year period (2016–2021) and analysed using Microsoft Excel and SPSS software.Results92 women who were diagnosed with stage 3/4 ovarian cancer did not have surgical treatment. 59.7% (55/92) had chemotherapy. The mean age was 76.2 years (55–100, n=92) and the mean Charlson Comorbidity Index was 9.9 (6–14, n=92). The majority of women had stage 4 disease (58.7%, 55/92) and high-grade serous pathology (83.7%, 77/92). The most common reason for not having surgery was unresectable disease (63%, 58/92) followed by ‘poor performance status’ (40.2%, 37/92) as detailed in MDT recommendations. Of those who did not have chemotherapy, the most common reason was poor performance status (59.3%, 16/27). 6.5% (6/92) had their treatment impacted by the COVID-19 pandemic.ConclusionsAlthough this reflects the correlation between poor performance status and likelihood of treatment, unresectability of disease may reflect geographical variation in timely diagnosis. Further work is needed to determine the impact of these factors on local 5-year survival rates.

Impact of the COVID-19 pandemic on the care of patients with ovarian cancer

ObjectivesWe studied the impact of the COVID-19 pandemic on the care of patients with epithelial ovarian cancer (EOC) in the Netherlands.MethodsData of the Netherlands Cancer Registry was used to perform a retrospective cohort study on women of 18+ years diagnosed with EOC in the period 2017–2020 who were treated in the Netherlands. Waiting times and treatment characteristics were compared for the period before the COVID-19 pandemic (2017–2019) with the period during the COVID-19 pandemic (2020).ResultsDuring the pandemic, more women were diagnosed with FIGO stage IV (28.7%) compared to the period before the pandemic (23.7%, p=0.034). Mean time between first hospital consultation and first treatment did not differ significantly between both periods;for stage I-IIA it was 34 days during the pandemic and 36 days before the pandemic, for stage IIB-IIIC it was 35 vs 37 days and for stage IV 37 vs 35 days, respectively. Time between cytoreductive surgery (CRS) and adjuvant chemotherapy was significantly shorter during the pandemic for stage IIB-IIIC (24 days vs 30 days before the pandemic, p<0.001).ConclusionsIn the Netherlands during the COVID-19 pandemic (2020), an increase in FIGO stage IV EOC was observed compared to the period before the pandemic (2017–2019). This might be due to patient-delay and/or delay in referral or to the introduction of HIPEC for stage IIIC. A decrease in the interval between CRS and adjuvant chemotherapy was observed. A decrease in elective procedures and treatments may be an important cause of the reduction in waiting time for chemotherapy.

Caregiver experience during the COVID-19 pandemic in the Netherlands

ObjectivesWe evaluated the experience of caregivers on the healthcare of gynaecological cancer patients during the first wave (March-June) of the COVID-19 pandemic in 2020 in the Netherlands.MethodsAn online questionnaire was sent to gynaecologists, gynaecological oncologists, medical- and radiation oncologists throughout the Netherlands. The self-developed questionnaire consisted of questions about gynaecological cancer in general and endometrial, ovarian, cervical and vulvar cancer specifically.ResultsSixty-four (63%) physicians participated: 33 gynaecologists (52%), 13 gynaecological oncologists (20%), 7 medical oncologists (11%) and 11 radiation oncologists (17%). Fifty-nine percent of the respondents (35/59) reported a change in the way of contact with patients during the ‘diagnostic phase’ : patients were more often contacted by telephone during the pandemic (80%, 28/35, e.g. first consult or discussing results). For ovarian cancer 17% (4/23) reported a change in type of surgery and 22% (11/49) in (neo)adjuvant treatment (e.g. delay, more cycles, referral). For endometrial 21% (12/56), cervical 26% (7/27) and vulvar cancer 32% (6/19) longer waiting times for surgery were reported (3% <1 week, 58% 1–3 weeks, 39% >3 weeks). Eighty-nine percent of the respondents (46/52) reported a change in follow-up: 91% (42/46) reported follow-up consultation by telephone or video, 63% (32/51) reported postponed follow-up appointments.ConclusionsThe questionnaire showed that during the first wave of the COVID-19 pandemic, most caregivers experienced a different way of contact during the diagnostic and follow-up phase. Consultation by telephone could a good alternative in the follow-up phase, e.g. for low risk patients without symptoms, even after the pandemic.

Preoperative CT score for predicting complete gross resection at primary and interval debulking surgery of advanced ovarian cancer during the COVID19 pandemic

15/#413 Table 1Preoperative CT score and residual disease at PDS and IDSConclusionsWhen exclusively assessing preoperative imaging, women with initial CT-score >7 should receive NACT or laparoscopic resectability-assessment. Women with CT-score ≤4 after NACT can be offered IDS.

Transition of ovarian granulosa cell tumor from a solid mass to a cystic mass in two months on MR imaging in an adult woman: A case report

Ovarian granulosa cell tumor (OGCT) is a relatively rare ovarian tumor originating from ovarian sex cord-stromal cells. It is generally believed that the tumor is mainly a solid mass in the early stage, and with the volume increasing, the tumor would undergo multiple cystic changes. But few such cases have been reported. This article reports a case of transition of ovarian granulosa cell tumor from a solid mass to a cystic mass in 2 months on MR imaging in an adult woman. In this case, a 55-year-old postmenopausal woman underwent MR imaging for irregular vaginal bleeding in March 2022, during which a 6-cm cystic-solid mass was detected in the right ovary with iso-hypo intensity on T1WI, iso-hyper intensity on T2WI, and hyper intensity on DWI. After injection of the contrast medium, the mass displayed progressive and obvious enhancement, which was diagnosed as OGCT. Due to the COVID-19 pandemic, the patient was unable to receive surgery in time. Two months later, the patient returned to the hospital and underwent MRI again, when a 20-cm cyst mass was detected in the pelvis, which contained little solid component at the edge. The patient was admitted and underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. The postoperative pathology confirmed the diagnosis of adult type stage IC1 OGCT. This finding may be precious in that it could help understand the initiation and progression of OGCT.

The Cancer and Research Center of Marche Region (Corm): A New Instrument to Offer Opportunities for Diagnosis and Treatment to Cancer Patients

Following the new health needs emerged during the covid pandemic, in June 2021, the Cancer and Research Center of Marches Region, CORM (www.corm-marche.it) was instituted at the Department of Oncology of the Academic Hospital Ospedali Riuniti, Ancona (IT) with the Italian Ministry of Health patronage. The CORM includes:-The digital platform for telemedicine to offer the ability to admit de novo diagnosis of solid tumors, as well as provide second opinions and to promote continutiy of care between hospital and territory-The Molecular Tumor Board, a multidisciplinary board including clinicians, pathologists and biologists to recommend personalized therapy in the "Precision Medicine" era. High throughput genomic profiling tests may be indicated by MTB team: foundation one cdx/liquid biopsy/ heme, 16 genes DNA panel and other panels that are relevant in different types of tumors, NTRK evaluation and PDL1 test. The molecular profiles are useful to indicate new treatment strategies, but also to understand the mechanism of resistance otherwise not justificable with a standard approach.-The Clinical Trial Unit which performs about 40 interventional trials/year and includes a phase 1 unit, certified by AIFA. Every year, 100 patients are enrolled in clinical trials, about 10/year in phase 1 trials.-The Regional Center of High Specialization in Oncological Genetics. In December 2004, the Regional Center of High Specialization in Oncological Genetics was instituted and we developed an increasing expertise in genetic counseling and tests for hereditary syndrome (hereditary breast and ovarian cancer syndrome and Lynch syndrome). Last year, we conducted 3166 genetic counseling, consisting of collecting genetic information and drawing pedigree, making or validating diagnosis, communicating clinical and genetic information and supporting the family to reach a decision and take appropriate actions. From January 2022, we activate the telemedicine platform also for genetic counseling to select patients who deserve genetic testing and come from distant territories. We aim to create a technological network between the oncology departments and general practitioners, patient associations and all the other specialists to guarantee the continuity of care and to overcome the disparities in oncological health services, simplifying cancer clinical management.

Mental distress, quality of life and physical symptoms in Chinese women with ovarian cancer receiving olaparib treatment during the COVID-19 pandemic.

Objectives: Women with ovarian cancer (OC) have experienced unprecedented challenges since the novel coronavirus disease-2019 (COVID-19) outbreak in China. We aim to evaluate the experience of psychological status, physical symptoms and quality of life (QoL) and investigate the impact of COVID-19 pandemic on OC patients receiving olaparib. Methods: The survey was conducted online from April 22 to May 12 in 2020. Demographic and clinical questions were listed to collect general information. The degree of insomnia, depression, anxiety, stress symptoms and QoL were assessed by the Chinese versions of the Insomnia Severity Index, the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7, the Impact of Event Scale-Revised, and the General Functional Assessment of Cancer Therapy, respectively. Multivariate logistic regression analysis was conducted to analyze the risk factors for mental distress and QoL. Results: A total of 56 respondents coming from 15 various provinces in China participated in the survey. The prevalence of insomnia, depressive, anxiety, stress symptoms and reduced QoL were 37.5, 51.8, 37.5, 30.4, and 51.8%, respectively. Unfavorable disease status, shorter period of olaparib administration, adverse events of olaparib and delay in cancer care were correlated with mental health problems. Reduced QoL was also significantly associated with psychological distress. Conclusions: This study emphasized that mental health problems and reduced QoL should gain more attention in women with OC who are receiving oral olaparib at home. Appropriate psychological healthcare strategies are necessary for OC patients during the COVID-19 pandemic.