Examining screening behaviors at a high-risk ovarian cancer clinic.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13047-e13047
Author(s):  
Courtney Lynam-Scherr ◽  
Kisha T Hope ◽  
Irene B. Helenowski ◽  
Masha Kocherginsky ◽  
Melissa Keene ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
High Risk ◽  
Insurance Coverage ◽  
Prophylactic Surgery ◽  
Ca 125 ◽  
Ovarian Cancer Risk ◽  
Race Ethnicity ◽  
The Impact ◽  
Screening Behaviors ◽  
High Risk Clinic

e13047 Background: Women with deleterious BRCA1/2mutations have a significantly increased lifetime risk to develop ovarian cancer. Prophylactic surgery can significantly reduce ovarian cancer risk. The Northwestern Ovarian Cancer Early Detection and Prevention Program (NOCEDPP) was established to monitor this high-risk population prior to risk-reducing surgery. For such patients, providers in the NOCEDPP recommend screening with CA-125 and transvaginal ultrasound (TVUS) biannually. The aim of this study was to examine screening rates of women who have not had surgery but attend the NOCEDPP. Methods: We reviewed electronic health records of 1,662 women who attended the NOCEDPP clinic between October 2005 – October 2015. Demographic and clinical characteristics and utilization of screening were analyzed retrospectively using descriptive statistics and Kruskal-Wallis H-tests to examine differences in screening rates by age, race, ethnicity and insurance type. Results: Of the 1,662 women initially identified, 385 had a known BRCA mutation, 303 had an appointment with at least 6 months between first and last procedure – the sample included in the final analysis. Compared with women ages 35-45 (median = 1.91) and 45+ (median = 1.18), women ages 20-35 attended the most screenings per year (median = 2.12) p = 0.001, a rate consistent with biannual recommendations. There were no significant differences in screening rate by race, ethnicity, or insurance coverage. Conclusions: Despite changes in national guidelines, providers in our high-risk clinic continue to recommend CA-125 and TVUS biannually. Our preliminary data indicates patients’ attendance is uninfluenced by race, ethnicity, or insurance coverage. Further exploration of the impact of age is warranted. Implication of findings indicate a high-risk clinic may positively impact screening behaviors above and beyond factors typically associated with non-adherence.

scholarly journals Ovarian Cancer Risk Scores Based on Immune-Related Pseudogenes to Predict Overall Survival and Guide Immunotherapy and Chemotherapy

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Jie Zhao ◽  
Rixiang Zhao ◽  
Xiaocen Wei ◽  
Xiaojing Jiang ◽  
Fan Su
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
High Risk ◽  
Cox Regression ◽  
High Risk Group ◽  
The Cancer Genome Atlas ◽  
Risk Scores ◽  
Ovarian Cancer Risk ◽  
Cox Regression Analysis ◽  
The Impact

Background. Ovarian cancer (OC) is the top of the aggressive malignancies in females with a poor survival rate. However, the roles of immune-related pseudogenes (irPseus) in the immune infiltration of OC and the impact on overall survival (OS) have not been adequately studied. Therefore, this study aims to identify a novel model constructed by irPseus to predict OS in OC and to determine its significance in immunotherapy and chemotherapy. Methods. In this study, with the use of The Cancer Genome Atlas (TCGA) combined with Genotype-Tissue Expression (GTEx), 55 differentially expressed irPseus (DEirPseus) were identified. Then, we constructed 10 irPseus pairs with the help of univariate, Lasso, and multivariate Cox regression analysis. The prognostic performance of the model was determined and measured by the Kaplan–Meier curve, a time-dependent receiver operating characteristic (ROC) curve. Results. After dividing OC subjects into high- and low-risk subgroups via the cut-off point, it was revealed that subjects in the high-risk group had a shorter OS. The multivariate Cox regression performed between the model and multiple clinicopathological variables revealed that the model could effectively and independently predict the prognosis of OC. The prognostic model characterized infiltration by various kinds of immune cells and demonstrated the immunotherapy response of subjects with cytotoxic lymphocyte antigen 4 (CTLA4), anti-programmed death-1 (PD-1), and anti-PD-ligand 1 (PD-L1) therapy. A high risk score was related to a higher inhibitory concentration (IC50) for etoposide ( P = 0.0099 ) and mitomycin C ( P = 0.0013 ). Conclusion. It was the first study to identify a novel signature developed by DEirPseus pairs and verify the role in predicting OS, immune infiltrates, immunotherapy, and chemosensitivity. The irPseus are vital factors predicting the prognosis of OC and could act as a novel potential treatment target.

scholarly journals BRCA1/2 associated cancer susceptibility: a clinical overview

2016 ◽  
Vol 7 (2) ◽  
pp. 16-24
Author(s):  
Georgios Lypas
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
High Risk ◽  
Physical Examination ◽  
Transvaginal Ultrasound ◽  
Parp Inhibitors ◽  
Prophylactic Surgery ◽  
Ca 125 ◽  
Cancer Risks ◽  
Increased Risk

Abstract The most frequently identified genetic cause of breast cancer is the germline mutation of BRCA1 and 2 genes. The carriers of these mutations are at high risk for breast and ovarian cancers and increased risk for pancreatic and prostate cancers. Personal and family history are routinely used to identify individuals at risk for carrying such mutations. Genetic counselling is required to guide them through genetic testing and risk management. Positive testing corresponds to a deleterious mutation, whereas negative testing is considered as uninformative; variants of unknown clinical significance are also classified as uninformative. The most effective risk reduction strategy involves bilateral prophylactic mastectomy and bilateral salpingo-oophorectomy, eliminating 90% of breast and 97% of ovarian cancer risks, respectively. Before and until such surgery, surveillance with physical examination, mammography and magnetic resonance mammography, starting at 25–30 years of age, are recommended for the early diagnosis of breast cancer; semi-annual surveillance with physical examination, transvaginal ultrasound and serum CA-125 is recommended for women who have not had prophylactic surgery. Carriers diagnosed with breast cancer run a high risk for a new breast primary and this information should be used accordingly. PARP inhibitors is a new class of antineoplastic agents, already approved for advanced BRCA1/2 mutant (germline or somatic) ovarian cancer. Multigene panel testing may follow a negative BRCA genetic test, often identifying other genetic causes of cancer, expanding its role in oncology. Further adoption of PARP inhibitors, refinement in estimation of BRCA-associated cancer risks and wider population testing, through NGS technology, may become available in the near future.

scholarly journals Predictors of risk-reducing surgery intentions following genetic counseling for hereditary breast and ovarian cancer

2018 ◽  
Vol 10 (2) ◽  
pp. 337-346 ◽  
Author(s):  
Mary Kathleen Ladd ◽  
Beth N Peshkin ◽  
Leigha Senter ◽  
Shari Baldinger ◽  
Claudine Isaacs ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Genetic Counseling ◽  
Cancer Risk ◽  
Prophylactic Surgery ◽  
Ovarian Cancer Risk ◽  
Breast And Ovarian Cancer ◽  
Affective Factors ◽  
Risk Reducing

Abstract Risk-reducing mastectomy (RRM) and salpingo-oophorectomy (RRSO) are increasingly used to reduce breast and ovarian cancer risk following BRCA1/BRCA2 testing. However, little is known about how genetic counseling influences decisions about these surgeries. Although previous studies have examined intentions prior to counseling, few have examined RRM and RRSO intentions in the critical window between genetic counseling and test result disclosure. Previous research has indicated that intentions at this time point predict subsequent uptake of surgery, suggesting that much decision-making has taken place prior to result disclosure. This period may be a critical time to better understand the drivers of prophylactic surgery intentions. The aim of this study was to examine predictors of RRM and RRSO intentions. We hypothesized that variables from the Health Belief Model would predict intentions, and we also examined the role of affective factors. Participants were 187 women, age 21–75, who received genetic counseling for hereditary breast and ovarian cancer. We utilized multiple logistic regression to identify independent predictors of intentions. 49.2% and 61.3% of participants reported intentions for RRM and RRSO, respectively. Variables associated with RRM intentions include: newly diagnosed with breast cancer (OR = 3.63, 95% CI = 1.20–11.04), perceived breast cancer risk (OR = 1.46, 95% CI = 1.17–1.81), perceived pros (OR = 1.79, 95% CI = 1.38–2.32) and cons of RRM (OR = 0.81, 95% CI = 0.65–0.996), and decision conflict (OR = 0.80, 95% CI = 0.66–0.98). Variables associated with RRSO intentions include: proband status (OR = 0.28, 95% CI = 0.09–0.89), perceived pros (OR = 1.35, 95% CI = 1.11–1.63) and cons of RRSO (OR = 0.72, 95% CI = 0.59–0.89), and ambiguity aversion (OR = 0.79, 95% CI = 0.65–0.95). These data provide support for the role of genetic counseling in fostering informed decisions about risk management, and suggest that the role of uncertainty should be explored further.

scholarly journals Variants in the Signaling Protein TSAd are Associated with Susceptibility to Ovarian Cancer in BRCA1/2 Negative High Risk Families

2012 ◽  
Vol 7 ◽  
pp. BMI.S10815 ◽  
Author(s):  
Ludmila Kaplun ◽  
Aviva Levine Fridman ◽  
Wei Chen ◽  
Nancy K. Levin ◽  
Sidra Ahsan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
High Risk ◽  
Cancer Risk ◽  
Allelic Variation ◽  
High Risk Population ◽  
Ovarian Cancer Risk ◽  
Familial Ovarian Cancer ◽  
Cell Growth And Differentiation ◽  
Brca1 Brca2 ◽  
High Risk Families

A substantial fraction of familial ovarian cancer cases cannot be attributed to specific genetic factors. The discovery of additional susceptibility genes will permit a more accurate assessment of hereditary cancer risk and allow for monitoring of predisposed women in order to intervene at the earliest possible stage. We focused on a population with elevated familial breast and ovarian cancer risk. In this study, we identified a SNP rs926103 whose minor allele is associated with predisposition to ovarian but not breast cancer in a Caucasian high-risk population without BRCA1/ BRCA2 mutations. We have found that the allelic variation of rs926103, which alters amino acid 52 of the encoded protein SH2D2A/TSAd, results in differences in the activity of this protein involved in multiple signal transduction pathways, including regulation of immune response, tumor vascularization, cell growth, and differentiation. Our observation provides a novel candidate genetic biomarker of elevated ovarian cancer risk in members of high-risk families without BRCA1/2 mutations, as well as a potential therapeutic target, TSAd.

scholarly journals Supporting surgeons in patient-centred complex decision-making: a qualitative analysis of the impact of a perioperative physician clinic

BMJ Open ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. e033277
Author(s):  
Clarabelle T Pham ◽  
Catherine L Gibb ◽  
Robert A Fitridge ◽  
Jon Karnon ◽  
Elizabeth Hoon
Keyword(s):  
Decision Making ◽  
High Risk ◽  
Elective Surgery ◽  
Structured Interviews ◽  
Complex Patients ◽  
Complex Decision Making ◽  
Complex Decision ◽  
Additional Value ◽  
The Impact ◽  
High Risk Clinic

ObjectivePatients with comorbidities can be referred to a physician-led high-risk clinic for medical optimisation prior to elective surgery at the discretion of the surgical consultant, but the factors that influence this referral are not well understood. The aims of this study were to understand the factors that influence a surgeon’s decision to refer a patient to the clinic, and how the clinic impacts on the management of complex patients.DesignQualitative study using theoretical thematic analysis to analyse transcribed semi-structured interviews.SettingInterviews were held in either the surgical consultant’s private office or a quiet office/room in the hospital ward.ParticipantsSeven surgical consultants who were eligible to refer patients to the clinic.ResultsWhen discussing the factors that influence a referral to the clinic, all participants initially described the optimisation of comorbidities and would then discuss with examples the challenges with managing complex patients and communicating the risks involved with having surgery. When discussing the role of the clinic, two related subthemes were dominant and focused on the management of risk in complex patients. The participants valued the involvement of the clinic in the decision-making and communication of risks to the patient.ConclusionsThe integration of the high-risk clinic in this study appears to offer additional value in supporting the decision-making process for the surgical team and patient beyond the clinical outcomes. The factors that influence a surgeon’s decision to refer a patient to the clinic appear to be driven by the aim to manage the uncertainty and risk to the patient regarding surgery and it was seen as a strategy for managing difficult and complex cases.

Decision analysis of prophylactic mastectomy and oophorectomy in BRCA1-positive or BRCA2-positive patients.

1998 ◽  
Vol 16 (3) ◽  
pp. 979-985 ◽  
Author(s):  
V R Grann ◽  
K S Panageas ◽  
W Whang ◽  
K H Antman ◽  
A I Neugut
Keyword(s):  
Quality Of Life ◽  
Ovarian Cancer ◽  
High Risk ◽  
Surgical Procedures ◽  
Brca2 Gene ◽  
Cost Effective ◽  
Prophylactic Surgery ◽  
Breast And Ovarian Cancer ◽  
Prophylactic Surgical Procedures

PURPOSE Young Ashkenazi Jewish women or those from high-risk families who test positive for BRCA1 or BRCA2 mutant genes have a significant risk of developing breast or ovarian cancer by the age of 70 years. Many question whether they should have prophylactic surgical procedures, ie, bilateral mastectomy and/or oophorectomy. METHODS A Markov model was developed to determine the survival, quality of life, and cost-effectiveness of prophylactic surgical procedures. The probabilities of developing breast and ovarian cancer were based on literature review among women with the BRCA1 or BRCA2 gene and mortality rates were determined from Surveillance, Epidemiology, and End Results (SEER) data for 1973 to 1992. The costs for hospital and ambulatory care were estimated from Health Care Financing Administration (HCFA) payments in 1995, supplemented by managed care and fee-for-service data. Utility measures for quality-adjusted life-years (QALYs) were explicitly determined using the time-trade off method. Estimated risks for breast and ovarian cancer after prophylactic surgeries were obtained from the literature. RESULTS For a 30-year-old woman, according to her cancer risks, prophylactic oophorectomy improved survival by 0.4 to 2.6 years; mastectomy, by 2.8 to 3.4 years; and mastectomy and oophorectomy, by 3.3 to 6.0 years over surveillance. The QALYs saved were 0.5 for oophorectomy and 1.9 for the combined procedures in the high-risk model. Prophylactic surgeries were cost-effective compared with surveillance for years of life saved, but not for QALYs. CONCLUSION Among women who test positive for a BRCA1 or BRCA2 gene mutation, prophylactic surgery at a young age substantially improves survival, but unless genetic risk of cancer is high, provides no benefit for quality of life. Prophylactic surgery is cost-effective for years of life saved compared with other medical interventions that are deemed cost-effective.

scholarly journals Prediction of a high-risk group based on postoperative nadir CA-125 levels in patients with advanced epithelial ovarian cancer

2011 ◽  
Vol 22 (4) ◽  
pp. 269 ◽  
Author(s):  
Sokbom Kang ◽  
Tae-Joong Kim ◽  
Sang-Soo Seo ◽  
Byoung-Gie Kim ◽  
Duk-Soo Bae ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
High Risk ◽  
Epithelial Ovarian Cancer ◽  
Risk Group ◽  
High Risk Group ◽  
Ca 125 ◽  
Advanced Epithelial Ovarian Cancer

scholarly journals Risk Algorithm Using Serial Biomarker Measurements Doubles the Number of Screen-Detected Cancers Compared With a Single-Threshold Rule in the United Kingdom Collaborative Trial of Ovarian Cancer Screening

2015 ◽  
Vol 33 (18) ◽  
pp. 2062-2071 ◽  
Author(s):  
Usha Menon ◽  
Andy Ryan ◽  
Jatinderpal Kalsi ◽  
Aleksandra Gentry-Maharaj ◽  
Anne Dawnay ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
United Kingdom ◽  
Cancer Screening ◽  
Ca 125 ◽  
Ovarian Cancer Screening ◽  
Collaborative Trial ◽  
The United Kingdom ◽  
Risk Algorithm ◽  
The Impact ◽  
Threshold Rule

Purpose Cancer screening strategies have commonly adopted single-biomarker thresholds to identify abnormality. We investigated the impact of serial biomarker change interpreted through a risk algorithm on cancer detection rates. Patients and Methods In the United Kingdom Collaborative Trial of Ovarian Cancer Screening, 46,237 women, age 50 years or older underwent incidence screening by using the multimodal strategy (MMS) in which annual serum cancer antigen 125 (CA-125) was interpreted with the risk of ovarian cancer algorithm (ROCA). Women were triaged by the ROCA: normal risk, returned to annual screening; intermediate risk, repeat CA-125; and elevated risk, repeat CA-125 and transvaginal ultrasound. Women with persistently increased risk were clinically evaluated. All participants were followed through national cancer and/or death registries. Performance characteristics of a single-threshold rule and the ROCA were compared by using receiver operating characteristic curves. Results After 296,911 women-years of annual incidence screening, 640 women underwent surgery. Of those, 133 had primary invasive epithelial ovarian or tubal cancers (iEOCs). In all, 22 interval iEOCs occurred within 1 year of screening, of which one was detected by ROCA but was managed conservatively after clinical assessment. The sensitivity and specificity of MMS for detection of iEOCs were 85.8% (95% CI, 79.3% to 90.9%) and 99.8% (95% CI, 99.8% to 99.8%), respectively, with 4.8 surgeries per iEOC. ROCA alone detected 87.1% (135 of 155) of the iEOCs. Using fixed CA-125 cutoffs at the last annual screen of more than 35, more than 30, and more than 22 U/mL would have identified 41.3% (64 of 155), 48.4% (75 of 155), and 66.5% (103 of 155), respectively. The area under the curve for ROCA (0.915) was significantly (P = .0027) higher than that for a single-threshold rule (0.869). Conclusion Screening by using ROCA doubled the number of screen-detected iEOCs compared with a fixed cutoff. In the context of cancer screening, reliance on predefined single-threshold rules may result in biomarkers of value being discarded.

Correlation of CA-125 and RECIST evaluation in recurrent ovarian cancer (ROC): Results from a randomized phase III study of trabectedin (T) with pegylated liposomal doxorubicin (PLD) versus PLD alone

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5550-5550
Author(s):  
T. J. Herzog ◽  
J. B. Vermorken ◽  
E. Pujade-Lauraine ◽  
J. Li ◽  
E. Bayever ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Predictive Value ◽  
Objective Response ◽  
Pegylated Liposomal Doxorubicin ◽  
Phase Iii ◽  
Ca 125 ◽  
Open Label ◽  
Significant Prolongation ◽  
Phase Iii Study ◽  
The Impact

5550 Background: OVA-301, an open-label, multicenter, randomized phase III study comparing the combination of T and PLD to PLD alone in 672 ovarian cancer patients, showed significant prolongation in Progression-Free Survival (PFS) and higher Objective Response (OR) in the combination arm (T-PLD) by three separate assessments, investigator assessment (IA), independent radiology (IR) and oncology review (IO). The purpose of this analysis is to examine: 1) the impact of early changes in CA-125 over the subsequent best OR by RECIST; 2) the concordance between best OR determined by CA-125 and RECIST; 3) the value of CA-125 to predict radiological response. Methods: Tumor assessments by imaging and CA-125 were performed at baseline, and every 8 weeks during study in both arms. Radiological tumor assessment, regardless of CA-125 changes, determined the study conduct. Early CA-125 changes were those assessed at the first and second evaluation. Analyses were based on “all randomized patients.” Results: Response rate by RECIST (IR)/CA-125 was 28%/48% for T-PLD vs. 19%/33% for PLD. The association between CA-125 and RECIST response was stronger for IA relative to IR/IO, with 79% concordance for both arms, 65% overall positive predictive value (PPV) and 89% negative predictive value (NPV) for IA and 74%/75% concordance, 46%/49% PPV and 93%/92% NPV for IR/IO. Early CA-125 changes were assessed in 514 patients. Early ≥25% CA-125 decreases in the first/second evaluation occurred in 85%/95% of RECIST responders in the T-PLD arm and in 81/82% responders treated with PLD. Conclusions: The predictive value of CA-125 response was high and similar in both arms. The addition of T to PLD resulted in superior efficacy in this patient population as assessed by IA, IR and IO, with a favorable trend for CA-125 response assessment. RECIST response was preceded by a significant CA-125 decrease in a high proportion of patients. [Table: see text]

Risk-reducing salpingo-oophorectomy and prophylactic mastectomy among BRCA mutation “previvors.”

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1518-1518
Author(s):  
Laura L. Holman ◽  
Molly S Daniels ◽  
Amanda C. Brandt ◽  
Banu Arun ◽  
Elizabeth Keeler ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Screening ◽  
High Risk ◽  
Prophylactic Mastectomy ◽  
Brca Mutation ◽  
Premenopausal Women ◽  
Prophylactic Surgery ◽  
Ovarian Cancer Screening ◽  
Brca Mutation Carriers ◽  
Risk Reducing

1518 Background: We prospectively evaluated the timing and uptake of risk-reducing surgery in a cohort of female BRCA mutation carriers that have no personal cancer history (“previvors”). Methods: Patients at high risk of breast and ovarian cancer were enrolled between 2007 and 2011 and followed in a high-risk ovarian cancer screening clinic. Women were offered risk-reducing salpingo-oophorectomy (RRSO) and/or prophylactic mastectomy (PM) per guidelines. Their clinical data were recorded and analyzed using descriptive statistics. Results: Of 260 BRCA mutation carriers enrolled, 73 have no personal history of cancer and are “previvors.” Patients have been followed for a median of 26.5 months (1-50 months). The median age is 38 years, 81.1% are white, 16.2% are Ashkenazi Jewish, and 79.7% are premenopausal. BRCA1 carriers account for 43.2% of participants and 55.4% have a BRCA2 mutation. The majority of patients (77.6%) presented for ovarian cancer screening <1 year after their BRCA testing. In all, 60.8% of women underwent prophylactic surgery: 28.4% chose RRSO, 18.9% chose PM, and 13.5% chose both procedures. Postmenopausal women were more likely to choose RRSO, while uptake for both procedures was common for premenopausal women (Table, p=0.04). RRSO was also more likely in parous than nulliparous premenopausal women (35.2% vs 9% p=0.001). PM was not associated with parity (p=0.79). Of women that had both surgeries, 20% had them concurrently and 20% had PM first. Of the 60% that underwent RRSO first, all had their second surgery within 14 months. Conclusions: BRCA mutation “previvors” have a high overall uptake of prophylactic surgery. Premenopausal women are more likely to choose PM than postmenopausal women; reasons for this are unclear. “Previvors” that choose RRSO and PM typically have both surgeries within a fairly short timeframe. With the growing population of “previvors” in the US, further study of patient preferences regarding preventative surgery and long-term consequences is needed. [Table: see text]

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