Multi-Institutional Study of Referral Patterns for Gynecologic Oncology Consultation.

PURPOSE: Evaluation by a gynecologic oncologist (GO) is associated with improved clinical outcomes for patients with gynecologic cancers, yet little is known about health care factors that influence patients' referrals to GO. METHODS: Medical records of 50 consecutive new patients seen in GO clinics at each of six referral centers across the United States were reviewed. Patient and disease characteristics were collected along with referral indication, evaluation and referral dates, diagnostic procedures, provider specialties, and zone improvement plan (ZIP) code of up to three referring providers per patient. The primary outcome was interval between first evaluation and referral. Univariate associations were evaluated with Chi-square and Wilcoxon rank-sum tests and multivariable associations with negative binomial regression models. Secondary outcome was prolonged time to GO referral, defined as greater than the 75th percentile. Logistic regression was used for multivariable modeling. RESULTS: Three hundred patient records were analyzed. The median time from first health care encounter to referral was 15 days (IQR, 5-43). The mean distance from residence to GO was 39.8 miles (standard deviation, 53.8). Seventy-one percent of GO referrals were initiated by obstetrician-gynecologists, 9% by family physicians, and 6% internists. Presentation-to-referral interval was 76% shorter for patients evaluated by an emergency medicine clinician (exp(Beta), 0.24; 95% CI, 0.11 to 0.53; P < .001). Public insurance was associated with 1.47 times longer time to referral compared with private insurance (exp(Beta), 1.47; 95% CI, 1.05 to 2.04; P = .001). Residents of nonmetropolitan ZIP codes were less likely to have prolonged time to referral (odds ratio [OR], 0.288; P = .017). Distance from residence to GO (per 10 miles) increased the likelihood of prolonged time to referral (OR, 1.10; P = .010). CONCLUSION: Interventions are needed to improve recognition and referral of patients for gynecologic oncology evaluation. Community outreach and engagement with obstetrician-gynecologists should be prioritized to improve times to referral.

Cardiovascular health assessment in routine cancer follow-up in community settings: survivor risk awareness and perspectives.

BACKGROUND: Guidelines recommend cardiovascular risk assessment and counseling for cancer survivors. For effective implementation, it is critical to understand survivor cardiovascular health (CVH) profiles and perspectives in community settings. We aimed to (1) Assess survivor CVH profiles, (2) compare self-reported and EHR-based categorization of CVH factors, and (3) describe perceptions regarding addressing CVH during oncology encounters. METHODS: This cross-sectional analysis utilized data from an ongoing NCI Community Oncology Research Program trial of an EHR heart health tool for cancer survivors (WF-1804CD). Survivors presenting for routine care after potentially curative treatment recruited from 8 oncology practices completed a pre-visit survey, including American Heart Association Simple 7 CVH factors (classified as ideal, intermediate, or poor). Medical record abstraction ascertained CVD risk factors and cancer characteristics. Likert-type questions assessed desired discussion during oncology care. RESULTS: Of 502 enrolled survivors (95.6% female; mean time since diagnosis = 4.2 years), most had breast cancer (79.7%). Many survivors had common cardiovascular comorbidities, including high cholesterol (48.3%), hypertension or high BP (47.8%) obesity (33.1%), and diabetes (20.5%); 30.5% of survivors received high cardiotoxicity potential cancer treatment. Less than half had ideal/non-missing levels for physical activity (48.0%), BMI (18.9%), cholesterol (17.9%), blood pressure (14.1%), healthy diet (11.0%), and glucose/ HbA1c (6.0%). While > 50% of survivors had concordant EHR-self-report categorization for smoking, BMI, and blood pressure; cholesterol, glucose, and A1C were unknown by survivors and/or missing in the EHR for most. Most survivors agreed oncology providers should talk about heart health (78.9%). CONCLUSIONS: Tools to promote CVH discussion can fill gaps in CVH knowledge and are likely to be well-received by survivors in community settings. TRIAL REGISTRATION: NCT03935282, Registered 10/01/2020.

Endometrial cancer survivors' perceptions of their cardiovascular disease risk (results from WF-1804CD AH-HA).

OBJECTIVE: Despite considerable burden of cardiovascular disease (CVD), data on endometrial cancer survivors' CVD perceptions are lacking. We assessed survivors' perspectives on addressing CVD risk during oncology care. METHODS: This cross-sectional analysis utilized data from an ongoing trial of an EHR heart health tool (R01CA226078 & UG1CA189824) conducted through the NCI Community Oncology Research Program (NCORP, WF-1804CD). Endometrial cancer survivors post-potentially curative treatment were recruited from community practices and completed a pre-visit baseline survey, including American Heart Association Simple 7 CVD factors. Likert-type questions assessed confidence in understanding CVD risk, CVD risk perception, and desired discussion during oncology care. Medical record abstraction ascertained data on CVD and cancer characteristics. RESULTS: Survivors (N = 55, median age = 62; 62% 0-2 years post-diagnosis) were predominately white, non-Hispanic (87%). Most agreed/strongly agreed heart disease poses a risk to their health (87%) and oncology providers should talk to patients about heart health (76%). Few survivors reported smoking (12%) but many had poor/intermediate values for blood pressure (95%), body mass index (93%), fasting glucose/A1c (60%), diet (60%), exercise (47%) and total cholesterol (53%). 16% had not seen a PCP in the last year; these survivors were more likely to report financial hardship (22% vs 0%; p = 0.02). Most reported readiness to take steps to maintain or improve heart health (84%). CONCLUSIONS: Discussions of CVD risk during routine oncology care are likely to be well received by endometrial cancer survivors. Strategies are needed to implement CVD risk assessment guidelines and to enhance communication and referrals with primary care. Clinical Trials #: NCT03935282.

Routine informed consent for mismatch repair testing in endometrial cancers: Review and ethical analysis.

OBJECTIVE: To review available data regarding consent for tumor testing for mismatch repair (MMR), and to make recommendation for ethical best practices based on synthesis of contemporary data and ethical principles. METHODS: PubMed and CINAHL databases were searched through September 2021; articles reporting on consent for MMR tumor testing for patients at risk for Lynch Syndrome were abstracted. Additional articles were identified through review of references. Key data and ethical principles were extracted, summarized, and analyzed in the context of contemporary clinical practice. RESULTS: 16 articles met inclusion criteria for this review, none of which specifically related to MMR testing for endometrial cancers. All but two studies were published prior to the approval of pembrolizumab for treatment of MMR-deficient tumors. Scant available data suggest that routine consent prior to tumor testing is uncommon; however, several decision aids improved patient knowledge and satisfaction prior to deciding whether to proceed with tumor testing. Previous ethical analyses invoke clinical utility, potential germline implications, and logistical factors in making recommendations regarding consent practices. These analyses varied in their final recommendations; however, all had significant deficits in their arguments related to contemporary clinical care for patients with endometrial cancer. CONCLUSION: Current data are needed to assess the impact of potential consent strategies for tumor testing. Based on available data, and consistent with contemporary ethical best practices, we recommend that planned MMR testing of endometrial cancers be discussed routinely with patients verbally or in surgical consent documents.

Less is more: Abdominal closure protocol does not reduce surgical site infection after hysterectomy.

OBJECTIVES: To determine rates of surgical site infection (SSI) with and without an abdominal closure protocol for gynecologic oncology patients undergoing abdominal hysterectomy. METHODS: Consecutive patients were identified using CPT codes who underwent total abdominal hysterectomy by gynecologic oncologists at a tertiary care center from January 1, 2015 to December 31, 2019, and stratified by use of the abdominal closure protocol. Demographic, perioperative, and pathologic variables were collected. Fisher's exact and Chi squared tests were used for categorical variables, logistic regression and student t-tests for continuous variables. Multiple logistic regression was used to analyze the relationships between these variables, use of the closure protocol, and development of SSI. RESULTS: 739 patients were included over the study period (n = 393 pre-implementation, n = 346 post-implementation of the abdominal closure protocol,). Baseline demographics including ASA score, BMI, diabetes, and smoking were similar between these groups (P = 0.14-0.94). The rate of SSI within 30 days was 5.9% (23/393) in the pre-protocol group and 8.1% (28/346) under the abdominal closure protocol (P = 0.25). On univariate analysis, factors associated with SSI were BMI >40, diabetes, bowel resection, ASA score 3 or 4, hypertension, and contaminated wound class (uOR 2.31-4.09). On multivariate analysis BMI >40, diabetes, and bowel resection remained independent risk factors (aOR 2.27-2.99), with the closure protocol not achieving significance (aOR 1.43, 95% CI 0.79-2.59). There were no potentially high-risk sub-groups in whom the closing protocol showed benefit. CONCLUSION: The abdominal closure protocol in isolation did not decrease SSI in those undergoing TAH by a gynecologic oncologist.

Practice patterns in post-treatment surveillance in patients with primary epithelial ovarian cancer.

BACKGROUND: The Society of Gynecologic Oncology created guidelines to standardize cost-effective clinical surveillance for detection of recurrence of gynecologic cancers. OBJECTIVE: To determine practice patterns for surveillance of primary ovarian cancer after complete response to therapy and to identify the percentage of clinicians who follow the surveillance guidelines endorsed by the Society of Gynecologic Oncology. METHODS: A single-institution retrospective cohort study was conducted including patients with epithelial ovarian cancer with a complete response to primary therapy between January 2012 and December 2016. Patients were excluded if they were participating in clinical trials that required routine imaging. Data on surveillance and recurrence were collected. Descriptive statistics as well as Fisher's exact test and chi-square test were performed due to the exploratory nature of the study. RESULTS: A total of 184 patients met the inclusion criteria. Median follow-up for the cohort was 37 months (range 6-80). Surveillance was completed in compliance with Society of Gynecologic Oncology guidelines in 78% of patients. Of 39 visits that were non-compliant, 44% (17) were patient initiated (scheduling conflict, missed appointment), 15% (6) were due to the provider intentionally scheduling alternative follow-up, while 41% (16) were off schedule due to problem visits (patient complaint of symptoms). Patients with early-stage cancers were more likely than advanced-stage patients to be non-compliant (33% vs 15%, p=0.006). Patients with non-serous histologies had a higher frequency of non-compliance (31% vs 16%, p=0.035). When stratified by early versus advanced stage, there was no difference in progression-free survival or overall survival based on compliance. CONCLUSIONS: Overall, there was a relatively high rate of compliance with Society of Gynecologic Oncology surveillance guidelines for patients with epithelial ovarian cancer. Patients with non-serous histologies and patients with early-stage disease had a higher rate of non-compliance, and these patients may represent special groups that would benefit from additional survivorship education.

CLTC as a clinically novel gene associated with multiple malformations and developmental delay.

Diagnostic exome sequencing has recently emerged as an invaluable tool in determining the molecular etiology of cases involving dysmorphism and developmental delay that are otherwise unexplained by more traditional methods of genetic testing. Our patient was large for gestational age at 35 weeks, delivered to a 27-year-old primigravid Caucasian whose pregnancy was complicated by preeclampsia. Neonatal period was notable for hypoglycemia, apnea, bradycardia, hyperbilirubinemia, grade I intraventricular hemorrhage, subdural hematoma, laryngomalacia, hypotonia, and feeding difficulties. The patient had numerous minor dysmorphic features. At three and a half years of age, she has global developmental delays and nystagmus, and is being followed for a mediastinal neuroblastoma that is currently in remission. Karyotype and oligo-microarray were normal. Whole-exome, next generation sequencing (NGS) coupled to bioinformatic filtering and expert medical review at Ambry Genetics revealed 14 mutations in 9 genes, and these genes underwent medical review. A heterozygous de novo frameshift mutation, c.2737_2738dupGA p.D913Efs*59, in which two nucleotides are duplicated in exon 17 of the CLTC gene, results in substitution of glutamic acid for aspartic acid at position 913 of the protein, as well as a frame shift that results in a premature termination codon situated 58 amino acids downstream. Clathrin Heavy Chain 1 (CHC1) has been shown to play an important role in the brain for vesicle recycling and neurotransmitter release at pre-synaptic nerve terminals. There is also evidence implicating it in the proper development of the placenta during the early stages of pregnancy. The CLTC alteration identified herein is likely to provide an explanation for the patient's adverse phenotype. Ongoing functional studies will further define the impact of this alteration on CHC1 function and consequently, human disease.

Evaluation of bioequivalency and toxicological effects of three sources of arachidonic acid (ARA) in domestic piglets.

Arachidonic acid (ARA) and docosahexaenoic acid (DHA) are routinely added to infant formula to support growth and development. We evaluated the bioequivalence and safety of three ARA-rich oils for potential use in infant formula using the neonatal pig model. The primary outcome for bioequivalence was brain accretion of ARA and DHA. Days 3-22 of age, domestic pigs were fed one of three formulas, each containing ARA at ∼0.64% and DHA at ∼0.34% total fatty acids (FA). Control diet ARA was provided by ARASCO and all diets had DHA from DHASCO (Martek Biosciences Corp., Columbia, MD). The experimental diets a1 and a2 provided ARA from Refined Arachidonic acid-rich Oil (RAO; Cargill, Inc., Wuhan, China) and SUNTGA40S (Nissui, Nippon Suisan Kaisha, Ltd., Tokyo, Japan), respectively. Formula intake and growth were similar across all diets, and ARA was bioequivalent across treatments in the brain, retina, heart, liver and day 21 RBC. DHA levels in the brain, retina and heart were unaffected by diet. Liver sections, clinical chemistry, and hematological parameters were normal. We conclude that RAO and SUNTGA40S, when added to formula to supply ∼0.64% ARA are safe and nutritionally bioequivalent to ARASCO in domestic piglets.