A One-Year Cross Sectional Analysis of Emergency Medical Services Utilization and Its Association with Hypertension in Pregnancy.

Objective: To evaluate the prehospital obstetric population that utilizes emergency medical services (EMS) and their association with hypertensive disorders of pregnancy. Methods: We conducted a retrospective evaluation of one year of all medical calls from a large, municipal, midwestern fire department. Inclusion criteria included all pregnant patients transported to a hospital by EMS. Descriptive statistics were calculated to evaluate prehospital event information (e.g., zip code, time, and duration of call), patient characteristics, and clinical management data regarding blood pressure. Census data were used to compare neighborhood information with poverty rates. Results: Of the 1,575 identified patients, 64.4% (1015/1575) presented with obstetric complaints, 57.4% (700/1220) were in their third trimester and 72.7% (686/944) were multiparous. The median call duration was 17 (interquartile range 12-22) minutes. In the areas where EMS usage was highest, one quarter of individuals lived below the poverty level. Of the studied population, 32.0% (504/1575) were found to be hypertensive; 14.9% (75/504) of hypertensive patients were found to have severe hypertension. Only one patient (1/1575, 0.06%) presented with a chief complaint of hypertension; the rest were discovered by EMS. The highest rates of hypertension were noted in wealthier areas of the city. Patients with severe hypertension were more likely to present with seizures, consistent with eclampsia. Conclusion: Hypertension is common in the obstetric population using EMS. Prehospital management of hypertensive disorders of pregnancy may focus on identification and treatment of severe pre-eclampsia or eclampsia. Areas with longer call times may consider treatment of severe hypertension. Prehospital treatment of hypertensive disorders of pregnancy could be optimized.

Conization pathologic features as a predictor of intermediate and high risk features on radical hysterectomy specimens in early stage cervical cancer.

OBJECTIVE: The impact of pathologic features of a cone biopsy on the management of women with early stage cervical cancer is understudied. Our objective was to evaluate the additive value of pathologic features of a cone biopsy toward identifying patients with high risk tumors for which adjuvant therapy may be indicated. METHODS: Patients with early stage cervical cancer undergoing a conization followed by radical hysterectomy from 1995 to 2016 were retrospectively identified. Clinical and pathologic data were abstracted from patient medical records. RESULTS: A total of 115 patients were identified. Based on final pathology, 70.5% were low risk, 10.4% intermediate risk, and 19.1% were high risk. The additive pathologic features of the conization specimen would have reclassified five patients from low into the intermediate risk group. Though depth of invasion did not correlate with final pathology results, when lymphovascular space invasion (LVSI) was present in the conization specimen, 51.2% of patients were noted to meet intermediate/high risk; compared to only 9.5% without LVSI. CONCLUSIONS: In women with early stage cervical cancer, additive pathology of the conization and hysterectomy specimen did not significantly impact risk stratification, only affecting 4.3% of patients. However, presence of LVSI in the conization was associated with intermediate risk criteria in 60% of cases and high risk criteria in 37% of cases. As patients with intermediate/high risk criteria would meet recommendations for adjuvant therapy, the evaluation of LVSI in conization specimens may influence the selection of primary treatment for women with cervical cancer.

Feasibility and Clinical Utility of Reporting Hereditary Cancer Predisposition Pathogenic Variants Identified in Research Germline Sequencing: A Prospective Interventional Study.

PURPOSE: Patients with cancer frequently undergo research-grade germline sequencing but clinically actionable results are not routinely disclosed. The objective of this study is to evaluate the feasibility of reporting clinically relevant secondary findings (SF) identified in germline research sequencing using the institutional molecular tumor board (MTB) and the treating oncology physician. METHODS: This prospective, interventional cohort study enrolled Total Cancer Care participants with any cancer diagnosis at a single institution. Patients underwent research-grade germline whole-exome sequencing, with bioinformatic analysis in a Clinical Laboratory Improvement Amendments-certified laboratory to verify pathogenic/likely pathogenic germline variants (PGVs) in any American College of Medical Genomics and Genetics SF v2.0 genes. After a protocol modification in consenting patients, the MTB reported PGVs to treating oncology physicians with recommendations for referral to a licensed genetic counselor and clinical confirmatory testing. RESULTS: Of the 781 enrolled participants, 32 (4.1%) harbored cancer predisposition PGVs, 24 (3.1%) were heterozygous carriers of an autosomal recessive cancer predisposition syndrome, and 14 (1.8%) had other hereditary disease PGVs. Guideline-directed testing would have missed 37.5% (12/32) of the inherited cancer predisposition PGVs, which included BRCA1, BRCA2, MSH6, SDHAF2, SDHB, and TP53 variants. Three hundred fifteen participants consented to reporting results; results for all living patients were reported to the clinical team with half referred to a licensed genetic counselor. There was concordance between all research variants identified in patients (n = 9) who underwent clinical confirmatory sequencing. CONCLUSION: MTB reporting of research-grade germline sequencing to the clinical oncology team is feasible. Over a third of PGVs identified using a universal testing strategy would have been missed by guideline-based approach, suggesting a role for expanding germline testing.

Robot-assisted laparoscopic removal of an extraperitoneal pelvic solitary fibrous tumor.

•Pelvic SFTs are rare, typically benign soft tissue neoplasms that pose a diagnostic challenge for gynecologists.•Retroperitoneal pelvic SFTs can mimic gynecologic malignancies and should be considered in diagnosis of a solitary pelvic mass.•Pathologic diagnosis is typically confirmed by immunohistochemistry staining positively for CD34 and STAT6.•Complete surgical excision is recommended for these tumors and can be completed with a minimally invasive approach.•Close long-term follow-up is necessary due to possible recurrence or metastasis, especially for high-risk pathologic features.

Bleeding from Gynecologic Malignancies.

Initial assessment of vaginal bleeding in gynecologic malignancies includes a thorough history and physical examination, identification of site and extent of disease, and patient goals of care. Patients who are initially hemodynamically unstable may require critical care services. Choice of treatment is disease site specific. Cervical cancer frequently is treated with chemoradiation. Uterine cancer may be treated surgically, with radiation, or pharmacologically. Gestational trophoblastic disease is treated surgically. Alternative treatment modalities include vascular embolization and topical hemostatic agents. Patients with bleeding gynecologic malignancies should be managed as inpatients in facilities with gynecologic oncology, radiation oncology, and critical care services.

Molecular Tumor Board-Assisted Care in an Advanced Cancer Population: Results of a Phase II Clinical Trial.

PURPOSE: Multidisciplinary molecular tumor boards (MTBs) interpret next-generation sequencing reports and help oncologists determine best therapeutic options; however, there is a paucity of data regarding their clinical utility. The purpose of this study was to determine if MTB-directed therapy improves progression-free survival (PFS) over immediately prior therapy in patients with advanced cancer. METHODS: This single-arm, prospective phase II clinical trial enrolled patients with advanced cancer with an actionable mutation who received MTB-recommended targeted therapy between January 1, 2017, and October 31, 2020. MTB-recommended both on-label (level 1 evidence) and off-label (evidence levels 2 and 3) therapies. Of the 93 enrolled patients, 43 were treated frontline and 50 received second-line or greater-line therapy. The primary outcome was the probability of patients treated with second-line or greater-line MTB-directed therapy who achieved a PFS ratio ≥ 1.3 (PFS on MTB-directed therapy divided by PFS on the patient's immediately prior therapy). Secondary outcomes included PFS for patients treated frontline and overall survival and adverse effects for the entire study population. RESULTS: The most common disease sites were lung (35 of 93, 38%), gynecologic (17 of 93, 18%), GI (16 of 93, 17%), and head and neck (7 of 93, 8%). The Kaplan-Meier estimate of the probability of PFS ratio ≥ 1.3 was 0.59 (95% CI, 0.47 to 0.75) for patients treated with second-line or greater-line MTB-directed therapy. The median PFS was 449 (range 42-1,125) days for patients treated frontline. The median overall survival was 768 (range 22-1,240) days. There were four nontreatment-related deaths. CONCLUSION: When treated with MTB-directed therapy, most patients experienced improved PFS compared with immediately prior treatment. MTB-directed targeted therapy may be a strategy to improve outcomes for patients with advanced cancer.

Significance of Pelvic Fluid Observed during Ovarian Cancer Screening with Transvaginal Sonogram.

The primary objective was to examine the role of pelvic fluid observed during transvaginal ultrasonography (TVS) in identifying ovarian malignancy. A single-institution, observational study was conducted within the University of Kentucky Ovarian Cancer Screening trial from January 1987 to September 2019. We analyzed true-positive (TP), false-positive (FP), true-negative (TN), and false-negative (FN) groups for the presence of pelvic fluid during screening encounters. Measured outcomes were the presence and duration of fluid over successive screening encounters. Of the 48,925 women surveyed, 2001 (4.1%) had pelvic fluid present during a TVS exam. The odds ratio (OR) of detecting fluid in the comparison group (TN screen; OR = 1) significantly differed from that of the FP cases (benign pathology; OR: 13.4; 95% confidence interval (CI): 9.1-19.8), the TP cases with a low malignant potential (LMP; OR: 28; 95% CI: 26.5-29.5), TP ovarian cancer cases (OR: 50.4; 95% CI: 27.2-93.2), and FN ovarian cancer cases (OR: 59.3; 95% CI: 19.7-178.1). The mean duration that pelvic fluid was present for women with TN screens was 2.2 ± 0.05 encounters, lasting 38.7 ± 1.3 months. In an asymptomatic screening population, free fluid identified in TVS exams was more associated with ovarian malignancy than in the control group or benign ovarian tumors. While pelvic free fluid may not solely discriminate malignancy from non-malignancy, it appears to be clinically relevant and warrants thoughtful consideration.

Differences in Health-Related Quality of Life and Health Behaviors Among Lesbian, Bisexual, and Heterosexual Women Surviving Cancer from the 2013 to 2018 National Health Interview Survey.

Purpose: Health-related quality of life (HRQoL) and health behaviors contribute to cancer morbidity and mortality, which are elevated in lesbian and bisexual women (LBW). The purpose of this study was to assess differences in HRQoL and health behaviors between heterosexual and lesbian women and heterosexual and bisexual women cancer survivors. Methods: We pooled 2013-2018 National Health Interview Survey data. HRQoL comprised physical, mental, financial, and social health domains. Health behaviors included tobacco and alcohol use, physical activity, and preventive health care. Weighted, multivariable logistic regression models estimated odds ratios (ORs) with 95% confidence intervals (CIs). Results: The sample included 10,830 heterosexual, 141 lesbian, and 95 bisexual cancer survivors. Lesbian women reported higher odds of fair/poor self-rated health (OR: 1.68, 95% CI 1.02-2.78), chronic obstructive pulmonary disease (OR: 1.98, 95% CI 1.09-3.56), and heart conditions (OR: 1.90, 95% CI 1.16-3.12) than heterosexual women. Bisexual women reported higher odds of severe psychological distress (OR: 3.03, 95% CI 1.36-6.76), heart conditions (OR: 1.98, 95% CI 1.12-3.53), and food insecurity (OR: 2.89, 95% CI 1.29-6.50) than heterosexual women. For health behaviors, lesbian women reported greater odds of current (OR: 2.34, 95% CI 1.26-4.34) and former tobacco use (OR: 1.89, 95% CI 1.21-2.96), and bisexual women had lower odds of a recent mammogram (OR: 0.42, 95% CI 0.23-0.78) than heterosexual women. Conclusions: LBW cancer survivors reported disparities in HRQoL and health behaviors. In cancer care settings, identification of LBW patients requiring physical and mental health promotion, financial services, and supported tobacco cessation may improve health and survival.

MUTYH as an Emerging Predictive Biomarker in Ovarian Cancer.

Approximately 18% of ovarian cancers have an underlying genetic predisposition and many of the genetic alterations have become intervention and therapy targets. Although mutations in MutY homolog (MUTYH) are best known for MUTYH associated polyposis and colorectal cancer, it plays a role in the development of ovarian cancer. In this review, we discuss the function of the MUTYH gene, mutation epidemiology, and its mechanism for carcinogenesis. We additionally examine its emerging role in the development of ovarian cancer and how it may be used as a predictive and targetable biomarker. MUTYH mutations may confer the risk of ovarian cancer by the failure of its well-known base excision repair mechanism or by failure to induce cell death. Biallelic germline MUTYH mutations confer a 14% risk of ovarian cancer by age 70. A monoallelic germline mutation in conjunction with a somatic MUTYH mutation may also contribute to the development of ovarian cancer. Resistance to platinum-based chemotherapeutic agents may be seen in tumors with monoallelic mutations, but platinum sensitivity in the biallelic setting. As MUTYH is intimately associated with targetable molecular partners, therapeutic options for MUTYH driven ovarian cancers include programed-death 1/programed-death ligand-1 inhibitors and poly-adenosine diphosphate ribose polymerase inhibitors. Understanding the function of MUTYH and its associated partners is critical for determining screening, risk reduction, and therapeutic approaches for MUTYH-driven ovarian cancers.

Salvaging Detection of Early-Stage Ovarian Malignancies When CA125 Is Not Informative.

BACKGROUND: Ovarian cancer is the deadliest gynecologic cancer, with no recommended screening test to assist with early detection. Cancer antigen 125 (CA125) is a serum biomarker commonly used by clinicians to assess preoperative cancer risk, but it underperforms in premenopausal women, early-stage malignancies, and several histologic subtypes. OVA1 is a multivariate index assay that combines CA125 and four other serum proteins to assess the malignant risk of an adnexal mass. OBJECTIVE: To evaluate the performance of OVA1 in a cohort of patients with low-risk serum CA125 values. STUDY DESIGN: We analyzed patient data from previous collections (N = 2305, prevalence = 4.5%) where CA125 levels were at or below 67 units/milliliter (U/mL) for pre-menopausal women and 35 U/mL for post-menopausal women. We compare the performance of OVA1 to CA125 in classifying the risk of malignancy in this cohort, including sensitivity, specificity, positive and negative predictive values. RESULTS: The overall sensitivity of OVA1 in patients with a low-risk serum CA125 was 59% with a false-positive rate of 30%. OVA1 detected over 50% of ovarian malignancies in premenopausal women despite a low-risk serum CA125. OVA1 also correctly identified 63% of early-stage cancers missed by CA125. The most common epithelial ovarian cancer subtypes in the study population were mucinous (25%) and serous (23%) carcinomas. Despite a low-risk CA125, OVA1 successfully detected 83% of serous, 58% of mucinous, and 50% of clear cell ovarian cancers. CONCLUSIONS: As a standalone test, CA125 misses a significant number of ovarian malignancies that can be detected by OVA1. This is particularly important for premenopausal women and early-stage cancers, which have a much better long-term survival than late-stage malignancies. Using OVA1 in the setting of a normal serum CA125 can help identify at-risk ovarian tumors for referral to a gynecologic oncologist, potentially improving overall survival.

Real-World Evaluation of Universal Germline Screening for Cancer Treatment-Relevant Pharmacogenes.

The purpose of this study was to determine the frequency of clinically actionable treatment-relevant germline pharmacogenomic variants in patients with cancer and assess the real-world clinical utility of universal screening using whole-exome sequencing in this population. Cancer patients underwent research-grade germline whole-exome sequencing as a component of sequencing for somatic variants. Analysis in a clinical bioinformatics pipeline identified clinically actionable pharmacogenomic variants. Clinical Pharmacogenetics Implementation Consortium guidelines defined clinical actionability. We assessed clinical utility by reviewing electronic health records to determine the frequency of patients receiving pharmacogenomically actionable anti-cancer agents and associated outcomes. This observational study evaluated 291 patients with cancer. More than 90% carried any clinically relevant pharmacogenetic variant. At least one disease-relevant variant impacting anti-cancer agents was identified in 26.5% (77/291). Nine patients with toxicity-associated pharmacogenomic variants were treated with a relevant medication: seven UGT1A1 intermediate metabolizers were treated with irinotecan, one intermediate DPYD metabolizer was treated with 5-fluorouracil, and one TPMT poor metabolizer was treated with mercaptopurine. These individuals were more likely to experience treatment-associated toxicities than their wild-type counterparts (p = 0.0567). One UGT1A1 heterozygote died after a single dose of irinotecan due to irinotecan-related adverse effects. Identifying germline pharmacogenomic variants was feasible using whole-exome sequencing. Actionable pharmacogenetic variants are common and relevant to patients undergoing cancer treatment. Universal pharmacogenomic screening can be performed using whole-exome sequencing data originally obtained for quality control purposes and could be considered for patients who are candidates for irinotecan, 5-fluorouracil, capecitabine, and mercaptopurine.

Current Fertility Preservation Options for Female Patients With Hodgkin Lymphoma.

IMPORTANCE: Many adolescents and young adults diagnosed with Hodgkin lymphoma (HL) experience disease progression requiring high-dose alkylating salvage therapy, which often results in permanent infertility. OBJECTIVE: The aim of this report is to discuss fertility preservation options in female patients with consideration of chemotherapeutic agents in HL. EVIDENCE ACQUISITION: An electronic literature review was performed utilizing a combination of the terms "Hodgkin lymphoma," "fertility preservation," "ovarian tissue cryopreservation," "oocyte cryopreservation," "embryo cryopreservation," and "gonadotropin-releasing hormone agonist." References and data from identified sources were searched and compiled to complete this review. RESULTS: Initial treatment of HL is often nonsterilizing; however, salvage therapy and conditioning for stem cell transplantation confer significant gonadotoxicity. Established fertility preservation options for pubertal females include embryo cryopreservation and oocyte cryopreservation. These options are contraindicated within 6 months of receipt of chemotherapy. Ovarian tissue cryopreservation is an option for patients who require salvage therapy within 6 months of first-line therapy. CONCLUSIONS: Timing and choice of fertility preservation techniques depends on planned first-line chemotherapy and response to treatment. In patients initially treated with low-risk chemotherapy, it is reasonable to defer invasive fertility techniques until treatment failure; however, upfront fertility preservation should be considered in patients planning to undergo primary treatment with high-risk therapy.