Cancer-associated thrombosis by cancer sites and inherited factors in a prospective population-based cohort.

Cancer-associated thrombosis (CAT) is common and associated with mortality. We estimated CAT rate by cancer sites and inherited factors among cancer patients from the UK Biobank (N =70,406). The 12-month CAT rate after cancer diagnosis was 2.37% overall but varied considerably among cancer sites. Among the 10 cancer sites classified as 'high-risk' of CAT by the National Comprehensive Cancer Network guidelines, 6 had CAT rate <5%. In contrast, 5 cancer sites classified as 'average-risk' by the guidelines had CAT rate >5%. For inherited risk factors, both known mutation carriers in two genes (F5/F2) and polygenic score for venous thromboembolism (VTE) (PGSVTE) were independently associated with increased CAT risk. While F5/F2 identified 6% patients with high genetic-risk for CAT, adding PGSVTE identified 13 % patients at equivalent/higher genetic-risk to CAT than that of F5/F2 mutations. Findings from this large prospective study, if confirmed, provide critical data to update guidelines for CAT risk assessment.

Surviving and thriving: What do survivors of gynecologic cancer want?

The purpose of this study was to characterize survivorship concerns and survivorship program preferences among gynecologic cancer survivors. Women treated for gynecologic malignancy at our cancer center were surveyed from 1/2019 to 10/2020 on concerns and preferences using a 5-point Likert scale. Descriptive analysis and multivariable logistic regression were performed to describe survivors' concerns/preferences. The most frequent survivorship concerns were fear of cancer recurrence (49.6%), desire to lose weight (40.0%), and long-term side effects (30.7%). The highest ranked survivorship program components included assistance with nutrition (36.5%), weight loss (30.4%), and stress reduction (29.0%). Older patients (≥64 y) were less likely to report concern with losing weight (OR 0.26, p < 0.05), sex life (OR 0.18, p < 0.01), and strain in family relationships (OR 0.27, p < 0.05) compared with younger patients. Compared with ovarian/fallopian tube/primary peritoneal cancer survivors, endometrial cancer survivors were less likely to desire nutritional education (OR 0.06, p < 0.01). Participants with advanced cancer were less likely to desire assistance with weight loss than those with early stage cancer (OR 0.23, p < 0.05). A significant portion of gynecologic cancer survivors reported a fear of cancer recurrence. Assistance with nutrition and weight loss were the most desired survivorship program components. Variation in patient preferences and differences among clinical subgroups highlight the need for tailored survivorship care.

Outcomes after targeted treatment based on somatic tumor genetic testing for women with gynecologic cancers.

OBJECTIVE: Molecular tumor profiling and next-generation sequencing are being increasingly utilized, but there are limited data on the therapeutic implications and potential benefits of targeted treatments. We aim to characterize gynecologic oncology patients referred for somatic tumor genetic mutation testing and assess survival outcomes, efficacy, and toxicities of those receiving targeted therapy. METHODS: We conducted a retrospective chart review of gynecologic oncology patients referred for somatic tumor testing by next generation sequencing between 1/1/2012-8/23/2019. The primary objective was to compare overall and progression free survival between those treated with targeted therapy (group 1) versus traditional treatment (group 2). RESULTS: Most patients (70%) had additional treatment options available based on actionable mutations. The median number of somatic mutations identified was 5 (range 0-53). Patients in group 1 had more actionable somatic mutations (median 2 versus 0, p < 0.001). There was no difference in OS (median 64 versus 76 months, p = 0.97) or PFS (median 2 versus 8 months, p = 0.05) between the groups. While fewer patients in group 1 experienced neuropathy (0 versus 5, p = 0.02), grade I/II thrombocytopenia (7 versus 13, p = 0.03), grade III/IV thrombocytopenia (0 versus 4, p = 0.02), and grade III/IV neutropenia (1 versus 9, p = 0.002), all other non-hematologic toxicities were similar in the two groups. CONCLUSIONS: Most gynecologic cancer patients have actionable mutations and may benefit from a personalized targeted therapy treatment plan. Next generation sequencing can be used to identify clinically actionable mutations in gynecologic cancers and guide the selection of treatments, thereby expanding treatment options without worsening survival or toxicity.

Estrogen hormone replacement therapy in incidental intracranial meningioma: a growth-rate analysis.

Incidental meningiomas (IMs) are the most common intracranial neoplasms, especially in perimenopausal women. There is ongoing debate on whether their incidence is increased by hormone replacement therapy. Meningiomas often express estrogen receptors, which were linked to higher proliferative activity according to some reports. Consequently, there is a theoretical risk of estrogen-based HRT (e-HRT) leading to an increase in tumor growth and thus altering the natural history of IMs. However, clinical data is lacking to support this notion. To identify differences in the natural history of IM after e-HRT exposure. We queried the NorthShore Meningioma Database for patients with ≥ 6 months of e-HRT. They were compared with age-matched IM controls. Forty patients were included in the e-HRT group (mean age 62.1 ± 12.0 years; mean duration of HRT 5.3 ± 4.5 years) and 80 in the no-HRT group (mean age 62.2 ± 12 years). Radiographic appearance was similar between groups. The average 2D tumor diameter was 35% lower in the e-HRT group (p = 0.02), with an absolute growth-rate of half of the no-HRT group (p = 0.02). Radiographic and clinical progression-free survival were 1.2 years and 3.3 years longer in the e-HRT group, respectively. These preliminary results suggest that e-HRT may be safe in incidental meningiomas.

Statin treatment is associated with survival in a nationally representative population of elderly women with epithelial ovarian cancer.

OBJECTIVE: Observational studies suggest that statin therapy for cardio-protection is associated with improved survival in cancer patients. We sought to evaluate the impact of statin treatment on ovarian cancer survival in a nationally representative elderly population. METHODS: The linked Surveillance, Epidemiology, and End Results (SEER) registries and Medicare claims data on patients diagnosed with epithelial ovarian cancer in 2007-2009 were used to extract data on statin prescription fills, population characteristics, primary treatment, comorbidity and survival. Cox regression models were used to examine the association between statin treatment and overall survival. RESULTS: Among the 1431 ovarian cancer patients who underwent surgical resection, 609 (42.6%) filled prescriptions for statin. The majority of statin-users (89%) were prescribed a lipophilic formulation. Mean overall survival among statin-users was 32.3months compared to 28.8months for non-users (p<0.0001). A 34% reduction in death was associated with statin therapy, independent of age, race, neighborhood median household income, stage, platinum therapy and comorbid conditions (HR=0.66, 95% CI 0.55-0.81). Improved overall survival with statin use was observed for both serous (HR=0.69, 95% CI 0.54-0.87) and non-serous (HR=0.63, 95% CI 0.44-0.90) histologies. When statin treatment was categorized by lipophilicity and intensity, a significant survival benefit was limited to lipophilic statin users and those who took statins of moderate intensity. CONCLUSIONS: This SEER-Medicare analysis demonstrates improvement in overall survival with lipophilic statin use after surgery in elderly patients with epithelial ovarian cancer. A clinical trial to evaluate the impact of statin treatment in ovarian cancer survival is warranted.

Digoxin therapy is not associated with improved survival in epithelial ovarian cancer: A SEER-Medicare database analysis.

OBJECTIVES: Both in vitro and clinical trial data suggest that cardiac glycosides demonstrate a synergistic anti-tumor effect when administered with platinum chemotherapy. Epidemiologic studies have also demonstrated improved cancer survival in colorectal, breast, head and neck and hepatocellular carcinoma patients on digoxin therapy at the time of cancer treatment. We sought to determine whether digoxin improves survival in epithelial ovarian cancer patients treated with platinum. METHODS: Surveillance, Epidemiology and End-Results (SEER) tumor registries program data on ovarian cancer patients diagnosed in 2007-2009 were linked to Medicare claims data to capture platinum administration, digoxin use and cardiac comorbidities. We analyzed 762 patients who underwent cancer-directed surgery and received platinum chemotherapy. Patients were considered digoxin users during platinum administration if a prescription was filled within 6months of cancer diagnosis. Cox proportional hazards regression models were used to determine the impact of digoxin use on overall survival (OS). RESULTS: Among 762 epithelial ovarian cancer patients treated with surgery and platinum chemotherapy, 53 (7%) used digoxin ever and 38 (5%) used digoxin specifically during platinum administration. Adjusting for age, heart disease and Charlson comorbidity score, digoxin use was not associated with OS (HR=1.29, 95% CI 0.81, 2.06). CONCLUSIONS: In this SEER-Medicare database analysis, digoxin use during chemotherapy was not associated with improved OS outcomes in patients with epithelial ovarian cancer treated with surgery and platinum chemotherapy. These conclusions are limited, however, by a small sample size and bias intrinsic to claims-based data and should be further evaluated in a larger cohort.

An analysis of current treatment practice in uterine papillary serous and clear cell carcinoma at two high volume cancer centers.

OBJECTIVE: Despite the rarity of uterine papillary serous carcinoma (UPSC) and uterine clear cell carcinoma (UCCC), they contribute disproportionately to endometrial cancer deaths. Sufficient clinical information regarding treatment and prognosis is lacking. The aim of this study is to evaluate treatment outcomes in a rare cancer cohort based on the experience at two tertiary care cancer centers. METHODS: Clinicopathologic data were retrospectively collected on 279 patients with UPSC and UCCC treated between 1995 to 2011. Mode of surgery, use of adjuvant treatment, and dissection of paraaoritc lymph nodes were evaluated for their association with overall survival (OS) and progression-free survival (PFS). RESULTS: 40.9% of patients presented with stage I disease, 6.8% of patients presented with stage II disease and 52.3% of patients presented with stages III and IV. Median follow-up was 31 months (range, 1 to 194 months). OS and PFS at 5 years were 63.0% and 51.9%, respectively. OS and PFS were not affected by mode of surgery (open vs. robotic approach; OS: hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.28 to 1.62; PFS: HR, 0.78; 95% CI, 0.40 to 1.56). Adjuvant treatment was associated with improved OS in stages IB-II (HR, 0.14; 95% CI, 0.02 to 0.78; p=0.026) but not in stage IA disease. There was no difference in OS or PFS based on the performance of a paraaoritc lymph node dissection. CONCLUSION: Minimally invasive surgical staging appears a reasonable strategy for patients with non-bulky UPSC and UCCC and was not associated with diminished survival. Adjuvant treatment improved 5-year survival in stages IB-II disease.

Angiogenic alterations associated with circulating neoplastic DNA in ovarian carcinoma.

OBJECTIVES: Forty percent of women with ovarian carcinoma have circulating free neoplastic DNA identified in plasma. Angiogenesis is critical in neoplastic growth and metastasis. We sought to determine whether circulating neoplastic DNA results from alterations in the balance of angiogenesis activators and inhibitors. METHODS: Sixty patients with invasive ovarian carcinomas with somatic TP53 mutations that had been characterized for circulating neoplastic DNA had carcinoma analyzed for microvessel density using immunohistochemistry with CD31 and for the expression of VEGF, ANGPT1, ANGPT2, PTGS2, PLAU, THBS1, CSF1, PIK3CA, HIF1A, IL8, MMP2, and MMP9 message by real-time quantitative polymerase chain reaction. The expression of each gene was calculated relative to GAPDH expression for each neoplasm. Patient plasma had been tested for circulating neoplastic DNA using a ligase detection reaction. RESULTS: MMP2 expression was significantly correlated with free plasma neoplastic DNA (P = .007). Microvessel density was not correlated with plasma neoplastic DNA or BRCA1/2 mutation status. The expression pattern of other angiogenic factors did not correlate with plasma neoplastic DNA but correlated with each other. BRCA1/2 mutated carcinomas had significantly different expression profiles of angiogenesis activators and inhibitors in comparison to sporadic carcinomas. CONCLUSIONS: MMP2 expression is associated with the presence of circulating neoplastic DNA in women with ovarian carcinoma. These data are consistent with the proinvasive properties of MMP2 and suggest that the presence of circulating neoplastic DNA indicates a more aggressive malignant phenotype. Carcinomas with germ line BRCA1/2 mutations had a lower angiogenic profile than those without mutations.

A self-administered family history questionnaire improves identification of women who warrant referral to genetic counseling for hereditary cancer risk.

OBJECTIVES: This study was undertaken to assess a self-administered family history questionnaire in order to better identify women within a gynecologic oncology practice for referral to genetic counseling services. METHODS: Returning patients at an outpatient gynecologic oncology clinic completed a self-administered family health history questionnaire and a detailed telephone interview. A genetic counselor separately assessed blinded information garnered from the questionnaire, structured genetic interview, and electronic medical records to determine whether these data warranted referral to genetic counseling based on established criteria. The structured genetic interview was considered the gold standard to which the questionnaire and medical record information were compared. RESULTS: Of the 45 total participants in the study, 26 (58%) were identified from the structured genetic interview as meeting criteria for referral to genetic counseling. The questionnaire identified 21 (81%) of these 26 referrals, while the medical record identified 13 (50%) of these 26 referrals. This led to a 62% increase in referral capture by the questionnaire. The median time to complete the questionnaire was 17 min (range 5-57 min). Thirty-four participants (75.6%) had more family members with cancer identified on the questionnaire compared to the electronic medical record. The questionnaire identified fewer family members with cancer in the five cases that were missed for appropriate referral. CONCLUSIONS: Current standard clinical practices are insufficient at identifying patients in need of referral to genetic counseling. A self-administered questionnaire improves recognition of candidates for genetic counseling in a gynecologic oncology practice.