Scholarly activity following National Institutes of Health Women's Reproductive Health Research K12 training-a cohort study.

BACKGROUND: National Institutes of Health funding to address basic reproductive health for common female conditions remains disproportionately low, in part because of low success rates of grant applications by obstetrician-gynecologists. OBJECTIVE: This study aimed to evaluate the scholarly productivity of individuals supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Women's Reproductive Health Research K12 career development award, created to advance careers of obstetrician-gynecologist physician-scientists. STUDY DESIGN: We performed a cohort study of individuals who completed at least 2 years of Women's Reproductive Health Research training by June 30, 2015, and had at least 5-year follow-up. Earliest training start date was December 1, 1998. Primary outcomes from public data sources (National Institutes of Health RePORTER, PubMed, iCite) were (1) number of total and R01 National Institutes of Health grants as principal investigator; (2) numbers of total and first and last author publications; and (3) median and highest publication impact factor measured by the relative citation ratio. Secondary outcomes from an email survey subcohort were total number of research grants, federally funded grants, and number of National Institutes of Health grants as coinvestigator; institutional promotions and academic appointments, national and National Institutes of Health leadership roles; and career and mentorship satisfaction. Outcomes were recorded at 5, 10, and 15 years postgraduation, and aggregate anonymized data were divided into 3 groups using Women's Reproductive Health Research completion dates: June 30 of 2005, 2010, and 2015. Temporal trends were assessed. Results were stratified by gender, number of awarded grant cycles (1-2 vs 3-4), and specialty type. Analyses used Fisher exact or Pearson chi-square tests, and Mantel-Haenszel tests of trend. RESULTS: The distribution of the cohort (N=178) by graduation completion date was: on or before June 30, 2005 (57 [32%]); July 1, 2005 to June 30, 2010 (60 [34%]); and July 1, 2010 to June 30, 2015 (61 [34%]). Most participants were female (112 [64%]) and maternal-fetal medicine trained (53 [30%]), followed by no fellowship (50 [28%]). Of the 178 participants, 72 (40%) received additional National Institutes of Health funding as a principal investigator, 45 (25%) received at least 1 R01, and 23 (13%) received 2 to 5 R01s. There were 52 (31%) scholars with >10 first author publications, 66 (39%) with >10 last author publications, and 108 (63%) with ≥25 publications. The highest relative citation ratio was a median of 8.07 (interquartile range, 4.20-15.16). There were 121 (71%) scholars with relative citation ratio ≥5, indicating >5-fold greater publication impact than that of other National Institutes of Health-funded scientists in similar areas of research. No differences by gender, institution, or temporal trends were observed. Of the full cohort, 69 (45.7%) responded to the survey; most self-identified as women (50 [73%]) and White (51 [74%]). CONCLUSION: Our findings suggest that the infrastructure provided by an institutional K award is an advantageous career development award mechanism for obstetrician-gynecologists, a group of predominantly women surgeons. It may serve as a corrective for the known inequities in National Institutes of Health funding by gender.

Timing and duration of bevacizumab treatment and survival in patients with recurrent ovarian, fallopian tube, and peritoneal cancer: a multi-institution study.

Bevacizumab has demonstrated significant benefit in recurrent ovarian, fallopian tube and peritoneal cancer (OC), but its optimal position within the sequence of systemic therapies remains controversial. Since rebound progression after bevacizumab has been observed in other cancers, and because bevacizumab is incorporated in several regimens used in the recurrent setting, the duration of treatment may impact survival. We sought to identify whether earlier bevacizumab exposure is associated with prolonged bevacizumab therapy and survival by conducting a multi-institution retrospective study of recurrent OC patients treated with bevacizumab from 2004-2014. Multivariate logistic regression identified factors associated with receiving more than six bevacizumab cycles. Overall survival by duration and ordinal sequence of bevacizumab therapy were evaluated using logrank testing and Cox regression. In total, 318 patients were identified. 89.1% had stage III or IV disease; 36% had primary platinum resistance; 40.5% received two or fewer prior chemotherapy regimens. Multivariate logistic regression demonstrated that primary platinum sensitivity (Odds Ratio (OR) 2.34, p = 0.001) or initiating bevacizumab at the first or second recurrence (OR 2.73, p < 0.001) were independently associated with receiving more than six cycles of bevacizumab. Receiving more cycles of bevacizumab was associated with improved overall survival whether measured from time of diagnosis (logrank p < 0.001), bevacizumab initiation (logrank p < 0.001), or bevacizumab discontinuation (logrank p = 0.017). Waiting one additional recurrence to initiate bevacizumab resulted in a 27% increased hazard of death (Hazard Ratio (HR) 1.27, p < 0.001) by multivariate analysis. In conclusion, patients with primary platinum sensitive disease who received fewer prior lines of chemotherapy were able to receive more cycles of bevacizumab, which was associated with improved overall survival. Survival worsened when bevacizumab was initiated later in the ordinal sequence of therapies.

How does patient-centered communication in ovarian cancer care enhance patient well-being? A mixed methods study.

OBJECTIVE: Greater perceived patient-centered communication (PCC) is associated with better health-related quality of life (HRQoL) in patients with ovarian cancer. Quantitative measures of PCC and HRQoL do little to explain this association. We interviewed patients with high and low ratings of PCC to understand how it is associated with HRQoL. METHODS: Explanatory sequential mixed methods study. Participants were English-speaking U.S. adults with ovarian cancer. We assessed PCC with the Patient-Centered Communication - Cancer (PCC-Ca)-36 (possible score range 1-5; higher scores represent greater patient-centeredness), and purposively sampled 14 participants with total scores in the top and bottom quartiles. Participants completed individual, semi-structured interviews about their communication experiences. Guided by the National Cancer Institute Framework for PCC in Cancer Care, we analyzed interview transcripts using directed content analysis. We integrated survey and interview findings in a joint display. RESULTS: Among 176 survey respondents, PCC-Ca-36 total scores ranged from 1.7 to 5.0. Participants with scores in the top quartile (4.8-5.0) perceived clinicians as proactive and attentive to psychosocial concerns. Those with scores in the bottom quartile (1.7-3.5) described not feeling known as an individual and receiving limited support for self-management. CONCLUSIONS: The association between PCC and QoL may be partially explained by differences in perceived support for psychosocial concerns and self-management. PCC may facilitate receipt of proactive, personalized care.

Perceived patient-centered communication, quality of life, and symptom burden in individuals with ovarian cancer.

OBJECTIVE: To describe perceptions of patient-centered communication (PCC); assess whether physician specialty, patient characteristics, or health system characteristics are associated with PCC; and identify associations between PCC, health-related quality of life (HRQoL), and symptom burden among individuals with ovarian cancer. METHODS: Cross-sectional, descriptive survey of English-speaking adults with ovarian cancer. PCC, HRQoL, and ovarian cancer symptom burden were assessed with the PCC-Ca-36, the FACT-G, and the FOSI-18, respectively. PCC-Ca-36 scores were summarized using descriptive statistics. Predictors of PCC-Ca-36, FACT-G, and FOSI-18 scores were identified using multiple linear regression. RESULTS: Participants (n = 176) had a mean age of 59.4 years (SD = 12.1). The majority (65.9%) had advanced-stage disease, while 42.0% were receiving treatment. The mean PCC-Ca-36 total score was 4.09 (SD = 0.78) out of a possible 5, indicating participants often perceived that clinicians engaged in PCC. Among the PCC functions, participants reported that clinicians least often enabled patient self-management (M = 3.65, SD = 0.99), responded to emotions (M = 3.84, SD = 1.04), and managed uncertainty (M = 3.91, SD = 0.93). In multivariable analyses, neither physician specialty nor patient and health system characteristics were significantly associated with overall PCC. Greater overall PCC predicted better overall HRQoL; better social/family, emotional, and functional well-being; and lower overall and physical symptom burden (all p ≤ 0.05). CONCLUSION: Greater PCC is significantly associated with better HRQoL and lower symptom burden among individuals with ovarian cancer. PRACTICE IMPLICATIONS: Promotion of PCC is a promising strategy to improve patient-reported outcomes in the ovarian cancer care setting.

Reengineering academic departments of obstetrics and gynecology to operate in a pandemic world and beyond: a joint American Gynecological and Obstetrical Society and Council of University Chairs of Obstetrics and Gynecology statement.

The coronavirus disease 2019 pandemic has significantly disrupted operations in academic departments of obstetrics and gynecology throughout the United States and will continue to affect them in the foreseeable future. It has also created an environment conducive to innovation and the accelerated implementation of new ideas. These departments will need to adapt their operations to accommodate coronavirus disease 2019 and to continue to meet their tripartite mission of clinical excellence, medical education, and women's health research. This "Call to Action" paper from the leaders of American Gynecological and Obstetrical Society and Council of University Chairs of Obstetrics and Gynecology provides a framework to help the leaders of departments of obstetrics and gynecology reimagine and reengineer their operations in light of the current coronavirus disease 2019 crisis and future pandemics.

The end of life costs for Medicare patients with advanced ovarian cancer.

OBJECTIVE: To describe the Medicare payments at the end of life for patients with advanced ovarian cancer, and assess factors responsible for payment variation METHODS: Using the linked Surveillance, Epidemiology and End Results (SEER)-Medicare database, we identified a cohort of women with stage III/IV epithelial ovarian cancer diagnosed between 1995 and 2007. We defined the end of life as the last 90days prior to death. Total medical costs were estimated from overall Medicare payments, and adjusted for geography and for inflation to the 2009 U.S. dollar. A generalized linear regression was performed to assess factors associated with variability in cost. RESULTS: Of 5509 patients, 78.9% died from ovarian cancer. In the 90days prior to death, 65.2% of patients had an inpatient admission, 53.7% received chemotherapy, 19.3% had a palliative procedure, and 62.5% had hospice services. The mean total payment per patient in the last 90days of life was $24,073 (range 0-$484,119) over the study time period. The mean cost of inpatient admissions was $14,529 (range 0-$483,932). On a multivariate analysis, costs at the end of life did not vary based on length of patient survival (p=0.77). Factors associated with significantly increased costs in the last 90days of life were medical comorbidity, chemotherapy, time spent as an inpatient, and admissions associated with emergency room visits. CONCLUSIONS: Reducing the prescription of chemotherapy and increasing the use of hospice services for ovarian cancer patients at the end of life will aid in lowering costs.

Combined symptom index and second-generation multivariate biomarker test for prediction of ovarian cancer in patients with an adnexal mass.

OBJECTIVE: To assess the performance of a symptom index (SI) and multivariate biomarker panel in the identification of ovarian cancer in women presenting for surgery with an adnexal mass. STUDY DESIGN: Prospective study of patients seen at a tertiary medical center. Following consent, patients completed an SI and preoperative serum was collected for individual markers (CA 125) and a second-generation FDA-cleared biomarker test (MIA2G). Results for the SI and MIA2G were correlated with operative findings and surgical pathology. Logistic regression modeling was performed to assess the interaction of the SI with MIA2G to determine the risk of malignancy (ROM). RESULTS: Of the 218 patients enrolled, the mean age was 53.6 years (range 18-86). One-hundred and forty-seven patients (67.4%) were postmenopausal. Sixty-four patients (29.4%) had epithelial ovarian cancer or fallopian tube cancer (EOC/FTC) and 17 (7.8%) had borderline ovarian tumors. A positive SI or MIA2G correctly identified 96.1% of patients with EOC/FTC. Using logistic regression, we found that both SI and MIA2G score were significantly associated with ROM (p < 0.001). In a simulation with disease prevalence set at 5%, patients with a negative SI and a MIA2G score of 6 had a ROM of 1.8% whereas patients with the same MIA2G and positive SI had a 10.5% ROM, nearly a 6-fold higher risk. CONCLUSIONS: The combination of a patient-reported symptom index and refined biomarker panel allows for improved accuracy in the assessment for ovarian cancer in patients with an adnexal mass. This strategy could offer a personalized approach to addressing ROM to triage patients with an adnexal mass to appropriate care.

Role of bleeding recognition and evaluation in Black-White disparities in endometrial cancer.

BACKGROUND: Advanced stage at diagnosis is an independent, unexplained contributor to racial disparity in endometrial cancer. OBJECTIVE: We sought to investigate whether, prior to diagnosis, provider recognition of the cardinal symptom of endometrial cancer, postmenopausal bleeding, differs by patient race. STUDY DESIGN: Black and White women diagnosed with endometrial cancer (2001 through 2011) from Surveillance, Epidemiology, and End Results-Medicare who had at least 2 years of claims prior to diagnosis were identified. Bleeding diagnoses along with procedures done prior to diagnosis were captured via claims data. Multinomial logistic regression was used to evaluate the association of race with diagnostic workup and multivariate models built to determine the association of appropriate diagnostic procedures with stage at diagnosis. RESULTS: In all, 4354 White and 537 Black women diagnosed with endometrial cancer were included. Compared to White women, Black women were less likely to have guideline-concordant care: postmenopausal bleeding and appropriate diagnostic evaluation (70% vs 79%, P < .001), with adjusted relative risk ratios of 1.12-1.73 for different nonguideline-concordant pathways: bleeding without diagnostic procedures, alternative bleeding descriptions, and neither bleeding nor procedures. These pathways were associated with higher odds of advanced stage at diagnosis (adjusted odds ratio, 1.90-2.88). CONCLUSION: The lack of recognition and evaluation of postmenopausal bleeding is associated with advanced stage at diagnosis in endometrial cancer. Older Black women are at highest risk for the most aggressive histology types, yet they are less likely to have guideline-concordant evaluation of vaginal bleeding. Efforts aimed at improving recognition-among patients and providers-of postmenopausal bleeding in Black women could substantially reduce disparities in endometrial cancer.

Robotic, Laparoscopic, or Open Hysterectomy: Surgical Outcomes by Approach in Endometrial Cancer.

STUDY OBJECTIVES: To compare patient outcomes by surgical approach in the management of endometrial cancer (EC) in Washington State from 2008 to 2013. DESIGN: Population-based retrospective cohort study (Canadian Task Force classification II-2). SETTING: Washington State. PATIENTS: EC patients treated with robotic-assisted surgery (RAS), laparoscopy (LS), or laparotomy (XLAP). INTERVENTIONS: Comprehensive Hospital Abstract Reporting System to identify patients and assess the association of surgical approach with length of stay, readmissions, and perioperative complications. MEASUREMENTS AND RESULTS: We identified 3712 cases of EC managed with either RAS, LS, or XLAP. Mean length of stay was not clinically different for RAS (1.5 days) and LS (1.6 days) but was 2.31 days longer for XLAP compared with LS (p < .001). Odds of any readmission did not differ for either RAS or XLAP compared with LS; however, early readmissions were half as likely for RAS compared with LS (p = .014). Complications were more than 2.5 times as likely for XLAP versus LS (p < .001), whereas complications did not differ for RAS versus LS (p = .931). CONCLUSIONS: RAS is as an alternative to LS in the treatment of EC and is preferable to XLAP. The use of RAS resulted in fewer early readmissions compared with LS and resulted in an increased proportion of cases via minimally invasive surgery.

Since surgery isn't getting any easier, why is reimbursement going down? An update from the SGO taskforce on coding and reimbursement.

In 2015, there was an 18% reduction in the Relative Value Units (RVUs) that the Center for Medicare and Medicaid Services (CMS) assigned to the Current Procedural Terminology (CPT) code 58571 (Laparoscopy, surgical, with total hysterectomy, for uterus 250g or less; with removal of tube(s) and/or ovary(s)→TLH+BSO). The other CPT codes for laparoscopic hysterectomy and laparoscopic supracervical hysterectomy (58541-58544 and 58570-58573) lost between 12 and 23% of their assigned RVUs. In 2016, the laparoscopic lymph node dissection codes 38570 (Laparoscopy, surgical; with retroperitoneal lymph node sampling (biopsy), single or multiple), 38571 (Laparoscopy, surgical; with bilateral total pelvic lymphadenectomy), and 38572 (Laparoscopy, surgical; with bilateral total pelvic lymphadenectomy and para-aortic lymph node sampling (biopsy), single or multiple) lost between 5.5 and 16.3% of their RVU's. The goals of this article from the Society of Gynecologic Oncology (SGO) Task force on Coding and Reimbursement are 1) to inform the SGO members on why CMS identified these codes as a part of their misvalued services screening program and then finalized a reduction in their payment levels; and 2) outline the role individual providers have in CMS' methodology used to determine the reimbursement of a surgical procedure.

Combining a symptom index, CA125 and HE4 (triple screen) to detect ovarian cancer in women with a pelvic mass.

OBJECTIVES: To assess a simple algorithm of CA125, HE4 and Symptom Index to predict ovarian cancer in women with a pelvic mass. METHODS: This was a prospective study of women referred to a gynecologic oncology clinic for surgical evaluation of a pelvic mass. Preoperatively, women completed a SI and had serum markers drawn. Results were correlated with pathology. A triple screen was considered positive if at least 2 of the 3 markers were abnormal (positive SI, CA125≥35U/mL, HE4≥140pmol/L). RESULTS: 218 patients enrolled in the study. 66 patients (30%) had ovarian or fallopian tube cancer (97% epithelial), 124 (57%) had benign masses, 17 (8%) had borderline tumors, and 11 (5%) had metastatic disease. The SI, CA125 and HE4 were positive in 87.9%, 74.2% and 60.6% of ovarian cancer patients, respectively. Of the 112 women with a positive SI 58 (52%) had ovarian cancer and 75 (67%) had non-benign masses. Excluding borderline and metastatic cancers the sensitivity of the triple screen was 79%; specificity 91%, PPV 83% and NPV 89%. CA125 alone had a sensitivity, specificity, PPV and NPV of 79%, 76%, 63% and 87% respectively. Requiring only one of the three tests to be abnormal resulted in a sensitivity of 97% but specificity dropped to 50%. CONCLUSIONS: An algorithm using SI, CA125 and HE4 has good performance statistics for predicting cancer in women with pelvic masses. The triple screen has higher specificity and PPV than CA125 alone but similar sensitivity and NPV for predicting ovarian cancer.

Phase II trial of albumin-bound paclitaxel and granulocyte macrophage colony-stimulating factor as an immune modulator in recurrent platinum resistant ovarian cancer.

BACKGROUND: Granulocyte macrophage colony-stimulating factor (GM-CSF) stimulates immunity via recruitment of antigen presenting cells and tumor specific T-cell stimulation. Albumin-bound paclitaxel (nab-paclitaxel) followed by GM-CSF may enhance antitumor responses and prolong remissions in ovarian cancer. Immune phenotypes present before treatment may identify responders to chemo-immunotherapy. METHODS: Recurrent platinum-resistant ovarian, peritoneal, or fallopian tube cancer patients received nab-paclitaxel, 100mg/m2 days 1, 8, 15 followed by GM-CSF 250µg days 16-26 every 28days for 6 planned cycles. The primary endpoint was remission duration compared to immediate prior remission. Peripheral blood was evaluated by flow cytometry and interferon-γ ELISPOT. RESULTS: Twenty-one patients were enrolled. Six patients (29%) achieved a biochemical complete response and 9 (43%) a partial response for an overall response rate of 72%. Median time to progression was 4months and 10% of patients achieved longer remissions than the immediate prior regimen. Median overall survival (OS) was 16.8months. Fewer myeloid derived suppressor cells (MDSC) at enrollment significantly associated with complete response (p=0.05). T-cell responses to IGF1R-p1332-1346 (r=0.827, p=0.0003) and IGF1R-p1242-1256 (r=0.850, p=0.0001) during treatment correlated with time to progression. CONCLUSIONS: Nab-paclitaxel combined with GM-CSF demonstrated biochemical responses in a majority of patients, although responses were not sustained. This combination did not demonstrate an advantage in OS over prior studies of nab-paclitaxel monotherapy. Agents that modulate MDSC should be studied as potential adjuvants to therapy. Strategies to expand T cells recognizing tumor-associated antigens biologically significant in ovarian cancer should also continue to be investigated.

Evaluation of a Validated Biomarker Test in Combination With a Symptom Index to Predict Ovarian Malignancy.

OBJECTIVE: This study aimed to evaluate the predictive ability of a multivariate biomarker test in combination with a symptom index (SI) to identify ovarian cancer in a cohort of women planning to undergo surgery for a pelvic mass. METHODS: This was a prospective study of patients seen at a tertiary care medical center. Following consent, patients completed an SI and preoperative serum was collected for a Food and Drug Administration-cleared multivariate biomarker test [multivariate index assay (MIA)]. Results for the SI and MIA were correlated with operative findings and surgical pathology. RESULTS: Of 218 patients enrolled, 124 (56.9%) had benign disease and 94 (43.1%) had borderline tumors or carcinomas. Sixty-six patients had a primary ovarian or fallopian tube cancer. The median age of patients enrolled in this study was 54 years (interquartile range, 44-63 years), of whom 148 (67.9%) were postmenopausal. More than a third (36.3%) of patients with benign masses was accurately identified as low risk by MIA and SI. The sensitivity and negative predictive value (NPV) of the SI relative to primary ovarian cancer was 87.9% (95% CI, 77.9%-93.7%) and 91.6% (95% CI, 84.3%-95.7%), respectively. The sensitivity and NPV of CA125 was 75.4% (95% CI, 63.7%-84.2%) and 86.4% (95% CI, 79.1%-91.5%), respectively, and the sensitivity and NPV of the MIA were 93.9% (95% CI, 85.4%-97.6%) and 94.5% (95% CI, 94.5%-100%), respectively. The overall sensitivity for the combination of MIA plus SI was 100% (66/66; 95% CI, 94.5%-100%), and specificity was 36.3% (45/124; 95% CI, 28.4%-45.0%), with an NPV of 100% (95% CI, 92.1%-100%). CONCLUSIONS: The addition of a patient-reported SI, which captures subjective symptoms in an objective manner, improved the sensitivity of MIA across all stages and subtypes of ovarian cancer.

Preoperative hyponatremia in women with ovarian cancer: An additional cause for concern?

OBJECTIVE: To determine if preoperative hyponatremia in women with ovarian, fallopian tube (FT), and primary peritoneal cancers (PPC) is associated with postoperative complications. METHODS: We performed a retrospective population-based cohort study of women with a postoperative diagnosis of ovarian, FT, or PPC who had a cytoreductive procedure in the National Surgical Quality Improvement Program (NSQIP) database from 2005 to 2013. The primary exposure, preoperative sodium, was classified as normal (135mEq/L-142mEq/L) or hyponatremic (≤134mEq/L). Where appropriate, preoperative characteristics were compared with Chi-squared or Fisher's exact tests. Multivariate logistic regression was used to determine adjusted odds ratios (aOR) with 95% confidence intervals (CI). RESULTS: 4009 subjects met inclusion criteria. Thirty day mortality was higher in the hyponatremic group compared to the normal serum sodium group (3.56% vs 1.18%). When patients of any age were noted to have at least two pertinent preoperative lab abnormalities, including hyponatremia, there was an increased risk of postoperative complications for patients over the age of 65 (Table 3). After adjusting for serum albumin and other confounders, preoperative hyponatremia was associated with an increased risk of hospital stay of >14days (aOR 1.69; 95% CI 1.11-2.57) and 30day postoperative mortality (aOR 2.37; 95% CI 1.13-4.98). CONCLUSIONS: Hyponatremia is associated with postoperative 30day mortality and morbidity in women with ovarian, FT, and PPC. Serum sodium in conjunction with other markers may have the potential to identify candidates for neoadjuvant chemotherapy. Additional work is needed to determine if correction of hyponatremia in the preoperative period alters outcomes.

Ovarian cancer outcomes: Predictors of early death.

OBJECTIVE: To describe the outcomes and mortality in advanced ovarian cancer patients in a population-based cohort in the 90 days after diagnosis. METHODS: Using the linked Surveillance, Epidemiology and End Results (SEER)-Medicare database, we identified a cohort of women with stage III/IV epithelial ovarian cancer diagnosed between 1995 and 2007. A χ(2) test was used to assess demographic and clinical factors. Kaplan-Meier curves and Cox proportional hazards models were used to assess factors associated with variation in survival. RESULTS: Of the 9491 patients with stage III/IV ovarian cancer identified from the SEER/Medicare system, 4131 (43.6%) patients died in the first year after diagnosis. Of these, 2472 (26.0%) patients died in the first 90 days after diagnosis. Over the study period, the number of patients who died in the first 90 days after diagnosis slightly increased (p=0.053). Older age (>75 years of age), increased comorbidity, stage IV disease, lack of a visit with a gynecologic oncologist, and surgery were associated with an increase in 90-day mortality. Chemotherapy was associated with a reduction in 90-day mortality. CONCLUSIONS: Approximately 25% of patients with advanced ovarian cancer in our study period died within 90 days of diagnosis, and more than 40% died within the first year of diagnosis. In addition, a substantial proportion of patients did not receive any treatment. Further research into the characteristics of these patients should be performed to elucidate clinical areas for intervention to either prevent these poor outcomes or allocate appropriate resources to patients with extremely poor prognoses.

Neoplastic cellularity is associated with clinical and molecular features of high-grade serous ovarian carcinoma.

OBJECTIVE: Most molecular analyses of high-grade serous ovarian, peritoneal and fallopian tube carcinomas (HGSC) require ≥70% tumor (neoplastic) cell nuclei. We characterized the distribution of the percentage of neoplastic nuclei (PNN) in a large cohort of HGSC and correlated PNN with clinical outcomes to determine the fraction of cases outside this range and whether this cut-off introduces selection bias. METHODS: Subjects were prospectively enrolled and normal and neoplastic tissues were snap-frozen. All subjects had grade 2 to 3 HGSC. Subjects that received neoadjuvant chemotherapy were excluded. PNN was determined by estimating the fraction of neoplastic nuclei relative to non-neoplastic nuclei on a representative hematoxylin and eosin stained frozen section from the primary neoplasm. Germline BRCA mutation status was determined with Sanger or BROCA sequencing. RESULTS: PNN was <70% in 101 (33%) of 306 cases. PNN was significantly higher among subjects without optimal cytoreduction (P=0.018). 55 subjects had germline BRCA1/BRCA2 mutations. HGSC associated with BRCA2 but not BRCA1 mutations had significantly lower PNN compared to HGSC in non-carriers (54% vs. 70%, P=0.018). Overall survival was not significantly different between subjects with <70% or ≥70% PNN (median survival 51.8 vs. 46.6months, P=0.858). CONCLUSIONS: One-third of HGSC has PNN <70%. Higher PNN is associated with suboptimal cytoreduction, while lower PNN is associated with inherited BRCA2 mutations. Our findings suggest a nonrandom distribution of PNN that may reflect cancer biology. Further studies exploring the stromal microenvironment are needed. Molecular analyses of HGSC selected for high PNN exclude a significant fraction of patients.

Route of hysterectomy and surgical outcomes from a statewide gynecologic oncology population: is there a role for vaginal hysterectomy?

BACKGROUND: Recent policy changes by insurance companies have been instituted to encourage vaginal hysterectomy (VH) as the preferred route for removal of the uterus. It is not known if advantages of VH for benign indications apply to women with gynecologic cancer. OBJECTIVE: The goal of this study was to assess trends in surgical approach to hysterectomy among gynecologic cancer patients and to evaluate outcomes by approach. We hypothesized that, among gynecologic oncology patients, postoperative complications and hospital stay would differ by surgical approach, and that advantages of VH for benign indications may not apply to gynecologic cancer patients. STUDY DESIGN: We performed a population-based retrospective cohort study of cervical, endometrial, or ovarian/fallopian tube cancer patients treated surgically in Washington State from 2004 through 2013 using the Comprehensive Hospital Abstract Reporting System. Surgery was categorized as abdominal hysterectomy (AH), laparoscopic hysterectomy (LH), or VH. We determined rate of surgical approach by year and the association with length of stay, 30-day readmission rate, and perioperative complications. RESULTS: We identified 10,117 patients who underwent surgery for gynecologic cancer, with 346 (3.4%) VH, 2698 (26.7%) LH, and 7073 (69.9%) AH. Patients undergoing AH had more comorbidities than patients with VH or LH (Charlson Comorbidity Index ≥2: 11.3%, 7.9%, and 8.1%, respectively; P < .001). From 2004 through 2013 AH and VH declined (94.4-47.9% and 4.4-0.8%, respectively; P < .001) while LH increased from 1.2-51.4% in 2013 (P < .001). Mean length of stay was 4.6 days for women undergoing AH and was 1.9 days shorter for VH (95% confidence interval, 1.6-2.3 days) and 2.6 days shorter for LH (95% confidence interval, 2.4-2.7 days) (P < .001). Risk of 30-day readmission for patients undergoing LH was 40% less likely compared to AH but not different for VH vs AH. CONCLUSION: AH and LH remain the preferred routes for hysterectomy in gynecologic oncology. Over the past decade, there has been a significant shift to LH with lower 30-day readmission and complication rates. There may be a limited role for VH in select patients. Current efforts to standardize the surgical approach to hysterectomy should not apply to patients with known or suspected gynecologic cancer.

The Cost of Initial Care for Medicare Patients With Advanced Ovarian Cancer.

OBJECTIVES: In preparation for payment reform, we evaluated Medicare payments for the initial treatment of patients with advanced ovarian cancer and assessed factors responsible for variation. METHODS: Using the linked SEER-Medicare database, we identified a cohort of 9,491 women aged 65 years or older with stage III/IV epithelial ovarian cancer diagnosed between 1995 and 2007. Diagnostic and procedural codes specific to the care of ovarian cancer were used to estimate total medical costs for the treatment of ovarian cancer. Costs were adjusted for geography and for inflation to the 2009 US dollar. NCCN Guideline-consistent care was defined as surgery and 6 cycles of chemotherapy. A generalized linear regression was performed to assess factors associated with variability in cost. RESULTS: The mean total payment per patient in the initial treatment period was $65,908 (range of means, $30,745-$96,360). Increasing medical comorbidity, use of PET/CT, surgical complications, and readmissions were associated with increased costs. Treatment with NCCN Guideline-consistent surgery and chemotherapy had a mean annual cost of $85,987 compared with $89,149 for non-NCCN Guideline-consistent treatment with surgery and chemotherapy. The cost of surgery and chemotherapy that was not consistent with NCCN Guidelines was approximately $7,000 more than the cost of therapy that was consistent (P<.001) CONCLUSIONS: The financial burden of caring for patients with ovarian cancer is substantial. Treatment that is consistent with NCCN recommendations for treating advanced ovarian cancer, which is shown to have improved outcomes, is not associated with higher cost.