K.N. Slaughter

The survival detriment of venous thromboembolism with epithelial ovarian cancer.

OBJECTIVE The aim of this study is to evaluate the effect of venous thromboembolism (VTE) chronology with respect to surgery on survival with epithelial ovarian cancer (EOC). METHODS An IRB approved, retrospective review was performed of patients treated for Stage I-IV EOC from 1996 to 2011. Cox proportional hazards model was used to assess associations between VTE and the primary outcomes of progression free survival (PFS) and overall survival (OS). SAS 9.3 was used for statistical analyses. RESULTS 586 patients met study criteria. Median age was 63 years (range, 17-94); median BMI was 27.1 kg/m(2) (range, 13.7-67.0). Most tumors were high grade serous (68.3%) and advanced stage (III/IV, 75.4%). 3.7% had a preoperative VTE; 13.2% had a postoperative VTE. Upon multivariate analysis adjusting for age, stage, histology, performance status, and residual disease, preoperative VTE was predictive of OS (HR 3.1, 95% CI: 1.6-6.1, p=0.001) but not PFS (p=0.55). Postoperative VTE was associated with shorter PFS (HR 1.45, 95% CI: 1.04-2.02, p=0.03) and OS (HR 1.8, 95% CI: 1.3-2.6, p=0.001). When VTE timing was modeled, preoperative VTE (HR 3.5, 95% CI: 1.8-6.9, p<0.001) and postoperative VTE after primary therapy (HR 2.3, 95% CI: 1.4-3.6, p=0.001) were predictive of OS. CONCLUSION Preoperative and postoperative VTE appear to have a detrimental effect on OS with EOC. When modeled as a binary variable, postoperative VTE attenuated PFS; however, when VTE timing was modeled, postoperative VTE was not associated with PFS. It is unclear whether VTE is an inherent poor prognostic marker or if improved VTE prophylaxis and treatment may enable similar survival to patients without these events.

Primary and acquired platinum-resistance among women with high grade serous ovarian cancer

OBJECTIVE Women with primary platinum resistant (PPR) high grade serous ovarian cancer (HGSOC) are known to have a poor prognosis. Less is known regarding outcomes in patients with acquired platinum resistance (APR). The goal of this study was to evaluate survival in both PPR and APR patients. METHODS A retrospective review of HGSOC patients diagnosed between 2000 and 2010 was performed. Descriptive statistics summarized clinical characteristics and demographics. The Kaplan-Meier method estimated progression free survival (PFS) and overall survival (OS). The association of OS and clinical factors was modeled using Cox proportional-hazards. RESULTS Of the 330 patients identified, 81 (25%) had PPR. Of the remaining women, 55 (22%) developed APR. Median PFS of PPR patients was 4.2months and median OS was 17.8months. On multivariate analysis, the number of biologic agents received was the only predictor of OS. Patients with APR had a median PFS of 14.2months and a median OS of 56months. OS from the date of platinum resistance was 21.9months, though this was not different than PPR patients (p=0.19). Multivariate analysis found cancer stage and clinical trial participation to be associated with OS. CONCLUSIONS Platinum resistance confers a poor prognosis in the APR and PPR setting. The number of biologic agents received is the strongest predictor of OS among women with PPR. Cancer stage and clinical trial participation predicts OS in patients with APR. Providing opportunities to participate in clinical trials, especially those involving targeted therapy, should be a priority in these populations.

Is age a prognostic biomarker for survival among women with locally advanced cervical cancer treated with chemoradiation? An NRG Oncology/Gynecologic Oncology Group ancillary data analysis

OBJECTIVE To determine the effect of age on completion of and toxicities following treatment of local regionally advanced cervical cancer (LACC) on Gynecologic Oncology Group (GOG) Phase I-III trials. METHODS An ancillary data analysis of GOG protocols 113, 120, 165, 219 data was performed. Wilcoxon, Pearson, and Kruskal-Wallis tests were used for univariate and multivariate analysis. Log rank tests were used to compare survival lengths. RESULTS One-thousand-three-hundred-nineteen women were included; 60.7% were Caucasian, 15% were age 60-70years and an additional 5% were >70; 87% had squamous histology, 55% had stage IIB disease and 34% had IIIB disease. Performance status declined with age (p=0.006). Histology and tumor stage did not significantly differ. Number of cycles of chemotherapy received, radiation treatment time, nor dose modifications varied with age. Notably, radiation protocol deviations and failure to complete brachytherapy (BT) did increase with age (p=0.022 and p<0.001 respectively). Only all grade lymphatic (p=0.006) and grade≥3 cardiovascular toxicities (p=0.019) were found to vary with age. A 2% increase in the risk of death for every year increase >50 for all-cause mortality (HR 1.02; 95% CI, 1.01-1.04) was found, but no association between age and disease specific mortality was found. CONCLUSION This represents a large analysis of patients treated for LACC with chemo/radiation, approximately 20% of whom were >60years of age. Older patients, had higher rates of incomplete brachytherapy which is not explained by collected toxicity data. Age did not adversely impact completion of chemotherapy and radiation or toxicities.

Central nervous system metastasis in gynecologic cancer: Symptom management, prognosis and palliative management strategies

INTRODUCTION CNS metastasis (CNSmet) with gynecologic malignancy (GM) is associated with poor prognosis and symptom burden. Two prognostic indices, the recursive partitioning analysis (RPA) and graded prognostic assessment (GPA), used in other solid tumors to guide intervention options were evaluated among GM patients. METHODS Retrospective chart review was performed to identify patients with primary GM diagnosed with CNSmet from 2005-2014. RPA and GPA were applied and evaluated for goodness of fit. Long-term survivors (LTS) were those with survival time from CNSmet ≥9 months. RESULTS 35 patients were identified with median age of 62 years (range, 41-78). The majority had ovarian cancer (54%). Median survival was 4.5 months (0.1-25.9), and median time from initial diagnosis was 2.6 years (0-19.6). Presenting symptoms varied but headache (57%) and altered mental status (23%) were most common. 37% had a solitary CNS lesion, 31% had 2-8, and 31% >8. 57% were treated with WBRT, 14% with stereotactic radiosurgery (SRS), and 20% with combinations of treatments, and 2 elected for hospice. 27% (9/33) of the patients were LTS. The GPA was not significantly associated with patient outcome (p=0.46). The RPA predicted time to death (p=.0010). CONCLUSION Prognostic indices used to guide therapeutic interventions perform poorly in GM. Detection and aggressive symptom management are critical in maintaining QOL. Multidisciplinary consultation is critical to optimize outcomes and symptom control.

Minimally invasive surgery for endometrial cancer: Does operative start time impact surgical and oncologic outcomes?

OBJECTIVE Recent literature in ovarian cancer suggests differences in surgical outcomes depending on operative start time. We sought to examine the effects of operative start time on surgical outcomes for patients undergoing minimally invasive surgery for endometrial cancer. METHODS A retrospective review was conducted of patients undergoing minimally invasive surgery for endometrial cancer at a single institution between 2000 and 2011. Surgical and oncologic outcomes were compared between patients with an operative start time before noon and those with a surgical start time after noon. RESULTS A total of 380 patients were included in the study (245 with start times before noon and 135 with start times after noon). There was no difference in age (p=0.57), number of prior surgeries (p=0.28), medical comorbidities (p=0.19), or surgical complexity of the case (p=0.43). Patients with surgery starting before noon had lower median BMI than those beginning after noon, 31.2 vs. 35.3 respectively (p=0.01). No significant differences were observed for intraoperative complications (4.4% of patients after noon vs. 3.7% of patients before noon, p=0.79), estimated blood loss (median 100 cc vs. 100 cc, p=0.75), blood transfusion rates (7.4% vs. 8.2%, p=0.85), and conversion to laparotomy (12.6% vs. 7.4%, p=0.10). There was no difference in operative times between the two groups (198 min vs. 216.5 min, p=0.10). There was no association between operative start time and postoperative non-infectious complications (11.9% vs. 11.0%, p=0.87), or postoperative infections (17.8% vs. 12.3%, p=0.78). Length of hospital stay was longer for surgeries starting after noon (median 2 days vs. 1 day, p=0.005). No differences were observed in rates of cancer recurrence (12.6% vs. 8.8%, p=0.39), recurrence-free survival (p=0.97), or overall survival (p=0.94). CONCLUSION Our results indicate equivalent surgical outcomes and no increased risk of postoperative complications regardless of operative start time in minimally invasive endometrial cancer staging, despite longer length of hospital stay for surgeries beginning after noon.

Geographic disparities in the distribution of the U.S. gynecologic oncology workforce: A Society of Gynecologic Oncology study

A recent ASCO workforce study projects a significant shortage of oncologists in the U.S. by 2020, especially in rural/underserved (R/US) areas. The current study aim was to determine the patterns of distribution of U.S. gynecologic oncologists (GO) and to identify provider-based attitudes and barriers that may prevent GOs from practicing in R/US regions. U.S. GOs (n = 743) were electronically solicited to participate in an on-line survey regarding geographic distribution and participation in outreach care. A total of 320 GOs (43%) responded; median age range was 35–45 years and 57% were male. Most practiced in an urban setting (72%) at a university hospital (43%). Only 13% of GOs practiced in an area with a population < 50,000. A desire to remain in academics and exposure to senior-level mentorship were the factors most influencing initial practice location. Approximately 50% believed geographic disparities exist in GO workforce distribution that pose access barriers to care; however, 39% “strongly agreed” that cancer patients who live in R/US regions should travel to urban cancer centers to receive care within a center of excellence model. GOs who practice within 50 miles of only 0–5 other GOs were more likely to provide R/US care compared to those practicing within 50 miles of ≥ 10 GOs (p < 0.0001). Most (39%) believed the major barriers to providing cancer care in R/US areas were volume and systems-based. Most also believed the best solution was a hybrid approach, with coordination of local and centralized cancer care services. Among GOs, a self-reported rural-urban disparity exists in the density of gynecologic oncologists. These study findings may help address barriers to providing cancer care in R/US practice environments.

How do palliative care needs vary across the disease trajectory in patients with gynecologic cancer

106 Background: The WHOs integrated model emphasizes that palliative care (PC) should be provided concurrently with curative and life-prolonging care, with disease-directed treatments decreasing and PC increasing over time. This study aimed to understand how accurately this theoretical model matches the PC needs of gynecologic cancer (GC) patients. METHODS GC patients at a comprehensive cancer center completed a symptom and needs assessment questionnaire as part of routine care. Needs were divided into physical, emotional, social, practical, and informational domains. Patients reporting at least one symptom score ≥ 4/10 made the physical need domain positive. For the remainder of the categories, patients endorsing at least one need in a given domain made that domain positive. Time points in the illness trajectory were categorized as diagnosis, primary treatment, remission, and progression/recurrence. Univariate analyses were utilized to assess differences in needs at various time points. RESULTS Questionnaires from 1348 patient visits over 3 months were included. Patients had ovarian (39%), uterine (36%), cervical (16%), and vulvar (5%) cancer. Visits occurred around the time of diagnosis (6%), during primary therapy (28%), during remission (42%), and during disease progression or recurrence (23%). Physical needs were most common at diagnosis and during progression/recurrence (p < 0.01). Emotional needs (p < 0.01), social needs (p < 0.01), and informational needs (p < 0.01) all varied throughout the course of disease and were highest at diagnosis. At each time point, at least 65% of patients had one or more PC needs. Having needs in multiple domains ( ≥ 3) was associated with time point, with patients around the time of diagnosis having the highest rate of need in multiple domains (p < 0.01). CONCLUSIONS GC patients have a broad range of PC needs across the trajectory of their illness. The WHO schema fails to capture the full scope of these needs and under-appreciates their prevalence earlier in the course of the disease. These results underscore the importance of training gynecologic oncologists in primary PC as well as increasing referrals to specialist PC providers.

Predictors of referral to outpatient specialty palliative care (SPC) in gynecologic cancer (GC) patients.

159 Background: Prior studies in GC patients have described predictors of inpatient palliative care (PC) consultation, but predictors of outpatient SPC consultation have not been elucidated. We sought to identify factors predictive of referral and associated care outcomes. METHODS We performed a cross-sectional study of GC patients seen in the gynecologic oncology clinic at a comprehensive cancer center over a three month period. As a part of routine care, patients completed a symptom questionnaire. Patients previously seen at the outpatient PC clinic were compared to those who had not with respect to demographics, disease characteristics, symptom scores, and provider factors using univariate statistics. A multivariate model was created to identify independent predictors of referral. RESULTS 913 patients completed the symptom survey. 76 patients (8%) had been seen in the outpatient PC clinic. Disease factors associated with referral included site (p < 0.01), stage (p < 0.01), evidence of disease (p < 0.01), active treatment (p < 0.01), and time point in the disease trajectory (p < 0.01). Women with moderate to severe pain (p < 0.01), sadness (p = 0.03), distress (p < 0.01), fatigue (p < 0.01), neuropathy (p = 0.03), and sexual dysfunction (p < 0.01) were more likely to have seen PC. Marital status, number of symptoms, and patient provider were also predictive of referral (all p < 0.01). In a multivariate model, site, stage, number of symptoms, moderate to severe sexual dysfunction, and provider were independently associated with referral. Compared to women who had not been referred, patients seen in the PC clinic were more likely to have a health care proxy documented in the electronic medical record (p < 0.01). Among patients with related symptoms, patients referred to PC more often had an opioid prescribed for pain (p < 0.01) and medications prescribed for depression (p < 0.01), anxiety (p = 0.04), insomnia (p < 0.01), and fatigue (p < 0.01). CONCLUSIONS Women with depression, anxiety, insomnia, and fatigue were more likely to receive pharmacologic treatment for these symptoms from a SPC provider. Future research should identify referral triggers for those patients most likely to benefit from outpatient SPC consultation.

Referrals to phase I clinical trials in a gynecologic oncology unit

OBJECTIVES Previous reviews of phase I clinical trials report limited response rates. Development of novel biologic agents and trials designs have increased these rates. A contemporary appraisal of phase I clinical trials in gynecologic malignancies could help validate these findings. METHODS Retrospectively reviewed records for 410 patients with gynecologic malignancies treated in a phase I unit, January 1999 to October 2012. Patient characteristics and treatment outcomes were abstracted and analyzed. RESULTS Patients enrolled in 43 different phase I trials, 17 phase Ia, 17 phase Ib dose escalation and 9 dose expansion. 9 trials (21%) investigated unique cytotoxic delivery methods, 15 (35%) conventional cytotoxic plus novel agents and 19 (44%) novel agents alone. For patients treated in the first-line setting, 90 (74.4%) achieved CR, 20 (16.5%) PR, 9 (7.4%) SD and 2 (1.7%) PD, yielding an overall response rate of 90.9%. In patients treated for recurrent disease, 2 (1.6%) achieved CR, 11 (8.9%) PR, 57 (46.0%) SD and 54 (43.5%) PD, yielding a response rate of 11% and an overall clinical benefit rate of 57%. Response rate for molecular targeted therapies was 11.5% with an overall clinical benefit rate of 46.2%. Patients with prior anti-angiogenic exposure had comparable median PFS to those who had not been previously exposed (3.5 vs. 4.0 months, p = 0.29). CONCLUSIONS Results support referral of gynecologic cancer patients for phase I clinical trials. Patients with advanced, heavily pretreated disease fare at least as well as they do on phase II trials and a proportion of them can attain an objective response or stabilization of their disease.

The use of biologic agents and clinical trials may prolong survival for women with primary platinum resistant ovarian carcinoma

Hispanic (8%), Asian (4%), and other races (3%). 29% were from the South, 26% from the Midwest, 25% Northeast, and 21% were from the West. 23% of hospitals were higher volume (N20 cases/year) vs. lower volume hospitals. 1647 (25%) underwent robotic surgery (RS), 820 (12%) laparoscopic (LS), vs. 4093 (62%) had open surgery (OS). The older (N 62 years, median) were more likely to have RS compared to younger (26% vs. 24%, p = 0.02). 29% of Whites had RS compared to only 20% Native Americans, 15% Hispanics, 12% Blacks, and 11% of Asians (p b 0.01). Patients from Midwest, Northeast, South and West had RS in 26%, 26%, 25%, and 23% of cases. Higher volume hospital performed 72% of all surgeries and 84% of all RS. Moreover, these higher volume hospitals were more likely to use RS compared to lower volume institutions (29% vs. 14%, p b 0.01). Those with low(b