A. Walter

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.

Contribution of age to clinical trial enrollment and tolerance with ovarian cancer

INTRODUCTION Increasing age has been correlated with shorter survival in ovarian cancer patients, a finding attributed to diminished tolerance of standard therapy. Elderly patients, however, are less likely to enroll on clinical trials; thus, limited data exists to evaluate their response to front line treatment. This study describes how elderly patients on trial fared, with respect to toxicity and response, compared to younger women. METHODS A retrospective cohort study was performed of ovarian cancer patients enrolled in front line chemotherapy trials at our institution between 2000 and 2013. Patients were dichotomized by age: <70 and ≥70years. Clinical, pathologic, and treatment characteristics were recorded and analyzed using SAS version 9.3. RESULTS 336 patients were enrolled. Of these, 79 (23.5%) were ≥70yrs. Demographics were similar between the two groups. Compared to patients <70, those ≥70 completed a comparable number of chemotherapy cycles (p=0.16) and had similar numbers of dose modifications (p=0.40) and delays (p=0.26). Both hematologic and non-hematologic toxicities occurred at similar rates as well. Age≥70 (HR 1.8, 95% CI 1.27-2.54, p=0.0009), stage III/IV (HR 3.44, 95% CI 1.08-10.95, p=0.036), and residual disease (HR 2.63, 95% CI 1.82-3.78, p<0.0001) were independently predictive of shorter overall survival. CONCLUSION Our data continues to support reports of shorter survival for older women with ovarian cancer. With physician bias removed and similar chemotherapy tolerance noted, our study suggests that inherent tumor biology may be a significant contributor. Further research is needed to identify the mechanisms which contribute to the inequality that age imposes on outcomes.

Evaluation of the efficacy and toxicity profile associated with intraperitoneal chemotherapy use in older women

OBJECTIVE Intraperitoneal (IP) chemotherapy (CT) for treatment of epithelial ovarian cancer (EOC) has been shown to provide a substantial OS advantage. This study aims to compare the toxicity and benefits of IP CT in patients ≥70 with those <70. METHODS We performed a single institution retrospective review of patients diagnosed with Stage IIA-IIIC EOC from 2000 to 2013 who received IP CT. Clinicopathologic characteristics were extracted, and survival was calculated. RESULTS 133 patients were included with 100 pts. <70years old and 33 pts. ≥70years old. Clinical trial enrollment was similar despite age. In trial enrolled patients, older patients received statistically fewer cycles of therapy (6.4 vs 5.8, p=0.002) but had similar dose delays (0.9 vs 0.7, p=0.72), and modifications (0.9 vs 0.36, p=0.11). Median PFS (27 vs 31months) and OS (71 and 62months) were not statistically different. Grade 3/4 neutropenia was significantly worse in the older patients (82% vs 100%, p=0.04). Neuropathy grade ≥2 and other non-hematologic toxicities were not different between age groups. CONCLUSIONS Despite completing fewer cycles of IP CT, older EOC patients had comparable survival to younger patients. The population of older patients receiving IP CT in this study were on clinical trial and likely to be heartier than the general older population. IP CT appears well tolerated and effective among select older patients and is likely under-utilized outside of clinical trials.

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.