Neuroendocrine neoplasms of the ovary: a review of 63 cases.

OBJECTIVE: To describe the clinicopathological characteristics and survival outcomes of ovarian neuroendocrine neoplasms from a curated registry. METHODS: This is a retrospective cross-sectional study of patients in our registry with confirmed ovarian neuroendocrine neoplasms. We excluded patients with small cell carcinoma not otherwise specified, small cell hypercalcemic type, and those with neuroendocrine 'features' or 'differentiation.' Clinicopathological characteristics were described in two separate groups: patients with carcinoid tumors and patients with neuroendocrine carcinomas. Progression-free and overall survival were estimated with the Kaplan-Meier product-limit estimator in these two groups, and multivariable analysis was done to identify predictors of survival for neuroendocrine carcinomas only. RESULTS: A total of 63 patients met inclusion criteria, 13 (21%) with carcinoid tumors and 50 (79%) with neuroendocrine carcinomas. In the carcinoid tumor group, one patient (8%) was misdiagnosed. Two patients (15%) had a recurrence and the 5-year overall survival rate was 80% (95% CI 45% to 100%), with a lower bound of the median survival of 4.8 years (95% CI). In the neuroendocrine carcinoma group, 23 patients (46%) were misdiagnosed, 16 of whom (69%) received therapy with the presumption of a non-neuroendocrine carcinoma diagnosis. Thirty patients (60%) had a recurrence, and the 5-year overall survival rate was 24% (10%, 38%), with a median survival of 1.6 years (1.3, 3.3). Patients with carcinomas stage III or IV had an increased risk of progression/recurrence (HR=5.6; 95% CI 1.9 to 17.0) and death (HR=8.1; 95% CI 2.2 to 29.7) compared with those with stage I or II. Pure histology was associated with an increased risk of progression/recurrence (HR=2.3; 95% CI 1.0 to 5.2) compared with admixed histology. CONCLUSION: Most patients had neuroendocrine carcinomas, which were associated with a higher recurrence rate and worse survival than carcinoid tumors. A high proportion of patients in both groups were initially misdiagnosed, and a new association with endometrial hyperplasia was observed. Neuroendocrine admixed histology is associated with a higher risk of progression.

Impact of pelvic radiation therapy in patients with early neuroendocrine cervical carcinoma and no residual disease in the radical hysterectomy specimen: a NeCTuR study.

OBJECTIVE: The impact of adjuvant pelvic radiation therapy on the rate and location of recurrences was evaluated in patients with early-stage (IA1-IB2) neuroendocrine cervical carcinoma who underwent prior conization or polypectomy with no residual disease and negative nodes in the subsequent upfront radical hysterectomy specimen. As a secondary objective, disease-free and overall survival were analyzed. METHODS: We searched the Neuroendocrine Cervical Tumor Registry (NeCTuR) to identify patients with clinical early-stage neuroendocrine cervical carcinoma with no residual disease in the specimen from upfront radical surgery and negative nodes. Patients who received pelvic radiation therapy were compared with those who did not, regardless of whether they received adjuvant chemotherapy. RESULTS: Twenty-seven patients met the inclusion criteria, representing 17% of all patients with clinical early-stage disease who underwent upfront radical hysterectomy included in the NeCTuR registry. The median age was 36.0 years (range 26.0-51.0). Six (22%) patients had stage IA, 20 (74%) had stage IB1, and one (4%) had stage IB2 disease. Seven (26%) patients received adjuvant radiation therapy and 20 (74%) did not. All seven patients in the radiation group and 14 (70%) in the no-radiation group received adjuvant chemotherapy (p=0.16). Fifteen percent (4/27) of patients had a recurrence, 14% (1/7) in the radiation group and 15% (3/20) in the no-radiation group (p=0.99). In the radiation group the recurrence was outside the pelvis, and in the no-radiation group, 67% (2/3) recurred outside the pelvis and 33% (1/3) recurred both inside and outside the pelvis (p=0.99). In the radiation group the 5-year disease-free and overall survival rates were 100% while, in the no-radiation group, the 5-year disease-free and overall survival rates were 81% (95% CI 61% to 100%) (p=0.99) and 80% (95% CI 58% to 100%) (p=0.95), respectively. CONCLUSIONS: For patients with no residual disease and negative nodes in the upfront radical hysterectomy specimen, our study did not find that pelvic radiation therapy improves survival.

Clinicopathologic characteristics, oncologic outcomes, and prognostic factors in neuroendocrine cervical carcinoma: a Neuroendocrine Cervical Tumor Registry study.

OBJECTIVE: To evaluate clinicopathologic features and oncologic outcomes of patients with neuroendocrine cervical carcinoma in an institutional neuroendocrine cervical tumor registry. METHODS: Retrospective study including patients with neuroendocrine cervical carcinomas diagnosed between 1986 and 2022. Patients were categorized into International Federation of Gynecology and Obstetrics 2018 stage groups: early-stage (IA1-IB2, IIA1); locally advanced (IB3, IIA2-IVA); and advanced (IVB). Clinicopathologic characteristics and oncologic outcomes were evaluated by stage. Survival was compared between patients diagnosed in 1986-2003 and those diagnosed in 2004-2016. Progression-free and overall survival were estimated using the Kaplan-Meier product-limit estimator. RESULTS: A total of 453 patients was included, 133 (29%) with early-stage, 226 (50%) with locally advanced, and 94 (21%) with advanced disease. Median age was 38 years (range 21-93). Sixty-nine percent (306/453) had pure and 32% (146/453) had mixed histology. The node positivity rate (surgical or radiological detection) was 19% (21/108) for tumors ≤2 cm, 37% (39/105) for tumors >2 to ≤4 cm, and 61% (138/226) for tumors >4 cm (p<0.0001). After primary treatment, rates of complete response were 86% (115/133) for early-stage, 65% (147/226) for locally advanced, and 19% (18/94) for advanced disease (p<0.0001). The recurrence/progression rate was 43% for early-stage, 69% for locally advanced, and 80% for advanced disease (p<0.0001). Five-year progression-free and overall survival rates were 59% (95% CI 50% to 68%) and 71% (95% CI 62% to 80%), respectively, for early-stage, 28% (95% CI 22% to 35%) and 36% (95% CI 29% to 43%), respectively, for locally advanced, and 6% (95% CI 0% to 11%) and 12% (95% CI 5% to 19%), respectively, for advanced disease. For early-stage disease, the 5-year progression-free survival rate was 68% for tumors ≤2 cm and 43% for tumors >2 to ≤4 cm (p=0.0013). Receiving cisplatin/carboplatin plus etoposide (HR=0.33, 95% CI 0.17 to 0.63, p=0.0008) and receiving curative radiotherapy (HR=0.32, 95% CI 0.17 to 0.6, p=0.0004) were positive predictors of survival for patients with advanced disease. CONCLUSION: Among patients with neuroendocrine cervical carcinomas, overall survival is favorable for patients with early-stage disease. However, most patients present with locally advanced disease, and overall survival remains poor in this subgroup. For patients with advanced disease, receiving cisplatin/carboplatin plus etoposide and curative radiation therapy is associated with improved overall survival.

Combination therapy with topotecan, paclitaxel, and bevacizumab improves progression-free survival in patients with recurrent high-grade neuroendocrine cervical cancer: a Neuroendocrine Cervical Tumor Registry (NeCTuR) study.

BACKGROUND: Recurrent high-grade neuroendocrine cervical cancer has a very poor prognosis and limited active treatment options. OBJECTIVE: This study aimed to evaluate the efficacy of the 3-drug regimen of topotecan, paclitaxel, and bevacizumab in women with recurrent high-grade neuroendocrine cervical cancer. STUDY DESIGN: This retrospective cohort study used data from the Neuroendocrine Cervical Tumor Registry (NeCTuR), which include data abstracted directly from medical records of women diagnosed with high-grade neuroendocrine carcinoma of the cervix from English- and Spanish-speaking countries. The study compared women with recurrent high-grade neuroendocrine cervical cancer who received the topotecan, paclitaxel, and bevacizumab regimen as first- or second-line therapy for recurrence and women with recurrent high-grade neuroendocrine cervical cancer who received chemotherapy but not the topotecan, paclitaxel, and bevacizumab regimen. Patients continued chemotherapy until disease progression or the development of unacceptable toxic effects. Progression-free survival from the start of therapy for recurrence to the next recurrence or death, overall survival from the first recurrence, and response rates were evaluated. RESULTS: The study included 62 patients who received the topotecan, paclitaxel, and bevacizumab regimen as first- or second-line therapy for recurrence and 56 patients who received chemotherapy but not the topotecan, paclitaxel, and bevacizumab regimen for recurrence. The median progression-free survival rates were 8.7 months in the topotecan, paclitaxel, and bevacizumab regimen group and 3.7 months in the non-topotecan, paclitaxel, and bevacizumab regimen group, with a hazard ratio for disease progression of 0.27 (95% confidence interval, 0.17-0.48; P<.0001). In the topotecan, paclitaxel, and bevacizumab regimen group, 15% of patients had stable disease, 39% of patients had a partial response, and 18% of patients had a complete response. Compared with patients in the non-topotecan, paclitaxel, and bevacizumab regimen group, significantly more patients in the topotecan, paclitaxel, and bevacizumab regimen group remained on treatment at 6 months (31% vs 67%, respectively; P=.0004) and 1 year (9% vs 24%, respectively; P=.02). The median overall survival rates were 16.8 months in the topotecan, paclitaxel, and bevacizumab regimen group and 14.0 months in the non-topotecan, paclitaxel, and bevacizumab regimen group, with a hazard ratio for death of 0.87 (95% confidence interval, 0.55-1.37). CONCLUSION: Combination therapy with topotecan, paclitaxel, and bevacizumab was an active regimen in women with recurrent high-grade neuroendocrine cervical cancer and improved progression-free survival while decreasing the hazard ratio for disease progression.

Definitive pelvic radiation therapy improves survival in stage IVB neuroendocrine cervical carcinoma: A NeCTuR study.

OBJECTIVE: To evaluate the survival impact of adding definitive pelvic radiation therapy (RT) to chemotherapy among patients with stage IVB neuroendocrine cervical carcinoma (NECC). METHODS: We retrospectively studied patients with FIGO 2018 stage IVB NECC diagnosed during 1998-2020 who received chemotherapy with or without definitive whole pelvic RT (concurrent or sequential). Demographic, oncologic, and treatment characteristics were summarized. Progression-free (PFS) and overall survival (OS) were plotted using the Kaplan-Meier method, and hazard ratios (HRs) were calculated using Cox regression. RESULTS: The study included 71 patients. Median age was 43 years (range, 24-75). Fifty-nine patients (83%) had pure neuroendocrine histology, and 57 (80%) had pretreatment tumor size >4 cm. Fifty-six patients (79%) received chemotherapy alone with (n = 15) or without (n = 41) palliative pelvic RT, and 15 (21%) received chemotherapy and definitive pelvic RT (chemo+RT). Median follow-up time was 20.1 months (range, 11.3-170.3) for the chemo+RT group and 13.5 months (range, 0.9-73.6) for the chemotherapy-alone group. Median PFS was 10.3 months (95% CI, 7.5-∞) for the chemo+RT group vs 6.6 months (95% CI, 6.1-8.7) for the chemotherapy-alone group (p = 0.0097). At 24 months, the PFS rate was 24% for chemo+RT vs 7.8% for chemotherapy alone. Median OS was 20.3 months (95% CI, 18.5-∞) for the chemo+RT group vs 13.6 months (95% CI, 11.3-19.2) for the chemotherapy-alone group (p = 0.0013). At 24 months, the OS rate was 49.2% for chemo+RT vs 21.5% for chemotherapy alone. In a Cox regression model, definitive RT was associated with improved PFS (HR, 0.44; 95% CI, 0.23-0.83; p = 0.0119) and OS (HR, 0.31; 95% CI, 0.14-0.65; p = 0.0022). CONCLUSIONS: Addition of definitive pelvic RT to chemotherapy may improve survival in patients with stage IVB NECC.

Role of radical hysterectomy in patients with early-stage high-grade neuroendocrine cervical carcinoma: a NeCTuR study.

OBJECTIVE: Patients with early-stage, high-grade neuroendocrine cervical carcinoma typically undergo radical hysterectomy with pelvic lymphadenectomy followed by adjuvant radiotherapy and/or chemotherapy. To explore the role of radical surgery in patients with this disease, who have a high likelihood of undergoing postoperative adjuvant therapy, we aimed to determine the rate of parametrial involvement and the rate of parametrial involvement without other indications for adjuvant treatment in these patients. METHODS: We retrospectively studied patients in the Neuroendocrine Cervical Tumor Registry (NeCTuR) at our institution to identify those with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IA1-IB2, high-grade neuroendocrine cervical carcinoma who underwent up-front radical surgery with or without adjuvant therapy. RESULTS: One hundred patients met the inclusion criteria. The median age was 35 years (range 22-65), and 51% (51/100) had pure high-grade neuroendocrine carcinoma. No patient had a tumor >4 cm or suspected parametrial or nodal disease before surgery. Ten patients (10%) had microscopic parametrial compromise in the final surgical specimens. Ninety-four (94%) patients underwent nodal assessment, and 19 (19%) had positive nodes. Ten patients underwent both sentinel lymph node biopsy and pelvic lymphadenectomy, and none had false-negative findings. Patients with parametrial compromise were more likely to have positive pelvic nodes (80% vs 12%, p<0.0001), and a positive vaginal margin (20% vs 1%, p=0.03). All patients with parametrial compromise had lymphovascular space invasion (100% vs 73%, p=0.10). Of the 100 patients, 95 (95%) were recommended adjuvant therapy and 89 (89%) were known to have received it. Adjuvant pelvic radiotherapy reduced the likelihood of local recurrence by 62%. CONCLUSIONS: In carefully selected patients with high-grade neuroendocrine cervical carcinoma, the rate of microscopic parametrial involvement is 10%. As most patients receive adjuvant treatment, we hypothesize that simple hysterectomy may be adequate when followed by adjuvant radiotherapy with concurrent cisplatin and etoposide followed by additional chemotherapy.

Implementation of a sentinel lymph node mapping algorithm for endometrial cancer: surgical outcomes and hospital charges.

INTRODUCTION: The purpose of this study was to compare operative times, surgical outcomes, resource utilization, and hospital charges before and after the implementation of a sentinel lymph node (SLN) mapping algorithm in endometrial cancer. METHODS: All patients with clinical stage I endometrial cancer were identified pre- (2012) and post- (2017) implementation of the SLN algorithm. Clinical data were summarized and compared between groups. Total hospital charges incurred on the day of surgery were extracted from the hospital financial system for each patient and all charges were adjusted to 2017 US dollars. RESULTS: A total of 203 patients were included: 71 patients in 2012 and 130 patients in 2017. There was no difference in median age, body mass index, or stage. In 2012, 35/71 patients (49.3%) underwent a lymphadenectomy. In 2017, SLN mapping was attempted in 120/130 patients (92.3%) and at least one SLN was identified in 110/120 (91.7%). Median estimated blood loss was similar between groups (100 mL vs 75 mL, p=0.081). There was a significant decrease in both median operative time (210 vs 171 min, p=0.007) and utilization of intraoperative frozen section (63.4% vs 14.6%, p<0.0001). No significant differences were noted in intraoperative (p=1.00) or 30 day postoperative complication rates (p=0.30). The median total hospital charges decreased by 2.73% in 2017 as compared with 2012 (p=0.96). DISCUSSION: Implementation of an SLN mapping algorithm for high- and low-risk endometrial cancer resulted in a decrease in both operative time and intraoperative frozen section utilization with no change in surgical morbidity. While hospital charges did not significantly change, further studies are warranted to assess the true cost of SLN mapping.

Prospective pilot trial with combination of propranolol with chemotherapy in patients with epithelial ovarian cancer and evaluation on circulating immune cell gene expression.

OBJECTIVE: To determine the feasibility of pharmacologic beta-adrenergic blockade in women with newly diagnosed stage II-IV epithelial ovarian cancer (EOC) throughout primary treatment. METHODS: Patients initiated propranolol prior to beginning chemotherapy or surgery. Feasibility was assessed as proportion able to complete 6 chemotherapy cycles while on adrenergic suppression. Descriptive statistics summarized surveys, and paired changes were analyzed using signed rank tests. Random-intercept Tobit models examined immune response. RESULTS: Median age was 59.9; 88.5% were stage IIIC/IV; and 38.5% underwent primary debulking. Thirty-two patients were enrolled; 3 excluded because they never took propranolol; an additional 3 didn't meet inclusion criteria, leaving 26 evaluable. Eighteen of 26 (69%), 90% credible interval (CI) of 53-81%, completed 6 chemotherapy cycles plus propranolol (an 82% posterior probability that the true proportion of success is ≥60%). Among the 23 patients with baseline and six month follow up data, overall QOL, anxiety, and depression improved (P < 0.05) and leukocyte expression of pro-inflammatory genes declined (P = 0.03) after completion of therapy. Decrease from baseline of serum IL-6 and IL-8 preceded response to chemotherapy (P < 0.0014). Change from baseline IL-10 preceded complete response. CONCLUSION: Use of propranolol during primary treatment of EOC is feasible and treatment resulted in decrease in markers of adrenergic stress response. In combination with chemotherapy, propranolol potentially results in improved QOL over baseline.

Frequency and characteristics of drowsiness, somnolence, or daytime sleepiness in patients with advanced cancer.

INTRODUCTION: Cancer-related drowsiness (CRD) is a distressing symptom in advanced cancer patients (ACP). The aim of this study was to determine the frequency and factors associated with severity of CRD. We also evaluated the screening performance of Edmonton Symptom Assessment Scale-drowsiness (ESAS-D) item against the Epworth Sedation Scale (ESS). METHOD: We prospectively assessed 180 consecutive ACP at a tertiary cancer hospital. Patients were surveyed using ESAS, ESS, Pittsburgh Sleep Quality Index, Insomnia Severity Index, and Hospital Anxiety Depression Scale. RESULT: Ninety of 150 evaluable patients had clinically significant CRD (ESS); median (interquartile ratio): ESS. 11 (7-14); ESAS-D. 5 (2-6); Pittsburgh Sleep Quality Index. 8 (5-11); Insomnia Severity Index. 13 (5-19); Stop Bang Scoring 3 (2-4), and Hospital Anxiety Depression Scale-D 6 (3-10). ESAS-D was associated with ESAS (r, p) sleep (0.38, <0.0001); pain (0.3, <0.0001); fatigue (0.51, <0.0001); depression (0.39, <0.0001); anxiety (0.44, <0.0001); shortness of breath (0.32, <0.0001); anorexia (0.36, <0.0001), feeling of well-being [(0.41, <0.0001), ESS (0.24, 0.001), and opioid daily dose (0.19, 0.01). Multivariate-analysis showed ESAS-D was associated with fatigue (odds ratio [OR] = 9.08, p < 0.0001), anxiety (3.0, p = 0.009); feeling of well-being (OR = 2.27, p = 0.04), and insomnia (OR = 2.35; p = 0.036). Insomnia (OR = 2.35; p = 0.036) cutoff score ≥3 (of 10) resulted in a sensitivity of 81% and 32% and specificity of 70% and 44% in the training and validation samples, respectively. SIGNIFICANCE OF RESULTS: Clinically significant CRD is frequent and seen in 50% of ACP. CRD was associated with severity of insomnia, fatigue, anxiety, and worse feeling of well-being. An ESAS-D score of ≥3 is likely to identify most of the ACP with significant CRD.

Bilateral salpingectomy with delayed oophorectomy for ovarian cancer risk reduction: A pilot study in women with BRCA1/2 mutations.

OBJECTIVE: Risk-reducing salpingo-oophorectomy (RRSO) reduces ovarian cancer risk in BRCA1/2 mutation carriers, but the adverse effects of the associated early-onset surgical menopause are problematic. Despite suggestive evidence, no data demonstrate whether bilateral salpingectomy alone lowers the risk of developing ovarian cancer in BRCA mutation carriers. We conducted a pilot study of bilateral salpingectomy with delayed oophorectomy (BS/DO) in BRCA mutation carriers to determine the safety and acceptability of the procedure. METHODS: In this prospective, multicenter, non-randomized pilot study, pre-menopausal BRCA1/2 mutation carriers aged 30 to 47 years chose screening, RRSO, or BS/DO. For those undergoing BS/DO, the delayed oophorectomy was recommended at age 40 years for BRCA1 and age 45 years for BRCA2 patients. We compared surgical and psychosocial outcomes between time points and between arms. RESULTS: Of the 43 patients enrolled, 19 (44%) chose BS/DO, 12 (28%) chose RRSO, and 12 (28%) chose screening. The cohort was 37% BRCA1 carriers and 63% BRCA2 carriers. One serous tubal intraepithelial carcinoma (STIC) was found in an RRSO patient, and no cases of occult ovarian cancers were found. There were no surgical complications. Twelve months after surgery, responses on the Cancer Worry Scale indicated decreased worry in the BS/DO (P < 0.0001) and RRSO (P = 0.01) arms, while responses on the State Anxiety Inventory indicated decreased anxiety in the BS/DO arm (P = 0.02) compared with preoperative responses. CONCLUSIONS: In this pilot study, BRCA mutation carriers who underwent bilateral salpingectomy had no intraoperative complications, were satisfied with their procedure choice, and had decreased cancer worry and anxiety after the procedure.

Genomic Rearrangement Signatures and Clinical Outcomes in High-Grade Serous Ovarian Cancer.

Background: To identify clinically relevant genomic rearrangement signatures in high-grade serous ovarian cancer (HGSOC), we conducted a retrospective analysis of sequenced HGSOC whole-tumor genomes. Methods: Clinical data and whole-genome sequencing (WGS) reads were obtained for primary HGSOC tumors sequenced by the Australian Ovarian Cancer Study (AOCS; n = 80). Genomic rearrangements were identified, and non-negative matrix factorization (NMF) was used to extract rearrangement signatures. The cohort was then dichotomized around the median signature contribution, and overall survival (OS) was analyzed. An independent cohort from The Cancer Genome Atlas (TCGA) ovarian cancer study (n = 490) was also examined. The TCGA cohort was dichotomized around the median similarity between tumor copy number profile and a prognostic rearrangement signature, and OS was analyzed. Outcomes were assessed using Kaplan-Meier and multivariable Cox regression methods. All statistical tests were two-sided. Results: We identified five genomic rearrangement signatures (Ov.RS1-5) in HGSOC. Ov.RS3 exhibited 10 kilobase to 10 megabase deletions and tandem duplications, and patients whose tumors exhibited a high contribution from Ov.RS3 had poor OS. The median OS was 22.7 months (95% confidence interval [CI] = 20.2 to 39.0 months) in the Ov.RS3-high group vs 38.2 months (95% CI = 22.7 to 69.1 months) in the Ov.RS3-low group (hazard ratio [HR] = 1.86, 95% CI = 1.12 to 3.09, P = .02). For the independent TCGA cohort, median OS rates were 38.0 months (95% CI = 35.3 to 41.4 months) in the Ov.RS3 high-similarity group vs 48.9 months (95% CI = 44.1 to 57.1 months) in the Ov.RS3 low-similarity group (HR = 1.54, 95% CI = 1.21 to 1.97, P < .001). Conclusion: A novel genomic rearrangement signature is associated with poor prognosis in HGSOC.

Factors associated with patient-reported subjective well-being among advanced lung or non-colonic gastrointestinal cancer patients.

OBJECTIVE: The aim of this study was to determine the factors associated with a feeling of well-being using the Edmonton Symptom Assessment Scale (ESAS)-Feeling of Well-Being item (ESAS-FWB; where 0 = best and 10 = worst) among advanced lung or non-colonic gastrointestinal cancer patients who were referred to an outpatient palliative care clinic (OPCC). We also examined the association of performance on the ESAS-FWB with overall survival (OS). METHOD: We reviewed the records of consecutive patients with incurable advanced lung cancer and non-colonic gastrointestinal cancer presenting to an OPCC from 1 January 2008 through to 31 December 2013. Descriptive statistics were employed to summarize patient characteristics. Multivariate regression analysis was used to determine the factors associated with ESAS-FWB severity. We also examined the association of ESAS-FWB scores and survival using Kaplan-Meier survival analysis. RESULTS: A total of 826 evaluable patients were analyzed (median age = 62 years, 57% male). Median ESAS-FWB scores were five times the interquartile range (5 × IQR; 3-7). ESAS-FWB score was found to be significantly associated with ESAS fatigue (OR = 2.31, p < 0.001); anxiety (OR = 1.98, p < 0.001); anorexia (OR = 2.31, p < 0.001); cut down, annoyed, guilty, eye opener (CAGE) score (hazard ratio [HR] = 1.80, p = 0.008); and family caregiver distress (HR = 1.93, p = 0.002). A worse ESAS-FWB score was significantly associated with decreased OS (r = -0.18, p < 0.001). However, ESAS-FWB score was not independently associated with OS in the final multivariate model (p = 0.35), which included known major clinical prognostic factors. CONCLUSIONS: Worse ESAS-FWB scores were significantly associated with high scores on ESAS fatigue, anorexia, anxiety, CAGE, and family caregiver distress. More research is necessary to understand how palliative care interventions are capable of improving the contributory factors related to ESAS-FWB score.

Factors influencing fertility-sparing treatment for gynecologic malignancies: A survey of Society of Gynecologic Oncology members.

OBJECTIVES: This study aims to examine practice patterns of gynecologic oncologists (GO) regarding fertility-sparing treatments (FST) for gynecology malignancies and explores attitudes toward collaboration with reproductive endocrinologists (RE). METHODS: An anonymous 23-question survey was sent to 1087 GO with a 14.0% completion rate. Descriptive statistics, Fisher's exact test, and Chi-square tests were used for data analysis. RESULTS: The majority of GOs offer FST for gynecologic malignancies. Providers seeing larger numbers of reproductive age women were more likely to consider cancer prognosis (p<0.03) and cancer stage (p<0.01) as key factors. Providers in the Midwestern US considered socioeconomic status more often when offering FST than those in the South (p<0.04). Those practicing in urban settings were more likely to feel that collaborating with a RE prior to treatment could improve treatment planning for women considering FST (p<0.02). Finally, providers in urban or suburban areas more often felt collaboration with a RE improves pregnancy outcomes in women who pursue FST (p<0.01, p<0.02) compared to rural practitioners. CONCLUSIONS: While FST offers women the chance to pursue pregnancy after cancer, there are minimal data on factors that influence whether FST is offered and if collaboration with a RE is sought in the management of these patients. The number of reproductive age women seen, geographic location, and practice setting are important variables that may influence current practice. Understanding these factors can help identify opportunities to improve oncologic and reproductive outcomes of this patient population.

Frequency of venous thromboembolism events during acute inpatient rehabilitation in a comprehensive cancer centre.

OBJECTIVE: To determine the frequency of venous thromboembolism, possible predictors, and the association between venous thromboembolism and Functional Independence Measure (FIM) scores and length of stay among cancer patients admitted to the inpatient rehabilitation unit at a cancer centre. DESIGN: Retrospective analysis of patients admitted to acute inpatient rehabilitation from September 2011 to June 2013. Subject/patients: Cancer patients in the acute inpatient rehabilitation unit within a tertiary cancer centre. METHODS: International Classification of Diseases (ICD-9) codes identified deep vein thrombosis, pulmonary embolism, and inferior vena cava filter. RESULTS: Venous thromboembolism occurred in 32/611 patients (5.2%): 23/611 (3.8%) during the course of hospitalization before admission to rehabilitation, and 9/611 patients (1.5%) during rehabilitation. Patients with lower extremity oedema at admission (p = 0.0218) had a higher chance of subsequently developing venous thromboembolism. Patients with venous thromboembolism during rehabilitation had a significantly lower FIM transfer score at admission to rehabilitation (p = 0.0247), a longer length of stay in rehabilitation (p = 0.0013) and overall hospitalization (p = 0.0580). CONCLUSION: Cancer patients with low FIM transfer scores and lower extremity oedema are at higher risk of venous thromboembolism. Patients with these clinical findings at admission may require measures for more aggressive surveillance for the presence of venous thromboembolism. Patients with venous thromboembolism had an increased length of stay in rehabilitation, but ultimately did not have significant differences in FIM score changes.

Timing to antibiotic therapy in septic oncologic patients presenting without hypotension.

PURPOSE: Sepsis accounts for only 2% of the hospitalizations worldwide but more than 17% of total in-hospital mortality. Inappropriate antimicrobial selection and delays in appropriate therapy have been associated with reduced survival in severe sepsis and septic shock. No studies to date have exclusively targeted septic oncologic patients without hypotension. METHODS: This study was a retrospective chart review of 100 adult cancer patients presenting to the emergency department with sepsis without hypotension. We investigated the effect of time to appropriate antibiotics on in-hospital mortality and hospital length of stay. It was hypothesized that increased time to antibiotic administration would worsen patient outcomes including in-hospital mortality and length of stay. RESULTS: Each 1-h delay in administration of appropriate antibiotic therapy increased the odds of in-hospital mortality by 16% (adjusted OR 1.16. 95% CI 1.04-1.34, p = 0.04). Time to appropriate antibiotics had no effect on hospital length of stay. CONCLUSIONS: Time to appropriate antibiotics and in-hospital mortality were associated in this population of adult oncologic patients with sepsis without hypotension. Clinicians in the emergency department should strive to ensure the timely administration of a complete and appropriate empiric antibiotic regimen in septic patients with active cancer even in the absence of hypotension.

Immune Microenvironment in Microsatellite-Instable Endometrial Cancers: Hereditary or Sporadic Origin Matters.

Purpose: Recent studies show that colorectal tumors with high microsatellite instability (MSI-H) have increased immunogenicity and response to immunotherapy compared with microsatellite-stable (MSS) tumors. It is not yet clear whether MSI-H endometrial cancer may also benefit from these therapies. It is also unknown whether immune response is equivalent in MSI-H endometrial cancer with sporadic or inherited Lynch syndrome origins.Experimental Design: Multiplexed fluorescent IHC was used to compare matched MSI-H (n = 60) and MSS (n = 96) endometrial cancer specimens by evaluating immune cell populations in tumor and stroma compartments. Sporadic MSI-H and Lynch syndrome-associated (LS) MSI-H endometrial cancers were also directly compared.Results: Increased immune cells were present in stroma of MSI-H endometrial cancer compared with MSS, including granzyme B+ cells, activated CTLs (CD8+granzyme B+), and PD-L1+ cells. Granzyme B+ cells and activated CTLs were also increased in the tumor compartment of MSI-H endometrial cancers. Comparing sporadic and LS MSI-H endometrial cancer showed distinct differences in immune cell populations, indicating that mechanisms underlying microsatellite instability alter immune response. Specifically, LS MSI-H endometrial cancer showed increased CD8+ cells and activated CTLs in stroma, with reduced macrophages in stroma and tumor compared with sporadic MSI-H. Sporadic MSI-H had increased PD-L1+ macrophages in stroma and tumor compared with LS MSI-H endometrial cancer.Conclusions: MSI-H endometrial cancer has increased immune cell infiltration compared with MSS endometrial cancer and the hereditary or sporadic origin of microsatellite instability impacts immune response. Clinical trials to determine the role of immunotherapy in patients with MSI-H endometrial cancer must evaluate Lynch syndrome-related and sporadic MSI-H tumors separately. Clin Cancer Res; 23(15); 4473-81. ©2017 AACR.

Patient-reported sleep disturbance in advanced cancer: frequency, predictors and screening performance of the Edmonton Symptom Assessment System sleep item.

AIMS: Sleep Disturbance (SD) is a severe debilitating symptom in advanced cancer patients (ACP). However, routine screening of SD is uncommon. The primary aim of this study was to determine the optimal cutoff score for SD screening for Edmonton Symptom Assessment system (ESAS) sleep item using Pittsburgh Sleep Quality Index (PSQI) as a gold standard. We also determined the frequency of SD, obstructive sleep apnea symptoms (OSA) and restless leg syndrome (RLS) and factors associated with SD. METHODS: We prospectively surveyed 180 consecutive ACP. Patients completed validated assessment for symptoms. We determined epidemiological performance, receiver operating characteristics, and correlations of SD. RESULTS: SD according to PSQI was diagnosed in 112/180 (62%), and median (IQR) ESAS sleep was 5 (2-7). ESAS sleep ≥ 4 had a sensitivity of 74% and 80%, and specificity of 71% and 64% in the training and validation samples, respectively for screening of SD. The frequency of OSA was 61%; RLS was 38%. ESAS sleep was associated [r, p-value] with PSQI (0.61, <0.0001), pain (0.4, <0.0001); fatigue (0.35, <0.0001); depression (0.20, 0.006); anxiety (0.385, <0.0001); drowsiness (0.385, <0.0001), shortness of breath (0.24, <0.0014); anorexia (0.32, <0.0001), well-being (0.36, <0.0001). Multivariate analysis found well-being (OR per point 1.34, p=0.0003), pain (OR 1.21, p<0.0037), dyspnea (OR 1.16, p=0.027), and OSA (OR 0.31, P=0.003) as independent predictors of SD. There was no association between SD and survival. CONCLUSIONS: SD is frequent and ESAS SD item ≥ 4 has good sensitivity for SD screening.

Role of cervical cytology in surveillance after radical trachelectomy for cervical cancer.

OBJECTIVE: There are currently no standard guidelines on the use of Papanicolaou (Pap) tests for surveillance after radical trachelectomy for cervical cancer. The goal of this study was to determine the usefulness of Pap tests in routine surveillance after radical trachelectomy for cervical cancer. METHODS: Cervical cancer patients who underwent radical trachelectomy from January 2004 through October 2015 and subsequently had at least one Pap test were retrospectively identified. Demographic and clinical characteristics were described and compared between patients with and without at least one abnormal Pap test. The Kaplan-Meier method was used to estimate time to first abnormal Pap test. RESULTS: Forty-one patients met inclusion criteria. Of these, 30 (73%) had at least one year in which more than one Pap test per year was obtained. Twenty-four (59%) had at least one abnormal Pap test. Of 238 total Pap tests collected, 44 (18%) were abnormal. The most common abnormality was ASCUS (52%, n=23). Other findings included LSIL (20%, n=9), HSIL (2%, n=1), and AGUS (25%, n=11). Median time from radical trachelectomy to first abnormal Pap test was 17.2months (range, 11.8-86.3). No patient had disease recurrence. Surgery type (laparoscopic, open, or robotic), trachelectomy specimen size, histology, device for stenosis prevention (pediatric Foley catheter or Smit Sleeve), and cerclage placement were not significant predictors of an abnormal Pap test. CONCLUSIONS: The rate of abnormal Pap tests after radical trachelectomy is high; however, the clinical significance of such abnormalities appears limited. The routine use of cervical cytology as surveillance after radical trachelectomy does not appear to substantially impact management decisions.

Patient Perception of Physician Compassion After a More Optimistic vs a Less Optimistic Message: A Randomized Clinical Trial.

IMPORTANCE: Information regarding treatment options and prognosis is essential for patient decision making. Patient perception of physicians as being less compassionate when they deliver bad news might be a contributor to physicians' reluctance in delivering these types of communication. OBJECTIVE: To compare patients' perception of physician compassion after watching video vignettes of 2 physicians conveying a more optimistic vs a less optimistic message, determine patients' physician preference after watching both videos, and establish demographic and clinical predictors of compassion. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial at an outpatient supportive care center in a cancer center in Houston, Texas, including English-speaking adult patients with advanced cancer who were able to understand the nature of the study and complete the consent process. Actors and patients were blinded to the purpose of the study. Investigators were blinded to the videos observed by the patient. INTERVENTION: One hundred patients were randomized to observe 2 standardized, roughly 4-minute videos depicting a physician discussing treatment information (more optimistic message vs less optimistic message) with a patient with advanced cancer. Both physicians made an identical number of empathetic statements (5) and displayed identical posture. After viewing each video, patients completed assessments including the Physician Compassion Questionnaire (0 = best, 50 = worst). MAIN OUTCOMES AND MEASURES: Patients' perception of physician compassion after being exposed to a more optimistic vs an equally empathetic but less optimistic message. RESULTS: Patients reported significantly better compassion scores after watching the more optimistic video as compared with the less optimistic video (median [interquartile range], 15 [5-23] vs 23 [10-31]; P < .001). There was a sequence effect favoring the second video on both compassion scores (P < .001) and physician preference (P < .001). Higher perception of compassion was found to be associated with greater trust in the medical profession independent of message type: 63 patients observing the more optimistic message ranked the physician as trustworthy vs 39 after the less optimistic message (P = .03). CONCLUSIONS AND RELEVANCE: Patients perceived a higher level of compassion and preferred physicians who provided a more optimistic message. More research is needed in structuring less optimistic message content to support health care professionals in delivering less optimistic news. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02357108.