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.

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.

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.

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.

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.

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.

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.

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.

Symptom profiles in children with advanced cancer: Patient, family caregiver, and oncologist ratings.

BACKGROUND: Systematic symptom assessment is not routinely performed in pediatric oncology. The objectives of the current study were to characterize the symptoms of pediatric oncology outpatients and evaluate agreement between patient and proxy reports and the association between children's ratings and oncologists' treatment recommendations. METHODS: Two versions of the pediatric Memorial Symptom Assessment Scale (pMSAS) were translated into Spanish. An age-appropriate and language-appropriate pMSAS was administered independently before visits to the oncologist to patients and family caregivers (caregivers) and after visits to consenting oncologists. Statistical analysis included Spearman correlation coefficients and weighted kappa values. RESULTS: English and Spanish results were similar and were combined. A total of 60 children and their caregivers completed the pMSAS. The children had a median age of 10 years (range, 7-18 years); approximately 62% were male and 33% were Spanish-speaking. Fourteen oncologists completed the pMSAS for 25 patients. Nine patients (15%) had no symptoms and 38 patients (63%) reported ≥2 symptoms. The most common symptoms were fatigue (12 patients; 40%) and itch (9 patients; 30%) for the younger children and pain (15 patients; 50%) and lack of energy (13 patients; 45%) among the older children. Total and subscale score agreement varied by proxy type and subscale, ranging from fair to good for most comparisons. Agreement for individual symptoms between the patient and proxy ranged from a kappa of -0.30 (95% confidence interval, -0.43 to -0.01) to 0.91 (95% confidence interval, 0.75 to 1.00). Three of 51 symptomatic patients (6%) had treatment recommendations documented in the electronic health record. CONCLUSIONS: Symptoms are common and cross several functional domains. Proxy and child reports are often not congruent, possibly explaining apparent undertreatment among this group of patients.

Changes in medication profile among patients with advanced cancer admitted to an acute palliative care unit.

PURPOSE: The decision-making process for medication use in the last weeks of life is complex because of patient frailty and poor prognosis. Limited literature is available on medication use in the palliative care setting, particularly in acute palliative care units (APCUs). We examined the changes in medication profile among hospitalized patients with advanced cancer before their palliative care inpatient consultation team referral, after palliative care consultation, at the time of APCU admission, and at APCU discharge or death. METHODS: We included consecutive patients with advanced cancer who were first seen by our inpatient palliative care consultation team and subsequently admitted to the APCU. We retrieved data on all scheduled medications at the prespecified time points. RESULTS: Among the 100 patients, the median duration of hospitalization was 10.5 days (interquartile range 8-15 days), and the median APCU stay was 5 days (interquartile range 3-7 days). The average number of medications before palliative care inpatient consultation team referral, after palliative care consultation, at APCU admission and at APCU discharge/death was 9.2 (standard deviation [SD] 4.5), 9.9 (SD 4.2), 10.3 (SD 3.8), and 10.1 (SD 3.8), respectively (P = 0.03). An increasing proportion of patients received medications for symptom control over their course of hospitalization, including systemic corticosteroids, laxatives, neuroleptics, and antiulcer agents (P < 0.05). In contrast, the frequency of several classes of medications such as antihypertensives, antilipemics, and anticonvulsants decreased over time (P < 0.05). CONCLUSIONS: Palliative care involvement was associated with an increase in symptom control medications and decrease in medications for comorbid conditions over time.

Cancer patients' perceptions regarding the value of the physical examination: a survey study.

BACKGROUND: Despite its clinical utility, progressive reliance on technology can lead to devaluing the physical examination in patients with advanced cancer. The primary objective of this study was to determine whether these patients have a positive or negative perception of the physical examination. A secondary objective was to determine whether these perceptions are related to interpersonal/relational values (symbolic) or diagnostic/objective values (pragmatic). METHODS: One hundred fifty patients with cancer who were receiving concurrent oncology and palliative care were administered a 26-item survey regarding their overall perception of the physical examination. The primary outcome-patient responses to "In the last 3 months, I believe my experience while being examined has been overall: very negative (a score of -5) to very positive (a score of +5),"-was analyzed using the Sign test. Other items were predefined as either symbolic or pragmatic statements, and patient responses from strongly disagree (a score of 1) to strongly agree (a score of 5) were further analyzed. Multivariable logistic regression was used to test for associations between baseline characteristics and the primary outcome. RESULTS: Most patients (83%) indicated that the overall experience of being examined was highly positive (median score, 4; interquartile range [IQR], 2-5; P ≤ .0001). Patients valued both the pragmatic aspects (median score, 5; IQR, 4-5) and symbolic aspects (median score, 4; IQR, 4-5) of the physical examination. Increasing age was independently associated with a more positive perception of the physical examination (odds ratio, 1.07 per year; 95% confidence interval, 1.02-1.12 per year; P = .01). CONCLUSIONS: Patients with advanced cancer indicate that the physical examination is a highly positive aspect of their care. These benefits are perceived as having both symbolic and pragmatic value. The physical examination should remain a cornerstone of clinical encounters.

Primary tumor resection as a component of multimodality treatment may improve local control and survival in patients with stage IV inflammatory breast cancer.

BACKGROUND: To the authors' knowledge, the benefit of primary tumor resection among patients with metastatic inflammatory breast cancer (IBC) is unknown. METHODS: The authors reviewed 172 cases of metastatic IBC. All patients received chemotherapy with or without radiotherapy and/or surgery. Patients were classified as responders or nonresponders to chemotherapy. The 5-year overall survival (OS) and distant progression-free survival (DPFS) and local control at the time of last follow-up were evaluated. RESULTS: A total of 79 patients (46%) underwent surgery. OS and DPFS were better among patients treated with surgery versus no surgery (47% vs 10%, respectively [P<.0001] and 30% vs 3%, respectively [P<.0001]). Surgery plus radiotherapy was associated with better survival compared with treatment with surgery or radiotherapy alone (OS rate: 50% vs 25% vs 14%, respectively; DPFS rate: 32% vs 18% vs 15%, respectively [P<.0001 for both]). Surgery was associated with better survival for both responders (OS rate for surgery vs no surgery: 49% vs 23% [P<.0001] and DPFS rate for surgery vs no surgery: 31% vs 8% [P<.0001]) and nonresponders (OS rate for surgery vs no surgery: 40% vs 6% [P<.0001] and DPFS rate for surgery vs no surgery: 30% vs 0% [P<.0001]). On multivariate analysis, treatment with surgery plus radiotherapy and response to chemotherapy were found to be significant predictors of better OS and DPFS. Local control at the time of last follow-up was 4-fold more likely in patients who underwent surgery with or without radiotherapy compared with patients who received chemotherapy alone (81% vs 18%; P<.0001). Surgery and response to chemotherapy independently predicted local control on multivariate analysis. CONCLUSIONS: The results of the current study demonstrate that for select patients with metastatic IBC, multimodality treatment including primary tumor resection may result in better local control and survival. However, a randomized trial is needed to validate these findings.

Patient-physician communication about code status preferences: a randomized controlled trial.

BACKGROUND: Code status discussions are important in cancer care, but the best modality for such discussions has not been established. The objective of this study was to determine the impact of a physician ending a code status discussion with a question (autonomy approach) versus a recommendation (beneficence approach) on patients' do-not-resuscitate (DNR) preference. METHODS: Patients in a supportive care clinic watched 2 videos showing a physician-patient discussion regarding code status. Both videos were identical except for the ending: one ended with the physician asking for the patient's code status preference and the other with the physician recommending DNR. Patients were randomly assigned to watch the videos in different sequences. The main outcome was the proportion of patients choosing DNR for the video patient. RESULTS: A total of 78 patients completed the study, and 74% chose DNR after the question video, whereas 73% chose DNR after the recommendation video. Median physician compassion score was very high and not different for both videos. All 30 of 30 patients who had chosen DNR for themselves and 30 of 48 patients who had not chosen DNR for themselves chose DNR for the video patient (100% versus 62%). Age (odds ratio = 1.1/year) and white ethnicity (odds ratio = 9.43) predicted DNR choice for the video patient. CONCLUSIONS: Ending DNR discussions with a question or a recommendation did not impact DNR choice or perception of physician compassion. Therefore, both approaches are clinically appropriate. All patients who chose DNR for themselves and most patients who did not choose DNR for themselves chose DNR for the video patient. Age and race predicted DNR choice.