Treatments and outcomes in high-risk gestational trophoblastic neoplasia: A systematic review and meta-analysis.

BACKGROUND: High-risk gestational trophoblastic neoplasia (GTN) is rare and treated with diverse approaches. Limited published institutional data has yet to be systematically reviewed. OBJECTIVES: To compile global high-risk GTN (prognostic score ≥7) cohorts to summarise treatments and outcomes by disease characteristics and primary chemotherapy. SEARCH STRATEGY: MEDLINE, Embase, Scopus, ClinicalTrials.gov and Cochrane were searched through March 2021. SELECTION CRITERIA: Full-text manuscripts reporting mortality among ≥10 high-risk GTN patients. DATA COLLECTION AND ANALYSIS: Binomial proportions were summed, and random-effects meta-analyses performed. MAIN RESULTS: From 1137 records, we included 35 studies, representing 20 countries. Among 2276 unique high-risk GTN patients, 99.7% received chemotherapy, 35.8% surgery and 4.9% radiation. Mortality was 10.9% (243/2236; meta-analysis: 10%, 95% confidence interval [CI] 7-12%) and likelihood of complete response to primary chemotherapy was 79.7% (1506/1890; meta-analysis: 78%, 95% CI: 74-83%). Across 24 reporting studies, modern preferred chemotherapy (EMA/CO or EMA/EP) was associated with lower mortality (overall: 8.8 versus 9.5%; comparative meta-analysis: 8.1 versus 12.4%, OR 0.42, 95% CI: 0.20-0.90%, 14 studies) and higher likelihood of complete response (overall: 76.6 versus 72.8%; comparative meta-analysis: 75.9 versus 60.7%, OR 2.98, 95% CI: 1.06-8.35%, 14 studies), though studies focused on non-preferred regimens reported comparable outcomes. Mortality was increased for ultra-high-risk disease (30 versus 7.5% high-risk; meta-analysis OR 7.44, 95% CI: 4.29-12.9%) and disease following term delivery (20.8 versus 7.3% following molar pregnancy; meta-analysis OR 2.64, 95% CI: 1.10-6.31%). Relapse rate estimates ranged from 3 to 6%. CONCLUSIONS: High-risk GTN is responsive to several chemotherapy regimens, with EMA/CO or EMA/EP associated with improved outcomes. Mortality is increased in patients with ultra-high-risk, relapsed and post-term pregnancy disease.

Reducing non-surgical readmissions on a gynecologic oncology service.

OBJECTIVE: To assess the effects of a quality improvement (QI) initiative designed to reduce non-surgical readmissions on a gynecologic oncology service. METHODS: A two-phase QI initiative was implemented on an inpatient gynecologic oncology service to reduce non-surgical 30-day readmissions. Phase 1, from July 2018 to June 2020, included trainee education, frequent physical therapy consultation, pharmacy discharge medication review, 72-h post-discharge telephone call, and standardized 10-day clinic follow-up after discharge. Phase 2, from July 2020 to December 2020, incorporated a nurse practitioner to perform discharge navigation and arrange outpatient follow-up. The incidence of non-surgical readmissions during these phases was compared to that of a baseline period (July 2017-June 2018). We also assessed readmissions to identify common indications and evaluate potential demographic and clinical risk factors. RESULTS: Of 390 total non-surgical gynecologic oncology admissions, 100 were readmitted within 30 days (25.6%). Gastrointestinal tract (GI) obstruction, malignancy-associated pain and infection were the most common symptomatic diagnoses at the index admission, and 30% of readmitted patients had an identical indication for readmission. Compared to the baseline period, we observed a reduction in non-surgical readmissions from 34.1% to 22.6% in Phase 1 and to 18.9% in Phase 2 (p < 0.03) based on internal review, and a reduction from 13.9% to 11.9% in Phase 1 and to 4.7% in Phase 2 (p = 0.04) based on healthcare performance tracking data. CONCLUSIONS: 30-day hospital readmission among non-surgical gynecologic oncology patients is common. Implementation of a multifaceted readmissions reduction QI initiative significantly improved readmission rates.

Promoting timely goals of care conversations between gynecologic cancer patients at high-risk of death and their providers.

OBJECTIVE: We designed a multi-faceted intervention to increase the rate of outpatient goals of care (GOC) conversations in women with gynecologic cancers who are at high-risk of death. METHODS AND MATERIALS: A multidisciplinary team developed an educational program around GOC conversations at end-of-life and chose criteria to prospectively identify patients at high-risk of death who might benefit from timely GOC conversations: recurrent or metastatic endometrial, cervical or vulvar cancer or platinum-resistant ovarian cancer. Gynecologic oncology provider consensus was built regarding the need to improve the quality and timing of GOC conversations. Eligible outpatients were prospectively identified and providers alerted pre-encounter; timely GOC documentation within 3 visits of high-risk identification was tracked. Our institution concurrently and subsequently tracked GOC documentation during the last 6 months of life among all established oncology patients. RESULTS: Of 220 pilot period high-risk patients (96 pre- and 124 during pilot period 2017-2018), timely GOC discussion documentation increased from 30.2% to 88.7% (p < 0.001) and this increase was sustained over time. In the post-pilot period (2019-2020), among patients seen by oncologists during last 6 months of life, compared to other cancer types, gynecologic cancer patients had a higher rate of GOC documentation (81% versus 9%; p < 0.001), a lower rate of receiving chemotherapy during the last 14 days of life (2% vs 5%; p = 0.051), and no difference in end-of-life admissions (29% vs 31%; p = NS). CONCLUSIONS: Implementation of systematic outpatient identification of high-risk gynecologic oncology patients is feasible, sustainable, and increases the timely conduct of GOC conversations.

Chemotherapy discontinuation processes in a gynecologic oncology population.

OBJECTIVE: We sought to categorize the processes by which gynecologic oncology patients stop chemotherapy and to evaluate associations between these processes and end-of-life outcome metrics. METHODS: A cohort of patients with metastatic or recurrent gynecologic cancer in an outpatient setting from January 2016 to May 2018 was identified. All deceased patients in this cohort were included for analysis. Processes of discontinuing chemotherapy were categorized as: 1) definitive decision inpatient; 2) definitive decision outpatient; 3) delayed decision (eg: treatment break and never resumed chemotherapy); 4) no decision. Associations between patient characteristics and clinical outcomes of those who made a definitive outpatient decision versus those who made any other type of decision were assessed. RESULTS: 220 patients were identified; 205 patients were deceased at time of analysis. Of these, 36.6% made a definitive decision to stop chemotherapy as an outpatient, while 41.5% never made a decision to discontinue chemotherapy. Making a definitive decision as an outpatient, when compared to all other decision types, was associated with significantly lower incidence of death in the hospital (5.6% vs 21.1%, p < 0.004) and hospitalization within 30 days of death (20.8% vs 56.6%, p < 0.001), and significantly increased median time from last chemotherapy to death (135.5 vs 62 days, p < 0.001). CONCLUSION: Only one in three women in this cohort of patients deceased from gynecologic cancer made a definitive decision to discontinue chemotherapy in an outpatient setting, and this process was associated with improved end-of-life outcomes. Future efforts should examine the impact of interventions designed to increase the proportion of patients who transition away from chemotherapy via shared decision making in the outpatient setting.

Primary cytoreductive surgery for advanced stage endometrial cancer: a systematic review and meta-analysis.

OBJECTIVE: Endometrial cancer uncommonly presents at an advanced stage and little prospective evidence exists to guide the management thereof. We aimed to summarize the evidence about primary cytoreductive surgery in the treatment of advanced stage endometrial cancer. DATA SOURCES: MEDLINE, Embase, and Scopus databases were searched from inception to September 11, 2020, using search terms representing the themes "endometrial cancer," "advanced stage," and "primary cytoreductive surgery." STUDY ELIGIBILITY CRITERIA: We included full-text, English reports that included ≥10 patients undergoing primary cytoreductive surgery for advanced stage endometrial cancer and that reported on the outcomes of primary cytoreductive surgery and survival rates based on the residual disease burden. METHODS: Two reviewers independently screened the studies and with disagreements between the reviewers resolved by a third reviewer. Data were extracted using a standardized form. The percentage of cases reaching maximal (no gross residual disease) and optimal (<1 cm or <2 cm residual disease) cytoreduction were assessed by summing binomials proportions, and the association with survival was assessed using an inverse variance-weighted meta-analysis of logarithmic hazard ratios. RESULTS: From 1219 unique records identified, 34 studies were selected for inclusion. Studies consisted of single or multi-institutional cohorts of patients collected over a period of 6 to 24 years and included various mixes of histologies (endometrioid, serous, clear cell, and carcinosarcoma) and disease stages (III or IV). In a meta-analysis of the extent of residual disease after primary cytoreductive surgery, we found that 52.1% of cases reached no gross residual disease status (n=18 studies; 1329 patients) and 75% reached <1 cm residual disease status (n=27 studies; 2343 patients). The proportion of cytoreduction for both thresholds was lower for studies of stage IV vs stage III to IV disease (41.4% vs 69.8% for no gross residual disease; 63.2% vs 82.2% for <1 cm residual disease) but did not vary notably by histology. In a meta-analysis of the reported hazard ratios, submaximal (any gross residual disease vs no gross residual disease) and suboptimal (≥1 cm vs <1 cm) cytoreduction thresholds were associated with worse progression-free survival (submaximal hazard ratio, 2.16; 95% confidence interval, 1.45-3.21; I2=68%; suboptimal hazard ratio, 2.55; 95% confidence interval, 1.93-3.37; I2=63%) and overall survival rates (submaximal hazard ratio, 2.57; 95% confidence interval, 2.13-3.10; I2=1%; suboptimal hazard ratio, 2.62; 95% confidence interval, 2.20-3.11; I2=15%). Sensitivity analyses limited to high-quality studies demonstrated consistent results. CONCLUSION: Among cases of advanced stage endometrial cancer undergoing primary cytoreductive surgery, a significant proportion of patients are left with residual disease, which is associated with worse survival outcomes. Further investigations about the roles of neoadjuvant chemotherapy and primary cytoreductive surgery in prospective trials is warranted in this population.

Development and Validation of a Model for Opioid Prescribing Following Gynecological Surgery.

Importance: Overprescription of opioid medications following surgery is well documented. Current prescribing models have been proposed in narrow patient populations, which limits their generalizability. Objective: To develop and validate a model for predicting outpatient opioid use following a range of gynecological surgical procedures. Design, Setting, and Participants: In this prognostic study, statistical models were explored using data from a training cohort of participants undergoing gynecological surgery for benign and malignant indications enrolled prospectively at a single institution's academic gynecologic oncology practice from February 2018 to March 2019 (cohort 1) and considering 39 candidate predictors of opioid use. Final models were internally validated using a separate testing cohort enrolled from May 2019 to February 2020 (cohort 2). The best final model was updated by combining cohorts, and an online calculator was created. Data analysis was performed from March to May 2020. Exposures: Participants completed a preoperative survey and weekly postoperative assessments (up to 6 weeks) following gynecological surgery. Pain management was at the discretion of clinical practitioners. Main Outcomes and Measures: The response variable used in model development was number of pills used postoperatively, and the primary outcome was model performance using ordinal concordance and Brier score. Results: Data from 382 female adult participants (mean age, 56 years; range, 18-87 years) undergoing gynecological surgery (minimally invasive procedures, 158 patients [73%] in cohort 1 and 118 patients [71%] in cohort 2; open surgical procedures, 58 patients [27%] in cohort 1 and 48 patients [29%] in cohort 2) were included in model development. One hundred forty-seven patients (38%) used 0 pills after hospital discharge, and the mean (SD) number of pills used was 7 (10) (median [IQR], 3 [0-10] pills). The model used 7 predictors: age, educational attainment, smoking history, anticipated pain medication use, anxiety regarding surgery, operative time, and preoperative pregabalin administration. The ordinal concordance was 0.65 (95% CI, 0.62-0.68) for predicting 5 or more pills (Brier score, 0.22), 0.65 (95% CI, 0.62-0.68) for predicting 10 or more pills (Brier score, 0.18), and 0.65 (95% CI, 0.62-0.68) for predicting 15 or more pills (Brier score, 0.14). Conclusions and Relevance: This model provides individualized estimates of outpatient opioid use following a range of gynecological surgical procedures for benign and malignant indications with all model inputs available at the time of procedure closing. Implementation of this model into the clinical setting is currently ongoing, with plans for additional validation in other surgical populations.

Understanding the needs and perspectives of ovarian cancer patients when considering PARP inhibitor maintenance therapy: Findings from two online community events.

Objective: The online environment is an ideal setting to understand how many women seek, receive, and understand information about cancer treatment. The purpose of this study was to understand women's needs and information-seeking around Poly ADP ribose polymerase (PARP) inhibitors, an oral medication commonly prescribed as maintenance therapy at the conclusion of primary chemotherapy for ovarian cancer. Methods: We held online discussion events with two social media communities, #gyncsm social media on Twitter and the Smart Patients ovarian cancer community, in November 2020, to sample ovarian cancer patient perceptions of, and information seeking about PARP inhibitors. Focused questions were presented to both communities, with participants able to answer and elaborate upon these questions, as well as to add their own comments or topics. Qualitative content analysis was performed on the transcripts from the two online events. Results: A total of 254 unique tweets and 71 messages were generated from the Twitter and Smart Patients conversations, respectively. The majority of the content from these two events could be categorized into five major themes: (1) concerns about side effects, (2) expectations of benefit, (3) desire for more information regarding clinical trials, ) (4) desire to better understand the relationship between mutation status and PARP inhibitor effectiveness, and (5) financial toxicity. Misinformation was rarely identified. Conclusions: Women with ovarian cancer who are engaged in online patient communities have numerous educational needs regarding PARP inhibitors. Given the complexity of clinical research on PARP inhibitors, patients would likely benefit from patient-centered educational tools.

Evaluation of the clinical Index of Stable febrile neutropenia risk stratification system for management of febrile neutropenia in gynecologic oncology patients.

OBJECTIVE: Scoring systems have been developed to identify low risk patients with febrile neutropenia (FN) who may be candidates for outpatient management. We sought to validate the predictive accuracy of the Clinical Index of Stable Febrile Neutropenia (CISNE) score alone and in conjunction with alternative scoring systems for risk of complications among gynecologic oncology patients. METHODS: We conducted a single institution retrospective cohort study of patients admitted to an academic gynecologic oncology service for FN. We examined the performance characteristics (sensitivity, specificity, positive and negative predictive value) of three scoring systems (Multinational Association of Supportive Care in Cancer (MASCC), CISNE cut-off 1 (Low risk = 0), CISNE cut-off 2 (Low risk = <3)), and the combination of MASCC and CISNE to predict complications: inpatient death, ICU admission, hypotension, respiratory/renal failure, mental status change, cardiac failure, bleeding, and arrhythmia. RESULTS: Fifty patients were identified for study inclusion. No low-risk CISNE patients died during hospitalization. Fewer CISNE low-risk patients experienced complications compared to high-risk patients, regardless of cut-off. Sensitivity, specificity, positive and negative predictive values of the scoring systems were: CISNE 1-37.1%, 86.7%, 86.7%, 37.1%; CISNE 2-85.7%, 46.7%, 78.9%, 58.3%; MASCC-82.9%, 66.7%, 85.3%, 62.5%; MASCC + CISNE 1-37.1%, 93.3%, 92.9%, 38.9%; MASCC + CISNE 2-80%, 73.3%, 87.5%, 61.1%. CONCLUSIONS: The CISNE scoring system is an appropriate tool for the identification of patients with gynecologic cancers and FN who may benefit from close outpatient management. CISNE cut-off 2 performed comparably to the MASCC, but CISNE cut-off 1 had a higher specificity and positive predictive value.

Image quality of EOS low-dose radiography in comparison with conventional radiography for assessment of ventriculoperitoneal shunt integrity.

OBJECTIVE: Patients with shunted hydrocephalus often accumulate high levels of radiation over their lifetimes during evaluation of hardware integrity. Current practice involves the use of a series of conventional radiographs for this purpose. Newer low-dose EOS radiography is currently used to evaluate scoliosis but has not been explored to evaluate shunt integrity on a large scale. The goal of this study was to compare the quality of imaging using EOS low-dose radiography to conventional radiography to evaluate shunt tubing. METHODS: A retrospective chart review was performed on 57 patients who previously had both conventional radiographs and low-dose EOS images of their cerebral shunt tubing from 2000 to 2018. Patient demographics (age, sex, type of shunt tubing, primary diagnosis) were collected. Conventional radiographic images and low-dose EOS images were independently analyzed by a neurosurgeon and neuroradiologist in three categories: image quality, delineation of shunt, and distinction of shunt compared to adjacent anatomy. RESULTS: All patients had shunted hydrocephalus due to spina bifida and Chiari type II malformation. Ratings of EOS and conventional radiographic images by both raters did not differ significantly in terms of image quality (rater 1, p = 0.499; rater 2, p = 0.578) or delineation of shunt (p = 0.107 and p = 0.256). Conventional radiographic images received significantly higher ratings than EOS on the ability to distinguish the shunt versus adjacent anatomy by rater 1 (p = 0.039), but not by rater 2 (p = 0.149). The overall score of the three categories combined was not significantly different between EOS and conventional radiography (rater 1, p = 0.818; rater 2, p = 0.186). In terms of cost, an EOS image was less costly than a conventional radiography shunt series ($236-$366 and $1300-$1547, respectively). The radiation dose was also lower for EOS images, with an effective dose of 0.086-0.140 mSv compared to approximately 1.6 mSv for a similar field of view with conventional radiography. CONCLUSIONS: The image quality of low-dose EOS radiography does not significantly differ from conventional radiography for the evaluation of cerebral shunts. In addition, EOS affords a much lower radiation dose and a lower cost.

Transcranial magnetic stimulation demonstrates a role for the ventrolateral prefrontal cortex in emotion perception.

The lateral prefrontal cortex, a region with both structural and functional connectivity to the amygdala, has been consistently implicated in the downregulation of subcortical-generated emotional responses. Although previous work has demonstrated that the ventral lateral prefrontal cortex (vlPFC) is important to emotion processing, no study has interrupted vlPFC function in order to test is role in emotion perception. In the current study, we acutely disrupted vlPFC function in twenty healthy adult participants by administering sham stimulation and transcranial magnetic stimulation (TMS), in randomized order, during performance of an emotional perception task. During sham stimulation, participants demonstrated increased perceptual sensitivity for happy faces compared to angry faces. Disruption of the vlPFC eliminated this difference: in this condition, perceptual sensitivity did not differ between happy and angry faces. Reaction times and response bias did not differ between emotions or TMS conditions. This pattern of perceptual bias is consistent with effects observed in a wide range of affective disorders, in which vlPFC dysfunction has also been reported. This study provides insight into a possible mechanism through which the vlPFC may contribute to emotion perception.

Adherence to Oral Anticancer Therapeutics in the Gynecologic Oncology Population.

INTRODUCTION: To gain a better understanding of gynecologic oncology patient adherence to oral anticancer agents through both a cross-sectional survey of adherence and qualitative interviews with patients and clinicians regarding their experience with these medications. METHODS: Eligible participants completed a survey for this cross-sectional study that included an assessment of adherence, distress, quality of life, and health literacy. Any woman taking an oral anticancer agent for a gynecologic malignancy at a tertiary academic medical center for 30 days or more was eligible. Semi-structured qualitative interviews (n=14) were then conducted to explore experiences with oral anticancer agents. We also conducted a qualitative group interview with physicians and nurse practitioners. RESULTS: One hundred women taking oral anticancer agents were enrolled. Fifty-four percent reported perfect adherence to their medication, 21% reported equivocal adherence (demonstrating at least one nonadherent behavior in the previous 7 days), and 25% reported nonadherence (demonstrating more than one nonadherent behavior in the previous 7 days). Qualitative analysis identified five major themes: ease of use compared with traditional therapy; the mental burden of self-administrated medication; perceived importance of the medication; management of side effects; and the desire for consistent physician communication. Common misperceptions expressed in the health care professional interviews included high adherence to oral medications and a belief that cost was the biggest barrier to adherence. CONCLUSION: Almost half of the patients surveyed reported equivocal or nonadherence to their oral anticancer agent. The qualitative interviews identified several important themes, many of which were not recognized by physicians and nurse practitioners. These findings highlight the need for patient and health care professional interventions to improve patient adherence.

An electroencephalographic signature predicts antidepressant response in major depression.

Antidepressants are widely prescribed, but their efficacy relative to placebo is modest, in part because the clinical diagnosis of major depression encompasses biologically heterogeneous conditions. Here, we sought to identify a neurobiological signature of response to antidepressant treatment as compared to placebo. We designed a latent-space machine-learning algorithm tailored for resting-state electroencephalography (EEG) and applied it to data from the largest imaging-coupled, placebo-controlled antidepressant study (n = 309). Symptom improvement was robustly predicted in a manner both specific for the antidepressant sertraline (versus placebo) and generalizable across different study sites and EEG equipment. This sertraline-predictive EEG signature generalized to two depression samples, wherein it reflected general antidepressant medication responsivity and related differentially to a repetitive transcranial magnetic stimulation treatment outcome. Furthermore, we found that the sertraline resting-state EEG signature indexed prefrontal neural responsivity, as measured by concurrent transcranial magnetic stimulation and EEG. Our findings advance the neurobiological understanding of antidepressant treatment through an EEG-tailored computational model and provide a clinical avenue for personalized treatment of depression.