Dynamic CD8+ T cell responses to cancer immunotherapy in human regional lymph nodes are disrupted in metastatic lymph nodes.

CD8+ T cell responses are critical for anti-tumor immunity. While extensively profiled in the tumor microenvironment, recent studies in mice identified responses in lymph nodes (LNs) as essential; however, the role of LNs in human cancer patients remains unknown. We examined CD8+ T cells in human head and neck squamous cell carcinomas, regional LNs, and blood using mass cytometry, single-cell genomics, and multiplexed ion beam imaging. We identified progenitor exhausted CD8+ T cells (Tpex) that were abundant in uninvolved LN and clonally related to terminally exhausted cells in the tumor. After anti-PD-L1 immunotherapy, Tpex in uninvolved LNs reduced in frequency but localized near dendritic cells and proliferating intermediate-exhausted CD8+ T cells (Tex-int), consistent with activation and differentiation. LN responses coincided with increased circulating Tex-int. In metastatic LNs, these response hallmarks were impaired, with immunosuppressive cellular niches. Our results identify important roles for LNs in anti-tumor immune responses in humans.

Discovering dominant tumor immune archetypes in a pan-cancer census.

Cancers display significant heterogeneity with respect to tissue of origin, driver mutations, and other features of the surrounding tissue. It is likely that individual tumors engage common patterns of the immune system-here "archetypes"-creating prototypical non-destructive tumor immune microenvironments (TMEs) and modulating tumor-targeting. To discover the dominant immune system archetypes, the University of California, San Francisco (UCSF) Immunoprofiler Initiative (IPI) processed 364 individual tumors across 12 cancer types using standardized protocols. Computational clustering of flow cytometry and transcriptomic data obtained from cell sub-compartments uncovered dominant patterns of immune composition across cancers. These archetypes were profound insofar as they also differentiated tumors based upon unique immune and tumor gene-expression patterns. They also partitioned well-established classifications of tumor biology. The IPI resource provides a template for understanding cancer immunity as a collection of dominant patterns of immune organization and provides a rational path forward to learn how to modulate these to improve therapy.

Antibody-Drug Conjugates in Gynecologic Cancers.

OPINION STATEMENT: Antibody-drug conjugates (ADCs) are a novel class of targeted cancer therapies with the ability to selectively deliver a cytotoxic drug to a tumor cell using a monoclonal antibody linked to a cytotoxic payload. The technology of ADCs allows for tumor-specificity, improved efficacy, and decreased toxicity compared to standard chemotherapy. Common toxicities associated with ADC use include ocular, pulmonary, hematologic, and neurologic toxicities. Several ADCs have been approved by the United States Food and Drug Administration (FDA) for the management of patients with recurrent or metastatic gynecologic cancers, a population with poor outcomes and limited effective treatment options. The first FDA-approved ADC for recurrent or metastatic cervical cancer was tisotumab vedotin, a tissue factor-targeting agent, after demonstrating response in the innovaTV 204 trial. Mirvetuximab soravtansine targets folate receptor alpha and is approved for use in patients with folate receptor alpha-positive, platinum-resistant, epithelial ovarian cancer based on results from the SORAYA trial. While there are no FDA-approved ADCs for the treatment of uterine cancer, trastuzumab deruxtecan, an anti-human epidermal growth factor receptor 2 (HER2) agent, is actively being investigated. In this review, we will describe the structure and mechanism of action of ADCs, discuss their toxicity profiles, review ADCs both approved and under investigation for the management of gynecologic cancers, and discuss mechanisms of ADC resistance.

Implementing guidelines for risk-stratified thromboprophylaxis among gynecologic oncology patients: A quality improvement initiative.

OBJECTIVE(S): Risk-stratified thromboprophylaxis is recommended for oncology patients with a Khorana risk score (KS) ≥ 2 receiving cancer-directed therapy. We describe a quality improvement (QI) initiative designed to increase adherence to thromboprophylaxis guidelines for patients with gynecologic malignancies initiating outpatient treatment. METHODS: Provider awareness and documentation of venous thromboembolism (VTE) risk assessment and thromboprophylaxis eligibility were identified as key QI drivers. Starting May 2021, a KS calculator and thromboprophylaxis algorithm were incorporated into outpatient documentation templates. Patients with gynecologic malignancies initiating outpatient therapy from January - December 2021 were eligible. The primary process measure was the percentage of patients with KS eligibility documented each month during the baseline (Jan - Apr) versus implementation (May - Dec) periods. Rate of appropriate thromboprophylaxis initiation and incidence of VTE served as outcome measures. Incidence of adverse bleeding events served as the balancing measure. RESULTS: 337 patients accounted for the initiation of 383 treatment regimens, including 128 in the baseline period and 255 in the implementation period. KS documentation increased significantly between the baseline and implementation periods (7% vs 62.4%, p < 0.001). 73 of the 177 eligible patients (46.2%; 166 unique patients) had appropriate documentation; of these, 57 initiated thromboprophylaxis. There was no difference in VTE rates or adverse bleeding events between eligible patients who initiated thromboprophylaxis compared with those who did not (12.3% vs 15.6%; p = 0.65 and 7.0% vs 8.2%; p = 1.0, respectively). CONCLUSION(S): This QI initiative resulted in greater adherence to risk-stratified thromboprophylaxis guidelines. No bleeding signals were identified. Studies addressing cost, medication adherence, and long-term outcomes are necessary.

Guidelines for goals of care discussions in patients with gynecologic cancer.

This article represents a distillation of literature to provide guidance for goals of care discussions with patients who have gynecologic malignancies. As clinicians who provide surgical care, chemotherapy, and targeted therapeutics, gynecologic oncology clinicians are uniquely positioned to form longitudinal relationships with patients that can enable patient-centered decision making. In this review, we describe optimal timing, components, and best practices for goals of care discussions in gynecologic oncology.

Understanding the spectrum of malignant bowel obstructions in gynecologic cancers and the application of the Henry score.

OBJECTIVE: Malignancy-associated bowel obstruction (MBO) is a potential sequela of advanced gynecologic cancers, adversely impacting both quality of life and prognosis. The Henry score (HS) was developed in a gastrointestinal cancer-predominant population to predict 30-day mortality. We aim to characterize MBO in gynecologic cancers and assess the utility of the HS in this population. METHODS: This is a retrospective review of patients with gynecologic cancer and MBO admitted to a single academic institution from 2016 to 2021. The primary outcome is to characterize malignant small and large bowel obstructions in primary and recurrent gynecologic cancer using readmission and mortality rates. Secondary outcomes are to assess the Henry score and inpatient MBO management. RESULTS: 179 patients totaling 269 were admissions identified, most commonly affecting patients with ovarian cancer. The majority (89.4%) were managed non-operatively while 10.6% were managed surgically. No significant differences were observed in survival for medical versus surgical management. Thirty-day mortality increased with increasing HS (0%, 0-1; 14.3%, 2-3; 40.9%, 4-5). Over 1/3 (34.1%) of patients were readmitted for recurrent or persistent MBO. Goals of care conversations were documented for 56.8% of patients with HS 4-5. Mortality rates across the entire cohort were high-20.1% and 60.9% had died by 1 and 6 months, respectively. CONCLUSIONS: Survival rates following an initial MBO admission are poor. The HS has utility in gynecologic cancers for assessing 30-day mortality and may be a useful tool to aid in the management and counseling of patients with gynecologic cancer and MBO.

"You start feeling comfortable, you just start sharing:" A qualitative study of patient distress screening in Black and White patients with endometrial cancer.

OBJECTIVES: Black patients with endometrial cancer are less likely to express distress and receive referrals for support services compared to White patients. We aim to characterize patient perceptions of the National Comprehensive Cancer Network Distress Thermometer and Problem List (NCCN DT & PL), a common distress screening tool, among Black and White patients with endometrial cancer and determine strategies to improve equity in referral to appropriate support services. METHODS: We conducted semi-structured interviews with 15 Black and 15 White patients with endometrial cancer who reported varying levels of distress on the NCCN DT & PL. Interviews were audio-recorded, transcribed, evaluated through staged content analysis, and salient themes were compared by patient race. RESULTS: The NCCN DT & PL was generally considered understandable, however the word "distress" could be alienating to participants who considered their stress to be less "drastic." Black participants mentioned fewer negative emotions such as worry and sadness in describing distress and spoke more often of a positive outlook. Additionally, Black participants emphasized the importance of relationship-building with clinicians for open communication on the NCCN DT & PL and clinical encounter. Finally, participants were divided on whether they would alter the way they completed the NCCN DT & PL given more information on cut off scores for referrals, but generally expressed a desire for more direct offers of support services. CONCLUSIONS: Relationship-building, open communication around emotion, and longitudinal direct offers of support emerged as avenues to reduce inequities in referral to supportive services for patients with endometrial cancer.

Radical hysterectomy case volume and cervical cancer treatment in the era of COVID-19: A multi-site analysis of National Cancer Institute-designated Comprehensive Cancer Centers.

OBJECTIVE: To compare radical hysterectomy case volume, cancer stage, and biopsy-to-treatment time of invasive cervical cancer diagnosed before and after onset of the COVID-19 pandemic. METHODS: In a multi-institution retrospective cohort study conducted at 6 large, geographically diverse National Cancer Institute-designated cancer centers, patients treated for newly diagnosed invasive cervical cancer were classified into 2 temporal cohorts based on date of first gynecologic oncology encounter: (1) Pre-Pandemic: 3/1/2018-2/28/2020; (2) Pandemic & Recovery: 4/1/2020-12/31/2021. The primary outcome was total monthly radical hysterectomy case volume. Secondary outcomes were stage at diagnosis and diagnosis-to-treatment time. Statistical analyses used chi-squared and two sample t-tests. RESULTS: Between 3/1/2018-12/31/2021, 561 patients were diagnosed with cervical cancer. The Pre-Pandemic and Pandemic & Recovery cohorts had similar age, race, ethnicity, smoking status, and Body Mass Index (BMI). During Pandemic & Recovery, the mean monthly radical hysterectomy case volume decreased from 7[SD 2.8] to 5[SD 2.0] (p = 0.001), the proportion of patients diagnosed with Stage I disease dropped from 278/561 (49.5%) to 155/381 (40.7%), and diagnosis of stage II-IV disease increased from 281/561 (50.1%) to 224/381 (58.8%). Primary surgical management was less frequent (38.3% Pandemic & Recovery versus 46.7% Pre-Pandemic, p = 0.013) and fewer surgically-treated patients received surgery within 6 weeks of diagnosis (27.4% versus 38.9%; p = 0.025). CONCLUSIONS: Lower radical hysterectomy case volume, a shift to higher cervical cancer stage, and delay in surgical therapy were observed across the United States following the COVID-19 outbreak. Decreased surgical volume may result from lower detection of early-stage disease or other factors.

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.

Cost-effectiveness of management strategies for patients with recurrent ovarian cancer and inoperable malignant bowel obstruction.

OBJECTIVES: Patients with recurrent platinum-resistant ovarian cancer often present with inoperable malignant bowel obstruction (MBO) from a large burden of abdominal disease. Interventions such as total parenteral nutrition (TPN) and chemotherapy may be used in this setting. We aim to describe the relative cost-effectiveness of these interventions to inform clinical decision making. METHODS: Four strategies for management of platinum-resistant recurrent ovarian cancer with inoperable MBO were compared from a societal perspective using a Monte Carlo simulation: (1) hospice, (2) TPN, (3) chemotherapy, and (4) TPN + chemotherapy. Survival, hospitalization rates, end-of-life (EOL) setting, and MBO-related utilities were obtained from literature review: hospice (survival 38 days, 6% hospitalization), chemotherapy (42 days, 29%), TPN (55 days, 25%), TPN + chemotherapy (74 days, 47%). Outcomes were the average cost per strategy and incremental cost-effectiveness ratios (ICERs) in US dollars per quality-adjusted life year (QALY) gained. RESULTS: In the base case scenario, TPN + chemotherapy was the most costly strategy (mean; 95% CI) ($49,741; $49,329-$50,162) and provided the highest QALYs (0.089; 0.089-0.090). The lowest cost strategy was hospice ($14,591; $14,527-$14,654). The TPN alone and chemotherapy alone strategies were dominated by a combination of hospice and TPN + chemotherapy. The ICER of TPN + chemotherapy was $918,538/QALY compared to hospice. With a societal willingness to pay threshold of $150,000/QALY, hospice was the strategy of choice in 71.6% of cases, chemotherapy alone in 28.4%, and TPN-containing strategies in 0%. CONCLUSIONS: TPN with or without chemotherapy is not cost-effective in management of inoperable malignant bowel obstruction and platinum-resistant ovarian cancer.

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.

Malnutrition as a risk factor for post-operative morbidity in gynecologic cancer: Analysis using a national surgical outcomes database.

OBJECTIVE: To assess, using a national surgical outcomes database, the association of various malnutrition definitions with post-operative morbidity in three gynecologic malignancies. METHODS: Patients undergoing resection of ovarian, uterine, or cervical cancer between 2005 and 2019 were identified using the National Surgical Quality Improvement Program (NSQIP) database. Patients were classified based on specific, pre-defined malnutrition criteria: severe malnutrition (Body Mass Index (BMI) <18.5 + 10% weight loss), European Society for Clinical Nutrition and Metabolism ((ESPEN1); BMI 18.5-22 + 10% weight loss), ESPEN2 (BMI < 18.5), American Cancer Society ((ACS); normal/overweight BMI + 10% weight loss), mild malnutrition (BMI 18.5-22), or albumin (<3.5 g/dL). Outcomes included 30-day major complications, readmission, reoperation. Modified Poisson regression estimated associations between definitions and outcomes. RESULTS: Of 76,290 total patients undergoing surgery, those meeting malnutrition definitions were: severe-98 (0.1%), ESPEN1-148 (0.2%), ESPEN2-877 (1.1%), ACS-1028 (1.3%), mild-2853 (3.7%), and albumin (11.1%). Complication rates were: unplanned readmission-5.5%, reoperation-1.7%, major complications-13.5%. For ovarian cancer, ESPEN2 malnutrition was associated with higher readmissions (risk ratio 1.69; 95% confidence interval 1.29-2.20), reoperations (2.53; 1.70-3.77), and complications (1.36; 1.20-1.54). For uterine cancer, ACS malnutrition was associated with readmissions (2.74; 2.09-3.59), reoperations (3.61; 2.29-5.71) and complications (3.92; 3.40-4.53). For cervical cancer, albumin<3.5 g/dL was associated with readmissions (1.48; 1.01-2.19), reoperations (2.25; 1.17-4.34), and complications (2.59; 2.11-3.17). Albumin<3.5 was associated with adverse outcomes in ovarian and uterine cancer. CONCLUSIONS: Preoperative risk assessments might be tailored using cancer-specific malnutrition criteria. Major complications, readmissions, and reoperations are all associated with the ESPEN2 definition for ovarian cancer, the ACS definition for uterine cancer, and with albumin<3.5 for all cancers.

Distress screening in endometrial cancer leads to disparity in referral to support services.

OBJECTIVES: Racial disparities in survival from endometrial cancer (EC) are well known. Cancer distress has also been associated with worse clinical outcomes. We characterized the association between race/ethnicity, patient distress reported on the National Comprehensive Cancer Network Distress Thermometer and Problem List (NCCN DT & PL), referral to support services, time to surgery, and acceptance of adjuvant therapy in patients with EC. METHODS: We included patients presenting at an academic gynecologic oncology practice from 1/2013-6/2020 who had not received prior EC-directed treatment. Demographics, NCCN DT scores, and treatment details were abstracted from the electronic medical record. Difference in initial DT scores by race/ethnicity and treatment type was tested using general linear modeling. The significance of interaction effects was tested using linear mixed models and logistic regression. RESULTS: 393 non-Hispanic White (NHW) and 134 non-Hispanic Black (NHB) patients were included. Median distress scores were higher in NHW patients compared to NHB patients (4 vs. 2, p < 0.001); 51% of NHW patients qualified for referral to support services compared to 40% of NHB patients (p = 0.03). Distress scores were highest at initial appointment and declined over time in NHW patients regardless of treatment, but were initially low and remained low over time in NHB patients. There was no association of initial distress score with time to surgery or acceptance of adjuvant treatment (p-values >0.25). CONCLUSIONS: An observed difference in NCCN DT leads to racial disparities in referral to support services. The NCCN DT may not adequately measure distress in NHB women with EC.

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.

Role of stereotactic body radiotherapy in gynecologic radiation oncology.

Stereotactic body radiotherapy (SBRT, also referred to as stereotactic ablative radiotherapy (SABR)) has been used in the treatment of primary and metastatic solid tumors, and increasingly so in gynecologic oncology. This review article aims to summarize the current literature describing the utility of SBRT in the primary, recurrent, and limited metastatic settings for gynecologic malignancies. The use of SBRT in both retrospective and prospective reports has been associated with adequate control of the treated site, particularly in the setting of oligometastatic disease. It is not, however, recommended as an alternative to brachytherapy for intact disease unless all efforts to use brachytherapy are exhausted. While phase I and II trials have established the relative safety and potential toxicities of SBRT, there remains a dearth of phase III randomized evidence, including the use of immunotherapy, in order to better establish the role of this technique as a method of improving more global outcomes for our patients with gynecologic cancers.

Measurement practices exacerbate the generalizability crisis: Novel digital measures can help.

Psychology's tendency to focus on confirmatory analyses before ensuring constructs are clearly defined and accurately measured is exacerbating the generalizability crisis. Our growing use of digital behaviors as predictors has revealed the fragility of subjective measures and the latent constructs they scaffold. However, new technologies can provide opportunities to improve conceptualizations, theories, and measurement practices.

Open-source smartphone app and tools for measuring, quantifying, and visualizing technology use.

Psychological science has spent many years attempting to understand the impact of new technology on people and society. However, the frequent use of self-report methods to quantify patterns of usage struggle to capture subtle nuances of human-computer interaction. This has become particularly problematic for devices like smartphones that are used frequently and for a variety of purposes. While commercial apps can provide an element of objectivity, these are 'closed' and cannot be adapted to deliver a researcher-focused 'open' platform that allows for straightforward replication. Therefore, we have developed an Android app that provides accurate, highly detailed, and customizable accounts of smartphone usage without compromising participants' privacy. Further recommendations and code are provided to assist with data analysis. All source code, materials, and data are freely available (see links in supplementary materials section).

Adherence to PARP inhibitor therapy among women with ovarian cancer.

OBJECTIVE: The objective of this study was to evaluate medical adherence for patients with ovarian cancer who initiated treatment with a PARP inhibitor therapy, and to identify factors associated with nonadherence. METHODS: We used the MarketScan Database to identify ovarian cancer patients who initiated PARP inhibitor therapy between January 1, 2008 and December 31, 2017. The primary outcome was adherence defined as ≥ 80% proportion of days covered (PDC). A secondary outcome included adherence assessed using the medication possession ratio (MPR). Multivariable logistic regression analysis was performed to assess relation between PDC and explanatory variables. Sensitivity analysis was performed to evaluate impact of dose-adjustments and toxicity-related delays on adherence. RESULTS: Among 170,976 patients diagnosed with ovarian cancer, 151 patients met inclusion criteria. The median time from diagnosis to initiating therapy was 33 months. Overall, 40 (26.5%) were non-adherent based on a PDC less than 80%. Non-adherent patients were more likely to receive niraparib and have a longer duration of therapy (p < 0.05). We found no significant impact of age, comorbidities, insurance plan, or year of PARP inhibitor initiation on non-adherence. In a sensitivity analysis to assess different definition of adherence, non-adherence ranged from 11.3% to 41.1%. When accounting for possible dose-adjustments, 21.2% of patients were non-adherent. CONCLUSION: This population based study of ovarian cancer patients found that a quarter of patients may be sub-optimally adherent to PARP inhibitor therapy. Future research should focus on identification of patients at risk for nonadherence and interventions to lower nonadherence among these patients.

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.

The preferences of women with ovarian cancer for oral versus intravenous recurrence regimens.

OBJECTIVE: To assess preferences of women with ovarian cancer regarding features of available anti-cancer regimens for platinum-resistant, biomarker-positive disease, with an emphasis on oral PARP inhibitor and standard intravenous (IV) chemotherapy regimens. METHODS: A discrete-choice-experiment preferences survey was designed, tested, and administered to women with ovarian cancer, with 11 pairs of treatment profiles defined using seven attributes (levels/ranges): regimen (oral daily, IV weekly, IV monthly); probability of progression-free (PFS) at 6 months (40%-60%); probability of PFS at 2 years (10%-20%); nausea (none, moderate); peripheral neuropathy (none, mild, moderate); memory problems (none, mild); and total out-of-pocket cost ($0 to $10,000). RESULTS: Of 123 participants, 38% had experienced recurrence, 25% were currently receiving chemotherapy, and 18% were currently taking a PARP inhibitor. Given attributes and levels, the relative importance weights (sum 100) were: 2-year PFS, 28; cost, 27; 6-month PFS, 19; neuropathy,14; memory problems, nausea, and regimen, all ≤5. To accept moderate neuropathy, participants required a 49% (versus 40%) chance of PFS at 6 months or 14% (versus 10%) chance at 2 years. Given a 3-way choice where PFS and cost were equal, 49% preferred a monthly IV regimen causing mild memory problems, 47% preferred an oral regimen causing moderate nausea, and 4% preferred a weekly IV regimen causing mild memory and mild neuropathy. CONCLUSIONS: These findings challenge the assumption that oral anti-cancer therapies are universally preferred by patients and demonstrate that there is no "one size fits all" regimen that is preferable to women with ovarian cancer when considering recurrence treatment regimens.