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Poly(ADP-ribose) polymerase inhibitors (PARPi) have dramatically changed treatment for advanced ovarian cancer, but nearly half of patients experience significant fatigue. We conducted a two-site pilot randomized trial to evaluate the feasibility, acceptability, and preliminary efficacy of a brief, acceptance-based telehealth intervention (REVITALIZE) designed to reduce fatigue interference in patients on PARPi. From June 2021 to April 2022, 44 participants were randomized 1:1 to REVITALIZE (6 weekly one-on-one sessions+booster) or enhanced usual care. Feasibility was defined as: ≥50% approach-to-consent among potentially eligible patients and ≥70% completion of 12-week follow-up assessment; acceptance was <20% participants reporting burden and <20% study withdrawal. Fatigue, anxiety, depression, and quality of life were assessed at baseline, 4-, 8- and 12-weeks. Among 44 participants (mean age = 62.5 years, 81.8% stage III/IV disease), the study was feasible (56.4% approach-to-consent ratio, 86.3% completion of 12-week assessment) and acceptable (0% reporting burden, 11.3% study withdrawal). At 12-week follow-up, REVITALIZE significantly reduced fatigue interference (Cohen's d = 0.94, p =.008) and fatigue severity (d = 0.54, p =.049), and improved fatigue levels (d = 0.62, p =.04) relative to enhanced usual care. REVITALIZE also showed promise for improved fatigue self-efficacy, fatigue catastrophizing, anxiety, depression, and quality of life (d s = 0.60–0.86, p ≥.05). Compared with enhanced usual care, REVITALIZE participants had fewer PARPi dose reductions (6.7% vs. 19.0%), and dose delays (6.7% vs. 23.8%). Among fatigued adults with ovarian cancer on PARPi, a brief, acceptance-based telehealth intervention was feasible, acceptable, and demonstrated preliminary efficacy in improving fatigue interference, severity, and levels. REVITALIZE is a novel, scalable telehealth intervention worthy of further investigation. • REVITALIZE, an ACT-based intervention, reduced fatigue in ovarian cancer patients with PARP-inhibitor associated fatigue. • REVITALIZE–a brief, acceptance-based telehealth intervention–is feasible, acceptable, and has preliminary efficacy. • Compared with the control, REVITALIZE improved fatigue interference, fatigue severity, and fatigue levels. • REVITALIZE improved fatigue catastrophizing, self-efficacy, depression, and quality of life outcomes relative to control. [ABSTRACT FROM AUTHOR]

Purpose To provide guidance to clinicians regarding the use of neoadjuvant chemotherapy and interval cytoreduction among women with stage IIIC or IV epithelial ovarian cancer. Methods The Society of Gynecologic Oncology and the American Society of Clinical Oncology convened an Expert Panel and conducted a systematic review of the literature. Results Four phase III clinical trials form the primary evidence base for the recommendations. The published studies suggest that for selected women with stage IIIC or IV epithelial ovarian cancer, neoadjuvant chemotherapy and interval cytoreduction are non-inferior to primary cytoreduction and adjuvant chemotherapy with respect to overall and progression-free survival and are associated with less perioperative morbidity and mortality. Recommendations All women with suspected stage IIIC or IV invasive epithelial ovarian cancer should be evaluated by a gynecologic oncologist prior to initiation of therapy. The primary clinical evaluation should include a CT of the abdomen and pelvis, and chest imaging (CT preferred). Women with a high perioperative risk profile or a low likelihood of achieving cytoreduction to < 1 cm of residual disease (ideally to no visible disease) should receive neoadjuvant chemotherapy. Women who are fit for primary cytoreductive surgery, and with potentially resectable disease, may receive either neoadjuvant chemotherapy or primary cytoreductive surgery. However, primary cytoreductive surgery is preferred if there is a high likelihood of achieving cytoreduction to < 1 cm (ideally to no visible disease) with acceptable morbidity. Before neoadjuvant chemotherapy is delivered, all patients should have confirmation of an invasive ovarian, fallopian tube, or peritoneal cancer. Additional information is available at www.asco.org/NACT-ovarian-guideline and www.asco.org/guidelineswiki . [ABSTRACT FROM AUTHOR]

Objective To describe the effects of obesity on the pharmacokinetics and dosing of chemotherapies and provide recommendations for chemotherapy management in obese women with gynecologic malignancies. Methods PubMEd and MEDLINE databases were searched for articles published before June 2014. Only English-language articles were considered. 84 manuscripts were reviewed and 66 were included. Search terms included: obesity, overweight, body mass index, body surface area, glomerular filtration rate, chemotherapy, ovarian cancer, endometrial cancer, inflammation, and pharmacokinetics, Results Obese cancer patients have worse clinical outcomes, compared with non-obese patients. This may be because of differences in pharmacokinetics, metabolic dysregulation, or physicians' decisions to reduce chemotherapy dose-intensity during treatment to minimize toxicities. A 2012 American Society of Clinical Oncology Clinical Practice Guideline recommends using actual body weight for chemotherapy dosing in all patients treated with curative intent, irrespective of obesity, to avoid compromising clinical outcomes, including progression free survival (PFS) and overall survival (OS). In women with gynecologic cancers most studies demonstrate no difference in PFS or OS when obese patients receive the same chemotherapy dose intensity as non-obese patients, except perhaps with bevacizumab. Conclusions Chemotherapy dose-intensity is a critical determinant of cancer outcomes and should be maintained in all patients, irrespective of obesity. Future studies should prospectively examine the impact of obesity on clinical outcomes (adverse events, survival) to improve the care of this growing population of patients who are at risk for inferior clinical outcomes. [ABSTRACT FROM AUTHOR]

Peritoneal carcinomatosis (PC) is common in patients with advanced gynecologic and gastrointestinal cancers. Frequently, patients with PC undergo palliative surgery or procedures to manage disease-related complications and side effects. However, there are limited data regarding patients' and family caregivers' decision-making processes about these procedures. Thus, we sought to describe the decision-making experiences of patients with PC who elect to pursue palliative surgical procedures and their family caregivers. We conducted a secondary analysis of qualitative data collected during a pilot randomized controlled trial of BOLSTER, a nurse-led telehealth intervention for patients with PC and their caregivers after an acute hospitalization and palliative procedure. Participants in both study arms described their experiences in semi-structured interviews. We re-analyzed coded qualitative data with a focus on understanding decision-making experiences surrounding palliative surgery and procedures using conventional content analysis. Interviews from 32 participants, 23 patients and 9 caregivers, were analyzed. Participants reported their decision-making was complicated by illness uncertainty and a desire for clear, effective communication with surgical and medical oncology teams. Participants requested more information about the impact of palliative procedures on their daily life. Several also noted that, without improved understanding, a misalignment between patient and family caregiver goals and palliative procedures may inadvertently increase suffering. Discussions related to patients' goals and preferences can improve the quality of treatment decision-making in patients with PC and their caregivers. Future research should test interventions to improve advanced cancer patients' illness understanding and decision-making surrounding palliative surgery and procedures. • Patients and their caregivers may feel poorly prepared to decide whether or not to proceed with a palliative procedure. • Increased decision-making support surrounding palliative procedures and surgery is necessary. • Interventions that foster human connection may improve treatment decision-making. [ABSTRACT FROM AUTHOR]

Patients with advanced gynecologic (GYN) and gastrointestinal (GI) cancers frequently develop peritoneal carcinomatosis (PC), which limits prognosis and diminishes health-related quality of life (HRQoL). Palliative procedures may improve PC symptoms, yet patients and caregivers report feeling unprepared to manage ostomies, catheters, and other complex needs. Our objectives were to (1) assess the feasibility of an efficacy trial of a nurse-led telehealth intervention (BOLSTER) for patients with PC and their caregivers; and (2) assess BOLSTER's acceptability, potential to improve patients' HRQoL and self-efficacy, and potential impact on advance care planning (ACP). Pilot feasibility RCT. Recently hospitalized adults with advanced GYN and GI cancers, PC, and a new complex care need and their caregivers were randomized 1:1 to BOLSTER or enhanced discharge planning (EDP). We defined feasibility as a ≥ 50% approach-to-consent ratio and acceptability as ≥70% satisfaction with BOLSTER. We assessed patients' HRQoL and self-efficacy at baseline and six weeks, then compared the proportion experiencing meaningful improvements by arm. ACP documentation was identified using natural language processing. We consented 77% of approached patients. In the BOLSTER arm, 91.0% of patients and 100.0% of caregivers were satisfied. Compared to EDP, more patients receiving BOLSTER experienced improvements in HRQoL (68.4% vs. 40.0%) and self-efficacy for managing symptoms (78.9% vs. 35.0%) and treatment (52.9% vs. 42.9%). The BOLSTER arm had more ACP documentation. BOLSTER is a feasible and acceptable intervention with the potential to improve patients' HRQoL and promote ACP. An efficacy trial comparing BOLSTER to usual care is underway. ClinicalTrials.gov : NCT03367247 ; PI: Wright. • An efficacy trial of a nurse-led telehealth intervention (BOLSTER) for patients with peritoneal carcinomatosis is feasible. • Patients and caregivers were satisfied with BOLSTER and said they would recommend it to others. • Patients in the BOLSTER arm experienced clinically meaningful improvements in quality of life and self-efficacy. • Patients in the BOLSTER arm had more advance care planning documentation than those in the control arm. [ABSTRACT FROM AUTHOR]

Patients with peritoneal carcinomatosis (PC) frequently undergo palliative procedures, yet these patients and their caregivers report being unprepared to manage ostomies, drains, and other complex care needs at home. The purpose of this study was to characterize the unique needs of these patients and their caregivers during care transitions. Patients completed measures of health status and advance care planning, caregivers completed measures of preparedness and burden, and all participants completed measures of depression and anxiety. Participants detailed their experiences in individual, semi-structured interviews. We analyzed data using descriptive statistics and conventional content analysis. Sixty-one patients and 39 caregivers completed baseline measures. Twenty-four (39.3%) patients acknowledged their terminal illness and seven (11.5%) had discussed end-of-life care preferences with clinicians. Most (26/39, 66.7%) caregivers provided daily care. Among caregivers who managed symptoms, few were taught how to do so (6/20, 30%). Seven patients (11.5%) and seven caregivers (17.9%) met case criteria for anxiety, while 15 patients (24.6%) and two caregivers (5.1%) met case criteria for depression. Interview participants described a diagnosis of PC as a turning point for which there is no road map and identified the need for health systems change to minimize suffering. Patients with PC and their caregivers are highly burdened by symptoms and care needs. Patients' prognostic understanding and advance care planning are suboptimal. Interventions that train patients with PC and their caregivers to perform clinical care tasks, facilitate serious illness conversations, and provide psychosocial support are needed. • Patients with peritoneal carcinomatosis and caregivers report complex physical, psychosocial, and existential challenges. • Patients' mean health-related quality of life score was below the 25th percentile for patients with cancer. • Caregivers reported worse mental health than the general population. • Just over one-third of patients acknowledged the terminal nature of their illness. • Patients and caregivers require training and psychosocial support after palliative procedures for peritoneal carcinomatosis. [ABSTRACT FROM AUTHOR]

Greater perceived patient-centered communication (PCC) is associated with better health-related quality of life (HRQoL) in patients with ovarian cancer. Quantitative measures of PCC and HRQoL do little to explain this association. We interviewed patients with high and low ratings of PCC to understand how it is associated with HRQoL. Explanatory sequential mixed methods study. Participants were English-speaking U.S. adults with ovarian cancer. We assessed PCC with the Patient-Centered Communication - Cancer (PCC-Ca)-36 (possible score range 1–5; higher scores represent greater patient-centeredness), and purposively sampled 14 participants with total scores in the top and bottom quartiles. Participants completed individual, semi-structured interviews about their communication experiences. Guided by the National Cancer Institute Framework for PCC in Cancer Care, we analyzed interview transcripts using directed content analysis. We integrated survey and interview findings in a joint display. Among 176 survey respondents, PCC-Ca-36 total scores ranged from 1.7 to 5.0. Participants with scores in the top quartile (4.8–5.0) perceived clinicians as proactive and attentive to psychosocial concerns. Those with scores in the bottom quartile (1.7–3.5) described not feeling known as an individual and receiving limited support for self-management. The association between PCC and QoL may be partially explained by differences in perceived support for psychosocial concerns and self-management. PCC may facilitate receipt of proactive, personalized care. • Patient-clinician communication is positively associated with health-related quality of life (HRQoL) in ovarian cancer care. • Patients' perceptions of clinicians' commitment, self-care burden, and psychosocial support may influence HRQoL. • Empathetic communication strategies and patient navigation services may shape these influences. • Eliciting information preferences prior to information exchange may promote well-being in these patients. [ABSTRACT FROM AUTHOR]

To describe perceptions of patient-centered communication (PCC); assess whether physician specialty, patient characteristics, or health system characteristics are associated with PCC; and identify associations between PCC, health-related quality of life (HRQoL), and symptom burden among individuals with ovarian cancer. Cross-sectional, descriptive survey of English-speaking adults with ovarian cancer. PCC, HRQoL, and ovarian cancer symptom burden were assessed with the PCC-Ca-36, the FACT-G, and the FOSI-18, respectively. PCC-Ca-36 scores were summarized using descriptive statistics. Predictors of PCC-Ca-36, FACT-G, and FOSI-18 scores were identified using multiple linear regression. Participants (n = 176) had a mean age of 59.4 years (SD = 12.1). The majority (65.9%) had advanced-stage disease, while 42.0% were receiving treatment. The mean PCC-Ca-36 total score was 4.09 (SD = 0.78) out of a possible 5, indicating participants often perceived that clinicians engaged in PCC. Among the PCC functions, participants reported that clinicians least often enabled patient self-management (M = 3.65, SD = 0.99), responded to emotions (M = 3.84, SD = 1.04), and managed uncertainty (M = 3.91, SD = 0.93). In multivariable analyses, neither physician specialty nor patient and health system characteristics were significantly associated with overall PCC. Greater overall PCC predicted better overall HRQoL; better social/family, emotional, and functional well-being; and lower overall and physical symptom burden (all p ≤ 0.05). Greater PCC is significantly associated with better HRQoL and lower symptom burden among individuals with ovarian cancer. Promotion of PCC is a promising strategy to improve patient-reported outcomes in the ovarian cancer care setting. • Participants least often perceived that clinicians enabled self-management, responded to emotions, or managed uncertainty • Physician specialty, patient characteristics, and health system characteristics did not predict overall PCC • Greater overall PCC predicted better health-related quality of life and lower symptom burden • Enabling patient self-management represents a key opportunity to improve PCC and health-related quality of life [ABSTRACT FROM AUTHOR]

Physical activity improves physical function, quality of life, and mental health, yet fewer than 80% of ovarian cancer survivors meet activity guidelines. This pilot intervention study aimed to increase physical activity in ovarian cancer survivors by leveraging principles of behavioral economics, gamification, and social support. This 24-week study (12-week intervention; 12-week follow-up) enrolled women with ovarian cancer after completion of first-line treatment with a self-selected "teammate." Participants used Fitbits to measure daily steps, select an increased step goal, and enroll in a collaborative game, including points and levels for achieving step goals. Primary outcomes were feasibility (defined a priori as ≥60% approach-to-consent ratio and ≥ 70% adherence to Fitbit), acceptability (≤20% of participants reporting burden or regret for participation) and preliminary efficacy (≥70% reporting increased motivation); exploratory outcomes included change in steps. We recruited 24 participants (mean age = 63 years, range = 37–79 years) with a 94% approach-to-consent ratio. All participants completed the intervention with 94% tracker adherence. At 24-week follow-up, 1/24 (≤5%) of participants reported burden; 0/24 (0%) reported regret for study participation; and 22/24 (>90%) agreed/strongly agreed that "the study motivated me to increase activity levels." Participants' mean daily steps were 6210.7 (±3328.1) at baseline and increased to 7643 (± 3610.9) steps (p < 0.001) during the 12-week intervention. This pilot study demonstrated feasibility, acceptability, and preliminary efficacy, justifying a larger randomized clinical trial to test efficacy at increasing activity levels. Future studies should examine strategies for maintaining increased activity levels in survivors over time. • Ovarian cancer survivors struggle to meet activity guidelines. • Walking is low-cost and safe for ovarian cancer survivors. • A game to increase steps was feasible and acceptable for survivors. • Daily steps significantly increased during the intervention. • A randomized control trial is needed to test the intervention's efficacy. [ABSTRACT FROM AUTHOR]

Germline genetic testing is crucial to the care of ovarian cancer patients, and as part of the guideline-based care for ovarian cancer patient's adherence to this recommendation has been low. We sought to determine whether embedding a genetic counselor (GC) within a medical and gynecologic oncology clinic would increase testing rates and improve the timeliness of testing. Prospective cohort study of 358 ovarian cancer patients seen by medical and gynecologic oncologists between 2013 and 2015. Rates of referrals, completion of counseling, and genetic testing and timeliness of counseling were abstracted before and after a GC was embedded in the clinic in 2014. An additional year of data (2015) was collected to evaluate sustainability of the intervention. Between 2013 and 2015, 88–92% of women were referred for genetic testing, but in 2013 only 66% completed counseling and 61% were tested. After a GC was embedded in the clinic in 2014, more than 80% of referred women completed counseling and germline genetic testing. Time to genetic counseling also decreased from a median of 107 to 40 days, irrespective of age and cancer family history (p < 0.01). Embedding a GC into the workflow for ovarian cancer patients is an effective way of improving access to genetic counseling, testing rates, and the timeliness of testing. • Embedding a GC resulted in greater completion and timeliness of genetic counseling. • An embedded GC promoted genetic testing for ovarian cancer patients irrespective of age at diagnosis or family history. • Improvements in GC access through this model were sustained over time. [ABSTRACT FROM AUTHOR]

Oral PARP inhibitors (PARPi) have dramatically changed the treatment landscape for patients with advanced ovarian cancer. However, a subset of patients discontinue PARPi due to treatment-related fatigue. The current study sought to explore patients' lived experiences with fatigue on PARPi. We conducted individual semi-structured interviews with N = 23 women receiving PARPi for advanced ovarian cancer who reported moderate to severe fatigue. Audiotaped interviews were transcribed and we used thematic analysis to code transcripts for emergent themes. Four overarching themes emerged. First, participants described their fatigue as milder than what they experienced on intravenous chemotherapy, but noted it consistently limited their daily activities, including work, and interfered with participation in family and social events. Second, fatigue negatively impacted participants' sense of self and identity. Third, most wanted to continue treatment and believed discontinuing PARPi would lead to a cancer recurrence or death. Finally, many participants reported that their support networks were unaware of their ongoing cancer treatment or the resulting fatigue; a situation that may prove isolating and result in reduced social support. Our findings underscore patients' persistent experience of fatigue on PARPi, the impact of fatigue on multiple domains of functioning, and a lack of understanding of side effects resulting from oral maintenance treatments among patients' social networks. Our findings highlight the need for interventions to address treatment-related fatigue to limit the negative impacts of fatigue on ovarian cancer patients' well-being. • PARP inhibitor-related fatigue consistently limited daily activities and interfered with work, family and social events. • PARP inhibitor-related fatigue negatively impacted patients' sense of self and identity. • Most patients believed discontinuing PARP inhibitor maintenance treatment would lead to a cancer recurrence or death. • Support networks were often unaware of patients' ongoing maintenance treatment or the resulting fatigue. [ABSTRACT FROM AUTHOR]

Pegylated liposomal doxorubicin (PLD) in vitro may have immunomodulatory abilities and preclinical evidence suggests it synergizes with immune checkpoint blockade. We hypothesized that combining PLD and pembrolizumab would be active in patients with platinum-resistant ovarian cancer (PROC). This was a single-arm, multi-center phase II trial. Eligible patients had PROC with ≤2 prior lines of cytotoxic therapy for recurrent or persistent disease. Twenty-six patients were enrolled and given pembrolizumab 200 mg intravenously (IV) every 3 weeks and PLD 40 mg/m2 IV every 4 weeks. Patients were assessed radiographically every 8 weeks. The primary endpoint was clinical benefit rate (CBR), defined as complete response (CR) + partial response (PR) + stable disease (SD) ≥24 weeks. The study was powered to detect an improvement in CBR from 25% to 50%, with rejection of the null hypothesis if at least 10 patients achieved clinical benefit. T-cell inflamed gene expression profiles (GEP) and PD-L1 were assessed and correlated with clinical outcome. Twenty-three patients were evaluable for best overall response. The study satisfied its primary endpoint, with 12 patients achieving clinical benefit for a CBR of 52.2% (95% CI 30.6–73.2%). There were 5 PRs (21.7%) and 1 CR (4.3%), for an overall response rate (ORR) of 26.1%. Six patients had SD lasting at least 24 weeks. Combination therapy was well tolerated without unexpected toxicities. The combination of pembrolizumab and PLD was manageable, without unexpected toxicities, and showed preliminary evidence of clinical benefit in the treatment of platinum resistant ovarian cancer. ORR and median PFS of combination therapy in this study was higher than historical comparisons of PLD alone or anti-PD-1/PD-L1 agents alone. Trial Registration: Clinicaltrials.gov identifier: NCT02865811 • Combination PLD/pembrolizumab met its primary endpoint in this study with a clinical benefit rate of 52.2%. • Combination PLD/pembrolizumab yielded an overall response rate of 26.1%. • One patient achieved a complete response, and one patient with stable disease remains on treatment after >36 months. [ABSTRACT FROM AUTHOR]

Background Neoadjuvant chemotherapy (NACT) may reduce perioperative morbidity in women undergoing primary treatment for ovarian cancer. We evaluated patterns of use and outcomes in a population-based cohort of elderly women with ovarian cancer (OC). Methods A cohort of patients ≥66 years old diagnosed between 2000 and 2013 with stage III-IV epithelial OC who received surgery and platinum/taxane chemotherapy for primary treatment was identified from the SEER-Medicare database. Propensity-score matching methods were used to examine differences in outcomes. Kaplan–Meier analysis was performed to compare overall survival (OS) in the matched cohort. Results From 2000 to 2013, 22.5% of older women received NACT. The use of NACT increased over time from 16% in 2000 to 35.4% in 2013 (p < .0001). Among women who received PCS, the rate of ostomy creation was higher compared with NACT (23.3% vs. 10.8%, p < .0001). Infectious and other surgical complications were higher among those who had PCS, regardless of stage. Median OS of women III ovarian cancer who underwent PCS was longer compared with NACT (38.8 vs. 28 months, p ≤ .0001). There were no survival differences between NACT and PCS in women with stage IV disease (29.4 vs. 29.8 months, p = .61) or for women aged >80. Conclusion Careful consideration should be given to older patients prior to undergoing PCS. Survival outcomes were similar for patients with stage IV disease, although NACT was associated with decreased perioperative morbidity compared with PCS. Among women with stage III disease, PCS was associated with improved overall survival, but higher rates of perioperative morbidity and acute care. [ABSTRACT FROM AUTHOR]

Objectives To determine the degree of consensus regarding the probabilities of outcomes associated with IP/IV and IV chemotherapy. Methods A survey was administered to an expert panel using the Delphi method. Ten ovarian cancer experts were asked to estimate outcomes for patients receiving IP/IV or IV chemotherapy. The clinical estimates were: 1) probability of completing six cycles of chemotherapy, 2) probability of surviving five years, 3) median survival, and 4) probability of ER/hospital visits during treatment. Estimates for two patients, one with a low comorbidity index (patient 1) and the other with a moderate index (patient 2), were included. The survey was administered in three rounds, and panelists could revise their subsequent responses based on review of the anonymous opinions of their peers. Results The ranges were smaller for IV compared with IP/IV therapy. Ranges decreased with each round. Consensus converged around outcomes related to IP/IV chemotherapy for: 1) completion of 6 cycles of therapy (type 1 patient, 62%, type 2 patient, 43%); 2) percentage of patients surviving 5 years (type 1 patient, 66%, type 2 patient, 47%); and 3) median survival (type 1 patient, 83 months, type 2 patient, 58 months). The group required three rounds to achieve consensus on the probabilities of ER/hospital visits (type 1 patient, 24%, type 2 patient, 35%). Conclusions Initial estimates of survival and adverse events associated with IP/IV chemotherapy differ among experts. The Delphi process works to build consensus and may be a pragmatic tool to inform patients of their expected outcomes. [ABSTRACT FROM AUTHOR]

Objectives: ER-positive ECs are characterized by PI3K and receptor tyrosine kinase (RTK)/RAS/b-catenin pathway alterations in approximately 90% and 80% of cases, respectively. Extensive crosstalk between ER, PI3K, and RTK/RAS/b-catenin pathways leads to both ligand-dependent and independent ER transcriptional activity as well as upregulation of cyclin D1 which, in complex with cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), is a critical regulator of cell cycle progression and a key mediator of resistance to hormonal therapy. Given that retinoblastoma (RB) loss is rare in ER-positive EC, we hypothesized that the combination of the aromatase inhibitor letrozole and CDK4/6 inhibitor abemaciclib would demonstrate promising activity and acceptable toxicity in this setting. Methods: This was an investigator-initiated, single-arm, phase II study of letrozole/abemaciclib in recurrent ER-positive EC (defined as ≥1% of tumor cell nuclei being immunoreactive by immunohistochemistry [IHC]). Eligibility criteria included measurable disease, no limit on prior therapies, and all EC histologies (in the 2nd stage, only endometrioid and carcinosarcomas with endometrioid epithelial components were allowed). Any prior hormonal therapy was allowed. Co-primary endpoints were objective response rate (ORR) by RECIST 1.1 and progression-free survival (PFS) rate at six months. Abemaciclib 150 mg PO twice daily and letrozole 2.5 mg daily were administered until progression or unacceptable toxicity. A two-stage design was employed whereby 16 pts were enrolled in the 1st stage; if there were ≥2 ORRs or ≥2 pts without disease progression or death at six months, accrual would continue to the 2nd stage with an enrollment of 19 additional pts. Overall, if there were ≥4 ORRs or ≥8 pts without disease progression or death at six months, letrozole/abemaciclib would be considered worthy of further study. Results: As of May 21, 2021, 28 pts-initiated therapy. Median follow-up was 10.2 months, median number of prior lines was 3 (range: 1-8) and 13 (46.4%) pts had prior hormonal therapy. Seven pts exhibited ORR (seven PRs, five confirmed as of the cut-off date, ORR 25% [95% CI: 10.7-44.9]), all in pts with endometrioid adenocarcinoma, including four pts with prior hormonal therapy. Responses were observed regardless of grade, mismatch repair and progesterone receptor (PR) status. Twelve pts (42.9%) exhibited stable disease as best response. PFS at six months was 42.9% (95% CI: 21%-63.1%), and median PFS was 5.3 months (95% CI: 2-16.5). Most common G3+ treatment-related toxicities were neutropenia (n =5, 17.6%) and anemia (n =3, 10.7%). Sixteen (57.1%) pts had at least one dose reduction of abemaciclib; two (7.1%) pts discontinued therapy because of toxicity. IHC and targeted next-generation sequencing will be reported at the meeting. Conclusions: Letrozole/abemaciclib met the predetermined criteria to be considered worthy of further evaluation in this population of recurrent ER-positive EC. [ABSTRACT FROM AUTHOR]

Abstract: Through an unusual differentiation process, human trophoblast progenitors (cytotrophoblasts) give rise to tumor-like cells that invade the uterus. By an unknown mechanism, invasive cytotrophoblasts exhibit permanent cell cycle withdrawal. Here, we report molecular cytogenetic data showing that ∼20 to 60% of these interphase cells had acquired aneusomies involving chromosomes X, Y, or 16. The incidence positively correlated with gestational age and differentiation to an invasive phenotype. Scoring 12 chromosomes in flow-sorted cytotrophoblasts showed that more than 95% of the cells were hyperdiploid. Thus, aneuploidy appears to be an important component of normal placentation, perhaps limiting the proliferative and invasive potential of cytotrophoblasts within the uterus. [Copyright &y& Elsevier]

As survival rates increase among women in the U.S. living with ovarian cancer (OC), quality of life (QOL) needs become more salient. Women treated for OC often report adverse sexual effects, yet evidence suggests oncology providers rarely discuss sexual health with their patients. We characterized sexual morbidity, QOL, and health care team (HCT) communication among a community sample of OC patients. 60 OC patients and survivors who enrolled in a cancer experience registry completed questions to assess sexual morbidity (6 items tallied to create a sexual morbidity score; range: 0-6) and its impact. Frequencies and correlations between sexual morbidity measures, HCT communication, QOL indices (assessed using PROMIS-29 v2.0 symptom burden subscales), and socio-demographics were examined. Participants were 83% non-Hispanic White, 7% Hispanic, and 5% Black/African American; mean age was 58 years (SD=11.3). Median time since diagnosis was 4 years (range: 0-25), 51% reported diagnosis in past 2 years, 35% were ever metastatic, 32% experienced a recurrence. 83% reported total abdominal hysterectomy with bilateral salpingo-oophorectomy. 70% of OC participants reported at least 1 sexual difficulty, 55% reported 2 or more of the following: 55% vaginal dryness, 52% no interest in sex, 39% anxious about having sex, 27% difficulty having an orgasm, 27% did not enjoy sex, and 25% pain during or after sex. Further, 47% reported OC negatively impacted their sexual life, 35% indicated sexual activity was a source of distress. 71% felt they could talk to a member of their HCT about sexual concerns; 49% indicated a member of their HCT offered help in coordinating distress-related care, but only 32% reported that a member of their HCT ever asked about sexual function. Greater sexual morbidity was positively correlated with PROMIS depression (r =.31, p <.05), anxiety (r =.29, p <.05), fatigue (r =.31, p <.05), and sleep disturbance (r =.30, p <.05). Furthermore, negative impact of cancer diagnosis on sexual life was positively correlated with depression (r =.46, p <.01), anxiety (r =.46, p <.001), and fatigue (r =.29, p <.05). OC patients report substantial concerns related to sexual function and well-being, with greater sexual morbidity associated with poorer emotional well-being, fatigue, and sleep disturbance. Few OC patients indicate being asked about sexual function by their HCT, despite a general willingness to talk about sexual concerns. Findings highlight a need for oncology care providers to initiate conversations surrounding sexual function and for the development of relevant evidence-based supportive care programs. [ABSTRACT FROM AUTHOR]