Evaluation of education initiatives to increase delivery of age-friendly care in retail clinics.

BACKGROUND: The Age-Friendly Health Systems model, encompassing four key elements (4Ms)-What Matters, Medication, Mentation, Mobility-is integral to delivering high-quality care to older adult patients. In May 2020, the MinuteClinic at CVS implemented the 4Ms model in all 1100+ store locations nationwide. To prepare healthcare providers to deliver 4Ms care, educational modules were developed to provide an understanding of the gerontology principles that support the 4Ms model of care. Our goal was to evaluate the effectiveness of these education modules on improving reliable 4Ms delivery during retail clinic visits. METHODS: Educational modules were provided to nurse practitioners and physician associates to complete in a self-directed manner. These included an orientation module with scenarios comparing usual care and 4Ms care, 12 monthly grand rounds focusing on 4Ms case studies, and 10 video vignettes on 4Ms integration. We examined the association between number of education modules completed with the average number of Ms delivered per visit (M-Score) using descriptive statistics and a generalized linear mixed-effects model. RESULTS: Over 70% of 2783 providers completed at least one education module. Rates of 4Ms care delivery were 1.37 (1.36-1.39, p < 0.001) times higher among those that completed an orientation course compared to those that did not. Higher uptake of education exhibited a dose-response relationship with rate ratios between 1.77 (1.74-1.80, p < 0.001) for 1-2 modules beyond orientation, up to 2.94 (2.90-2.99, p < 0.001) for eight or more modules. CONCLUSIONS: The self-directed learning environment (e.g., providers self-select the number and type of courses) reflects real-world variation in engagement. Despite this variation, significant improvements in 4Ms delivery were observed at any level of educational exposure, underscoring the value of prioritizing education time with quality improvement initiatives.

A non-comparative, randomized, phase II trial of atezolizumab or atezolizumab plus tiragolumab for programmed death-ligand 1-positive recurrent cervical cancer (SKYSCRAPER-04).

OBJECTIVE: To evaluate tiragolumab (anti-TIGIT) and atezolizumab (anti-PD-L1) as second- or third-line therapy for PD-L1-positive persistent/recurrent cervical cancer. METHODS: In the open-label, non-comparative, randomized phase II SKYSCRAPER-04 trial (NCT04300647), patients with PD-L1-positive (SP263 tumor area positivity ≥5%) recurrent/persistent cervical cancer after 1-2 chemotherapy lines (≥1 platinum-based) were randomized 3:1 to atezolizumab 1200 mg with/without tiragolumab 600 mg every 3 weeks until disease progression or unacceptable toxicity. Stratification factors were performance status, prior (chemo)radiotherapy, and disease status. The primary endpoint was independent review committee-assessed confirmed objective response rate per RECIST v1.1 in patients receiving tiragolumab plus atezolizumab. An objective response rate ≥21% (one-sample z-test p≤0.0245) was required for statistical significance versus a historical reference. RESULTS: Protocol-defined independent review committee-assessed objective response rates were 19.0% (95% CI 12.6 to 27.0) in 126 patients receiving tiragolumab plus atezolizumab (p=0.0787 vs historical reference) and 15.6% (95% CI 6.5 to 29.5) in 45 atezolizumab-treated patients. Response rates were higher in PD-L1high (tumor area positivity ≥10%) than PD-L1low (tumor area positivity 5%-9%) subgroups with both regimens. At 8.5 months' median follow-up, independent review committee-assessed progression-free survival was 2.8 months (95% CI 1.7 to 4.1) with tiragolumab plus atezolizumab and 1.9 months (95% CI 1.5 to 3.0) with atezolizumab. In post hoc analyses (10.4 months' median follow-up), median overall survival was 11.1 months (95% CI 9.6 to 14.5) with the combination and 10.6 months (95% CI 6.9 to 13.8) with atezolizumab (crossover permitted). In the combination group, 3% of patients had adverse events requiring treatment discontinuation and 8% had grade ≥3 adverse events of special interest; corresponding values in the single-agent arm were 4% and 11%. There were no treatment-related deaths or new safety findings. CONCLUSION: The objective response rate with the tiragolumab-plus-atezolizumab combination was numerically higher than the historical reference but did not reach statistical significance.

Outcomes of minimal access retroperitoneal para-aortic lymphadenectomy in patients with locally advanced cervical cancer.

BACKGROUND: To evaluate outcomes of laparoscopic retroperitoneal para-aortic lymphadenectomy for stage 1b3-3b cervical cancer. METHODS: Pathology databases searched for all para-aortic lymphadenectomy cases 2005-2016. Descriptive statistics were used to analyse baseline characteristics, cox models for treatment affect after accounting for variables, and Kaplan Meier curves for survival (STATA v15). RESULTS: 191 patients had 1b3-3b cervical cancer of which 110 patients had Para-aortic lymphadenectomy. 8 (7.3%) patients stage 1b3, 82 (74.6%) stage 2b, and 20 (18.1%) stage 3b cervical cancer. Mean lymph node count 11.7 (SD7.6). The intra-operative and post-operative 30 day complication rates were 8.8% (CI: 4.3%, 15.7%) and 5.3% (CI: 1.9%, 11.2%) respectively.Para-aortic nodes were apparently positive on CT/MRI in 5/110 (5%) cases. Cancer was found in 10 (8.9%, CI: 4.3%, 15.7%) cases on histology, all received extended field radiotherapy. Only 2 were identified on pre-operative CT/MRI imaging. 3 of 10 suspected node-positive cases on CT/MRI had negative histology. Para-aortic lymphadenectomy led to alteration in staging and radiotherapy management in 8 (8%, CI: 3.7%, 14.6%) patients. Mean overall survival 42.81 months (SD = 31.79 months). Survival was significantly higher for women undergoing PAN (50.57 (SD 30.7) months) compared to those who didn't (31.27 (SD 32.5) months). CONCLUSION: Laparoscopic retroperitoneal para-aortic lymphadenectomy is an acceptable procedure which can guide treatment in women with locally advanced cervical cancer.

We evaluated outcomes for patients with stage 1b3-3b cervical cancer that had lymph nodes removed prior to planning their chemoradiotherapy. There were 3 groups ­ patients that had their lymph nodes removed, those that did not and those that had their procedure abandoned so didn't have their lymph nodes removed. We looked at the lymph nodes down the microscope to see if they contained cancer and compared this to their pre-operative imaging. 8 patients had a change to their staging and treatment because they were found to have cancer in the lymph nodes. We found that the keyhole procedure to remove lymph nodes is an acceptable procedure which can guide treatment in women with locally advanced cervical cancer.

Differential regulation of G protein-coupled receptor-associated proteins in the caudate and the putamen of cynomolgus macaques following chronic ethanol drinking.

The dorsal striatum is composed of the caudate nucleus and the putamen in human and non-human primates. These two regions receive different cortical projections and are functionally distinct. The caudate is involved in the control of goal-directed behaviors, while the putamen is implicated in habit learning and formation. Previous reports indicate that ethanol differentially influences neurotransmission in these two regions. Because neurotransmitters primarily signal through G protein-coupled receptors (GPCRs) to modulate neuronal activity, the present study aimed to determine whether ethanol had a region-dependent impact on the expression of proteins that are involved in the trafficking and function of GPCRs, including G protein subunits and their effectors, protein kinases, and elements of the cytoskeleton. Western blotting was performed to examine protein levels in the caudate and the putamen of male cynomolgus macaques that self-administered ethanol for 1 year under free access conditions, along with control animals that self-administered an isocaloric sweetened solution under identical operant conditions. Among the 18 proteins studied, we found that the levels of one protein (PKCß) were increased, and 13 proteins (Gαi1/3, Gαi2, Gαo, Gß1γ, PKCα, PKCε, CaMKII, GSK3ß, ß-actin, cofilin, α-tubulin, and tubulin polymerization promoting protein) were reduced in the caudate of alcohol-drinking macaques. However, ethanol did not alter the expression of any proteins examined in the putamen. These observations underscore the unique vulnerability of the caudate nucleus to changes in protein expression induced by chronic ethanol exposure. Whether these alterations are associated with ethanol-induced dysregulation of GPCR function and neurotransmission warrants future investigation.

Grit as a Predictor of Academic Success Among Associate Degree Nursing Students.

AIM: The purpose of this study was to explore whether grit is a predictor of success in associate degree nursing (ADN) programs. BACKGROUND: A question that challenges admission decision-making in nursing programs is "Who will succeed?" This question is particularly relevant in ADN programs, which often have higher attrition rates than baccalaureate programs. METHOD: This longitudinal, mixed-methods study was conducted with 451 ADN students across nine programs, including interviews with seven unsuccessful students and nine successful students. RESULTS: Short Grit Scale scores were not found to be statistically significant as a predictor of academic success; however, themes that emerged from the interviews do align with the theory of grit. CONCLUSION: Further research is needed to explore whether recognizing the level of grit in students during admission processes would help identify students who are likely to succeed.

Health-Related Quality of Life in Patients With Advanced Endometrial Cancer Treated With Lenvatinib Plus Pembrolizumab or Treatment of Physician's Choice.

PURPOSE: Lenvatinib and pembrolizumab (LEN+PEMBRO) demonstrated clinically meaningful and statistically significant improvements in efficacy versus treatment of physician's choice (TPC) in patients with advanced endometrial cancer (aEC) in the phase 3 Study 309/KEYNOTE-775. Health-related quality-of-life (HRQoL) is reported. PATIENTS AND METHODS: Patients were randomly assigned to receive LEN+PEMBRO (n = 411; LEN 20 mg/day; PEMBRO 200 mg Q3W) or TPC (n = 416; doxorubicin 60 mg/m2 Q3W or paclitaxel 80 mg/m2 [weekly, 3 weeks on/1 week off]). Impact of treatment on HRQoL assessed by the global health status/quality of life (GHS/QoL) score of the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30) was a secondary objective; other scales of the Quality-of-Life Questionnaire (QLQ-C30), EORTC QLQ-Endometrial, 24 questions (EORTC QLQ-EN24), and EuroQoL 5 dimensions, 5 levels (EQ-5D-5L) were exploratory objectives. HRQoL was assessed on day 1 of each cycle. Completion/compliance, change from baseline, time to first and definitive deterioration were assessed. No multiplicity adjustments were applied for HRQoL endpoints. RESULTS: The latest timepoint at which the predefined rates of completion (≥60%) and compliance (≥80%) were met was week 12. HRQoL at week 12 between treatment groups was generally similar. Time to first deterioration symptom scales favoured LEN+PEMBRO for QLQ-C30 dyspnoea, and QLQ-EN24 for poor body image, tingling/numbness, and hair loss; and TPC was favoured for QLQ-C30 pain, appetite loss, and diarrhoea, and QLQ-EN24 muscular pain. While the QLQ-C30 physical functional scale favoured TPC, other functional scales were generally similar between arms. Time to definitive deterioration favoured LEN+PEMBRO on most scales. CONCLUSION: HRQoL data from Study 309/KEYNOTE-775, with previously published efficacy and safety results, indicate that LEN+PEMBRO has an overall favourable benefit/risk profile versus TPC for the treatment of patients with aEC. CLINICALTRIALS: GOV: NCT03517449.

Endometrial carcinosarcoma.

Endometrial carcinosarcoma is a rare and aggressive high-grade endometrial carcinoma with secondary sarcomatous trans-differentiation (conversion theory). The clinical presentation and diagnostic work-up roughly align with those of the more common endometrioid counterpart, although endometrial carcinosarcoma is more frequently diagnosed at an advanced stage. Endometrial carcinosarcoma is not a single entity but encompasses different histological subtypes, depending on the type of carcinomatous and sarcomatous elements. The majority of endometrial carcinosarcomas are characterized by p53 abnormalities. The proportion of POLE and microsatellite instablity-high (MSI-H) is directly related to the epithelial component, being approximately 25% and 3% in endometrioid and non-endometrioid components.The management of non-metastatic disease is based on a multimodal approach with optimal surgery followed by (concomitant or sequential) chemotherapy and radiotherapy, even for early stages. Palliative chemotherapy is recommended in the metastatic or recurrent setting, with carboplatin/paclitaxel doublet being the first-line regimen. Although the introduction of immunotherapy plus/minus a tyrosine kinase inhibitor shifted the paradigm of treatment of patients with recurrent endometrial cancer, patients with endometrial carcinosarcoma were excluded from most studies evaluating single-agent immunotherapy or the combination. However, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved the use of pembrolizumab and lenvatinib in endometrial cancer (all histotypes) after progression on chemotherapy and single-agent immunotherapy in MSI-H cancers. In the era of precision medicine, emerging knowledge on molecular endometrial carcinosarcoma is opening new promising therapeutic options for more personalized treatment. The present review outlines state-of-the-art knowledge and future directions for patients with endometrial carcinosarcoma.

Achievement of age-friendly health systems committed to care excellence designation in a convenient care health care system.

OBJECTIVE: To describe the implementation of the age-friendly health systems (AFHS) 4Ms Framework, an evidence-based framework to assess and act on "What Matters, Medication, Mentation and Mobility to deliver Age-Friendly health care for patients 65 and older", to achieve the Institute for Health care Improvement (IHI) Committed to Care Excellence recognition in a convenient care health system and test two novel implementation strategies. SETTING: The study was conducted in over 1100 convenient care clinics in 35 states and DC. MinuteClinics are located in community-based retail pharmacies in rural, suburban, and urban areas and staffed with approximately 3300 nurse practitioners and physician associates. DESIGN: In Year 1, the project used a quality improvement design, and in Year 2, a quasi-experimental implementation research design to pilot two strategies at the provider level (Virtual Clinic and Plan-Do-Study-Act (PDSA)). Statistical process control charts were used to assess changes in 4Ms documentation over time. Mixed-effects Poisson regression was used to assess the effectiveness of the pilot studies. DATA COLLECTION: The electronic health record (EHR) was enhanced to capture documentation of the AFHS 4Ms assessments and actions. A learning platform was created to teach and evaluate provider 4Ms competency, and the two data sources were merged into a registry. A formative evaluation was conducted using Tableau and reporting dashboards. FINDINGS: After 18 months and the implementation of 20 strategies to improve the uptake of the 4Ms, MinuteClinic achieved the IHI Committed to Care Excellence recognition. A significant increase over time in the reliable delivery of all 4Ms and each M component individually was found. For the research, there were significant improvements in the mean number of Ms delivered per visit (M-Score) in the Virtual Clinic (Incident Rate Ratio [IRR]: 2.47, p = 0.001) and PDSA (IRR: 3.08, p = 0.002) strategy intervention groups when compared to controls. CONCLUSIONS: Application of quality improvement and implementation methodologies contributed to the success of implementing age-friendly 4Ms evidence-based practice.

A quality improvement approach to develop an educational initiative for an age-friendly health system.

Authors describe a quality improvement approach to develop and pilot test educational materials with an aim to educate MinuteClinic providers in the provision of age-friendly care using the 4Ms Framework: What Matters, Medication, Mentation, Mobility. The team used surveys, focus groups and site visits to develop educational prototypes with Plan-Do-Study-Act iterative cycles to improve the education. Educational materials introduced providers to 4Ms assessment and evidence-based act on strategies for older adults in the convenient care setting. The education activities included an interactive orientation module comparing standard care to 4Ms care, 10 video vignettes with experts addressing gerontological topics, and 12 grand rounds presented monthly on topics applying the 4Ms with older adults. The information gained from the staff aided in the development and the iterative improvement of the materials. This article highlights the benefits of using a quality improvement approach in development of clinician education in provision of age-friendly care.

ALS-associated KIF5A mutations abolish autoinhibition resulting in a toxic gain of function.

Understanding the pathogenic mechanisms of disease mutations is critical to advancing treatments. ALS-associated mutations in the gene encoding the microtubule motor KIF5A result in skipping of exon 27 (KIF5AΔExon27) and the encoding of a protein with a novel 39 amino acid residue C-terminal sequence. Here, we report that expression of ALS-linked mutant KIF5A results in dysregulated motor activity, cellular mislocalization, altered axonal transport, and decreased neuronal survival. Single-molecule analysis revealed that the altered C terminus of mutant KIF5A results in a constitutively active state. Furthermore, mutant KIF5A possesses altered protein and RNA interactions and its expression results in altered gene expression/splicing. Taken together, our data support the hypothesis that causative ALS mutations result in a toxic gain of function in the intracellular motor KIF5A that disrupts intracellular trafficking and neuronal homeostasis.

Integration of immunotherapy into treatment of cervical cancer: Recent data and ongoing trials.

Cervical cancer constitutes a significant health burden for women globally. While most patients with early-stage disease can be cured with radical surgery or chemoradiotherapy, patients with high-risk locally advanced disease or with recurrent/metastatic disease have a poor prognosis with standard treatments. Immunotherapies are a rational treatment for this HPV-driven cancer that commonly expresses programmed cell death ligand-1. Before 2021, pembrolizumab was the only United States Food and Drug Administration-approved immunotherapy in cervical cancer, specifically for the second-line recurrent or metastatic (r/m) setting. In late 2021, the antibody-drug conjugate tisotumab vedotin was approved for second-line r/m cervical cancer and pembrolizumab combined with chemotherapy ± bevacizumab was approved for first-line r/m disease based on results from KEYNOTE-826. Moreover, with at least 2 dozen additional immunotherapy clinical trials in the second-line and first-line r/m setting, as well as in locally advanced disease, the treatment landscape for cervical cancer may eventually encounter a potential paradigm shift. Pivotal trials of immunotherapies for cervical cancer that were recently approved or with the potential for regulatory consideration through 2024 are reviewed. As immunotherapy has the opportunity to establish new standards of care in the treatment of cervical cancers, new biomarkers to identify the ideal patient populations for these therapies may also become important. However, issues with access, affordability, and compliance in low- and middle-income countries are anticipated.

Clear cell carcinoma of the endometrium.

Clear cell endometrial carcinoma represents an uncommon and poorly understood entity. Data from molecular/genomic profiling highlighted the importance of various signatures in assessing the prognosis of endometrial cancer according to four classes of risk (POLE mutated, MMRd, NSMP, and p53 abnormal). Unfortunately, data specific to clear cell histological subtype endometrial cancer are lacking. More recently, data has emerged to suggest that most of the patients (more than 80%) with clear cell endometrial carcinoma are characterized by p53 abnormality or NSMP type. This classification has important therapeutic implications. Although it is an uncommon entity, clear cell endometrial cancer patients with POLE mutation seem characterized by a good prognosis. Chemotherapy is effective in patients with NSMP (especially in stage III and IV) and patients with p53 abnormal disease (all stages). While, preliminary data suggested that patients with MMRd are less likely to benefit from chemotherapy. The latter group appears to benefit much more from immune checkpoint inhibitors: recent data from clinical trials on pembrolizumab plus lenvatinib and nivolumab plus cabozantinib supported that immunotherapy plus tyrosine kinase inhibitors (TKI) would be the most appropriate treatment for recurrent non-endometrioid endometrial cancer (including clear cell carcinoma) after the failure of platinum-based chemotherapy. Moreover, ongoing clinical trials testing the anti-tumor activity of innovative products will clarify the better strategies for advanced/recurrent clear cell endometrial carcinoma. Further prospective evidence is urgently needed to better characterize clear cell endometrial carcinoma.

Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer.

BACKGROUND: Standard therapy for advanced endometrial cancer after failure of platinum-based chemotherapy remains unclear. METHODS: In this phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with advanced endometrial cancer who had previously received at least one platinum-based chemotherapy regimen to receive either lenvatinib (20 mg, administered orally once daily) plus pembrolizumab (200 mg, administered intravenously every 3 weeks) or chemotherapy of the treating physician's choice (doxorubicin at 60 mg per square meter of body-surface area, administered intravenously every 3 weeks, or paclitaxel at 80 mg per square meter, administered intravenously weekly [with a cycle of 3 weeks on and 1 week off]). The two primary end points were progression-free survival as assessed on blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1, and overall survival. The end points were evaluated in patients with mismatch repair-proficient (pMMR) disease and in all patients. Safety was also assessed. RESULTS: A total of 827 patients (697 with pMMR disease and 130 with mismatch repair-deficient disease) were randomly assigned to receive lenvatinib plus pembrolizumab (411 patients) or chemotherapy (416 patients). The median progression-free survival was longer with lenvatinib plus pembrolizumab than with chemotherapy (pMMR population: 6.6 vs. 3.8 months; hazard ratio for progression or death, 0.60; 95% confidence interval [CI], 0.50 to 0.72; P<0.001; overall: 7.2 vs. 3.8 months; hazard ratio, 0.56; 95% CI, 0.47 to 0.66; P<0.001). The median overall survival was longer with lenvatinib plus pembrolizumab than with chemotherapy (pMMR population: 17.4 vs. 12.0 months; hazard ratio for death, 0.68; 95% CI, 0.56 to 0.84; P<0.001; overall: 18.3 vs. 11.4 months; hazard ratio, 0.62; 95% CI, 0.51 to 0.75; P<0.001). Adverse events of grade 3 or higher occurred in 88.9% of the patients who received lenvatinib plus pembrolizumab and in 72.7% of those who received chemotherapy. CONCLUSIONS: Lenvatinib plus pembrolizumab led to significantly longer progression-free survival and overall survival than chemotherapy among patients with advanced endometrial cancer. (Funded by Eisai and Merck Sharp and Dohme [a subsidiary of Merck]; Study 309-KEYNOTE-775 ClinicalTrials.gov number, NCT03517449.).

Radiation Therapy Techniques and Treatment-Related Toxicity in the PORTEC-3 Trial: Comparison of 3-Dimensional Conformal Radiation Therapy Versus Intensity-Modulated Radiation Therapy.

PURPOSE: Radiation therapy techniques have developed from 3-dimensional conformal radiation therapy (3DCRT) to intensity modulated radiation therapy (IMRT), with better sparing of the surrounding normal tissues. The current analysis aimed to investigate whether IMRT, compared to 3DCRT, resulted in fewer adverse events (AEs) and patient-reported symptoms in the randomized PORTEC-3 trial for high-risk endometrial cancer. METHODS AND MATERIALS: Data on AEs and patient-reported quality of life (QoL) of the PORTEC-3 trial were available for analysis. Physician-reported AEs were graded using Common Terminology Criteria for Adverse Events v3.0. QoL was assessed by the European Organisation for Research and Treatment of Cancer QLQC30, CX24, and OV28 questionnaires. Data were compared between 3DCRT and IMRT. A P value of ≤ .01 was considered statistically significant due to the risk of multiple testing. For QoL, combined scores 1 to 2 ("not at all" and "a little") versus 3 to 4 ("quite a bit" and "very much") were compared between the techniques. RESULTS: Of 658 evaluable patients, 559 received 3DCRT and 99 IMRT. Median follow-up was 74.6 months. During treatment no significant differences were observed, with a trend for more grade ≥3 AEs, mostly hematologic and gastrointestinal, after 3DCRT (37.7% vs 26.3%, P = .03). During follow-up, 15.4% (vs 4%) had grade ≥2 diarrhea, and 26.1% (vs 13.1%) had grade ≥2 hematologic AEs after 3DCRT (vs IMRT) (both P < .01). Among 574 (87%) patients evaluable for QoL, 494 received 3DCRT and 80 IMRT. During treatment, 37.5% (vs 28.6%) reported diarrhea after 3DCRT (vs IMRT) (P = .125); 22.1% (versus 10.0%) bowel urgency (P = 0039), and 18.2% and 8.6% abdominal cramps (P = .058). Other QoL scores showed no differences. CONCLUSIONS: IMRT resulted in fewer grade ≥3 AEs during treatment and significantly lower rates of grade ≥2 diarrhea and hematologic AEs during follow-up. Trends toward fewer patient-reported bowel urgency and abdominal cramps were observed after IMRT compared to 3DCRT.

Stratified follow-up for endometrial cancer: a move to more personalized cancer care.

OBJECTIVE: Hospital based follow-up has been the standard of care for endometrial cancer. Patient initiated follow-up is a useful adjunct for lower risk cancers. The purpose of this study was to evaluate outcomes of endometrial cancer patients after stratification into risk groupings, with particular attention to salvageable relapses. METHODS: All patients treated surgically for International Federation of Gynecology and Obstetrics (FIGO) stage I-IVA endometrial cancer of all histological subtypes, from January 2009 until March 2019, were analyzed. Patient and tumor characteristics, treatment details, relapse, death, and last follow-up dates were collected. Site of relapse, presence of symptoms, and whether relapses were salvageable were also identified. The European Society of Medical Oncology-European Society of Gynecological Oncology 2020 risk stratification was assigned, and relapse free and overall survival were estimated. RESULTS: 900 patients met the eligibility criteria. Median age was 66 years (range 28-96) and follow-up duration was 35 months (interquartile range 19-57). In total, 16% (n=144) of patients relapsed, 1.3% (n=12) from the low risk group, 3.9% (n=35) from the intermediate risk group, 2.2% (n=20) from the high-intermediate risk group, and 8.7% (n=77) from the high risk group. Salvageable relapses were less frequent at 2% (n=18), of which 33% (n=6) were from the low risk group, 22% (n=4) from the intermediate risk group, 11% (n=2) from the high-intermediate risk group, and 33% (n=6) from the high risk group. There were only three asymptomatic relapses in the low risk patients, accounting for 0.33% of the entire cohort. CONCLUSIONS: Relapses were infrequent and most presented with symptoms; prognosis after relapse remains favorable. Overall salvageable relapses were infrequent and cannot justify intensive hospital based follow-up. Use of patient initiated follow-up is therefore appropriate, as per the British Gynaecological Cancer Society's guidelines, for all risk groupings.

Pre-Implementation of the Age-Friendly Health Systems Evidence-Based 4Ms Framework in a Multi-State Convenient Care Practice.

BACKGROUND: Quality issues in the delivery of healthcare services to older adults and changes in societal demographics call for a social movement to improve the care of older adults in a variety of healthcare settings, including ambulatory care and convenient care clinics. AIMS: To describe the pre-implementation phase to integrate the Age-Friendly Health Systems (AFHS) 4Ms (i.e., What Matters, Medication, Mentation, and Mobility) Framework in 1,100 MinuteClinics (the retail medical clinic of CVS Health) using the Consolidated Framework for Implementation Research (CFIR) and RE-AIM (an evaluation implementation framework). METHODS: The CFIR and RE-AIM models guided data collection. Data were collected from all stakeholders (patients, healthcare providers, managers, educators, informatics staff, communications staff, and implementation consultants) via observations, surveys, interviews, focus groups, organizational readiness assessment, stakeholder assessment, and workflow mapping during a 15-month period to identify potential barriers, facilitators, and other opportunities for implementation. RESULTS: The CFIR and RE-AIM implementation frameworks provided a comprehensive approach to guide the pre-implementation phase of the AFHS 4Ms Framework at the MinuteClinic. The baseline assessments guided by the CFIR revealed important insights in the choice of implementation strategies that were developed and tested in the pre-implementation phase, and the RE-AIM guided meaningful components to the development of the logic model. LINKING ACTION TO EVIDENCE: As more healthcare systems integrate the AFHS 4Ms Framework, the approach reported in this quality improvement project can be used in other settings to facilitate a comprehensive implementation.

The Cervical Cancer Research Network (Gynecologic Cancer InterGroup) roadmap to expand research in low- and middle-income countries.

Cervical cancer is a global health problem which disproportionally affects women in low- and middle- income countries. The World Health Organization recently launched its global strategy to eliminate this disease in the next two decades. For those women diagnosed today with cervical cancer better strategies are needed to improve outcome and reduce treatment-related morbidity. Clinical trials are critical to shaping future treatment, and much has been achieved already. However, such opportunities are limited in low resource settings, and the Cervical Cancer Research Network is dedicated to expanding access to new technologies in surgery, radiation, and medical oncology. In this article we review the status of the trials portfolio and outline future objectives, including the launch of a number of research grants for aspiring or established researchers in low- and middle-income settings.

Long-Term Toxicity and Health-Related Quality of Life After Adjuvant Chemoradiation Therapy or Radiation Therapy Alone for High-Risk Endometrial Cancer in the Randomized PORTEC-3 Trial.

PURPOSE: The survival results of the PORTEC-3 trial showed a significant improvement in both overall and failure-free survival with chemoradiation therapy versus pelvic radiation therapy alone. The present analysis was performed to compare long-term adverse events (AE) and health-related quality of life (HRQOL). METHODS AND MATERIALS: In the study, 660 women with high-risk endometrial cancer were randomly assigned to receive chemoradiation therapy (2 concurrent cycles of cisplatin followed by 4 cycles of carboplatin/paclitaxel) or radiation therapy alone. Toxicity was graded using Common Terminology Criteria for Adverse Events, version 3.0. HRQOL was measured using EORTC QLQ-C30 and CX24/OV28 subscales and compared with normative data. An as-treated analysis was performed. RESULTS: Median follow-up was 74.6 months; 574 (87%) patients were evaluable for HRQOL. At 5 years, grade ≥2 AE were scored for 78 (38%) patients who had received chemoradiation therapy versus 46 (24%) who had received radiation therapy alone (P = .008). Grade 3 AE did not differ significantly between the groups (8% vs 5%, P = .18) at 5 years, and only one new late grade 4 toxicity had been reported. At 3 and 5 years, sensory neuropathy toxicity grade ≥2 persisted after chemoradiation therapy in 6% (vs 0% after radiation therapy, P < .001) and more patients reported significant tingling or numbness at HRQOL (27% vs 8%, P < .001 at 3 years; 24% vs 9%, P = .002 at 5 years). Up to 3 years, more patients who had chemoradiation therapy reported limb weakness (21% vs 5%, P < .001) and lower physical (79 vs 87, P < .001) and role functioning (78 vs 88, P < .001) scores. Both treatment groups reported similar long-term global health/quality of life scores, which were better than those of the normative population. CONCLUSIONS: This study shows a long-lasting, clinically relevant, negative impact of chemoradiation therapy on toxicity and HRQOL, most importantly persistent peripheral sensory neuropathy. Physical and role functioning impairments were seen until 3 years. These long-term data are essential for patient information and shared decision-making regarding adjuvant chemotherapy for high-risk endometrial cancer.

Cervical cancer in Eastern Europe: review and proceedings from the Cervical Cancer Research Conference.

Cervical cancer is the third most common cancer among women worldwide, with a disproportionately high burden of disease in less-developed regions of the world. The Cervix Cancer Research Network was founded by the Gynecologic Cancer InterGroup with a mission to improve outcomes in cervical cancer by enhancing international access to clinical trials, specifically in under-represented, underdeveloped areas. The Cervix Cancer Research Network held its third international educational symposium in Bucharest in 2018 and is the subject of this report. The purpose of this symposium was to advance the international understanding of cervical cancer treatment patterns, to foster recruitment to Cervix Cancer Research Network clinical trials, and identify key Cervix Cancer Research Network clinical trial concepts to improve cervical cancer care worldwide.

Primary results from CECILIA, a global single-arm phase II study evaluating bevacizumab, carboplatin and paclitaxel for advanced cervical cancer.

OBJECTIVE: Adding bevacizumab to cisplatin-paclitaxel for advanced cervical cancer significantly improves overall and progression-free survival. We evaluated bevacizumab with a widely used carboplatin-paclitaxel backbone. METHODS: Patients with metastatic/recurrent/persistent cervical cancer not amenable to curative surgery and/or radiotherapy received 3-weekly bevacizumab 15 mg/kg, paclitaxel 175 mg/m2, and carboplatin AUC 5 until progression or unacceptable toxicity. Maintenance bevacizumab was allowed. Patients with ongoing bladder/rectal involvement, prior cobalt radiotherapy, a history of fistula/gastrointestinal perforation, or recent bowel resection/chemoradiation were excluded. The primary objective was to determine incidences of gastrointestinal perforation/fistula, gastrointestinal-vaginal fistula, and genitourinary fistula. RESULTS: Among 150 treated patients, disease at study entry was persistent in 21%, recurrent in 56%, and newly diagnosed metastatic in 23%. After 27.8 months' median follow-up, median bevacizumab duration was 6.7 months; 57% received maintenance bevacizumab. Seventeen patients (11.3%; 95% CI: 6.7-17.5%) experienced ≥1 perforation/fistula event: gastrointestinal perforation/fistula in 4.7% (1.9-9.4%), gastrointestinal-vaginal fistula in 4.0% (1.5-8.5%), and genitourinary fistula in 4.7% (1.9-9.4%). Of these, 16 were previously irradiated, several with ongoing radiation effects. The most common grade 3/4 adverse events were neutropenia (25%), anemia (19%), and hypertension (14%). Five patients (3%) had fatal adverse events. Objective response rate was 61% (95% CI: 52-69%), median progression-free survival was 10.9 (10.1-13.7) months, and median overall survival was 25.0 (20.9-30.4) months. CONCLUSIONS: Bevacizumab can be combined with carboplatin-paclitaxel in the CECILIA study population. The fistula/gastrointestinal perforation incidence is in line with GOG-0240; efficacy results are encouraging. TRIAL REGISTRATION NUMBER: NCT02467907 (ClinicalTrials.gov).