Single-tube four-target lateral flow assay detects human papillomavirus types associated with majority of cervical cancers.

Isothermal nucleic acid amplification methods have many advantages for use at the point of care. However, there is a lack of multiplexed isothermal amplification tests to detect multiple targets in a single reaction, which would be valuable for many diseases, such as infection with high-risk human papillomavirus (hrHPV). In this study, we developed a multiplexed loop-mediated isothermal amplification (LAMP) reaction to detect the three most common hrHPV types that cause cervical cancer (HPV16, HPV18, and HPV45) and a cellular control for sample adequacy. First, we characterized the assay limit of detection (LOD) in a real-time reaction with fluorescence readout; after 30 min of amplification the LOD was 100, 10, and 10 copies/reaction of HPV16, HPV18, and HPV45, respectively, and 0.1 ng/reaction of human genomic DNA (gDNA). Next, we implemented the assay on lateral flow strips, and the LOD was maintained for HPV16 and HPV18, but increased to 100 copies/reaction for HPV45 and to 1 ng/reaction for gDNA. Lastly, we used the LAMP test to evaluate total nucleic acid extracted from 38 clinical samples; compared to qPCR, the LAMP test had 89% sensitivity and 95% specificity. When integrated with sample preparation, this multiplexed LAMP assay could be useful for point-of-care testing.

A colostomy for large bowel obstruction at the end of life: What do patients gain from palliative surgery?

OBJECTIVES: Malignant large bowel obstruction (LBO) is a frequent complication affecting women with gynecologic cancers and is an indication for emergent surgery. However, the life expectancy and subsequent medical care utilization are unknown. We sought to estimate overall survival (OS) following colostomy and describe subsequent healthcare utilization among patients with advanced gynecologic malignancies. METHODS: We conducted a retrospective analysis of patients with advanced gynecologic cancers who underwent colostomy with palliative intent due to LBO at our institution between March 2014 and January 2023. Summary statistics were used to describe the clinical and demographic characteristics of the study population. OS was estimated using the Kaplan-Meier method, and we defined healthcare utilization at the end-of-life using criteria published by the National Quality Forum. RESULTS: A total of 78 patients were included. The median age at the time of surgery was 61 (range: 34-83), and most patients had recurrent ovarian, fallopian tube, or primary peritoneal cancer (n = 51, 65.4%), followed by cervical cancer (n = 16, 20.5%), and uterine cancer (n = 10, 12.8%). The median Charlson comorbidity index was 3 and median postoperative length of stay was five days (range: 1-26). The median follow-up for all patients was 4.5 months (range: 0.07-46.2), and the median OS was 4.5 months (95% CI: 2.9-6.0), including 12 patients (15.4%) with <30-day OS and 21 (26.9%) with <60-day OS. In the last 30 days of life, 62.7% of patients were re-admitted to the hospital, 53.0% were seen in the emergency department, and 18.5% were admitted to an intensive care unit. CONCLUSIONS: A significant proportion of patients died within 60 days of surgery, and many had high healthcare utilization at the end of life.

Efficacy, safety, and feasibility of Apixaban for postoperative venous thromboembolism prophylaxis following open gynecologic cancer surgery at a comprehensive cancer center.

OBJECTIVES: To evaluate safety, efficacy, and feasibility of apixaban for postoperative venous thromboembolism (VTE) prophylaxis following open gynecologic cancer surgery at a comprehensive cancer center. METHODS: This retrospective, cohort study included patients with gynecologic cancer who underwent open surgery between 3/2021 and 3/2023 and received 28-day postoperative VTE prophylaxis. Patients on therapeutic anticoagulation preoperatively were excluded. Predictors of 90- and 30-day VTE and 30-day bleeding events were determined using multivariable logistic regression, adjusting for known confounders. RESULTS: 452 patients were included in the cohort: 348 received apixaban and 104 received enoxaparin. Those who received enoxaparin were more likely to be American Society of Anesthesiologists class III/IV (compared to I/II) (p = 0.033), current or former smokers (p = 0.012) and have a higher BMI (p < 0.001), Charlson Comorbidity Index (p = 0.005), and age (p = 0.046). 30-day VTE rate was significantly lower in the apixaban group (0.6%) compared to the enoxaparin group (6.2%) (adjusted OR 0.13, 95% CI 0.03-0.56; p = 0.006). 90-day VTE rate was 2.7% and 6.2% in the apixaban and enoxaparin groups, respectively (adjusted OR 0.85, 95% CI 0.38-1.92; p = 0.704). Major bleeding complications (2.4% vs. 2.0%) and minor bleeding complications (0.9% vs. 3.0%) were similar in the apixaban and enoxaparin groups, respectively, on multivariate analyses. The median patient out of pocket cost was $10 (IQR 0.0-40.0) for apixaban and $20 (IQR 3.7-67.7) for enoxaparin (p = 0.001). CONCLUSIONS: Our findings along with previously published data suggest that apixaban should be considered the standard of care for VTE prophylaxis in patients undergoing open surgery for gynecologic malignancies.

Metronidazole and cefazolin vs cefazolin alone for surgical site infection prophylaxis in gynecologic surgery at a comprehensive cancer center.

BACKGROUND: Surgical site infection is one of the most common complications of gynecologic cancer surgery. Current guidelines recommend the administration of cefazolin preoperatively to reduce surgical site infection rates for patients undergoing clean-contaminated surgeries such as hysterectomy. OBJECTIVE: To evaluate the impact of a quality improvement project adding metronidazole to cefazolin for antibiotic prophylaxis on surgical site infection rate for women undergoing gynecologic surgery at a comprehensive cancer center. STUDY DESIGN: This retrospective, single-center cohort study included patients who underwent surgery in the gynecologic oncology department from May 2017 to June 2023. Patients with penicillin allergies and those undergoing concomitant bowel resections and/or joint cases were excluded. The preintervention group patients had surgery from May 2017 to April 2022, and the postintervention group patients had surgery from April 2022 to June 2023. The primary outcome was a 30-day surgical site infection rate. Sensitivity analyses were performed to compare surgical site infection rates on the basis of actual antibiotics received and for those who had a hysterectomy. Factors independently associated with surgical site infection were identified using a multivariable logistic regression model adjusting for confounding variables. RESULTS: Of 3343 patients, 2572 (76.9%) and 771 (23.1%) were in the pre-post intervention groups, respectively. Most patients (74.7%) had a hysterectomy performed. Thirty-four percent of cases were for nononcologic (benign) indications. Preintervention patients were more likely to receive appropriate preoperative antibiotics (95.6% vs 90.7%; P<.001). The overall surgical site infection rate before the intervention was 4.7% compared with 2.6% after (P=.010). The surgical site infection rate for all patients who underwent hysterectomy was 4.9% (preintervention) vs 2.8% (postintervention) (P=.036); a similar trend was seen for benign cases (4.4% vs 2.4%; P=.159). On multivariable analysis, the odds ratio for surgical site infection was 0.49 (95% confidence interval, 0.38-0.63) for the postintervention compared with the preintervention group (P<.001). In a sensitivity analysis (n=3087), the surgical site infection rate was 4.5% for those who received cefazolin alone compared with 2.3% for those who received cefazolin plus metronidazole, with significantly decreased odds of surgical site infection for the cefazolin plus metronidazole group (adjusted odds ratio, 0.40 [95% confidence interval, 0.30-0.53]; P<.001). Among only those who had a hysterectomy performed, the odds of surgical site infection were significantly reduced for those in the postintervention group (adjusted odds ratio, 0.63 [95% confidence interval, 0.47-0.86]; P=.003). CONCLUSION: The addition of metronidazole to cefazolin before gynecologic surgery decreased the surgical site infection rate by half, even after accounting for other known predictors of surgical site infection and differences in practice patterns over time. Providers should consider this combination regimen in women undergoing gynecologic surgery, especially for cases involving hysterectomy.

A Comprehensive Program to Improve Treatment of Precancerous Cervical Lesions in the Rio Grande Valley of Texas.

OBJECTIVE: To assess the impact of a multicomponent intervention in women with cervical dysplasia who were treated with loop electrosurgical excision procedure (LEEP), as well as the time between colposcopy and treatment. DESIGN: Retrospective cohort study. INTERVENTION: Clinic participation in a multicomponent cervical cancer prevention program that included community outreach, patient in-reach, and navigation, as well as provider capacity building with in-person training and ongoing telementoring through Project ECHO. MAIN OUTCOME MEASURES: Medical records were reviewed to evaluate women with cervical dysplasia undergoing treatment with LEEP within 90 days of colposcopy, as well as time between colposcopy and treatment. Baseline data from year 1 were compared with each subsequent year of implementation. Additional variables examined included patient's age, history of abnormal screening results, and percentage of families living below poverty line based on county of residence, parity, and clinic site. We performed logistic regression and multiple linear regression analyses to assess the programmatic impact in the outcomes of interest by year of program implementation. RESULTS: A total of 290 women were included in the study. The proportion of women undergoing treatment within 90 days of colposcopy increased from 76.2% at baseline to 91.3% in year 3 and 92.9% in year 4 of program implementation. The odds of undergoing treatment within 90 days were 5.11 times higher in year 4 of program implementation than at baseline. The mean time between colposcopy and LEEP decreased from 62 days at baseline to 45 days by year 4 of program implementation. CONCLUSIONS: Implementation of our multicomponent cervical cancer prevention program increased the proportion of women undergoing LEEP within 90 days of colposcopy and decreased the time between colposcopy and LEEP. This program has the potential to support cervical cancer prevention efforts and could be implemented in other low-resource settings.

Collision Tumor of the Ovary Involving Sertoli-Leydig Cell Tumor and High-Grade Serous Carcinoma-Report of the First Case.

We report a collision tumor in the ovary of a 60-yr-old woman composed of high-grade serous carcinoma and Sertoli-Leydig cell tumor. Collision tumors in the ovary are rare and to the best of our knowledge, combination of ovarian high-grade serous carcinoma and Sertoli-Leydig cell tumor has not been described before.

The Mulher Study: cervical cancer screening with primary HPV testing in Mozambique.

OBJECTIVE: To evaluate cervical cancer screening with primary human papillomavirus (HPV) testing in Mozambique, a country with one of the highest burdens of cervical cancer globally. METHODS: Women aged 30-49 years were prospectively enrolled and offered primary HPV testing using either self-collected or provider-collected specimens. Patients who tested positive for HPV underwent visual assessment for treatment using visual inspection with acetic acid to determine eligibility for thermal ablation. If ineligible, they were referred for excision with a loop electrosurgical excision procedure, for cold knife conization, or for cervical biopsy if malignancy was suspected. RESULTS: Between January 2020 and January 2023, 9014 patients underwent cervical cancer screening. Median age was 37 years (range 30-49) and 4122 women (45.7%) were patients living with HIV. Most (n=8792, 97.5%) chose self-collection. The HPV positivity rate was 31.1% overall and 39.5% among patients living with HIV. Of the 2805 HPV-positive patients, 2588 (92.3%) returned for all steps of their diagnostic work-up and treatment, including ablation (n=2383, 92.1%), loop electrosurgical excision procedure (n=169, 6.5%), and cold knife conization (n=5, 0.2%). Thirty-one patients (1.2%) were diagnosed with cancer and referred to gynecologic oncology. CONCLUSION: It is feasible to perform cervical cancer screening with primary HPV testing and follow-up in low-resource settings. Participants preferred self-collection, and the majority of screen-positive patients completed all steps of their diagnostic work-up and treatment. Our findings provide important information for further implementation and scale-up of cervical cancer screening and treatment services as part of the WHO global strategy for the elimination of cervical cancer.

Cervical cancer screening among English- and Spanish-speaking Hispanic women in an urban safety net health system, 2015-2020.

BACKGROUND: The Hispanic population is heterogeneous with differences in health behaviors across subgroups by nativity and preferred language. We evaluated cervical cancer screening adherence among English- and Spanish-speaking Hispanic patients receiving care at a safety net health system. METHODS: Electronic health records were used to identify 46,094 women aged 30-65. Up to date (UTD) screening was defined based on date of last Pap test, human papillomavirus (HPV) test, or Pap/HPV co-test. RESULTS: Overall, 81.5% of 31,297 Hispanic women were UTD. English-speaking Hispanic women had a lower prevalence of being UTD when compared to Spanish-speaking Hispanic women (aPR: 0.94, 95% CI: 0.93 - 0.96). Further, those with indigent healthcare plans had a higher prevalence of being UTD when compared to those with private insurance (aPR: 1.10, 95% CI: 1.09 - 1.12), while all other health insurance plans were associated with lower UTD screening when compared to private insurance. CONCLUSIONS: These findings suggest screening differences within the Hispanic population, highlighting the need for disaggregated research assessing heterogeneity within racial/ethnic groups, specifically among Hispanic populations.

Elimination of cervical cancer in Latin America (Project ECHO-ELA): lessons from phase one of implementation.

We describe the outcomes of The Extension for Community Healthcare Outcomes-Elimination of Cervical Cancer in The Americas (ECHO-ELA) program, which was developed as a tri-lateral cooperation between Pan American Health Organization (PAHO), the U.S. National Cancer Institute (NCI) and The University of Texas MD Anderson Cancer Center (MD Anderson). The program's purpose is to disseminate strategies for cervical cancer prevention and is structured around the three pillars of the World Health Organization's (WHO) Cervical Cancer Elimination Strategy and the associated 90-70-90 target goals. The target audience includes health authorities from Latin American and Caribbean countries, as well as PAHO's non-communicable disease Focal Points in country offices as well as clinical and public health collaborators. The virtual sessions are held in Spanish for 1.5 hours every month using the ECHO® format. From May 2020 to June 2021, 14 ECHO sessions were held with an average of 74 participants per session (range: 46 - 142). We conducted two anonymous surveys (baseline and follow up) and two focus groups. Respondents stated that the topics they learned the most about included the state of HPV vaccination in the region and strategies for implementing HPV vaccination. Identified needs included support between ECHO sessions and country-specific technical assistance. The ECHO-ELA program provides a forum for increased collaboration between countries in Latin America/Caribbean and the dissemination of best-practice strategies to reach the WHO Cervical Cancer Elimination target goals.

Se describen los resultados del programa ECHO® (Extension for Community Healthcare Outcomes) para la eliminación del cáncer cervicouterino en las Américas (ECHO-ELA), que se concibió como una cooperación trilateral entre la Organización Panamericana de la Salud (OPS), el Instituto Nacional del Cáncer de los Estados Unidos (NCI) y el centro contra el cáncer MD Anderson (MD Anderson) de la Universidad de Texas. La finalidad del programa es difundir las estrategias para la prevención del cáncer cervicouterino, y está estructurado en torno a los tres pilares de la estrategia para la eliminación del cáncer cervicouterino de la Organización Mundial de la Salud (OMS) y los objetivos 90-70-90 conexos. El público destinatario comprende autoridades de salud de países de América Latina y el Caribe, así como los puntos focales de la OPS para las enfermedades no transmisibles en las Representaciones en los países, además de colaboradores en el ámbito clínico y de la salud pública. Las sesiones virtuales se llevan a cabo en español, durante 1,5 horas cada mes, utilizando el formato ECHO®. De mayo del 2020 a junio del 2021 se celebraron 14 sesiones de ECHO, con un promedio de 74 participantes por sesión (límites: 46-142). Se realizaron dos encuestas anónimas (al inicio y de seguimiento) y dos grupos de opinión. Los encuestados declararon que los temas sobre los que más aprendieron fueron la situación de la vacunación contra el VPH en la región y las estrategias para poner en marcha la vacunación contra el VPH. Entre las necesidades mencionadas figuraban el apoyo entre las sesiones de ECHO y la asistencia técnica específica para cada país. El programa ECHO-ELA brinda un foro para una mayor colaboración entre los países de América Latina y el Caribe y para difundir las estrategias sobre las mejores prácticas, a fin de alcanzar los objetivos de la OMS de eliminación del cáncer cervicouterino.

Este trabalho descreve os resultados do programa Extension for Community Healthcare Outcomes para eliminação do câncer do colo do útero nas Américas (ECHO ELA), desenvolvido na forma de cooperação trilateral entre a Organização Pan-Americana da Saúde (OPAS), o Instituto Nacional do Câncer dos Estados Unidos (NCI) e o MD Anderson Cancer Center da Universidade do Texas (MD Anderson). O programa visa a disseminar estratégias para a prevenção do câncer do colo do útero e está estruturado em torno dos três pilares da estratégia de eliminação do câncer do colo do útero da Organização Mundial da Saúde (OMS) e das Metas 90-70-90 associadas. O público-alvo inclui autoridades sanitárias de países da América Latina e do Caribe, bem como os pontos focais de doenças não transmissíveis nas representações da OPAS nos países, além de colaboradores clínicos e de saúde pública. Todos os meses, são realizadas sessões virtuais de uma hora e meia em espanhol usando o formato ECHO®. No período de maio de 2020 a junho de 2021, foram realizadas 14 sessões do ECHO, com uma média de 74 participantes por sessão (variação: 46 a 142). Foram realizadas duas enquetes anônimas (linha de base e acompanhamento) e dois grupos focais. Os entrevistados afirmaram que os tópicos sobre os quais mais aprenderam foram a situação da vacinação contra o HPV na região e as estratégias para implementar a vacinação contra o HPV. As necessidades identificadas incluíam apoio entre as sessões do ECHO e assistência técnica específica para o país. O programa ECHO ELA oferece um fórum para aumentar a colaboração entre os países da América Latina e do Caribe e difundir melhores práticas para atingir as metas de eliminação do câncer do colo do útero da OMS.

Metagenomes of rectal swabs in larger, advanced stage cervical cancers have enhanced mucus degrading functionalities and distinct taxonomic structure.

BACKGROUND: Gut microbiome community composition differs between cervical cancer (CC) patients and healthy controls, and increased gut diversity is associated with improved outcomes after treatment. We proposed that functions of specific microbial species adjoining the mucus layer may directly impact the biology of CC. METHOD: Metagenomes of rectal swabs in 41 CC patients were examined by whole-genome shotgun sequencing to link taxonomic structures, molecular functions, and metabolic pathway to patient's clinical characteristics. RESULTS: Significant association of molecular functions encoded by the metagenomes was found with initial tumor size and stage. Profiling of the molecular function abundances and their distributions identified 2 microbial communities co-existing in each metagenome but having distinct metabolism and taxonomic structures. Community A (Clostridia and Proteobacteria predominant) was characterized by high activity of pathways involved in stress response, mucus glycan degradation and utilization of degradation byproducts. This community was prevalent in patients with larger, advanced stage tumors. Conversely, community B (Bacteroidia predominant) was characterized by fast growth, active oxidative phosphorylation, and production of vitamins. This community was prevalent in patients with smaller, early-stage tumors. CONCLUSIONS: In this study, enrichment of mucus degrading microbial communities in rectal metagenomes of CC patients was associated with larger, more advanced stage tumors.

Human Papillomavirus Vaccinations During the COVID-19 Pandemic in Middle Schools in the Rio Grande Valley of Texas.

This quasi-experimental study (a community-based, physician-led human papillomavirus [HPV] education campaign and school-based vaccination program) followed 6481 students at eight Pharr-San Juan-Alamo Independent School District (Rio Grande Valley, Texas) middle schools between August 2016 and March 2021. We describe the successes and challenges experienced during the COVID-19 pandemic. HPV vaccine initiation and completion rates increased 1.29-fold and 1.47-fold, respectively, between June 2019 and March 2021. Between March 2020 and March 2021, 268 HPV vaccine doses were provided through 24 school-based interventions. Our program continued successes seen in increasing HPV vaccination rates and reducing possible HPV-associated cancers. (Am J Public Health. 2022;112(9):1269-1272. https://doi.org/10.2105/AJPH.2022.306970).

Fertility-Sparing and Less Radical Surgery for Cervical Cancer.

PURPOSE OF REVIEW: Patients with early-stage cervical cancer who desire future fertility may be candidates for less radical surgery. We review the literature supporting this approach in early-stage disease. RECENT FINDINGS: Retrospective data have shown that in carefully selected patients, the risk of parametrial involvement is less than 1%. This has led to interest in moving away from radical surgery towards more conservative approaches. Data from the newly published ConCerv trial, a prospective study evaluating the feasibility of conservative surgery in women with early-stage, low-risk cervical carcinoma, suggest that conservative surgery is feasible and safe in this patient population. Furthermore, neoadjuvant chemotherapy is being assessed as an option to extend fertility-sparing treatment to a larger group of women. Less radical surgery may be appropriate for carefully selected women with early-stage, low-risk cervical cancer, including those desiring future fertility.

Cervical cancer prevention in El Salvador: A prospective evaluation of screening and triage strategies incorporating high-resolution microendoscopy to detect cervical precancer.

Cervical cancer remains a leading cause of cancer death for women in low- and middle-income countries. The goal of our study was to evaluate screening and triage strategies, including high-resolution microendoscopy (HRME), to detect cervical abnormalities concerning for precancer at the point of care. Women (n = 1824) were enrolled at the Instituto de Cáncer de El Salvador. All underwent screening by both human papillomavirus (HPV) testing using careHPV and visual inspection with acetic acid (VIA). Screen-positives, along with 10% of screen-negatives, were invited to return for a follow-up examination that included triage with VIA, colposcopy and HRME imaging. Biopsies were taken of any abnormalities identified. If no abnormalities were identified, then the worst scoring site by HRME was biopsied. The sensitivities of HPV testing and VIA to screen for cervical intraepithelial neoplasia Grade 2 or more severe diagnoses (CIN2+) were 82.1% and 75% (P = .77), while the specificities were 90.4% and 80.9% (P < .001), respectively. The sensitivities of VIA, colposcopy and HRME as triage tests for CIN2+ were 82.1%, 82.1% and 71.4%, respectively (P ≥ .38). HRME had a significantly higher specificity (66.7%) than VIA (51.9%) (P < .001) and colposcopy (53.3%) (P < .001). When evaluating different theoretical screening and triage strategies, screening with HPV testing followed by triage with HRME would result in more women receiving appropriate care (97%) compared to screening with VIA (75%) or HPV alone (90%). Our findings demonstrate that screening with HPV is superior to VIA, and that triage with HRME imaging increases the specificity of detecting CIN2+ at the point of care in a low-resource setting.

Cervical lesion assessment using real-time microendoscopy image analysis in Brazil: The CLARA study.

We conducted a prospective evaluation of the diagnostic performance of high-resolution microendoscopy (HRME) to detect cervical intraepithelial neoplasia (CIN) in women with abnormal screening tests. Study participants underwent colposcopy, HRME and cervical biopsy. The prospective diagnostic performance of HRME using an automated morphologic image analysis algorithm was compared to that of colposcopy using histopathologic detection of CIN as the gold standard. To assess the potential to further improve performance of HRME image analysis, we also conducted a retrospective analysis assessing performance of a multi-task convolutional neural network to segment and classify HRME images. One thousand four hundred eighty-six subjects completed the study; 435 (29%) subjects had CIN Grade 2 or more severe (CIN2+) diagnosis. HRME with morphologic image analysis for detection of CIN Grade 3 or more severe diagnoses (CIN3+) was similarly sensitive (95.6% vs 96.2%, P = .81) and specific (56.6% vs 58.7%, P = .18) as colposcopy. HRME with morphologic image analysis for detection of CIN2+ was slightly less sensitive (91.7% vs 95.6%, P < .01) and specific (59.7% vs 63.4%, P = .02) than colposcopy. Images from 870 subjects were used to train a multi-task convolutional neural network-based algorithm and images from the remaining 616 were used to validate its performance. There were no significant differences in the sensitivity and specificity of HRME with neural network analysis vs colposcopy for detection of CIN2+ or CIN3+. Using a neural network-based algorithm, HRME has comparable sensitivity and specificity to colposcopy for detection of CIN2+. HRME could provide a low-cost, point-of-care alternative to colposcopy and biopsy in the prevention of cervical cancer.

Dasatinib, paclitaxel, and carboplatin in women with advanced-stage or recurrent endometrial cancer: A pilot clinical and translational study.

PURPOSE: To evaluate the effect of dasatinib therapy on EphA2 signaling in cancers of women with measurable (biopsy amenable) advanced-stage, chemo-naïve primary or recurrent endometrial cancer. Preliminary efficacy was also assessed. PATIENTS AND METHODS: We performed a pilot study of single-agent dasatinib lead-in, followed by triplet dasatinib, paclitaxel, and carboplatin. We measured the downstream effectors of EphA2 signaling in pre- and post-dasatinib treatment biopsy tissue samples; we also determined the severity of adverse events and patients' progression-free survival and overall survival durations. RESULTS: Eighteen patients were recruited and given dasatinib (150 mg orally daily for 14 days), followed by paclitaxel, carboplatin and dasatinib (daily) for six cycles (21-day cycles). Seventeen patients were evaluable for toxicity and 11 patients for response. A reverse phase protein array and proximity ligation assay revealed that CRAF/BRAF dimerization, caveolin-1 level, and Notch pathway signaling were predictive of response and resistance to dasatinib. Overall, the objective response rate was 45% (95% CI: 17%-77%), with median progression-free survival duration of 10.5 months and median overall survival duration of 30.4 months. The most common grade 3 or 4 adverse events were neutropenia (76%), thrombocytopenia (53%), anemia (53%), and fatigue (12%). CONCLUSIONS: Caveolin-1 expression, in combination with CRAF/BRAF heterodimerization, is associated with resistance to EphA2 targeting by dasatinib. The triplet combination showed interesting clinical activity in endometrial cancer with acceptable toxicity. Pretreatment with dasatinib may accentuate combination therapy toxicity.

Prospective phase II trial of levonorgestrel intrauterine device: nonsurgical approach for complex atypical hyperplasia and early-stage endometrial cancer.

BACKGROUND: The incidence of complex atypical hyperplasia and early-stage endometrioid endometrial cancer is increasing, in part owing to the epidemic of obesity, which is a risk factor tightly linked to the development of endometrial hyperplasia and cancer. The standard upfront treatment for complex atypical hyperplasia and early-stage endometrial cancer is hysterectomy. However, nonsurgical treatment of early-stage endometrial neoplasia may be necessary owing to medical comorbidities precluding surgery or desired future fertility. OBJECTIVE: This study aimed to evaluate the efficacy of the levonorgestrel intrauterine device to treat complex atypical hyperplasia and grade 1 endometrioid endometrial carcinoma. STUDY DESIGN: A single-institution, single-arm, phase II study of the levonorgestrel intrauterine device (52 mg levonorgestrel, Mirena) was conducted in patients with complex atypical hyperplasia or grade 1 endometrioid endometrial cancer. The primary endpoint was pathologic response rate at 12 months, including complete or partial response. Quality of life and toxicity were assessed. Molecular analyses for proliferation markers, hormone-regulated genes, and wingless-related integration site pathway activation were performed at baseline and 3 months. RESULTS: A total of 57 patients were treated (21 endometrial cancer, 36 complex atypical hyperplasia). The median age was 48.0 years, and the median body mass index was 45.5 kg/m2. Of the 47 evaluable patients, 12-month response rate was 83% (90% credible interval, 72.7-90.3)-37 were complete responders (8 endometrial cancer; 29 complex atypical hyperplasia), 2 were partial responders (2 endometrial cancer), 3 had stable disease (2 endometrial cancer; 1 complex atypical hyperplasia), and 5 had progressive disease (3 endometrial cancer; 2 complex atypical hyperplasia). After stratification for histology, the response rate was 90.6% for complex atypical hyperplasia and 66.7% for grade 1 endometrioid endometrial cancer. Notably, 4 patients (9.5%) experienced relapse after the initial response. Adverse events were mild, primarily irregular bleeding and cramping. Quality of life was not negatively affected. At 3 months, exogenous progesterone effect was present in 96.9% of responders (31 of 32) vs 25% of nonresponders (2 of 8) (P=.001). Nonresponders had higher baseline proliferation (Ki67) and lower dickkopf homolog 3 gene expression than responders (P=.023 and P=.030). Nonresponders had significantly different changes in secreted frizzled-related protein 1, frizzled class receptor 8, and retinaldehyde dehydrogenase 2 compared with responders. CONCLUSION: The levonorgestrel intrauterine device has a substantial activity in complex atypical hyperplasia and grade 1 endometrioid endometrial cancer, with a modest proportion demonstrating upfront progesterone resistance. Potential biomarkers were identified that may correlate with resistance to therapy; further exploration is warranted.

ConCerv: a prospective trial of conservative surgery for low-risk early-stage cervical cancer.

OBJECTIVE: The objective of the ConCerv Trial was to prospectively evaluate the feasibility of conservative surgery in women with early-stage, low-risk cervical cancer. METHODS: From April 2010 to March 2019, a prospective, single-arm, multicenter study evaluated conservative surgery in participants from 16 sites in nine countries. Eligibility criteria included: (1) FIGO 2009 stage IA2-IB1 cervical carcinoma; (2) squamous cell (any grade) or adenocarcinoma (grade 1 or 2 only) histology; (3) tumor size <2 cm; (4) no lymphovascular space invasion; (5) depth of invasion <10 mm; (6) negative imaging for metastatic disease; and (7) negative conization margins. Cervical conization was performed to determine eligibility, with one repeat cone permitted. Eligible women desiring fertility preservation underwent a second surgery with pelvic lymph node assessment, consisting of sentinel lymph node biopsy and/or full pelvic lymph node dissection. Those not desiring fertility preservation underwent simple hysterectomy with lymph node assessment. Women who had undergone an 'inadvertent' simple hysterectomy with an unexpected post-operative diagnosis of cancer were also eligible if they met the above inclusion criteria and underwent a second surgery with pelvic lymph node dissection only. RESULTS: 100 evaluable patients were enrolled. Median age at surgery was 38 years (range 23-67). Stage was IA2 (33%) and IB1 (67%). Surgery included conization followed by lymph node assessment in 44 women, conization followed by simple hysterectomy with lymph node assessment in 40 women, and inadvertent simple hysterectomy followed by lymph node dissection in 16 women. Positive lymph nodes were noted in 5 patients (5%). Residual disease in the post-conization hysterectomy specimen was noted in 1/40 patients-that is, an immediate failure rate of 2.5%. Median follow-up was 36.3 months (range 0.0-68.3). Three patients developed recurrent disease within 2 years of surgery-that is, a cumulative incidence of 3.5% (95% CI 0.9% to 9.0%). DISCUSSION: Our prospective data show that select patients with early-stage, low-risk cervical carcinoma may be offered conservative surgery.

Cervical Cancer Prevention in Low- and Middle-Income Countries.

Cervical cancer is one of the commonest cancers afflicting women in low and middle income countries, however, both primary prevention with human papillomavirus vaccination, and secondary prevention with screening programs and treatment of preinvasive disease are possible. A coordinated approach to eliminating cervical cancer, as has been called for by the World Health Organization, requires a complex series of steps at all levels of a health system. This article outlines the current state of cervical cancer prevention in low and middle income countries, the innovations being employed to improve outcomes, and consideration of the next steps needed as we move towards global elimination.

Project ECHO Cancer Initiative: a Tool to Improve Care and Increase Capacity Along the Continuum of Cancer Care.

Solving health problems requires not only the development of new medical knowledge but also its dissemination, particularly to underserved communities. The barriers to effective dissemination also contribute to the disparities in cancer care experienced most everywhere. This concern is particularly acute in low and middle-income countries which already bear a disproportionate burden of cancer, a situation that is projected to worsen. Project ECHO (Extension for Community Healthcare Outcomes) is a knowledge dissemination platform that can increase workforce capacity across many fields, including cancer care by scaling best practices. Here we describe how Project ECHO works and illustrate this with existing programs that span the cancer care continuum and the globe. The examples provided combined with the explanation of how to build effective Project ECHO communities provide an accessible guide on how this education strategy can be integrated into existing work to help respond to the challenge of cancer.