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PURPOSE: This study assessed the safety and tolerability of therapeutic immunization against the human papillomavirus (HPV) viral oncoproteins E6 and E7 in patients with cervical cancer after chemoradiation. METHODS AND MATERIALS: MEDI0457 (INO-3112) is a DNA-based vaccine targeting E6 and E7 of HPV-16/18 that is coinjected with an IL-12 plasmid followed by electroporation with the CELLECTRA 5P device. At 2 to 4 weeks after chemoradiation, patients with newly diagnosed stage IB1-IVA (cohort 1) or persistent/recurrent (cohort 2) cervical cancers were treated with 4 immunizations of MEDI0457 every 4 weeks. The primary endpoints were incidence of adverse events and injection site reactions. Immune responses against HPV antigens were measured by ELISpot for interferon-γ (IFNγ), enzyme-linked immunosorbent assay for antibody responses and multiplexed immunofluorescence for immune cells in cervical biopsy specimens. RESULTS: Ten patients (cohort 1, n = 7; cohort 2, n = 3) with HPV16 (n = 7) or HPV18 (n = 3) cervical cancers received MEDI0457 after chemoradiation. Treatment-related adverse events were all grade 1, primarily related to the injection site. Eight of 10 patients had detectable cellular or humoral immune responses against HPV antigens after chemoradiation and vaccination: 6 of 10 patients generated anti-HPV antibody responses and 6 of 10 patients generated IFNγ-producing T cell responses. At the completion of chemoradiation and vaccination, cervical biopsy specimens had detectable CD8(+) T cells and decreased PD-1(+)CD8(+), PD-L1(+)CD8(+), and PD-L1(+)CD68(+) subpopulations. All patients cleared detectable HPV DNA in cervical biopsies by completion of chemoradiation and vaccination. CONCLUSIONS: Adjuvant MEDI0457 is safe and well tolerated after chemoradiation for locally advanced or recurrent cervical cancers, supporting further investigation into combining tumor-specific vaccines with radiation therapy.

UCRShiny is an intelligent user interface application that utilizes R and R-Shiny tools and statistical intelligence to allow users to visualize geospatial cancer data and perform advanced analyses and predictive modeling. UCRShiny's focus is the catchment area (in Illinois and Indiana) near UCCC and utilizes various metadata. This includes fitting univariate and multivariate models to make statistically sound inferences from the data. It also allows the user to plot specific data on a map of the catchment area as layers for descriptive analysis and visual geospatial assessment. As well as assessing the significance of the relation between these factors. These statistical tools should have a level of intelligence that can determine the correctness of the model's assumptions. An advantage of our tool is that it provides an overall diagnosis of the model to the user without the need for the intervention of an expert statistician. The data selected for analysis are assessed to ensure they meet the assumptions of the statistical model being used, and proper data transformations are applied. The presence of confounding factors is assessed using linear models in sequence. Initially, a single variable linear model is fit using the primary variable of interest (i.e., Cancer mortality) as the response variable and the second variable in the univariate analysis as the covariate. The second model adds the internal metadata columns as potential confounders to the model. In the third step, the percent change in the coefficient of the second variable in the first and second linear models is calculated. Multivariate analysis using ML is used to simultaneously assess the effect of multiple variables on the outcome variable. Here, we use various ML algorithms based on the problem and data at hand, report the significant features, and quantify their impact on the response of interest. The tool allows users to utilize the in-app data, load their dataset, or combine both datasets. It helps to visualize geospatial health data on a map, perform statistical analysis and build ML/AI models without being concerned about the validity of the statistical models. After uploading data and selecting the appropriate statistical test/analysis, results will be visualized as a plot on a map with the specified layers collared by the layer variable values. The layers can be turned on or off using specific buttons on the map. GIS maps may be easily shared and included in apps and are available to almost everyone, anywhere. The user can study the effect of multiple variables and rank their importance in predicting the response variable using multivariate ML/AI models. The UI allows the user to select an appropriate ML algorithm for the model or the application's intelligent backend algorithms to choose the proper ML model (This will be implemented in phase II). The outcome feature and the covariates to use in the model can be selected using searchable textboxes in the UI, and the model is run using the Run model button. Citation Format: Ahmed Fadiel Metwaly, Adam Thomas Koster, Mohammad Abbasi, Aya Hassouneh, Jasmin Tiro, Nita Lee, Adekunle Odunsi. A geo inelegant approach to cancer disparity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1973.

Purpose: To utilize data on hospital admissions among patients with cervical cancer during treatment and long-term surveillance to better understand disease and treatment related burdens, explore inpatient utilization of services, and identify risk factors for admission. Methods: Retrospective chart review was performed on patients treated for cervical cancer from 2014 to 2020 at a single academic institution. Clinical, demographic and treatment information and hospital admission characteristics were collected. Discharge diagnoses were grouped and summarized with descriptive statistics. Univariate and multivariate regression were used to examine associations between patient characteristics and likelihood of admission. Results: Of 366 patients identified, 188 (51%) were admitted to the hospital for cancer or treatment-related reasons excluding planned admissions for initial treatment, in the median follow-up period of 3.6 years (IQR 1.4-6.4), with a median number of 2 admissions (IQR 1-4) and median length of stay 4 days (IQR 2-7). Of those admitted, 65 (35%) had discharge diagnoses belonging to more than one clinical category. The five most common discharge diagnoses were gastrointestinal problems (40%), genitourinary problems (35%), infection (35%), pain control (21%), and vaginal bleeding (19%). A significant proportion of admitted patients underwent inpatient interventions including imaging (68%), surgical procedures (57%), antibiotics (52%), transfusion of blood products (40%), and interventional radiology procedures (28%) and utilized supportive and specialty care including case management (53%), physical therapy (40%), occupational therapy (36%), social work (36%), nutrition (31%), and palliative care (23%). On univariate analysis, Black patients (OR 3.0, p Citation Format: Rayne Peerenboom, Sarah Ackroyd, Chuanhong Liao, Aarthi Koripelly, Nita Lee. Disparities in non-surgical admissions for survivors of cervical cancer: Understanding morbidity and survivorship needs through hospital admissions [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B117.

Purpose We sought to investigate the patient and physician approaches to malignant bowel obstruction (MBO) due to recurrent gynecologic cancer by 1) comparing patient and physician expectations and priorities during a new MBO diagnosis, and 2) highlighting factors that facilitate patient-doctor communication.Methods Patients were interviewed about their experience during an admission for MBO, and physicians were interviewed about their general approach towards MBO. Interviews were analyzed for themes using QDAMiner qualitative analysis software. The analysis utilized the framework analysis and used both predetermined themes and those that emerged from the data.Results We interviewed 14 patients admitted with MBO from recurrent gynecologic cancer and 15 gynecologic oncologists. We found differences between patients and physicians regarding plans for next chemotherapy treatments, foremost priorities, communication styles, and end-of-life discussions. Both patients and physicians felt that the patient-physician communication was improved in situations of trust, understanding patient preferences, corroboration of information, and increased time spent with patients during and before the MBO.Conclusion Gaps in patient-physician communication could be targeted to improve the patient experience and physician counseling during a difficulty diagnosis by focusing on education, symptoms, home support, nutrition, and end-of-life care.

Objectives: 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. Methods: 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. Results: 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 Conclusions: 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.

Purpose: Radiotherapy patient education materials fail to meet readability standards, impairing access for patients with low educational attainment, disabilities, or limited-English proficiency. Design professionals and physicians developed graphic narrative discussion guides, Communication of the Gynecologic Brachytherapy Experience (CoGBE), for cylinder, intracavitary, and interstitial high-dose rate (HDR) gynecologic brachytherapy. This study assesses perceived clinical benefits, usability, and anxiety-reduction of CoGBE. Methods: An electronic survey was sent to members of the American Brachytherapy Society. Participants were assigned to assess one of the three modality-specific CoGBE guides using a modified Systems Usability Scale (mSUS), modified state-trait anxiety index (mSTAI), and Likert-type questions. Free response data was analyzed using modified grounded theory. Results: Median mSUS score was 76.3 (interquartile range [IQR], 71.3-82.5) and there were no significant differences between guide types. Median mSTAI was 40 (IQR, 40-43.3) for all guides collectively. The cylinder guide had a significantly higher median mSTAI than the intracavitary and interstitial guides (41.6 vs 40.0 and 40.0; p=0.04) suggesting the cylinder guide may have less impact on reducing anxiety. 72.7% rated CoGBE as “quite” or “extremely” helpful compared to a text-only pamphlet. When compared to their current education practices, 77.3% reported patients would understand “more” or “a lot more” after initial consultation and 81.8% reported CoGBE would be at least moderately helpful in making initial consultations more memorable for patients. Lastly, 79.5% reported at least a moderate likelihood of using CoGBE. Qualitative analysis themes included personalization, relatability, and graphic narrative (positive domains); generalizability and character affect (negative domains). Conclusion: Clinicians rate CoGBE as usable with potential to reduce patient anxiety, especially with more invasive treatment modalities including intracavitary or interstitial HDR. The CoGBE guides (including multilingual versions) have global applicability, in low resource settings with high cervical cancer burdens and patient populations that may benefit from the graphic narrative format. Citation Format: Santiago Avila, María J. Ruiz, Ritu Arya, Brian Callender, Yasmin Hasan, Josephine S. Kim, Nita Lee, Anne McCall, Christina H. Son, Kate Stack, Sabah Asif, Tyler Besecker, Arushi Juneja, Zhongyang Li, Pinakee Naik, Tanvi Ranka, Prachi Saxena, Brian Siegfried, Tomoko Ichikawa, Daniel W. Golden. Communicating the Gynecologic Brachytherapy Experience (CoGBE): Clinician Perceived Benefits of a Graphic Narrative Patient Education Tool [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 105.

Progesterone inhibits the proliferative growth effects of estrogen in the endometrium and prevents the development of endometrial hyperplasia and Type I adenocarcinoma. The exact mechanism of this action is unknown. The progesterone-induced helix-loop-helix transcription factor Heart and Neural Crest Derivatives Expressed 2 (Hand2) was recently shown to suppress production of growth factors in the endometrium. In Hand2 knockout mice, continuous proliferation of the endometrium was observed. In this study, archival paraffin-embedded tissue from 56 hysterectomy specimens was examined by immunohistochemistry for the expression and localization of Hand2, estrogen receptor (ER), progesterone receptor (PR), and Ki-67. Diagnoses included disordered proliferative endometrium, simple and complex hyperplasia with or without atypia, and endometrioid adenocarcinoma. Hand2 expression is localized to endometrial stromal nuclei. In benign endometrium, Hand2 expression was moderate to strong (10/11; 91%), with weak Hand2 expression in only 1 case (1/11; 9%). Similar Hand2 expression patterns were observed in disordered proliferative endometrium and simple hyperplasia without atypia, with moderate to strong expression in 91% of cases (10/11) and weak expression in 9% of cases (1/11). In contrast, simple and complex hyperplasia with atypia exhibited moderate to strong Hand2 expression in 8% of cases (1/12) and a loss of expression or weak expression in 92% of cases (11/12). In endometrioid adenocarcinomas, Hand2 expression was absent in all cases (22/22). Hand2 is expressed in the stroma of benign endometrium, but expression is significantly reduced or lost in atypical hyperplasia and endometrioid carcinoma. Thus, the absence of Hand2 expression may be a useful biomarker for atypical hyperplasia and endometrioid carcinoma.

We prospectively studied immune reconstitution in 102 children who underwent T-lymphocyte depleted bone marrow transplants using either closely matched unrelated donors or partially matched familial donors by assaying total lymphocyte counts (TLC), T-cell subsets, B cells, and natural killer cells. TLC, CD3+, and CD4+ T-cell counts remained depressed until 2 to 3 years posttransplant, whereas CD8+ T-cell counts normalized by 18 months, resulting in an inverted CD4:CD8 ratio until 12 months posttransplant. Although the percentage of NK cells was elevated early posttransplant, their absolute numbers remained normal. CD20+ B cells were depressed until 12 to 18 months posttransplant. Factors affecting immunophenotypic recovery were analyzed by nonparametric statistics. Younger patients tended to have higher TLC posttransplant. Higher marrow cell doses were not associated with hastened immunophenotypic recovery. Graft-versus-host disease (GVHD) and/or its treatment significantly delayed the immune reconstitution of CD3+, CD4+, and CD20+ cells. The presence of cytomegalovirus was associated with increased CD8+ counts and a decrease in the percentages of CD4+ and CD20+ cells.