High-res Image Research Articles

A Survey of Data-Driven 2D Diffusion Models for Generating Images from Text

This paper explores recent advances in generative modeling, focusing on DDPMs, HighLDM, and Imagen. DDPMs utilize denoising score matching and iterative refinement to reverse diffusion processes, enhancing likelihood estimation and lossless compression capabilities. HighLDM breaks new ground with high-res image synthesis by conditioning latent diffusion on efficient autoencoders, excelling in tasks through latent space denoising with cross-attention for adaptability to diverse conditions. Imagen combines transformer-based language models with HD diffusion for cutting-edge text-to-image generation. It uses pre-trained language encoders to generate highly realistic and semantically coherent images, surpassing competitors based on FID scores and human evaluations in DrawBench and similar benchmarks. The review critically examines each model's methods, contributions, performance, and limitations, providing a comprehensive comparison of their theoretical underpinnings and practical implications. The aim is to inform future generative modeling research across various applications.

Crosslinked polymer electrolyte constructed by metal-oxo clusters for solid lithium metal batteries

By using structurally well-defined metal-oxo clusters as crosslinkable nanofillers, the authors develop a hybrid inorganic/organic crosslinked polymer electrolyte. With the favorable electrochemical and mechanical properties, as well as the enhanced lithium dendrite-suppressing capability, the metal-oxo cluster crosslinked polymer electrolyte can significantly improve the capacities, rate capabilities, and cycling stabilities of solid lithium metal batteries. Download : Download high-res image (175KB)Download : Download full-size image

39 Treatment efficacy of aromatase inhibitors for leiomyosarcoma of the uterus

The objective of this study was to assess whether aromatase inhibitors (AIs) improve overall and survival in patients with uterine leiomyosarcoma (uLMS). We conducted an institutional review board-approved, retrospective cohort study at Kaiser Permanente, Riverside Medical Center. All patients who received a diagnosis of uLMS on pathology from 2012–2021 were reviewed. Demographics and outcomes were compared between patients that received AIs versus those that did not. The study included a total 17 patients with uLMS, including five who received an AI (29%). A Log-rank (Mantel-Cox) test demonstrated a significant difference in overall survival (OS) between patients who received Anastrozole versus patients who did not receive hormonal treatment, p=0.0305, hazard ratio (HR) 0.165, 95% confidence interval (CI) [0.032, 0.844] (Fig. 1).Download : Download high-res image (104KB)Download : Download full-size image Uterine leiomyosarcoma (uLMS) is a rare and aggressive malignancy that generally portends a poor prognosis. Generally speaking, surgical therapy is the standard of care for early-stage disease. Despite complete resection of the tumor, the risk of recurrence of leiomyosarcoma remains high due to its high-grade histopathology. Hormonal therapy has been successful in decreasing rates of recurrence and improving survival in a subset of patients with uLMS. More specifically, aromatase inhibitors (AIs) have been utilized as post-operative adjuvant therapy for patients with estrogen receptor (ER) and progesterone receptor (PR) positive stage I uLMS and for patients with recurrent, metastatic and unresectable disease. Our study demonstrates that there may be a role for AIs in the treatment of recurrent uLMS. Due to its high recurrence rate and low response to chemotherapy and radiation, other forms of treatment need to be explored and identified.

23 Identifying HPV vaccination initiation hot and cold spots and associated disparities in Texas

Over 90% of HPV-associated cancers are preventable through HPV vaccination. Only 43.5% of Texas adolescents, however, have completed the vaccine series, and the state ranks 47th in vaccination rates across the country. The goal of this study was to examine the geospatial uptake of the HPV vaccine in Texas and the associated disparities. HPV vaccine data from 2017–2021 was obtained from the Texas Department of State Health Services. Zip code-level estimates of individuals 9 years and older who received at least one HPV vaccine since 2017 in the Texas Immunization Information System (ImmTrac2) database were used to create a choropleth map. Through the Environmental Science Research Institute's (ESRI) ArcGIS Pro Version 2.2.0 software, the Cluster and Outlier Analysis Tool was used to determine a “neighborhood” around each zip code. Zip codes were subsequently demarcated as hot or cold spots (or neither) based off Local Moran's I score calculations, meaning they had a statistically significant greater or lesser concentration of vaccinations than would be expected from a random distribution. After identifying hot spots and cold spots of vaccine initiation, we explored the demographic neighborhood characteristics. 346 statistically significant hot and 374 cold spot zip codes of HPV vaccine initiation were identified (Fig. 1). The remainder of the zip codes (1115) were outliers or not part of statistically significant clusters. Hot spot zip codes, or areas of high vaccine initiation, were found along the Gulf coast, in large cities, and in less developed areas near the Texas panhandle. Cold spot zip codes were in the northern Texas panhandle, along the Texas–Louisiana border, and on the periphery of major cities. Compared to cold spot zips, hot spots had significantly higher percentages of children on public insurance, had higher poverty rates, and had higher percentages of African American and Hispanic residents.Download : Download high-res image (217KB)Download : Download full-size image In Texas, areas with higher poverty rates, increased use of public insurance, and higher percentages of minority populations had significantly higher rates of HPV vaccine initiation. This may be due to differences in patient interest in the vaccine, to vaccine access through government insurance, or to outreach efforts that have promoted the vaccine in especially vulnerable populations.

25 Comparison of three testing strategies for germline genetic testing for homologous recombination deficiency mutations in women with epithelial ovarian cancer

One in five women with epithelial ovarian cancer (EOC) will have an inherited germline mutation, yet testing rates are low. Point-of-care testing, where abbreviated counseling with in-office testing is offered, may increase testing rates. We aimed to compare testing rates among three different testing strategies used in our practice over time. All patients with EOC were identified in the electronic medical record (EMR) using diagnosis codes at an urban academic gynecologic oncology practice from 1/2015 to 12/2020. IRB approval was obtained. EMR review was performed. Trends in genetic counseling and testing rates were analyzed across three different practice models: embedded genetic counselor in the clinic (before 5/2017), referral out for genetic counseling (5/2017–10/2017) and point-of-care office testing (after 10/2017). Descriptive statistics and chi-square tests were performed. 431 patients with EOC patients were identified. Patients were predominantly white (88%), older women (average age 67.9), with Medicare (58%) or private insurance (39%), and advanced stage disease (63% Stage III, 17% Stage IV) of high-grade serous (77%) histology. Germline BRCA1 or 2 mutations were identified in 10.5% and 4.5% of patients, and 10.6% of patients had a different homologous recombination deficiency mutation. Significant differences in genetic testing rates were identified by strategy (p<0.0001). During the embedded genetic counselor period, 66% (173/263) of patients underwent genetic testing. Testing dropped to 13% (13/104) when patients were referred out, then improved to 65% (160/245) with the initiation of point-of-care testing (Fig. 1). 80% of patients eventually received germline genetic testing; 44% of patients initially not tested (40/91) underwent catch-up testing after initiation of point-of-care testing.Download : Download high-res image (101KB)Download : Download full-size image Germline genetic testing rates for women with EOC were comparable for embedded genetic counselor and point-of-care testing strategies. Point-of-care testing has allowed catch-up testing over time, whereas the referral out strategy presented a substantial barrier. To achieve guideline-concordant care, point-of-care testing with post-test counseling represents a feasible strategy for gynecologic oncology practices where access to an embedded genetic counselor is not possible.

Seasonal rainfall distribution drives nitrogen use efficiency and losses in dryland summer sorghum

Nitrogen (N) fertiliser inputs represent one of the largest variable costs in dryland cropping systems, and a key determinant of water-limited yield. Despite extensive research into microbial N losses via intermediate denitrification products such as N2O, limited research exists on total N losses, and the effect of increasing soil N surplus has on fertiliser use-efficiency is not clear. In this study, the fate of banded urea fertiliser N across crop uptake, soil residual N and N losses was determined using the 15N recovery technique over nine trials with four N rates (0, plus low, medium and high industry rates) across N responsive and non-N responsive sites over 3 years in dryland sorghum (Sorghum bicolor). On average, crop uptake efficiency ranged from 50% at the low and medium N rate (80 kg N ha−1) to < 38% at the highest N rate, and was as low as 5%. Nitrogen losses averaged 26.5% across all rates and trials. At the medium N rate, losses exceeded 18% in all trials, despite relatively dry seasons, and in some trials exceeded 34%. Losses of N were driven by large cumulative rain events and high early-season rainfall. In dryland systems, the inability of crops to acquire banded N fertiliser can potentially leave fertiliser stranded in the topsoil, leaving it vulnerable to losses.Download : Download high-res image (141KB)Download : Download full-size image

7 - Method for Detecting Calcium Phosphate Mineralization on Dental Composites

The purpose of the study is to develop a procedure for determining the in-vitro calcium phosphate mineralization potential of dental composites. A dental material containing Methacrylate-Functionalized Calcium Phosphate (MCP), was studied to determine a procedure to identify and quantify its capacity to create calcium phosphate mineralization. This study used Activa Presto, a dental composite containing 3 wt.% MCP (3MCP), and a control with the same chemical formulation as Presto, but without MCP (0MCP). Using ISO 23317:2007 as a guideline, six cylindrical samples were created with an approximate diameter of 9.5 mm and height of 4 mm. Each sample was fabricated with an embedded nylon thread, which was used to suspend each sample in 25 mL of phosphate buffered saline (PBS) in individual plastic bottles. The samples were stored in a 37 C incubator for time periods of one, two and four weeks, and the PBS solution was replaced twice weekly. Once the designated time period elapsed, the samples were removed from the solution, placed back in the 37 C incubator and desiccated for scanning electron microscopy (SEM) with energy dispersive spectroscopy (EDS) evaluation. The SEM of the 0MCP sample was uniform throughout. At 3000x magnification the surface was granular and showed no sign of crystal formation. All the SEMs of the 3MCP samples had areas of crystal formation and areas where crystals had not yet formed (nucleation areas). The nucleation areas on the 3MCP sample looked granular, like the control, but EDS revealed a different surface composition. The EDS shows that the 0MCP sample had minimal calcium and phosphorus, elements essential for mineralization. This sample had a high amount of silicon, which comes from the silica inherent in dental composites. The nucleation area of the 3MCP sample had over five times the amount of calcium and phosphorus compared to the control, which indicates that there is an increase in potential for mineralization. The crystal area of the 3MCP sample shows about three times the amount of calcium and phosphorus when compared to the nucleation area, these values confirm the surface has been mineralized. Additionally, silicon was not detectable in this area, which suggests that the crystals are dense, and completely cover the underlying silica in the composite. The results of this study confirm that this procedure is suitable to determine the in-vitro mineralization potential of dental composites.Download : Download high-res image (307KB)Download : Download full-size image

AML-347: A Preliminary Analysis of FLAM (Italian Non-Interventional Multi-Center Study of FLT3-Mutated AML Patients): FLT3 Receptor Gene Mutational Analysis and FLT3 Inhibitor Administration in Real-Life Clinical Practice

AML-347: A Preliminary Analysis of FLAM (Italian Non-Interventional Multi-Center Study of FLT3-Mutated AML Patients): FLT3 Receptor Gene Mutational Analysis and FLT3 Inhibitor Administration in Real-Life Clinical Practice

AML-468: Outcomes of FLT3-Mutated Acute Myeloid Leukemia Patients: A Single-Center, Real-World Experience

Background:Internal tandem duplications (ITDs) within the FMS-like tyrosine kinase 3 (FLT3) gene (FLT3-ITD) is a common driver mutation and confers a poor prognosis in patients (pts) with acute myeloid leukemia (AML) due to proliferative presentation, short remission durations and early relapse. The addition of midostaurin to induction therapy has become standard therapy in newly diagnosedFLT3-mutated (FLT3-mu) AML. Next-generation FLT3 inhibitors (FLT3i) as gilteritinib and quizartinib are more specific, more potent, and may have fewer toxicities associated with off-target therapies but are only available in clinical trials or for salvage therapy. Real-world experience in smaller academic institutions is scanty. Methods:We reviewedFLT3-ITD mu AML pts at our institution from October 2016-December 2019. FLT3i were given as a single agent or in combination with cytotoxic chemotherapy (CCT) or low intensity therapy (LIT) (hypomethylating agents). AllFLT3-ITD DNA was subjected to PCR amplification using primers targeting the juxtamembrane domain of FLT3, and products were analyzed by capillary electrophoresis. We analyzed the characteristics of these pts, responses to therapy, and outcomes. Results:Sixteen pts with newly diagnosedFLT3-ITD mu AML were identified. The median age was 47 years [range, 17-76 years] and the median follow-up was 9.3 months [range, 1.2-29.5 months]. The median time from AML diagnoses to FLT3 detection was 4 days [range, 3-5 days]. Patient characteristics are shown in Table 1. The most common co-occurring mutations wereNPM1(44%) andNRAS(31%); 2 pts (12%) had both mutations. Five pts (31%) received CCT and 11 pts (69%) received CCT+FLT3i. The most frequently used FLT3i was midostaurin 25 mg twice daily on days 8 through 21 (14 days) (10 pts, 63% of all pts); 1 pt received sorafenib (6% of all pts). The complete remission rate (CR) and the overall response rate (ORR) (CR+CR with incomplete hematologic recovery [CRi]) were 31% and 88%, respectively. The two pts who did not achieve a remission were older than 65 years. Among the pts who received CCT+FLT3i, CR and OOR were 50% and 100%, respectively. The median number of cycles to remission was 1 [range, 1-2 cycles], and the median number of consolidation cycles was 0 [range, 0-3 cycles]. Overall, the median duration of response in frontlineFLT3-ITD pts who did not receive allogeneic hematopoietic stem cell transplantation (Allo-HSCT) was 5 months [range, 1-9 months] (all of them received CCT+FLT3i). There was no statistically significant difference in response in pts with NPM1 mutation compared with pts with NRAS mutation (P=0.7), or with no additional mutations. Seven pts (44%) received an Allo-HSCT (6 after CCT+FT3i, and 1 after CCT alone): 2 (28%) from matched unrelated donor, 1 (14%) from a haploidentical transplant, 1 (14%) from dual cord transplant, and the remaining (44%) from matched related donors. Two patients relapsed after Allo-HSCT (28%). Both of these patients had received FLT3i before Allo-HSCT; one of the two relapsed pts received ivosidenib and azacitidine (IDH1 mutation) after Allo-HSCT, achieved remission then received the 2nd Allo-HSCT with subsequent remission. Two pts (29%) received maintenance therapy after Allo-HSCT, one with midostaurin, and the other with azacitidine + gilteritinib; both pts are still on remission (24 and 6 months after CR, respectively). All 7FLT3-ITD pts who did not receive Allo-HSCT relapsed. Gilteritinib was used as a single agent (n=3) or in combination with LIT (n=1) in these pts after relapse. CR rate was 25% and CRI 50%; one pt relapsed (33%). All pts who responded are still receiving gilteritinib. Conclusion:Combination of FLT3i based therapy with CCT is effective therapy inFLT3-ITD frontline pts in real-world setting. Duration of response is short in the absence of Allo-HSCT. Download : Download high-res image (299KB) Download : Download full-size image Disclosures Cortes:Arog:Research Funding;Pfizer:Consultancy, Research Funding;Amphivena Therapeutics:Research Funding;Daiichi Sankyo:Consultancy, Research Funding;Astellas:Research Funding;Telios:Research Funding;Novartis:Consultancy, Research Funding;BioPath Holdings:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Merus:Research Funding;Bristol-Myers Squibb:Research Funding;Takeda:Consultancy, Research Funding;Sun Pharma:Research Funding;BiolineRx:Consultancy, Research Funding;Immunogen:Research Funding;Jazz Pharmaceuticals:Consultancy, Research Funding.

Peritoneal cytology evaluation at hysterectomy for endometrial cancer: changes in guideline adherence in the United States

Objectives: In 2009, the International Federation of Gynecology and Obstetrics revised 30 cancer staging schema for endometrial cancer and removed peritoneal cytology from the staging criteria. This study examined population-based trends, characteristics, and outcomes of peritoneal cytologic sampling for endometrial cancer surgery following the 2009 staging revision in the United States. Methods: This is a retrospective observational study querying the National Cancer Institute's Surveillance, Epidemiology, and End Results Program to examine women with stage I-III endometrial cancer who underwent hysterectomy from 2010-2017. Trends, characteristics, and survival associated with peritoneal cytologic evaluation at the time of hysterectomy were assessed in multivariable analysis and with propensity score weighting. Results: Among 62,809 women who underwent hysterectomy, 43,873 (69.9%) had peritoneal cytologic evaluation at surgery and 18,936 (30.1%) did not. Utilization of peritoneal cytologic evaluation decreased from 75.5% to 64.9% during the study period (P Download : Download high-res image (94KB) Download : Download full-size image Conclusions: Despite guideline recommendations, performance of peritoneal cytologic sampling has gradually decreased following the 2009 staging revision in the United States. Our study suggested that peritoneal cytology evaluation at hysterectomy may be associated with improved survival in endometrial cancer.

Survival after primary surgery compared with neoadjuvant chemotherapy in early-stage ovarian cancer

Objectives: Our study evaluates survival of women with early-stage ovarian cancer treated with neoadjuvant chemotherapy (NAC) vs primary debulking surgery (PDS). Methods: We used the 2004-2015 NCDB to identify women with early ovarian cancer treated with multiagent chemotherapy and appropriate surgery. Logistic regression was used to identify predictors of NAC. Overall survival estimates were compared using Kaplan-Meier analysis and Cox proportional hazards regression models were used to examine variables. Results: In total, 14,627 women were included. The majority (96%) underwent PDS while (4%) underwent NAC. Median survival times were 40 months (95% CI [37.190-47.280], P Download : Download high-res image (124KB) Download : Download full-size image Conclusions: Women treated with neoadjuvant chemotherapy (NAC) had worse overall and 5-year survival. This finding agrees with the accepted convention of reserving NAC for women with advanced, unresectable disease.

Optimizing timing of palliative care referral in platinum resistant ovarian cancer

Objectives: An exploration of clinical characteristics, palliative care involvement, and survival in platinum resistant ovarian cancer. Methods: This is a single institution retrospective study of all patients receiving chemotherapy for ovarian, fallopian tube, or peritoneal high-grade carcinoma since 2011. Platinum resistant patients were identified based on chemotherapy regimen or provider definition, then confirmed with clinical data. Data was extracted evaluating platinum resistant treatment, time to progression, and overall survival. Palliative care and hospice referrals were recorded. Descriptive and overall survival analyses were performed. Results: Two hundred and seventy-five platinum resistant patients were identified. Of 100 charts reviewed to date, 78 patients were deceased. The median survival from time of diagnosis of platinum resistant to death was 11.4 months (range 0.5-66 months). Of the 78 deceased patients, 25 (32%) lived less than 6 months from time of diagnosis of platinum resistance (range 0.5-5.9 months), 23 (29.5%) lived 6-12 months, and 30 (38.5%) lived more than 12 months (range 12.9-66 months). Of the 25 patients who lived less than 6 months, 17 (68%) were referred to palliative care and 6 (24%) were referred directly to hospice, 3 of which were within one month of death. Of the 23 patients who lived 6-12 months, 16 (69.5%) were referred to palliative care and 6 (26%) were referred directly to hospice, 5 of which were within one month of death. Finally, of the 30 patients who lived greater than 12 months, 23 (76.7%) were referred to palliative care and 5 (16.7%) were referred directly to hospice. In 17 (57%) of the patients living greater than 12 months after platinum resistance, referral to palliative care or hospice did not happen until the 3 months prior to death (Figure 1). Of the living patients with platinum resistant disease, median survival since diagnosis is 9.8 months. Of these patients, 11 (50%) have been referred to palliative care and 11 (50%) have no documentation of palliative care referral. Data extraction and analysis is on-going, with 175 remaining charts to review. Conclusions: Diagnosis of platinum resistance is a pivotal point in ovarian cancer treatment. Survival from time of diagnosis of platinum resistance to death is limited. National recommendations encourage routine integration of palliative care within eight weeks of diagnosis of advanced cancer in order to optimize patient and caregiver outcomes. Our work found room for improvement in the timing of palliative care referrals in platinum resistant ovarian cancer patients. Even more strikingly, we found a pattern of direct referral to hospice, without palliative care referral prior, often within a month of death. This highlights a significant missed opportunity in utilization of palliative care in the months, and potentially years, leading up to the end of life. Diagnosis of platinum resistance should serve as a stimulus for involvement of palliative care services. Download : Download high-res image (179KB) Download : Download full-size image

Rate of fracture among women undergoing treatment for gynecologic malignancies

Objectives: Women undergoing treatment for gynecologic malignancies have multiple risk factors for developing fractures, including surgically-induced menopause, cytotoxic chemotherapy, and radiation therapy. The incidence of fracture among women treated for gynecologic cancers is estimated to be as high as 20%, however there is limited data regarding the rate of and risk factors for fracture in this population. The objective of this study was to evaluate the incidence of fracture and characteristics of patients with fracture among women undergoing treatment for gynecologic malignancies. Methods: This was a single-institution retrospective cohort study of patients who received surgery, chemotherapy, hormonal therapy, and/or radiation for the treatment of cervical, uterine, and/or vulvar cancer between January 2012 and December 2014. Data on patient demographics, comorbidities, cancer therapies, and risk factors for fracture were manually extracted from patients’ medical records. Results: Of the 469 women included in the analysis, most (93.8%) were White or African American (3.6%), with a mean age of 58.2 (SD=13.7) years at the time of cancer diagnosis. The mean BMI was 34.8 (SD=9.8) kg/m2. Most (70.4%) patients were menopausal prior to cancer treatment and 16.4% underwent surgically-induced menopause. The majority (69.7%) of patients had a diagnosis of uterine cancer, followed by cervical cancer (16.8%) and vulvar cancer (8.5%). One third (33.7, n=158) received neoadjuvant or adjuvant chemotherapy and 28.4% (n=133) underwent adjuvant radiation. The mean pre- and post-treatment risk of major osteoporotic fracture by FRAX score was 6.9% (SD=5.7) and 8.5% (SD=6.5). Only 20 patients (4.3%) had a DXA scan performed prior to cancer treatment. The proportion of post-treatment fracture within the first two years following treatment was 3.6% (n=17). Of these, most (88.2%, n=15) were diagnosed by x-ray (n=9, 54.8%), followed by MRI (n=4, 23.5%) and CT (n=2, 11.8%). Patients with post-treatment fractures tended to be older at time of treatment (61.9 vs 57.6 years), current tobacco users (47.1% vs 14.1%), and postmenopausal prior to cancer therapy (100% vs 69.7%). Patients with post-treatment fractures also tended to have one or more comorbidity (100% vs 89.4%), have cervical cancer (41.2% vs 15.9%), and to have undergone radiation treatment (64.7% vs 27.4%) as well as chemotherapy treatment (70.6% vs 32.7%). Download : Download high-res image (274KB) Download : Download full-size image Conclusions: Our findings indicate the rate of fracture in the first two years following treatment for gynecologic malignancies is approximately 3.6%. Few women undergo bone mineral density screening prior to cancer treatment. Women with cervical cancer who are postmenopausal with multiple co-morbidities prior to treatment who receive chemotherapy and/or radiation are at higher risk. The mean post-treatment FRAX of 8.5% suggests that many patients may benefit from bone mineral density testing and risk stratification for osteoporosis following cancer therapy.

The role of obesity in treatment planning for early-stage cervical cancer

Objectives: There is limited data comparing radical hysterectomy (RH) to definitive radiation therapy (RT) for early stage cervical cancer. National guidelines recommend RH when feasible given the potential for long term morbidity with definitive RT. Management of obese patients with early stage cervical cancer is controversial despite evidence of non-inferior survival in obese patients undergoing RH. Our aims were to 1) describe patient factors affecting disposition to RH versus RT in patients who were RH candidates by clinical stage (CS), 2) compare differences in progression free survival (PFS) and overall survival (OS), and 3) compare RH outcomes for obese (BMI of 30) and non-obese patients. Download : Download high-res image (469KB) Download : Download full-size image Methods: This was a single institution retrospective chart review of all cervical cancer patients from 2001-2019. Patients who had a primary RH or were candidates for RH based on CS at presentation were included in the final cohort. Demographic, clinicopathologic and treatment outcomes were collected for each group. Univariable and multivariable analyses were used to identify factors influencing disposition to RH versus RT. Kaplan-Meier and Cox proportional hazard (PH) models were used to analyze PFS and OS. Results: The final cohort included 260 patients (RH=221 (85%), RT=39 (15%)). RT patients were significantly older (58.2 years vs 43.8 years, p Conclusions: There is limited data comparing RH vs RT for early stage disease; however, RT can be associated with long-term morbidity. In this cohort of RH-eligible cervical cancer patients, obesity was a driving factor for disposition to RT. Studies demonstrate that RH is feasible and safe in obese patients with no statistically significant difference in PFS or OS when compared to non-obese patients. Thus, we advocate that the decision for disposition to RT should not be based on obesity alone.

Trends in palliative medicine and aggressive care at the end of life for women with gynecologic malignancies: a 15-year single institutional experience

Objectives: For over a decade palliative medicine in conjunction with disease modifying therapy has been recommended for women with metastatic, recurrent and symptomatic malignancies. The objective of this study was to compare the prevalence of palliative care consultations as well as aggressive care at the end of life (ACE) scores between women who died from gynecologic malignancies from 2005-2010 verse 2015-2020 as stratified by timely verses no/untimely consultation. We hypothesize that in the past fifteen years there has been an increase in palliative medicine consultation. Methods: After IRB approval data including patient demographics, histopathology, treatment and metrics of quality palliative care were abstracted from patients who died from gynecologic malignancies between 2005-2010 and 2015-2020 at a tertiary care medical center. Timely palliative consultation was defined as ≥to 30 days before death. Metrics contributing one point each to the ACE scores were 1) admission to ICU within 30 days of death, 2) hospital admission more than 14 days in the last 30 days of life, 3) more than one hospital admission during the past 30 days of life,4) more than one emergency room visit during the last 30 days of life,5) death in an acute care setting, 6) initiation of a new chemotherapy during the last 30 days of life, 7)last chemotherapy within 14 days of death, and 8) hospice admission less than 3 days before death. Data were reported in a descriptive fashion and analyzed using Student's T test, Wilcoxon Scores, and chi-square analysis with Stata 14.2. Results: Of 147 women in 2015-2020 cohort, 59(40%) had timely referral to palliative medicine compared to 18(18%) of the 2005-2010 cohort (p Download : Download high-res image (142KB) Download : Download full-size image Conclusions: There has been an increased consultation frequency and proportion of timely referrals to palliative medicine comparing contemporary to historical deaths from gynecologic malignancies. In both time periods overall ACE scores and some component scores were improved for women who received timely referral to palliative medicine. These data should be interpreted with caution secondary to baseline differences in cohorts who received timely palliative consultation verses untimely/no consultation

Thyroid function and survival outcomes in women with uterine cancer

Objectives: Loss of estrogen and progesterone receptor expression has historically been associated with poor survival outcomes in women with uterine cancer, but the role of the remaining 46 nuclear hormone receptors remains unclear. Recently, data from The Cancer Genome Atlas demonstrated a novel association between loss of thyroid hormone receptor beta expression and increased survival in uterine cancer patients.1 The purpose of this study was to explore the association between clinical indices of thyroid function and survival outcomes in women diagnosed with uterine cancer. 1. Pique, D.G., Greally, J.M. & Mar, J.C. Identification of a novel subgroup of endometrial cancer patients with loss of thyroid hormone receptor beta expression and improved survival. BMC Cancer 20:857 (2020). Methods: A single-institution retrospective cohort study was performed examining all women diagnosed with uterine cancer from 2006-2016. Data regarding patient demographics, medical co-morbidities, histology, stage and treatment course were abstracted from the medical record. Historical records and thyroid function studies (TSH, T3, free T4) were used to identify patients who were euthyroid, hypothyroid, or hyperthyroid within 1 year prior to their cancer diagnosis until the end of the follow-up period. The primary outcome was time to death from cancer diagnosis. A Cox proportional hazards model was used to identify the association between thyroid dysfunction and survival by using thyroid status as a time-dependent covariate and adjusting for age, grade and stage of disease. Download : Download high-res image (177KB) Download : Download full-size image Results: A total of 1201 patients were included for analysis. One thousand thirty (86%) patients had no thyroid dysfunction at time of cancer diagnosis, 145 patients (12%) carried the baseline diagnosis of hypothyroidism and 26 patients (2%) had hyperthyroidism. Twenty three women with normal thyroid function at baseline developed thyroid dysfunction during follow-up (91% hypothyroid, 9% hyperthyroid). A total of 218 deaths were observed. There were no differences in survival among patients with hypothyroidism or hyperthyroidism compared to euthyroid patients [HR 0.72 (95% CI 0.47-1.12, p=0.15); HR 0.51 (95% CI 0.16-1.58, p=0.24) respectively]. Women diagnosed with thyroid dysfunction prior to cancer diagnosis were observed to have a 30% lower hazard of death compared to euthyroid women, although this did not achieve statistical significance [HR 0.70 (95% CI 0.46-1.07, p=0.10)]. Patients who developed thyroid dysfunction after cancer diagnosis were observed to have a 3.7 fold higher hazard of death compared to patients who remained euthyroid during followup [HR 3.70 (95% CI 1.60-8.30), p=0.01], but this did not maintain significance in models adjusting for age, grade and stage of disease. Conclusions: Thyroid dysfunction was not associated with a difference in survival in women with uterine cancer in our cohort. Timing of thyroid dysfunction relative to uterine cancer diagnosis may affect clinical outcomes. Additional studies are needed to explore the relationship of thyroid dysfunction and uterine cancer.

Predictive validity of ACS-NSQIP risk calculator in ovarian cancer patients undergoing interval debulking surgery

Objectives: To determine whether the American College of Surgery-National Surgery Quality Improvement Program (ACS-NSQIP) risk calculator accurately predicts postoperative complications and length of stay in patients undergoing interval debulking surgery (IDS) for advanced stage epithelial ovarian cancer. Methods: Pre-operative risk factors, post-operative complication rates, and Current Procedural Terminology codes were abstracted from records of ovarian cancer patients managed with IDS from 01/2010-07/2015. A power calculation was done to estimate the minimum number of complications needed to evaluate accuracy of the ACS-NSQIP risk calculator. Predicted risk compared with observed risk was calculated using logistic regression. The predictive accuracy of the ACS-NSQIP risk calculator in estimating post-operative complications or length of stay (LOS) was assessed using c-statistics and Briar scores. Complications with a c-statistic of >0.70 and Brier score of Results: 261 patients underwent IDS, encompassing 21 unique CPT codes. Readmission(n=25), surgical site infection(n=35), urinary tract infection(n=35), and serious postoperative complications(n=57) met the minimum event threshold (n>10). All predicted complication rates fell within the interquartile range of the observed incidence rates, however the ACS-NSQIP calculator demonstrated neither discriminative ability nor accuracy for any postoperative complications based on c-statistics and Brier scores. The calculator accurately predicted LOS within 1 day for only 32% of patients and could not accurately predict patients likely to have a prolonged LOS (c-statistic=0.65). Download : Download high-res image (99KB) Download : Download full-size image Conclusions: Among patients undergoing IDS, the ACS-NSQIP did not accurately discriminate which patients were at increased risk of complications or extended LOS. The risk calculator should be considered to have limited utility in informing preoperative counseling or surgical planning.

WT1 expression associated with platinum-sensitivity and improved progression-free survival in uterine serous carcinoma

Objectives: Wilms tumor gene 1 (WT1) expression is a hallmark of ovarian serous carcinoma (OSC) and considered to be diagnostic marker of these tumors, differentiating them from uterine serous carcinoma (USC), traditionally thought to rarely express WT1. However, recent data indicates a significant percentage of USC may express WT1, limiting its use as a differentiating marker between these two tumors. Additionally, the clinical implications of WT1 positivity in USC remain unclear. Methods: A multicenter retrospective analysis of patients with USC was conducted from 2000 - 2019. Inclusion criteria were patients who had undergone comprehensive surgical staging/tumor debulking with archival tissue available for WT1 assessment via immunohistochemistry (IHC). Platinum-sensitive patients were defined as those recurring >6 months from last platinum-based chemotherapy. Differences in the frequencies of stage, race, chemosensitivity and sites of disease recurrence were identified using Pearson's chi-square test. Progression free survival (PFS) and overall survival (OS) analysis was performed using Kaplan-Meier estimates. Multivariate analysis (MVA) was performed using Cox proportional hazards model. Results: WT1 status was evaluated in 61 patients with USC. 13 (21.3%) were positive for WT1 by IHC. Of these 61 patients, 56 had follow-up information available for review and were included in final analysis. The mean age was 67-years and the majority of patients were African American (97%). Stage distribution included 32% stage I, 5% stage II, 25% stage III and 38% stage IV. The majority of patients were designated as platinum-sensitive (63%). 36 (64%) patients recurred during the study period, 8 (62%) of the WT1 positive and 28 (65%) of the WT1 negative cohort. The most common location of recurrence was the abdomen followed by the pelvis and extra-abdominopelvic sites. There was no difference in the stage (p=0.158), race (p=0.227) or distribution of recurrence sites (p=0.581) between WT1 positive and WT1 negative tumors. Platinum-sensitivity was significantly improved in WT1 positive (92.3%) vs. WT1 negative tumors (55.8%) (p=0.016). For the entire cohort, the median PFS was 20 months and the median OS was 29 months. The median PFS and OS did not differ significantly based on WT1 status (p=0.544 and p=0.759, respectively). However, we did observe a trend towards improved PFS among WT1 positive tumors (21 vs. 16 months, respectively). On MVA, stage (p Download : Download high-res image (147KB) Download : Download full-size image Conclusions: WT1 positivity is observed in over 20% of USC, limiting its utility to differentiating OSC and USC. Additionally, WT1 status holds prognostic significance as expression was associated with improved platinum-sensitivity and a clinically significant 5-month improvement in PFS.

Perioperative outcomes and survival in elderly women with ovarian cancer

Objectives: The rate of perioperative adverse events, postoperative outcomes and survival between patients aged 60-69 yo versus those ≥70 yo undergoing surgery for the primary treatment of advanced ovarian cancer (OC). Methods: We retrospectively identified all patients ≥60 years old treated surgically for primary advanced high-grade OC at our institution between January 2016 and December 2018. Institutional National Surgical Quality Improvement Program data were obtained for post-operative complications. Additional data were abstracted from medical records. Results are stratified based on the treatment approach: primary debulking surgery (PDS) or neo-adjuvant chemotherapy followed by interval debulking surgery (NACT/IDS). Appropriate statistical tests were performed. Results: A total of 77 patients were analyzed; 45 were between 60-69 years and 32 were ≥70 years. There were no differences in preoperative BMI, ECOG, ASA, CCI, polypharmacy, baseline bloodwork and stage (Table 1). Only 2 patients ≥70 years (0.6%) saw a geriatric oncology specialist prior to treatment. A total of 32 patients underwent PDS (60-69yo: n=18, ≥70yo: n=14), and 45 patients had NACT/IDS (60-69yo: n=27, ≥70yo: n=18). In both PDS and NACT/IDS groups, there were no differences in the post-operative adverse events between the two age groups. Older patients in the NACT/IDS group received less total platinum and taxane chemotherapy before and after surgery compared to NACT/IDS patients aged 60-69 years (p Download : Download high-res image (144KB) Download : Download full-size image Download : Download high-res image (263KB) Download : Download full-size image Conclusions: Although baseline characteristics were comparable between younger and older OC patients, reasons for PDS versus NACT/IDS were difficult to extrapolate from the medical record. Age was not a factor influencing perioperative outcomes of advanced ovarian cancer patients and the main predictor of outcomes was treatment approach. Since PDS is the main predictor of survival, a standardized, multi-disciplinary approach to optimize the management of older patients with ovarian cancer is necessary. Use of a formal assessment tool and consultation with a geriatric specialist may facilitate more patients undergoing PDS.

TP53 variant allelic frequency is associated with differential outcomes in endometrial cancer

Objectives: Endometrial cancers with TP53 mutations (mTP53) are a poor prognosis group, most often comprised of high-grade carcinomas with high somatic copy number alterations (sCNA). A recent sub-analysis of PORTEC-3 demonstrated that patients with TP53 mutant tumors, based on immunohistochemistry, benefit from treatment escalation with systemic chemotherapy. Herein we demonstrate that outcomes may vary dependent on variant allelic frequency (VAF) of TP53 missense mutations, not just the presence of a mutation alone. Methods: De-identified clinical data from the TCGA endometrial cancer cohort was obtained via cbioportal.org. Only patients with information regarding stage, histology, somatic copy-number burden, TP53 sequencing with variant allelic frequency, and exposure to RT were included. Patients with multiple TP53 alterations and stage IV disease were excluded from the analysis. T-test was performed to test for differences in sCNA burden, age, and stage between groups. Kaplan-Meieir analyses were performed to determine progression free survival (PFS) on each cohort, stratified into a VAF high or low using a 0.5 cutoff. Cox regression analysis was used to calculate hazard ratios. Download : Download high-res image (131KB) Download : Download full-size image Results: In total, 389 had genomic and treatment data available for analysis. Of these, 133 (34%) had a TP53 missense mutation. The average age was 64 years, with no significant difference between the RT and not RT groups (p=0.3). The mean sCNA for the RT and no RT, groups were 0.19 and 0.18, respectively (p=0.65). When analyzing the impact of TP53 status on PFS, mTP53 patients who did not receive RT had worse outcomes compared to wild-type TP53 (HR 3.5 [1.8-6.9], p Conclusions: This data highlights that TP53 VAF is a valuable prognostic marker and may be predictive of poor outcomes after radiotherapy alone. Residual wild-type p53 signaling in tumors with a low VAF may help explain outcomes similar to wild-type tumors. This genomic signal could help stratify patients with mTP53 tumors to multimodal therapy or de-escalation of therapy to radiotherapy alone. Further work remains to be done to determine a functional and biologic explanation for these findings.