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Purpose: Glioblastoma represents the most common primary brain tumor. Although antiangiogenics are used in the recurrent setting, they do not prolong survival. Glioblastoma is known to upregulate fatty acid synthase (FASN) to facilitate lipid biosynthesis. TVB-2640, a FASN inhibitor, impairs this activity. Experimental Design: We conducted a prospective, single-center, open-label, unblinded, phase II study of TVB-2640 plus bevacizumab in patients with recurrent high-grade astrocytoma. Patients were randomly assigned to TVB-2640 (100 mg/m2 oral daily) plus bevacizumab (10 mg/kg i.v., D1 and D15) or bevacizumab monotherapy for cycle 1 only (28 days) for biomarker analysis. Thereafter, all patients received TVB-2640 plus bevacizumab until treatment-related toxicity or progressive disease (PD). The primary endpoint was progression-free survival (PFS). Results: A total of 25 patients were enrolled. The most frequently reported adverse events (AE) were palmar–plantar erythrodysesthesia, hypertension, mucositis, dry eye, fatigue, and skin infection. Most were grade 1 or 2 in intensity. The overall response rate (ORR) for TVB-2640 plus bevacizumab was 56% (complete response, 17%; partial response, 39%). PFS6 for TVB-2640 plus bevacizumab was 31.4%. This represented a statistically significant improvement in PFS6 over historical bevacizumab monotherapy (BELOB 16%; P = 0.008) and met the primary study endpoint. The observed OS6 was 68%, with survival not reaching significance by log-rank test (P = 0.56). Conclusions: In this phase II study of relapsed high-grade astrocytoma, TVB-2640 was found to be a well-tolerated oral drug that could be safely combined with bevacizumab. The favorable safety profile and response signals support the initiation of a larger multicenter trial of TVB-2640 plus bevacizumab in astrocytoma.

Representativeness of Study Participants

RNA Analysis Summary

CONSORT flow diagram with patient disposition and treatment

Exosome Analysis Summary

Purpose:Glioblastoma represents the most common primary brain tumor. Although antiangiogenics are used in the recurrent setting, they do not prolong survival. Glioblastoma is known to upregulate fatty acid synthase (FASN) to facilitate lipid biosynthesis. TVB-2640, a FASN inhibitor, impairs this activity.Experimental Design:We conducted a prospective, single-center, open-label, unblinded, phase II study of TVB-2640 plus bevacizumab in patients with recurrent high-grade astrocytoma. Patients were randomly assigned to TVB-2640 (100 mg/m2 oral daily) plus bevacizumab (10 mg/kg i.v., D1 and D15) or bevacizumab monotherapy for cycle 1 only (28 days) for biomarker analysis. Thereafter, all patients received TVB-2640 plus bevacizumab until treatment-related toxicity or progressive disease (PD). The primary endpoint was progression-free survival (PFS).Results:A total of 25 patients were enrolled. The most frequently reported adverse events (AE) were palmar–plantar erythrodysesthesia, hypertension, mucositis, dry eye, fatigue, and skin infection. Most were grade 1 or 2 in intensity. The overall response rate (ORR) for TVB-2640 plus bevacizumab was 56% (complete response, 17%; partial response, 39%). PFS6 for TVB-2640 plus bevacizumab was 31.4%. This represented a statistically significant improvement in PFS6 over historical bevacizumab monotherapy (BELOB 16%; P = 0.008) and met the primary study endpoint. The observed OS6 was 68%, with survival not reaching significance by log-rank test (P = 0.56).Conclusions:In this phase II study of relapsed high-grade astrocytoma, TVB-2640 was found to be a well-tolerated oral drug that could be safely combined with bevacizumab. The favorable safety profile and response signals support the initiation of a larger multicenter trial of TVB-2640 plus bevacizumab in astrocytoma.

BACKGROUND: In metastatic colorectal cancer (mCRC), regorafenib (RGF), a multi-kinase inhibitor with angiogenic inhibition has modest effects on survival. We reported that autophagy modulation using hydroxychloroquine (HCQ), enhances the anticancer activity of the histone deacetylase inhibitor, vorinostat (VOR), in mCRC, is well tolerated, and has comparable activity to RGF. Thus, we conducted a prospective study of VOR/HCQ versus RGF in mCRC. METHODS: This is a randomised, controlled trial of VOR 400 mg and HCQ 600 mg orally daily versus RGF 160 mg orally daily (3 weeks on/1 week off), every 4 weeks, in patients with mCRC. Primary endpoint: median progression-free survival (mPFS). Secondary endpoints: median overall survival (mOS); adverse events; pharmacodynamic analyses. RESULTS: From 2/2015-10/2017, 42 patients were randomised to VOR/HCQ and RGF. Median age was 58.4 years. mPFS on VOR/HCQ was 1.9 months versus 4.35 months with RGF (P = 0.032). There was no difference in mOS (P = 0.9). Treatment was tolerated in both arms. In both arms, there was improved anti-tumour immunity. CONCLUSIONS: VOR/HCQ had an inferior PFS when compared to RGF, although there was an increase in anti-tumour immunity in mCRC. VOR/HCQ has a favourable safety profile, and immune or tumour biomarkers may be used to identify clinical benefit of autophagy modulation in mCRC. CLINICAL TRIAL REGISTRATION: NCT02316340.

This study aimed to determine benefits of the Enhanced Recovery After Surgery (ERAS) pathway implementation in free flap breast reconstruction related to postoperative narcotic use and health care resource utilization.A retrospective analysis of consecutive patients undergoing deep inferior epigastric perforator flap breast reconstruction from November of 2015 to April of 2018 was performed before and after implementation of the ERAS protocol.Four hundred nine patients met inclusion criteria. The pre-ERAS group comprised 205 patients, and 204 patients were managed through the ERAS pathway. Mean age, laterality, timing of reconstruction, and number of previous abdominal surgical procedures were similar ( p0.05) between groups. Mean operative time between both groups (450.1 ± 92.7 minutes versus 440.7 ± 93.5 minutes) and complications were similar ( p0.05). Mean intraoperative (58.9 ± 32.5 versus 31.7 ± 23.4) and postoperative (129.5 ± 80.1 versus 90 ± 93.9) morphine milligram equivalents used were significantly ( p0.001) higher in the pre-ERAS group. Mean length of stay was significantly ( p0.001) longer in the pre-ERAS group (4.5 ± 0.8 days versus 3.2 ± 0.6 days). Bivariate linear regression analysis demonstrated that operative time was positively associated with total narcotic requirements ( p0.001) and length of stay ( p0.001).ERAS pathways in microsurgical breast reconstruction promote reduction in intraoperative and postoperative narcotic utilization with concomitant decrease in hospital length of stay. In this study, patients managed through ERAS pathways required 46 percent less intraoperative and 31 percent less postoperative narcotics and had a 29 percent reduction in hospital length of stay.Therapeutic, III.

Background: Although screening mammography leads to an early detection of breast cancer and a reduction in breast cancer mortality, many women have apprehension about mammograms due to reported discomfort and pain [would cite the source]. A study showed that pain was the cause of non-reattendance of screening mammograms in 25-46% of reported cases by women. Despite this, there is limited research on strategies to reduce discomfort and anxiety associated with mammography screening and improve patient experience and compliance with national screening recommendations. Herein, we performed a double-blind randomized clinical study to determine if the use of local analgesia and calming music can improve patient satisfaction during routine screening mammogram. Methods: This study was designed as a double-blind randomized clinical trial with a 2 × 2 factorial design. A total of 251 patients who presented for mammographic screening were randomized to receive: breast lidocaine gel at a dose of 1200 mg or placebo gel on both breast and experience calming music or no music Patients with history of mastectomy, breast cancer or recent (within 24 hours) analgesic use were excluded. Pain was measured with a 5-point face pain scale. Benjamini-Hochberg false discovery rate was used for analysis Results: Of the 251 patients who were randomized between June 2017 and October 2019, 195 self-identified as Hispanics (77%). Median age was 58.5 years old and there were no differences in between groups. 100% were female. 99.3% presented for screening with no concerning symptoms. A total of 126 patients were randomized to music vs 125 to no Music. 79 patients in music group and 51 patients in no music group were randomized to lidocaine. Regarding pain assessment, 18.96% of patients had a pain score of 4 and 5 in the music group randomized to lidocaine gel as opposed to 10.64% to placebo gel. In the non-music group, 17.65% of patients expressed pain score of 4 and 5 to lidocaine gel vs. 18.91% to placebo gel. (P value music: 0.95, P value lidocaine: 0.93 P value music and lidocaine: 1). Patients randomized to lidocaine gel to music reported their prior mammogram to be at a pain score of 4 to 5 in 41.7% of the subjects vs 45% of patients in the no music group. (P value music: 0.45, P value lidocaine: 0.93 P value music and lidocaine: 1). Despite this, majority patients in both groups expressed no reluctance for future mammograms. Conclusion: The addition of calming music and breast lidocaine gel did not show a statistically significant difference in the level of pain perceived by patients getting screening mammography. The data appear to suggest less severe pain (pain score 4 and 5) when these strategies are combined. Further prospective trials with larger patient populations are needed to explore these interventions. Despite the perceived pain most patients were still willing to return for a mammogram the following year. Citation Format: Marcela Mazo-Canola, Heidi C. Ko, Kenneth Kist, Joel Michalek, Lillian Franco, Pamela Otto, Virginia Kaklamani. A randomized study assessing interventions to improve comfort during screening mammography [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-05.

605 Background: BTC are genetically diverse and heterogeneous. Despite knowledge of molecular subtypes of BTC, the distribution of molecular aberrations in the Latinx population has been understudied. These may have prognostic and/or predictive implications. Therefore, we analyzed our cohort of Latinx-rich patients with advanced BTC. Methods: We analyzed patients with advanced BTC, who were seen at the Mays Cancer Center from Jan 2018-Dec 2021. Tumor samples profiled by Next Generation Sequencing (NGS) were identified retrospectively. Associations between demographics, clinical characteristics, and genetic alterations were identified. Results: 88 patients with locally advanced/metastatic BTC were identified. 50 (56.2%) were Latinx. 42 (47.7%) had intrahepatic CA (IHCA), 14 (15.9%) had extrahepatic CA (EHCA), 16 (18.2%) had Gall Bladder Carcinoma (GBC) and 16 (18.2%) had Ampullary/Periampullary Carcinoma (APC). 49 (56%) had NGS on their tumors out of which 30 (61.2%) were Latinx and 19 (38.8%) were non-Latinx. The most commonly altered genes were TP53 (34.7%), KRAS (24.5%), ARID1A (16.3%), BRCA-2 (12.2%), PDL-1 (12.2%), FGFR (12.2%), MET (10.2%), PTEN (10.2%) and HER-2 (8.2%). 14.3% patients had no identifiable mutations. There was no significant difference observed in the rates of different molecular mutations between Latinx and non-Latinx (p=1) and among different histologies of IHCA, EHCA, GBC and APC (p=1). The Median Overall Survival (OS) for Latinx population was 16.1 months (95% CI 12.3-28.2) which was similar to the median OS for non-Latinx population of 15.5 months (95% CI 11.6-28.6) (p=0.69). The median OS was not different due to the presence or absence of any one mutation (p values ranged from 0.04 to 0.9). Conclusions: BTCs are genetically diverse. Somatic alterations were identified in 85% patients who were tested. Only 56 % had molecular testing, when it should be 100% in advanced BTC, per NCCN guidelines. This may be due to inadequate tissue, lack of funding, use of alternate ctDNA, or the patient may have died before getting to testing/repeat biopsy. The likelihood of having a genetic alteration was similar between Latinx and non-Latinx patients and among different sites of disease. Latinx and Non Latinx with advanced BTC had similar survival rates. Survival rate was not different due to the presence or absence of any one mutation. Future studies should prospectively investigate implementation programs for NGS in tumor and blood in all patients with BTCs.

Background Metformin may reduce frailty through improving insulin resistance and inflammation, aging mechanisms known to increase frailty risk. We describe a randomized clinical trial of metformin for frailty prevention in community-dwelling older adults with pre-diabetes and provide baseline characteristics of randomized participants. Methods Older adults (65+ years) are studied in this randomized, double-blind, placebo-controlled trial of metformin (max 2,000 mg/day). Pre-diabetes, required for inclusion, is assessed by 2-hour oral glucose tolerance test (OGTT). Individuals with glomerular filtration rate < 45 mL/min and frail individuals (Fried criteria) are excluded. The primary outcome, frailty, is assessed by both Fried criteria and frailty index. Secondary outcomes are physical function (short physical performance battery), lower extremity strength (Biodex), 6-minute walk, inflammation (systemic and skeletal muscle tissue), muscle insulin signaling, insulin sensitivity (insulin clamp), glucose tolerance (OGTT), and body composition (dual-energy x-ray absorptiometry). Subjects are followed for 2 years with safety assessments every 3 months and frailty assessment and OGTT every 6 months. Results 145 participants (49% female, 35% Hispanic) are randomized. Mean age is 71.8 ± 5.4 years (range: 65-88), body mass index is 30.8 ±6 kg/m2, and Hemoglobin A1c is 5.6 ±0.4%. Using Fried criteria, 63.4% have frailty score of 0, 30.3% a score of 1, and 6.2% a score of 2. Conclusion Metformin is being examined as a potential therapeutic agent to prevent frailty in older adults with pre-diabetes. Findings from this trial may have future implications for screening and treatment of pre-diabetes in older adults for the prevention of frailty.

Frailty is a progressive physical decline leading to higher morbidity and mortality in older adults. Previous studies have demonstrated shared mechanisms between insulin resistance, inflammation, and frailty. The purpose of this trial is to determine whether metformin prevents frailty in non-frail, community-dwelling older adults (≥65 years) with pre-diabetes, determined by 2-hour oral glucose tolerance test (OGTT). Frail individuals (Fried criteria) and those with renal impairment (glomerular filtration rate

Dynamic tumor microenvironments contain a myriad of cell subtypes, each providing a unique functionality in support of malignant growth. To prepare a metastatic niche, a tight network must be present to coordinate the delivery and sharing of co-stimulatory signals among malignant tumor epithelial cells and supportive host cells. AXL and STAT3 cascades are critical components of intracellular signaling networks, as they translate multiple external stimuli into specific cellular responses. Single cell profiling of lung tumors reveals that AXL collaborates with STAT3 to create a unified tumor ecosystem favoring hybrid epithelial-to-mesenchymal transition states of lung epithelial cells, pro-tumorigenic remodeling of fibroblasts and M2 polarization of macrophages. Disruption of AXL-STAT3 circuit with AXL inhibitor and JAK inhibitor not only compromises this co-dependency in A549 lung cancer cells implanted in xenograft mice, but also limits their ability to conscript murine fibroblasts, macrophages and other immune cells that form a symbiotic community for tumor growth. Our preclinical work suggests that combined targeting of AXL-STAT3 circuit could disturb the communication among diverse cell subtypes in the lung tumor microenvironment, thus limiting the metastatic progression. Our co-culture studies reveal that AXL signaling in lung cancer cells and fibroblasts exerts an IL-11 mediated paracrine effect on macrophages to sustain STAT3 signaling for M2 polarization and cancer stemness mimicry. In vivo drug testing in A549 mouse xenograft model demonstrate that AXL-STAT3 inhibition leads to reduction in host cell recruitment and attenuates M2 polarization of macrophages and pro-tumorigenic remodeling of stromal fibroblasts. AXL-STAT3 targeting to dismantle lung tumor microenvironments is a promising therapeutic strategy and may establish new treatment paradigms for patients with lung adenocarcinoma. Citation Format: Josephine Amalia Taverna, Chia-Nung Hung, Meizhen Chen, Joel Michalek, Chun-Liang Chen, Nameer Kirma, Chih-Wei Chou, Xi Tan, Chiou-Miin Wang, Zhang Zhao, Duy Nguyen, Daniel DeArmond, Tim Huang. AXL-STAT3 targeting of lung tumor microenvironments [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1623.

e18562 Background: DLBCL is the most common type of non-Hodgkin lymphoma worldwide. Hispanics (H) in Texas (TX) and Florida (FL) represent 39.7% and 26.4% of the population of each state, respectively. This is the first population-based two statewide study looking at demographics, treatment patterns, and survival outcomes, in years (y), comparing those two Hispanic enriched states. We hope that identifying differences among state populations and provide interventions for the future. Methods: A retrospective cohort study of patients diagnosed with DLBCL between 2006-2017 using the Texas Cancer Registry and the Florida Cancer Data System. Standard demographic, socioeconomic, clinical, survival variables were reviewed. The Fisher's Exact tests and Chi-Square tests were assessed for categorical outcomes by ethnicity; Survival distributions were depicted using Kaplan-Meier curves. Results: From 2006 to 2017, 16,529 patients from TX and 18,641 patients from FL were diagnosed with DLBCL. At 20-100% poverty index, H in FL and TX had higher poverty percentages than non-Hispanic (NH), with TX H having the higher percentage (55%) compared to FL H (33%). Median survival time in FL was 5.4y for H compared to TX 3.7y H. Overall survival probability at 10y did show a statistically significant difference for H vs. NH when comparing FL (p < 0.001) and TX (p = 0.95). Conclusions: In patients with DLBCL, two statistically significant differences were survival probability at 10y and median survival time comparing H populations in FL and TX. While most demographic variables were homogenous, one difference was observed; poverty index at 20-100% was higher for H in TX than FL. Higher poverty rates in TX to FL among the H population may explain why the median survival time and probability are higher and can provide further opportunities for structured interventions.[Table: see text] [Table: see text]

e19567 Background: Peripheral T-cell lymphomas (PCTLs) are an aggressive group of lymphomas that comprise less than 15% of all non-Hodgkin lymphomas in adults. There is limited literature regarding differences in outcomes for Hispanics (H). Some studies indicate worse outcomes in H compared to non-Hispanics (NH), whereas others have shown comparable outcomes. The purpose of this study is to evaluate demographics, treatment patterns and survival outcomes of PCTLs among H vs. NH in Texas (TX) and Florida (FL). Methods: This is a retrospective analysis of patients with PTCLs from the Texas Cancer Registry (TCR) and the Florida Cancer Data System (FCDS), from 2006-2017. Inclusion criteria was histopathologic proven PTCLs. Patients were divided into H and NH for comparison. Standard demographic, socioeconomic, clinical, and survival variables were reviewed. All statistical testing was determined using Fisher’s Exact test, Pearson’s Chi-square test, T-test or Wilcoxon test, as appropriate. Survival time was measured using the day of diagnosis to last date of follow up or death. Survival distributions were calculated based on Kaplan-Meier curves. Results: We identified 3358 patients. In TX 51% were H, and 49% were NH. In FL 27% were H, and 73% were NH. Median age at diagnosis of H was 70-79 years (y) (19%) and NH was 60-69 (23%) in TX (p < 0.001). Median age at diagnosis of H was 50-59 y (26%) and NH was 70-7 y (26%) in FL (p < 0.001). Most frequent poverty index was 20-100% for H vs 10-19.9% for NH (p < 0.001) in TX and 10-19% for both H and NH (p < 0.001) in FL. Government-sponsored insurance (GSI) was 40% in H vs 46% in NH (p < 0.001) in TX and 35% vs 31% in NH (p < 0.001) in FL. Most common stage at diagnosis for both groups was III/IV with 50% in H vs 49% in NH (p = 0.01) in TX; and stage I with 53% H vs 42% in NH (p = 0.05) in FL. Median overall survival (MOS) in TX for H was 1.4 years vs 1.5 in NH; survival probability (SP) for H vs NH at 2 y was 0.42 vs 0.44, at 5 y 0.32 vs 0.31, and at 10 y 0.21 vs 0.14 with no statistically significant difference in overall survival (OS). MOS in FL for H was 1.9 y vs 1.8 y in NH; SP for H vs NH at 2 y was 0.48 vs 0.47, at 5 y 0.36 vs 0.33, and at 10 y 0.24 vs 0.20 with no statistically significant difference in OS. Conclusions: Amongst the population of TX and FL, H with PTCLs have similar outcomes when compared to NH. There were no statistically significant differences in MOS or SP at 2, 5, and 10 y among the H cohorts. There were statistically significant differences between H and NH patients in median age of diagnosis, poverty index, and insurance status at diagnosis. These disparities were observed in both states and may be a direct reflection of the significantly higher rates of poverty and lack of insurance among H. Within the context of healthcare equality, we ascertained similar outcomes amongst groups, which agrees with previous reports claiming homogeneity of medical care.

Acute kidney injury (AKI) following transcatheter aortic valve replacement (TAVR) is a known complication. The prospective validation of various AKI definitions and estimated baseline renal function equations in the context of TAVR remains an ongoing area of research. This study examined the Valve Academic Research Consortium (VARC) 1 and 2 criteria for AKI, and impact of three estimated glomerular filtration rate (eGFR) equations (CKD-EPI, MDRD, and Cockcroft-Gault) on AKI incidence in TAVR patients.Retrospective review of 120 consecutive TAVR procedures over a 4-year period was performed. AKI, including stage, was defined using the VARC 1 and VARC 2 criteria. Univariate and multivariate analyses were performed for association between AKI and known patient, hemodynamic, and procedural variables. Further logistic regression, stepwise logistic regression, and association plots were performed for the three different eGFR calculations.AKI occurred in 22% of VARC 1 patients and 23% of VARC 2 patients. On multivariate analysis, baseline eGFR was predictive of stage 1 AKI by CKD-EPI classification (VARC 1: odds ratio [OR], 0.93; 95% confidence interval [CI], 0.88-0.99; P=.02; VARC 2: OR, 0.93; 95% CI, 0.87-0.99; P=.03) and MDRD (OR, 0.93; 95% CI, 0.88-0.99; P=.03). Non-transfemoral approach was predictive of stage 1 AKI by VARC 2 (OR, 33.33; 95% CI, 1.6-696.41; P=.02).The risk factor associations for AKI post TAVR vary by definitions used. Decreased GFR at baseline by both MDRD and CKD-EPI and non-transfemoral approach were associated with an increased risk of AKI post TAVR.

Introduction: Patients undergoing endovascular therapy (EVT) for lower extremity peripheral arterial disease (PAD) are at risk for acute kidney injury (AKI). The purpose of this study was to determine the incidence, risk factors, and outcomes of AKI in the context of EVT from the National Inpatient Sample (NIS). Methods: Patient admissions in the NIS were queried from 2003-2012. The admissions were limited to non-dialysis patients with either critical limb ischemia (CLI) or claudication undergoing either EVT and/or angiography. AKI was defined using a composite of ICD-9 codes which have been previously validated in this context. Available comorbidity data, demographics, and inpatient outcomes (AKI, mortality) were analyzed using multivariable logistic regression models with age expressed in decades. Results: 552,484 admissions for CLI and 441,736 for claudication were included. The incidence of AKI is shown in the figure. The multivariate predictors of AKI in patients with claudication undergoing EVT only included age (OR 1.05, CI [1.02-1.09], P Conclusions: AKI occurs in approximately 3.5% of patients undergoing endovascular procedures for claudication and 10.9% in CLI patients. CKD and heart failure are the strongest risk factors for AKI. AKI is an independent predictor of inpatient mortality.

Introduction: Despite overall decrease in incidence of cancers in U.S., kidney cancer is one out of the only seven cancers with increasing incidence. Limited research has been conducted using national, state-wide, and regional data, especially comparing racial and ethnic disparities in incidence and outcomes for kidney cancer. Methods: Kidney cancer incidence and outcomes from 2004 to 2014 were compared using Texas Cancer Registry, National Program for Cancer Registries, and Surveillance, Epidemiology and End Results. Age-adjusted incidence rates (per 100,000 population) and temporal trends, reporting sources, diagnosis, patient and tumor characteristics between Hispanics and Non-Hispanic Whites (NHWs) were compared for each state. The Kaplan-Meier method was used for relative survival analyses, which were limited to Texas due to data availability. Results: A total of 566,716 patients were identified. The temporal trend shows a sustained increase in kidney cancers in U.S. and a consistently higher incidence in TX and South Texas (STX) over the past decade, with Hispanics in particular having the highest annual percent change (APC) among the 20-29 year old age group (5.3 in U.S. and 7.7 in TX, respectively). Age-adjusted kidney cancer incidence was 26.2 in STX, 24.5 in TX and 21.8 in U.S. Both males and females had a higher incidence in STX and TX compared to U.S. (35.1, 32.5 vs. 29.6 for males and 18.8, 17.9 vs.15.2 for females). Overall, Hispanic males in STX had the highest kidney cancer incidence (37.7) throughout U.S. The difference in incidence rate in Hispanics compared to NHWs was significant in STX (4.9) and TX (3.4), compared to U.S. (-0.9). Tumor grade was only available in 60% of cancers in TCR compared to 70% in U.S. Despite localized tumor stage being the most common presentation for all regions, the 5-year survival was lower in Hispanics compared to NHWs in STX (68% vs. 73%) and TX (69% vs. 71%). Conclusions: Kidney cancer rates were higher in STX and TX when compared to U.S., especially among Hispanic males. Relative 5-year survival between Hispanics and NHWs were similar in TX and STX. Improvement in cancer reporting and detailed studies examining causes for racial/ethnic disparities in incidence in the top 15 states with highest disparities, especially TX, are needed. Citation Format: Casey Perez, Pankil K. Shah, Aaron Mathews, Edgar Munoz, Alex Bokov, Dharam Kaushik, Joel Michalek, Amelie Ramirez, Ronald Rodriguez, Dimpy P. Shah. Racial disparities in kidney cancer incidence across South Texas, Texas, and United States using TCR, SEER and NPCR registries (2004-2014) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4187.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with appallingly poor outcome. Recent years have witnessed the development of a number of combination therapies that have produced modest survival improvement but at the cost of increased adverse effects. A phenomenon that contributes to the dismal prognosis and therapeutic resistance is a unique characteristic of PDAC called desmoplasia. Desmoplasia is initiated by activation of pancreatic stellate cells (PSCs), which through excessive deposition of extracellular matrix components, leads to expansion of tumor stroma that hinders drug penetration. We have recently shown that glutamine mediates communication between PSCs and pancreatic cancer cells (PCCs). Remarkably, a small molecule inhibitor palmatine (PMT) suppresses glutamine-induced PSC-PCC communication and potentiates gemcitabine (GEM) activity in part through downregulation of survivin. Survivin expression is correlated not only with unfavorable overall survival but also therapeutic resistance. In this study we therefore examined the mechanism associated with glutamine-mediated PSC-PCC interaction. We also designed experiments to test the hypothesis that PMT inhibits survivin to disrupt these interactions to potentiate anti-proliferative activity of GEM. Our results indicate that PMT not only interacts with pTyr p705 binding site in the SH2 domain of STAT3 (canonical), but also interacts at the interface of DNA and the linker domain (non-canonical). PMT-STAT3 interaction resulted in decreased phosphorylation with no significant effect on total levels of STAT3 in pancreatic cancer cells following treatment with PMT. Furthermore, PMT treatment attenuated (i) glutamine-mediated increased levels of pSTAT3 and its downstream target survivin; (ii) glutamine-mediated increased survivin reporter activity and (iii) glutamine-mediated enhanced proliferation and clonogenicity in multiple cell lines. Collectively, these data suggest that PMT abrogates glutamine-induced biological outcome through reduced STAT3/survivin signaling. We further tested the preclinical efficacy of PMT in combination with GEM using the syngeneic orthotopic KPC mouse model. Our results show significantly decreased mean log 10 tumor weight in response to treatment with PMT plus GEM (0.08±1.13) relative to controls (1.87±0.21) or single agent treatment (1.48+0.67; p Citation Format: Xiaoyu Yang, Amanda R. Muñoz, Shih-Bo Huang, Martha Hanes, Roble G. Bedolla, Divya Chakravarthy, Angel Su, Varsha Mulamreddy, Dmytro Kovalskyy, Paul Rivas, Joel Michalek, Rita Ghosh, Addanki P Kumar. Targeting glutamine addiction in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 116.

Supraglottic injection of botulinum toxin (Botox) has been described as an effective treatment for adductor spasmodic dysphonia (ADSD). Anecdotal evidence suggests that the patients have little to no breathiness after injection, but no formal longitudinal studies have been carried out to date. The purpose of this study was to examine the voice outcomes in patients with ADSD after supraglottic Botox injection.Retrospective case series.Patients with ADSD who were treated with supraglottic Botox injections completed a qualitative self-evaluation of voice function after injection using the percentage of normal function (PNF) scale, a validated, quantitative scale from 0% (no function) to 100% (normal function). Posttreatment voice improvement after injection was determined using a Voice Handicap Index-10 (VHI-10) questionnaire.A total of 198 supraglottic injections were performed between July 2011 and October 2014. Twenty-five questionnaires were completed. Mean postinjection PNF was 95.0% ± 8.4% and was significantly increased from the preinjection mean PNF (62.5%) ± 22.6% (P0.001). The mean best VHI-10 for all injections was 7.23. In 19 of 25 patients (76%), there was no reduction in PNF in the early postinjection period. In the remaining six patients (24%), the decline in mean vocal function was 9.2%.Supraglottic Botox injection is an effective treatment for ADSD. Postinjection voice is significantly improved, and the majority of patients do not experience breathy voice/decline in vocal function after injection.

Current trauma resuscitation guidelines recommend giving an initial crystalloid bolus as first line for resuscitation. Recent studies have shown a survival benefit for trauma patients resuscitated with high ratios of fresh frozen plasma (FFP) to packed red blood cells (PRBC). Our aim was to determine whether the volume of crystalloid given during resuscitation correlated with differences in morbidity or mortality based on the ratio of FFP:PRBC given.This was a retrospective review of 2,473 transfused trauma patients at 23 Level I trauma centers from July 2005 to October 2007. Patients were separated based on the ratios of FFP:PRBC they received (1:4, 1:4-1:1, and1:1) and then analyzed for morbidity and mortality based on whether or not they received at least 1 L crystalloid for each unit of PRBC. Outcomes analyzed were 6-hour, 24-hour, and 30-day survival as well as intensive care unit (ICU)-free days, ventilator-free days, and hospital-free days.Massive transfusion patients who received1:4 ratios of FFP:PRBC had significantly improved 6-hour, 24-hour, and 30-day mortality and significantly more ventilator-free days if they received at least 1 L of crystalloid for each unit of PRBC. Nonmassive transfusion patients who received1:4 ratios of FFP:PRBC had significantly improved 6-hour, 24-hour, and 30-day mortality and significantly more ICU-free days, ventilator-free days, and hospital-free days if they received at least 1 L crystalloid for each unit of PRBC. In both massive and nonmassive transfusion groups, the survival benefit and morbidity benefit was progressively less for the 1:4 to 1:1 FFP:PRBC groups and1:1 FFP:PRBC groups.If high ratios of FFP:PRBC are unable to be given to trauma patients, resuscitation with at least 1 L of crystalloid per unit of PRBC is associated with improved overall mortality.

Background: Music education affects the mathematical and visuo-spatial skills of school-age children. Visuo-spatial abilities have a significant effect on laparoscopic suturing performance. We hypothesize that prior music experience influences the performance of laparoscopic suturing tasks. Methods: Thirty novices observed a laparoscopic suturing task video. Each performed 3 timed suturing task trials. Demographics were recorded. A repeated measures linear mixed model was used to examine the effects of prior music experience on suturing task time. Results: Twelve women and 18 men completed the tasks. When adjusted for video game experience, participants who currently played an instrument performed significantly faster than those who did not (P