Introduction: Our institution cares for a largely underserved urban population, treating about 120 children annually with radiation therapy; roughly 10% are referred for proton therapy elsewhere. COVID-19 led to some decreases in medical care due to uncertainties regarding the state of public health. The purpose of this study is to evaluate existing socioeconomic disparities using the University of Wisconsin Area Deprivation Index (ADI) and whether the pandemic impacted this referral pattern. Methods: Over the last twenty years, approximately 2,275 children have presented to our institution for radiation treatment. A retrospective chart review was conducted and a patient database of demographic and clinical information was created. We used demographic data to obtain the ADI, and compared relative disparity rankings between proton therapy recipients and a random sample of patients from the 25 most common zip codes (representative of over 20% of the total cohort). We compared the number of patients treated only at the closest proton facility before and after the onset of the pandemic. Results: The demographic make-up of our patient population is approximately 53.7% Latino, 22.6% White, 9.5% African American, 9.2% Asian, and 5% Other. Of these patients, about 500 had diagnoses typically referred for proton therapy (such as brain tumors, neuroblastoma, sarcomas, and Hodgkin lymphoma). At baseline, we found a statistically significant difference in the median state ADI decile of 3 and 7 for protons and photons, respectively, reflecting lower socioeconomic disadvantage in the proton group. There was a difference in the median household income (based on zip code) of $102,028 and $70,479 between the proton and photon groups (p < 0.0001). There was also a difference in median household income of $57,871 and $76,808 between Latino and Non-Latino patients (p < 0.0001). Demographic data for the proton therapy cohort showed that 46.2% of these patients were White, 15.4% were Latino, 15.4% were African American, 7.7% were Asian, and 15.4% were Other. At the closest proton facility, between 2014-2019, 16 of our patients received radiation therapy. Since the beginning of pandemic associated restrictions in March 2020, 19 patients have received proton therapy at this center. Conclusions: Disparities preventing patients from receiving proton therapy have been described. Our work adds granular census block data and uses the ADI which takes into account median family income, unemployment rate, households without access to a vehicle, English language proficiency and more. Those with lower ADI risk rankings were overrepresented in the proton therapy group. Despite the pandemic and added referral challenges, the number of patients able to receive proton therapy did not decrease which we hypothesize may be due to many factors, including the unanticipated flexibility of remote work amongst those with lower ADI rankings. Latinos were least likely to have proton therapy, and further research is needed to ameliorate the disparities and barriers to care which they face. Citation Format: Samuel P. McKinnon, Zara I. Kazmierczak, Arthur J. Olch, Daniel Roh, Ethan Nguyen, Kristen Pang, Iain J. MacEwan, Kenneth K. Wong. Disparities in pediatric patients receiving proton therapy during the COVID-19 pandemic - A single institutional experience [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 B087.
<p>Supplementary methods, Supplementary Figures S1-S3, and Supplementary tables</p>
<div><p>Stromal antigen 2 (STAG2), in healthy somatic cells, functions in sister chromatid cohesion, DNA damage repair, and genome organization, but its role in muscle-invasive bladder cancer (MIBC) remains unknown. Here, using whole-exome and targeted sequencing (<i>n</i> = 119 bladder cancer clinical samples), we found several <i>STAG2</i> mutations in MIBC that correlate with loss of protein expression. The analysis of a bladder cancer tissue microarray (<i>n</i> = 346) revealed that decreased STAG2 protein expression is associated with improved overall and progression-free survival for patients with MIBC. In mouse xenograft studies, STAG2 knockdown (KD) decelerated MIBC tumor growth<i>,</i> whereas STAG2 overexpression accelerated tumor growth. In cell line studies, STAG2 loss augmented treatment with cisplatin, a first-line therapy for MIBC. STAG2 KD or overexpression did not alter degree of aneuploidy, copy-number variations, or cell-cycle distribution. However, unbiased RNA-sequencing analysis revealed that STAG2 KD altered gene expression. STAG2 KD led to significant downregulation of several gene sets, such as collagen containing extracellular matrix, external encapsulating structure organization, and regulation of chemotaxis. Therefore, we investigated the effect of STAG2 KD on cell migration and invasion <i>in vitro</i>. We found that STAG2 KD minimized cell speed, displacement, and invasion. Altogether, our results present a noncanonical function of STAG2 in promoting cell motility and invasion of MIBC cells. This work forms the basis for additional investigation into the role of STAG2 in transcriptional regulation and how it becomes dysregulated in <i>STAG2</i>-mutant MIBC.</p>Significance:<p>The cohesin component STAG2 regulates cell motility and invasion. STAG2 expression is associated with decreased MIBC survival and may be a useful biomarker to guide bladder cancer treatment.</p></div>
<div><p>Stromal antigen 2 (STAG2), in healthy somatic cells, functions in sister chromatid cohesion, DNA damage repair, and genome organization, but its role in muscle-invasive bladder cancer (MIBC) remains unknown. Here, using whole-exome and targeted sequencing (<i>n</i> = 119 bladder cancer clinical samples), we found several <i>STAG2</i> mutations in MIBC that correlate with loss of protein expression. The analysis of a bladder cancer tissue microarray (<i>n</i> = 346) revealed that decreased STAG2 protein expression is associated with improved overall and progression-free survival for patients with MIBC. In mouse xenograft studies, STAG2 knockdown (KD) decelerated MIBC tumor growth<i>,</i> whereas STAG2 overexpression accelerated tumor growth. In cell line studies, STAG2 loss augmented treatment with cisplatin, a first-line therapy for MIBC. STAG2 KD or overexpression did not alter degree of aneuploidy, copy-number variations, or cell-cycle distribution. However, unbiased RNA-sequencing analysis revealed that STAG2 KD altered gene expression. STAG2 KD led to significant downregulation of several gene sets, such as collagen containing extracellular matrix, external encapsulating structure organization, and regulation of chemotaxis. Therefore, we investigated the effect of STAG2 KD on cell migration and invasion <i>in vitro</i>. We found that STAG2 KD minimized cell speed, displacement, and invasion. Altogether, our results present a noncanonical function of STAG2 in promoting cell motility and invasion of MIBC cells. This work forms the basis for additional investigation into the role of STAG2 in transcriptional regulation and how it becomes dysregulated in <i>STAG2</i>-mutant MIBC.</p>Significance:<p>The cohesin component STAG2 regulates cell motility and invasion. STAG2 expression is associated with decreased MIBC survival and may be a useful biomarker to guide bladder cancer treatment.</p></div>
<p>Supplementary methods, Supplementary Figures S1-S3, and Supplementary tables</p>
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