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Background Although immunotherapy (IO) in combination with chemotherapy has improved progression free and overall survival in patients with PD-L1+ metastatic triple negative breast cancer (mTNBC), prognosis remains poor. A potential therapeutic strategy to restore sensitivity to IO in patients with progressive disease is to introduce agents that re-sensitize the immune system to IO leading to a more tumor-specific and less toxic treatment in the second-line setting or beyond. Both talazoparib, a PARP inhibitor, and radiation (XRT) independently increase PD-L1 expression on the tumor cell surface resulting in heightened sensitivity to IO agents like atezolizumab, a PD-L1 inhibitor. Although a local treatment, XRT has the ability to produce an abscopal effect resulting in systemic shrinkage of non-irradiated tumors outside/distant to the XRT field, a phenomenon observed in patients receiving concurrent IO. While talazoparib is standard treatment in patients with gBRCA1 and 2 mutations, it is also a potent radiosensitizing agent that suppresses homologous recombination and PARP-1-dependent nonhomologous end joining (NHEJ) repair while promoting error-prone alt-NHEJ. When combined with IO, talazoparib can amplify immune responses by generating immunogenic neo-antigens independent of gBRCA1/2 status. We, therefore, hypothesize that the combination of talazoparib, XRT, and atezolizumab will re-sensitize mTNBC tumors to IO and promote a durable tumor-specific response that spares patients from toxicities associated with traditional chemotherapy regimens. Methods This is a Phase II multi-institutional study designed to assess efficacy and safety of talazoparib, high dose XRT, and atezolizumab given in the second-, third-, or fourth-line settings to patients with mTNBC that is PD-L1 positive. A total of 23 patients with mTNBC who do not carry gBRCA pathogenic variants will be enrolled. All patients will be treated with induction talazoparib of 1mg PO daily starting Day 1 of a 28-day cycle. Patients will then receive 8 Gy x 3 fractions to 1-4 metastatic lesions QOD beginning Day 12, 13, or 14. Atezolizumab will be given intravenously (840 mg)) on Day 15 of the 1st cycle and then on Day 1 and Day 15 of the subsequent cycles. Talazoparib and atezolizumab treatment will continue until progression or severe toxicity. The primary endpoint is objective response rate (ORR) in non-irradiated lesions 8 weeks after the first dose of atezolizumab. Key inclusion criteria include biopsy proven mTNBC (ER< 10%, PR< 10%, Her2-) with at least 2 extracranial metastatic lesions. Patients must have at least 1 extracranial metastatic lesion amenable to high dose radiotherapy and at least one additional extracranial lesion of measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) that will not receive radiotherapy. Tumors must be PD-L1 positive as defined as >1% on IHC using the SP142 Ventana Assay. Key exclusion criteria include patients with germline BRCA pathogenic variants, more than three previous lines of chemotherapy treatment in the advanced setting with or without IO, and breast cancer progression within the first 3 months of previous IO treatment for non-metastatic or metastatic breast cancer. Sample size was determined using Simon’s 2-stage Minimax design to detect a 20% increase in ORR. The null hypothesis that the true response rate among gBRCA1/2 negative patients of 10% will be tested against a one-sided alternative. Inflammatory cytokines, circulating B cells, and ctDNA will be collected for correlative analysis. Enrollment began in April 2021. The study is managed by the Hoosier Cancer Research Network and is open to accrual at Emory University and University of Alabama at Birmingham. Clinical trial information: NCT04690855 Citation Format: Mylin A. Torres, Kevin Kalinsky, Erica Stringer-Reasor, Ahmed Elkhanany, Jolinta Lin, David M. Schuster, Sarah Friend, Jeffrey Switchenko, Manali Bhave. HCRN BRE 19-433: A Multi-institutional Phase II Study to Evaluate Efficacy and Safety of TAlazoparib, Radiotherapy and Atezolizumab in gBRCA 1/2 negative Patients with PD-L1+ Metastatic Triple Negative Breast Cancer (TARA) [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 OT2-10-03.

Background: Patients with metastatic triple negative breast cancer (mTNBC) have a poor prognosis with median survival of 18 months or less. While the combination of immune checkpoint inhibitors (ICIs) and chemotherapy has shown promise in mTNBC, biomarkers beyond PDL-1 are needed to better predict which individuals will benefit from this treatment approach. In this study, we assessed the ability of spatial characteristics in predicting clinical best response in patients with PDL-1 positive mTNBC treated with an ICI and chemotherapy. Methods: Women with advanced unresectable or mTNBC treated with an ICI plus chemotherapy at Emory University between 2019 and 2021 with available biopsy specimens were retrospectively evaluated. Different cell types (tumor, stroma, immune cells) were identified by morphology on H&E staining. A cellular network was created by connecting each cell centroid to its adjacent centroids within a 30-μm distance. The resulting spatial neighborhood network was used to assess tumor density and quantify immune infiltration. The immune infiltration score was defined as the number of immune to tumor cell neighbors divided by the total number of immune cell neighbors in a region of 75-μm. A final immunoscore was calculated for each patient by averaging the immune infiltration scores in regions with high tumor cell density. Tumor infiltrating lymphocytes (TILs) were manually quantified. Responders were defined as those with a complete response (CR), partial response (PR), or stable disease (SD), while those with progressive disease (PD) were categorized as non-responders. A continuous response score was developed from tumor measurements of a target lesion on serial imaging. Pearson’s correlation coefficients were used to assess the relationship between continuous response scores and tumor characteristics. Responders and non-responders were compared using Mann-Whitney U tests. Results: Fifteen women with PDL-1 positive mTNBC treated with ICI plus chemotherapy and available tissue were included. All patients had relapsed disease, and 10 patients (67%) received an ICI and chemotherapy as first line treatment for mTNBC. Eight patients (53%) received atezolizumab and nab-paclitaxel while the remaining 7 (47%) patients received pembrolizumab with an approved chemotherapeutic agent. Seven patients (47%) experienced a PR, 3 (20%) with a CR, and 1 (7%) had SD. Four patients (27%) had PD with no clinical benefit. Higher immunoscores (-0.17, p=0.6) and TILs (-0.21, p=0.5) were numerically associated with continuous response scores. However, there were no significant differences in immunoscores (0.28 vs 0.26, p=0.6) or TIL counts (2 vs 5, p=0.6) between responders (N=11) and non-responders (N=4). Interestingly, patients with response to treatment had lower tumor densities compared to non-responders (7.5 vs 17.3, p=0.02). Conclusions: Spatial analysis of tumor density and immune infiltration, including immunoscore shows evidence of correlation with response. Tumor density was the only parameter significantly associated with response. The study identified novel tumor characteristics that need to be considered in the prediction of response to ICIs plus chemotherapy in mTNBC. The current findings are hypothesis generating and need validation in additional tissue samples to determine the role of tumor density as a predictor of response to ICI. Citation Format: Jeffrey Aldrich, Thomas Hu, Jeffrey Switchenko, Ahmet Coskun, Yesim Gokmen-Polar, Sunil Badve, Manali Bhave. Predicting the likelihood of response in PDL-1 positive metastatic triple negative breast cancer treated with an immune checkpoint inhibitor [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 P1-04-14.

Introduction: Checkpoint inhibitors (CPI) have significantly improved survival among patients with various cancer types. Prior studies have shown a correlation between immune cell infiltration and poorly differentiated cancers. This study evaluated the impact of poorly differentiated histology on survival in patients with advanced gastrointestinal cancers treated with immunotherapy. Methods: This study was a retrospective, single-center analysis of patients with gastrointestinal cancers treated with CPIs between 2016 and 2021. Univariate and multivariable analyses were performed to identify factors associated with patient outcome. Kaplan-Meier analysis and Cox proportional hazards models were used to assess the association between tumor and patient characteristics, progression-free survival, and overall survival. Results: A total of 123 patients were eligible and included in the analysis. Median age was 66 years (23–88 years). Majority had stage IV disease (89%), were white (65.5%), and were male (64.5%). Most common diagnoses were hepatocellular carcinoma (30.5%), gastric adenocarcinoma (16.5%), esophageal adenocarcinoma (17%), and colorectal cancer (19.8%). About 32% of the tumors were microsatellite instability-high (MSI-High/dMMR), with BRAF V600E mutation rate of 10%. About 25% of the patients received CPIs as initial treatment, while 35.5% had received two or more prior lines of therapy. Compared with well and moderately differentiated histology, patients with poorly differentiated tumors had a shorter median overall survival (mOS) (not reached [NR] vs. NR vs. 9.3 months, p = 0.0264). There was no statistically significant difference in median progression-free survival (mPFS) between histology types (2.5 vs. 4.2 vs. 2 months, p = 0.1314). On univariate survival analysis, moderately differentiated tumors correlated with a significantly longer mOS (HR: 0.48, CI: 0.24–0.93, p = 0.030) and mPFS (HR: 0.62, 95% CI: 0.38–1.00, p = 0.048) compared to poorly differentiated histology. Female patients (HR: 0.55, 95% CI: 0.34–0.90, p = 0.018) and the Eastern Cooperative Oncology Group (ECOG) of 1 (vs. ≥2) had significantly longer mPFS (HR: 0.58, 95% CI: 0.35–0.97, p = 0.036). ECOG of 1 also correlated with longer mOS (HR: 0.47, 95% CI: 0.23–0.94, p = 0.034). Microsatellite stable (MSS) tumors had significantly shorter mPFS (HR: 5.74, 95% CI: 2.41–13.63, p < 0.001) and mOS (HR: 5.45, 95% CI: 1.64–18.12, p = 0.006). The number of prior systemic therapies was also associated with shorter mPFS (HR: 1.19, 95% CI: 1.03–1.39, p = 0.022) and mOS (HR: 1.23, 95% CI: 1.01–1.50, p = 0.045). On multivariable analyses, ECOG status of 0/1 versus ≥2 and MSI-High/dMMR versus MSS remained significantly associated with longer mPFS and mOS. There was no correlation with histologic differentiation status, race, or mutations such as BRAF V600E or KRAS. Conclusion: Results from this study demonstrate that poorly differentiated histology was associated with shorter mOS but was not associated with improved PFS in patients treated with CPI. Treatment-naïve patients, moderately differentiated tumors, female gender, ECOG 1, and MSI-High/dMMR were most likely to benefit from CPI.

PURPOSE To examine COVID-19 mRNA vaccine–induced binding and neutralizing antibody responses in patients with non–small-cell lung cancer (NSCLC) to SARS-CoV-2 614D (wild type [WT]) strain and variants of concern after the primary 2-dose and booster vaccination. METHODS Eighty-two patients with NSCLC and 53 healthy volunteers who received SARS-CoV-2 mRNA vaccines were included in the study. Blood was collected longitudinally, and SARS-CoV-2–specific binding and neutralizing antibody responses were evaluated by Meso Scale Discovery assay and live virus Focus Reduction Neutralization Assay, respectively. RESULTS A majority of patients with NSCLC generated binding and neutralizing antibody titers comparable with the healthy vaccinees after mRNA vaccination, but a subset of patients with NSCLC (25%) made poor responses, resulting in overall lower (six- to seven-fold) titers compared with the healthy cohort ( P = < .0001). Although patients age > 70 years had lower immunoglobulin G titers ( P = < .01), patients receiving programmed death-1 monotherapy, chemotherapy, or a combination of both did not have a significant impact on the antibody response. Neutralizing antibody titers to the B.1.617.2 (Delta), B.1.351 (Beta), and in particular, B.1.1.529 (Omicron) variants were significantly lower ( P = < .0001) compared with the 614D (WT) strain. Booster vaccination led to a significant increase ( P = .0001) in the binding and neutralizing antibody titers to the WT and Omicron variant. However, 2-4 months after the booster, we observed a five- to seven-fold decrease in neutralizing titers to WT and Omicron viruses. CONCLUSION A subset of patients with NSCLC responded poorly to the SARS-CoV-2 mRNA vaccination and had low neutralizing antibodies to the B.1.1.529 Omicron variant. Booster vaccination increased binding and neutralizing antibody titers to Omicron, but antibody titers declined after 3 months. These data highlight the concern for patients with cancer given the rapid spread of SARS-CoV-2 Omicron variant.

Background: Neighborhood deprivation is hypothesized as a potential driver of racial disparities in breast cancer mortality. However, research shows that neighborhood deprivation is associated with increased breast cancer mortality among White women, but has little to no association among Black women. No study has previously considered the intersections of race, social cohesion, or urban/rural status in the association between neighborhood deprivation and breast cancer mortality. Methods: Neighborhood deprivation was examined in relation to breast cancer mortality among 31,358 non-Hispanic Black and non-Hispanic White women diagnosed with invasive breast cancer (stage I-IIIA) between 2010-2017, followed through 2019, and identified by the Georgia Cancer Registry. Two composite scores, the Area Deprivation Index (ADI) and neighborhood deprivation index (NDI), were used to characterize neighborhood deprivation. A third composite score, the Yost index, was assessed as a measure of neighborhood socioeconomic status (SES). Each composite score was composed of factors representing six domains: poverty, income, occupation, housing, employment, and education. Data on ADI were obtained from the Neighborhood Atlas and was assessed in deciles. American Community Survey data from 2011-2015 and principal components analysis were used to derive the NDI and Yost index. Both measures were assessed in quartiles. Each composite variable was measured at the block group level and linked to patient data. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between each composite variable and breast cancer mortality, overall and by race/ethnicity. Intersectionality will be examined by considering the joint effects of race/ethnicity, social cohesion, and urban/rural status. Results: During the 9-year follow-up period, 2,353 (1,347 non-Hispanic White, 1,006 non-Hispanic Black) women died from breast cancer. Regardless of which composite score was assessed, living in the most deprived or lowest SES neighborhoods was associated with an increased risk of breast cancer mortality in models adjusted for age and race (ADI decile 10 vs. 1: HR=1.57, 95% CI 1.26-1.96; NDI quartile 4 vs. 1: HR=1.43, 95% CI 1.26-1.63; Yost index quartile 1 vs 4: HR= 1.34, 95% CI 1.18-1.51). Stratification by race/ethnicity showed associations were slightly stronger among non-Hispanic White women but null among non-Hispanic Black women. Results from analyses examining the joint effects of race/ethnicity, social cohesion, and urban/rural status are forthcoming and will be presented in December. Conclusions: Consistent with previous studies, our study found that living in a deprived neighborhood may increase breast cancer mortality among non-Hispanic White women, but not non-Hispanic Black women. Investigating the association with an intersectionality framework may help identify subgroups of women who are particularly susceptible to the adverse impact of neighborhood deprivation on breast cancer mortality. Citation Format: Lauren E. Barber, Jasmine M. Miller-Kleinhenz, Maret L. Maliniak, Leah Moubadder, Jeffrey Switchenko, Lauren E. McCullough. Neighborhood deprivation and breast cancer mortality among Black and White women [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 PD1-03.

In phase I trials, some biospecimens are used both for research and patient care and some for research only. Some research participants have therapeutic misconception, assuming all biospecimens are for patient care. This study’s aim was to test if a simple information chart would improve understanding of nontherapeutic research procedures. A two-arm study was conducted. Participants in the control group (C) were asked whether biospecimens were for their care, for research only, or for both. The experimental group (E) was asked the same questions but provided with a study-specific information chart labeling the purpose of each biospecimen. One hundred one patients were interviewed. In both arms, understanding that pretreatment blood draws were for patient care and research was moderate (49% for C and 62% for E). Understanding that posttreatment blood draws were for research only was significantly higher in the experimental arm (16% for C and 44% for E; p = 0.002). Providing a simple information chart may help alleviate this aspect of therapeutic misconception.

We conducted a randomized controlled trial evaluating the feasibility of a personalized out-of-pocket cost communication, remote financial navigation and counseling (CostCOM) intervention in decreasing financial hardship among patients with multiple sclerosis (MS).Sixty-two adult patients with diagnosis of MS and a prescription for a disease modifying therapy were randomized into: (1) Usual care (n=30) and (2) CostCOM (n=32). CostCOM included patient-specific out-of-pocket cost communication, remote financial navigation and counseling delivered at enrollment and 3 months. Usual care included routine neurology visits, use of available ancillary staff, and internal or external resources for financial assistance per normal clinic procedures. Feasibility outcomes included participation in and satisfaction with CostCOM. Exploratory financial hardship outcomes included cost-related care nonadherence, material hardship, and financial worry using Comprehensive Score for Financial Toxicity (COST).Mean age was 41.5 (81.0% female; 41.4% White and 51.7% Black race). Of 32 CostCOM patients, 96.8% and 68.7% completed baseline and follow-up intervention. A financial assistance application was completed for 80%. Mean general satisfaction (out of 5) with CostCOM was 3.1±1.0. In multivariable analyses, CostCOM patients had less financial worry (i.e., higher COST scores) at 3 months compared to usual care patients (B coefficient, 3.6; 95% CI (0.1 - 7.1). While CostCOM patients had significant decreases in 3 months non-adherence (72.7%) compared to enrollment (50%), their 3 months nonadherence and material hardship were not significantly different between the two arms.CostCOM interventions are feasible, acceptable, and yield potential benefits in decreasing financial hardship.This study is registered at ClinicalTrials.gov (NCT04257071).

PurposeWe investigated SARS-CoV-2 mRNA vaccine-induced binding and live-virus neutralizing antibody response in NSCLC patients to the SARS-CoV-2 wild type strain and the emerging Delta and Omicron variants.Methods82 NSCLC patients and 53 healthy adult volunteers who received SARS-CoV-2 mRNA vaccines were included in the study. Blood was collected longitudinally, and SARS-CoV-2-specific binding and live-virus neutralization response to 614D (WT), B.1.617.2 (Delta), B.1.351 (Beta) and B.1.1.529 (Omicron) variants were evaluated by Meso Scale Discovery (MSD) assay and Focus Reduction Neutralization Assay (FRNT) respectively. We determined the longevity and persistence of vaccine-induced antibody response in NSCLC patients. The effect of vaccine-type, age, gender, race and cancer therapy on the antibody response was evaluated.ResultsBinding antibody titer to the mRNA vaccines were lower in the NSCLC patients compared to the healthy volunteers (P=70 years had lower IgG titers (P=50 titers to Delta (6-fold), and Omicron (79-fold) variants (P=ConclusionsBinding and live-virus neutralizing antibody titers to SARS-CoV-2 mRNA vaccines in NSCLC patients were lower than the healthy vaccinees, with significantly lower live-virus neutralization of B.1.617.2 (Delta), and more importantly, the B.1.1.529 (Omicron) variant compared to the wild-type strain. These data highlight the concern for cancer patients given the rapid spread of SARS-CoV-2 Omicron variant.

Despite an overall decline in breast cancer (BC) mortality due to advancements in cancer therapy, mortality disparities by race, rurality, and socioeconomic status (SES) persist among women diagnosed with metastatic disease in the US. Women residing in high-poverty or rural areas or who are non-Hispanic Black (NHB) experience higher rates of BC mortality relative to their counterparts. Although mortality disparities among late-stage BC patients are well-documented, few studies have examined the drivers of these disparities, which are likely multifactorial. We sought to identify tumor, treatment, and patient characteristics that may contribute to differences in BC mortality by race, rurality, and SES among women diagnosed with a first primary stage IIIB - IV BC in Georgia.Using the Georgia Cancer Registry, we identified 3085 patients with an initial diagnosis of stage IIIB-IV primary BC between January 2013 and December 2017. Cox proportional hazards regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) to compare NHB vs. non-Hispanic White (NHW), rural vs. urban residents, and residents of low- vs. high-SES neighborhoods by tumor (stage, grade, ER status, and molecular subtype), treatment (surgery type, receipt of chemotherapy, radiation, hormonal, neoadjuvant, and immunotherapy), and patient (race, insurance, age group, marital status, region, SES) characteristics. Using an extension of the counterfactual framework, we estimated the mediating effects of subtype, stage, SES, rurality, and insurance on the association between race and BC mortality. Among the study population, 41% were NHB, 21% resided in rural counties, and 72% resided in low SES neighborhoods. Overall, we observed mortality disparities by race (HR=1.27, 95% CI: 1.13, 1.41) and rurality (HR=1.14, 95% CI: 1.00, 1.30), but not by SES (HR=1.04, 95% CI: 0.91, 1.19). In the stratified analyses, racial disparities were the most pronounced among women with HER2 overexpressing tumors (HR=2.30, 95% CI: 1.53, 3.45). Residing in a rural neighborhood was associated with increased mortality among uninsured women (HR=2.25, 95% CI: 1.31, 3.86) or receipt of breast-conserving surgery (HR=2.21, 95 CI%: 1.32, 3.71). The most pronounced socioeconomic disparities were among younger women ( Citation Format: Leah Moubadder, Lindsay J. Collin, Rebecca Nash, Jeffrey Switchenko, Jasmine Miller-Kleinhenz, Keerthi Gogineni, Kevin C. Ward, Lauren E. McCullough. Drivers of racial, regional, and socioeconomic disparities in metastatic breast cancer mortality [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 3678.

In the US, breast cancer mortality is 40% greater among Black than White women. The mortality disparity varies geographically and has persisted despite improvements in survival. Georgia is one of six states where breast cancer recently surpassed lung cancer as the leading cause of cancer death among Black but not White women, is a large and diverse state, and thus, an ideal setting to study race disparities. Our work in the Atlanta Metro area has shown that the mortality disparity is pronounced among patients with clinically favorable subtypes, low Oncotype DX® recurrence scores, guideline-concordant care, and similar access to surgical facilities. The disparity also persists among patients with private insurance and those living in areas of low poverty, suggesting clinical and sociodemographic differences do not fully account for the observed disparity. Recent evidence suggests area-level factors may contribute to the disparity. Our group reported that neighborhood-level redlining (i.e., mortgage denial based on place) is associated with an increase in breast cancer mortality while neighborhood-level lending bias (i.e., mortgage denial based on race) is associated with a decrease in breast cancer mortality. In Atlanta, Black patients are more likely to live in redlined areas and less likely to live in areas with lending bias, than White patients, further suggesting place is an important driver of disparities. We investigated the role of other area-level factors on race-specific mortality in Georgia. Race-specific standardized mortality ratios were computed for each county in Georgia. Observed breast cancer deaths among non-Hispanic White (NHW) and non-Hispanic Black (NHB) women within 5 years of a stage I-III breast cancer diagnosis (2005-2013) were obtained from the Georgia Cancer Registry. County-level characteristics were derived from the American Community Survey and Georgia Department of Public Health. A Bayesian model-based approach was used to stabilize local estimates and estimate associations with area-level factors. Smoothed estimates of relative disparity ranged from 1.2 to 1.7, with pronounced disparity for counties surrounding the Atlanta and Savannah metropolitan areas and least pronounced disparity in Metro Albany counties. Among NHB women, living in a rural (versus non-rural) county was associated with a nearly 20% increase in breast cancer mortality (RR=1.19, 95% credible interval (CI): 0.96, 1.48); an association not observed in NHW patients (RR=0.93, 95% CI: 0.79, 1.07). In contrast, a 10-point increase in the percent of adults with ≤high school education was associated with a 10% increase (95% CI: 1.05, 1.17) in mortality for NHW patients only. The race disparity in Georgia is not evenly distributed across counties. We identified area-level characteristics associated with race-specific mortality. Identifying other area-level drivers of breast cancer mortality is an important area of inquiry. Citation Format: Rebecca Nash, Lindsay J. Collin, Jeffrey Switchenko, Lauren E. McCullough. Area-level drivers of the breast cancer mortality race disparity in Georgia [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 3672.

Introduction: Breast cancer mortality in the US is 40% higher among Black than White women. Even among patients with prognostically favorable tumors, disparities persist, suggesting clinical features do not fully account for mortality differences. Area-level factors (e.g., rurality) influence health outcomes and may explain spatial variation in mortality disparities. Rurality can impact access to and quality of care, and socioeconomic status. Georgia is an ideal place to study spatial heterogeneity in race disparities because of the diverse population (>30% Black), large number of counties (159), and pronounced disparities in breast cancer mortality in the Atlanta area. Methods: Race-specific standardized mortality ratios (SMRs) were calculated for each county in Georgia to account for sparsely populated areas and areas with high residential segregation. Observed deaths among women diagnosed with localized or regional breast cancer between 2005 and 2013 were obtained from the Georgia Cancer Registry. To ensure equal follow-up, only deaths within five years of diagnosis were included. Expected deaths were estimated using race-specific population counts, race-specific breast cancer incidence rates, and the pooled (Black and White) mortality rate among Georgia women, with indirect age adjustment (20–44, 45–54, 55+ years). Spatial smoothing methods, including adding neighboring data to meet a threshold and Bayesian models with conditionally autoregressive priors, were used to stabilize local estimates. Counties were classified by 2013 RUC codes (urban: 1–3, rural: 4–9). Results: A total of 3,235 breast cancer deaths were observed during the study period, with 42% among Black women. The median SMR was lower for White (0.8, IQR: 0.7, 1.1) than Black women (1.4, IQR: 1.1, 2.0). Among Black women only, median SMR was greater in rural (1.7, IQR: 1.1, 2.5) than urban counties (1.3, IQR: 1.1, 1.6). After sequentially adding neighboring data to meet a race-specific threshold of 30 observed deaths, smoothed median SMRs were 0.9 (IQR: 0.8, 0.9) and 1.4 (IQR: 1.2, 1.6) for White and Black women, respectively. For Black women, median SMR was attenuated in rural counties (1.4, IQR: 1.2, 1.7) but unchanged in urban counties (1.3, IQR: 1.2, 1.5). The greatest SMRs for Black women were observed in urban counties comprising the Atlanta area and rural southeast Georgia. For example, Fulton County SMRs were 1.6 and 0.7, for Black and White women, respectively. Highest SMRs for White women were observed in southwest Georgia, but were similar to SMRs among Black women in this region. The spatial distribution of SMRs using same neighbor smoothing and Bayesian models were similar. Conclusion: Breast cancer mortality race disparities vary widely across Georgia. These results highlight specific areas for public health intervention, especially among Black women. This work presents a potential mechanism to monitor trends in small area cancer mortality race disparities over time. Future work will model the impact of area-level factors on the disparity magnitude. Citation Format: Rebecca J. Nash, Lauren E. McCullough, T.J. Pierce, Lindsay J. Collin, Anne H. Gaglioti, Kevin C. Ward, Michael Kramer, Jeffrey Switchenko. Spatial heterogeneity and rural-urban differences in the Black-White breast cancer mortality disparity in Georgia [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-173.

Qualitative assessment of PET/CT results in post therapy is very important to provide a reproducible and systemic reporting. A recently introduced response criteria, known as the Hopkins criteria showed promising results. Our aim is to externally validate the Hopkins interpretation system to assess therapy response in head and neck squamous cell cancer (HNSCC). The study included 69 biopsy proven HNSCC patients who underwent post therapy PET/CT between 5-24 weeks after completion of therapy. PET/CT images were interpreted by one nuclear medicine physician and one nuclear radiologist, independently. The studies were scored according to the Hopkins criteria for right neck, left neck, primary tumor site, and overall assessment. Scores 1, 2, 3 were considered as negative and scores 4 and 5 were considered as positive for tumors. Inter-reader variability was assessed using percent agreement and Kappa statistics. Progression-free survival (PFS) was estimated using the Kaplan-Meier method and analyzed using Cox proportional hazards regression. Of the 69 patients, 59 (85.5%) were males, with a mean age of 62.8 years. The percent agreement between readers for overall, right neck, left neck, and primary tumor site were 91.3%, 97.6%, 97.6%, 91.3% respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of the overall therapy assessment were 66.7%, 87.3%, 33%, 96.5% respectively. Cox univariate regression analysis showed positive primary tumor site scores and overall scores were associated with a higher risk of progression (p

As systemic therapy has improved for locally advanced pancreatic cancer (LAPC), efforts to improve local control with optimal radiotherapy may be critical. Although conventionally fractionated radiation therapy (CFRT) has more recently shown a limited role in LAPC, stereotactic body radiation therapy (SBRT) is an emerging approach with promising results. With no studies to date comparing SBRT with CFRT for LAPC, this study used the National Cancer Data Base (NCDB) to evaluate these 2 modalities.With the NCDB, patients with American Joint Committee on Cancer cT2-4/N0-1/M0 adenocarcinoma of the pancreas diagnosed from 2004 to 2013 were analyzed. Radiation therapy delivered at ≤2 Gy was deemed CFRT, and radiation therapy delivered at ≥4 Gy per fraction was considered SBRT. Kaplan-Meier analysis, log-rank testing, and multivariate Cox proportional hazards regression were performed with overall survival (OS) as the primary outcome. Propensity score matching was used.Among 8450 patients, 7819 (92.5%) were treated with CFRT, and 631 (7.5%) underwent SBRT. Receipt of SBRT was associated with superior OS in the multivariate analysis (hazard ratio, 0.84; 95% confidence interval, 0.75-0.93; P .001). With propensity score matching, 988 patients in all were matched, with 494 patients in each cohort. Within the propensity-matched cohorts, the median OS (13.9 vs 11.6 months) and the 2-year OS rate (21.7% vs 16.5%) were significantly higher with SBRT versus CFRT (P = .0014).In this retrospective review using a large national database, SBRT was associated with superior OS in comparison with CFRT for LAPC, and these findings remained significant in a propensity-matched analysis. Further prospective studies investigating these hypothesis-generating results are warranted. Cancer 2017;123:3486-93. © 2017 American Cancer Society.