Purpose To determine the dosimetric effects of rotational errors on target coverage using volumetric modulated arc therapy (VMAT) for multi-target stereotactic radiosurgery (SRS). Methods and Materials This retrospective study includes 50 SRS cases, each with 2 intracranial planning target volumes (PTVs). Both PTVs were planned for simultaneous treatment to 21 Gy using a single-isocenter, non-coplanar VMAT SRS technique. Rotational errors of 0.5°, 1.0°, and 2.0° were simulated about all axes. The dose to 95% of the PTV (D95) and the volume covered by 95% of the prescribed dose (V95) were evaluated using multivariate analysis to determine how PTV coverage is related to PTV volume, PTV separation, and rotational error. Results At 0.5° rotational error, D95 values and V95 coverage rates were ≥ 95% in all cases. For rotational errors of 1.0°, 7% of targets had D95 and V95 values below 95%. Coverage worsened substantially when the rotational error increased to 2.0°: D95 and V95 values were > 95% for only 63% of the targets. Multivariate analysis showed that PTV volume and distance to isocenter were strong predictors of target coverage. Conclusions The effects of rotational errors on target coverage were studied across a broad range of SRS cases. In general, the risk of compromised coverage increases with decreasing target volume, increasing rotational error and increasing distance between targets. Multivariate regression models from this study may be used to quantify the dosimetric effects of rotational errors on target coverage given patient-specific input parameters of PTV volume and distance to isocenter.

Glioblastoma (GBM) is the most aggressive malignant primary brain tumor in adults, with a median survival of 14.6 months. Recent efforts have focused on identifying clinically relevant subgroups to improve our understanding of pathogenetic mechanisms and patient stratification. Concurrently, the role of immune cells in the tumor microenvironment has received increasing attention, especially T cells and tumor-associated macrophages (TAM). The latter are a mixed population of activated brain-resident microglia and infiltrating monocytes/monocyte-derived macrophages, both of which express ionized calcium-binding adapter molecule 1 (IBA1). This study investigated differences in immune cell subpopulations among distinct transcriptional subtypes of GBM. Human GBM samples were molecularly characterized and assigned to Proneural, Mesenchymal or Classical subtypes as defined by NanoString nCounter Technology. Subsequently, we performed and analyzed automated immunohistochemical stainings for TAM as well as specific T cell populations. The Mesenchymal subtype of GBM showed the highest presence of TAM, CD8 + , CD3 + and FOXP3 + T cells, as compared to Proneural and Classical subtypes. High expression levels of the TAM-related gene AIF1, which encodes the TAM-specific protein IBA1, correlated with a worse prognosis in Proneural GBM, but conferred a survival benefit in Mesenchymal tumors. We used our data to construct a mathematical model that could reliably identify Mesenchymal GBM with high sensitivity using a combination of the aforementioned cell-specific IHC markers. In conclusion, we demonstrated that molecularly distinct GBM subtypes are characterized by profound differences in the composition of their immune microenvironment, which could potentially help to identify tumors amenable to immunotherapy.

BACKGROUND 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. METHODS 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. RESULTS 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). CONCLUSIONS 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.

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Background: Structural inequities have important implications for the health of marginalized groups. Neighborhood-level redlining and lending bias represent state-sponsored systems of segregation, potential drivers of adverse health outcomes. We sought to estimate the effect of redlining and lending bias on breast cancer mortality and explore differences by race. Methods: Using Georgia Cancer Registry data, we included 4,943 non-Hispanic White (NHW) and 3,580 non-Hispanic Black (NHB) women with a first primary invasive breast cancer diagnosis in metro-Atlanta (2010–2014). Redlining and lending bias were derived for census tracts using the Home Mortgage Disclosure Act database. We calculated hazard ratios and 95% confidence intervals (CI) for the associations of redlining, lending bias on breast cancer mortality and estimated race-stratified associations. Results: Overall, 20% of NHW and 80% of NHB women lived in redlined census tracts, and 60% of NHW and 26% of NHB women lived in census tracts with pronounced lending bias. Living in redlined census tracts was associated with a nearly 1.60-fold increase in breast cancer mortality (hazard ratio = 1.58; 95% CI, 1.37–1.82) while residing in areas with substantial lending bias reduced the hazard of breast cancer mortality (hazard ratio = 0.86; 95% CI, 0.75–0.99). Among NHB women living in redlined census tracts, we observed a slight increase in breast cancer mortality (hazard ratio = 1.13; 95% CI, 0.90–1.42); among NHW women the association was more pronounced (hazard ratio = 1.39; 95% CI, 1.09–1.78). Conclusions: These findings underscore the role of ecologic measures of structural racism on cancer outcomes. Impact: Place-based measures are important contributors to health outcomes, an important unexplored area that offers potential interventions to address disparities.