Citations

159 Background: Intensity-modulated proton therapy (IMPT) with small spot size has the potential to reduce dose to normal tissues but also introduces new confounding factors such as setup uncertainty, range uncertainty, and interplay effects due to breathing motion. We investigated plan quality and robustness of IMPT with small spot size for distal esophageal adenocarcinoma (DEA). Methods: 19 patients with DEA treated by IMPT were retrospectively evaluated. Spot sizes ranged from 2 to 6mm, with spot spacing of 5mm. All plans were generated using a commercial treatment planning system. In-house-developed dose-evaluation software modeled time-dependent spot delivery to incorporate interplay effects. Dose-volume-histogram (DVH) indices were used to evaluate plan quality and robustness was evaluated using the DVH band method. Results: For plan quality, median values of clinical target volume D95% and D5%-D95% (normalized to the prescribed doses), total lung mean dose, heart mean dose, and cord Dmax were 1.014, 0.035, 3.82Gy[RBE], 7.73Gy[RBE], 39.16Gy[RBE], respectively. For plan robustness, median band widths of the aforementioned DVH indices were 0.018, 0.048, 0.60Gy[RBE], 4.17Gy[RBE], and 2.36Gy[RBE], respectively. For interplay effects, median values of the aforementioned DVH indices were 0.99, 0.061, 4.07Gy[RBE], 7.87Gy[RBE], and 39.66Gy[RBE], respectively. Seven patients underwent esophagectomy after neoadjuvant chemoradiation, and five, three, and one of them achieved downstaging, near complete response, and pathologic complete response, respectively; R0 resection was achieved in all cases. For all patients, acute side effects were mostly limited to grades 1-2 only. The only grade 3 adverse events were related to feeding tube placement (8 patients); there were no RT-induced pneumonitis or other lung-related toxicities. Conclusions: IMPT plans with small spot size for DEA have good target dose coverage, homogeneity and normal tissue protection. Treatment plans are also robust to uncertainties and interplay effects. Early clinical results demonstrate low acute toxicity and encouraging clinical and pathologic response.

The prevalence, clinicopathologic correlates, and outcomes of previously untreated chronic lymphocytic leukemia (CLL) patients with IGH‐BCL2 and IGH‐BCL3 translocations are not well known. Using the Mayo Clinic CLL database, we identified patients seen between March 1, 2002 and September 30, 2016 who had FISH testing performed within 3 years of CLL diagnosis. The prognostic profile, time to first therapy (TTT), and overall survival (OS) of patients with IGH‐BCL2 and IGH‐BCL3 translocation were compared to patients without these abnormalities (non‐IGH group). Of 1684 patients who met the inclusion criteria, 38 (2.2%) had IGH‐BCL2, and 16 (0.9%) had IGH‐BCL3 translocation at diagnosis. Patients with IGH‐BCL3 translocation were more likely to have high and very‐high CLL‐International Prognostic Index, compared to patients with IGH‐BCL2 translocation and the non‐IGH group. The 5‐year probability of requiring therapy was significantly higher for IGH‐BCL3 compared to IGH‐BCL2 and non‐IGH groups (84% vs 33% vs 29%, respectively, P < 0.0001). The 5‐year OS was significantly shorter for IGH‐BCL3 compared to IGH‐BCL2 and non‐IGH groups (45% vs 89% vs 86%, respectively, P < 0.0001). On multivariable analyses, IGH‐BCL3 translocation was associated with a shorter TTT (hazard ratio [HR] = 2.7; P = 0.005) and shorter OS (HR = 5.5; P < 0.0001); IGH‐BCL2 translocation did not impact TTT and OS. In conclusion, approximately 3% of all newly diagnosed CLL patients have either an IGH‐BCL2 or IGH‐BCL3 translocation. Patients with IGH‐BCL3 translocations have a distinct prognostic profile and outcome. These results support the inclusion of an IGH probe during the routine evaluation of FISH abnormalities in newly diagnosed CLL.

Objectives The aim of this study was to investigate the impact on metal artifacts and dose efficiency of using a tin filter in combination with high-energy threshold (TH) images of a photon-counting detector (PCD) computed tomography (CT) system. Materials and Methods A 3D-printed spine with pedicle screws was scanned on a PCD-CT system with and without tin filtration. Image noise and severity of artifacts were measured for low-energy threshold (TL) and TH images. In a prospective, institutional review board–approved, Health Insurance Portability and Accountability Act-compliant study, 20 patients having a clinical energy-integrating detector (EID) CT were scanned on a PCD-CT system using tin filtration. Images were reviewed by 3 radiologists to evaluate visualization of anatomic structures, diagnostic confidence, and image preference. Artifact severity and image noise were measured. Wilcoxon signed rank was used to test differences between PCD-CT TH and EID-CT images. Results Phantom TH images with tin filtration reduced metal artifacts and had comparable noise (32 HU) to TL images (29 HU) acquired without tin filtration. Visualization scores for the cortex, trabeculae, and implant-trabecular interface from PCD-CT TH images (4.4 ± 0.9, 4.4 ± 1.0, and 4.4 ± 1.0) were significantly higher (P < 0.0001) than EID-CT images (3.3 ± 1.3, 3.3 ± 1.2, and 3.3 ± 1.6). A strong preference was shown for PCD-CT TH images due to improved diagnostic confidence and decreased artifact severity. Noise in PCD-CT TH images (93 ± 41 HU) was significantly lower than that in EID-CT images (133 ± 92 HU, P < 0.05). Conclusions Threshold high images acquired with tin filtration on PCD-CT demonstrated a substantial decrease in metal artifacts and an increase in dose efficiency compared with EID-CT.

Abstract DNA methylation is instrumental for gene regulation. Global changes in the epigenetic landscape have been recognized as a hallmark of cancer. However, the role of DNA methylation in epithelial ovarian cancer (EOC) remains unclear. In this study, high-density genetic and DNA methylation data in white blood cells from the Framingham Heart Study (N = 1,595) were used to build genetic models to predict DNA methylation levels. These prediction models were then applied to the summary statistics of a genome-wide association study (GWAS) of ovarian cancer including 22,406 EOC cases and 40,941 controls to investigate genetically predicted DNA methylation levels in association with EOC risk. Among 62,938 CpG sites investigated, genetically predicted methylation levels at 89 CpG were significantly associated with EOC risk at a Bonferroni-corrected threshold of P &lt; 7.94 × 10−7. Of them, 87 were located at GWAS-identified EOC susceptibility regions and two resided in a genomic region not previously reported to be associated with EOC risk. Integrative analyses of genetic, methylation, and gene expression data identified consistent directions of associations across 12 CpG, five genes, and EOC risk, suggesting that methylation at these 12 CpG may influence EOC risk by regulating expression of these five genes, namely MAPT, HOXB3, ABHD8, ARHGAP27, and SKAP1. We identified novel DNA methylation markers associated with EOC risk and propose that methylation at multiple CpG may affect EOC risk via regulation of gene expression. Significance: Identification of novel DNA methylation markers associated with EOC risk suggests that methylation at multiple CpG may affect EOC risk through regulation of gene expression.

Respiratory viral infections are associated with a wide range of acute syndromes and infectious disease processes in children and adults worldwide. Many viruses are implicated in these infections, and these viruses are spread largely via respiratory means between humans but also occasionally from animals to humans.

Background Deceased-donor kidney discard rates vary by region, but it is unknown whether discard rates and transplant outcomes vary during the American Transplant Congress (ATC) each year. Methods Using national registry data, we determined rates of kidney discard, delayed graft function, graft failure, and mortality from December 31, 1999, through December 30, 2015, during ATC dates and compared these rates with those on the same days of the week during the 2 weeks before and after the ATC (non-ATC). We used multivariable regression to determine associations between ATC and these outcomes. Results From 7902 donors (1575 ATC; 6327 non-ATC), 12 588 recipients received kidney transplants (2455 ATC; 10 133 non-ATC), and 2666 kidneys were discarded (582 ATC; 2084 non-ATC). Kidneys were more often discarded during ATC (19% vs 17%, P = 0.006; adjusted odds ratio, 1.21; 95% confidence interval, 1.05-1.40). There were no significant differences in donor, transplant, or recipient characteristics by ATC/non-ATC dates or by ATC/non-ATC transplant dates for delayed graft function, graft failure, or mortality. Conclusions On the basis of a 21% increased odds of discard, the ATC itself may result in 5 additional kidney discards during this important conference every year, which suggests the need for innovative staffing or other logistic solutions during these planned meetings.