Faculty Bibliography

PURPOSE/OBJECTIVE:To compare dual-source dual-energy CT enterography (dsDECTE) obtained iodine density (I) (mg/mL) and I normalized to the aorta (I%) with Crohn's disease (CD) phenotypes defined by the SAR-AGA small bowel CD consensus statement. METHODS:Fifty CD patients (31 male, 19 female; mean [SD] age: 50.4 [15.2] years) who underwent dsDECTE were retrospectively identified. Two abdominal radiologists assigned CD phenotypes: no active inflammation (group-2), active inflammation without (group-3) or with luminal narrowing (group-4), stricture with active inflammation (group-5), stricture without active inflammation (group-1), and penetrating disease (group-6). Semiautomatic prototype software was used to determine the median I and I% of CD-affected small bowel mucosa for each patient. The means of the I and I% medians were compared among 4 groups ("1 + 2", "3 + 4", "5", "6") using one-way ANOVA (significance level 0.05 for each outcome) for each outcome individually followed by Tukey's range test for pairwise comparisons with adjusted p-values (overall alpha = 0.05). RESULTS:Mean [SD] I was 2.14 [1.07] mg/mL for groups 1 + 2 (n = 16), 3.54 [1.71] mg/mL for groups 3 + 4 (n = 15), 5.5 [3.27] mg/mL for group- "5" (n = 9), and 3.36 [1.43] mg/mL for group-"6" (n = 10) (ANOVA p = .001; group "1 + 2" versus "5" adj-p = .0005). Mean [SD] I% was 21.2 [6.13]% for groups 1 + 2, 39.47 [9.71]% for groups 3 + 4, 40.98 [11.76]% for group-5, and 35.01 [7.58]% for group-6 (ANOVA p < .0001; groups "1 + 2" versus "3 + 4" adj-p < .0001, group "1 + 2" versus "5" adj-p < .0001, and groups "1 + 2" versus "6" adj-p = .002). CONCLUSION/CONCLUSIONS:Iodine density obtained from dsDECTE significantly differed among CD phenotypes defined by SAR-AGA, with I (mg/mL) increasing with phenotype severity and decreasing for penetrating disease. I and I% can be used to phenotype CD.

BACKGROUND:Adjuvant therapy for high-risk resected melanoma with programmed cell-death 1 blockade results in a median relapse-free survival (RFS) of 5 years. The addition of low dose ipilimumab (IPI) to a regimen of adjuvant nivolumab (NIVO) in CheckMate-915 did not result in increased RFS. A pilot phase II adjuvant study of either standard dose or low dose IPI with NIVO was conducted at two centers to evaluate RFS with correlative biomarker studies. METHODS:Patients with resected stages IIIB/IIIC/IV melanoma received either IPI 3 mg/kg and NIVO 1 mg/kg (cohort 4) or IPI 1 mg/kg and NIVO 3 mg/kg (cohorts 5 and 6) induction therapy every 3 weeks for 12 weeks, followed by maintenance NIVO. In an amalgamated subset of patients across cohorts, peripheral T cells at baseline and on-treatment were assessed by flow cytometry and RNA sequencing for exploratory biomarkers. RESULTS:High rates of grade 3-4 adverse events precluded completion of induction therapy in 50%, 35% and 7% of the patients in cohorts 4, 5 and 6, respectively. At a median of 63.9 months of follow-up, 16/56 patients (29%) relapsed. For all patients, at 5 years, RFS was 71% (95% CI: 60 to 84), and overall survival was 94% (95% CI: 88 to 100). Expansion of CD3+CD4+CD38+CD127-GARP- T cells, an on-treatment increase in CD39 expression in CD8+ T cells, and T-cell expression of phosphorylated signal-transducer-and-activator-of-transcription (STAT)2 and STAT5 were associated with relapse. CONCLUSIONS:Adjuvant IPI/NIVO at the induction doses used resulted in promising relapse-free and overall survival, although with a high rate of grade 3-4 adverse events. Biomarker analyses highlight an association of ectoenzyme-expressing T cells and STAT signaling pathways with relapse, warranting future validation. TRIAL REGISTRATION NUMBER:NCT01176474 and NCT02970981.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Adherence to evidence-based guidelines in gastric cancer is low. We aimed to evaluate adherence to National Comprehensive Cancer Network (NCCN) Guidelines for gastric cancer at both patient- and hospital-levels and examine associations between guideline adherence and treatment outcomes, including overall survival (OS). METHODS:We applied stage-specific, annual NCCN Guidelines (2004-2015) to patients with gastric cancer treated with curative-intent within the National Cancer Database and compared characteristics of patients who did and did not receive guideline-adherent care. Hospitals were evaluated by guideline adherence rate. We identified associations with OS through multivariable Cox regression. RESULTS:Of 37 659 patients included, 32% received NCCN Guideline-adherent treatment. OS was significantly associated with both guideline adherence (51 months for patients receiving guideline-adherent treatment vs. 22 for patients receiving nonadherent treatment, p < 0.001). Treatment at a hospital with higher adherence was associated with longer OS (21 months for patients treated at lowest adherence quartile hospitals vs. 37 months at highest adherence quartile hospitals, p < 0.001), regardless of type of treatment received. CONCLUSIONS:Guideline-adherent treatment was strongly associated with longer median OS. Guideline adherence should be used as a benchmark for focused quality improvement for physicians taking care of patients with gastric cancer and institutions at large.

The goal of therapy for essential thrombocythemia (ET) and polycythemia vera (PV) patients is to reduce thrombotic events by normalizing blood counts. Hydroxyurea (HU) and interferon-α (IFN-α) are the most frequently used cytoreductive options for ET and PV patients at high-risk for vascular complications. Myeloproliferative Disorders Research Consortium 112 was an investigator-initiated, phase 3 trial comparing HU to pegylated IFN-α (PEG) in treatment naïve, high-risk ET/PV patients. The primary endpoint was complete response (CR) rate at 12 months. A total of 168 patients were treated for a median of 81.0 weeks. CR for HU was 37% and 35% for PEG (p=0.80) at 12 months. At 24/36 months, CR was 20%/17% for HU and 29%/33% for PEG. PEG led to a greater reduction in JAK2V617F at 24 months, but histopathologic responses were more frequent with HU. Thrombotic events and disease progression were infrequent in both arms, while grade 3/4 adverse events were more frequent with PEG (46% vs. 28%). At 12 months of treatment there was no significant difference in CR rates between HU and PEG. This study indicates that PEG and HU are both effective treatments for PV and ET. With longer treatment PEG was more effective in normalizing blood counts and reducing driver mutation burden, while HU produced more histopathologic responses. Despite these differences, both agents did not differ in limiting thrombotic events and disease progression in high-risk ET/PV patients. (Funded by the National Cancer Institute, 5P01CA108671-09; clinicaltrials.gov number (NCT01259856).