Inter-reader agreement of pancreatic adenocarcinoma resectability assessment with photon counting versus energy integrating detector CT.

PURPOSE: To compare the inter-reader agreement of pancreatic adenocarcinoma resectability assessment at pancreatic protocol photon-counting CT (PCCT) with conventional energy-integrating detector CT (EID-CT). METHODS: A retrospective single institution database search identified all contrast-enhanced pancreatic mass protocol abdominal CT performed at an outpatient facility with both a PCCT and EID-CT from 4/11/2022 to 10/30/2022. Patients without pancreatic adenocarcinoma were excluded. Four fellowship-trained abdominal radiologists, blinded to CT type, independently assessed vascular tumor involvement (uninvolved, abuts ≤ 180°, encases > 180°; celiac, superior mesenteric artery (SMA), common hepatic artery (CHA), superior mesenteric vein (SMV), main portal vein), the presence/absence of metastases, overall tumor resectability (resectable, borderline resectable, locally advanced, metastatic), and diagnostic confidence. Fleiss's kappa was used to calculate inter-reader agreement. CTDIvol was recorded. Radiation dose metrics were compared with a two-sample t-test. A p < .05 indicated statistical significance. RESULTS: 145 patients (71 men, mean[SD] age: 66[9] years) were included. There was substantial inter-reader agreement, for celiac artery, SMA, and SMV involvement at PCCT (kappa = 0.61-0.69) versus moderate agreement at EID-CT (kappa = 0.56-0.59). CHA had substantial inter-reader agreement at both PCCT (kappa = 0.67) and EIDCT (kappa = 0.70). For metastasis identification, radiologists had substantial inter-reader agreement at PCCT (kappa = 0.78) versus moderate agreement at EID-CT (kappa = 0.56). CTDIvol for PCCT and EID-CT were 16.9[7.4]mGy and 29.8[26.6]mGy, respectively (p < .001). CONCLUSION: There was substantial inter-reader agreement for involvement of 4/5 major peripancreatic vessels (celiac artery, SMA, CHA, and SMV) at PCCT compared with 2/5 for EID-CT. PCCT also afforded substantial inter-reader agreement for metastasis detection versus moderate agreement at EID-CT with statistically significant radiation dose reduction.

Pancreatic cyst prevalence and detection with photon counting CT compared with conventional energy integrating detector CT.

PURPOSE: To calculate the prevalence of pancreatic cysts on photon counting CT (PCCT) and compare with that of 128-slice conventional energy-integrating detector CT (EIDCT). METHOD: A retrospective single institution database search identified all contrast-enhanced abdominal CT examinations performed at an outpatient facility that has both a PCCT and EIDCT between 4/11/2022 and 7/26/2022. The presence and size of pancreatic cysts were recorded. In patients with PCCT reported pancreatic cysts, prior CT imaging (EIDCT) was reviewed for reported pancreatic cysts. Fisher's exact test was used to compare the pancreatic cyst detection rate for PCCT and EIDCT. Wilcoxon rank sum test was used to compare cyst size and patient age. A p <.05 indicated statistical significance. RESULTS: 2494 patients were included. Our pancreatic cyst detection rate was 4.9 % (49/1009) with PCCT and 3.0 % (44/1485) for EIDCT (p =.017). For CT angiograms, pancreatic cysts were detected in 6.6 % (21/319) with PCCT and 0.0 % (0/141) with EIDCT (p <.001). Pancreatic cyst detection rate was not statistically different for portal venous, enterography, renal mass, pancreas, 3-phase liver, or venogram protocols (all p >.05). Mean[SD] pancreatic cyst size was 13.7[9.7]mm for PCCT and 15.3[14.7] for EIDCT (p =.95). 55.1 % (27/49) of PCCT and 61.4 % (27/44) of EIDCT that described pancreatic cysts had prior contrast-enhanced EIDCTs. Of these, 40.7 % (11/27) of PCCT and 14.8 % (4/27) of EIDCT described pancreatic cysts were not previously reported (p =.027). CONCLUSIONS: Photon-counting CT afforded greater pancreatic cyst detection than conventional energy-integrating detector CT, particularly with CT angiograms.

A dominant-negative effect drives selection of TP53 missense mutations in myeloid malignancies.

TP53, which encodes the tumor suppressor p53, is the most frequently mutated gene in human cancer. The selective pressures shaping its mutational spectrum, dominated by missense mutations, are enigmatic, and neomorphic gain-of-function (GOF) activities have been implicated. We used CRISPR-Cas9 to generate isogenic human leukemia cell lines of the most common TP53 missense mutations. Functional, DNA-binding, and transcriptional analyses revealed loss of function but no GOF effects. Comprehensive mutational scanning of p53 single-amino acid variants demonstrated that missense variants in the DNA-binding domain exert a dominant-negative effect (DNE). In mice, the DNE of p53 missense variants confers a selective advantage to hematopoietic cells on DNA damage. Analysis of clinical outcomes in patients with acute myeloid leukemia showed no evidence of GOF for TP53 missense mutations. Thus, a DNE is the primary unit of selection for TP53 missense mutations in myeloid malignancies.