• CT Textural Analysis (CTTA) of Metastatic Treatment‐Resistant Pancreatic Adenocarcinoma (PDAC): Identifying Biomarkers for Genetic Instability and Overall Survival

      Campbell, David; The University of Arizona College of Medicine - Phoenix; Korn, Ronald (The University of Arizona., 2016-03-23)
      Metastatic, treatment‐resistant pancreatic ductal adenocarcinoma (PDAC) is a rapidly fatal disease that typically carries a bleak prognosis. Contrast‐enhanced CT is the current standard of care tool for imaging evaluation, and repeat imaging is routinely performed in clinical trials. The availability of these imaging data render them exploitable for further analysis. CT texural analysis (CTTA), a quantitative tool for examining a region of interest on CT and generating statistical parameters based on gray‐level pixel data, is powerful technique that has been studied in other cancers and shown to correlate with features such as tumor grade, stage, and prognosis. However, the application of CTTA to PDAC has not been studied. Given the paucity of diagnostic tests to guide therapy, validated CTTA biomarkers could be immensely useful. Identifying PDAC variants that have a relative deficit in DNA repair might allow these cancers to be treated with targeted cytotoxic regimens sooner. Additionally, identifying prognostic CTTA parameters would be useful in gauging the severity of disease. We sought to perform quantitative textural analysis on CT imaging from a clinical trial cohort of patients with metastatic, treatment‐resistant PDAC. We aimed to correlate CTTA features to molecular profiling results (copy number variations obtained by array CGH) and clinical features (overall survival). Metastatic tumor sites from patients with treatment‐resistant PDAC were biopsied and molecularly profiled. Intrachromosal copy number were assessed by CGH in tumor specimens, and patients were treated based on these individual molecular profiling results. Pre‐biopsy portal‐venous phase and non‐contrast CT scans were obtained for retrospective analysis (n=15). CTTA was performed by drawing regions of interest around the primary pancreas adenocarcinoma and the normal pancreas tissue. CTTA parameters including mean positive pixels, entropy, kurtosis, and skewness were derived using the TexRAD platform at texture filtering densities of 0, 2, 3, 4, 5, and 6 pixels. CTTA values were then compared to intrachromosomal copy number variation (CNV) per tumor and overall survival (OS) post treatment using a Spearman’s rank correlation coefficient. Additional linear regression analysis was performed for positive correlations, and a Kaplan‐Meier statistic was generated for OS using median CTTA entropy. Multivariate analyses for CNV and OS were also performed. CNV were negatively correlated with the kurtosis value of the primary tumor mass using medium texture filtering (p=0.034, n=15). Linear regression revealed a significant negative correlation between kurtosis and CNV (p=0.038). Secondary analysis of the normal pancreas using coarse texture filtering revealed that increasing entropy was associated with decreased OS (p=0.0014, n=12). Using median entropy as a cutoff value (median: 4.165), median OS was greater in the entropy < 4.165 group versus the entropy > 4.165 group (179 days v 43 days; 95% CI 73.137 – 166.87; p=0.004, n=12). This exploratory study with admittedly limited sample size raises interesting questions about the use of CTTA parameters as diagnostic tools and/or biopsy adjuncts in assessing PDAC susceptibility to commercially available cytotoxics. Secondarily, entropy, a potential marker of heterogeneity and inflammation in the normal pancreas, represents an intriguing possibility for gauging prognosis.
    • The Use of Clinical Decision Rules to Reduce Unnecessary Head Ct Scans in Pediatric Populations

      Barrett, Jeffrey; The University of Arizona College of Medicine - Phoenix; Panchanathan, Sarada (The University of Arizona., 2016-04-20)
      Background: Head computed tomography (CT) imaging is the gold standard study for rapidly identifying emergent traumatic brain injuries (TBIs). Exposure to the ionizing radiation utilized in CT increases lifetime risk for developing neoplasms. Currently there is little consensus on appropriate use of CT imaging for children with mild head injury. Clinical decision rules (CDRs) have been developed to identify children at very low risk of clinically significant brain injury. While these CDRs have been validated, their implementation has not been as well studied. Objective: To evaluate the efficacy of two CDRs in decreasing CT scan rate without missing clinically significant brain injuries. The two CDRs used in this study were the Children's Head Injury Algorithm for the Prediction of Important Clinical Events (CHALICE) and the Pediatric Emergency Care Applied Research Network (PECARN) algorithm. Both variations of the PECARN criteria for age 2 years and older and age <2 years were studied. Design/Methods: The medical records for patients with the diagnosis of head injury evaluated at the Maricopa Medical Center Pediatric Emergency Department for all of 2011 and 2012 were reviewed. A total of 331 charts were identified. The PECARN and CHALICE inclusion criteria and algorithms were applied to these charts to determine if the patients met criteria for CT scan. Patients with suspected non‐accidental injuries were excluded. Results: Of 331 patients, 238 met the inclusion criteria for CHALICE. 96 (40.3%) had CT scans performed. According to the algorithm, only 52 (21.8%) met criteria, which is an absolute rate reduction of 18.5%. One TBI was missed. 129 patients met the inclusion criteria for PECARN age 2 years and older. 73 (56.6%) had CT scans performed. 61 (47.2%) met criteria resulting in an absolute rate reduction of 9.4%. No TBIs were missed. 74 patients met inclusion criteria for PECARN age <2 years. Of these, 25 (33.7%) had CT scans performed and the same number met criteria resulting in no change in number of scans. One TBI was missed. Conclusions: Both the CHALICE and PECARN CDRs have the potential to reduce scan rates in our home institution. The CHALICE CDR would have resulted in a greater reduction in CT scans. PECARN also would have reduced the number of scans in children 2 years and older, but not in children <2 years old. The TBI that did not meet CDR criteria was also missed by clinical suspicion and a CT scan done on a later encounter was suspicious for a non‐accidental injury.