Importance Cancer is caused by a diverse array of somatic and germline genomic aberrations. Advances in genomic sequencing technologies have improved the ability to detect these molecular aberrations with greater sensitivity. However, integrating them into clinical management in an individualized manner has proven challenging. Objective To evaluate the use of integrative clinical sequencing and genetic counseling in the assessment and treatment of children and young adults with cancer. Design, Settings and Participants An observational, consecutive case series (May 2012–October 2014) of 102 children and young adults (mean age, 10.6; median age, 11.5, range: 0–22 years) with relapsed, refractory, or rare cancer at a single major academic medical center. Exposures Each participant underwent integrative clinical exome (tumor and germline DNA) and transcriptome (tumor RNA) sequencing along with genetic counseling. Results were discussed in a multi-disciplinary Precision Medicine Tumor Board (PMTB) and recommendations were reported to treating physicians and families. Main Outcomes and Measures Proportion of patients with potentially actionable findings (PAF), results of clinical actions based on integrative clinical sequencing (ICS), and estimated proportion of patients or their families at risk for future cancer. PAF was defined as any genomic findings discovered during sequencing analysis that could lead to a 1) change in patient management by providing a targetable molecular aberration, 2) change in diagnosis or risk stratification or 3) provides cancer-related germline findings, which inform patients/families about a potential future risk of various cancers; Results We screened 104 patients and enrolled 102 patients of which 91 (89%) had adequate tumor tissue available to complete sequencing and only these patients were included in all subsequent calculations, including 28 (31%) with hematological malignancies and 63 (69%) with solid tumors. Overall, 42 (46%) patients had PAFs which changed patient management including, 54% (15/28) with hematological malignancies and 43% (27/63) with solid tumors. Overall, individualized actions were taken in 23 of the 91 (25%) patients and families based on actionable ICS findings, including change in treatment in 14 (15%) and genetic counseling for future cancer risk in 9 (10%) patients. 9/91 (10%) of these personalized clinical interventions resulted in ongoing partial clinical remission of 8–16 months duration or help sustain complete clinical remission of 6–21 months duration. All 9 (10%) patients and families with actionable incidental genetic findings agreed to formal genetic counseling and screening. Conclusions and Relevance In this single center case series of children and young adults with relapsed or refractory cancer, incorporation of data from integrative clinical sequencing into clinical management was feasible, revealed potentially actionable findings in 46% of patients, and was associated with change in treatment and family genetic counseling in a s...

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Purpose:To determine the effect of intravenous (IV) low-osmolality iodinated contrast material (LOCM) on the development of post-computed tomography (CT) acute kidney injury (AKI), stratified by pre-CT estimated glomerular filtration rate (eGFR), in patients with stable renal function. Materials and Methods:Institutional review board approval was obtained and patient consent waived for this HIPAA-compliant, retrospective study. CT examinations performed over a 10-year period on unique adult inpatients with sufficient serum creatinine (SCr) data and stable renal function (difference between baseline and pre-CT SCr within 0.3 mg/dL and 50% of baseline) were identified. A 1:1 propensity score matched cohort analysis with multivariate analysis of effects was performed with post-CT AKI as the primary outcome measure (8826 nonenhanced and 8826 IV contrast agent-enhanced CT studies in 17 652 patients). Propensity matching was performed with respect to likelihood of receiving IV contrast material (19 tested covariates). Post-CT AKI with Acute Kidney Injury Network SCr criteria was the primary endpoint. A stepwise multivariate conditional logistic regression model was performed to identify the effect of IV LOCM on post-CT AKI. Results:After 1:1 propensity matching, IV LOCM had a significant effect on the development of post-CT AKI (P = .04). This risk increased with decreases in pre-CT eGFR (60 mL/ min/1.73 m 2 : odds ratio, Conclusion:IV LOCM is a nephrotoxic risk factor in patients with a stable eGFR less than 30 mL/min/1.73 m 2 , with a trend toward significance at 30-44 mL/min/1.73 m 2 . IV LOCM does not appear to be a nephrotoxic risk factor in patients with a pre-CT eGFR of 45 mL/min/1.73 m 2 or greater.q RSNA, 2013

Purpose:To determine whether intravenous low-osmolality iodinated contrast material is associated with post-computed tomography (CT) acute kidney injury (AKI). Materials and Methods:Institutional review board approval was obtained and patient consent waived for this HIPAA-compliant retrospective study. CT examinations performed over a 10-year period in adult inpatients with sufficient serum creatinine (SCr) data were identified. A one-to-one propensity-matched matched cohort analysis with multivariate analysis of effects was performed with post-CT AKI as the primary outcome measure (10 121 unenhanced and 10 121 intravenous contrast-enhanced CT examinations in 20 242 patients). Propensity matching was performed with respect to likelihood of patient receiving intravenous contrast material (36 tested covariates). The primary endpoint was post-CT AKI by using Acute Kidney Injury Network SCr criteria; the secondary endpoint was post-CT AKI by using traditional SCr criteria for contrast material-induced nephrotoxicity (CIN Results:Intravenous low-osmolality iodinated contrast material had a significant effect on the development of post-CT AKI for patients with pre-CT SCr levels of 1.6 mg/dL (141.44 mmol/L) or greater (odds ratio, 1.45; 95% confidence interval [CI]: 1.11, 1.89;P = .007). This effect strengthened as pre-CT SCr increased. Patients with stable SCr less than 1.5 mg/dL (132.60 mmol/L) were not at risk for developing CIN (P = .25, power . 95%). Both endpoints demonstrated similar results (eg, SCr 1.6 mg/dL [141.44 mmol/L] by using traditional CIN criteria: odds ratio, 1.64; 95% CI: 1.18, 2.28; P = .003). Post-CT AKI was prevalent in both the unenhanced and contrast-enhanced CT subgroups, and it increased with increases in pre-CT SCr. Many risk factors contributed to development of post-CT AKI, regardless of iodinated contrast material. Conclusion:Intravenous low-osmolality iodinated contrast material is a nephrotoxic risk factor, but not in patients with a stable SCr level less than 1.5 mg/dL. Many factors other than contrast material can affect post-CT AKI rates.q RSNA, 2013