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Exome and Genome Sequencing and Parallels in Radiology: Searching for Patient-Centered Management of Incidental and Secondary Findings

Kang, Stella K; Spector-Bagdady, Kayte; Caplan, Arthur L; Braithwaite, R Scott
Incidental and secondary findings have become an important by-product of diagnostic testing, and their ramifications affect clinical care, research, and policy. Given parallels in the reporting and management of such findings on diagnostic imaging, radiologists may draw from ongoing discussions in medical genetics to rethink more patient-centered approaches to analogous clinical, ethical, and medicolegal dilemmas. Low-risk incidental findings in particular may be drivers of unnecessary testing, invasive procedures, and overtreatment, with associated financial, psychological, and clinical consequences. As radiologists act in patients' best interests by strengthening standardized guidelines on how each finding merits further diagnostic testing or treatment, perhaps the greatest challenge for producing such guidelines is for low-risk incidental findings, for which adverse consequences are unlikely but associated with substantial uncertainty because of the lack of strong evidence on which to base the recommendations. More uniform recommendations for managing low-risk radiologic incidental findings should therefore aim to provide reasonable options that apply across a spectrum of patient preferences. These will require evaluation through research and will ultimately influence the quality of care. Specific areas for exploration may include (1) better gauging of patient attitudes and preferences regarding low-risk incidental findings, (2) using patient preferences to inform more uniform recommendations for low-risk findings that apply across a spectrum of preferences and help guide shared decision making, and (3) when patients endorse a strong preference not to discover low-risk incidental findings, how it might be possible for professional standards to curtail their generation in specific circumstances.
PMID: 27595197
ISSN: 1558-349x
CID: 2238492

Tumor Anatomy Scoring and Renal Function for Nephron-Sparing Treatment Selection in Patients With Small Renal Masses: A Microsimulation-Based Decision Analysis

Kang, Stella K; Huang, William C; Skolnik, Edward Y; Gervais, Debra A; Braithwaite, R Scott; Pandharipande, Pari V
OBJECTIVE: The purpose of this article is to compare the effectiveness of a treatment algorithm for small renal tumors incorporating the nephrometry score, a renal tumor anatomy scoring system developed by urologists, with the current standard of uniformly recommended partial nephrectomy in patients with mild-to-moderate chronic kidney disease (CKD). MATERIALS AND METHODS: We developed a state-transition microsimulation model to project life expectancy (LE) in hypothetic patients with baseline mild or moderate CKD undergoing treatment of small renal masses. Our model incorporated the nephrometry score, which is predictive of postsurgical renal function loss. The two tested strategies were uniform treatment with partial nephrectomy and selective treatment based on nephrometry score and CKD stage, including percutaneous ablation for CKD stages 2 or 3a and intermediate-to-high nephrometry score or stage 3b CKD and any nephrometry score; otherwise, partial nephrectomy was assumed for other CKD stages and nephrometry scores. The model accounted for benign and malignant lesions, renal function decline, recurrence, and metastatic disease rates specific to each treatment, mortality by CKD stage, and comorbidities. Sensitivity analysis tested the stability of results when varying key parameters. RESULTS: Selective treatment with partial nephrectomy resulted in an average LE benefit of 0.48 year (95% interpercentile range, 0.42-0.54 year) in 65-year-old men and 0.37 year (95% interpercentile range, 0.30-0.43 year) in 65-year-old women relative to nondiscriminatory surgery, due to worsening CKD and cardiovascular mortality associated with partial nephrectomy. Model results were most sensitive to the rate of renal function decline and CKD-related mortality. CONCLUSION: Nephron-sparing treatment selection for small renal masses based on nephrometry score may improve LE in patients with mild or moderate CKD.
PMID: 27305103
ISSN: 1546-3141
CID: 2145162

Designing Radiology Outcomes Studies-Essential Principles

Kang, Stella K; Mushlin, Alvin I
Health outcomes research is essential to align radiology with current standards of high-value patient care, through the assessment of end results of diagnostic tests, interventions, or policy on patient health. To bridge studies of diagnostic test accuracy and health outcomes research, key considerations include: (1) how to determine when a diagnostic test merits evaluation of impact on outcomes, (2) when study of intermediate/surrogate outcomes can be useful, (3) how to consider the possible harms as well as potential benefits of a test, and (4) how to integrate evidence of an imaging test's efficacy/effectiveness with clinical data to assess outcomes. Due to challenges in conducting studies of long-term outcomes consequent to imaging use, intermediate health outcomes may capture a test's impact on successful diagnosis and therapy, and can provide readily measurable, incremental insights into the role of imaging in health-care delivery and efficiency. In an era marked by recognition of quality and value of care, outcomes research will provide essential evidence to inform radiologists' guidance of imaging use toward improved patient care, creation of clinical guidelines, and policy decisions.
PMID: 27066756
ISSN: 1878-4046
CID: 2078292

ACR Appropriateness Criteria(R) Acute Pelvic Pain in the Reproductive Age Group

Bhosale, Priyadarshani R; Javitt, Marcia C; Atri, Mostafa; Harris, Robert D; Kang, Stella K; Meyer, Benjamin J; Pandharipande, Pari V; Reinhold, Caroline; Salazar, Gloria M; Shipp, Thomas D; Simpson, Lynn; Sussman, Betsy L; Uyeda, Jennifer; Wall, Darci J; Zelop, Carolyn M; Glanc, Phyllis
Acute pelvic pain in premenopausal women frequently poses a diagnostic dilemma. These patients may exhibit nonspecific signs and symptoms such as nausea, vomiting and leukocytosis. The cause of pelvic pain includes a myriad of diagnostic possibilities such as obstetric, gynecologic, urologic, gastrointestinal, and vascular etiologies. The choice of the imaging modality is usually determined by a suspected clinical differential diagnosis. Thus the patient should undergo careful evaluation and the suspected differential diagnosis should be narrowed before an optimal imaging modality is chosen. Transvaginal and transabdominal pelvic sonography is the modality of choice, to assess for pelvic pain, when an obstetric or gynecologic etiology is suspected and computed tomography is often more useful when gastrointestinal or genitourinary pathology is thought to be more likely. Magnetic resonance imaging, when available in the acute setting, is favored over computed tomography for assessing pregnant patients for nongynecologic etiologies owing to its lack of ionizing radiation.The American College of Radiology Appropriateness Criteria(R) are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
PMID: 26588104
ISSN: 1536-0253
CID: 2040502

Efficacy and Safety of Selective Vascular Endothelial Growth Factor Receptor Inhibitors Compared with Sorafenib for Metastatic Renal Cell Carcinoma: a Meta-analysis of Randomised Controlled Trials

Kang, S K; Volodarskiy, A; Ohmann, E L; Balar, A V; Bangalore, S
AIMS: Selective vascular endothelial growth factor receptor (VEGFR) inhibitors have the potential for greater potency and less off-target toxicity compared with multikinase tyrosine kinase inhibitors in the treatment of metastatic renal cell carcinoma. We carried out a meta-analysis to determine quantitatively the differences in comparative efficacy and tolerability between these newer, selective agents and the multikinase inhibitors. MATERIALS AND METHODS: We searched four electronic databases for published randomised controlled trials comparing selective VEGFR inhibitors with multikinase tyrosine kinase inhibitors for metastatic renal cell carcinoma and carried out a meta-analysis. Outcomes of interest were progression-free survival, objective response rate (ORR), overall survival, discontinuation of treatment due to adverse events (DAE) and occurrence of specific toxicities. RESULTS: Four trials involving the selective VEGFR inhibitors axitinib, tivozanib and dovitinib were analysed, all using sorafenib as the comparator. There was a 22% reduction in risk of disease progression with selective VEGFR inhibitors (relative risk 0.78; 95% confidence interval 0.69-0.87) compared with sorafenib, the tyrosine kinase inhibitor in all trials, and similar whether the agents were first-line or subsequent therapy. ORR was improved with selective VEGFR inhibitors, with 91% increased odds over sorafenib (odds ratio 1.91; 95% confidence interval 1.35-2.69). Overall survival was similar between groups (relative risk 1.03; 95% confidence interval 0.88-1.21) and DAE differed only in sensitivity analysis with exclusion of dovitinib (odds ratio 0.62; 95% confidence interval 0.41-0.94). Frequencies of the most common toxicities were overall similar, but differences included more frequent grade 3 or 4 fatigue and less frequent palmar-plantar erythrodysesthesia with selective VEGFR therapy. CONCLUSION: Although selective VEGFR inhibitors are associated with similar overall survival as multikinase inhibitor sorafenib, they show significant improvement in progression-free survival, regardless of first-line or later use, and ORR compared with sorafenib. Tolerability due to toxicities is similar.
PMID: 26723100
ISSN: 1433-2981
CID: 1895342

Response [Letter]

Rosenkrantz, Andrew B; Kang, Stella K; Kierans, Andrea S
PMID: 27556126
ISSN: 1527-1315
CID: 3098402

The Diagnostic Performance of Dynamic Contrast-enhanced MR Imaging for Detection of Small Hepatocellular Carcinoma Measuring Up to 2 cm: A Meta-Analysis

Kierans, Andrea S; Kang, Stella K; Rosenkrantz, Andrew B
Purpose To determine the performance of dynamic contrast material-enhanced magnetic resonance (MR) imaging in the diagnosis of small (/= .122). At pairwise meta-regression analysis with either study origin from Asia or performance of hepatobiliary phase imaging, only gadoxetate disodium contrast agent showed significant independent association with higher sensitivity (P = .002-.007). Conclusion Results of this meta-analysis suggest that dynamic contrast-enhanced MR imaging has moderate sensitivity and excellent specificity in the detection of HCC up to 2 cm. Gadoxetate disodium contrast agent showed the strongest association with increased sensitivity. (c) RSNA, 2015 Online supplemental material is available for this article.
PMID: 26098460
ISSN: 1527-1315
CID: 1640832

A Roadmap for Personalized Care in Radiology

Kang, Stella K; Fagerlin, Angela; Braithwaite, R Scott
PMID: 26599924
ISSN: 1527-1315
CID: 1856852

Acute Appendicitis: Use of Clinical and CT Findings for Modeling Hospital Resource Utilization

Viradia, Neal K; Gaing, Byron; Kang, Stella K; Rosenkrantz, Andrew B
OBJECTIVE: The purpose of this study was to retrospectively investigate associations between baseline CT findings in suspected acute appendicitis and subsequent hospital resource utilization. MATERIALS AND METHODS: One hundred thirty-eight patients (76 male and 62 female patients; mean [+/- SD] age, 40 +/- 21 years) who were admitted for suspected acute appendicitis and underwent baseline CT were included. A single radiologist reviewed CT examinations for appendiceal-related findings. Linear and logistic regressions were performed to identify independent predictors of payer and hospital resource utilization. Combined performance of identified independent factors for predicting outcomes was determined. RESULTS: Greater age, lower Charlson comorbidity index (CCI), lesser appendiceal wall thickness, absence of loculated fluid collection, and absence of periappendiceal fluid were significant independent predictors of inpatient surgery (joint sensitivity, 92.7%; specificity, 65.8%). Smaller appendiceal diameter, absence of periappendiceal fluid, and laparoscopic surgery were significant independent predictors of same-day discharge (joint sensitivity, 79.1%; specificity, 64.2%). Greater CCI, greater wall thickness, and presence of periappendiceal fluid were significant independent predictors of repeat abdominopelvic CT (joint sensitivity, 82.5%; specificity, 68.1%). Presence of an appendicolith was the only significant predictor of repeat emergency department visit within 30 days (sensitivity, 61.2%; specificity, 68.8%) and the only significant predictor of repeat inpatient admission within 30 days (sensitivity, 63.6%; specificity, 68.5%). Greater appendiceal diameter and presence of free air were significant predictors of inpatient costs, and predicted costs were as follows: $8047 + ($745 x appendiceal diameter) if free air was absent; and $-39,261 + ($4426 x appendiceal diameter) if free air was present. However, costs were poorly predicted when greater than $45,000. Sex, WBC count, and payer category were not independent predictors, relative to CT findings, of any outcome. CONCLUSION: Admission CT findings serve as independent predictors of hospital resource utilization in suspected acute appendicitis.
PMID: 26295663
ISSN: 1546-3141
CID: 1732542

DWI for Renal Mass Characterization: Systematic Review and Meta-Analysis of Diagnostic Test Performance

Kang, Stella K; Zhang, Angela; Pandharipande, Pari V; Chandarana, Hersh; Braithwaite, R Scott; Littenberg, Benjamin
OBJECTIVE: The objective of our study was to perform a systematic review and meta-analysis of the test performance of DWI in the characterization of renal masses. MATERIALS AND METHODS: We performed searches of three electronic databases for studies on renal mass characterization using DWI. Methodologic quality was assessed for each study. We quantitatively analyzed test performance for three clinical problems: first, benign versus malignant lesions; second, clear cell renal cell carcinoma (RCC) versus other malignancies; and, third, high-versus low-grade clear cell RCCs. We summarized performance as a single pair of sensitivity and specificity values or a summary ROC curve. RESULTS: The studies in the literature were limited in both quantity and quality. For classification of benign versus malignant lesions, four studies with 279 lesions yielded a single summary estimate of 86% sensitivity and 78% specificity. For differentiation of clear cell RCC from other malignancies, five studies showed marked heterogeneity not conducive to meta-analysis. For differentiation of high-from low-grade clear cell RCCs, three studies with 110 lesions showed a threshold effect appropriate for summary ROC construction: The AUC was 0.83. CONCLUSION: Evidence suggests moderate accuracy of DWI for the prediction of malignancy and high-grade clear cell cancers, whereas DWI performance for ascertaining clear cell histologic grade remains unclear. To develop DWI as a noninvasive approach for the evaluation of solid renal masses, prospective studies with standardized test parameters are needed to better establish DWI performance and its impact on patient outcomes.
PMID: 26204281
ISSN: 1546-3141
CID: 1684042