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Outcome Prediction in Patients with Glioblastoma by Using Imaging, Clinical, and Genomic Biomarkers: Focus on the Nonenhancing Component of the Tumor

Jain, Rajan; Poisson, Laila M; Gutman, David; Scarpace, Lisa; Hwang, Scott N; Holder, Chad A; Wintermark, Max; Rao, Arvind; Colen, Rivka R; Kirby, Justin; Freymann, John; Jaffe, C Carl; Mikkelsen, Tom; Flanders, Adam
Purpose To correlate patient survival with morphologic imaging features and hemodynamic parameters obtained from the nonenhancing region (NER) of glioblastoma (GBM), along with clinical and genomic markers. Materials and Methods An institutional review board waiver was obtained for this HIPAA-compliant retrospective study. Forty-five patients with GBM underwent baseline imaging with contrast material-enhanced magnetic resonance (MR) imaging and dynamic susceptibility contrast-enhanced T2*-weighted perfusion MR imaging. Molecular and clinical predictors of survival were obtained. Single and multivariable models of overall survival (OS) and progression-free survival (PFS) were explored with Kaplan-Meier estimates, Cox regression, and random survival forests. Results Worsening OS (log-rank test, P = .0103) and PFS (log-rank test, P = .0223) were associated with increasing relative cerebral blood volume of NER (rCBVNER), which was higher with deep white matter involvement (t test, P = .0482) and poor NER margin definition (t test, P = .0147). NER crossing the midline was the only morphologic feature of NER associated with poor survival (log-rank test, P = .0125). Preoperative Karnofsky performance score (KPS) and resection extent (n = 30) were clinically significant OS predictors (log-rank test, P = .0176 and P = .0038, respectively). No genomic alterations were associated with survival, except patients with high rCBVNER and wild-type epidermal growth factor receptor (EGFR) mutation had significantly poor survival (log-rank test, P = .0306; area under the receiver operating characteristic curve = 0.62). Combining resection extent with rCBVNER marginally improved prognostic ability (permutation, P = .084). Random forest models of presurgical predictors indicated rCBVNER as the top predictor; also important were KPS, age at diagnosis, and NER crossing the midline. A multivariable model containing rCBVNER, age at diagnosis, and KPS can be used to group patients with more than 1 year of difference in observed median survival (0.49-1.79 years). Conclusion Patients with high rCBVNER and NER crossing the midline and those with high rCBVNER and wild-type EGFR mutation showed poor survival. In multivariable survival models, however, rCBVNER provided unique prognostic information that went above and beyond the assessment of all NER imaging features, as well as clinical and genomic features. (c) RSNA, 2014 Online supplemental material is available for this article.
PMCID:4263660
PMID: 24646147
ISSN: 0033-8419
CID: 950912

Improving imaging utilization through practice quality improvement (maintenance of certification part IV): a review of requirements and approach to implementation

Griffith, Brent; Brown, Manuel L; Jain, Rajan
OBJECTIVE: The purposes of this article are to review the American Board of Radiology requirements for practice quality improvement and to describe our approach to improving imaging utilization while offering a guide to implementing similar projects at other institutions, emphasizing the plan-do-study-act approach. CONCLUSION: There is increased emphasis on improving quality in health care. Our institution has undertaken a multiphase practice quality improvement project addressing the appropriate utilization of screening cervical spinal CT in an emergency department.
PMID: 24660709
ISSN: 0361-803x
CID: 950922

Key determinants of short-term and long-term glioblastoma survival: A 14-year retrospective study of patients from the Hermelin Brain Tumor Center at Henry Ford Hospital

Mazaris, Paul; Hong, Xin; Altshuler, David; Schultz, Lonni; Poisson, Laila M; Jain, Rajan; Mikkelsen, Tom; Rosenblum, Mark; Kalkanis, Steven
OBJECTIVE: Glioblastoma (GBM) is a heterogeneous neoplasm with a small percentage of long-term survivors. Despite aggressive surgical resection and advances in radiotherapy and chemotherapy, the median survival for patients with GBM is 12-14 months. Factors associated with a favorable prognosis include young age, high performance status, gross resection >98%, non-eloquent tumor location and O6-methylguanine methyltransferase (MGMT) promoter methylation. We retrospectively analyzed the relationship of clinical, epidemiologic, genetic and molecular characteristics with survival in patients with GBM. METHODS: This retrospective analysis of overall survival looked at the outcomes of 480 patients diagnosed with GBM over 14 years at a single institution. Multivariate analysis was performed examining multiple patient characteristics. RESULTS: Median survival time improved from 11.8 months in patients diagnosed from 1995 to 1999 to 15.9 months in those diagnosed from 2005 to 2008. Factors associated with survivor groups were age, KPS, tumor resection, treatment received and early progression. 18 cancer-related genes were upregulated in short-term survivors and five genes were downregulated in short-term survivors. CONCLUSIONS: Epidemiologic, clinical, and molecular characteristics all contribute to GBM prognosis. Identifying factors associated with survival is important for treatment strategies as well as research for novel therapeutics and technologies. This study demonstrated improved survival for patients over time as well as significant differences among survivor groups.
PMID: 24731587
ISSN: 0303-8467
CID: 950932

Screening Cervical Spine CT in the Emergency Department, Phase 3: Increasing Effectiveness of Imaging

Griffith, Brent; Vallee, Phyllis; Krupp, Seth; Jung, Melissa; Slezak, Michelle; Nagarwala, Jumana; Loeckner, C Patrick; Schultz, Lonni R; Jain, Rajan
PURPOSE: The aim of this study was to determine the effect of a clinical education initiative on the appropriate utilization of screening cervical spine CT in the emergency department. The purpose was to assess if clinical education can produce stricter adherence to the ACR Appropriateness Criteria and improve the utilization of screening CT examinations in the emergency department. METHODS: Institutional review board approval was obtained for this HIPAA-compliant study. All adult patients presenting to a level 1 trauma center with blunt trauma prompting screening cervical spine CT were eligible. For each study, the requesting clinician completed a survey selecting all clinical indications. CT examinations were evaluated by a board-certified radiologist blinded to survey data. Results were compared with retrospective and prospective studies performed before the institution of the education initiative. RESULTS: Of the 388 cervical spine CT examinations performed, 12 (3.1%) were positive for acute cervical spine injury, compared to only 1.0% before the clinical education program (phase 2). Of the 376 examinations without injury, 13% met all 5 National Emergency X-Radiography Utilization Study criteria for nonimaging (down from 16.1% in phase 2), and 15 (4%) required no imaging when both National Emergency X-Radiography Utilization Study and abbreviated Canadian cervical spine rule criteria were applied. CONCLUSIONS: Implementation of a clinical education initiative resulted in improved adherence to ACR Appropriateness Criteria and improved clinical effectiveness of the studies by increasing fracture detection rate. Initiatives such as these could potentially influence imaging overutilization without burdening emergency department clinicians with excessive roadblocks to image ordering.
PMID: 24035123
ISSN: 1546-1440
CID: 542062

Effects of tyrosine kinase inhibitors and CXCR4 antagonist on tumor growth and angiogenesis in rat glioma model: MRI and protein analysis study

Ali, Meser M; Kumar, Sanath; Shankar, Adarsh; Varma, Nadimpalli R S; Iskander, A S M; Janic, Branislava; Chwang, Wilson B; Jain, Rajan; Babajeni-Feremi, Abbas; Borin, Thaiz F; Bagher-Ebadian, Hassan; Brown, Stephen L; Ewing, James R; Arbab, Ali S
The aim of the study was to determine the antiangiogenic efficacy of vatalanib, sunitinib, and AMD3100 in an animal model of human glioblastoma (GBM) by using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and tumor protein expression analysis. Orthotopic GBM-bearing animals were randomly assigned either to control group or vatalanib, sunitinib, and AMD3100 treatment groups. Following 2 weeks of drug treatment, tumor growth and vascular parameters were measured using DCE-MRI. Expression of different angiogenic factors in tumor extracts was measured using a membrane-based human antibody array kit. Tumor angiogenesis and invasion were determined by immunohistochemistry. DCE-MRI showed a significant increase in tumor size after vatalanib treatment. AMD3100-treated group showed a significant decrease in a number of vascular parameters determined by DCE-MRI. AMD3100 significantly decreased the expression of different angiogenic factors compared to sunitinib or vatalanib; however, there were no significant changes in vascular density among the groups. Sunitinib-treated animals showed significantly higher migration of the invasive cells, whereas in both vatalanib- and AMD3100-treated animals the invasive cell migration distance was significantly lower compared to that of control. Vatalanib and sunitinib resulted in suboptimal therapeutic effect, but AMD3100 treatment resulted in a significant reduction in tumor growth, permeability, interstitial space volume, and invasion of tumor cells in an animal model of GBM.
PMCID:3890700
PMID: 24466368
ISSN: 1936-5233
CID: 950892

OUTCOME PREDICTION IN PATIENTS WITH GLIOBLASTOMA USING IMAGING, CLINICAL AND GENOMIC BIOMARKERS: FOCUS ON THE NON-ENHANCING COMPONENT OF THE TUMOR [Meeting Abstract]

Jain, Rajan; Poisson, Laila; Scarpace, Lisa; Mikkelsen, Tom; Kirby, Justin; Freymann, John; Hwang, Scott; Gutman, David; Jaffe, Carl; Brat, Daniel; Flanders, Adam
ISI:000327456200449
ISSN: 1522-8517
CID: 950942

A RADIOGENOMIC ANALYSIS OF THE TCGA GLIOBLASTOMA DATA SET [Meeting Abstract]

Gutman, David; Holder, Chad; Colen, Rivka; Dunn, William; Jain, Rajan; Cooper, Lee; Hwang, Scott; Flanders, Adam; Brat, Daniel
ISI:000327456200566
ISSN: 1522-8517
CID: 950952

IMAGING GENOMIC CORRELATION OF INVASIVE GENOMIC COMPOSITION AND PATIENT SURVIVAL DEMONSTRATES METABOLIC DYSFUNCTION: A TCGA GLIOMA PHENOTYPE RESEARCH GROUP PROJECT [Meeting Abstract]

Colen, Rivka; Vangel, Mark; Gutman, David; Hwang, Scott; Wintermark, Max; Jain, Rajan; Jilwan-Nicolas, Manal; Chen, James; Raghavan, Prashant; Holder, Chad; Rubin, Daniel; Huang, Eric; Kirby, Justin; Freymann, John; Jaffe, Carl; Flanders, Adam; Zinn, Pascal
ISI:000327456200755
ISSN: 1522-8517
CID: 950962

GLIOMA ANGIOGENESIS, ANGIOGENIC SWITCH AND PERFUSION IMAGING [Meeting Abstract]

Jain, Rajan; Griffith, Brent; Khalil, Kamal; Scarpace, Lisa; Mikkelsen, Tom; Kalkanis, Steve; Schultz, Lonni
ISI:000327456200014
ISSN: 1522-8517
CID: 950972

Bilateral iliopsoas hematoma: Case report and literature review

Basheer, Azam; Jain, Rajan; Anton, Toomas; Rock, Jack
BACKGROUND: Clinically significant spontaneous bilateral iliopsoas hematoma is a rare complication of anticoagulation therapy. Definitive treatment of spontaneous iliopsoas hematomas is not well-established and varies between observation and surgical intervention. The intramuscular hematoma causes severe pain, muscle dysfunction, and occasionally nerve palsy with the femoral nerve most commonly affected. Most patients are neurologically normal but when a significant neurological deficit is associated with iliopsoas hematoma, optimal treatment recommendations vary. We report a case of spontaneous bilateral iliopsoas hematomas causing significant bilateral femoral nerve dysfunction. CASE DESCRIPTION: The authors present the case of a 63-year-old female who developed bilateral femoral nerve palsy due to anticoagulation bleeding complication. Magnetic resonance imaging demonstrated large bilateral intramuscular psoas hematomas causing femoral nerve compression. Surgical evacuation and decompression of the femoral nerves was performed with rapid neurological improvement. CONCLUSION: Management recommendations depend on the volume and cause of the hematoma, timing of diagnosis, and the degree of neurological impairment. A conservative approach with bed rest and correction of bleeding abnormalities to allow the hematoma to spontaneously resorb has been utilized for patients with small hematomas and little to no neurological symptoms. In contrast, more aggressive recommendations have been made for patients with large hematomas, severe motor function deficits, or hemodynamic instability.
PMCID:3815018
PMID: 24232386
ISSN: 2152-7806
CID: 651982