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1.
AJR Am J Roentgenol ; 212(1): 166-172, 2019 01.
Article in English | MEDLINE | ID: mdl-30403530

ABSTRACT

OBJECTIVE: The objective of our study was to compare anterior inferior iliac spine (AIIS) morphology in symptomatic hips with femoroacetabular impingement (FAI) and in asymptomatic hips, determine the prevalence of impingement morphology in patients with a radiographic "crossover" sign, and identify potential risk factors for having impingement morphology. MATERIALS AND METHODS: For this retrospective study, we identified consecutive symptomatic hips with FAI (n = 54) and asymptomatic hips (n = 35) in patients who underwent CT from 2015 to 2017. Two radiologists blindly and independently evaluated 3D CT images of each hip and graded the AIIS morphology according to the Hetsroni classification scheme. The prevalence of AIIS morphology types was calculated. Associations of AIIS morphology types with symptoms and the crossover sign were evaluated with a chi-square test. A multivariable logistic regression determined risk factors for abnormal AIIS morphology (i.e., type 2 or 3). RESULTS: There was no difference in the prevalence of AIIS morphology types for symptomatic hips with FAI versus asymptomatic hips (p = 0.44) or for hips with a positive versus those with a negative crossover sign (p = 0.21). There was moderate interobserver agreement (κ = 0.44) and good-to-excellent intraobserver agreement (κ = 0.67 and 0.90) for grading AIIS morphology. Age, sex, femoral version, acetabular version, alpha angle, lateral center edge angle, and the crossover sign were not significant risk factors for abnormal AIIS morphology in patients with FAI (p = 0.11-0.79). CONCLUSION: There is no difference in AIIS morphology between symptomatic hips with FAI versus asymptomatic hips or between hips with and those without the radiographic crossover sign. Age, sex, and other FAI parameters are not risk factors for developing AIIS impingement morphology.


Subject(s)
Femoracetabular Impingement/diagnostic imaging , Ilium/diagnostic imaging , Tomography, X-Ray Computed/methods , Adult , Asymptomatic Diseases , Female , Humans , Imaging, Three-Dimensional , Male , Reproducibility of Results , Retrospective Studies , Risk Factors
2.
Neuro Oncol ; 16(10): 1408-16, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24803676

ABSTRACT

BACKGROUND: Activation of the RAS-RAF-MEK-ERK signaling pathway is thought to be the key driver of pediatric low-grade astrocytoma (PLGA) growth. Sorafenib is a multikinase inhibitor targeting BRAF, VEGFR, PDGFR, and c-kit. This multicenter phase II study was conducted to determine the response rate to sorafenib in patients with recurrent or progressive PLGA. METHODS: Key eligibility criteria included age ≥ 2 years, progressive PLGA evaluable on MRI, and at least one prior chemotherapy treatment. Sorafenib was administered twice daily at 200 mg/m(2)/dose (maximum of 400 mg/dose) in continuous 28-day cycles. MRI, including 3-dimensional volumetric tumor analysis, was performed every 12 weeks. BRAF molecular testing was performed on tumor tissue when available. RESULTS: Eleven patients, including 3 with neurofibromatosis type 1 (NF1), were evaluable for response; 5 tested positive for BRAF duplication. Nine patients (82%) came off trial due to radiological tumor progression after 2 or 3 cycles, including 3 patients with confirmed BRAF duplication. Median time to progression was 2.8 months (95% CI, 2.1-31.0 months). Enrollment was terminated early due to this rapid and unexpectedly high progression rate. Tumor tissue obtained from 4 patients after termination of the study showed viable pilocytic or pilomyxoid astrocytoma. CONCLUSIONS: Sorafenib produced unexpected and unprecedented acceleration of tumor growth in children with PLGA, irrespective of NF1 or tumor BRAF status. In vitro studies with sorafenib indicate that this effect is likely related to paradoxical ERK activation. Close monitoring for early tumor progression should be included in trials of novel agents that modulate signal transduction.


Subject(s)
Antineoplastic Agents/therapeutic use , Astrocytoma/drug therapy , Brain Neoplasms/drug therapy , Niacinamide/analogs & derivatives , Phenylurea Compounds/therapeutic use , Adolescent , Animals , Astrocytoma/mortality , Astrocytoma/pathology , Brain Neoplasms/mortality , Brain Neoplasms/pathology , Child, Preschool , Female , Humans , Kaplan-Meier Estimate , MAP Kinase Signaling System/drug effects , Magnetic Resonance Imaging , Male , Mice , NIH 3T3 Cells , Niacinamide/administration & dosage , Niacinamide/therapeutic use , Phenylurea Compounds/administration & dosage , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/therapeutic use , Sorafenib , Treatment Outcome
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