Sharon Hain

Pediatric and Adolescent Lymphoma: Comparison of Whole-Body STIR Half-Fourier RARE MR Imaging with an Enhanced PET/CT Reference for Initial Staging

PURPOSE To compare the diagnostic performance of rapid whole-body anatomic magnetic resonance (MR) staging of pediatric and adolescent lymphoma to an enhanced positron emission tomographic (PET)/computed tomographic (CT) reference standard. MATERIALS AND METHODS Ethical permission was given by the University College London Hospital ethics committee, and informed written consent was obtained from all participants and/or parents or guardians. Thirty-one subjects (age range, 7.3-18.0 years; 18 male, 11 female) with histologically proved lymphoma were prospectively recruited. Pretreatment staging was performed with whole-body short inversion time inversion-recovery (STIR) half-Fourier rapid acquisition with relaxation enhancement (RARE) MR imaging, fluorine 18 fluorodeoxyglucose PET/CT, and contrast agent-enhanced chest CT. Twenty-six subjects had posttreatment PET/CT and compromised our final cohort. Eleven nodal and 11 extranodal sites per patient were assessed on MR imaging by two radiologists in consensus, with a nodal short-axis threshold of >1 cm and predefined extranodal positivity criteria. The same sites were independantly evaluated by two nuclear medicine physicians on PET/CT images. Disease positivity was defined as a maximum standardized uptake value >2.5 or nodal size >1 cm. An unblinded expert panel reevaluated the imaging findings, removing perceptual errors, and derived an enhanced PET/CT reference standard (taking into account chest CT and 3-month follow-up imaging) against which the reported and intrinsic performance of MR imaging was assessed by using the kappa statistic. RESULTS There was very good agreement between MR imaging and the enhanced PET/CT reference standard for nodal and extranodal staging (kappa = 0.96 and 0.86, respectively) which improved following elimination of perceptual errors (kappa = 0.97 and 0.91, respectively). The sensitivity and specificity of MR imaging (following removal of perceptual error) were 98% and 99%, respectively, for nodal disease and 91% and 99%, respectively, for extranodal disease. CONCLUSION Whole-body STIR half-Fourier RARE MR imaging of pediatric and adolescent lymphoma can accurately depict nodal and extranodal disease and may provide an alternative nonionizing imaging method for anatomic disease assessment at initial staging.

Target-driven exploratory study of imatinib mesylate in children with solid malignancies by the Innovative Therapies for Children with Cancer (ITCC) European Consortium

AIM To explore imatinib efficacy and pharmacokinetics in children and adolescents with refractory/relapsing solid tumours, expressing imatinib-sensitive receptor tyrosine kinases. METHODS Exploratory study on imatinib in tumours expressing, at least, one of the receptors KIT or platelet-derived growth factor receptor (PDGFR). Standard radiological response evaluation, pharmacokinetics, gene mutations and positron emission tomography imaging were assessed. RESULTS Thirty-six patients (median age: 13.7 years) with brain (12), mesenchymal/bone (14) or other solid tumours, received imatinib 340 mg/m(2)/d over a total of 255 months. Fifteen tumours expressed KIT in 30% cells, 19 expressed PDGFRA and 25 expressed PDGFRB. Twenty patients experienced grades 1-2 treatment-related toxicities. Ten patients achieved stable disease; one chordoma had metabolic response. Pharmacokinetic data showed high inter-patient variability (variation coefficient: 44% and 53% for plasma imatinib and CGP 74588 AUCs, respectively). CONCLUSIONS Imatinib was tolerated well, but failed to show efficacy according to standard criteria in paediatric malignancies expressing KIT or PDGFR.

Phase II study of gemcitabine combined with oxaliplatin in relapsed or refractory paediatric solid malignancies: An innovative therapy for children with Cancer European Consortium Study

AIM To assess objective response rates after 4 cycles of gemcitabine in combination with oxaliplatin in children and adolescents with relapsed or refractory solid tumours. METHODS This multicentre, non-randomised Phase II study included five strata: neuroblastoma, osteosarcoma, medulloblastoma and other CNS tumours strata with two-stage Simon designs and a miscellaneous, extra-cranial solid tumour stratum with descriptive design. Eligibility criteria included: age 6 months to 21 years; measurable, relapsed or refractory solid malignancy; no more than one previous salvage therapy. Gemcitabine was administered intravenously at 1000 mg/m(2) over 100 min followed by oxaliplatin at 100mg/m(2) over 120 min on Day 1 of a 14-d cycle. Tumour response was assessed every 4 cycles according to WHO criteria. RESULTS Ninety-three out of 95 patients enrolled in 25 centres received treatment: 12 neuroblastoma; 12 osteosarcoma; 14 medulloblastoma; 13 other CNS tumours and 42 miscellaneous non-CNS solid tumours. Median age was 11.7 years (range, 1.3-20.8 years). Tumour control (CR+PR+SD) at 4 cycles was obtained in 30/93 evaluable patients (32.3%; 95% confidence interval (CI), 22.9-42.7%), including four PR: 1/12 patients with osteosarcoma, 1/12 with medulloblastoma, 1/12 with rhabdomyosarcoma and 1/4 with other sarcoma. Five out of 12 eligible patients with neuroblastoma experienced stable disease. During a total of 481 treatment cycles (median 4, range 1-24 per patient), the most common treatment-related toxicities were haematologic (leukopenia, neutropenia, thrombocytopenia) and neurological (dysesthesia, paresthesia). CONCLUDING STATEMENT The gemcitabine-oxaliplatin combination administered in a bi-weekly schedule has acceptable safety profile with limited activity in children with relapsed or refractory solid tumours.

Quantitative diffusion weighted MRI: A functional biomarker of nodal disease in Hodgkin lymphoma?

PURPOSE This study explores the relationship between MRI Apparent Diffusion Coefficient (ADC) and PET Standardized Uptake Value (SUV) measurements in pediatric Hodgkin lymphoma. METHODS Sixteen patients (mean age 15.4 yrs, 8 male) with proven Hodgkin lymphoma were recruited and staged using PET-CT, anatomical MRI and additional 1.5T diffusion weighted imaging (DWI) prior to and following chemotherapy. Pre-treatment lymph nodes and anatomically paired post-treatment residual tissue located on MRI were matched to the corresponding PET-CT. Region of interest (ROI) analysis was used to extract quantitative measurements. Mean ADC (ADC(mean)) and maximum SUV (SUV(max)) were recorded and correlation assessed using Spearman statistics. RESULTS Fifty-three ROIs were sampled. Pre- and post-treatment ADC(mean) ranged from 0.77 × 10(−3) to 1.79 × 10(−3) (median 1.15 × 10(−3) mm(2)s(−1)) and 1.08 × 10(−3) to 3.18 ×10(−3) (median 1.88 × 10(−3) mm(2)s(−1)), and SUV(max) from 2.60 to 25.4 (median 8.85 mg/ml) and 1.00 to 3.50 mg/ml (median 1.90 mg/ml). Median post-treatment ADC(mean) was higher, and median SUV(max) lower than pretreatment values (p < 0.0001). There was an inverse correlation between pre-treatment ADC(mean) and SUV(max) (p = 0.005) and between fractional change ([post-treatment – pre-treatment]/pre-treatment)in ADC(mean) and SUV(max) (p =0.002). CONCLUSION Our results confirm a strong reciprocal relationship between nodal ADC(mean) and SUV(max) in Hodgkin lymphoma;supporting the potential application of quantitative DWI as a functional biomarker of disease.

Dynamic contrast-enhanced MRI improves accuracy for detecting focal splenic involvement in children and adolescents with Hodgkin disease.

BackgroundAccurate assessment of splenic disease is important for staging Hodgkin lymphoma.ObjectiveThe purpose of this study was to assess T2-weighted imaging with and without dynamic contrast-enhanced (DCE) MRI for evaluation of splenic Hodgkin disease.Materials and methodsThirty-one children with Hodgkin lymphoma underwent whole-body T2-weighted MRI with supplementary DCE splenic imaging, and whole-body PET-CT before and following chemotherapy. Two experienced nuclear medicine physicians derived a PET-CT reference standard for splenic disease, augmented by follow-up imaging. Unaware of the PET-CT, two experienced radiologists independently evaluated MRI exercising a locked sequential read paradigm (T2-weighted then DCE review) and recorded the presence/absence of splenic disease at each stage. Performance of each radiologist was determined prior to and following review of DCE-MRI. Incorrect MRI findings were ascribed to reader (lesion present on MRI but missed by reader) or technical (lesion not present on MRI) error.ResultsSeven children had splenic disease. Sensitivity/specificity of both radiologists for the detection of splenic involvement using T2-weighted images alone was 57%/100% and increased to 100%/100% with DCE-MRI. There were three instances of technical error on T2-weighted imaging; all lesions were visible on DCE-MRI.ConclusionsT2-weighted imaging when complemented by DCE-MRI imaging may improve evaluation of Hodgkin disease splenic involvement.