Midtreatment ¹8F-FDG PET/CT Scan for Early Response Assessment of SMILE Therapy in Natural Killer/T-Cell Lymphoma: A Prospective Study from a Single Center.

UNLABELLED: In a prospective study of newly diagnosed or relapsed histologically proven extranodal natural killer/T-cell lymphoma (ENKTL) patients, we aimed to determine the accuracy of midtreatment (18)F-FDG PET for response assessment using both visual and quantitative analyses. METHODS: Twenty-four patients (12 men, 12 women; median age, 50 y; age range, 16-83 y) were referred for pre-, mid- (after 2-3 cycles of SMILE [prednisolone, methotrexate, ifosfamide, L-asparaginase, etoposide] chemotherapy), and end-treatment PET/CT scans (n = 24, 24, and 17, respectively) using a standardized protocol. Sixty-five PET/CT scans were analyzed visually using the Deauville 5-point score (DS), and the lesion with the highest maximum standardized uptake value (SUV(max)) was recorded. Survival curves were obtained using Kaplan-Meier analysis and compared using the log rank test, followed by multivariate analysis using the Cox proportional hazards model to assess the independent effects of International Prognostic Index (IPI) score (0-1 vs. 2-5), stage (stage I/II vs. stage III/IV), sex, DS (1-3 vs. 4-5), SUV(max), and change in SUV(max) on overall survival (OS) and progression-free survival (PFS). The mean (±SD) follow-up period was 32 mo (±21 mo). RESULTS: For 2-y OS, the following parameters were predictive: IPI score (P = 0.047), DS at mid- and end-treatment (P < 0.001), and SUV(max) at mid- and end-treatment (P < 0.001 and 0.045, respectively). For 2-y PFS, the following parameters were predictive: sex (P = 0.006), stage (P = 0.034), IPI score (P = 0.038), DS at mid- and end-treatment (P < 0.001 and 0.001, respectively), and SUV(max) at midtreatment (P = 0.001). Multivariate analysis showed DS on mid- and end-treatment scans to be the only significant independent predictor of both OS (P = 0.004 and 0.018, respectively) and PFS (P = 0.004 and 0.014, respectively). The 2-y estimate for OS and PFS was 81% and 62%, respectively, in patients with a DS of 1-3, compared with 17% in patients with a DS of 4-5 (P < 0.001 and 0.001, respectively). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the midtreatment DS for prediction of OS and PFS were 63%, 94%, 83%, 83%, and 83%, respectively. CONCLUSION: Midtreatment PET/CT is a valuable tool for early treatment response assessment in extranodal natural killer/T-cell lymphoma patients.

Reduced transverse relaxation rate (RR2) for improved sensitivity in monitoring myocardial iron in thalassemia.

PURPOSE: To evaluate the reduced transverse relaxation rate (RR2), a new relaxation index which has been shown recently to be primarily sensitive to intracellular ferritin iron, as a means of detecting short-term changes in myocardial storage iron produced by iron-chelating therapy in transfusion-dependent thalassemia patients. MATERIALS AND METHODS: A single-breathhold multi-echo fast spin-echo sequence was implemented at 3 Tesla (T) to estimate RR2 by acquiring signal decays with interecho times of 5, 9 and 13 ms. Transfusion-dependent thalassemia patients (N = 8) were examined immediately before suspending iron-chelating therapy for 1 week (Day 0), after a 1-week suspension of chelation (Day 7), and after a 1-week resumption of chelation (Day 14). RESULTS: The mean percent changes in RR2, R2, and R2* off chelation (between Day 0 and 7) were 11.9 ± 8.9%, 5.4 ± 7.7% and -4.4 ± 25.0%; and, after resuming chelation (between Day 7 and 14), -10.6 ± 13.9%, -8.9 ± 8.0% and -8.5 ± 24.3%, respectively. Significant differences in R2 and RR2 were observed between Day 0 and 7, and between Day 7 and 14, with the greatest proportional changes in RR2. No significant differences in R2* were found. CONCLUSION: These initial results demonstrate that significant differences in RR2 are detectable after a single week of changes in iron-chelating therapy, likely as a result of superior sensitivity to soluble ferritin iron, which is in close equilibrium with the chelatable cytosolic iron pool. RR2 measurement may provide a new means of monitoring the short-term effectiveness of iron-chelating agents in patients with myocardial iron overload.

T2-weighted hyperintensities (unidentified bright objects) in children with neurofibromatosis 1: their impact on cognitive function.

The impact of magnetic resonance imaging (MRI)-identified T2-weighted hyperintensities (unidentified bright objects) on the cognitive function of children with neurofibromatosis 1 is controversial. We recruited 32 right-handed children with neurofibromatosis 1 (22 boys, 10 girls) aged between 5 and 16 years (mean age 10.2 years) for magnetic resonance imaging examinations and neuropsychologic evaluation. Statistical analysis was performed to evaluate the significance of the hyperintensities. Twenty-four children had unidentified bright objects, whereas eight children did not. Using the t-test, thalamic lesions were associated with lower intellectual function (P = .031). Left globus pallidus hyperintensities were associated with a lower attention score (P = .04), and right middle cerebellar peduncle hyperintensities were associated with a lower sensorimotor score (P = .05). The size of the thalamic lesions correlated with cognitive function (P < .05). Among the group with unidentified bright objects, there was a significant association between more involved sites on the dominant hemisphere and impaired verbal function (r = -.55; P = .005). Unidentified bright objects in the thalamus, globus pallidus, and middle cerebellar peduncles and the laterality of the lesions had an impact on cognitive function.

Magnetic resonance spectroscopy and analysis of MECP2 in Rett syndrome.

We studied the in vivo cerebral metabolites and documented the presence of MECP2 gene mutations in six Chinese females with Rett syndrome. Magnetic resonance spectroscopy spectra from the frontal lobe (gray and white matter) and deep gray nuclei (basal ganglia and thalamus) of either side were obtained. N-acetylaspartate/total creatine, choline/total creatine, and N-acetylaspartate/choline ratios were analyzed and compared with six healthy age-matched female control subjects. MECP2 gene mutation was identified in four patients; one patient had polymorphism and one patient did not have gene mutation. N-acetylaspartate/total creatine of the frontal lobe of all patients (mean: 2.63, S.D. = 0.33) was decreased compared with age-matched control subjects (mean: 3.15, S.D. = 0.27), and the difference was statistically significant (P = 0.017) with a mean difference of 0.52 (95% CI = 0.68-0.36). The difference in all other metabolite ratios in the frontal lobe and deep gray nuclei were not statistically significant compared with age-matched control subjects. Mild frontal lobe and anterior temporal lobe atrophy was present in three patients. Proton-magnetic resonance spectroscopy is a sensitive method capable of detecting the biochemical changes in Rett syndrome and is able to detect changes before conventional magnetic resonance imaging. Our preliminary results suggest that reduction in N-acetylaspartate/total creatine ratio may not be related to the MECP2 mutation.