Brain glucose metabolism in diffuse large B-cell lymphoma patients as assessed with FDG-PET: impact on outcome and chemotherapy effects.

BACKGROUND: There is a lack of data on the effect of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy on brain glucose metabolism of diffuse large B-cell lymphoma (DLBCL) patients, as measured by 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET). Moreover, the prognostic value of brain glucose metabolism measurements is currently unknown. PURPOSE: To investigate the use of FDG-PET for measurement of brain glucose metabolism in R-CHOP-treated DLBCL patients, and to assess its prognostic value. MATERIAL AND METHODS: This retrospective study included DLBCL patients who underwent FDG-PET including the brain. FDG-PET metabolic volume products (MVPs) of the entire brain, cerebral cortex, basal ganglia, and cerebellum were measured, before and after R-CHOP therapy. Whole-body total lesion glycolysis (TLG) was also measured. RESULTS: Thirty-eight patients were included, of whom 18 had an appropriate end-of-treatment FDG-PET scan. There were no significant differences (P > 0.199) between pre- and post-treatment brain glucose metabolism metrics. Low basal ganglia MVP was associated with a significantly worse progression-free survival (PFS) and overall survival (OS) (P = 0.020 and P = 0.032), and low cerebellar MVP was associated with a significantly worse OS (P = 0.034). There were non-significant very weak correlations between pretreatment brain glucose metabolism metrics and TLG. In the multivariate Cox regression, only the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) remained an independent predictor of PFS (hazard ratio 3.787, P = 0.007) and OS (hazard ratio 2.903, P = 0.0345). CONCLUSION: Brain glucose metabolism was not affected by R-CHOP therapy. Low pretreatment brain glucose metabolism was associated with a worse outcome, but did not surpass the predictive value of the NCCN-IPI.

Accuracy of whole-body MRI in the assessment of splenic involvement in lymphoma.

BACKGROUND: Accurate evaluation of the spleen is an important component of staging lymphoma, because this may have prognostic and therapeutic implications. PURPOSE: To determine the diagnostic value of whole-body magnetic resonance imaging (MRI), including diffusion-weighted imaging (whole-body MRI-DWI) in the detection of splenic involvement in lymphoma. MATERIAL AND METHODS: This IRB approved, prospective multicenter study included a total of 107 patients with newly diagnosed, histologically proven lymphoma who underwent 1.5 T whole-body MRI-DWI and FDG-PET/CT. Whole-body MRI-DWI and FDG-PET/CT were independently evaluated by a radiologist and a nuclear medicine physician, in a blinded manner. Splenic involvement at MRI was defined as splenic index > 725 cm(3) or discrete nodules. At FDG-PET/CT splenic involvement was defined as splenic uptake greater than liver uptake or hypodense nodules at contrast-enhanced CT. FDG-PET/CT augmented with follow-up imaging after treatment was used as reference standard. RESULTS: Splenic involvement was detected with FDG-PET/CT in 21 patients, all demonstrating response to treatment. The sensitivity, specificity, positive predictive value, and negative predictive value of whole-body MRI-DWI for the detection of splenic involvement were 85.7 %, 96.5 %, 85.7%, and 96.5%, respectively. Three out of six discrepancies were related to suboptimal criterion of splenic size used with whole-body MRI-DWI versus the size-independent FDG uptake. CONCLUSION: Whole-body MRI-DWI is reasonably accurate in the detection of splenic lymphomatous involvement.

Diffusion-weighted imaging changes in cerebral watershed distribution following neonatal encephalopathy are not invariably associated with an adverse outcome.

AIM: Patterns of injury in term-born infants with neonatal encephalopathy following hypoxia-ischaemia are seen earlier and are more conspicuous on diffusion-weighted magnetic resonance imaging (DW-MRI) than on conventional imaging. Although the prognostic value of DW-MRI in infants with basal ganglia and thalamic damage has been established, data in infants in whom there is extensive injury in a watershed distribution are limited. The aim of this study was to assess cognitive and functional motor outcome in a cohort of infants with changes in a predominantly watershed distribution injury on neonatal cerebral MRI, including DWI. METHOD: DW-MRI findings in infants with neonatal encephalopathy following hypoxia-ischaemia were evaluated retrospectively. Twenty-two infants in whom DWI changes exhibited a predominantly watershed distribution were enrolled in the study (10 males, 12 females; mean birthweight 3337 g, 2830-3900 g; mean gestational age 40.5 wks, 37.9-42.1 wks). Follow-up MRI data at the age of 3 months (n=15) and over the age of 18 months (n=7) were analysed. In survivors, neurodevelopmental outcome was assessed with the Griffiths Mental Development Scales at the age of at least 18 months. Amplitude-integrated electroencephalography was used to score background patterns and the occurrence of epileptiform activity. RESULTS: DW-MRI revealed abnormalities that were bilateral in all infants and symmetrical in 10. The posterior regions were more severely affected in five infants and the anterior regions in three. Watershed injury occurred in isolation in 10 out of 22 infants and was associated with involvement of the basal ganglia and thalami in the other 12, of whom seven died. Cystic evolution, seen on MRI at age 3 months, occurred in three of the 15 surviving infants. Neurodevelopmental assessment of the surviving infants was performed at a median age of 35 months (range 18-48 mo). Of the five survivors with basal ganglia and thalamic involvement, two developed cerebral palsy, one had a developmental quotient of less than 85, and two had a normal outcome. Of the 10 infants with isolated watershed injury, nine had an early normal motor and cognitive outcome. In all infants with a favourable outcome, background recovery was seen on amplitude integrated EEG within 48 hours after birth. CONCLUSION: Extensive DWI changes in a watershed distribution in term-born neonates are not invariably associated with adverse sequelae, even in the presence of cystic evolution. Associated lesions of the basal ganglia and thalami are a better predictor of adverse sequelae than the extent and severity of the watershed abnormalities seen on DW-MRI.

Agenesis of the corpus callosum and gray matter heterotopia in three patients with constitutional mismatch repair deficiency syndrome.

Constitutional mismatch repair deficiency (CMMR-D) syndrome is a rare inherited childhood cancer predisposition caused by biallelic germline mutations in one of the four mismatch repair (MMR)-genes, MLH1, MSH2, MSH6 or PMS2. Owing to a wide tumor spectrum, the lack of specific clinical features and the overlap with other cancer predisposing syndromes, diagnosis of CMMR-D is often delayed in pediatric cancer patients. Here, we report of three new CMMR-D patients all of whom developed more than one malignancy. The common finding in these three patients is agenesis of the corpus callosum (ACC). Gray matter heterotopia is present in two patients. One of the 57 previously reported CMMR-D patients with brain tumors (therefore all likely had cerebral imaging) also had ACC. With the present report the prevalence of cerebral malformations is at least 4/60 (6.6%). This number is well above the population birth prevalence of 0.09-0.36 live births with these cerebral malformations, suggesting that ACC and heterotopia are features of CMMR-D. Therefore, the presence of cerebral malformations in pediatric cancer patients should alert to the possible diagnosis of CMMR-D. ACC and gray matter heterotopia are the first congenital malformations described to occur at higher frequency in CMMR-D patients than in the general population. Further systematic evaluations of CMMR-D patients are needed to identify possible other malformations associated with this syndrome.