Diffusion-weighted imaging in patients with progressive multifocal leukoencephalopathy

Abstract Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease of the central nervous system due to JC polyoma virus infection of oligodendrocytes. PML develops in patients with impaired T-cell function as occurs in HIV, malignancy or immunosuppressive drugs users. Until now no imaging methods have been reported to correlate with clinical status. Diffusion-weighted imaging (DWI) is a robust MRI tool in investigating white matter architecture and diseases. The aim of our work was to assess diffusion abnormalities in focal white matter lesions in patients with PML and to correlate the lesion load measured with conventional MRI and DWI to clinical variables. We evaluated eight patients with a biopsy or laboratory-supported diagnosis of PML. All patients underwent MRI including conventional sequences (fluid attenuated inversion recovery-FLAIR) and DWI. Mean diffusivity (MD) maps were used to quantify diffusion on white matter lesions. Global lesion load was calculated by manually tracing lesions on FLAIR images, while total, central core and peripheral lesion loads were calculated by manually tracing lesions on DWI images. Lesion load obtained with the conventional or DWI-based methods were correlated with clinical variables such as disease duration, disease severity and survival. White matter focal lesions are characterized by a central core with low signal on DWI images and high MD (1.853 x 10(-3) mm2/s), surrounded by a rim of high signal intensity on DWI and lower MD (1.1 x 10(-3) mm2/s). The MD value of normal-appearing white matter is higher although not statistically significant (0.783 x 10(-3) mm2/s) with respect to control subjects (0.750 x 10(-3) mm2/s). Inter-rater correlations of global lesion load between FLAIR (3.96%) and DWI (3.43%) was excellent (ICC=0.87). Global lesion load on FLAIR and DWI correlates with disease duration and severity (respectively, p=0.037, p=0.0272 with Karnofsky scale and p=0.0338 with EDSS on FLAIR images; p=0.043, p=0.0296 with Karnofsky scale and p=0.0365 with EDSS on DW images). Central core lesion load on DWI correlates with disease duration and severity (respectively p=0.043, p=0.0103 with Karnofsky scale and p=0.0112 with EDSS), while peripheral lesion load does not correlate with any clinical variable. The global lesion load in PML correlates with disease duration and severity. DWI images, which can distinguish within lesions a central core from a peripheral rim, reveal that a larger central core component correlates to a worsened clinical status and longer disease duration. On the other hand the peripheral rim lesion load visualized on DWI images does not correlate with clinical variables and does not achieve obtaining further prognostic information with respect to conventional imaging

Safety and Quality-of-Life Data from an Italian Expanded Access Program of Lenvatinib for Treatment of Thyroid Cancer

Background: Lenvatinib, a multikinase inhibitor, is for progressive radioiodine-refractory-differentiated thyroid cancer (RR-DTC) patients. However, there are a lot of drug-related adverse events (AEs) that can affect the quality of life (QoL) of patients. The aims of this study were (a) to evaluate, and compared with other series, the safety of lenvatinib used in RR-DTC patients enrolled in an Italian expanded access program (EAP), and (b) to evaluate their QoL during treatment with lenvatinib. Methods: To evaluate the safety, we recorded and graded all AEs during the 6 months of lenvatinib treatment in 39 RR-DTC patients. We compared the safety profile of lenvatinib observed in our patients with that reported in the study of (E7080) levatinib in differentiated cancer of the thyroid (SELECT) and tumeurs thyroidiennes refractaires (TUTHYREF) network studies. Moreover, we evaluated the QoL in our series by using the European Organization for Research and Treatment (EORTC) Quality of Life Questionnaire-Core 30 and the pain visual analogue scale (VAS). Results: The most frequent AEs among our 39 RR-DTC patients were hypertension (80.5%), fatigue (58.3%), diarrhea (36.1%), stomatitis (33.3%), hand/foot syndrome (33.3%), and weight loss (30.5%). The most prevalent grade 3/4 AE was hypertension (25%). When compared with previous studies (i.e., SELECT and TUTHYREF), a significantly lower percentage of our patients experienced diarrhea, nausea, proteinuria, and weight loss. No statistically significant differences in the QoL of our patients evaluated before, during, and at the end of follow-up (6 months after starting the therapy) were found. However, a slight improvement of the general health and emotional and cognitive status associated with a slightly worsening of physical role and social functioning was observed during these 6 months. Pain, dyspnea, insomnia, and constipation moved toward better values, while fatigue, nausea and vomiting, appetite loss, and diarrhea worsened. By comparing the pain VAS, an overall reduction of the level of pain was found. Conclusions: The safety profile of the drug was similar to that already reported with some differences in the prevalence and severity of the AEs. Regarding the QoL, the EAP showed a trend of improvement of the global health status and a reduction of symptoms correlated to the disease. The clinical impact of fatigue, anorexia/weight loss and stomatitis, mainly due to the drug itself, continues to represent the major issue in the management of these patients