Lack of clinical efficacy of imatinib in metastatic melanoma

This two-centre phase-II trial aimed at investigating the efficacy of imatinib in metastasised melanoma patients in correlation to the tumour expression profile of the imatinib targets c-kit and platelet-derived growth factor receptor (PDGF-R). The primary study end point was objective response according to RECIST, secondary end points were safety, overall and progression-free survival. In all, 18 patients with treatment-refractory advanced melanoma received imatinib 800 mg day−1. In 16 evaluable patients no objective responses could be observed. The median overall survival was 3.9 months, the median time to progression was 1.9 months. Tumour biopsy specimens were obtained from 12 patients prior to imatinib therapy and analysed for c-kit, PDGF-Rα and -Rβ expression by immunohistochemistry. In four cases, cell lines established from these tumour specimens were tested for the antiproliferative effects of imatinib and for functional mutations of genes encoding the imatinib target molecules. The tumour specimens stained positive for CD117/c-kit in nine out of 12 cases (75%), for PDGF-Rα in seven out of 12 cases (58%) and for PDGF-Rβ in eight out of 12 cases (67%). The melanoma cell lines showed a heterogenous expression of the imatinib target molecules without functional mutations in the corresponding amino-acid sequences. In vitro imatinib treatment of the cell lines showed no antiproliferative effect. In conclusion, this study did not reveal an efficacy of imatinib in advanced metastatic melanoma, regardless of the expression pattern of the imatinib target molecules c-kit and PDGF-R

Radiotherapeutic alternatives for previously irradiated recurrent gliomas

Re-irradiation for recurrent gliomas has been discussed controversially in the past. This was mainly due to only marginal palliation while being associated with a high risk for side effects using conventional radiotherapy

Development of a new assessment tool for cervical myelopathy using hand-tracking sensor: Part 1: validity and reliability

Purpose To assess the reliability and validity of a hand motion sensor, Leap Motion Controller (LMC), in the 15-s hand grip-and-release test, as compared against human inspection of an external digital camera recording. Methods Fifty healthy participants were asked to fully grip-and-release their dominant hand as rapidly as possible for two trials with a 10-min rest in-between, while wearing a non-metal wrist splint. Each test lasted for 15 s, and a digital camera was used to film the anterolateral side of the hand on the first test. Three assessors counted the frequency of grip-and-release (G-R) cycles independently and in a blinded fashion. The average mean of the three was compared with that measured by LMC using the Bland–Altman method. Test–retest reliability was examined by comparing the two 15-s tests. Results The mean number of G-R cycles recorded was: 47.8 ± 6.4 (test 1, video observer); 47.7 ± 6.5 (test 1, LMC); and 50.2 ± 6.5 (test 2, LMC). Bland–Altman indicated good agreement, with a low bias (0.15 cycles) and narrow limits of agreement. The ICC showed high inter-rater agreement and the coefficient of repeatability for the number of cycles was ±5.393, with a mean bias of 3.63. Conclusions LMC appears to be valid and reliable in the 15-s grip-and-release test. This serves as a first step towards the development of an objective myelopathy assessment device and platform for the assessment of neuromotor hand function in general. Further assessment in a clinical setting and to gauge healthy benchmark values is warranted

Differences in the preferential location and invasiveness of diffuse low-grade gliomas and their impact on outcome

BACKGROUND: Low-grade gliomas (LGGs) are primary diffuse slow-growing brain tumors derived from glial cells. The management of these tumors is dependent on their location, which often harbors eloquent areas. We retrospectively recorded the location of diffuse gliomas to identify whether specific differences exist between the histological types. METHODS: We analyzed 102 patients with previous histological diagnosis of WHO-II astrocytomas (62) and WHO-II oligodendrogliomas (40) according to WHO-2016 classification. MRI sequences (T2-FLAIR) were used for tumor volume segmentation and to create a frequency map of their locations within the Montreal Neurological Institute (MNI) space. The Brain-Grid (BG) system (standardized radiological tool of intersected lines according to anatomical landmarks) was created and merged with a tractography atlas for infiltration analysis. RESULTS: Astrocytomas frequently infiltrated association and projection white matter pathways within fronto-temporo-insular regions on the left side. Oligodendrogliomas infiltrated larger white matter networks (association-commissural-projection) of the frontal lobe bilaterally. A critical number of infiltrated BG voxels (7 for astrocytomas, 10 for oligodendrogliomas) significantly predicted shorter overall survival (OS) in both groups. Bilateral tumor extension in astrocytomas and preoperative tumor volume in oligodendrogliomas were independent prognostic factors for shorter OS. CONCLUSIONS: Astrocytomas and oligodendrogliomas differ in preferential location, and this has an impact on the type and the extent of white matter involvement. The number of BG voxels infiltrated reflected different tumor invasiveness and its impact on OS in both groups. All this new information may be valuable in neurosurgical oncology to classify and plan treatment for patients with diffuse gliomas