F. Zairi

Molecular targeted therapies in advanced or metastatic chordoma patients: Facts and hypotheses

Chordomas, derived from undifferentiated notochordal remnants, represent less than 4% of bone primary tumors. Despite surgery followed by radiotherapy, local and metastatic relapses are frequent. In case of locally advanced or metastatic chordomas, medical treatment is frequently discussed. While chemotherapy is ineffective, it would appear that some molecular targeted therapies, in particular imatinib, could slow down the tumor growth in case-reports, retrospective series, and phase I or II trials. Nineteen publications, between January 1990 and September 2014, have been found describing the activity of these targeted therapies. A systematic analysis of these publications shows that the best objective response with targeted therapies was stabilization in 52 to 69% of chordomas. Given the indolent course of advanced chordoma and because of the absence of randomized trial, the level of evidence to treat chordomas with molecular therapy is low (level III), whatever the drug. Furthermore, we could not draw firm conclusion on the activity of imatinib. Other putative targets have also been described. Therefore, further clinical trials are expected, especially with these targets. Nevertheless, it seems essential, in those future studies, to consider the naturally slow course of the disease.

Evaluation of non-supervised MALDI mass spectrometry imaging combined with microproteomics for glioma grade III classification ☆

An integrated diagnosis using molecular features is recommended in the 2016 World Health Organization (WHO) classification. Our aim was to explore non-targeted molecular classification using MALDI mass spectrometry imaging (MALDI MSI) associated to microproteomics in order to classify anaplastic glioma by integration of clinical data. We used fresh-frozen tissue sections to perform MALDI MSI of proteins based on their digestion peptides after in-situ trypsin digestion of the tissue sections and matrix deposition by micro-spraying. The generated 70μm spatial resolution image datasets were further processed by individual or global segmentation in order to cluster the tissues according to their molecular protein signature. The clustering gives 3 main distinct groups. Within the tissues the ROIs (regions of interest) defined by these groups were used for microproteomics by micro-extraction of the tryptic peptides after on-tissue enzymatic digestion. More than 2500 proteins including 22 alternative proteins (AltProt) are identified by the Shotgun microproteomics. Statistical analysis on the basis of the label free quantification of the proteins shows a similar classification to the MALDI MSI segmentation into 3 groups. Functional analysis performed on each group reveals sub-networks related to neoplasia for group 1, glioma with inflammation for group 2 and neurogenesis for group 3. This demonstrates the interest on these new non-targeted large molecular data combining both MALDI MSI and microproteomics data, for tumor classification. This analysis provides new insights into grade III glioma organization. This specific information could allow a more accurate classification of the biopsies according to the prognosis and the identification of potential new targeted therapeutic options. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann.

Management of cardiac migration of a distal shunt catheter: the radiological pitfalls.

Cardiac migration is a rare complication of the ventriculoperitoneal shunt. We report a case of a late migration of the distal shunt into the pulmonary arteries. The authors underline the radiological features that suggested the presence of a knot. Preoperative planning and the assistance of a vascular surgeon were required due to the presence of a knot.

P08.15RELEVANCE OF GAMMA KNIFE RADIOSURGERY ALONE FOR THE TREATMENT OF NON-SMALL CELL LUNG CANCER BRAIN METASTASES

BACKGROUND AND PURPOSE: Stereotactic radiosurgery (SRS) followed by close follow-up is becoming a popular strategy for the management of brain metastases (BM) since cancer patients live longer and late adverse effects of whole brain radiotherapy (WBRT) are increasingly reported. The authors report their experience in consecutively treated patients with limited brain metastases from non-small cell lung cancer (NSCLC), who underwent SRS in isolation followed by a close follow-up. METHODS: This study is the retrospective analysis of prospectively collected data. We included 89 consecutive patients (80 men and 19 women; mean age 59.7 years) with a KPS score of 60 or greater at BM diagnosis, who underwent Gamma Knife SRS for 1-4 metastases, at Lille University Hospital between January 2004 and December 2010. The mean radiation dose was 23.41 Gy (range 18-26 Gy) and the mean tumor volume was 2.47 cm3 (range 0.3-6.7 cm3). After treatment, clinical and radiological (MRI) monitoring was scheduled at 2, 4, 8 and 12 months in the first year and at 4-month intervals thereafter. RESULTS: Overall survival was 70.8% at 1 year and 50% at 2 years. The actuarial local control rate was 91.5% at 1 year and 85.5% at 2 years. Ten of 89 patients experienced a local failure, which required a salvage treatment. The distant brain control rate was 79.2% at 1 year, and 67.1% at 2 years. A total of 25 patients developed new brain metastases, 10 patients were treated with a new radiosurgical procedure, 12 underwent a WBRT while 3 patients developed a leptomeningeal disease. We reported an overall complication rate of 10.1% per patient and 7.8% per treated tumor; all complications were classified grade 1 or 2. CONCLUSION: In patients with limited brain metastases from NSCLC, SRS is an effective treatment associated with high local control rate with low morbidity. When performed in isolation, close follow-up is mandatory and radiosurgery can be renewed as salvage treatment for distant brain progression, limiting the use of WBRT.