Non-randomized therapy trial to determine the safety and efficacy of heavy ion radiotherapy in patients with non-resectable osteosarcoma

<p>Abstract</p> <p>Background</p> <p>Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. For effective treatment, local control of the tumor is absolutely critical, because the chances of long term survival are <10% and might effectively approach zero if a complete surgical resection of the tumor is not possible. Up to date there is no curative treatment protocol for patients with non-resectable osteosarcomas, who are excluded from current osteosarcoma trials, e.g. <it>EURAMOS1</it>. Local photon radiotherapy has previously been used in small series and in an uncontrolled, highly individualized fashion, which, however, documented that high dose radiotherapy can, in principle, be used to achieve local control. Generally the radiation dose that is necessary for a curative approach can hardly be achieved with conventional photon radiotherapy in patients with non-resectable tumors that are usually located near radiosensitive critical organs such as the brain, the spine or the pelvis. In these cases particle Radiotherapy (proton therapy (PT)/heavy ion therapy (HIT) may offer a promising new alternative. Moreover, compared with photons, heavy ion beams provide a higher physical selectivity because of their finite depth coverage in tissue. They achieve a higher relative biological effectiveness. Phase I/II dose escalation studies of HIT in adults with non-resectable bone and soft tissue sarcomas have already shown favorable results.</p> <p>Methods/Design</p> <p>This is a monocenter, single-arm study for patients ≥ 6 years of age with non-resectable osteosarcoma. Desired target dose is 60-66 Cobalt Gray Equivalent (Gy E) with 45 Gy PT (proton therapy) and a carbon ion boost of 15-21 GyE. Weekly fractionation of 5-6 × 3 Gy E is used. PT/HIT will be administered exclusively at the Ion Radiotherapy Center in Heidelberg. Furthermore, FDG-PET imaging characteristics of non-resectable osteosarcoma before and after PT/HIT will be investigated prospectively. Systemic disease before and after PT/HIT is targeted by standard chemotherapy protocols and is not part of this trial.</p> <p>Discussion</p> <p>The primary objectives of this trial are the determination of feasibility and toxicity of HIT. Secondary objectives are tumor response, disease free survival and overall survival. The aim is to improve outcome for patients with non-resectable osteosarcoma.</p> <p>Trail Registration</p> <p>Registration number (ClinicalTrials.gov): NCT01005043</p

Prognostic significance of IDH-1 and MGMT in patients with glioblastoma: One step forward, and one step back?

A group of 160 patients with primary glioblastoma treated with radiotherapy and temozolomide was analyzed for the impact of O6-methly-guanly-methyl-transferase (MGMT)-promoter methylation as well as isocitrate dehydrogenase (IDH)1-mutational status. Unexpectedly, overall survival or progression-free survival were not longer in the group with methylated MGMT-promoter as compared to patients without that methylation. IDH-1 mutations were significantly associated with increased overall survival

Hittitology today: Studies on Hittite and Neo-Hittite Anatolia in Honor of Emmanuel Laroche’s 100th Birthday

Il y a 100 ans, Emmanuel Laroche voyait le jour. Savant à la fois passionné de linguistique indo-européenne et d’Antiquité, il marqua durablement l’hittitologie par ses nombreuses contributions dans des domaines aussi variés que l’histoire des religions proche-orientales, la philologie cunéiforme ou encore la grammaire du hittite, du louvite et du hourrite. Ce colloque organisé en l’honneur de son centenaire a été l’occasion de faire le point sur les avancées de l’hittitologie actuelle, avancées auxquelles il participa tout au long de sa vie et qui se poursuivent après lui. Les axes thématiques qui sont abordés dans ce volume sont ceux qu’Emmanuel Laroche développa de son vivant, à savoir la linguistique des langues anatoliennes, la philologie et l’épigraphie cunéiforme et hiéroglyphique, les religions de l’Anatolie hittite et néo-hittite, l’histoire et la géographie historique, mais aussi l’archéologie proche-orientale, domaine qu’Emmanuel Laroche côtoya de près. Ajoutons à ces domaines celui de l’historiographie qui illustre, entre autres choses, l’impact des travaux d’Emmanuel Laroche dans l’hittitologie d’aujourd’hui.100 years ago, Emmanuel Laroche was born. As a scholar who was fascinated both by Indo-European Linguistics and Ancient Near Eastern and Classical Studies, he had a durable impact on Hittitology through his numerous contributions. His publications dealt with History of Near Eastern Religions, Cuneiform Philology, and Hittite, Luwian, and Hurrian grammar, among many other topics. This conference was organized in honor of his 100th birthday. Its aim was to discuss the recent developments in Hittitology, the ones to whom Emmanuel Laroche contributed and the ones which occurred after his time. The following themes are dealt with in this volume: Anatolian Linguistics, Cuneiform and Hieroglyphic Philology and Epigraphy, Religions of Bronze and Early Iron Age Anatolia, History and Historical Geography of Asia Minor, but also Near Eastern Archaeology, as Emmanuel Laroche was also very close to this discipline. Let us add to those fields Historiography which illustrates, among other things, the impact of Emmanuel Laroche’s work on today’s Hittitology