Preoperative stereotactic radiosurgery (SRS) of brain metastases may achieve similar local control and better leptomeningeal control rates than postoperative fractionated stereotactic radiotherapy (FSRT) in patients treated with elective metastasectomy. To plan a multicentre trial of preoperative SRS compared with postoperative FSRT, a survey of experts was conducted to determine current practice. A survey with 15 questions was distributed to the DEGRO Radiosurgery and Stereotactic Radiotherapy Working Group. Participants were asked under what circumstances they offered SRS, FSRT, partial and/or whole brain radiotherapy before or after resection of a brain metastasis, as well as the feasibility of preoperative stereotactic radiosurgery and neurosurgical resection within 6 days. Of 25 participants from 24 centres, 22 completed 100% of the questions. 24 respondents were radiation oncologists and 1 was a neurosurgeon. All 24 centres have one or more dedicated radiosurgery platform and all offer postoperative FSRT. Preoperative SRS is offered by 4/24 (16.7%) centres, and 9/24 (37.5%) sometimes recommend single-fraction postoperative SRS. Partial brain irradiation is offered by 8/24 (33.3%) centres and 12/24 (50%) occasionally recommend whole-brain irradiation. Two centres are participating in clinical trials of preoperative SRS. SRS techniques and fractionation varied between centres. All responding centres currently offer postoperative FSRT after brain metastasectomy. Approximately one third offer single-fraction postoperative SRS and four already perform preoperative SRS. With regard to potential co-investigators, 18 were identified for the PREOP‑2 multicentre trial, which will randomise between preoperative SRS and postoperative FSRT.

Background: Preclinical studies in oncology are often performed in subcutaneous tumor models, where therapy success is validated by measuring changes in tumor size. We first characterized subcutaneous (sc) versus orthotopically grown neuroendocrine tumors of the pancreas (NET) with high versus low somatostatin receptor subtype 2 (SSTR2) by multimodal imaging and validated the apparent diffusion coefficient (ADC) as a potential biomarker for early therapy response following SSTR2-specific PRRT. Methods: NET cells (native, SSTR2-transfected BON) were inoculated sc or orthotopically (n = 20) in SCID mice. Tumor characteristics were monitored using a small animal nanoScanPET/MRI: (T1/T2w anatomy, diffusion-weighted imaging, dynamic contrast-enhanced MRI, angiography; PET: Ga-68-DOTATOC, F-18-FDG. PRRT: ADC values and tumor growth were measured to monitor PRRT effects following Lu-177-DOTATOC injection. Results: Native BON tumors showed different morphologic and metabolic patterns between sc and orthotopic tumors. Sc BON/SSTR2 tumors were similar to native sc BON tumors, while orthotopic BON/SSTR2 tumors were strongly growth delayed and developed necrosis at an early stage compared to native orthotopic BON tumors. Accept of the orthotopic BON/SSTR2 tumors, small tumors appeared solid with high FDG uptake. During tumor growth necrosis increased and FDG decreased. Perfusion was increased in orthotopic versus sc tumors (ktrans = 0,49 min−1 and 0,31 min−1). Interestingly, Lu-177-DOTATOC uptake was ∼4 times higher in sc than in orthotopic BON/SSTR2 tumors. While the ADC reflected the early effects of PRRT (first 9 days) precisely in orthotopic tumors, therapy response could not be validated by ADC in sc tumors due to initial high liquid content in the tissue. Conclusions: Successful therapy validation presupposes precise knowledge about the used xenograft und the tumor morphology in order to allow correct interpretation of therapeutic effects. In particular, the orthotopic SSTR2- tumors do reflect the physiological situation better than sc tumors and allow to use the ADC as a potential biomarker for early validation of PRRT effects. Legal entity responsible for the study: DKTK German Cancer Konsortium/DKFZ German Cancer Research Center Funding: DKTK - German Cancer Konsortium, German Cancer Center (DKFZ) Disclosure: All authors have declared no conflicts of interest.

Purpose. The purpose of this study was to analyse the feasibility, safety, and long-term efficacy of linear accelerator-based fractionated stereotactic radiotherapy for meningiomas of the skull base. We evaluated the long-term clinical outcome of patients and identified prognostic factors after fractionated stereotactic radiotherapy.Patients and methods. Between 10/1995 and 03/2009, 136 patients with a median age of 57 years with skull base meningioma received fractionated stereotactic radiotherapy. A total of 34 patients had a grade I meningioma, in 102 cases no histology was obtained (grade 0). Fractionated stereotactic radiotherapy was delivered as primary treatment for 57 patients and postoperatively for 79. The patients received a mean total dose of 56.95 (min/max 32.4/63) Gy.Results. Median follow-up was 44.9 months. Overall progression-free survival was 96.9% after 3 years, 93.8% after 5 years, and 91.5% after 10 years. Patients with unknown histology showed progressionfree survival rates of 100%, 98.7%, and 93.5% at 3, 5, and 10 years and patients with biopsy-proven grade I meningioma showed rates of 100% after 3 years, 91.7% after 5 years and 85.9% after 10 years. Patients with adjuvant radiotherapy showed significantly worse progression-free survival rates than patients who had been treated with primary radiotherapy (P=0.043), progression-free survival rates were independent of tumour size. The most common acute grade I symptoms were headache, fatigue, and local alopecia. The most common chronic grade I symptoms were fatigue and headache.Conclusions. This large study showed that fractionated stereotactic radiotherapy is an effective and safe treatment modality with high progression-free survival rates for intracranial meningioma. We identified "prior surgery" as significant poor prognostic factor. (C) 2014 Societe francaise de radiotherapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.

The Fas ligand (FasL) pathway is one of the two major effector mechanisms of T‐cell‐mediated cell death. FasL expression by extralymphatic tissues is thought to maintain a status of immunity. Accordingly, it has been proposed that tumor cells express FasL as a mechanism of immunologic escape. However, data regarding FasL expression in normal or neoplastic tissues remain controversial. In the present study, we investigated the expression of FasL in normal peripheral blood B lymphocytes or malignant cells of the B‐lymphocyte lineage to elucidate a possible immunologic counterattack mechanism. FasL gene expression was analyzed by reverse transcriptase polymerase chain reaction in two non‐Hodgkin's lymphoma (NHL) entities: the highly aggressive Burkitt's lymphoma (BL) and indolent NHL chronic lymphocytic leukemia (CLL). FasL expression was found to be consistently negative in all BL cell lines and purified samples from patients with CLL. FasL is not constitutively expressed in normal peripheral blood or neoplastic B lymphocytes making the Fas counterattack, as described for gastrointestinal cancer, unlikely as a mechanism of immunologic escape of lymphoma cells.