The median OS following standard temozolomide treatment concurrent with and adjuvant to radiotherapy given to (72.8% of) patients aged ≤70 years is consistent with findings reported from randomized phase III trials. The volume and expertise of the treatment center should be further investigated as a prognostic factor.

Locoregional radioimmunotherapy (LR-RIT) was administered to 111 patients (20 were recruited in a phase I and 91 in a phase II study) with malignant gliomas: 1 patient with oligodendroglioma, 7 patients with anaplastic oligodendroglioma, 2 with grade II astrocytoma, 10 with anaplastic astrocytoma and 91 with glioblastoma, amounting to 58 newly diagnosed and 53 recurrent tumours. The 131I-labelled monoclonal antibodies BC-2 and BC-4 were used in order to recognize stromal and intracellular glycoprotein tenascin, an antigen present particularly in glioblastoma. The patients were enrolled between February 1990 and December 1997 after conventional therapy. The radiopharmaceutical was injected directly into the tumour site. Sequential scintigraphies demonstrated a high and enduring uptake in the tumour. The mean irradiation dose in the tumour was 300 Gy per cycle. In the group of 74 phase II glioblastoma patients the clinical responses were as follows: 10 patients with stable disease (SD), 9 with partial responses (PR), 23 with no evidence of disease (NED) and 1 patient with complete response (CR). The median survival was 19 months. The response rate (CR + PR + NED) was 17.8% for those patients with bulky lesions, with a median survival of 17 months, but 66.6% for patients with small lesions, with a median survival of 25 months. Better outcomes were recorded in cases with less aggressive diseases: oligodendroglioma, anaplastic oligodendroglioma and anaplastic astrocytoma. We conclude that fractionated LR-RIT can be safely performed, with promising results especially in patients with minimal disease.

Abstract. We previously described a cohort of grade II oligodendroglioma (OII) patients, in whom the loss of heterozygosity (LOH) 19q was present in the subgroup at a higher risk of relapse. In this study, we evaluated the CpG methylation of the putative tumor suppressor epithelial membrane protein 3 (EMP3, 19q13.3) gene promoter in the same OII cohort, to investigate whether a correlation could be found between EMP3 cytogenetic and epigenetic loss and higher risk of relapse. Twenty-three tumor samples from OII patients were collected over a period of 10 years. Seventeen glioblastoma (GBM) samples (2 of which were relapses) were collected from 15 patients. The EMP3, O 6 -methylguanine methyltransferase (MGMT) and cyclooxygenase 2 (COX2) promoter methylation, evaluated by methylation-specific PCR, and the isocitrate dehydrogenase 1 (IDH1) mutation, identified by sequencing, were compared between the OII and GBM histotypes. The EMP3 promoter methylation was correlated with the analysis of LOH 19q, performed by microsatellite amplification, in OII patients. Disease progression-free interval was evaluated in the OII patients with the EMP3 methylation with either LOH 19q or conserved chromosome 19 arms. The EMP3 and MGMT promoter methylation was more frequent in OII than in GBM patients, and the IDH1 mutation was absent in GBM. The COX2 promoter was unmethylated in both histotypes. Both LOH +/-19q OII patients showed EMP3 hypermethylation. Concomitant LOH 19q and EMP3 gene promoter methylation was observed in the OII patients at a higher risk of relapse. Our results suggest that a total (cytogenetic and epigenetic) functional loss of both EMP3 alleles accounts for the reduced disease progression-free interval in OII patients. Although the small sample size limits the strength of this study, our results support testing this hypothesis in larger cohorts of patients, considering the methylation of the EMP3 gene promoter together with LOH 19q as an indication for treatment with adjuvant therapy ab initio in order to improve the overall survival of OII patients.

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2057 Background: The role of temozolomide (TMZ) concurrent with and adjuvant to radiotherapy (RT) in the treatment of glioblastoma (GBM) has been demonstrated by the EORTC 22981/26981-NCIC CE.3 (EORTC/NCIC) randomized trial, and has been widely accepted as the standard treatment. The impact of RT/TMZ in the general patient population was assessed in the context of the Registry of the Project of Emilia-Romagna Region in Neuro-Oncology (PERNO), that represents the first italian prospectic observational population-based study in neuro-oncology. Methods: Approvals from local Ethical Committees were obtained by 8 participating centres. Patients (pts) who met the following inclusion criteria were evaluated: age ≥18 years; PS 0-3; histologically confirmed GBM, no previous or concomitant non glial tumoral disease, resident in Emilia Romagna region. The data were prospectively collected. Results: From January 2009 to January 2011, 194 GBM pts were enrolled. The median age was 62.5, with 26% of pts over 70 years. After surgery pts received RT/TMZ (73%), RT alone (19%), TMZ alone (5%) or no further treatment (3%); 22% were included in clinical trials. Median overall survival (OS) was 12.9 months. Pts <70 years received RT/TMZ in 85% of cases. In this group of pts mOS was 17 months (95%CI: 15.4–18.6). Interestingly, pts <70 years included in experimental clinical trials showed a significant OS improvement (p=0.04). In multivariate analysis, only extent of surgery (p=0.047), KPS (p=0.01) and RT/TMZ (p<0.001) were associated with OS in pts <70 years. Conclusions: Our population data reproduces the beneficial effect of RT/TMZ from the EORTC/NCIC randomized trial, confirming how this successful approach as been widely incorporated in daily practice. Interestingly, our data suggest that the survival of GBM pts treated with RT/TMZ could be greater than patients treated with RT/TMZ in the EORTC/NCIC trial at the beginning of this century.