S. Rizzato

423PO6-METHYLGUANINE-DNA METHYLTRANSFERASE (MGMT) CUT-OFF METHYLATION LEVEL DETERMINED BY PYROSEQUENCING AND CLINICAL OUTCOME IN PATIENTS WITH GLIOBLASTOMA MULTIFORME (GBM): A SINGLE-INSTITUTION EXPERIENCE

ABSTRACT Aim: MGMT gene is epigenetically silenced by its promoter hypermethylation in GBM. Hypermethylation is relevant predictor of response to temozolomide. Yet, there is debate around the best technique for MGMT assessment. One of the most interesting methods is pyrosequencing (PyroS) that allows defining a cut-off value for MGMT methylation Aim of our retrospective analysis was to explore if predefined levels of MGMT methylation could impact on overall survival (OS) in a cohort of GBM patients. We also analyzed the potential prognostic role of isocitrate dehydrogenase-1 (IDH1) by PyroS. Methods: Clinical and pathological data of 108 consecutive GBM patients referred to our Department between January 2008 and December 2013 were retrieved. Three groups of patients were identified: unmethylated with MGMT methylation 29% (HM). We calculated median (m) OS and compared the Kaplan Mayer survival curves across the groups through log rank test. Results: 51 cases (47.2%) were UM, 24 (22.2%) IM and 33 (30.6%) HM. The median follow-up is 38.5 months. mOS, months (95%CI) N 108 mOS, months (95%CI) Standard Stupp regimen, N 66 MGMT methylation 13.2 (8.3-15.2) 15.1 (12.8-17.4) MGMT methylation 9-29% 15.8 (9.8-30.8) 25.9 (6.93-53.5) MGMT methylation >29% 19.5 (11.5-47.1) 47 (18.5-57.6) P = 0.0002 P = 0.0001 mOS of IDH1 mutated patients (11 out of 108) was 53.5 months compared to 14.2 months in those wild type (p = 0.01). Conclusions: Our study confirms that a cut-off level of 9% in MGMT methylation has prognostic and predictive value in GBM patients treated with standard therapy. IDH1 mutation may have a prognostic role, although the small patient number does not allow drawing definitive conclusions. Disclosure: All authors have declared no conflicts of interest.

Integrated care pathways (ICPs) for non-small cell lung cancer (NSCLC) patients (Pts): A multidisciplinary quality improvement project.

e16573 Background: ICPs are structured multidisciplinary care plans for a specific clinical condition; they describe the tasks to be carried out together with their timing and sequence and the discipline involved in completing the task. They have been proposed as quality improvement strategies of both clinical and organizational aspects of patient-oriented care. Nowadays few data are available to detail existing ICPs for NSCLC pts and the methodology for designing an optimal care plan. Aim of this project was to review current clinical pathways in the care of NSCLC pts who were referred to the University Hospital of Udine, Italy. METHODS A multidisciplinary focus group was established to: 1) map existing local care pathways for NSCLC pts; 2) review the literature and available guidelines to identify quality benchmarks and corresponding, specific indicators; 3) apply these indicators to assess the quality of existing ICPs; 4) recognize key areas for process improvement. RESULTS Eleven quality indicators were identified. They consist in intermediate outputs of the care process and may assess both clinical, organizational and economical aspects of pts care. Indicators were used to survey the ICPs of 175 NSCLC pts who were referred to our Hospital in 2008; data for 6 representative indicators are shown below (Table). CONCLUSIONS By means of a limited set of quality indicators, we were able to verify the adherence of routine clinical practice to clinical guidelines and to elicit some critical issues in the care of NSCLC pts. Results need to be shared and discussed with Hospital Managers, with the aim of guiding the redesign of ICPs and improving the clinical, organizational and economic efficiency of the care process. [Table: see text].