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e13556 Background: The combination of epigenetic drug decitabine with genistein, a natural isoflavone, produces synergistic responses in preclinical studies with particular activity shown in lung c...

BACKGROUND: American Academy of Neurology's 2000 practice parameter do not support routine use of prophylactic antiepileptic drugs (AEDs) in newly diagnosed brain tumors. If used in the perioperative setting, they should be discontinued after the first postoperative week. However, it remains unclear whether such recommendations are followed. OBJECTIVE: To compare our use of long-term prophylactic AEDs in patients with gliomas to published practice guidelines by the AAN. METHODS: A retrospective chart review was performed on 578 glioma cases evaluated in a single tertiary care center from 2006-2013. Data collected included demographic factors, surgical procedure and tumor characteristics. Seizures and AED use were assessed at surgery, 3 months post-operatively and death/last visit/16 months. Long-term prophylactic AED use was defined as continued use of AED at 3 months post-surgery in the absence of seizures. Patients were divided into three groups at surgery: seizure-free with and without prophylactic AEDs, and seizure-patients. Survival, prophylaxis efficacy and factors influencing its use were calculated. RESULTS: Out of 578 patients operated between 2006-2013, 330(57.1%) were seizure-naïve pre-operatively. 205/330(62.1%) received prophylactic AED at surgery. 96/205(46.9%) 95%CI(40.2-54.7) were still on AED 3 months post-surgery (median use = 58 days; 95%CI(31-152)). Rate of long-term prophylaxis use decreased by 13.5% over 6 years (70.3%-2006;56.8%-2012). Dilantin was the preferred agent in 2006(98.2%) with increasing use of Keppra over the years (44.6%-2012). There were no significant differences in age, histology, localisation and resected status between the seizure-free populations with and without prophylaxis. However, seizure-population had more men (p = 0.0068), younger patients (p < 0.0001), lower-grade gliomas (p = 0.0003) and lived longer (p = 0.0012,HR = 0.5423,95%CI(0.3742, 0.7859)) compared to seizure-free populations. The only predictive factor for prophylactic AEDs use was complete resection (p = 0.0069,OR = 2.0292,95%CI(1.2202, 3.4177)). Prevalence of first seizure was similar in both seizure-free populations (p = 0.9104, HR = 0.9627, 95%CI(0.5153, 1.806)). CONCLUSIONS: In our centre, long-term prophylactic AED use is high, deviating from current AAN Guidelines. Corrective measures are warranted.

e19126 Background: Lepidic bronchioalveolar adenocarcinomas (LBA) are tumors with historically longer survival and a good response rate to EGFR TKIs, as they are more frequently associated with EGF...

e22159 Background: Recent advances in lung cancer treatment embrace the recognition of molecular pathways implicated in its pathogenicity, paving the path to personalized therapies. We conducted a retrospective analysis to characterize the molecular features of the population treated for non-squamous non-small cell lung cancer (NS-NSCLC) in the province of Quebec. Methods: 622 patients with NS-NSCLC and adequate tumor blocks, treated at the CHUM between 2006 and 2008, were included. All samples were tested for ALK translocations (by IHC and FISH), EGFR classical exon 19 and 21 mutations by PCR (fragment analysis and qPCR) and for KRAS codon 12 and 13 mutations by mismatch PCR-RFLP. Molecular features were matched to demographic characteristics and clinical outcomes. Results: So far, complete results are available for 153 patients. Considering the amount of tumor tissue available, this population is largely represented by patients with local or loco-regional disease (n= 140, 91.5%). A minority of patients (10.3%) was never or light smokers (< 10 pack-yrs). Only 2 patients (1.3%) were of Asian descent. The following table depicts the outcomes of this cohort of patients segregated according to mutation status and extent of disease. Conclusions: ALK rearrangements were not identified in this unselected NS-NSCLC population characterized by localized disease and strong smoking history. ALK translocation prevalence in different populations is likely to be largely influenced by its tumor stage distribution, tobacco exposure and the use of selection criteria for molecular testing. An expanded cohort of patients will be presented at the meeting. [Table: see text]

2102 Background: Less than 200 CD4 lymphocytopenia happens frequently with temozolomide treatment of glioblastoma. This immunosuppression is associated with many opportunistic infections and antibiotic prophylaxis is given in some centers to prevent Pneumocystis pneumonia. Methods: We analyzed the association between documented culture-proved infections and CD4 lymphocytes level in 140 patients treated with temozolomide in first-line glioblastoma in Notre-Dame Hospital from 2006 to 2009. Demographic and treatment data were collected and analyzed with Kaplan-Meier survival plots and Log Rank tests. Results: The cohort of infected patients was represented by 31 patients who developed 49 culture-proved infections: 21 urinary origin, 8 pulmonary (1 Pneumocytis and 2 Aspergillosis), 5 brain, 5 bacteremia and 2 other. The infected cohort (n=31) had similar demographs, but also similar outcome compared to our control non infected glioblastoma treated patients cohort (n=109) with a 2 year survival of 40.8% vs 50.2% (p=). The median CD4 lymphocytes level was 260, but clearly infections were associated with less than 200 CD4 lymphocytes. During their infection, 20 patients had a CD4 level less than 200, compared with 11 patients with more than 200 CD4 lymphocytes count. Conclusions: CD4 lymphocytopenia less than 200 is associated with increase in number of documented culture-proven infections in patients treated with temozolomide, but the survival is not altered by the infection.

e18120 Background: Up to 20% of patients with localized NSCLC develop brain metastasis, and twice more with metastatic NSCLC. We analyze retrospectively 216 unselected consecutive patients diagnosed with stage I to IV NSCLC treated at Notre-Dame Hospital from 2006 to 2010. Methods: Patients who developed their brain metastasis within 6 months of the NSCLC diagnostic were considered to have synchronous brain metastasis although those who developed more than 6 months later were designated metachronous. We compared the survival Kaplan-Meyer plots with log-rank tests in between each group category: synchronous brain metastasis with localized NSCLC (Sync Loc), synchronous brain metastasis with metastatic NSCLC (Sync Meta), metachronous brain metastasis in patients with localized NSCLC (Mec Loc) and metachronous brain metastasis in patients with already metastatic extracranial NSCLC (Mec Meta). Results: Comparing the 38 patients of Sync Loc with the 95 patients of Sync Meta, we found a not statistical significant difference in median survival with 15.4 months (Sync Loc) vs 6.8 months (Sync Meta) (p=0.18), but a similar 2 years survival 20.4% (Sync Loc) vs 15.7% (Sync Meta). Despite, only 27% of patients of Sync Loc received systemic treatment compared with 43% of patients Sync Meta, the two groups had no statistically significant difference in the median brain-relapse free survival with 18.5 months vs 14.1 months (p=0.335). The metachronous brain metastasis group had a significant difference in the median overall survival with 32.1months for the 61 patients Mec Loc and 18.1months for the 24 patients Mec Meta. Interestingly, stage I NSCLC patients with metachronous metastasis have a 2 year overall survival of 81.6%, stage II of 64.2% and stage III of 49.2%, similar to patients with no brain metastasis. Conclusions: Patients with localized NSCLC diagnosed with synchronous brain metastasis have probably already a metastatic disseminated disease with the same outcome than patients with NSCLC with extracranial metastatic disease. However, patients with metachronous brain metastasis and treated localized NSCLC have a very good prognostic.

e17507 Background: Malignant mesothelioma is a rare pleural cancer heavily correlated to asbestos exposure. However, the number of mesotheliomas without any known exposure to asbestos is surely increasing. The impact of asbestos exposure on patient survival and response to standard treatment is unknown. We retrospectively analyzed 49 consecutive patients diagnosed with malignant mesothelioma using an unselected SARDO database at Notre-Dame Hospital from 2006 to 2009. Methods: Patients were sorted into 2 groups based on reported asbestos exposure status, mostly on patient’s working exposure. Demographic and treatment data were collected and analyzed with Kaplan-Meier survival plots and log-rank tests. Results: The median survival was 22.6 months for the entire 49 patients, overall survival at 1 year 86.4% and at 2 years 47.3%. Median survival of exposed patients (n = 20) was 22.6 months and that of non-exposed patients (n = 29) was 59.5 months. However, survival was not significantly different between the 2 groups (p = 0.450), despite there was no treatment difference in between 2 cohorts. Most patients were men (n = 42) and women (n=7) generally belonged to the non-exposed group. 3 patients had surgical treatment (pleurectomy with either pneumonectomy or lobectomy), but their survival was not statistically superior (p = 0.091) despite a clear trend. Patients younger than 65 years did not have better survival. Conclusions: Although asbestos exposure clearly increases the risk of mesothelioma, it does not seem to have an impact on the overall survival of patients with malignant mesothelioma neither on the efficiency of their treatment. However, a reliable serum biomarker of asbestos exposure would probably be necessary to make sure patients with no working exposure have really no exposure in other circumstances to asbestos.

Introduction: The usefulness of performing a cytocentrifuge preparation (CCP) analysis on cerebrospinal fluid (CSF) containing less than 5 cells has never been studied. To determine if the CCP analysis has a clinical impact on central nervous system (CNS) management of patients with CSF samples containing less than five cells, we correlated the result of CCP to cytomorphology and flow cytometry. Methods: From November 20th 2005 to July 18th 2007, CCP analysis were performed on 105 CSF consecutive samples containing less than 5 cells from patients with various cancers. For each of these samples, a research via computerized data was conducted to obtain cytomorphology and flow cytometry results. If results were positive or inconclusive, the clinical history and treatment were reviewed. Results: All 105 samples had negative CCP results. Of the 105 samples, 74 (70,5%) had available cytomorphologies, with 5 (6,8%) being positive, confirming central nervous system infiltration. All 5 patients received treatment for their CNS involvement. The sensitivity of cytomorphology was 83,3%(5/6) and its specificity 100% (68/68).Of the 105 samples, 23 (21,9%) had available flow cytometries: 4 of the 23 (17,4%) cytometries were positive, 2 correlated by positive cytomorphology and treated. 2 had negative cytomorphology with one patient receiving treatment. The sensitivity of cytometry was 75% (3/4) and the specificity 94,7% (19/20). Conclusion: We found no advantage to performing CCP analysis on CSF samples of less than 5 cells. However, this suggests that performing both cytomorphology and flow cytometry allows a better detection and management of CNS infiltration.

7161 Background: Despite a 9% response rate, BR.21 demonstrated significant survival benefit for patients receiving erlotinib as 2nd/3rd line therapy for NSCLC. We undertook to characterize, by exploratory subset analysis, patients less likely to benefit from erlotinib. To identify factors for consideration, we first identified baseline characteristics associated with early progression by eight wks and early death by 3 mos. Methods: Using stratification factors and potential prognostic factors from BR.21, the Cox regression model with stepwise selection was used to establish a prognostic model to separate erlotinib patients into 4 risk categories based on the 10th, 50th & 90th percentiles of prognostic index scores. 7 variables (smoking history, PS, weight loss, anemia, high LDH, response to prior chemo and time from diagnosis to randomization) were used in the final model. The hypothesis was that the characteristics of the treated patients in the highest risk group would also be predictive of lack of benefit from erlotinib when erlotinib and placebo patients with the same characteristics were compared. Results: Factors associated with PD by 8 wks were: PS2–3 (p = 0.009), weight loss (p = 0.0004), anemia (p = 0.008), PD to prior chemo (p = 0.006), non-Asian (p = 0.047), EGFR IHC-negative (p = 0.005), Factors associated with survival < 3 mos were: PS2–3 (p < 0.0001), weight loss (p < 0.0001), anemia (p < 0.0001), PD to prior chemo (p < 0.0001), non-Asian (p = 0.008), high LDH (p < 0.0001), time to randomization [Table: see text]

7155 Background: NCIC CTG JBR.10 is among the landmark trials to establish 3rd generation platinum-based adjuvant chemotherapy as standard of care after complete resection of stages IB-II NSCLC, improving 5-year survival by 15% and median survival by 21 months (p 0.04). The cost-effectiveness of adjuvant chemotherapy from the perspective of Canada’s public health care system was undertaken in a retrospective analysis based on the JBR.10 study population. Methods: Direct medical resource utilization data, from prospective trial data of patients enrolled onto the BR.10 trial at the 5 largest accruing Canadian centres, were identified and collected retrospectively. Direct medical costs included treatment, hospitalization and procedures. Data were captured from the time of randomization until death or study closure (April, 2004). Non-medical direct and indirect costs were not included. Available costs are presented both with and without discounting at 5% per year. Costs (2005 $CAN) were obtained from provincial sources. Average costs per treatment arm (adjuvant chemotherapy vs. observation) were calculated. Basic demographic statistics were calculated. Results: Utilization data were collected from 172 patients (36% of the trial population), 83 randomized to observation and 89 to chemotherapy. Preliminary results are available for the non-drug related costs of direct medical care including hospitalization and procedures. The mean cost of treatment for patients in the observation arm is $15,323 (25–75% IQR $1,933-$17,831), and $18,701 (25–75% IQR $2,873-$18,781) for patients in the adjuvant chemotherapy arm (2005 $CAN). Conclusion: Non-drug related costs are only slightly higher in patients treated with adjuvant chemotherapy in the NCIC BR.10 trial, despite substantially longer survival for this group of patients. These preliminary results will be updated and cost effectiveness data will be available in May 2006. No significant financial relationships to disclose.