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Background: Epidermal growth factor receptor (EGFR) is the most common oncogenic mutation in lung adenocarcinoma and tyrosine kinase inhibitors (TKIs) have been considered standard treatment for more than a decade. However, time to initiation of TKIs (TTIT) from diagnosis is often delayed and represents a challenge for clinicians. We aimed to assess the impact of TTIT on clinical outcomes and complications. Method: TTIT was defined as the time between confirmed advanced diagnosis and the initiation of a TKI. Complications during this pre-TKI period were retrospectively collected from all patients with EGFR-mutant non small cell lung cancer (NSCLC) in our institution. Results: 102 patients were diagnosed with EGFR mutated NSCLC between 2006 and 2019. The median PFS and OS were 12.9 and 22.5 months, respectively. TTIT was 5.7 months (95% CI 3.4–8) with a significant decrease in the latter years of this cohort. During the pre-TKI period, 23 patients received chemotherapy as first line treatment, of which 5 developed severe adverse events and 3 were not fit to receive TKI thereafter. Additionally, 29 patients had rapid clinical deterioration before initiation of first line TKI and 16 had to be hospitalized. Among the patients presenting a performance status deterioration, their prognosis was markedly affected compared to the remainder of the cohort (p = 0.01). Conclusion: Our real-world evidence study supports the concept that a delay to treat EGFR mutant NSCLC with TKIs is associated with adverse events, patient progression, hospitalization, and decreased overall survival. Rapid molecular diagnosis, including access to ctDNA technology may circumvent these deleterious delays.

Background: Studies have shown that aggressive treatment of non-small cell lung cancer (NSCLC) with oligometastatic disease improves the overall survival (OS) compared to a palliative approach and some immunotherapy checkpoint inhibitors, such as anti-programmed cell death ligand 1 (PD-L1), anti-programmed cell death protein 1 (PD-1), and T-Lymphocyte-associated antigen 4 (CTLA-4) inhibitors are now part of the standard of care for advanced NSCLC. However, the prognostic impact of PD-L1 expression in the oligometastatic setting remains unknown. Methods: Patients with oligometastatic NSCLC were identified from the patient database of the Centre hospitalier de l&rsquo, Universit&eacute, de Montr&eacute, al (CHUM). &ldquo, Oligometastatic disease&rdquo, definition chosen is one synchronous metastasis based on the M1b staging of the eight IASLC (The International Association for the Study of Lung Cancer) Classification (within sixth months of diagnosis) or up to three cerebral metastasis based on the methodology of the previous major phase II randomized study of Gomez et al. We compared the OS between patients receiving aggressive treatment at both metastatic and primary sites (Group A) and patients receiving non-aggressive treatment (Group B). Subgroup analysis was performed using tumor PD-L1 expression. Results: Among 643 metastatic NSCLC patients, we identified 67 patients with oligometastasis (10%). Median follow-up was 13.3 months. Twenty-nine patients (43%) received radical treatment at metastatic and primary sites (Group A), and 38 patients (57%) received non-aggressive treatment (Group B). The median OS (mOS) of Group A was significantly longer than for Group B (26 months vs. 5 months, p = 0.0001). Median progression-free survival (mPFS) of Group A was superior than Group B (17.5 months vs. 3.4 months, p = 0.0001). This difference was still significant when controlled for primary tumor staging: stage I (p = 0.316), stage II (p = 0.024), and stage III (p = 0.001). In the cohort of patients who were not treated with PD-L1 inhibitors, PD-L1 expression negatively correlated with mOS. Conclusions: Aggressive treatments of oligometastatic NSCLC significantly improve mOS and mPFS compared to a more palliative approach. PD-L1 expression is a negative prognostic factor which suggests a possible role for immunotherapy in this setting.

The PACIFIC trial demonstrated that durvalumab therapy following chemoradiation (CRT) was associated with improved overall survival (OS) in patients with stage III non-small cell lung cancer (NSCLC). It is unclear whether the results obtained as part of randomised controlled trials are a reflection of real-world (RW) data. Several questions remain unanswered with regard to RW durvalumab use, such as optimal time to durvalumab initiation, incidence of pneumonitis and response in PD-L1 subgroups.In this multicentre retrospective analysis, 147 patients with stage III NSCLC treated with CRT followed by durvalumab were compared with a historical cohort of 121 patients treated with CRT alone. Survival curves were estimated using the Kaplan-Meier method and compared with the log-rank test in univariate analysis. Multivariate analysis was performed to evaluate the effect of standard prognostic factors for durvalumab use.Median OS was not reached in the durvalumab group, compared with 26.9 months in the historical group (hazard ratio [HR]: 0.56, 95% confidence interval [CI]: 0.37-0.85, p = 0.001). In the durvalumab group, our data suggest improved 12-month OS in patients with PD-L1 expression ≥50% (100% vs 86%, HR: 0.25, 95% CI: 0.11-0.58, p = 0.007). There was no difference in OS between patients with a PD-L1 expression of 1-49% and patients with PD-L1 expression1%. Delay in durvalumab initiation beyond 42 days did not impact OS. Incidence of pneumonitis was similar in the durvalumab and historical groups. In the durvalumab group, patients who experienced any-grade pneumonitis had a lower 12-month OS than patients without pneumonitis (85% vs 95%, respectively; HR: 3.3, 95% CI: 1.2-9.0, p = 0.006).This multicentre analysis suggests that PD-L1 expression ≥50% was associated with favourable OS in patients with stage III NSCLC treated with durvalumab after CRT, whereas the presence of pneumonitis represented a negative prognostic factor.

Introduction Nivolumab is a programmed death 1 (PD-1) inhibitor approved by the Food and Drug Administration (FDA) for the treatment of eight different cancers including metastatic melanoma. Immune checkpoint blockade may lead to a range of neurologic immune-related adverse events (irAEs) with severity varying from mild to life-threatening, including encephalitis. Case report We describe a case of a 68-year-old man who developed alteration in mental status, physical weakness and fatigue after nine cycles of nivolumab 3 mg/kg every two weeks. These symptoms were compatible with a clinical diagnosis of autoimmune limbic encephalitis, although no specific antibodies were detected and the initial MRI was normal. Management and outcome The patient received intravenous methylprednisolone 1 g daily for 5 days, which was then converted to a maintenance dose of oral prednisone. The patient made a full clinical recovery but relapsed clinically upon steroid tapering, while hypersignal in the left mesial temporal suggestive of limbic encephalitis was observed on repeated MRI. Discussion Because of the prevailing usage of nivolumab in many cancer protocols, this case highlights the importance of rapidly recognising neurological impairment in patients treated with nivolumab and of initiating very high doses of corticosteroids.

Medulloblastoma is an aggressive primary brain tumor that is extremely rare in adults, therefore, prospective studies are limited. We reviewed the information of all MB patients treated at the CHUM between 2006 and 2017. We divided our cohort by age and further divided adult patients (53%) in two groups, those diagnosed between 2006–2012 and 2013–2017. In our adult population, median follow up was 26 months and SHH-activated MB comprised 39% of tumors. Adult 5yOS was 80% and first-line therapy led to a 5yPFS of 77%. The absence of radiosensitizing chemotherapy (100% vs. 50%, p = 0.033) negatively influenced 5yPFS. 96% of adult patients received radiotherapy and 48% of them received concomitant radiosensitizing chemotherapy. Complete surgical resection was performed on 85% of adults, but the extent of resection did not have a discernable impact on survival and did not change with time. Adjuvant chemotherapy did not clearly affect prognosis (5yOS 80% vs. 67%, p = 0.155, 5yPFS 78% vs. 67%, p = 0.114). From 2006–2012, the most common chemotherapy regimen (69%) was Cisplatinum, Lomustine and Vincristine, which was replaced in 2013 by Cisplatinum, Etoposide and Cyclophosphamide (77%) with a trend for worse survival. Nine patients recurred and seven of these (78%) were treated with palliative chemotherapy. In conclusion, we did not identify prognostic demographic or tumor factors in our adult MB population. The presence of radiosensitizing chemotherapy was associated with a more favorable PFS. Cisplatinum, Lomustine and Vincristine regimen might be a better adjuvant chemotherapy regimen.

Alterations in c-MET, a tyrosine kinase receptor encoded by the MET gene, have been reported in approximately 3% of non-small cell lung cancer (NSCLC) cases and carry important treatment implications. The best studied genetic alterations are exon 14 skipping and gene amplification; however, gene rearrangement has also been described, and multiple fusion partners have been reported. Recently, in METex14-mutated NSCLC, multitarget tyrosine kinase inhibitors (TKIs), such as crizotinib and cabozantinib, as well as MET-selective TKIs, such as tepotinib and capmatinib, have demonstrated durable responses. In this study, we present the case of a 41-year-old woman with advanced NSCLC harboring an HLA-DRB1-MET gene fusion. The patient was offered successively two different MET multikinase inhibitors, crizotinib and cabozantinib, and the selective inhibitor tepotinib. Each time, including under tepotinib, the patient experienced rapid and complete responses associated with a tremendous improvement in her physical function. Key Points To our knowledge, this is the first report of a patient with non-small cell lung cancer harboring an HLA-DRB1-MET gene fusion demonstrating a clinical response to multiple MET inhibitors, including tepotinib. This finding illustrates the efficacy and rationale to targeting MET regardless of fusion partner and gives insight to pooling of patients with different MET fusion products in trials assessing safety and efficacy of novel molecules.

Brain metastasis from breast cancer (bca) in young women is doubly devastating because both quality of life and life expectancy are significantly reduced. With new radiation technology and drugs that have emerged, survival is expected to increase for these young women. Using the oacis and sardo patient databases, we identified 121 patients diagnosed with bca and brain metastasis between 2006 and 2016 at the University of Montreal Hospital Centre. Those patients were divided into Group A, patients who developed brain metastasis during the evolution of metastatic bca, and Group B, patients whose first metastasis was to the brain. For each group, we compared young patients (, 40 years of age). Among the 121 patients with brain metastasis, median overall survival (mos) was significantly longer for those less than 40 years of age than for those 40 or more years of age (18 months vs. 4 months, p < 0.001). With respect to the timing of brain metastasis, survival was significantly longer in Group B than in Group A (7 months vs. 4 months, p = 0.032). In Group A, mos was significantly longer for patients less than 40 years of age than for patients 40 or more years of age (18 months vs. 3 months, p = 0.0089). In Group B, the 2-year overall survival rate was 57% for patients less than 40 years of age and 12% for those 40 or more years of age (mos: not reached vs. 7 months, p = 0.259). In our single-centre retrospective cohort of women with brain metastasis from bca, prognosis was better for young women (, 40 years). Survival was also longer for patients whose initial metastasis was to the brain than for patients whose brain metastasis developed later in the disease course. In patients who received systemic treatment, median survival remained significantly higher in women less than 40 years of age. Further studies are needed to validate those results.

Lung cancer is the most commonly diagnosed cancer in Canada and remains associated with high mortality. Nevertheless, recent advances in the fields of immuno-oncology and precision medicine have led to significant improvements in clinical outcome in metastatic non-small-cell lung cancer (nsclc). Those improvements were facilitated by a greater understanding of the biologic classification of nsclc, which catalyzed discoveries of novel therapies. Here, we present a comprehensive review of the recent avalanche of practice-changing trials in metastatic nsclc, and we offer an approach to the management of this disease from a Canadian perspective. We begin with an overview of the pathologic and molecular characterization of metastatic nsclc. Next, we review the indications for currently approved immune checkpoint inhibitors, and we provide an approach to the management of disease with a driver mutation. Finally, we address future avenues in both diagnostics and therapeutics for patients with advanced and metastatic nsclc.

Procarbazine, lomustine, and vincristine (pcv) significantly improve survival outcomes in lgg (low-grade gliomas). Administration of pcv to lgg patients increased tremendously over the past years as it went from 2 patients per year between 2005 and 2012 to 23 patients in 2015 only in our centre. However, serious hematological and non-hematological adverse events may occur. The purpose of this study was to evaluate the toxicity of pcv and its clinical relevance in our practice. We retrospectively reviewed the charts of 57 patients with lgg who received pcv at the Centre hospitalier de l&rsquo, Universit&eacute, de Montr&eacute, al between 1 January 2005 and 27 July 2016. Procarbazine, lomustine, and vincristine were associated with severe hematological toxicity as clinically significant grade 3 anemia, neutropenia, and thrombocytopenia occurred in 7%, 10%, and 28% of patients, respectively. Other frequent adverse events such as the increase of liver enzymes, cutaneous rash, neurotoxicity, and vomiting occurred in 65%, 26%, 60%, and 40% of patients, respectively. Patients with prophylactic trimethoprim/sulfamethoxazole had more grade 3 hematological toxicity with pcv, especially anemia (p = 0.040) and thrombocytopenia (p = 0.003) but we found no increase in pcv toxicity in patients on concurrent anticonvulsants. Patients with grade 3 neutropenia had a significantly lower survival (median survival 44.0 months vs. 114.0 months, p = 0.001). Patients who were given pcv at diagnosis had more grade 3 anemia than those who received it at subsequent lines of treatment (p = 0.042). Procarbazine, lomustine, and vincristine increase survival in lgg but were also associated with major hematologic, hepatic, neurologic, and cutaneous toxicity. Anti-Pneumocystis jiroveci pneumonia (pjp) prophylaxis, but not anticonvulsants, enhances hematologic toxicity.

Despite numerous breakthrough therapies, inoperable lung cancer still places a heavy burden on patients who might not be candidates for chemotherapy. To identify potential candidates for the newly emerging immunotherapy-based treatment paradigms, we explored the clinical and biologic factors affecting treatment decisions. We retrospectively reviewed the records of patients diagnosed at our university-affiliated cancer centre between 1 January 2011 and 31 December 2013. Patient demographics, systemic treatment, and survival were examined. During the 3-year study period, 683 patients fitting the inclusion criteria were identified. First-line therapy was administered in 49.5% of patients, only 22.4% received further lines of therapy. The main reasons for withholding therapy were poor performance status [ps (43.2%)], rapidly deteriorating ps (31.9%), patient refusal of therapy (20.9%), and associated comorbidities (4%). Older age, the presence of brain metastasis at diagnosis, and non-small-cell histology were also associated with therapeutic restraint. Oncology referrals were infrequent in patients who did not receive therapy (32.2%). Older patients and those with a poor ps experienced superior survival when treatment was administered (hazard ratio: 0.25, 95% confidence interval: 0.16 to 0.38, and hazard ratio: 0.44, 95% confidence interval: 0.23 to 0.87 respectively, p < 0.001). Advanced lung cancer still poses a therapeutic challenge, with a high proportion of patients being deemed unfit for therapy. This issue cannot be resolved until appropriate measures are taken to ensure the inclusion of older patients and those with a relatively poor ps in large clinical trials. Immunotherapy might be interesting in this setting, given that it appears to be more tolerable. Another consequential undertaking would be the deployment of strategies to reduce wait times during the diagnostic process for patients with a high index of suspicion for lung cancer.

Background.Uncertainty persists about the survival advantage of concomitant and adjuvant temozolomide (TMZ) plus radiotherapy (RT) in elderly patients with newly diagnosed glioblastoma (GBM). We compared the clinical outcome of unselected elderly GBM patients treated with 4 adjuvant treatment modalities, including the Stupp protocol.Methods.From 2010 to 2014, retrospective chart review was performed on 171 GBM patients aged ≥55 who received either concurrent chemoradiation therapy (CCRT) with standard 60 Gy/30 (SRT); CCRT with hypofractionated 40 Gy/15 (HRT); HRT alone; or TMZ alone. Stratification is by age (55–69, ≥70), KPS (Results.Out of 171 patients identified, 128(75%) had surgical resection, median age was 66(55–83), and median overall survival (mOS) 11.4mo. Majority (109/171) were treated according to the Stupp protocol (CCRT-SRT), and 106/171 received post-CCRT adjuvant TMZ (median of 3 cycles). In our population, age Conclusions.Our data suggests that, despite having a worse global prognostic than their younger counterparts, GBM patients ≥70yo with a good performance status could be treated according to the Stupp protocol with similar survival. Theses results need prospective confirmation.

Introduction Activation of the RAS/RAF/MEK/ERK pathway may confer resistance to chemotherapy in non-small cell lung cancer (NSCLC). Selumetinib (AZD6244, ARRY142886), a MEK1/2 inhibitor combined with chemotherapy in patients with NSCLC was evaluated in two schedules to evaluate efficacy and toxicity. Methods IND.219 was a three-arm study of first line pemetrexed/platinum chemotherapy with two schedules of selumetinib (Arm A: intermittent given on days 2–19; Arm B: continuous given on days 1–21) versus chemotherapy alone (Arm C). The primary endpoint was objective response rate (ORR); secondary objectives were tolerability, progression-free survival (PFS), overall survival (OS). The trial was stopped at the planned interim analysis. Results Arms A/B/C enrolled 20/21/21 patients, ORR was 35% (95% CI 15–59% median duration 3.8 months), 62% (95% CI 38–82%; median duration 6.3 months), 24% (95% CI 8–47%; median duration 11.6 months) respectively. The PFS (months Arm A, B, C) was 7.5, 6.7, 4.0 respectively (hazard ratio (HR) PFS Arm A over Arm C: 0.76 [95% CI, 0.38–1.51, 2-sided p = 0.42]; Arm B over Arm C 0.75 [95% CI 0.37–1.54, p = 0.43]. Skin and gastrointestinal adverse events were more common with the addition of selumetinib. A high incidence of venous thromboembolism was seen in all arms. Conclusions Selumetinib combined with chemotherapy was associated with a higher response rate. Continuous selumetinib appeared to be superior to an intermittent schedule. PFS was prolonged with the addition of selumetinib, however this was not statistically significant.

12054 Background: Patients with advanced NSCLC experience fatigue and physical deconditioning altering their quality of life. Safety and feasibility of high intensity exercise in advanced NSCLC has not been explored yet. Methods: We report the results of a single-center, prospective two-arm study. Patients with advanced NSCLC actively receiving systemic therapy or having completed treatment less than 2 months prior to enrollment were included. Patients were allocated to either an intervention arm consisting of kinesiologist supervised high intensity interval training (HIIT) at 2 sessions per week for a total of 12 weeks; or a control arm of home exercise guided by an informative pamphlet. All patients were evaluated at baseline, 6 and 12 weeks by a kinesiologist. Quality of life (QoL) exercise surveys and measurement of strength were measured. Results: Sixty patients were enrolled between January 2018 and March 2020. The study was interrupted due to COVID-19. Thirty-two patients were included in the exercise program and 28 patients in the control group. Both groups were balanced in respect to baseline characteristics. A total of 32 (53%) patients went off protocol, 13 (18%) patients stopped due to symptomatic disease progression which included 2 (3%) deaths, 2 (3%) stopped due to COVID-19 preoccupations and the remaining patients withdrew for other reasons. 42 (70%) patients were evaluated at 6-weeks and 28 (47%) completed the 12-week follow-up, with equal distribution in each group. There were no significant difference at 12 weeks in the physical assessment nor the overall QoL scores between both groups: FACT-L on 135 points (+4.1 vs +1.7, p = 0.342) and FACIT on 52 points (+3 vs -0.2, p = 0.832). Patients in the exercise group demonstrated a significant improvement at 12 weeks in the Lung Cancer Symptoms domain on 28 points (22.3 vs 19.8, p = 0.015) as well as the Physical Wellbeing domain on 28 points (23.6 vs 20.6, p = 0.056) compared to the control group, respectively. No significant exercise related complications were reported. After the study, 9 of the 14 patients (64%) who completed the HIIT program continued to exercise virtually with a kinesiologist in contrast to none in the control group. Conclusions: This study demonstrated the safety and potential benefit of a HIIT program on lung-specific and physical wellbeing in patients with advanced NSCLC on active treatment. This study provides further support on the role of supervised physical exercise in patients living with cancer. Clinical trial information: 16.229.

2023 Background: Previous studies suggested activity of anti-PD-1 in brain metastases from non-small cell lung cancer (NSCLC) and renal cell cancer (RCC). This investigator initiated phase 2 trial examined the safety and efficacy of combining nivolumab with radiosurgery (SRS) in the treatment of patients with brain metastases from NSCLC and RCC. Methods: This is a multicentre open-label trial (NCT02978404) in which patients diagnosed with NSCLC or RCC, having ≤ 10 cc of un-irradiated brain metastases, no whole brain radiotherapy and no prior immunotherapy were eligible. Study treatment commenced with a dose of nivolumab (240mg or 480mg IV), which was continued for up to 2 years at bi-weekly or monthly intervals until progression. SRS (15-21Gy) to all visible un-irradiated brain lesions was administered within 14 days after the first dose of nivolumab (cycle 1). Patients were followed by brain MRI, CT scan of the chest, abdomen and pelvis, neurocognitive and quality of life questionnaires (FACT-Br) every 3 months. The primary endpoint was intracranial progression free survival (icPFS), with death and disease progression within the brain as events. Results from NSCLC patients are presented here. Results: Of the 26 study patients, 22 NSCLC patients were enrolled between Aug 2017 and January 2020. Patients had a median of 2 (1-9) brain metastases. The median diagnosis-specific graded prognostic score was 2 (1-3). Median treatment and follow-up durations were 4.3 months (0-24.8 months) and 11 months (0-24.8 months), respectively. Forty-two percent of the patients had received prior cytotoxic chemotherapy, and 1 patient had received prior brain SRS. PD-L1 status was known for 21 of the 22 NSCLC (12 with ≥50% PD-L1 expression (DAKO 22C3). Median icPFS was 5.0 months (3 intracranial progression and 8 deaths without progression in the brain). Accounting for death as a competing risk, the 1-year cumulative incidence of intracranial relapse was 17.4%. Median extracranial PFS and overall survival were 2.9 months and 14 months, respectively. Four grade 3 adverse events in 2 patients were related to nivolumab or SRS. The rate of survival free of neurocognitive decline (Hopkins Verbal Learning Test total recall) was estimated to be 89% by 4 months. Mean FACT-Br total scores were 89.4 at baseline and improved (p = 0.01) to 139.3 within 2-4 months. Conclusions: Neurocognitive and quality of life assessments suggest that upfront SRS during nivolumab is well tolerated. High intracranial control was observed, but deaths from extracranial disease progression resulted in short icPFS. Studies evaluating the strategic addition of SRS combined with more efficacious systemic treatments are needed. Clinical trial information: 02978404.

e21010 Background: ICIs changed the way NSCLC is treated, but not all patients benefit from it. PD-L1 level is used to predict response to therapy, but its performance is sub-optimal. KRAS is important in NSCLC tumorigenesis, but the impact of its mutations in patients treated with ICIs is unclear. Similarly, studies evaluating co-mutations in TP53, STK11 and KEAP1 as well as the NLR showed that they may predict the benefit of ICIs. Methods: We conducted a retrospective study including all consenting patients with NSCLC treated with ICIs at the CHUM between July 2015 and June 2020. OS and PFS were compared in co-mutation subgroups using Kaplan-Meier and logrank methods. Co-mutations in TP53, STK11 and KEAP1 as well as the NLR were accounted for. Overall response rate (ORR) and safety data was also compared in subgroups and will be detailed at the meeting. Results: We included 100 patients with known KRAS status. From these, 50 were wild-type ( KRASWT) and 50 were mutated ( KRASMut). The most frequent mutation was G12C (54%). Co-mutation status for TP53, STK11 and KEAP1 were known for, respectively, 40, 39 and 38 patients. Co-mutations for these genes were present in respectively 19 (47.5%), 8 (20.5%) and 4 (10.5%). Data comparing KRASMut and KRASWT showed non-significant differences in survival (median OS of respectively 21.1 vs. 17.7 months, p = 0.27). The presence of STK11 and/or KEAP1 mutations was associated with a negative impact on survival when compared with wild-type (median OS 7.4 vs 20.4 months, p = 0.001). When the presence of a KRAS mutation was compounded with STK11 and KEAP1, KRASMut (vs KRASWT) trended to a better prognosis in STK11+KEAP1WT tumors (median OS of 21.1 for KRASMut vs 15.8 for KRASWT, p = 0.15), but not in STK11+/-KEAP1Mut tumors (7.4 for KRASMut vs 7.0 for KRASWT). No influence on survival was seen in relationship to the TP53 co-mutation. Interestingly, the NLR was significantly higher with STK11 mutations (6.66Mut vs 3.59WT, p = 00012), slightly lower with TP53 mutations (3.23Mut vs 4.82WT, p = 0.047) but not impacted by KEAP1 (3.72Mut vs 4.20WT, p = 0.72) or KRAS mutations (4.32Mut vs 5.21WT, p = 0.34). Conclusions: The STK11 and KEAP1 mutations are significant adverse predictors of ICI therapy benefit. The NLR is strongly impacted by STK11 mutations but not by KEAP1 mutations suggesting marked differences in the resistance mechanism for both mutations. In STK11-KEAP1WT tumors, KRAS mutations seems to be associated with improved survival in NSCLC patient treated with ICIs.

BACKGROUND In glioblastomas (GBM) patients the first post-radiation MRI is usually difficult to interpret given the post-radiotherapy enhancement and possible pseudo-progression which is present in almost 50% of the patients. METHODS We retrospectively analyzed all patients with GBM treated between 2006 and 2017 at the CHUM (SARDO database). If the first brain MRI done within 3 months after the systemic treatment showed progression of contrast, these patients were considered pseudoprogressors (PsP) while the patients who had stable or response to treatment were the non-progressors (nP). If progression persisted in subsequent MRI with a change of treatment within 6 months, they were considered early progressors (eP). If subsequent MRI improved or was stable, they were classified as nP (or true pseudo-progression). RESULTS In our cohort of 470 patients with GBM, 57.7% were nP and 42.3% were PsP after the first post-treatment imagery. The median follow-up was 10 months. The nP had a longer mOS 15.3m vs 11.3m, p < 0.001, regardless of subsequent evolution. After the second assessment, 67.8% of PsP patients were then considered as eP and 36.4% of nP patients also progressed within 6 months. The nP either after the first or second evaluation had the same mOS (19.9m vs 18.3m), just like the eP (9.3m vs 8.6m), independently of the subsequent treatment. No demographic, molecular or clinical factor predicted PsP, except for tumor size (> 5cm, p=0.024). PsP incidence was similar between 2006–2011 (PsP 57.8%) and 2012–2017 (42.2%). The 1y OS with pseudo progression at the first MRI was 39.7% vs 54.8% with no progression (p=0.001) which has a meaningful impact for the patient. CONCLUSION Pseudo-progression is frequent (42%) in glioblastoma and predicts a poorer prognosis with 1y OS of 39,7%. In fact, PsP patients have more than two-thirds chance to progress precociously.

Background The American Academy of Neurology (AAN) does not recommend routine use of prophylactic antiepileptic drugs (pAEDs) in patients with newly diagnosed brain tumors. If used in the perioperative setting, discontinuation is suggested after the first postoperative week. It is unclear whether such recommendations are followed. Our objective was to compare our perioperative and long-term pAED use in glioma patients with AAN practice parameters. Methods Retrospective chart review was performed on 578 glioma patients from 2006 to 2013. Seizures and AED use were assessed at surgery, 3 months postoperatively and death, last visit or 16 months postoperatively. Patients were divided into three groups at surgery: seizure-free with pAED, seizure-free without pAED, and seizure patients. Long-term pAED use was defined as continued use at 3 months postsurgery without seizures. pAEDs efficacy, factors influencing its use, and survival were examined. Results Out of 578 patients identified, 330 (57.1%) were seizure-naïve preoperatively. There were no significant differences in age, histology, tumor location or resection status between seizure-free populations with and without prophylaxis. Of 330 seizure-naïve patients, 205 (62.1%) received pAEDs at surgery. Ninety-six (46.9%) of those patients were still on pAEDs 3 months postsurgery (median use = 58 days). Rate of long-term prophylaxis use decreased by 13.5% over 6 years (70.3% in 2006; 56.8% in 2012). Phenytoin was preferred in 2006 (98.2%) with increasing use of levetiracetam over 6 years (44.6% in 2012). The only predictive factor for pAED use was complete resection (P = .0069). First seizure prevalence was similar in both seizure-free populations (P = .91). The seizure population had more men (P = .007), younger patients (P < .0001), lower-grade gliomas (P = .0003) and survived longer (P = .001) compared with seizure-free populations. Conclusions In our center, long-term prophylactic AED use is high, deviating from current AAN Guidelines. Corrective measures are warranted.

Introduction The association of venous thromboembolic events (VTE) and lung cancer is highly prevalent. Additionally, the occurrence of a VTE with cancer has been associated with a worse prognosis and a poor quality of life. Underlying cancer biological features such as tumour mutations may contribute to VTE risk and cancer prognosis. Since preclinical data suggest a link between thrombosis and KRAS mutations in tumours, we aimed to validate this association in a patient registry cohort. Methods: A retrospective case control study was performed using the CHUM NSCLC registry. Cases had VTE occurring 6 months previous to or after a diagnosis of NSCLC. Diagnosis of VTE (venous thrombosis, pulmonary embolism, and migratory superficial thrombophlebitis) was confirmed by a review of the imaging reports. Controls were patients with NSCLC without thrombosis matched for age and stage (I-IIIA/IIIB-IV). Exclusion criteria included insufficient tissue for KRAS/EGFR mutation analysis or insufficient clinical information. Results Between Jan 2000 and Dec 2009 a total of 57 cases with VTE and 102 controls without VTE were included. The OR for thrombosis in KRAS and EGFR mutated NSCLC patients are respectively 2.67 (1.12-6.42; p = 0.014) and 0.99 (0.27-3.48; p = 0.99). Conclusions KRAS mutation is associated with an increased risk of VTE in this NSCLC cohort. These findings are consistent with preclinical studies. Prospective data on VTE rates from clinical trials with molecularly defined NSCLC are needed to confirm these findings.

BACKGROUND Before 2012, Temozolomide (TMZ) was used for low-grade gliomas (LGG) to avoid Lomustine toxicity. After 2012 RTOG data, Procarbazine, Lomustine and Vincristine (PCV) given sequentially with radiotherapy became standard treatment with the side effects burden associated. METHODS We retrospectively reviewed our SARDO clinical database of patients with low-grade glioma LGG grades 2 and 3 between 2006 and 2017 at CHUM University Health Center. Molecular profile for these tumors is reflex and standard in our institution since 2016. RESULTS A total of 123 patients were identified with grade 2 and grade 3 LGG; 37 (30%) treated with PCV and 86 (70%) received TMZ. Median follow up was 11mo for PCV 11mo vs 22mo TMZ. Both groups were balanced in terms of median age, sex, neurologic symptoms and surgery rate. 53% patients had tumor untested for IDH1-2 and codeletion1p19q because of diagnostic before 2016. Disparities were noted with a predominance of grade 3 in the TMZ group (74% vs 27%, p< 0.01). TMZ was the preferred regimen before 2012 (100% vs 43%) and PCV became the standard of care after 2012 (0% vs 57%). Radiation use as first line treatment was 90%. The 4y OS was not significantly longer for PCV 50% compared with TMZ 47% with mOS between both groups (PCV NR vs TMZ 39.9mo, p=0.158). When controlled for tumor grade, the 2y OS was 80% for PCV vs 64% for TMZ,p=0.542. The 4y PFS was trendly longer for PCV group 78% than TMZ group 45%, p=0.148. CONCLUSION As we are still waiting for the prospective ongoing prospective trials comparing these 2 regimens, PCV and radiation are still standard of care regimens for grade 2 and 3 LGG. This retrospective data is not reassuring for a replacement for PCV with TMZ.

e20082 Background: Small cell lung cancer (SCLC) remains an aggressive cancer, with a reported mOS of 15-20 mo when localized (L-SCLC) and 9-11 mo when extensive (E-SCLC). Paraneoplastic syndromes (PNS) are a debilitating condition either related to the embryogenic stem cell origin or to auto-immune antibodies produced against the tumor. These mechanisms may be even more relevant with the use of immunotherapy for first-line treatment of E-SCLC. Methods: We retrospectively reviewed our clinical database of patients diagnosed with SCLC between 2006 and 2017 at CHUM University Center. The primary outcome was to compare OS of patients with and without PNS in L-SCLC and E-SCLC. No patients received immunotherapy. Results: We identified 426 unselected SCLC patients, 39% L-SCLC and 61% E-SCLC. 84 patients (20%) were diagnosed with a PNS: 66 (15%) SIADH, 8 (2%) paraneoplastic Cushing syndromes, 2 (1%) humoral hypercalcemia and 8 (2%) paraneoplastic neurologic syndromes. 25% of patients with PNS vs 14% without PNS had a PS 3-4 and would not have been eligible to a clinical trial. 65% of patients with PNS received chemotherapy vs 63% without PNS. Neurologic PNS were all diagnosed in patients with L-SCLC. PNS affecting the central nervous system (4 limbic encephalitis and 1 cerebellar degeneration) were associated with a poorer prognosis than L-SCLC without PNS (mOS 3,5 mo vs 16,7 mo (p = 0,003)). The 2 patients with Lambert-Eaton myasthenic syndrome had a long survival (29 and 82 mo), but persistence of the neurologic symptoms. 86% of patients with paraneoplastic Cushing syndrome were diagnosed with an E-SCLC and had a worse prognosis than E-SCLC without PNS (mOS 1,1 mo vs 4,63 mo (p = 0,022)). SIADH had a significative poor impact on OS in patients with L-SCLC (mOS 10,1 mo vs 16,7 mo (p = 0,016)), but no impact in survival for patients with E-SCLC (mOS 3,63 mo vs 4,63 mo (p = 0,735)). Conclusions: PNS either in patients with L-SCLC or E-SCLC worsen the overall prognosis, except for Lambert-Eaton myasthenic syndrome. A more systematic detection of these syndromes is suggested before starting immunotherapy as first-line standard treatment for E-SCLC. Furthermore, this real-world unselected clinical cohort shows our E-SCLC patients have a worse prognosis than the clinical trial experience.

e20512 Background: Angiotensin converting enzyme (ACE) inhibitors are used to treat hyperblood pressure and congestive heart failure. Preclinical evidence show that ACE has a role in both innate and adaptive responses thus suggesting a capacity of ACE to promote antitumor immunity. Interaction between ACE inhibitors and Immune checkpoint blockers (ICB) has not been investigated in cancer patients (pts). Our study evaluated the effect of ACE inhibitors in Non Small cell lung cancer (NSCLC) pts treated with PD-1/PD-L1 inhibitors. Methods: We conducted a retrospective multicohort retrospective analysis of pts treated with PD-1/PD-L1 inhibitors for NSCLC at Dijon Cancer Center, and at the University of Montreal Hospital. ACE inhibitors groups were defined as pts treated with ACE inhibitors given during the treatment with ICB. PFS and OS were compared between both groups among all pts. Statistical analyses were performed using the Kaplan-Meier method and Cox univariate analysis. Multivariate Cox regression analyses was used to adjust for classical prognostic factors. Tumor RNA sequencing were performed and CIBERSORT was used to estimate immune cell infiltration in ACE inhibitors group and None ACE inhibitors group. Results: Among 283 pts included (177 pts from Dijon, and 106 pts from Montreal), 27 (10%) received ACE inhibitors. ACE inhibitors group did not differ from None ACE inhibitors group for main clinical prognostic characteristics. However, ACE inhibitors group are more frequently treated with statin, beta blocker and metformin. ACE inhibitors group had shorter median PFS compared to None ACE inhibitors group : 2.5 vs. 3.8 months, p = 0.02 (HR = 1.7 IC95% 1.1-2.5 p = 0.02 Cox Univariate). The negative impact of ACE inhibitors group was maintained after multivariate analyses adjusting for risk factors (HR = 1.9 IC95% 1.1-3.5 p = 0.02 for PFS and HR = 2.3 IC95% 1.2-4.4 p = 0.01 for OS). RNA sequencing and CIBERSORT analysis underlines that ACE inhibitors group has lower M1 macrophage, activated Mast cells, NK cells and memory activated T cells thus suggesting an immunosuppressive state. Conclusions: ACE inhibitors prescription concomitant to the PD-1/PD-L1 inhibitors treatment impairs the outcome in patients with advanced NSCLC pts. This reduction is independent of classical prognostic factors. Biological date underlines an immunosuppressive state in ACE inhibitors group. These data should be validated in larger cohort.

e20676 Background: Age and body mass index (BMI) are important factors in patients treated with chemotherapy. However, in the era of immune checkpoint inhibitors (ICI), the importance of these baseline characteristics is unclear. For example, pooled analysis of age did not influence the clinical response to ICI, whereas patients with BMI > 35 had better outcomes in melanoma and renal cell carcinoma. More data are needed to clarify the role of these two characteristics in non-small cell lung cancer (NSCLC) patients amenable ICI. Methods: We conducted a retrospective analysis of patients treated with anti-PD1 ICI for advanced NSCLC at the Dijon Cancer Center (n = 177), University of Montreal University Hospital (n = 106) and Quebec Heart and Lung Institute (n = 98). BMI and age were considered as continuous or categorical variables. Patients’ baseline characteristics were compared using the Chi-squared test. Survival curves were estimated by the Kaplan-Meier method and compared with the Log-rank test in a univariate analysis. Multivariate cox regression model was used to determine hazard ratios and 95% confidence intervals for progression-free survival (PFS) and overall survival (OS) between the groups, adjusting for other clinicopathologic features. Results: Among 381 patients included, the median BMI was 24.5 (range 16.2-43.4) and 32.7% and 13.6% were classified as overweight or obese respectively. The median age was 66 (range 37-89) and 29% were older than 70 years-of-age. Considering BMI and age as continuous or categorical variables, they were not associated with PFS or OS, with the exception of BMI in the Dijon cohort (continuous: HR = 0.95, 95%CI[0.91-0.99]; < 25 vs > 25: HR = 0.68, 95%CI[0.47-0.99]). Subgroup analysis and multivariate cox regression did not reveal significant interaction of these two factors with outcomes. There was no difference in toxicity between the groups. ECOG performance status was the only significant factor in the three cohorts. Conclusions: Unlike previously described in the era of chemotherapy, obesity and age were not associated with outcomes in NSCLC patients treated with ICI.

e21095Background: Radiation is known to be the main risk factor for secondary malignancies. However, metastatic lung cancer prognosis when thoracic radiation was previously given is unknown. Method...

e21064Background: First/second generation EGFR-TKI are eventually met with therapeutic failure in EGFRm aNSCLC, but treatment continuation beyond initial progression can delay the need for second l...

e20561Background: Asbestos exposure is main risk factor for pleural mesothelioma. We decided to look to the impact of different risk factors (Tabaco, obesity, sex, stage, histology, prior radiation...

IntroductionBR.21 demonstrated significant survival benefit for non-small cell lung cancer patients receiving erlotinib compared with placebo. We undertook to characterize, by exploratory subset analysis, patients less likely to benefit from erlotinib.MethodsUsing stratification and potential prognostic factors, Cox regression with stepwise selection with minimum Akaike Information Criteria was used to separate erlotinib patients into risk categories based on 10th, 50th, and 90th percentiles of prognostic index scores. The hypothesis was that characteristics of treated patients in the highest risk group would be predictive of lack of benefit from erlotinib when comparing erlotinib to placebo patients in the same risk group.ResultsTen factors (smoking history, performance status, weight loss, anemia, lactic dehydrogenase, response to prior chemotherapy, time from diagnosis, number of prior regimens, epidermal growth factor receptor copy, and ethnicity) were predictive of overall survival for erlotinib-treated patients and were used in the final model. Four risk groups were derived from the index score of the Prognostic Model: Low Risk (HR = 0.34, p < 0.001), Intermediate Low and Intermediate High Risk (HR 0.76, p = 0.05; HR 0.92; p = 0.51) and High Risk (HR 1.07; p = 0.78). Median survivals for erlotinib (placebo) patients in each group were 20.6 (8.9), 10.4 (7.6), 4.0 (4.1), 1.9 (2.3) months. The trend test showed that higher risk was associated with shorter survival (p < 0.001) and less treatment effect (p = 0.03).ConclusionsBy establishing a prognostic model, we identified a small group of patients who did not seem to benefit from erlotinib in this study. This model requires prospective validation to confirm that it is both prognostic and predictive of outcome.

BACKGROUND: Treatment of glioblastoma multiforme (GBM) among patients older than 70 with standard 60Gy radiotherapy (SRT) plus temozolomide (TMZ) is challenging in terms of tolerability. Hypofractionated RT (HRT) alone or combined with TMZ is proposed, but results of these prospective randomized trials with favourable KPS patients are pending. METHODS: We retrospectively reviewed all GBM patients aged over 55 treated in our institution from 2010 to 2014. Demographic and tumor characteristics were extracted. Log-rank test and Cox proportional hazards model were used to estimate Kaplan Meier survival and hazard ratio. We divided our cohort in 4 groups according to treatment: concomitant chemoradiotherapy (CCRT) with SRT; CCRT with HRT; HRT alone; TMZ alone. RESULTS: Among the 171 patients identified, the median overall survival (mOS) in patients

e20089 Background: Adjuvant chemotherapy with Cisplatinum/Vinorelbine is an established regimen since a decade in selected resected NSCLC population in order to improve DFS and overall survival. However, the outcome of patients treated outside the research protocols is not as good as in clinical trials. Methods: We retrospectively reviewed 209pts resected stage I to III NSCLC patients using our SARDO database, treated in our University hospital between 2006 and 2015 with a median follow-up of 13mos. Any adjuvant chemotherapy was recorded. Results: Amongst 209 resected NSCLC patients, 185pts (89%) had negative margins and 24pts (11%) have positive margins resection. The observation group and the chemotherapy group in both settings were well-balanced in terms of demographic, co-morbidities and tumor characteristics. As expected, the median overall survival (mOS) in negative margins was significantly better than in positive margins patients (43mos vs 24mos p = 0.029). In negative margins patients, no survival benefit was seen in stage I (A and B) (57 mos for chemo group vs 77 mos for observation group p = 0,217) and stage III (A and B) (39mos mOS for chemo group vs 40mos for observation group, p = 0.37), but a trend for improved mOS was seen in stage II (52 mos for chemo group vs 38 mos for observation group, p = 0.114), also consistent with mPFS results for each group. However, for the small number of patients with positive margins, a significant improvement in survival was seen in chemotherapy arm (mOS 37mos) compared to observational arm (mOS 11mos p = 0,039). No significant difference in survival was seen between Carbo/Taxol regimen and Cisplatinum/Vinorelbine regimen (43 mos vs 38 mos p = 0,658). Conclusions: In our unselected population, adjuvant chemotherapy did not show the improvement in survival expected with margin negative resected NSCLC. In positive resected NSCLC, adjuvant chemotherapy benefit was statistically significant, emphasizing need to treatment to these patients.

e20669 Background: The new 2016lung cancer classification differentiates oligometastatic (M1b) better prognostic from plurimetastatic (M1c) disease. A prospective study presented at 2016 ASCO showed improved PFS in patients with oligometastatic brain disease treated aggressively compared to a more palliative treatment but OS data is pending. Methods: This study is a single-center retrospective study including 643 patients with metastatic lung cancer diagnosed in an University center (CHUM) from 2005-2015 and followed more than 6 months (median follow up 13.3mo) . Only 67 patients (10.4%) were found to have synchronous oligometastatic disease at diagnosis. Results: Amongst the 67 patients, the localization of metastatic disease was as follows: 74% brain (n = 50), 9% adrenal gland (n = 6), 7% contralateral pulmonary lobe (n = 5), 6% bone (n = 4) and 3% liver (n = 2). 29 patients received radical treatment to primary and metastatic site (group A) and 36 patients received non-aggressive treatments (group B). There was no statistically significant difference between the two groups in terms of demographic and histological characteristics. The radical treatment group A had a mOS of 26mo and a mPFS of 12.8m compared to mOS of 5mo (p = 0.0001) and mPFS of 4.8mo (p = 0.010) for group B. This difference was observed when stratifying according to stage of primary lung disease (stage I mOS 42mo vs 16mo, stage II mOS 34mo vs 6mo and stage III mOS 22mo vs 4mo) and according to to oligometastatic site. Interestingly, addressing aggressively the primary lung cancer improved median survival even when the oligometastasis was not resected (26mo v and 24mo respectively), but not when oligometastasis only was resected and primary was treated palliatively (5mo vs 3 mo). Adjuvant chemotherapy given after radical treatment did not improve mPFS or mOS (12.83 vs12.47 months, p = 0.860). Conclusions: Radical treatment of oligometastatic NSCLC in this unselected population improved mPFS and mOS compared to other treatment strategies. As overall survival data of the prospective trial presented at 2016 ASCO meeting is pending, the more radical approach should be emphasized when patients present with oligometastatic lung cancer disease.

e20579 Background: Diabetes is a frequent diagnostic (9.3%) in general Western population, and because of its complications, becomes a comorbidity in NSCLC patients that could impact on prognostic. Impact of diabetes on NSCLC prognosis is unknown but the majority of patients fear eating desserts because feeding mostly the NSCLC tumor cells. Methods: Using our SARDO database and hospital files, we retrospectively reviewed 548 patients with metastatic NSCLC diagnosed and treated in our University hospital between 2006 and 2015. Uncontrolled diabetes was established when Hb1Ac > 7% or with more than 2 hospital glycemia over 11 mmol/L. Results: Amongst 418 metastatic NSCLC patients, 294pts (70%) had synchronous metastasis at diagnostic and 117pts (30%) have metachronous metastasis. As expected metachronous metastasis patients had a better survival (mOS 25mo) than synchronous metastasis (mOS 6mo). Then, we divided our patients in 4 subgroups: 1) Patients with diagnosed and uncontrolled diabetes (n = 78); 2) Patients with high glycemia but not previously diabetes diagnostic (n = 19); 3) Patients with controlled diagnosed diabetes (n = 59); 4) Control patients with normal glycemias or HBA1c (n = 262). Some tumor stage and demographic disparities were seen between the 4 groups but we controlled for them. In upfront metastatic NSCLC patients, mOS was 4.0 months for group 1, 4.0 months for group 2, 4.0 months for group 3 and 7.0 months for our control group, not statistically different, which is lower than literature but expected for this unselected population treated before 2015. In metachronous patients, group 1 mOS was 21mo, group 2 was 58mo, group 3 was 30mo and mOS was 23mo for control patients, with no statistically difference between groups. Women had a better mOS 8 mo compared to 4 mo in men (p = 0,003) independently of diabetes or sugar status. Conclusions: This retrospective data is reassuring regarding patients blood glycemia during the metastatic lung cancer treatment. Even in a long term metachronous disease perspective, blood sugar or diabetes diagnostic did not seem to influence the outcome. However, these data should be validated in a prospective study that could acknowledge if blood sugar control could improve lung cancer outcome.

Purpose National Cancer Institute of Canada Clinical Trials Group JBR.10 study is among the landmark trials that have established third generation platinum-based adjuvant chemotherapy as the standard of care after resection of stages IB-II NSCLC, improving absolute 5-year survival by 15% and median survival by 21 months. This cost-effectiveness analysis of adjuvant chemotherapy from the perspective of Canada's public health care system was undertaken based on the JBR.10 study population. Patients and Methods The primary outcome of the study was the incremental cost effectiveness ratio (ICER) expressed in dollars per life-year gained (LYG). Direct medical resource utilization data were collected retrospectively from trial data and medical records of patients enrolled in the JBR.10 study at the five largest accruing Canadian centers, from the time of random assignment until death or study closure (April 2004). Survival and available costs (2005 Canadian dollars [$CAD]) are presented both with and without discounting at 5% per year. Results Utilization data were collected from 172 Canadian patients (36% of the trial population), 85 randomly assigned to observation and 87 randomly assigned to chemotherapy. The mean costs of treatment per patient in the observation and adjuvant chemotherapy arms were $23,878 and $31,319, respectively, with an ICER of CAD$7,175/LYG discounted (95% CI, −$3,463 to $41,565), and $10,096/LYG undiscounted (95% CI, −$819 to $55,651). Conclusion Adjuvant vinorelbine plus cisplatin is a highly cost effective treatment that compares very favorably with other standard health care interventions.

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.