CHUM Hopital Notre Dame

Montréal, Canada

CHUM Hopital Notre Dame

Montréal, Canada
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Kwok J.C.W.,CHUM Hopital Notre Dame | Gelinas I.,McGill University | Benoit D.,Constance Lethbridge Rehabilitation Center | Chilingaryan G.,Jewish Rehabilitation Hospital
British Journal of Occupational Therapy | Year: 2015

Introduction: The objectives of this study are to determine (1) the ability of the Montreal Cognitive Assessment to predict on-road driving performance in drivers with a neurological condition and elderly drivers with suspected cognitive decline, and (2) the association between the performance on the Useful Field of View and the performance on the Montreal Cognitive Assessment. Method: This study used a retrospective design. Clients were included who had completed the Montreal Cognitive Assessment and the on-road driving evaluation from November 2006 to May 2009 (n =154) in a driving rehabilitation program in the Montreal Area. Total scores on the Montreal Cognitive Assessment, Useful Field of View risk categories, pass or fail outcomes from an on-road evaluation, as well as demographic and clinical characteristics were recorded from participants' medical charts. Results: The Montreal Cognitive Assessment was found to have a sensitivity of 84.5% and a specificity of 50% with a cut-off of ≤25. It was significantly associated with the Useful Field of View risk category. Conclusion: The Montreal Cognitive Assessment could be a valuable screening tool. However, its predictive validity is not strong enough to recommend its use as the sole instrument for identifying unfit drivers. © The Author(s) 2015.

El-Bared N.,CHUM Hopital Notre Dame | Taussky D.,CHUM Hopital Notre Dame | Mehiri S.,CHUM Hopital Notre Dame | Patocskai E.,Center Hospitalier Of Luniverstie Of Montreal Hopital Notre Dame | And 3 more authors.
Technology in Cancer Research and Treatment | Year: 2014

The use of intensity modulated radiation therapy (IMRT) has allowed for the administration of high doses to retroperitoneal sarcomas (RSTS) while limiting toxicity to adjacent organs. The purpose of our study is to assess the outcome and toxicities of patients with RSTS treated with neo-adjuvant external beam radiation (EBRT) therapy using IMRT. This is a retrospective study of 21 patients treated with preoperative IMRT for primary or recurrent RSTS between 2005 and 2011. Overall survival (OS) and local recurrence free survival (LRFS) were computed using the Kaplan-Meier method (log-rank test). Acute and chronic toxicities were assessed using the CTCAE v. 3 criteria. The actuarial 2 and 3-year OS was 66% for both and the 5-year OS was 51%. As for LRFS it was 57% at 2 and 3-year and 51% for the 5-year LRFS. Factors predictive for local control were microscopically negative margins (p = 0.022), a median tumor diameter <15 cm (p = 0.007) and pathology of liposarcoma (p = 0.021). Furthermore, patients treated for recurrent disease fared worse (p = 0.04) in local control than patients treated for primary disease. As for OS, patients treated for Grade 1 histology had a better outcome (p = 0.05). EBRT was generally well tolerated. Acute gastrointestinal (GI) Grade 1 or 2 toxicities occurred in 33% of patients and one patient had unexplained post-radiation Grade 2 fever that resolved after tumor resection. As for chronic toxicities 24% of our patients presented Grade 1 GI toxicity and one patient presented Grade 3 small bowel stenosis not clearly due to radiation toxicity. Despite the location and volume of the tumors treated, preoperative IMRT was very well tolerated in our patients with retroperitoneal sarcoma. Unfortunately local recurrences remain common and dose escalation is to be considered. © Adenine Press (2014).

Thiessen B.,BC Cancer Agency | Stewart C.,St Judes Childrens Research Hospital | Tsao M.,Princess Margaret Hospital | Kamel-Reid S.,Princess Margaret Hospital | And 7 more authors.
Cancer Chemotherapy and Pharmacology | Year: 2010

Purpose: We undertook a phase I/II study of the EGFR/erbB2 inhibitor lapatinib in patients with recurrent glioblastoma multiforme (GBM) to determine response rate, pharmacokinetics (PK) and recommended dose in patients taking enzyme-inducing anti-epileptic drugs (EIAEDs) and to explore relationships of molecular genetics to outcome. Methods: Recurrent GBM patients taking EIAEDs were enrolled on the phase I portion (starting dose of lapatinib 1,000 mg po bid). In the absence of dose-limiting toxicity (DLT), escalation continued in cohorts of three patients. Patients not on EIAEDs enrolled in the phase II arm (lapatinib 750 mg bid po). Immunohistochemical and quantitative RT PCR studies were performed on tumor to determine PTEN and EGFRvIII status, respectively. Lapatinib PK was analyzed using HPLC with tandem mass spectrometry. Results: Phase II: Of 17 patients, 4 had stable disease and 13 progressed. Accrual ceased because of no responses. Phase I: Four patients received 1,000 mg bid and three, 1,500 mg bid. No DLT occurred, but escalation stopped because of lack of phase II efficacy. Lapatinib apparent oral clearance in patients taking EIAEDs was 106.9 L h-1 m-2 in comparison to 12.1 L h-1 m-2 in those not on EIAEDs. In 16 phase II patients, PTEN loss was seen in 6 and EGFRvIII expression in 4. No correlation was seen with outcome and molecular results. Conclusions: Lapatinib apparent oral clearance increased by approximately tenfold when given with EIAEDs. In this small sample, EGFRvIII expression and PTEN loss did not predict a favorable subtype. Overall, lapatinib did not show significant activity in GBM patients. © 2009 Springer-Verlag.

Lambert L.,CHUM Hopital Notre Dame | Fortin B.,CHUM Hopital Notre Dame | Soulieres D.,CHUM Hopital Notre Dame | Guertin L.,CHUM Hopital Notre Dame | And 6 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2010

Purpose: To determine the rates of organ preservation and function in patients with advanced laryngeal and hypopharyngeal carcinomas treated with concurrent chemoradiotherapy (CRT). Methods and Materials: Between April 1999 and September 2005, 82 patients with advanced laryngeal (67%) and hypopharyngeal carcinomas (33%) underwent conventional radiotherapy and concurrent platinum-based chemotherapy with curative intent. Sixty-two patients were male (75.6%). The median age was 59 years. Eighteen patients (22%) were in Stage III and 64 (78%) were in Stage IV. The median radiation dose was 70 Gy. The median potential follow-up was 3.9 years. Results: Overall survival and disease-free survival were respectively 63% and 73% at 3 years. Complete response rate from CRT was 75%. Nineteen patients (23%) experienced significant long-term toxicity after CRT: 6 (7.3%) required a percutaneous endoscopic gastrostomy, 5 (6%) had persistent Grade 2 or 3 dysphagia, 2 (2.4%) had pharyngoesophageal stenosis requiring multiple dilations, 2 (2.4%) had chronic lung aspiration, and 7 (8.5%) required a permanent tracheostomy. Four patients (4.9%) underwent laryngectomy without pathologic evidence of disease. At last follow-up, 5 (6%) patients were still dependent on a gastrostomy. Overall, 42 patients (52%) were alive, in complete response, with a functional larynx and no other major complications. Conclusions: In our institution, CRT for advanced hypopharyngeal and laryngeal carcinoma has provided good overall survival and locoregional control in the majority of patients, but a significant proportion did not benefit from this approach because of either locoregional failure or late complications. Better organ preservation approaches are necessary to improve locoregional control and to reduce long-term toxicities. © 2010 Elsevier Inc. All rights reserved.

Weller M.,University of Zürich | Weller M.,University of Tübingen | Gorlia T.,European Organisation for Research and Treatment of Cancer | Cairncross J.G.,University of Calgary | And 12 more authors.
Neurology | Year: 2011

Objective: This analysis was performed to assess whether antiepileptic drugs (AEDs) modulate the effectiveness of temozolomide radiochemotherapy in patients with newly diagnosed glioblastoma. Methods: The European Organization for Research and Treatment of Cancer (EORTC) 26981- 22981/National Cancer Institute of Canada (NCIC) CE.3 clinical trial database of radiotherapy (RT) with or without temozolomide (TMZ) for newly diagnosed glioblastoma was examined to assess the impact of the interaction between AED use and chemoradiotherapy on survival. Data were adjusted for known prognostic factors. Results: When treatment began, 175 patients (30.5%) were AED-free, 277 (48.3%) were taking any enzyme-inducing AED (EIAED) and 135 (23.4%) were taking any non-EIAED. Patients receiving valproic acid (VPA) only had more grade 3/4 thrombopenia and leukopenia than patients without an AED or patients taking an EIAED only. The overall survival (OS) of patients who were receiving an AED at baseline vs not receiving any AED was similar. Patients receiving VPA alone (97 [16.9%]) appeared to derive more survival benefit from TMZ/RT (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.24-0.63) than patients receiving an EIAED only (252 [44%]) (HR 0.69, 95% CI 0.53-0.90) or patients not receiving any AED (HR 0.67, 95% CI 0.49-0.93). Conclusions: VPA may be preferred over an EIAED in patients with glioblastoma who require an AED during TMZ-based chemoradiotherapy. Future studies are needed to determine whether VPA increases TMZ bioavailability or acts as an inhibitor of histone deacetylases and thereby sensitizes for radiochemotherapy in vivo. Copyright © 2011 by AAN Enterprises, Inc.

Chiappori A.A.,H. Lee Moffitt Cancer Center and Research Institute | Kolevska T.,Kaiser Permanente | Spigel D.R.,Sarah Cannon Research Institute | Hager S.,Cancer Care Associates of Fresno Medical Group | And 9 more authors.
Annals of Oncology | Year: 2015

Imetelstat, a novel telomerase inhibitor, failed to improve significantly median PFS and OS as maintenance therapy (±bevacizumab) in advanced NSCLC. Telomere length (TL) biomarker results were consistent with the hypothesis that telomerase inhibition is of greater benefit to patients with tumors possessing shorter telomeres; the patients with shorter TL had a trend toward longer median PFS and OS. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Gourishankar S.,University of Alberta | Houde I.,Hotel Dieu de Quebec | Keown P.A.,University of British Columbia | Landsberg D.,St Pauls Hospital | And 6 more authors.
Clinical Journal of the American Society of Nephrology | Year: 2010

Background and objectives: Adequate early mycophenolic acid (MPA) exposure is associated with lower rates of acute rejection in renal transplantation. The aim of this randomized controlled trial was to determine if higher initial mycophenolate mofetil (MMF) doses increased the proportion of patients reaching therapeutic MPA levels (30 to 60 mg•h/L) by day 5. Design, setting, participants, & measurements: De novo renal transplant patients were randomized to receive intensified dosing of MMF (1.5 g twice daily on days 1 to 5, then 1.0 g twice daily) or standard dosing (1.0 g twice daily). All recipients received tacrolimus and prednisone. Full MPA areas under the curve (AUCs) were completed on days 3 and 5, whereas a limited sampling strategy was utilized at four subsequent time points. Results: At day 5, 47.5% of the MMF 3-g arm achieved the MPA therapeutic window versus 54.4% of the MMF 2-g arm. However, MPA AUC levels were significantly higher in the 3-g arm at day 3 and 5. This resulted in a trend for fewer treated acute rejections at 6 months. Significantly more acute rejections (treated, biopsy-proven including and excluding borderline) occurred in patients with MPA AUC levels <30 mg•h/L compared with those ≥30 mg•h/L at day 5. No significant differences were seen in common adverse events. Conclusions: A limited intensified dose of MMF increased early MPA exposure and was well tolerated. Further studies are required to determine whether limited intensified MMF dosing can reduce acute rejection. Copyright © 2010 by the American Society of Nephrology.

Labidi M.,CHU de Quebec | Lavoie P.,CHU de Quebec | Lapointe G.,CHU de Quebec | Obaid S.,CHUM Hopital Notre Dame | And 3 more authors.
Journal of Neurosurgery | Year: 2015

Object Endoscopic third ventriculostomy (ETV) has become the first line of treatment in obstructive hydrocephalus. The Toronto group (Kulkarni et al.) developed the ETV Success Score (ETVSS) to predict the clinical response following ETV based on age, previous shunt, and cause of hydrocephalus in a pediatric population. However, the use of the ETVSS has not been validated for a population comprising adults. The objective of this study was to validate the ETVSS in a "closed-skull" population, including patients 2 years of age and older. Methods In this retrospective observational study, medical charts of all consecutive cases of ETV performed in two university hospitals were reviewed. The primary outcome, the success of ETV, was defined as the absence of reoperation or death attributable to hydrocephalus at 6 months. The ETVSS was calculated for all patients. Discriminative properties along with calibration of the ETVSS were established for the study population. The secondary outcome is the reoperation-free survival. Results This study included 168 primary ETVs. The mean age was 40 years (range 3-85 years). ETV was successful at 6 months in 126 patients (75%) compared with a mean ETVSS of 82.4%. The area under the receiver operating characteristic curve was 0.61, revealing insufficient discrimination from the ETVSS in this population. In contrast, calibration of the ETVSS was excellent (calibration slope = 1.01), although the expected low numbers were obtained for scores < 70. Decision curve analyses demonstrate that ETVSS is marginally beneficial in clinical decision-making, a reduction of 4 and 2 avoidable ETVs per 100 cases if the threshold used on the ETVSS is set at 70 and 60, respectively. However, the use of the ETVSS showed inferior net benefit when compared with the strategy of not recommending ETV at all as a surgical option for thresholds set at 80 and 90. In this cohort, neither age nor previous shunt were significantly associated with unsuccessful ETV. However, better outcomes were achieved in patients with aqueductal stenosis, tectal compressions, and other tumor-associated hydrocephalus than in cases secondary to myelomeningocele, infection, or hemorrhage (p = 0.03). Conclusions The ETVSS did not show adequate discrimination but demonstrated excellent calibration in this population of patients 2 years and older. According to decision-curve analyses, the ETVSS is marginally useful in clinical scenarios in which 60% or 70% success rates are the thresholds for preferring ETV to CSF shunt. Previous history of CSF shunt and age were not associated with worse outcomes, whereas posthemorrhagic and postinfectious causes of the hydrocephalus were significantly associated with reduced success rates following ETV. © AANS, 2015.

Delouya G.,CHUM Hopital Notre Dame | Igidbashian L.,CHUM Hopital Notre Dame | Houle A.,CHUM Hopital Notre Dame | Belair M.,Center Hospitalier Of Luniversite Of Montreal Chum | And 9 more authors.
Radiotherapy and Oncology | Year: 2011

Purpose: To determine the impact of 18F-fluorodeoxyglucose positron emission tomography (PET) in radiotherapy target delineation and patient management for head and neck squamous cell carcinoma (HNSCC) compared to computed tomography (CT) alone. Materials and methods: Twenty-nine patients with HNSCC were included. CT and PET/CT obtained for treatment planning purposes were reviewed respectively by a neuroradiologist and a nuclear medicine specialist who were blinded to the findings from each other. The attending radiation oncologist together with the neuroradiologist initially defined all gross tumor volume of the primary (GTVp) and the suspicious lymph nodes (GTVn) on CT. Subsequently, the same radiation oncologist and the nuclear medicine specialist defined the GTVp and GTVn on 18F-FDG-PET/CT. Upon disagreement between CT and 18F-FDG-PET on the status of a particular lymph node, an ultrasound-guided fine needle aspiration was performed. Volumes based on CT and 18F-FDG-PET were compared with a paired Student's t-test. Results: For the primary disease, four patients had previous diagnostic tonsillectomy and therefore, FDG uptake occurred in 25 patients. For these patients, GTVp contoured on 18F-FDG-PET (GTVp-PET) were smaller than the GTVp contoured on CT (GTVp-CT) in 80% of the cases, leading to a statistically significant volume difference (p = 0.001). Of the 60 lymph nodes suspicious on PET, 55 were also detected on CT. No volume change was observed (p = 0.08). Ten biopsies were performed for lymph nodes that were discordant between modalities and all were of benign histology. Distant metastases were found in two patients and one had a newly diagnosed lung adenocarcinoma. Conclusions: GTVp-CT was significantly larger when compared to GTVp-PET. No such change was observed for the lymph nodes. 18F-FDG-PET modified treatment management in three patients, including two for which no curative radiotherapy was attempted. Larger multicenter studies are needed to ascertain whether combined 18F-FDG-PET/CT in target delineation can influence the main clinical outcomes. © 2011 Elsevier Ireland Ltd. All rights reserved.

PubMed | CHUM Hopital Notre Dame
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

22087 Background: The PI3K/Akt/NF-B pathway activation is central to prostate cancer progression and therefore an attractive therapeutic target. There is in vitro evidence that the ErbB family of epidermal growth factor receptors are involved in the constitutive activation of the PI3K/Akt/NF-B pathway, while activated PTEN can inhibit the activation of Akt by PI3K. However, the in vivo mechanismsby which ErbB family receptors activate the PI3K/Akt/NF-B pathway in prostate cancer cells is still unknown. A preliminary investigation of pathway markers was undertaken to identify patterns of expression in prostate cancer tissues using immunohistochemistry (IHC). Furthermore, marker expression was correlated with clinical outcomes.IHC was done on an in-house prostate tissue array containing 368 cores from 63 cancer patients. We investigated the correlation of the clinicopathological parameters predicting outcome for native and appropriate activated phospho isoforms for EGFR, phospho-EGFR, Her2, phospho-Her2, ErbB3, PI3K, phospho-Akt, PTEN, phospho-PTEN and p65 NF-B and phospho-p65. HCA was used to organize score data and to identify the best protein profile associated with biochemical recurrence (BCR).Phospho-EGFR and phospho-Her2 expression were significantly increased in Gleason 6 and correlated with the activation of Akt (r=0.728, p<0.0001) and p65 NF-B (p=0.012). No correlation was observed between PTEN or phospho-PTEN and Akt activation. Interestingly, Kaplan-Meier analyses of several proteins including ErbB3, p65 NF-B, phospho-Akt were associated with BCR, with the activated forms of EGFR and Her2 having the best predictive values (p<0.001). HCA categorized 4 groups of patients primarily based on EGFR activation status. We observed a strong statistically significant difference in the BCR between the 4 groups, which confirmed the observation of the strong association between activation of EGFR, Her2 and Akt with BCR.Our in vivo study support the in vitro evidence that activated EGFR and activated Her2 are involved in the activation of the PI3K/Akt/NF-B pathway. In addition our results suggest that in vivo PTEN-independent mechanisms are also involved in the activation of Akt in prostate cancer. No significant financial relationships to disclose.

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