Albert Moghrabi

Université de Montréal, Montréal, Quebec, Canada

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Publications (100)562.22 Total impact

  • C Rae · W Furlong · M Jankovic · Albert Moghrabi · A Naqvi · A Sala · Y Samson · S Depauw · D Feeny · R Barr ·
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    ABSTRACT: Berlin-Frankfurt-Munster (BFM) and Dana-Farber Cancer Institute (DFCI) consortia's treatment strategies for acute lymphoblastic leukaemia (ALL) in children are widely used. We compared the health effects and monetary costs of hospital treatments for these two strategies. Parents of children treated at seven centres in Canada, Italy and the USA completed health-related quality of life (HRQL) assessments during four active treatment phases and at 2 years after treatment. Mean HRQL scores were used to calculate quality-adjusted life years (QALYs) for a period of 5 years following diagnosis. Total costs of treatment were determined from variables in administrative databases in a universally accessible and publicly funded healthcare system. Valid HRQL assessments (n = 1200) were collected for 307 BFM and 317 DFCI patients, with costs measured for 66 BFM and 28 DFCI patients. QALYs per patient were <1.0% greater for BFM than DFCI. Median HRQL scores revealed no difference in QALYs. The difference in mean total costs for BFM (US$88 480) and DFCI (US$93 026) was not significant (P = 0.600). This study provides no evidence of superiority for one treatment strategy over the other. Current BFM or DFCI strategies should represent conventional management for the next economic evaluation of treatments for ALL in childhood.
    European Journal of Cancer Care 01/2014; 23(6). DOI:10.1111/ecc.12173 · 1.56 Impact Factor
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    ABSTRACT: Background Osteonecrosis (ON) is a severe complication of acute lymphoblastic leukemia (ALL) treatments. Recent studies suggest that bisphosphonates might reduce pain and loss of motor function in patients with ON. We assessed the effects of pamidronate compared to standard care in patients with symptomatic ON (sON) and studied whether steroids might be continued after diagnosis of ON in some patients. Methods We evaluated 17 patients with sON as complication of primary ALL treatment between 2000 and 2008. Fourteen patients were treated with pamidronate. Mobility and pain control were monitored in all patients. Affected joints were classified by magnetic resonance imaging (MRI) at ON diagnosis and after 6–72 months. ResultsOut of 220 patients with ALL, 17 (7.7%) patients developed sON. The median age at ALL diagnosis was 11 years (range: 2.7–16.6 years) and sON occurred a median of 13.4 months (range: 2.5–34 months) after ALL diagnosis. Affected joints were hip, knee and ankle. MRI scans showed 7 severe, 4 moderate, and 6 mild ON lesions. Fourteen patients showed improvement in pain (77% of patients) and motor function (59% of patients), even though corticoids were reintroduced in 4 patients. MRI demonstrated improvement, stability or worsening in 6, 3, and 5 cases, respectively. Conclusions Pamidronate seems to be effective in the management of pain and motor function recovery in sON. Further studies are needed to provide evidence as to whether bisphosphonates can be recommended for the treatment or the prevention of ON in childhood ALL patients. Pediatr Blood Cancer 2013; 60: 741–747. © 2012 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 05/2013; 60(5). DOI:10.1002/pbc.24313 · 2.39 Impact Factor
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    ABSTRACT: : Neuropsychological problems occurrence varies among childhood cancer survivors, and associated risk factors have not been fully deciphered. We wanted to study the role of genetic variants in behavioral problems in this population. : Behavioral problems in pediatric acute lymphoblastic leukemia patients (n=138) were investigated longitudinally, using the Child Behavior Checklist questionnaire and multilevel statistical modeling. Thirty-four candidate polymorphisms, related to anticancer drug effects, were investigated. : NOS3 gene functional polymorphisms showed significant association: patients homozygous for the minor allele at investigated loci showed decreased externalizing behavioral problems scores over time (t tests: T-786C n=69, P=0.003; G894T n=71, P=0.065). The effect was even more pronounced for individuals that are homozygous for the -786C844T haplotype (t test, n=69, P<0.001) and results were supported by multilevel modeling analyses (P<0.001). No such association was observed for internalizing behavioral problems. : NOS3 variants modulate externalizing problems individual trajectories, likely in relationship with glucocorticoid exposure.
    Journal of Pediatric Hematology/Oncology 05/2013; 35(4):e157-62. DOI:10.1097/MPH.0b013e31828e518d · 0.90 Impact Factor
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    ABSTRACT: Pediatric cancer survivors are at increased risk of various neurological and psychological problems. The prevalence of behavioral problems was assessed in a longitudinal study in pediatric patients with an acute lymphoblastic leukemia (ALL). Multilevel modeling was used to identify associated predictive factors. ALL patients and their parents (n = 138) took part to this study. Patients were treated according to the Dana-Farber Cancer Institute (DFCI) consortium protocols 91-01 or 95-01. Mothers filled out questionnaires providing a measure of behavioral problems for their child at diagnosis and during the subsequent 4 years, and of their perceived familial stress at diagnosis and post-induction. Prevalence of internalized behavioral problems at diagnosis was increased [42% above 1 standard deviation (SD); P < 0.001], but it normalized over time. Internalized problems resolved more slowly in the presence of medical variables associated with increased stress related to the disease (hospitalization duration, P < 0.001; relapse risk at diagnosis, P < 0.001). Externalized behavioral problems were within the expected normal range, but more sustained over time with the 95-01 than with the 91-01 treatment protocols (P < 0.05), likely due to the type of corticosteroid (CS) used (dexamethasone vs. prednisone). Assessment of both internalized and externalized problems is required in this population. The impact of pharmacological variables on externalized behavioral problems is likely related to CS use.
    Pediatric Blood & Cancer 06/2012; 58(6):971-7. DOI:10.1002/pbc.24079 · 2.39 Impact Factor
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    ABSTRACT: Asparaginase is a standard and critical component in the therapy of childhood acute lymphoblastic leukemia. Asparagine synthetase (ASNS) and the basic region leucine zipper activating transcription factor 5 (ATF5) and arginosuccinate synthase 1 (ASS1) have been shown to mediate the antileukemic effect of asparaginase and to display variable expression between leukemia cells that are resistant and sensitive to treatment. Fourteen polymorphisms in the regulatory and coding regions of these genes were investigated for an association with acute lymphoblastic leukemia outcome. Lower event-free survival (EFS) was associated with ATF5 T1562C, tandem-repeat ASNS polymorphism, derived haplotype, and ASS1 G1343T and G34T substitutions (P ≤ .03). Associations were limited to patients who received Escherichia coli asparaginase. Variations that sustained correction for multiple testing (ATF5 T1562C, P = .005; ASNS tandem-repeat and related haplotype, P ≤ .01) were subsequently analyzed in the replication cohort. The E coli-dependent association of the ATF5 T1562 allele with reduced EFS was confirmed (P = .01). A gene-reporter assay showed that the haplotype tagged by T1562 had higher promoter activity (P ≤ .01). The remaining regulatory polymorphisms also appeared to affect ATF5 function; 2 additional high-activity haplotypes were identified (P ≤ .02) and were further corroborated by quantitative mRNA analysis in lymphoblastoid cell lines. The ATF5-regulated increase in ASNS expression in response to more efficacious E coli-induced asparagine depletion may explain our observed results.
    Blood 11/2011; 118(22):5883-90. DOI:10.1182/blood-2011-05-355560 · 10.45 Impact Factor
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    ABSTRACT: Tumors of the spinal cord are exceedingly rare in infancy and only a paucity of literature exists describing the spectrum of this disease and its management. The objectives of our study were to describe the demographic characteristics of spinal cord tumors (SCT) in children less than 3 years of age at diagnosis and to review their treatment and outcome. A national retrospective chart review was conducted on patients under the age of 3 years diagnosed with a primary tumor of the central nervous system (CNS) between 1990 and 2005 across Canada. Inclusion criteria were: age ≤ 3 years, histologic confirmation of the diagnosis, and residency in Canada. A centralized database was created and information regarding SCT was extracted. Twenty-five of five hundred seventy-nine patients (4.3%) in the data bank had a SCT. The majority of tumors were low-grade astrocytomas (14/25). Leptomeningeal dissemination based on neuroradiologic imaging and/or cerebrospinal fluid cytology was present in five (20%) patients. The majority of patients underwent an incomplete surgical resection (52%). Most patients (64%) did not receive postoperative radiotherapy or chemotherapy. Seventy-two percent (18/25) developed recurrent/progression of disease. Overall 2- and 5-year survival for low- and high-grade malignancies was 93 ± 6.4% and 37.5 ± 17.1% respectively. Significant predictors of survival included mean duration of symptoms prior to initial diagnosis and recurrence/progression of disease. Relapse/progression of disease in infant SCT is frequent. Prolonged survival of low-grade tumors is possible with further therapy; however, the prognosis of high-grade malignancies remains poor.
    Child s Nervous System 07/2011; 27(7):1089-94. DOI:10.1007/s00381-011-1393-1 · 1.11 Impact Factor
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    ABSTRACT: Multidrug resistance-related proteins (MRPs) 2, 3 and 5 are involved in the efflux of drugs used in acute lymphoblastic leukemia (ALL) treatment. Polymorphisms of these genes were investigated for an association with treatment responses in 273 childhood ALL patients. The MRP3 A-189 allele of the regulatory AT polymorphism was associated with reduced event-free survival (P=0.01). The results remained significant after adjustment for multiple comparisons and in the multivariate analysis. Among patients with an event, the A-189 carriers had significantly higher methotrexate plasma levels (P=0.03). MRP3 A-189 also conferred four times higher risk of a relapse in central nervous system (P=0.01). Patients with this allele tended to have lower frequency of thrombocytopenia grade 2 (P=0.06). Gene reporter assay showed that the haplotype tagged by the A-189 had higher promoter activity (P0.01). In conclusion, MRP3 A-189 T polymorphism was associated with treatment responses in ALL, likely due to the change in MRP3 efflux.
    The Pharmacogenomics Journal 05/2011; 12(5):386-94. DOI:10.1038/tpj.2011.17 · 4.23 Impact Factor
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    ABSTRACT: Doxorubicin chemotherapy is associated with cardiomyopathy. Dexrazoxane reduces cardiac damage during treatment with doxorubicin in children with acute lymphoblastic leukaemia (ALL). We aimed to establish the long-term effect of dexrazoxane on the subclinical state of cardiac health in survivors of childhood high-risk ALL 5 years after completion of doxorubicin treatment. Between January, 1996, and September, 2000, children with high-risk ALL were enrolled from nine centres in the USA, Canada, and Puerto Rico. Patients were assigned by block randomisation to receive ten doses of 30 mg/m² doxorubicin alone or the same dose of doxorubicin preceded by 300 mg/m² dexrazoxane. Treatment assignment was obtained through a telephone call to a centralised registrar to conceal allocation. Investigators were masked to treatment assignment but treating physicians and patients were not; however, investigators, physicians, and patients were masked to study serum cardiac troponin-T concentrations and echocardiographic measurements. The primary endpoints were late left ventricular structure and function abnormalities as assessed by echocardiography; analyses were done including all patients with data available after treatment completion. This trial has been completed and is registered with, number NCT00165087. 100 children were assigned to doxorubicin (66 analysed) and 105 to doxorubicin plus dexrazoxane (68 analysed). 5 years after the completion of doxorubicin chemotherapy, mean left ventricular fractional shortening and end-systolic dimension Z scores were significantly worse than normal for children who received doxorubicin alone (left ventricular fractional shortening: -0·82, 95% CI -1·31 to -0·33; end-systolic dimension: 0·57, 0·21-0·93) but not for those who also received dexrazoxane (-0·41, -0·88 to 0·06; 0·15, -0·20 to 0·51). The protective effect of dexrazoxane, relative to doxorubicin alone, on left ventricular wall thickness (difference between groups: 0·47, 0·46-0·48) and thickness-to-dimension ratio (0·66, 0·64-0·68) were the only statistically significant characteristics at 5 years. Subgroup analysis showed dexrazoxane protection (p=0·04) for left ventricular fractional shortening at 5 years in girls (1·17, 0·24-2·11), but not in boys (-0·10, -0·87 to 0·68). Similarly, subgroup analysis showed dexrazoxane protection (p=0·046) for the left ventricular thickness-to-dimension ratio at 5 years in girls (1·15, 0·44-1·85), but not in boys (0·19, -0·42 to 0·81). With a median follow-up for recurrence and death of 8·7 years (range 1·3-12·1), event-free survival was 77% (95% CI 67-84) for children in the doxorubicin-alone group, and 76% (67-84) for children in the doxorubicin plus dexrazoxane group (p=0·99). Dexrazoxane provides long-term cardioprotection without compromising oncological efficacy in doxorubicin-treated children with high-risk ALL. Dexrazoxane exerts greater long-term cardioprotective effects in girls than in boys. US National Institutes of Health, Children's Cardiomyopathy Foundation, University of Miami Women's Cancer Association, Lance Armstrong Foundation, Roche Diagnostics, Pfizer, and Novartis.
    The Lancet Oncology 10/2010; 11(10):950-61. DOI:10.1016/S1470-2045(10)70204-7 · 24.69 Impact Factor
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    ABSTRACT: The pathogenesis and the impact of therapy on thrombin activation in children with acute lymphoblastic leukemia (ALL) are unknown. Steroids may contribute to ALL-associated thrombosis. We explored the hemostatic effects of methylprednisolone monotherapy (MpMT) (32 mg/m2/day IV x 3 days) in children with newly diagnosed ALL. Children (>1 to < or = 18 years of age) enrolled on DFCI ALL05-01 protocol (n = 30; mean age 6.3 years), without prior steroid therapy, were eligible for study. Overnight fasting pre- and post-MpMT samples were analyzed for coagulation factors [FVIII:C, von Willebrand factor antigen (vWF:Ag) and fibrinogen] and parameters of thrombin generation [prothrombin fragments 1.2 (F1.2), thrombin-antithrombin complex (TAT), and D-dimer]. At diagnosis F1.2 (1.5 nmol/L), TAT (10.9 microg/L), and D-dimers (2,766 ng/ml) levels were increased indicating endogenous thrombin activation. Patients with peripheral blasts (n = 17) had higher levels of vWF:Ag (1.89 vs. 1.14 P = 0.001), TAT (15.39 vs. 5.02 P = 0.038), and D-dimer (3,640 vs. 1,623 P = 0.019) compared to those without peripheral blasts. Following MpMT the blast count decreased significantly from 24% to 3.5% (P < 0.001) with reduction in level of vWF:Ag (1.5, P < 0.01), TAT (8.9, P = 0.42), and D-dimer (P = 0.018) despite 30% increase in FVIII:C levels (P = 0.005). However, patients without peripheral blasts had no significant change in vWF:Ag levels (1.14 vs. 1.25; P = 0.142) and had an increase in thrombin generation parameters. We postulate that peripheral blasts through endothelial activation stimulate vWF:Ag production/secretion causing coagulation activation. Methylprednisolone therapy reduces the blast count and indirectly suppresses the coagulation activation. Future studies are required to confirm these findings.
    Pediatric Blood & Cancer 07/2010; 54(7):963-9. DOI:10.1002/pbc.22466 · 2.39 Impact Factor
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    ABSTRACT: In children under the age of 3, the most common solid tumours are brain tumors. Treatment for many of these patients includes surgery, chemotherapy and rarely radiation therapy. Many clinical trials have been performed in an attempt to establish the best treatment for these patients. Patients enrolled on clinical trials contribute to the establishment of the best therapy. We performed a national survey of all children less than the age of three with brain tumours and examined the contribution these patients made to clinical trials. A data bank was established using data collected from Canadian pediatric oncology centers on children less than age 3 diagnosed with brain tumours between 1990 and 2005. Data were collected on the use of adjunctive treatment after surgery, treatment on a protocol, reasons patients were not registered on a protocol, and reasons for discontinuation of therapy. From the 579 cases in the data bank, 302 (52%) patients were treated with further therapy after surgery. The use of further therapy after surgery was significantly higher in patients with cerebellar and brain stem tumors, patients who were over 1 year of age, patients with ependymal and embryonal tumors, and patients with high grade malignant tumors. Only 62 (21%) patients were enrolled on a protocol for therapy. No factor was significant for being enrolled on a protocol. Reasons for not being registered on a protocol were mainly that there was no open COG/POG/CCG study or the study was not open at the institution. The therapy was stopped because of completion of the protocol in 50% and because of disease progression in 34%. In Canada, about half of children under the age of 36 months with brain tumors are undergoing therapy following surgery for their malignancy but only a small fraction of them are enrolled on a clinical trial. There needs to be improved availability of clinical trials for these patients so that novel therapies can be evaluated and survival improved.
    Journal of Neuro-Oncology 02/2010; 99(2):243-9. DOI:10.1007/s11060-010-0123-y · 3.07 Impact Factor
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    ABSTRACT: Dihydrofolate reductase (DHFR) is the major target of methotrexate, a key component in childhood acute lymphoblastic leukemia (ALL) treatment. We recently reported an association of DHFR promoter polymorphisms with ALL outcome. Lower event-free survival correlated with haplotype *1, defined by A(-317) and C(-1610) alleles. Haplotype *1 was also associated higher DHFR expression. Here, we analyzed adjacent 400-bp region participating in DHFR regulation as both a major promoter and a noncoding minor transcript. Six polymorphisms were identified, of which five were single nucleotide polymorphisms and one was length polymorphism composed of variable number of 9-bp elements and 9-bp insertion/deletion. Haplotype analysis including all promoter polymorphisms revealed diversification of haplotype *1 into five subtypes (*1a-*1e). DNA variations of major promoter/noncoding transcript region and haplotype *1 subtypes were subsequently analyzed for the association with ALL outcome. Lower event-free survival was associated with an A allele of G(308)A polymorphism (P = 0.02) and with *1b haplotype (P = 0.01). This association was particularly striking in high-risk patients (P = 0.001) and was subsequently confirmed in independent patient cohort (P = 0.02). Haplotype *1b was the only haplotype *1 subtype associated with higher mRNA levels. The study provides a new insight into DHFR regulatory variations predisposing to an event in ALL patients.
    Clinical Cancer Research 10/2009; 15(22):6931-8. DOI:10.1158/1078-0432.CCR-09-0641 · 8.72 Impact Factor
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    ABSTRACT: Childhood acute lymphoblastic leukemia patients (n=310) were analyzed for four SNPs in the NR3C1 gene. Polymorphisms -627A/G, intron 2 +646C/G and 9bT/C were all associated with reduced event-free survival. Haplotypes composed of AGT alleles at these loci and tagged by the intron 2 +646G variant also associated with lower event-free survival (p=0.03). The progressive impact of this haplotype on outcome was seen with two copies associated with reduced overall survival (p=0.05). Quantitative mRNA analysis in lymphoblastoid cell lines showed that carriers of the AGT haplotype had a higher ratio of GR gamma/alpha isoforms (p=0.04), which possibly explains its association with reduced event-free survival and overall survival.
    Leukemia research 09/2009; 34(4):492-7. DOI:10.1016/j.leukres.2009.08.007 · 2.35 Impact Factor
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    ABSTRACT: Low rates of participation of adolescents and young adults (AYAs) in clinical oncology trials may contribute to poorer outcomes. Factors that influence the decision of AYAs to participate in health research and whether these factors are different from those that affect the participation of parents of children with cancer. This is a secondary analysis of data from validated questionnaires provided to adolescents (>12 years old) diagnosed with cancer and parents of children with cancer at 3 sites in Canada (Halifax, Vancouver, and Montreal) and 2 in the United States (Atlanta, GA, and Memphis, TN). Respondents reported their own research participation and cited factors that would influence their own decision to participate in, or to provide parental authorization for their child to participate in health research. Completed questionnaire rates for AYAs and parents were 86 (46.5%) of 185 and 409 (65.2%) of 627, respectively. AYAs (n = 86 [67%]) and parents (n = 409 [85%]) cited that they would participate in research because it would help others. AYAs perceived pressure by their family and friends (16%) and their physician (19%). Having too much to think about at the time of accrual was an impediment to both groups (36% AYAs and 47% parents). The main deterrent for AYAs was that research would take up too much time (45%). Nonwhite parents (7 of 56 [12.5%]) were more apt to decline than white parents (12 of 32 [3.7%]; P < .01). AYAs identified time commitment and having too much to think about as significant impediments to research participation. Addressing these barriers by minimizing time requirements and further supporting decision-making may improve informed consent and impact on enrollment in trials.
    PEDIATRICS 09/2009; 124(3):959-65. DOI:10.1542/peds.2008-2878 · 5.47 Impact Factor
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    ABSTRACT: Life-threatening infections from ubiquitous fungi are becoming more prevalent in adults and children because of the increased use of immunosuppressive agents and broad-spectrum anti-infective drugs. Extremely low birth weight premature neonates and patients with a disrupted epidermal barrier are also at increased risk. Lethality is high, particularly with delayed diagnosis. As cutaneous lesions are often the first manifestation of such infections, early recognition of suspicious lesions is crucial to decrease associated morbidity and mortality. The clinical features of deep cutaneous fungal infection (DCFI) in immunocompromised children deserve special attention. This study aimed to characterize our pediatric patients with DCFI, the causative fungi, and the associated risk factors. A medical record review was conducted of pediatric patients with DCFI treated at out institution using data retrieved from the hospital's pathology and microbiology database (1980-2008). In all, 26 patients with DCFI were identified (9 girls and 17 boys) ranging in age from 1 day to 18 years (mean age: 8 years), the majority of whom had a hematologic disorder. All patients were immunocompromised, 90% were receiving broad-spectrum antibiotics, and 50% had severe neutropenia (absolute neutrophilic count < or = 500 x 10(6)/L). Necrotic ulcers (42%) and papules (34%) represented the most frequent lesion morphology. Fungal species were identified by culture in 20 (87%) of 23 patients tested and were observed histopathologically in 20 of 23 patients tested. Aspergillus was identified in 12 (44%) patients and Candida in 9 (33%). The other species included Fusarium (one), Exserohilum rostratum (one), Alternaria (one), Zygomycetes (two), and Blatomycetes (one). All but two patients received systemic antifungal therapy; wide surgical excision was performed in 13. Infection resolved in 20 (77%), whereas 6 (23%) died of disseminated infection. This study was limited by the small number of cases and the retrospective nature of the collected data. DCFI should rank high in the differential diagnosis of any suspicious skin lesions in immunocompromised children. Early biopsies should be performed for histopathology and microbiological analysis, as lethality is high if appropriate treatment is delayed.
    Journal of the American Academy of Dermatology 09/2009; 61(5):857-64. DOI:10.1016/j.jaad.2009.02.052 · 4.45 Impact Factor
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    ABSTRACT: Children under the age of 3 with medulloblastoma have an inferior survival to older children with this disease. This study reviewed the incidence, characteristics, therapy, and outcome of children less than 36 months of age diagnosed with medulloblastoma from 1990 to 2005 in Canada. Ninety-six cases were identified with a median age at diagnosis of 19.5 months. Forty-seven percent of patients had a complete resection, 25% a 90-95% near complete resection, 20% an incomplete (10-90%) resection, and 3% biopsy only. Therapy consisted of chemotherapy (90%), high dose chemotherapy with stem cell rescue (13%), and radiation therapy (21%). The median survival time was 45 +/- 13.82 months. There was no significant difference in survival when comparing patients with <90% resection versus >90% resection, nor when comparing the presence of metastases versus their absence. There was a significant increase in survival time in patients who received radiation therapy compared to those who were not treated with this modality, as well as for those who were over 18 months at diagnosis compared to those under 18 months.
    Journal of Neuro-Oncology 08/2009; 94(1):51-6. DOI:10.1007/s11060-009-9799-2 · 3.07 Impact Factor
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    ABSTRACT: A carboplatin-based chemotherapy regimen was used as primary postoperative therapy in infants with central nervous system (CNS) tumors to limit renal and ototoxicity and to target systemic exposure. Fifty-three patients aged <age 3 years with embryonal CNS tumor medulloblastoma (n = 20), ependymoma (EP, n = 21), choroid plexus carcinoma (CPCA, n = 5), and primitive embryonal neoplasms including atypical teratoid rhabdoid tumors (n = 7) were treated with cyclophosphamide, etoposide, and carboplatin. Radiation therapy was used only for residual disease at the end of chemotherapy or disease progression. The response rate after 2 cycles of chemotherapy was 34% (complete response, 13.8%; partial response, 20.7%). Myelosuppression was the dominant toxicity; 2 patients had toxic deaths related to thrombocytopenia with trauma. The 5-year overall survival (OS) was 49% +/- 7%, and the progression-free survival (PFS) was 31% +/- 7%, with a median follow-up of 11.4 years (range, 5.2-15.0 years). For medulloblastoma, the 5-year PFS was 26% +/- 9%; for EP it was 33% +/- 10%; for CPCA it was 80% +/- 18%; and for primitive neuroectodermal and atypical teratoid rhabdoid tumors it was 0%. Localized EP patients with gross total resection who did not undergo radiotherapy had a 5-year PFS of 57% +/- 17% and OS of 71% +/- 16%. Two patients developed late second malignancies; 1 was associated with germline p53 mutation. The results confirm that carboplatin has similar activity to cisplatin in otherwise similar regimens. Five-year survival data are comparable to those reported in other recent studies, including high-dose chemotherapy studies. Of note is the marked activity in CPCA and gross totally resected EP.
    Cancer 07/2009; 115(14):3243-53. DOI:10.1002/cncr.24362 · 4.89 Impact Factor
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    ABSTRACT: Atypical choroid plexus papilloma (APP) represents a novel intermediate-grade subtype of choroid plexus tumor (CPT), the clinical outcome of which has not been described yet. We present the first analysis of a group of APP patients enrolled in the ongoing CPT-SIOP-2000 study of CPTs. A worldwide registration and a randomized trial for those patients who require chemotherapy started in 2000. For APP, maximal surgical resection was recommended. After surgery, patients who had undergone complete resection were observed, whereas patients with incompletely resected or metastasized APP were treated with six chemotherapy courses (etoposide and vincristine, combined with either carboplatin or cyclophosphamide). Risk-adapted radiotherapy was given only to patients older than 3 years of age. Of the 106 patients with a centrally confirmed CPT histology, 30 had APP, 42 CPP and 34 CPC. APP patients were significantly younger (median = 0.7 years) than patients with CPP or CPC (both medians = 2.3 years). Complete resection was achieved in 68 (64%) patients (79% in CPP, 63% in APP, and 47% in CPC). Metastases were present at diagnosis in 17% of APP patients, 5% of CPP patients, and 21% of CPC patients. All nine APP patients who received postoperative chemotherapy showed an early response after two cycles: two had complete remission, four had partial response, and three had stable disease. In the observation group of 15 patients, one event was seen, and all patients were alive. In the treatment group, one patient with a metastasized tumor and incompletely resected APP died. While APP was defined histologically, median percentages of both the Ki-67/MIB-1 proliferation marker and the p53 tumor suppressor protein increased across the three histological subtypes (from CPP to APP and then CPC), suggesting that the subtypes comprise an ordinal categorization of increasingly severe CPT tumors. This ordering was reiterated by clinical outcome in the 92 patients treated per the study protocol, with 5-year EFS rates of 92% in 39 CPP patients, 83% in 24 APP patients, and 28% in 29 CPC patients. A similar ordering was seen when all 106 patients were evaluated for EFS. APP responded favorably to chemotherapy. The intermediate position of APP between CPP and CPC was supported by the clinical data.
    Journal of Neuro-Oncology 07/2009; 95(3):383-92. DOI:10.1007/s11060-009-9936-y · 3.07 Impact Factor
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    ABSTRACT: Methotrexate and 6-mercaptopurine, important components of acute lymphoblastic leukemia treatment, are substrates for multidrug resistance-associated protein MRP4. Eight single nucleotide polymorphisms were analyzed in MRP4 gene, and 4 variants were identified as tagSNPs with frequency more than or equal to 5%. They were investigated for association with treatment responses in 275 children with acute lymphoblastic leukemia. The TC genotype of the regulatory T-1393C polymorphism was associated with better event-free survival (P = .02) and lower methotrexate plasma levels (P = .01). The CA genotype of A934C (Lys304Asn) substitution correlated in contrast with lower event-free survival (P = .02) and higher frequency of high-grade thrombocytopenia (P = .01). Gene reporter assay showed that the promoter haplotype uniquely tagged by the C-1393 allele conferred higher promoter activity compared with remaining haplotypes (P < .001). Further analyses are needed to replicate this pilot study and get closer insight into the functional effect of these polymorphisms.
    Blood 06/2009; 114(7):1383-6. DOI:10.1182/blood-2008-11-191098 · 10.45 Impact Factor

  • 17th International Conference on Brain Tumor Research and Therapy; 04/2009
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    ABSTRACT: There is an increasing demand for researchers to provide research results to participants. Our aim was to define an appropriate process for this, based on needs and attitudes of participants. A multicenter survey in five sites in the United States and Canada was offered to parents of children with cancer and adolescents with cancer. Respondents indicated their preferred mode of communication of research results with respect to implications; timing, provider, and content of the results; reasons for and against providing results; and barriers to providing results. Four hundred nine parents (including 19 of deceased children) and 86 adolescents responded. Most parents (n = 385; 94.2%) felt that they had a strong right to research results. For positive results, most wanted a letter or e-mail summary (n = 238; 58.2%) or a phone call followed by a letter (n = 100; 24.4%). If the results were negative, phone call (n = 136; 33.3%) or personal visits (n = 150; 36.7%) were preferred. Parents wanted the summary to include long-term sequelae and suggestions for participants (n = 341; 83.4%), effect on future treatments (n = 341; 83.4%), and subsequent research steps (n = 284; 69.5%). Understanding the researcher was a main concern about receiving results (n = 145; 35.5%). Parents felt that results provide information to support quality of life (n = 315; 77%) and raise public awareness of research (n = 282; 68.9%). Adolescents identified similar preferences. Parents of children with cancer and adolescents with cancer feel strongly that they have a right to be offered research results and have specific preferences of how and what information should be communicated.
    Journal of Clinical Oncology 02/2009; 27(6):878-83. DOI:10.1200/JCO.2008.18.5223 · 18.43 Impact Factor

Publication Stats

4k Citations
562.22 Total Impact Points


  • 1998-2013
    • Université de Montréal
      • • Department of Psychiatry
      • • Department of Pediatrics
      • • Department of Psychology
      Montréal, Quebec, Canada
    • University of Rochester
      • Department of Pediatrics
      Rochester, New York, United States
  • 1995-2011
    • CHU Sainte-Justine
      • • Department of Hematology-Oncology
      • • Department of Pharmacy
      Montréal, Quebec, Canada
  • 2001-2010
    • Université du Québec à Montréal
      • Department of Chemistry
      Montréal, Quebec, Canada
  • 2009
    • Dalhousie University
      Halifax, Nova Scotia, Canada
  • 2007
    • Centre Hospitalier Universitaire de Québec (CHUQ)
      Québec, Quebec, Canada
    • IWK Health Centre
      Halifax, Nova Scotia, Canada
  • 2003
    • Dana-Farber Cancer Institute
      • Department of Pediatric Oncology
      Boston, Massachusetts, United States
  • 2002
    • St. Jude Children's Research Hospital
      Memphis, Tennessee, United States
  • 1999
    • Duke University
      Durham, North Carolina, United States
  • 1993-1995
    • Duke University Medical Center
      • Department of Pediatrics
      Durham, NC, United States