C Kalifa

Institut de Cancérologie Gustave Roussy, Île-de-France, France

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Publications (229)720.08 Total impact

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    ABSTRACT: In the European Union, the pediatric medicines regulation in 2007 modified significantly the access to new agents in pediatric oncology. Early oncology trials are still thought to be associated with limited benefit and substantial risk. We report the characteristics and outcome of patients below 21 years enrolled in investigational trials in the Pediatric and Adolescent Department at Gustave Roussy between January 2000 and December 2012. A total of 235 patients (median age, 10.4 [0.8 to 20.7] y) were included in 26 trials (16 cytotoxic and 10 targeted agents) for a total of 260 inclusions. A total of 117 patients (50%) had brain tumors and 68 (29%) had various soft tissue and bone sarcoma. Thirteen of the 106 patients in a phase I trial experienced dose-limiting toxicity. Main severe toxicity was hematologic; none had toxic death. Grade 3 to 4 toxicities were associated with combination trials, cytotoxic agent, and at least 1 previous line of therapy. Thirty patients (12%) had objective response and 42 (16%) had stable disease for >4 months. Median overall survival was 9.0 months (95% CI, 7.5-10.5) and 73% of patients received further anticancer treatment. Phase I to II pediatric oncology trials are safe, associated with clinical benefit, and can be successfully integrated in current relapse strategies.
    Journal of Pediatric Hematology/Oncology 08/2014; 37(2). DOI:10.1097/MPH.0000000000000237 · 0.96 Impact Factor
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    ABSTRACT: Purpose. To correlate the radiological aspects of metastases, the response to chemotherapy, and patient outcome in disseminated childhood medulloblastoma. Patients and Methods. This population-based study concerned 117 newly diagnosed children with disseminated medulloblastoma treated at the Institute Gustave Roussy between 1988 and 2008. Metastatic disease was assessed using the Chang staging system, their form (positive cerebrospinal fluid (CSF), nodular or laminar), and their extension (positive cerebrospinal fluid, local, extensive). All patients received preirradiation chemotherapy. Results. The overall survival did not differ according to Chang M-stage. The 5-year overall survival was 59% in patients with nodular metastases compared to 35% in those with laminar metastases. The 5-year overall survival was 76% in patients without disease at the end of pre-irradiation chemotherapy compared to 34% in those without a complete response (P = 0.0008). Conclusions. Radiological characteristics of metastases correlated with survival in patients with medulloblastoma. Complete response to sandwich chemotherapy was a strong predictor of survival.
    01/2012; 2012:245385. DOI:10.1155/2012/245385
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    ABSTRACT: We report herein our institutional experience in the treatment of diffuse intrinsic pontine glioma (DIPG) with a hypofractionated external-beam radiotherapy schedule. Between April 1996 and January 2004, 22 patients (age 2.9-12.5 years) with newly diagnosed DIPG were treated by hypofractionated radiation therapy delivering a total dose of 45 Gy in daily fractions of 3 Gy, given over 3 weeks. No other treatment was applied concomitantly. Fourteen of the 22 patients received the prescribed dose of 45 Gy in 15 fractions of 3 Gy, and 2 patients received a total dose of 60 and 45 Gy with a combination of two different beams (photons and neutrons). In five cases the daily fraction was modified to 2 Gy due to intolerance, and one patient died due to serious intracranial hypertension after two fractions of 3 Gy and one of 2 Gy. Among 22 children, 14 patients showed clinical improvement, usually starting in the second week of treatment. No grade 3 or 4 acute toxicity from radiotherapy was observed. No treatment interruption was needed. In six patients, steroids could be discontinued within 1 month after the end of radiotherapy. Median time to progression and median overall survival were 5.7 months and 7.6 months, respectively. External radiotherapy with a radical hypofractionated regimen is feasible and well tolerated in children with newly diagnosed DIPG. However, this regimen does not seem to change overall survival in this setting. It could represent a short-duration alternative to more protracted regimens.
    Journal of Neuro-Oncology 02/2011; 104(3):773-7. DOI:10.1007/s11060-011-0542-4 · 3.12 Impact Factor
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    ABSTRACT: Le but de cette étude est de décrire le devenir à long terme d’une large cohorte d’enfants atteints de GVO. Les dossiers médicaux de 192 enfants pris en charge entre 1952 et 2004 à l’Institut Gustave Roussy ont été analysés. La survie globale (OS) à 5, 10, 20 et 30 ans était respectivement de 90 %, 83 %, 70 % et 56 %. La mortalité était plus sévère chez les enfants de moins d’un an au diagnostic, sans influence du traitement. Parmi ceux traités par chimiothérapie, la survie était meilleure en cas de réponse radiologique OS à 10 ans=90 % contre 66 %, p = 0,017). Les deux causes principales de décès (n = 57) étaient la progression tumorale (27) et les secondes tumeurs (11), pouvant survenir tardivement. Les secondes tumeurs étaient plus fréquentes chez les enfants irradiés (p = 0,008), particulièrement avant l’âge de 7 ans (p = 0,008) et/ou en cas de NF1 (p = 0,003). Le pronostic visuel était sévère, surtout chez les jeunes enfants (p = 0,05) avec 35 (20 %) cécité complète et 73 (40 %) cécité monoculaire. Les complications vasculaires (p = 0,08), l’épilepsie (p = 0,002), l’atteinte neurocognitive (p < 104) et le déficit en GH (p < 104) étaient plus fréquents chez les enfants irradiés. Une surveillance pluridisciplinaire à long terme et un affinement des stratégies thérapeutiques apparaissent nécessaire.
    Archives de Pédiatrie 06/2010; 17(6):24-25. DOI:10.1016/S0929-693X(10)70304-3 · 0.41 Impact Factor
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    ABSTRACT: To evaluate bone mineral density (BMD), fractures, and vitamin D deficiency in pediatric patients in complete remission of solid tumor; and to identify risk factors for these three abnormalities. Data were collected prospectively after completion of cancer treatment. Hormonal and vitamin D deficiencies were treated. The patients were evaluated again 1 year later. 52 consecutive patients, 30 boys and 22 girls. Among them, 21 completed the second evaluation. A clinical examination, nutritional assessment, and laboratory workup were performed. BMD was measured by absorptiometry. Calcium intake was inadequate in 75% of patients and vitamin D reserves were low in 61.5%. BMD was low at the spine in 32.7%, and at the femur in 24% of patients. Spinal and femoral BMD Z-scores correlated significantly with each other. Femoral BMD Z-score showed significant positive correlations with changes in body mass index, urinary calcium/creatinine ratio, and time since treatment completion, and a significant negative correlation with treatment duration. Fractures were noted in 10 patients but were not correlated with BMD. In the 21 re-evaluated patients, no significant improvements were found in calcium intake, vitamin D status, or BMD Z-score. Survivors of childhood solid cancer have high rates of insufficient calcium intake, vitamin D deficiency, low bone mass and fractures.
    Hormone Research in Paediatrics 01/2010; 74(5):319-27. DOI:10.1159/000313378 · 1.55 Impact Factor
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    ABSTRACT: Pediatric tumors still represent a formidable challenge despite the considerable therapeutical advances that have been reported for the past 30 years. This is largely related with the untowards side-effects of local therapy that are still acknowledged as the “price for cure”. In this setting, Proton therapy a sophisticated radiotherapeutical modality seems to represent a real breakthrough due to its unique ability to spare close and distant normal organs compared with modern photons techniques. We summarize in this paper current clinical and dosimetrical evidences including an update of the Orsay series on 108 children.
    Cancer/Radiothérapie 10/2009; 13(6):550-555. DOI:10.1016/j.canrad.2009.07.001 · 1.11 Impact Factor
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    ABSTRACT: Pediatric tumors still represent a formidable challenge despite the considerable therapeutical advances that have been reported for the past 30 years. This is largely related with the untowards side-effects of local therapy that are still acknowledged as the "price for cure". In this setting, Proton therapy a sophisticated radiotherapeutical modality seems to represent a real breakthrough due to its unique ability to spare close and distant normal organs compared with modern photons techniques. We summarize in this paper current clinical and dosimetrical evidences including an update of the Orsay series on 108 children.
    Cancer/Radiothérapie 09/2009; 13(6-7):550-5. · 1.11 Impact Factor
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    ABSTRACT: Background Chemotherapy is accepted as first-line conservative treatment of optic pathway tumors in patients younger than 5. Limited data are available on the outcome of patients with recurrence/progression after initial chemotherapy.ProcedureData on 68 children with Optic Pathway Tumors (OPT) treated with first-line Baby Brain (BBSFOP) chemotherapy at the Gustave Roussy Institute in Villejuif between 1990 and 2005 were reviewed.ResultsDuring a median follow-up of 6 years, 44 (65%) patients were diagnosed with one or more relapses. Most of the relapses occurred during the first 6 years of life. Overall and progression-free survival rates at 5 years after first relapse were 64% and 14%, respectively. First relapse was treated with chemotherapy, radiotherapy or surgery in 28, 9, and 6 patients, respectively. Best response to second-line chemotherapy was partial response in 10, stable disease in 10, and progressive disease in 8 patients. Patients with objective radiologic response to first-line chemotherapy, had a greater chance to respond again to second-line chemotherapy (RR = 90% vs. 15%, P = 0.003). Median time to progression after first relapse was 1.7, 2.5, and 3.1 years after surgery, chemotherapy and radiotherapy, respectively. Finally, 25 (37%) patients received radiotherapy at a median age of 6.7 years.Conclusions Second-line chemotherapy can be effective in the treatment of relapses after first-line chemotherapy and delay further the need for RT, especially in patients whose tumor initially responded to chemotherapy. Despite the desire to avoid irradiation in treatment of young patients with OPT, radiotherapy was used for 37% of patients, usually before the age of 10. Pediatr Blood Cancer 2009;52:575–580. © 2009 Wiley-Liss, Inc.
    Pediatric Blood & Cancer 05/2009; 52(5):575 - 580. DOI:10.1002/pbc.21911 · 2.35 Impact Factor
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    ABSTRACT: Children treated for a malignant posterior fossa tumor (PFT) are at risk of intellectual impairment. Its severity is not explained by age and radiotherapy alone. The current study was designed to define the correlations between the anatomical damage and the neurological/neuropsychological deficits in children with a malignant PFT. Sixty-one consecutive children (mean age, 6.0 years) treated for a malignant PFT with surgery, chemotherapy, and radiotherapy underwent a detailed neuropsychological evaluation, including a full-scale intelligence quotient (FSIQ), on average 5.6 years after the diagnosis. The neurological examination was recorded 1 month after surgery and at the time of the neuropsychological evaluation. Cerebellar and brain injuries were scored based on the magnetic resonance imaging (MRI). Correlation of these injuries with neurological and cognitive outcome were performed after adjustment for other potential risk factors (radiotherapy schedule, age, hydrocephalus, duration of symptoms, socioeconomic status, and surgical complications). Neurological deficits were strong predictors of low cognitive performances irrespective of the other risk factors. The extent of cerebellar deficits and fine motor dexterity impairment were correlated with the degree of damage to the dentate nuclei and inferior vermis. The IQ scores were inversely correlated with the severity of the damage to the dentate nuclei; mean FSIQ was 83 if they were both intact and 65 in the case of bilateral damage (P=.009). Damage to the dentate nuclei and to the inferior vermis, observed on MRI, predict the degree of impairment of neurological and neuropsychological functions in children treated for a malignant PFT.
    Cancer 03/2009; 115(6):1338-47. DOI:10.1002/cncr.24150 · 4.90 Impact Factor
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    ABSTRACT: This chapter presents guidelines for the follow-up of children with brain tumors, whether benign or malignant, in their transition to adulthood. The consequences of their disease and its treatment overlap greatly. The complications and long-term follow-up are detailed based on the specialists involved.
    Neurochirurgie 10/2008; 54(5):623-41. · 0.47 Impact Factor
  • Archives de Pédiatrie 06/2008; 15(5):1009-1009. DOI:10.1016/S0929-693X(08)72352-2 · 0.41 Impact Factor
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    ABSTRACT: To investigate the neuropsychological outcome of children treated with surgery and posterior fossa irradiation for localized infratentorial ependymoma. 23 patients (age 0.3 - 14 years at diagnosis) who were treated with local posterior fossa irradiation (54 Gy) underwent one (4 patients) or sequential (19 patients) neuropsychologic evaluation. The last evaluation was performed at a median of 4.5 (1 to 15.5) years after RT. Mean last full scale IQ (FSIQ), verbal IQ (VIQ) and PIQ were 89.1, 94.0, and 86.2 respectively. All patients had difficulties with reading, and individual patients showed deficits in visuospatial, memory and attentional tasks. There was no trend for deterioration of intellectual outcome over time. All 5 children with IQ scores < or = 75 were under the age of four at diagnosis. There was a significant association between the presence of cerebellar deficits and impaired IQ (72.0 vs 95.2, p < 0,001). The absence of hydrocephalus was an indicator of better neuropsychologic outcome (mean FSIQ of 102.6 vs 83.9, p = 0.025). Within the evaluated cohort, intellectual functions were moderately impaired. Markedly reduced IQ scores were only seen with early disease manifestation and treatment, and postoperative neurological deficits had a strong impact on intellectual outcome.
    BMC Cancer 02/2008; 8:15. DOI:10.1186/1471-2407-8-15 · 3.32 Impact Factor
  • Neuropediatrics 01/2008; 10(S 01):434-434. DOI:10.1055/s-0028-1085373 · 1.10 Impact Factor
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    ABSTRACT: School achievement of children with brain tumors is hampered by progressive neurologic and cognitive sequelae. To help the children and their family, we have created in 1997 a multidisciplinary consultation together with Necker's hospital. MATERIAL AND METHODS: The study describes the organization of the consultation and analyses the files of 69 children seen between September 2001 and June 2002. RESULTS AND CONCLUSION: The authors conclude that this consultation is an irreplaceable mean to coordinate the complex rehabilitation process of a child treated for a brain tumor.
    Archives de Pédiatrie 12/2007; 14(11):1282-9. DOI:10.1016/j.areped.2007.08.009 · 0.41 Impact Factor
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    ABSTRACT: To evaluate the efficacy of BCNU, cisplatin, and vincristine (BCV regimen) in a prospective nonrandomized study among newly diagnosed children with high-grade glioma. Following surgery, patients received a combination of BCNU + cisplatin + VP16 (BCV), over 3 consecutive days. Patients with residual tumor continued this regimen unless no further improvement was observed on MRI, for a maximum of six courses. Patients who underwent complete surgical resection received six courses of adjuvant BCV. Seventy-three patients were enrolled. Out of 66 eligible patients with central pathology review, the diagnosis of high-grade glioma was confirmed in 53 cases. The response rate was 20%. With a median follow-up of 128 months, 5- and 10-year event free survival rates are 16 +/- 9 and 13.3 +/- 9.4%. In univariate analysis, two prognostic factors were statistically significant: extent of resection and tumor location, while macroscopic total resection was the only significant prognostic factor in the multivariate analysis. The response to BCV did not translate into improved event free survival. Interstitial pneumonitis occurred in seven patients, leading to six deaths. This BCV regimen could not be recommended in the treatment of high-grade gliomas in children, according to its lack of efficacy and its unacceptable pulmonary toxicity.
    Pediatric Blood & Cancer 12/2007; 49(6):803-7. · 2.56 Impact Factor
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    ABSTRACT: School achievement of children with brain tumors is hampered by progressive neurologic and cognitive sequelae. To help the children and their family, we have created in 1997 a multidisciplinary consultation together with Necker's hospital.
    Archives de Pédiatrie 11/2007; 14(11):1282-1289. DOI:10.1016/j.arcped.2007.08.009 · 0.41 Impact Factor
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    ABSTRACT: Dysregulated cell growth or differentiation due to misexpression of developmental critical factors seems to be a decisive event in oncogenesis. As osteosarcomas are histologically defined by malignant osteoblasts producing an osteoid component, we prospected in pediatric osteosarcomas treated with OS94 protocol the genomic status of several genes implied in ossification processes. In 91 osteosarcoma cases, we focused on the analysis of the fibroblast growth factor receptors (FGFRs) TWIST, APC, and MET by allelotyping, real-time quantitative polymerase chain reaction, gene sequencing, and protein polymorphism study. Our study supports the frequent role of TWIST, APC, and MET as osteosarcoma markers (50%, 62%, and 50%, respectively). TWIST and MET were mainly found to be deleted, and no additional APC mutation was identified. Surprisingly, FGFRs are abnormal in only < 30%. Most of these factors and their abnormalities seem to be linked more or less to one clinical subgroup, but the most significant correlation is the link of MET, TWIST, and APC abnormalities to a worse outcome and their combination within abnormal tumors. A wider cohort is mandatory to define more robust molecular conclusions, but these results are to be considered as the beginning of a more accurate basis for diagnosis, in search of targeted therapies, and to further characterize prognostic markers.
    Neoplasia (New York, N.Y.) 08/2007; 9(8):678-88. DOI:10.1593/neo.07367 · 5.40 Impact Factor
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    ABSTRACT: The objective of the current study was to determine the outcome of children with local recurrence or progression of medulloblastoma in patients who received high-dose chemotherapy (HDC) and posterior fossa (PF) irradiation. HDC consisted in busulfan at a dose of 600 mg/m(2) and thiotepa at a dose of 900 mg/m(2) followed by autologous stem cells transplantation (ASCT). PF radiotherapy was delivered at doses from 50 grays (Gy) to 55 Gy on Day +70 after ASCT. Twenty-seven patients developed local recurrence of an initially completely resected medulloblastoma. Twelve patients had local residual disease after surgery and were enrolled into the salvage protocol at the time of local disease progression under conventional chemotherapy. Acute toxicity consisted mainly in hepatic veno-occlusive disease (33% of patients) and bone marrow aplasia. Two toxic deaths (5%) from infections were reported. The 5-year overall survival rate after this salvage treatment (OS(5y)) for the 39 children who were treated was 68.8% (95% confidence interval [95% CI], 53-81.2%). In the group of patients who were treated for local recurrence, the OS(5y) was 77.2% (95% CI, 58.3-89.1%). Patients with local residual disease who were treated at the time of disease progression had an OS(5y) after salvage treatment of only 50% (95% CI, 25.4-74.6%; P = .09). The treatment strategy that was used in this study had manageable immediate toxicity and resulted in a high overall survival rate in the setting of young children with medulloblastoma who developed local recurrence or disease progression.
    Cancer 07/2007; 110(1):156-63. DOI:10.1002/cncr.22761 · 4.90 Impact Factor
  • Chantal Kalifa
    La Revue du praticien 06/2007; 57(10):1058-60.
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    ABSTRACT: In our previous study, a frequent rearrangement at 4q12 has been identified by allelotyping in our large and homogeneous population of pediatric osteosarcomas and it was significantly linked to c-kit protein overexpression. To confirm and understand the involvement of KIT in this tumor, the next step of the study was designed to detect the potential mutations of KIT gene by sequencing the frequently mutated exons 6, 8, 10, 11, 13, 17 and 21 and, in case of unmutated samples, to confirm the genomic amplifications of the wild-type receptor by real-time quantitative PCR (QPCR). A new microsatellite and QPCR targeting PDGFRA was also added to check the accuracy of the 4q11-12 locus. These techniques were performed in 74 pediatric high-grade osteosarcomas treated with the OS94 protocol. Surprisingly, no mutations were found, but, only DNA amplification of KIT gene in the entire population. PDGFRA gene QPCR revealed an unexpected result of predominant deletions in the rearranged tumors. All these results confirm the major role of the 4q11-12 locus and specifically the involvement of c-kit wild-type receptor overexpression in pediatric osteosarcomas and leads us to believe that inhibitors targeting this receptor could have a therapeutic effect in a selected group of patients.
    International Journal of Cancer 06/2007; 120(11):2510-6. DOI:10.1002/ijc.22593 · 5.01 Impact Factor

Publication Stats

5k Citations
720.08 Total Impact Points

Institutions

  • 1984–2012
    • Institut de Cancérologie Gustave Roussy
      • • Department of Radiotherapy
      • • Department of Paediatrics
      Île-de-France, France
  • 2010
    • Université Paris-Sud 11
      Orsay, Île-de-France, France
  • 2009
    • Institut Curie - Centre de Protonthérapie
      Orsay, Île-de-France, France
  • 2000–2005
    • Centre Léon Bérard
      Lyons, Rhône-Alpes, France
  • 2002
    • Hôpital Saint-Vincent-de-Paul – Hôpitaux universitaires Paris Centre
      Lutetia Parisorum, Île-de-France, France
    • CHU de Lyon - Groupement Hospitalier Edouard Herriot
      Lyons, Rhône-Alpes, France
  • 2001
    • Centre Hospitalier Régional Universitaire de Lille
      Lille, Nord-Pas-de-Calais, France
  • 1997–1998
    • Centre Oscar Lambret
      Lille, Nord-Pas-de-Calais, France
  • 1993
    • Centre Hospitalier Universitaire de Nancy
      Nancy, Lorraine, France