Jean Bourhis

Groupe Oncologie Radiothérapie Tête et Cou, GORTEC, Lutetia Parisorum, Île-de-France, France

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Publications (195)1246.86 Total impact

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    ABSTRACT: To assess the use of radiotherapy (RT) or concurrent chemoradiotherapy (CRT) following taxane-based induction chemotherapy (T-ICT) in locally advanced head and neck squamous cell carcinoma (LAHNSCC) and to evaluate the tolerability of CRT after T-ICT. From 01/2006 to 08/2012, 173 LAHNSCC patients treated as a curative intent by T-ICT, followed by definitive RT/CRT were included in this analysis. There was an 86% objective response (OR) after ICT among 154 evaluable patients. Forty-four patients received less than three cycles (25%) and 20 received only one cycle of T-ICT. The 3-year actuarial overall survival (OS) was 49% and there was no OS difference according to the type of ICT (regimen or number of cycle) or the addition of concurrent CT (cisplatin, carboplatin, or cetuximab) to RT. In multivariate analysis (MVA), clinically involved lymph node (cN+), age more than 60 years, the absence of OR after ICT, and performance status of at least 1 predicted for a decreased OS, with hazard ratios (HR) of 2.8, 2.2, 2.1, and 2, respectively. The 3-year actuarial locoregional control (LRC) and distant control (DC) rates were 52 and 73%, respectively. In MVA, the absence of OR after ICT (HR: 3.2), cN+ (HR: 3), and age more than 60 years (HR: 1.7) were prognostic for a lower LRC whereas cN+ (HR: 4.2) and carboplatin-based T-ICT (HR: 2.9) were prognostic for a lower DC. The number of cycles (≤2) received during ICT was borderline significant for DC in the MVA (P=0.08). Among patients receiving less than or equal to three cycles of ICT, higher outcomes were observed in patients who received cisplatin-based T-ICT (vs. carboplatin-based T-ICT) or subsequent CRT (vs. RT). T-ICT in our experience, followed by RT or CRT, raises several questions on the role and type of induction, and the efficacy of CRT over RT. The role of RT or CRT following induction, although feasible in these advanced patients, awaits answers from randomized trials.
    Anti-cancer drugs. 08/2014;
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    ABSTRACT: We have previously shown that human umbilical cord blood CD34 progenitor cells undergo in vitro differentiation into functional natural killer (NK) cells and that their coculture in the presence of HOXB4-transduced stromal MS-5 cells resulted in an increase in differentiated NK number. The present study was conducted to compare the stromal effect on NK lytic potential in the presence and absence of HOXB4. Our results provide evidence that HOXB4-transduced MS-5 cells as compared with transduced GFP (+) MS-5 cells induced highly differentiated cytotoxic NK cells. Importantly, this difference was not because of the expression of activating NK receptors but was associated with an increased induction of granzyme B degranulation in response to stimulation with NK cell susceptible targets. DNA microarray-based global transcriptional profiling confirmed the upregulation of granzyme B. These findings provide further evidence that HOXB4 is a crucial regulator of NK function and that its use in generating functional NK cells with increased lytic potential may be significant for cancer immunotherapy.
    Journal of immunotherapy (Hagerstown, Md.: 1997) 06/2014; 37(5):278-82. · 3.20 Impact Factor
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    ABSTRACT: Squamous cell carcinomas of larynx and hypopharynx can be treated by surgery and/or radiotherapy according to tumor size. For small tumors, the results are similar. For locally advanced tumors, the surgical approach is mutilating and requires a total (pharyngo)laryngectomy. Exclusive chemoradiotherapy has shown its interest at the cost of late sequelae. In order to reduce these effects and mutilation, induction chemotherapy with cisplatin, docetaxel and 5FU for organ preservation becomes the standard treatment but there are no solid studies comparing this approach with the exclusive chemoradiotherapy. And it is not possible to conclude as to the superiority of a scheme in terms of overall survival. When chemotherapy is chosen, the modalities of any potentiation of radiation have not been yet established.
    Bulletin du cancer. 05/2014; 101(5):438-444.
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    ABSTRACT: Cancer of the nasopharynx is an uncommon malignancy in France (incidence = 0.5/year/100,000 men) but is endemic in areas like in South-East Asia. Exclusive radiation therapy used to be the standard and results in local control rates for T3-T4 tumors around 50-75 %. Intensity-modulated radiotherapy (IMRT) improves tumor coverage with a sparing of organs at risk and has to be privileged. Concurrent chemotherapy with IMRT achieved significant survival benefice with 5-year overall survival above 75 %. Concurrent radiochemotherapy with platinium is the most frequent scheme but induction and adjuvant chemotherapies are discussed to reduce distant failure: studies are currently ongoing. Follow-up aims to detect early local failures with a chance of cure and to manage long-term toxicities.
    Bulletin du cancer. 05/2014; 101(5):445-454.
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    ABSTRACT: The aim of radiotherapy is to deliver enough radiation to the tumor in order to achieve maximum tumour control in the irradiated volume with as few serious complications as possible with an irradiation dose as low as possible to normal tissue. The quality of radiotherapy is essential for optimal treatment and quality control is to reduce the bias in clinical trials avoiding possible major deviations. The assurance and quality control programs have been developed in large european (EORTC, GORTEC) and american cooperative groups (RTOG) of radiation oncology since the 1980s. We insist here on the importance of quality assurance in radiotherapy and the current status in this domain and the criteria for quality control especially for current clinical trials within GORTEC are discussed here.
    Bulletin du cancer. 05/2014; 101(5):481-485.
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    ABSTRACT: Cytarabine (cytosine arabinoside) is one of the most effective drugs for the treatment of patients diagnosed with acute myeloid leukemia (AML). Despite its efficiency against AML cells, emergence of drug resistance due to prolonged chemotherapy in most patients is still a major obstacle. Several studies have shown that drug resistance mechanisms alter the sensitivity of leukemia cells to immune system effector cells. To investigate this phenomenon, parental acute myeloid cell lines HL-60 and KG-1 were continuously exposed to increasing doses of cytarabine in order to establish equivalent resistant cell lines, HL-60 (R), and KG-1(R). Our data indicate that cytarabine-resistant cells are more susceptible to NK-mediated cell lysis as compared to parental cytarabine-sensitive cells. The increased susceptibility correlates with the induction of ULBP1/2/3, NKG2D ligands, on target cells by a mechanism involving c-Myc induction. More importantly, chromatin immunoprecipitation assay revealed that ULBP1/3 are direct targets of c-Myc. Using drug resistant primary AML blasts as target cells, inhibition of c-Myc resulted in decreased expression of NKG2D ligands and the subsequent impairment of NK cell lysis. This study provides for the first time the c-Myc dependent regulation of NKG2D ligands in acute myeloid leukemia.
    Blood 03/2014; · 9.78 Impact Factor
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    ABSTRACT: The goal of the present work was to compare outcomes of definitive concurrent cisplatin-based chemoradiotherapy (CRT) with cetuximab-based bioradiotherapy (BRT) in locally advanced head-and-neck squamous cell carcinoma (HNSCC). Between 2006 and 2012, 265 patients with locally advanced HNSCC were treated at our institution with CRT (n = 194; 73 %) with three cycles of cisplatin (100 mg/m(2), every 3 weeks) or BRT (n = 71; 27 %) with weekly cetuximab. Patients receiving BRT had more pre-existing conditions (Charlson index ≥ 2) than the CRT group (p = 0.005). Median follow-up was 29 months. In all, 56 % of patients treated with CRT received the planned three cycles (92 % at least two cycles) and 79 % patients treated with BRT received six cycles or more. The 2-year actuarial overall survival (OS) and progression-free survival (PFS) were 72 % and 61 %, respectively. In the multivariate analysis (MVA), T4 stage, N2-3 stage, smoking status (current smoker as compared with never smoker), and non-oropharyngeal locations predicted for OS, whereas BRT association with OS was of borderline significance (p = 0.054). The 2-year actuarial locoregional control (LRC) and distant control (DC) rates were 73 and 79 %, respectively. CRT was independently associated with an improved LRC (2-year LRC: 76 % for CRT vs. 61 % for BRT) and DC (2-year LRC: 81 % for CRT vs. 68 % for BRT) in comparison with BRT (p < 0.001 and p = 0.01 in the MVA). Subgroup analyses showed that T4 patients benefited significantly from CRT (vs. BRT) in LRC, while T1-3 did not. BRT patients had more G3-4 skin complications (p < 0.001) and CRT patients had higher rates of feeding tube placement (p = 0.006) and G3-4 gastrointestinal toxicities (p < 0.001). This retrospective analysis showed a better LRC in locally advanced HNSCC treated by cisplatin-based CRT than cetuximab-based BRT, and a nonsignificant trend towards an improved OS.
    Strahlentherapie und Onkologie 03/2014; · 4.16 Impact Factor
  • Journal of Clinical Oncology 12/2013; · 18.04 Impact Factor
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    ABSTRACT: PURPOSECisplatin plus fluorouracil (PF) induction chemotherapy has been compared with taxane (docetaxel or paclitaxel), cisplatin, and fluorouracil (Tax-PF) in randomized trials in locoregionally advanced head and neck cancers (LAHNCs). The aim of this meta-analysis was to study the efficacy and toxicity of Tax-PF and PF and identify differences in outcomes in subsets of patients. METHODS Five randomized trials representing 1,772 patients were identified. Updated individual patient data (IPD) were retrieved for all trials. The log-rank test, stratified by trial, was used for comparison. Interaction or trend tests were used to study the interaction between covariates and treatment. 7.4%) in favor of Tax-PF. Heterogeneity was significant (P = .08, I(2) = 51%) and related to one trial. There was no more heterogeneity after exclusion of this trial (P = .99, I(2) = 0%), and HR of death was 0.72 (95% CI, 0.63 to 0.83) in favor of Tax-PF. There was no interaction between treatment effect and the following patient covariates: age, sex, performance status, tumor stage, or site. Tax-PF was associated with significant reductions of progression, locoregional failure, and distant failure compared with PF, with HRs of 0.78 (95% CI, 0.69 to 0.87; P < .001), 0.79 (95% CI, 0.66 to 0.94; P = .007), and 0.63 (95% CI, 0.45 to 0.89; P = .009) respectively. CONCLUSION This IPD meta-analysis shows the superiority of Tax-PF over PF as induction chemotherapy. Its precise role in the management of LAHNC remains to be determined.
    Journal of Clinical Oncology 07/2013; · 18.04 Impact Factor
  • Journal of Clinical Oncology. 07/2013;
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    ABSTRACT: Purpose: This study sought to determine the maximum tolerated dose (MTD) of oral etoposide in combination with radiotherapy in head and neck squamous cell carcinoma (HNSCC).Patients and Methods: Phase I, multicenter, open-labelled, non-comparative and dose escalating trial. Patients with locally advanced HNSCC were enrolled onto cohorts of escalating dose of etoposide. Oral etoposide was administered on five consecutive days every week for 7 weeks (7 treatment cycles) in combination with daily radiotherapy (70Gy /35 fractions). Two dose levels (25 mg/day and 50 mg/day) of etoposide were planned and three to six patients were to be enrolled at each level according to the potential DLTs. RESULTS: Fourteen patients were allocated to two dose levels: 25 mg/day (3) and 50 mg/day (11). Cisplatin was contra-indicated in all the patients included. Only one patient (50 mg/day) presents a grade 4 neutropenia (DLT), no other DLTs were observed. The most frequently adverse events (AEs) were radiomucositis. Two deaths before 3 months of end of treatment were not related to treatment. Seven patients were still alive with a median follow-up of 30 months (12--58 months). Nine patients had a complete response (CR) at 3 months after the radiotherapy; Among the 9 patients, 3 patients had a local relapse; one patient with local and distant relapse. CONCLUSION: Due to only one DLT experienced, it is possible to a dose of 50 mg/day for phase II studies, however this should be considered with caution.
    Radiation Oncology 02/2013; 8(1):40. · 2.11 Impact Factor
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    ABSTRACT: PURPOSE: Esthesioneuroblastomas, also called olfactory neuroblastomas (ENB) represent a rare sinonasal neurectodermal tumour which prognostic factors are unsteadily described. PATIENTS AND METHODS: Clinical and pathological characteristics were analysed in patients treated at Gustave Roussy Institute between 1979 and 2009. RESULTS: Out of 63 patients, 19 patients were reclassified and 44 patients were eligible for the analysis. Multivariate analysis revealed that T staging of the modified Dulguerov TNM staging and Hyams grade>III (that we termed high-grade ENB) were the only independent prognostic factors for overall survival (OS). As compared to patients with low-grade ENB (Hyams grade⩽III), patients with high-grade ENB have higher T4 staging (p=0.02), have frequent lymph node involvement (p=0.009) and are more often unresectable (p=0.005). Resected patients with high-grade ENB frequently displayed mainly leptomeningeal metastasis (n=4/6) in contrast to patients with low-grade ENB who typically experience late loco-regional recurrence (n=10/25). With a median follow-up of 9.6years, median DFS and OS for resected low-grade ENB were 5.4 and 20.5years, respectively. Conversely, median DFS and OS for high-grade ENB were 1.5 and 2.5years, respectively. CONCLUSION: Low and high-grade ENB display distinct patterns at presentation and relapse, leading to different prognosis. Therefore, they may be regarded as distinct entities.
    European journal of cancer (Oxford, England: 1990) 01/2013; · 4.12 Impact Factor
  • Annales de Dermatologie et de Vénéréologie 01/2013; 140(12):S371. · 0.60 Impact Factor
  • Annales de Dermatologie et de Vénéréologie 01/2013; 140(12):S376–S377. · 0.60 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE: To report the long-term results after definitive radiotherapy (RT) for pyriform sinus squamous cell carcinoma (SCC). MATERIAL AND METHODS: The data concerning all patients treated for pyriform sinus SCC with RT with a curative intent between 1990 and 2006 were reviewed. RESULTS: A total of 249 patients were included. The median follow-up is 6.5years. Overall 123 patients had relapsed. For the entire population, the 5-year local control, regional control, freedom-from-distant metastasis, and overall survival rate were 68%, 69%, 78% and 38%, respectively. The 5-year local control rate for the 107 T1-T2 tumors was 85% (95% confidence interval (CI): 75-91). N stage was the main risk factor for the development of distant metastases, with a hazard ratio of 8.9 (95% CI: 2.1-39) and 15.6 (95% CI: 3.6-67.8) for N2 and N3 patients respectively. For patients with N2-N3 disease, pre-RT neck dissection improved regional control but not overall survival. Moderate to severe late complications occurred in 50 patients (28% of the patients without local relapse). CONCLUSION: A high local control rate can be achieved when treating T1-T2 hypopharynx cancers with definitive radiotherapy. The high rate of nodal and distant relapses among patients with N2-N3 disease warrants intensification of therapy.
    Radiotherapy and Oncology 10/2012; · 4.52 Impact Factor
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    ABSTRACT: Aim: There is considerable interest in approaches that could improve the therapeutic window of radiotherapy. In this study, hafnium oxide nanoparticles were designed that concentrate in tumor cells to achieve intracellular high-energy dose deposit. Materials & methods: Conventional methods were used, implemented in different ways, to explore interactions of these high-atomic-number nanoparticles and ionizing radiation with biological systems. Results: Using the Monte Carlo simulation, these nanoparticles, when exposed to high-energy photons, were shown to demonstrate an approximately ninefold radiation dose enhancement compared with water. Importantly, the nanoparticles show satisfactory dispersion and persistence within the tumor and they form clusters in the cytoplasm of cancer cells. Marked antitumor activity is demonstrated in human cancer models. Safety is similar in treated and control animals as demonstrated by a broad program of toxicology evaluation. Conclusion: These findings, supported by good tolerance, provide the basis for developing this new type of nanoparticle as a promising anticancer approach in human patients.
    Future Oncology 09/2012; 8(9):1167-81. · 3.20 Impact Factor
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    ABSTRACT: The correlation between the incidence of GVHD and the number of infused CD34(+) cells remains controversial for PBSC transplantation after a reduced-intensity-conditioning (RIC) regimen. We evaluated 99 patients transplanted with an HLA-identical sibling after the same RIC (2-Gy-TBI/fludarabine). Donor and recipient characteristics, donor's blood G-CSF-mobilized CD34(+) cell count, and number of infused CD34(+) and CD3(+) cells were analyzed as risk factors for acute and chronic GVHD There was a trend for an increased incidence of extensive chronic GVHD in the quartile of patients receiving more than 10 × 10(6) CD34(+) cells/kg (P=0.05). Interestingly, the number of donor's blood CD34(+) cells at day 5 of G-CSF mobilization was closely associated with the incidence of extensive chronic GVHD, that is, 48% (95% CI: 28-68) at 24-months in the quartile of patients whose donors had the highest CD34(+) cell counts versus 24.3% (95% CI: 14-34) in the other patients (P=0.007). In multivariate analysis, the only factor correlating with extensive chronic GVHD (cGVHD) was the donor's blood CD34(+) cell count after G-CSF (HR 2.49; 95% CI: 1.16-5.35, P=0.019). This study shows that the incidence of cGVHD is more strongly associated with the donor's ability to mobilize CD34(+) cells than with the number of infused CD34(+) cells.Bone Marrow Transplantation advance online publication, 21 May 2012; doi:10.1038/bmt.2012.75.
    Bone marrow transplantation 05/2012; · 3.00 Impact Factor
  • The Lancet Oncology 04/2012; 13(4):e136-7. · 25.12 Impact Factor
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    Investigational New Drugs 03/2012; · 3.50 Impact Factor
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    ABSTRACT: Concomitant chemoradiotherapy and accelerated radiotherapy independently improve outcomes for patients with locally advanced head and neck squamous-cell carcinoma (HNSCC). We aimed to assess the efficacy and safety of a combination of these approaches. In our open-label phase 3 randomised trial, we enrolled patients with locally advanced, stage III and IV (non-metastatic) HNSCC and an Eastern Cooperative Oncology Group performance status of 0-2. We randomly allocated patients centrally with a computer program (with centre, T stage, N stage, and localisation as minimisation factors) in a 1:1:1 ratio to receive conventional chemoradiotherapy (70 Gy in 7 weeks plus three cycles of 4 days' concomitant carboplatin-fluorouracil), accelerated radiotherapy-chemotherapy (70 Gy in 6 weeks plus two cycles of 5 days' concomitant carboplatin-fluorouracil), or very accelerated radiotherapy alone (64·8 Gy [1·8 Gy twice daily] in 3·5 weeks). The primary endpoint, progression-free survival (PFS), was assessed in all enrolled patients. This trial is completed. The trial is registered with ClinicalTrials.gov, number NCT00828386. Between Feb 29, 2000, and May 9, 2007, we randomly allocated 279 patients to receive conventional chemoradiotherapy, 280 to accelerated radiotherapy-chemotherapy, and 281 to very accelerated radiotherapy. Median follow-up was 5·2 years (IQR 4·9-6·2); rates of chemotherapy and radiotherapy compliance were good in all groups. Accelerated radiotherapy-chemotherapy offered no PFS benefit compared with conventional chemoradiotherapy (HR 1·02, 95% CI 0·84-1·23; p=0·88) or very accelerated radiotherapy (0·83, 0·69-1·01; p=0·060); conventional chemoradiotherapy improved PFS compared with very accelerated radiotherapy (0·82, 0·67-0·99; p=0·041). 3-year PFS was 37·6% (95% CI 32·1-43·4) after conventional chemoradiotherapy, 34·1% (28·7-39·8) after accelerated radiotherapy-chemotherapy, and 32·2% (27·0-37·9) after very accelerated radiotherapy. More patients in the very accelerated radiotherapy group had RTOG grade 3-4 acute mucosal toxicity (226 [84%] of 268 patients) compared with accelerated radiotherapy-chemotherapy (205 [76%] of 271 patients) or conventional chemoradiotherapy (180 [69%] of 262; p=0·0001). 158 (60%) of 265 patients in the conventional chemoradiotherapy group, 176 (64%) of 276 patients in the accelerated radiotherapy-chemotherapy group, and 190 (70%) of 272 patients in the very accelerated radiotherapy group were intubated with feeding tubes during treatment (p=0·045). Chemotherapy has a substantial treatment effect given concomitantly with radiotherapy and acceleration of radiotherapy cannot compensate for the absence of chemotherapy. We noted the most favourable outcomes for conventional chemoradiotherapy, suggesting that acceleration of radiotherapy is probably not beneficial in concomitant chemoradiotherapy schedules. French Ministry of Health.
    The Lancet Oncology 02/2012; 13(2):145-53. · 25.12 Impact Factor

Publication Stats

6k Citations
1,246.86 Total Impact Points

Institutions

  • 2014
    • Groupe Oncologie Radiothérapie Tête et Cou, GORTEC
      Lutetia Parisorum, Île-de-France, France
    • University Hospital of Lausanne
      Lausanne, Vaud, Switzerland
  • 1993–2013
    • Institut de Cancérologie Gustave Roussy
      • Department of Radiotherapy
      Île-de-France, France
  • 2003–2011
    • Centre Jean Perrin
      Clermont, Auvergne, France
  • 2009
    • Institute of Cancer Research
      Londinium, England, United Kingdom
  • 2004–2009
    • Institut de Radioprotection et de Sûreté Nucléaire (IRSN)
      Fontenay, Île-de-France, France
  • 2008
    • Άγιος Σάββας Αντικαρκινικό Νοσοκομείο
      Athínai, Attica, Greece
  • 2007
    • University of Chicago
      • Department of Medicine
      Chicago, IL, United States
    • University of Groningen
      • Department of Radiotherapy
      Groningen, Province of Groningen, Netherlands
  • 2006
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 1992–1994
    • Memorial Sloan-Kettering Cancer Center
      • Department of Pediatrics
      New York City, NY, United States
  • 1989
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France