Eric Deutsch

Unité Inserm U1077, Caen, Lower Normandy, France

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Publications (207)993.91 Total impact

  • Frontiers in Oncology 09/2015; 5. DOI:10.3389/fonc.2015.00199
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    ABSTRACT: Background: Although a third of all cancers are diagnosed after the age of 75, only 9% of elderly people are recruited in clinical trials, because of fear of the risk of toxicity. The aim of this study was to compare the tolerance and efficacy observed in phase I trials among patients aged over 75 years with that observed in younger patients. Methods: Patients treated from 2007 to 2012 at Institut Gustave Roussy in phase I trials were included. The conditional Cox proportional hazards model was used to compare the occurrence of AE and overall survival in a subpopulation of elderly people (EP, aged > 75 years) matched with patients aged < 75 years (YP) according to the same phase I protocol and the same Royal Marsden Hospital (RMH) prognostic score. Results: Among the 32 EP and the 158 YP, 63% and 61% experienced grade 3-4 AEs and dose-limiting toxicities occurred in 6% and 11% in each group respectively. Age over 75 years was neither associated with a greater risk of high toxicity (HR=0.90 [CI95%, 0.47-1.70], p=0.74) nor of death (HR=0.86; CI95%: 0.38-1.93; p=0.71). Conclusions: Age over 75 years had no impact on the occurrence of either high toxicity or of death. This article is protected by copyright. All rights reserved.
    International Journal of Cancer 09/2015; DOI:10.1002/ijc.29849 · 5.09 Impact Factor
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    ABSTRACT: Thyroid carcinoma is a frequent complication of childhood cancer radiotherapy. The dose-response to thyroid radiation dose is now well established, but the potential modifier effect of other factors still requires further investigation. To investigate the role of potential modifiers of the dose-response. We followed, over an average of 27 years, a cohort of 4338 5-year survivors of solid childhood cancer treated before 1986. The dose received by the thyroid gland and some other anatomical sites during radiotherapy was estimated after reconstruction of the actual conditions in which irradiation was delivered. Fifty-five (55) patients developed a thyroid carcinoma. The risk of thyroid carcinoma increased with a radiation dose to the thyroid of up to two tenths of Gy, then leveled off for higher doses. When taking into account the thyroid radiation dose, a surgical or radiological splenectomy (>20 Gy to the spleen) increased thyroid cancer risk (RR=2.3, 95%CI:1.3-4.0), high radiation doses (> 5 Gy) to pituitary gland lowered this risk (RR=0.2, 95%CI:0.1-0.6). Patients who received nitrosourea chemotherapy had a 6.6-fold (95%CI: 2.5-15.7) higher risk than those who did not. The excess relative risk per Gy of radiation to the thyroid was 4.7 (95%CI: 1.7 to 22.6). It was 7.6 (95%CI: 1.6 to 33.3) if body mass index at time of interview was equal or higher than 25, and 4.1 (95%CI: 0.9-17.7) if not (p-value for interaction=0.1). Predicting thyroid cancer risk following childhood cancer radiation therapy probably requires the assessment of more than just the radiation dose to the thyroid. Chemotherapy, splenectomy, radiation dose to pituitary gland, and obesity also play a role.
    The Journal of Clinical Endocrinology and Metabolism 09/2015; DOI:10.1210/jc.2015-1690 · 6.21 Impact Factor
  • É Deutsch · A Lévy · C Chargari
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    ABSTRACT: The immunosuppressive effects of radiation therapy have long been the only ones considered. It has been demonstrated that exposure to ionizing radiation induces the release of tumour antigens which activates both the innate immune system and the adaptive immune response of the host. The purpose of tumour immunotherapy is based on the principle that reversal of tolerance to immunogenic tumours would be able to activate an immune response against tumour cells. Preclinical data and clinical studies early phase suggest a potential therapeutic benefit of immunotherapy combined with radiation therapy. The objective of this article is to review how tumour cells interact with the immune system and how ionizing radiation modulate this interaction and finally the combination of perspectives of immunotherapy and ionizing radiation by focusing on existing clinical data. Copyright © 2015. Published by Elsevier SAS.
    Cancer/Radiothérapie 08/2015; DOI:10.1016/j.canrad.2015.05.018 · 1.41 Impact Factor
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    ABSTRACT: Background and purpose The dose effect-effect relationship for cardiac diseases following radiotherapy suffers from uncertainties. Three dimensional coronary artery (CA) dose calculation after mediastinal Hodgkin lymphoma radiotherapy was performed, using the patient’s coronary CT angiography (CCTA), and the relationship between the coronary arteries’ radiation doses and the risk of stenosis was estimated. Materials and methods Radiotherapy simulation CT scans and CCTAs of patients treated for a mediastinal Hodgkin lymphoma were used to merge thoracic and detailed cardiovascular anatomies. Radiation treatment parameters were used to estimate CA radiation doses. Twenty-one patients without coronary stenosis (controls) were matched with twelve patients with stenosis (cases). CA segments were considered as sub-volumes of interest. Radiation doses to stenotic segments were compared with those received by normal segments (from cases and controls) using a logistic regression. Results In eleven cases out of twelve, the highest of the coronary dose distribution was on a damaged segment. Logistic regression with CA segments yielded an odds ratio associated with the risk of coronary stenosis of 1.049 per additional gray with the CA segment median dose (95% confidence interval, 1.004–1.095; p-value <0.05). Conclusion The CA segment dose significantly increased the risk of stenosis on the segment. Such personalized CA dose calculations on larger cohorts are expected to improve the understanding of the cardiovascular radiation dose–effect relationship.
    Radiotherapy and Oncology 08/2015; DOI:10.1016/j.radonc.2015.07.043 · 4.36 Impact Factor
  • Cancer Research 08/2015; 75(15 Supplement):2568-2568. DOI:10.1158/1538-7445.AM2015-2568 · 9.33 Impact Factor
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    ABSTRACT: Adjuvant radiotherapy, after breast conserving surgery or mastectomy for breast cancer, improves overall survival while decreasing the risk of recurrence. However, prophylactic postoperative radiotherapy of locoregional lymph nodes for breast cancer, particularly of the axillary region, is still controversial since the benefits and the risks due to axillary irradiation have not been well defined. To begin with, when performing conformal radiotherapy, volume definition is crucial for the analysis of the risk–benefit balance of any radiation treatment. Definition and contouring of the axillary lymph node region is discussed in this work, as per the recommendations of the European Society for Radiotherapy and Oncology (ESTRO). Axillary recurrences are rare, and the recent trend leads toward less aggressive surgery with regard to the axilla. In this literature review we present the data that lead us to avoid adjuvant axillary radiotherapy in pN0, pN0i+ and pN1mi patients even without axillary clearance and to perform it in some other situations. Finally, we propose an update about the potential toxicity of adjuvant axillary irradiation, which is essential for therapeutic decision-making based on current evidence, and to guide us in the evolution of our techniques and indications of axillary radiotherapy.
    Cancer/Radiothérapie 06/2015; 19(4). DOI:10.1016/j.canrad.2015.05.001 · 1.41 Impact Factor
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    ABSTRACT: To perform a systematic review and meta-analysis of severe adverse events (SAE) reported in early trials combining molecularly targeted therapies (MTT) with radiotherapy (RT), and to compare them to standard therapy. A summary data meta-analysis was performed and compared to the historical standard. Inclusion criteria were phase I and/or II trials published between 2000 and 2011, with glioblastoma multiforme patients treated with RT and MTT. Pooled incidence rates (IR) of SAE were estimated as well as the pooled median progression-free survival (PFS) and overall survival (OS). Nineteen prospective trials (9 phase I, 1 phase I/II and 9 phase II) out of 29 initially selected were included (n = 755 patients). The exact number of patients who had experienced SAE was mentioned in 37 % of the trials, concerning only 17 % of the patients. Information such as the period during which adverse events were monitored, the planned treatment duration, and late toxicity were not reported in the trials. The pooled IR of overall SAE was 131.2 (95 % CI 88.8-193.7) per 1000 person-months compared to 74.7 (63.6-87.8) for standard therapy (p < 0.01). Significant differences were observed for gastrointestinal events (p = 0.05) and treatment-related deaths (p = 0.02), in favour of standard therapy. No significant difference was observed in PFS and OS. Reporting a summary of toxicity data in early clinical trials should be stringently standardized. The use of MTT with RT compared to standard therapy increased SAE while yielded comparable survival in glioblastoma multiforme patients.
    Journal of Neuro-Oncology 05/2015; 123(2). DOI:10.1007/s11060-015-1802-5 · 3.07 Impact Factor
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    ABSTRACT: To evaluate in head and neck squamous cell carcinoma (HNSCC) the tolerability of concurrent radiotherapy and cetuximab (BRT) after taxane-based induction chemotherapy (ICT). 104 patients with HNSCC received BRT with (29%), or without (71%) prior taxane-based ICT. Radiodermatitis (97%) and skin rash (65%) occurred frequently but no difference of occurrence or at any grade was observed in the two populations. Patients receiving taxane-based ICT had however less severe rash as compared with patients without ICT. Mucositis and dysphagia were frequent and comparable in the two groups. The occurrence of a skin rash (or at any grade) did not predict an increased overall survival (OS) in the overall population but it was associated with an improved 3 year-OS in patients receiving taxane-based ICT. OS was not influenced by the skin rash grade in the overall population/any of the two treatments-subgroups. Taxane-based ICT did not increase the rate of cetuximab-related toxicities. This article is protected by copyright. All rights reserved. © 2015 Wiley Periodicals, Inc.
    Head & Neck 05/2015; DOI:10.1002/hed.24125 · 2.64 Impact Factor
  • E Rivin · G. Brusadin · S. Corbin · F. Hubert · D. Motto · E. Deutsch · S. Rivera
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    ABSTRACT: There is growing interest in the association of radiotherapy and immunotherapy for the treatment of solid tumors. Here, we report an extremely effective combination of local irradiation (IR) and Shiga Toxin B (STxB)-based human papillomavirus (HPV) vaccination for the treatment of HPV-associated head and neck squamous cell carcinoma (HNSCC). The efficacy of the irradiation and vaccine association was tested using a model of HNSCC obtained by grafting TC-1/luciferase cells at a submucosal site of the inner lip of immunocompetent mice. IR and the STxB-E7 vaccine acted synergistically with both single and fractionated irradiation schemes, resulting in complete tumor clearance in the majority of the treated mice. A dose threshold of 7.5 Gy was required to elicit the dramatic antitumor response. The combined treatment induced high levels of tumor-infiltrating, antigen-specific CD8+ T cells, which were required to trigger the antitumor activity. Treatment with STxB-E7 and IR induced CD8+ T-cell memory, which was sufficient to exert complete antitumor responses in both local recurrences and distant metastases. We also report for the first time that a combination therapy based on local IR and vaccination induces an increased pericyte coverage (as shown by αSMA and NG2 staining) and ICAM-1 expression on vessels. This was associated with enhanced intra-tumor vascular permeability that correlated with the antitumor response, suggesting that the combination therapy could also act through an increased accessibility for immune cells. The combination strategy proposed here offers a promising approach that could potentially be transferred into early phase clinical trials. Copyright © 2015, American Association for Cancer Research.
    Molecular Cancer Therapeutics 04/2015; 14(6). DOI:10.1158/1535-7163.MCT-14-1015 · 5.68 Impact Factor
  • E. Deutsch · C. Clemenson · M. Mondini
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    ABSTRACT: The purpose of this study was to investigate the suitability of a graphics library based model for the assessment of linear accelerator radiation leakage. Transmission through the shielding elements was evaluated using the build-up factor corrected exponential attenuation law and the contribution from the electron guide was estimated using the approximation of a linear isotropic radioactive source. Model parameters were estimated by a fitting series of thermoluminescent dosimeter leakage measurements, achieved up to 100 cm from the beam central axis along three directions. The distribution of leakage data at the patient plane reflected the architecture of the shielding elements. Thus, the maximum leakage dose was found under the collimator when only one jaw shielded the primary beam and was about 0.08% of the dose at isocentre. Overall, we observe that the main contributor to leakage dose according to our model was the electron beam guide. Concerning the discrepancies between the measurements used to calibrate the model and the calculations from the model, the average difference was about 7%. Finally, graphics library modelling is a readily and suitable way to estimate leakage dose distribution on a personal computer. Such data could be useful for dosimetric evaluations in late effect studies.
    Physics in Medicine and Biology 03/2015; 60(5). DOI:10.1088/0031-9155/60/5/2103 · 2.76 Impact Factor
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    ABSTRACT: This phase I study evaluated the safety and efficacy of the oral mTOR inhibitor everolimus in combination with thoracic radiotherapy followed by consolidation chemotherapy in locally advanced or oligometastatic untreated non-small cell lung cancer (NSCLC). Everolimus dose was escalated in incremental steps (sequential cohorts of 3 patients until the occurrence of dose-limiting toxicity [DLT]) and administered orally weekly (weekly group:dose of 10,20 or 50 mg) or daily (daily group:2.5,5 or 10 mg), one week before, and during radiotherapy until 3.5 weeks after the end of radiotherapy. Two cycles of chemotherapy (cisplatin-navelbine) were administrated 4.5 weeks after the end of radiotherapy. Twenty six patients were included in two centers, 56% had adenocarcinoma and 84% had stage III disease. In the weekly group (12 evaluable patients), everolimus could be administered safely up to the maximum planned weekly dose of 50 mg;however, one patient experienced a DLT of interstitial pneumonitis at the weekly dose level of 20 mg. In the daily group (9 evaluable patients):one DLT of interstitial pneumonitis with a fatal outcome was observed at the daily dose level of 2.5 mg;2 other DLTs (one grade 3 oesophagitis and one bilateral interstitial pneumonitis) were found at the daily dose level of 5 mg. Overall there were 5 patients with G3-4 interstitial pneumonitis related to treatment. In 22 evaluable patients for response, there were 9 (41%) partial response, and 7 (32%) stable disease. At a median follow-up of 29 months, the 2-year overall survival and progression-free survival actuarial rates were 31% and 12%, respectively. In previously untreated and unselected NSCLC patients, the recommended phase II dose of everolimus in combination with thoracic radiotherapy is 50 mg/week. Pulmonary toxicity is of concern and should be carefully monitored to establish the potential role of mTOR inhibitor with concomitant radiotherapy. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email:
    Annals of Oncology 02/2015; 26(6). DOI:10.1093/annonc/mdv105 · 7.04 Impact Factor
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    ABSTRACT: Lapatinib is a dual epidermal growth factor receptor (EGFR) and HER2 inhibitor. Overexpression of these receptors is frequently observed in head and neck squamous cell carcinoma (HNSCC). As growing proportion of HNSCC is characterized by human papillomavirus (HPV) infection, we aimed at evaluating the efficacy of lapatinib as function of HPV status in HNSCC cell lines. Two HPV-positive and two HPV-negative HNSCC cell lines were used. Proliferation, cell cycle, and Annexin V assays were performed to test their sensitivity to lapatinib. Combination of lapatinib and ionizing radiation was evaluated with clonogenic survival assays. Akt, EGFR and HER2, and E6/E7 expression and activation were analyzed by immunoblotting and quantitative reverse transcription polymerase chain reaction. Lapatinib reduced E6 and E7 expression and Akt phosphorylation, inhibited cell proliferation and induced cell death in HPV-positive cell lines. An additive effect of lapatinib with radiation was observed in these cells. Lapatinib had no effect on HPV-negative cells. Lapatinib efficacy restricted to the HPV-positive cells suggests that HPV status could be a potential marker for enhanced response to lapatinib in HNSCC.
    OncoTargets and Therapy 02/2015; 8:335-345. DOI:10.2147/OTT.S68235 · 2.31 Impact Factor
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    ABSTRACT: Stroma mediated wound healing signals may share similarities with the ones produced by tumor's microenvironment and their modulation may impact tumor response to the various anti-cancer treatments including radiation therapy. Therefore we conducted this study, to assess the crosstalk between stromal and carcinoma cells in response to radiotherapy by genetic modulation of the stroma and irradiation. We found that fibroblasts irrespective of their RhoB status do not modulate intrinsic radiosensitivity of TC-1 but produce diffusible factors able to modify tumor cell fate. Then we found that Wt and RhoB deficient fibroblasts stimulated TC-1 migration through distinct mechanisms which are TGF-β1 and MMP-mediated respectively. Lastly, we found that simultaneous irradiation of fibroblasts and TC-1 abrogated the pro-migratory phenotype by repression of TGF-β and MMP secretion. This last result is highly relevant to the clinical situation and suggests that conversely to, the current view; irradiated stroma would not enhance carcinoma migration and could be manipulated to promote anti-tumor immune response.
    PLoS ONE 01/2015; 10(1). DOI:10.1371/journal.pone.0115447 · 3.23 Impact Factor
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    ABSTRACT: Purpose: To report the application of the global risk analysis (GRA) in the pulsed-dose rate (PDR) brachytherapy workflow. Material and methods: Analyses were led by a multidisciplinary working group established within the unit with the guidance of a quality engineer. First, a mapping of hazardous situations was developed as a result of interactions between the patient workflow for a treatment using PDR brachytherapy split into 51 sub-phases with a comprehensive list of the hazards that he/she faces (44). Interactions, when relevant, were sorted by level of priority: to be treated immediately, secondarily (the group is not entitled to treat the situation), or later (safe situation). Secondly, for each high priority dangerous situation, scenarios were developed to anticipate their potential consequences. Criticality was assessed, using likelihood and severity scales and a matrix, which allocated risks into categories: acceptable (C1), tolerable under control (C2) and unacceptable (C3). Then, corrective actions were proposed and planned when relevant, after assessment of their feasibility with a scale of effort. Finally, the criticality of the scenarios was reevaluated, taking into account the implementation of these actions, leading to a residual risk mapping, which could trigger additional proposals of actions. Results: Two thousand one hundred and eighty-four potential interactions between the list of hazards and the workflow were analyzed. Mapping of dangerous situations identified 213 relevant interactions, from which 61 were considered with high priority. One hundred and twenty-six scenarios were generated: 68 with a low criticality (74.3%), 58 with an intermediate score (25.7%). No scenario with the highest criticality was individualized. Twenty-one corrective actions were planned. Mapping of residual risk resulted in the disappearance of most C2 risks, leaving 5 C2 scenarios (4%), for which four monitoring indicators were implemented in addition to the corrected actions decided on. Conclusion: The implementation of the GRA appeared feasible, and led to implement 21 corrective actions, based on scenarios and not on incidents.
    Cancer/Radiothérapie 01/2015; 19(2). DOI:10.1016/j.canrad.2014.11.002 · 1.41 Impact Factor
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    ABSTRACT: Communication training programs in oncology have demonstrated some efficacy to improve doctors' communication skills. The goal of our study was to evaluate the impact of such training in the particular context of phase I clinical trials. Self-satisfaction and self-efficacy scales evaluating doctor-patient communication was completed by 6 medical oncologists (3 juniors and 3 seniors) before and after their communication training for a total of sixty visits. Two types of visit have been distinguished: the visits between the oncologist and the patient alone (a dual situation) and those with a third party (a trilateral situation). For all the doctors in dual and trialateral situations, self-efficacy scores improved significantly after training. This improvement was more pronounced for juniors oncologists in trilateral situations. Before training, satisfactory scores were worst in duel versus trilateral situations (P=0.01). This was particularly pronounced for junior compared to senior doctors (P=0.035). After training, in trilateral situations, the satisfaction scores of junior doctors matched that of the senior doctors. The communication training programs appear to benefit junior oncologists to a greater extent in trilateral situations. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.
    Bulletin du cancer 01/2015; 102(2). DOI:10.1016/j.bulcan.2014.12.013 · 0.60 Impact Factor
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    ABSTRACT: To assess the interest of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET/CT) to evaluate the tumor response after radiotherapy (RT) in anaplastic thyroid cancer (ATC) patients. 92 patients were treated for ATC at our institution from 1987 to 2012, out of which 64 (70%) received an aggressive multimodal treatment and 28 (30%) a palliative treatment. In the multimodal treatment group, curative-intended surgery, chemotherapy, and RT were delivered in 35 (55%), 59 (92%), and 56 (88%) patients. The maximum standardized uptake value (SUVmax) was determined in tumor (T), nodes (N) and metastases (M) in each available (18)F-FDG PET/CT. The median follow-up was 3.2years. The 1-year actuarial overall survival (OS) was 18% (median: 5.2months) in the entire population and 27% (median: 7months) in the multimodal treatment group. In the multivariate analysis, RT, surgery, and pre-RT chemotherapy independently predicted for OS, with HRs respectively of 0.1, 0.3, and 0.5. Quantification of FDG uptake with SUVmax was assessable in 26 (40%), 19 (30%), and 25 (39%) of (18)F-FDG PET/CT performed initially (prior to any treatment), prior to RT, and after RT, respectively. Mean SUVmax significantly decreased in T (p<0.001), but not in N (p=0.1) and M (p=0.3) during the assessment period, which might be related to the local effect of RT. Comparing pre- and post-RT (18)F-FDG PET/CT, the T mean relative SUVmax decrease was lower (23±54%) in the 4 patients that had a local relapse (LR) as compared with others in the 12 others patients (62±33%; p=0.3). A relative SUVmax decrease inferior to 20% significantly predicted for LR (p=0.02). The prognosis of ATC patients remains dismal despite an aggressive multimodal treatment. Although our results were not significant, (18)F-FDG PET/CT could potentially serve as a surrogate marker of treatment response in ATC. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Oral Oncology 01/2015; 51(4). DOI:10.1016/j.oraloncology.2014.12.014 · 3.61 Impact Factor

Publication Stats

2k Citations
993.91 Total Impact Points


  • 2015
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2009–2015
    • Université Paris-Sud 11
      Orsay, Île-de-France, France
    • Institut de Radioprotection et de Sûreté Nucléaire (IRSN)
      Fontenay, Île-de-France, France
  • 2000–2015
    • Institut de Cancérologie Gustave Roussy
      • Department of Radiotherapy
      Villejuif, Île-de-France, France
  • 2011
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 2006
    • University of Florence
      Florens, Tuscany, Italy
    • University of Pennsylvania
      • Department of Radiation Oncology
      Philadelphia, PA, United States