Eric Deutsch

Unité Inserm U1077, Caen, Lower Normandy, France

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Publications (174)870.43 Total impact

  • [Show abstract] [Hide abstract]
    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; DOI:10.1158/1535-7163.MCT-14-1015 · 6.11 Impact Factor
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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 · 2.92 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: journals.permissions@oup.com.
    Annals of Oncology 02/2015; DOI:10.1093/annonc/mdv105 · 6.58 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 · 3.53 Impact Factor
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    ABSTRACT: To report the application of the global risk analysis (GRA) in the pulsed-dose rate (PDR) brachytherapy workflow.
    Cancer/Radiothérapie 01/2015; 19(2). DOI:10.1016/j.canrad.2014.11.002 · 1.11 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.
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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; DOI:10.1016/j.oraloncology.2014.12.014 · 3.03 Impact Factor
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    ABSTRACT: Purpose/Objective(s) To describe a novel method to explore radiation dose-volume effects. Functional data analysis is used to investigate the information contained in differential dose-volume histograms. The method is applied to the normal tissue complication probability modeling of rectal bleeding (RB) for patients irradiated in the prostatic bed by 3-dimensional conformal radiation therapy. Methods and Materials Kernel density estimation was used to estimate the individual probability density functions from each of the 141 rectum differential dose-volume histograms. Functional principal component analysis was performed on the estimated probability density functions to explore the variation modes in the dose distribution. The functional principal components were then tested for association with RB using logistic regression adapted to functional covariates (FLR). For comparison, 3 other normal tissue complication probability models were considered: the Lyman-Kutcher-Burman model, logistic model based on standard dosimetric parameters (LM), and logistic model based on multivariate principal component analysis (PCA). Results The incidence rate of grade ≥2 RB was 14%. V65Gy was the most predictive factor for the LM (P=.058). The best fit for the Lyman-Kutcher-Burman model was obtained with n=0.12, m = 0.17, and TD50 = 72.6 Gy. In PCA and FLR, the components that describe the interdependence between the relative volumes exposed at intermediate and high doses were the most correlated to the complication. The FLR parameter function leads to a better understanding of the volume effect by including the treatment specificity in the delivered mechanistic information. For RB grade ≥2, patients with advanced age are significantly at risk (odds ratio, 1.123; 95% confidence interval, 1.03-1.22), and the fits of the LM, PCA, and functional principal component analysis models are significantly improved by including this clinical factor. Conclusion Functional data analysis provides an attractive method for flexibly estimating the dose-volume effect for normal tissues in external radiation therapy.
    International journal of radiation oncology, biology, physics 11/2014; 90(3):654–663. DOI:10.1016/j.ijrobp.2014.07.008 · 4.18 Impact Factor
  • E Deutsch, F Dhermain, C Chargari
    Annals of Oncology 10/2014; DOI:10.1093/annonc/mdu477 · 6.58 Impact Factor
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    ABSTRACT: Purpose To report the application of the Global Risk Analysis (GRA), an innovative proactive risk analysis method, to a radiotherapy department. Material and methods Analyses were conducted by a multidisciplinary working group with the support of a quality engineer. First, a mapping of hazardous situations was developed. For this, a double entry table was filled in, crossing the process of patient care divided into steps with a comprehensive list of pre-established hazards. The cells of the table represented interactions, which were, when relevant, considered as dangerous situations and then sorted by level of priority. For each high priority dangerous situation, scenarios were developed. Their criticality was assessed, using likelihood and severity scales, and a criticality matrix was used to allocate them into categories: acceptable (C1), tolerable (C2) and unacceptable (C3). Corrective actions were planned when relevant. Afterward, the criticality of the scenarios was reevaluated, leading to a residual risk mapping. Results The number of high priority dangerous situations to analyze was 78, for which 205 scenarios were generated: 95 C1, 98 C2, and 12 C3 scenarios. Twenty-two corrective actions were planned. Mapping of residual risk resulted in the disappearance of C3 risks, leaving 18 C2 scenarios, for which six monitoring indicators were implemented. Conclusion The implementation of the GRA appeared feasible and led to the implementation of 22 corrective actions based on scenarios, without the occurrence of any incidents.
    Radiotherapy and Oncology 09/2014; 112(2). DOI:10.1016/j.radonc.2014.08.037 · 4.86 Impact Factor
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    ABSTRACT: Radiotherapy has a critical role in the treatment of small-cell lung cancer (SCLC). The effectiveness of radiation in SCLC remains limited as resistance results from defects in apoptosis. In the current study, we investigated whether using the Bcl-2/Bcl-XL inhibitor S44563 can enhance radiosensitivity of SCLC cells in vitro and in vivo. In vitro studies confirmed that S44563 caused SCLC cells to acquire hallmarks of apoptosis. S44563 markedly enhanced the sensitivity of SCLC cells to radiation, as determined by a clonogenic assay. The combination of S44563 and cisplatin-based chemo-radiation showed a significant tumor growth delay and increased overall survival in mouse xenograft models. This positive interaction was greater when S44563 was given after the completion of the radiation, which might be explained by the radiation-induced overexpression of anti-apoptotic proteins secondary to activation of the NF-κB pathway. These data underline the possibility of combining IR and Bcl-2/Bcl-XL inhibition in the treatment of SCLC as they underscore the importance of administering conventional and targeted therapies in an optimal sequence.
    Cell Death & Disease 09/2014; 5:e1423. DOI:10.1038/cddis.2014.365 · 5.18 Impact Factor
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    ABSTRACT: Age is an important feature at the time of early breast cancer diagnosis. Radiotherapy is a mandatory com-ponent of treatment for breast-conserving strategies in early disease stages. Breast radiotherapy has rapidly evolved in the last 20 years. A tendency to less treatment volume (partial-breast irradiation) and less treatment time (hypofractiona-tion) is consolidated in modern radiation oncology practice. Age and risk for local recurrence guide the decision-making process to electro-optimal treatment. Radiotherapy technological versatility offers multiple options for indi-vidualized (risk–age adapted) recommendations.
    Clinical and Translational Oncology 08/2014; 3(8). DOI:10.1007/s12094-014-1164-z · 1.60 Impact Factor
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    ABSTRACT: Background: Patients with locally advanced rectal cancer (LARC) have a dismal prognosis. We investigated outcomes and risk factors for locoregional recurrence (LRR) in patients treated with preoperative chemoradiotherapy (CRT), surgery and IOERT. Methods: A total of 335 patients with LARC [>= cT3 93% and/or cN+ 69%) were studied. In multivariate analyses, risk factors for LRR, IFLR and OFLR were assessed. Results: Median follow-up was 72.6 months (range, 4-205). In multivariate analysis distal margin distance <= 10 mm [HR 2.46, p = 0.03], R1 resection [HR 5.06, p = 0.02], tumor regression grade 1-2 [HR 2.63, p = 0.05] and tumor grade 3 [HR 7.79, p < 0.001] were associated with an increased risk of LRR. A risk model was generated to determine a prognostic index for individual patients with LARC. Conclusions: Overall results after multimodality treatment of LARC are promising. Classification of risk factors for LRR has contributed to propose a prognostic index that could allow us to guide risk-adapted tailored treatment.
    Radiotherapy and Oncology 07/2014; 112(1). DOI:10.1016/j.radonc.2014.05.012 · 4.86 Impact Factor
  • 04/2014; 24(2). DOI:10.1684/ejd.2014.2300
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    ABSTRACT: Cardiac toxicity is a side-effect of anti-cancer treatment including radiotherapy and this translational study was initiated to characterize radiation-induced cardiac side effects in a population of breast cancer patients and in experimental models in order to identify novel therapeutic target. The size of the heart was evaluated in CO-HO-RT patients by measuring the Cardiac-Contact-Distance before and after radiotherapy (48months of follow-up). In parallel, fibrogenic signals were studied in a severe case of human radiation-induced pericarditis. Lastly, radiation-induced cardiac damage was studied in mice and in rat neonatal cardiac cardiomyocytes. In patients, time dependent enhancement of the CCD was measured suggesting occurrence of cardiac hypertrophy. In the case of human radiation-induced pericarditis, we measured the activation of fibrogenic (CTGF, RhoA) and remodeling (MMP2) signals. In irradiated mice, we documented decreased contractile function, enlargement of the ventricular cavity and long-term modification of the time constant of decay of Ca(2+) transients. Both hypertrophy and amyloid deposition were correlated with the induction of Epac-1; whereas radiation-induced fibrosis correlated with Rho/CTGF activation. Transactivation studies support Epac contribution in hypertrophy stimulation and showed that radiotherapy and Epac displayed specific and synergistic signals. Epac-1 has been identified as a novel regulator of radiation-induced hypertrophy and amyloidosis but not fibrosis in the heart.
    Radiotherapy and Oncology 04/2014; DOI:10.1016/j.radonc.2014.01.025 · 4.86 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; DOI:10.1007/s00066-014-0626-0 · 2.73 Impact Factor
  • International journal of radiation oncology, biology, physics 03/2014; 88(3):755–756. DOI:10.1016/j.ijrobp.2013.11.224 · 4.18 Impact Factor
  • Molecular Cancer Therapeutics 01/2014; 12(11_Supplement):C219-C219. DOI:10.1158/1535-7163.TARG-13-C219 · 6.11 Impact Factor
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    ABSTRACT: Background Patients with locally advanced rectal cancer (LARC) have a dismal prognosis. We investigated outcomes and risk factors for locoregional recurrence (LRR) in patients treated with preoperative chemoradiotherapy (CRT), surgery and IOERT. Methods A total of 335 patients with LARC [⩾cT3 93% and/or cN+ 69%) were studied. In multivariate analyses, risk factors for LRR, IFLR and OFLR were assessed. Results Median follow-up was 72.6 months (range, 4–205). In multivariate analysis distal margin distance ⩽10 mm [HR 2.46, p = 0.03], R1 resection [HR 5.06, p = 0.02], tumor regression grade 1–2 [HR 2.63, p = 0.05] and tumor grade 3 [HR 7.79, p < 0.001] were associated with an increased risk of LRR. A risk model was generated to determine a prognostic index for individual patients with LARC. Conclusions Overall results after multimodality treatment of LARC are promising. Classification of risk factors for LRR has contributed to propose a prognostic index that could allow us to guide risk-adapted tailored treatment.
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    ABSTRACT: Cancer research has received a fresh impetus from the concept of cancer stem cell (CSC) which postulates the existence of a tumor cell population uniquely endowed with self-renewal capacity and therapy resistance. Despite recent progresses including targeted therapy, lung cancer treatment remains a challenge owing largely to disease recurrence. Providing a conceptual model of tumor resistance and disease relapse, the lung CSC has received extensive attention, leading to a flourishing literature and several ongoing clinical trials. In this study, we will discuss the data suggesting the existence of CSC in lung tumors and the potential clinical utility of CSCs as prognostic markers or cellular targets of new therapeutic strategies. We will also touch on the new fundamental developments of the CSC concept that ought to be considered if the integration of the CSC concept into clinical practice is to be successful and impact on lung cancer treatment.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 01/2014; 9(1):7-17. DOI:10.1097/JTO.0000000000000028 · 5.80 Impact Factor

Publication Stats

2k Citations
870.43 Total Impact Points

Institutions

  • 2015
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2011–2015
    • Université Paris-Sud 11
      Orsay, Île-de-France, France
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 2000–2015
    • Institut de Cancérologie Gustave Roussy
      • Department of Radiotherapy
      Villejuif, Île-de-France, France
  • 2009
    • Institute of Cancer Research
      Londinium, England, United Kingdom
    • Institut de Radioprotection et de Sûreté Nucléaire (IRSN)
      Fontenay, Île-de-France, France
  • 2005–2006
    • University of Pennsylvania
      • Department of Radiation Oncology
      Philadelphia, PA, United States
    • William Penn University
      Filadelfia, Pennsylvania, United States