H Loiseau

Université Victor Segalen Bordeaux 2, Bordeaux, Aquitaine, France

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Publications (118)264.84 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The carcinogenic effect of radiofrequency electromagnetic fields in humans remains controversial. However, it has been suggested that they could be involved in the aetiology of some types of brain tumours. The objective was to analyse the association between mobile phone exposure and primary central nervous system tumours (gliomas and meningiomas) in adults. CERENAT is a multicenter case-control study carried out in four areas in France in 2004-2006. Data about mobile phone use were collected through a detailed questionnaire delivered in a face-to-face manner. Conditional logistic regression for matched sets was used to estimate adjusted ORs and 95% CIs. A total of 253 gliomas, 194 meningiomas and 892 matched controls selected from the local electoral rolls were analysed. No association with brain tumours was observed when comparing regular mobile phone users with non-users (OR=1.24; 95% CI 0.86 to 1.77 for gliomas, OR=0.90; 95% CI 0.61 to 1.34 for meningiomas). However, the positive association was statistically significant in the heaviest users when considering life-long cumulative duration (≥896 h, OR=2.89; 95% CI 1.41 to 5.93 for gliomas; OR=2.57; 95% CI 1.02 to 6.44 for meningiomas) and number of calls for gliomas (≥18 360 calls, OR=2.10, 95% CI 1.03 to 4.31). Risks were higher for gliomas, temporal tumours, occupational and urban mobile phone use. These additional data support previous findings concerning a possible association between heavy mobile phone use and brain tumours.
    Occupational and environmental medicine 05/2014; · 3.64 Impact Factor
  • Neurosurgery 04/2014; · 2.53 Impact Factor
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    ABSTRACT: The incidence of glioblastoma (GBM) has increased in patients aged 70 years or older, and will continue to grow. Elderly GBM patients have been excluded from most clinical trials; furthermore, optimal care management as well as benefit/risk ratio of GBM treatments are still being debated. This study describes oncological patterns of care, prognostic factors, and survival for patients ≥70 years in France. We identified patients over 70 with newly diagnosed and histologically confirmed GBM on data previously published by the French Brain Tumor DataBase. We included 265 patients. Neurological deficits and mental status disorders were the most frequent symptoms. The surgery consisted of resection (RS n = 95) or biopsy (B n = 170); 98 patients did not have subsequent oncological treatment. After surgery, first-line treatment consisted of radiotherapy (RT n = 76), chemotherapy (CT n = 52), and concomitant radiochemotherapy (CRC n = 39). The median age at diagnosis was 76, 74, and 73 years, respectively, for the untreated, B + RT and/or CT, RS ± RT and/or CT groups. Median survival (in days, 95 % CI) with these main strategies, when analyzed according to surgical groups, was: B-CT n = 41, 199[155-280]; B-CRC n = 21, 318[166-480]; B-RT n = 37, 149[130-214]; RS-CT n = 11, 245[211-na]; RS-CRC n = 18, 372[349-593]; RS-RT n = 39, 269[218-343]. This population study for elderly GBM patients is one of the most important in Europe, and could be considered as a historical cohort to compare future treatments. Moreover, we can hypothesize that elderly patients (versus patients <70 years) are undertreated. Karnofsky performance status seems to be the most relevant clinical predictive factor, and RS and CRC have a positive impact on survival for elderly GBM patients in the general population, at least when feasible.
    Neurosurgical Review 02/2014; · 1.97 Impact Factor
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    ABSTRACT: Background The aim of this study was to correlate MRI features and molecular characteristics in anaplastic oligodendrogliomas (AOs).Methods The MRI characteristics of 50 AO patients enrolled in the French national network for high-grade oligodendroglial tumors were analyzed. The genomic profiles and IDH mutational statuses were assessed using high-resolution single-nucleotide polymorphism arrays and direct sequencing, respectively. The gene expression profiles of 25 1p/19q-codeleted AOs were studied on Affymetrix expression arrays.ResultsMost of the cases were frontal lobe contrast-enhanced tumors (52%), but the radiological presentations of these cases were heterogeneous, ranging from low-grade glioma-like aspects (26%) to glioblastoma-like aspects (22%). The 1p/19q codeletion (n = 39) was associated with locations in the frontal lobe (P = .001), with heterogeneous intratumoral signal intensities (P = .003) and with no or nonmeasurable contrast enhancements (P = .01). The IDH wild-type AOs (n = 7) more frequently displayed ringlike contrast enhancements (P = .03) and were more frequently located outside of the frontal lobe (P = .01). However, no specific imaging pattern could be identified for the 1p/19q-codeleted AO or the IDH-mutated AO. Within the 1p/19q-codeleted AO, the contrast enhancement was associated with larger tumor volumes (P = .001), chromosome 9p loss and CDKN2A loss (P = .006), genomic instability (P = .03), and angiogenesis-related gene expression (P < .001), particularly for vascular endothelial growth factor A and angiopoietin 2.Conclusion In AOs, the 1p/19q codeletion and the IDH mutation are associated with preferential (but not with specific) imaging characteristics. Within 1p/19q-codeleted AO, imaging heterogeneity is related to additional molecular alterations, especially chromosome 9p loss, which is associated with contrast enhancement and larger tumor volume.
    Neuro-Oncology 12/2013; · 6.18 Impact Factor
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    ABSTRACT: Growing evidence supports a role for the Unfolded Protein Response (UPR) in carcinogenesis, however the precise molecular mechanisms underlying this phenomenon remain elusive. Herein, we identified the circadian clock PER1 mRNA as a novel substrate of the endoribonuclease activity of the UPR sensor IRE1α. Analysis of the mechanism demonstrates that IRE1α endoribonuclease activity decreased PER1 mRNA in tumor cells without affecting PER1 gene transcription. Inhibition of IRE1α signaling using either siRNA-mediated silencing or a dominant-negative strategy prevented PER1 mRNA decay, reduced tumorigenesis, and increased survival, features that were reversed upon PER1 silencing. Further analysis also identifies the chemokine CXCL3 as an IRE1α/PER1 target mediating these cellular effects. Clinically, patients showing reduced survival have lower levels of PER1 mRNA expression and increase splicing of XBP1, a known IRE1α substrate, thereby pointing towards an increase IRE1α activity in these patients. Hence, we describe a novel mechanism connecting the UPR and circadian clock components in tumor cells, thereby highlighting the importance of this interplay in tumor development.
    Cancer Research 06/2013; · 9.28 Impact Factor
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    ABSTRACT: Background: Brain metastases (BM) from differentiated thyroid carcinoma (DTC) are uncommon and many questions about their management remain unsolved. The objective of this retrospective study is to analyze the characteristics, treatments and outcomes of patients with BM from DTC. Methods: Among the 1523 patients with a DTC prospectively recorded in institutional databases between 1989-2012, 21 patients (1.4%) with BM were retrospectively retrieved. Patient characteristics, histological findings on initial thyroidectomy specimen, treatments, and time to death were reviewed. Overall survival (OS) was calculated using the Kaplan-Meier method. Survival curves for various subgroups of patients according to baseline characteristics and treatment received were compared. Results: Mean age at initial and BM diagnosis were respectively 52.7 and 63.2 years. World Health Organization performance status (WHO PS) at BM diagnosis was good (< 2) for 12 patients and poor (≥ 2) for nine. The initial carcinoma was papillary for twelve patients, follicular for five, and poorly differentiated for four. Eighteen patients had other previous and/or synchronous distant metastases: lung (11), bone (10) and others (2 peritoneum, 1 liver, 1 adrenal gland and 1 uterine cervix). The average interval between the first metastasis and the BM was three years (range, 0-35.6y). The mean number and the mean size of BM were respectively 2.8 (range, 1-10) and 22.5 mm (range, 3-44 mm). Surgery was performed for ten patients and radiotherapy (RT) for 18 with two stereotactic radiosurgeries (SRS), two conformal RT limited to the metastasis and 15 whole brain radiotherapies (WBRT). The median OS after BM was 7.1 months. OS at 1 and 2 years were 41.6% and 35.6%. PS and realization of surgery or SRS had an impact on survival, with OS of 27 months when PS < 2 vs. 3 months when PS ≥ 2 (p=0.0009); and OS of 11.9 months after surgery or SRS vs. 3.6 months in their absence (p=0.04). Conclusions: BM from TC may have an indolent evolution with survival of one to two years or longer for specific groups of patients. Therefore, aggressive treatment options like neurosurgery and radiotherapy should be strongly considered in patients with good PS.
    Thyroid: official journal of the American Thyroid Association 06/2013; · 2.60 Impact Factor
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    ABSTRACT: The human matrix metalloprotease 9 (hMMP-9) is involved in many physiological processes such as tissue remodeling. Its overexpression in tumors promotes the release of cancer cells thus contributing to tumor metastasis. It is a relevant marker of malignant tumors. We selected an RNA aptamer containing 2'fluoro, pyrimidine ribonucleosides, that exhibits a strong affinity for hMMP-9 (Kd = 20 nM) and that discriminates other human MMPs: no binding was detected to either hMMP-2 or -7. Investigating the binding properties of different MMP-9 aptamer variants by surface plasmon resonance allowed the determination of recognition elements. As a result, a truncated aptamer, 36 nucleotide long was made fully resistant to nuclease following the substitution of every purine ribonucleoside residue by 2'-O-methyl analogues and was conjugated to S-acetylmercaptoacetyltriglycine for imaging purposes. The resulting modified aptamer retained the binding properties of the originally selected sequence. Following 99mTc labelling this aptamer was used for ex vivo imaging slices of human brain tumors. We were able to specifically detect the presence of hMMP-9 in such tissues.
    Bioconjugate Chemistry 10/2012; · 4.58 Impact Factor
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    ABSTRACT: Cancer registries cover 18% of the French population. A national surveillance might be warranted for some potentially environment-related cancers such as tumors of the central nervous system (CNS) to detect abnormal incidence variations. The PMSI database provides an interesting source of comprehensive, standardized and mandatory data collected from all health facilities. The aim of this work was to develop methods to identify incident CNS tumors using the PMSI database. A selection of patients living in Gironde was made in the 2004 PMSI database of the hospital of Bordeaux, using the CNS tumors codification. Cases were validated via the CNS primary tumor registry of Gironde taken as the reference, or medical records. Various combinations of criteria were defined and tested. The first selection based on diagnoses identified patients with a sensitivity of 84% and a positive predictive value (PPV) of 34%. Patients wrongly identified by the PMSI were non-incident cases (49%) or patients without a CNS tumor (45%). Patients with a tumor not identified by the PMSI had been hospitalized in 2005 (44%) or had no code for CNS tumor (42%). According to the algorithms, the sensitivity ranged from 64% to 84%, and the PPV from 34% to 69%. The best combination had a sensitivity of 67% and a PPV of 69% and was obtained with codes for CNS tumor in 2004 associated with a diagnostic or therapeutic code for persons under 70 years without code for CNS tumor in previous years or code for metastasis in 2004. According to these results, the PMSI database cannot be used alone to calculate the incidence of these complex tumors. However the PMSI database plays an important role in cancer surveillance, in combination with other information sources and the expertise of cancer registries. This role could increase with further reflection and improvement of data quality.
    Revue d Épidémiologie et de Santé Publique 06/2012; 60(4):295-304. · 0.69 Impact Factor
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    ABSTRACT: Objective To establish Guidelines for the management of Concussions for Professional and High Level (International) Rugby in France.Material and methodsLiterature from the last ten years, IRB recommendations and consensus statements on concussions in sports were analysed by a group of experts and adapted to the practice of Professional and High Level (international) Rugby in France.ResultsThe guidelines contain the description of the clinical signs and symptoms for the concussion sideline diagnosis justifying the definitive exit of the player, the immediate management recommandations, the organisation of a specialized consultation beyond 48 hours of strict rest to establish a prognostic classification and the conditions and delay of the return to play which can be made only after a new specialized consultation.Conclusion These recommendations are intended to be already applied and may evolve according to the scientific data which will be annually followed by the group of experts.
    Journal de Traumatologie du Sport 12/2011; 28(4):227–242.
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    ABSTRACT: An increase in the incidence of CNS tumors has been observed in many countries in the last decades. The reality of this trend has been much debated, as it has happened during a period when computer-assisted tomography and MRI have dramatically improved the detection of these tumors. The Gironde CNS Tumor Registry provides here the first data on CNS tumor incidence and trends in France for all histological types, including benign and malignant tumors, for the period 2000-2007. Incidence rates were calculated globally and for each histological subtype. For trends, a piecewise log-linear model was used. The overall annual incidence rate was found to be 17.6/100 000. Of this rate, 7.9/100 000 were neuroepithelial tumors and 6.0/100 000 were meningiomas. An overall increase in CNS tumor incidence was observed from 2000 to 2007, with an annual percent change (APC) of +2.33%, which was explained mainly by an increase in the incidence of meningiomas over the 8-year period (APC = +5.4%), and also more recently by an increase in neuroepithelial tumors (APC = +7.45% from 2003). The overall increase was more pronounced in women and in the elderly, with an APC peaking at +24.65% in subjects 85 and over. The increase in the incidence rates we observed may have several explanations: not only improvements in registration, diagnosis, and clinical practice, but also changes in potential risk factors.
    Neuro-Oncology 12/2011; 13(12):1370-8. · 6.18 Impact Factor
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    ABSTRACT: The etiology of brain tumors remains largely unknown. Among potential risk factors, exposure to electromagnetic fields is suspected. We analyzed the relationship between residential and occupational exposure to electromagnetic field and brain tumors in adults. A case-control study was carried out in southwestern France between May 1999 and April 2001. A total of 221 central nervous system tumors (105 gliomas, 67 meningiomas, 33 neurinomas and 16 others) and 442 individually age- and sex-matched controls selected from general population were included. Electromagnetic field exposure [extremely low frequency (ELF) and radiofrequency separately was assessed in occupational settings through expert judgement based on complete job calendar, and at home by assessing the distance to power lines with the help of a geographical information system. Confounders such as education, use of home pesticide, residency in a rural area and occupational exposure to chemicals were taken into account. Separate analyses were performed for gliomas, meningiomas and acoustic neurinomas. A nonsignificant increase in risk was found for occupational exposure to electromagnetic fields [odds ratio (OR = 1.52, 0.92-2.51)]. This increase became significant for meningiomas, especially when considering ELF separately [OR = 3.02; 95 percent confidence interval (95% CI) =1.10-8.25]. The risk of meningioma was also higher in subjects living in the vicinity of power lines (<100 m), even if not significant (OR = 2.99, 95% CI 0.86-10.40). These data suggest that occupational or residential exposure to ELF may play a role in the occurrence of meningioma.
    International Journal of Cancer 09/2011; 129(6):1477-84. · 6.20 Impact Factor
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    ABSTRACT: Gliomas are the most common malignant primary brain tumors in adults. The median survival never exceeds 12 months, owing to inherent resistance to both radio and chemotherapies. Epidermal Growth Factor Receptor (EGFR) is amplified, overexpressed, and/or mutated in glioblastomas (GBM), making it a rational for therapy. Erlotinib, an EGFR kinase inhibitor is strongly associated with clinical response in several cancers. Inhibition of cell proliferation and induction of apoptosis by erlotinib were investigated in U87-MG and DBTRG-05MG, two human glioblastoma cell lines. The expression of several apoptosis-related proteins was investigated in these cell lines and in tumoral tissue from glioblastomas. Both cell lines expressed wild-type EGFR but were deficient for PTEN. Erlotinib induced a marked accumulation of the BIM protein, but the activation of caspase-3 machinery was missing, regardless of the decrease in XIAP. Moreover, in U87-MG, erlotinib promoted accumulation of αB-crystallin a small heat shock protein capable to impair caspase activation. DBTRG-05MG was found deficient for procaspase 3 and constitutively overexpressed αB-crystallin. Similarly, deficiencies in PTEN and procaspase 3 were constantly found in samples from glioblastoma samples, while αB-crystallin expression was inconsistent. In cell lines, high concentrations of erlotinib induced cell death through a caspase independent process and an autophagic process was evidenced in U87-MG. Inhibition of autophagy induced a marked increase in the death-inducing activity of erlotinib. These results confirm that glioblastoma cell lines exhibit several anti-apoptotic mechanisms, and underline that EGFR targeted therapy must be associated to other inhibitors to achieve an antitumoral effect.
    Cancer biology & therapy 06/2011; 11(12):1017-27. · 3.29 Impact Factor
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    International Journal of Cancer 03/2011; · 6.20 Impact Factor
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    ABSTRACT: To date, the etiology of primary tumors of the central nervous system (mainly gliomas and meningiomas) is poorly understood. The role of sex hormones has been suggested, based on clinical, experimental, biological, and epidemiological data. To review the epidemiological studies on the relation between hormonal factors and the occurrence of glioma and meningioma, in order to identify new research developments. Articles published until September 2010 were selected by considering exogenous and endogenous exposures and specific brain tumors. Standardized information was collected from 20 articles: 15 concerning gliomas and 13 meningiomas. An increased glioma risk was observed with later menarche and menopause, while a reduced glioma risk was observed with hormone replacement therapy (HRT) and oral contraceptive use, despite duration of use had no effect on risk. Meningioma risk increased after menopause and with HRT use. No clear association was found with pregnancy and breastfeeding. Results are globally concordant with the biologic hypothesis assuming that female sex hormones are protective against glioma and may increase the risk of meningioma. However, new epidemiological studies should be conducted in order to confirm these associations and to refine the role of hormonal factors in brain etiology.
    Cancer Causes and Control 02/2011; 22(5):697-714. · 3.20 Impact Factor
  • Cancer Radiotherapie - CANCER RADIOTHER. 01/2011; 15(6):614-615.
  • I Baldi, A Huchet, L Bauchet, H Loiseau
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    ABSTRACT: An increasing incidence of glioblastoma has been observed over the last 30 years. Improvements in diagnostic tools such as CT scans and MRI, changes observed in histological classifications, and adjustments in neurosurgical practices have contributed substantially to this increase. Moreover, the aging of the population and the increasing occurrence of glioblastoma beyond 60 years of age are additional explanations. In Gironde (France), where a specialized registry has been established, the annual incidence of glioblastoma is 4.96/100,000. Wide geographic variations are observed, possibly linked to ethnicity. However, the role of intrinsic and/or extrinsic factors cannot be ruled out. Comparing data between registries is difficult and requires taking into account periods of recruitment and diagnostic tools. Ethnicity, age, sex, hereditary syndromes, some constitutive polymorphisms, and brain irradiation are the established risk factors Allergies or asthma, certain viral infections, autoimmune diseases, nonsteroidal anti-inflammatory drug intake, substitutive hormonal therapy, and dietary antioxidant intake are the established protective factors. Many studies on electromagnetic fields - in particular cellular phones - pesticides, solvents, and other factors have been published. Until now, the results are discordant or are not confirmed because of methodological limitations. Future studies combining constitutive polymorphisms and exposure assessment are likely to provide consistent and important data that will improve our knowledge in the epidemiology of glioblastoma.
    Neurochirurgie 12/2010; 56(6):433-40. · 0.32 Impact Factor
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    ABSTRACT: A third case of corpus callosum hemangioblastoma (HB) is presented. With no preoperative embolization, surgery was uneventful and the postoperative course was excellent. Based on the literature, we attempted to clarify the histogenesis of HB and to explain why they are exceptional in the supratentorial region in contrast to the posterior cranial fossa. The VHL gene is expressed particularly in Purkinje cells of the cerebellum, but this expression is also possible in supratentorial structures. Its mutation leads to developmental arrest of angioblasts that become potentially neoplastic cells. These CD133-positive pluripotent neoplastic angioblasts, similar to stem cells, may be immature HB in the brain. They also express VEGF, coexpress Epo/EpoR, and are capable of differentiation into primitive vascular structures. This coexpression may not only mediate developmental stagnation, but may also induce HB proliferation. Therefore, HB tumorigenesis may be initiated during embryogenesis and may originate from angiomesenchyma because of the expression of three cell types (stromal cells, pericytes, and endothelial cells) in vimentin. Their capacity for proliferation and differentiation in HB depends on the microenvironment.
    Neurochirurgie 10/2010; 56(5):382-5. · 0.32 Impact Factor
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    ABSTRACT: Malignant gliomas are very aggressive tumors, highly angiogenic and invading heterogeneously the surrounding brain parenchyma, making their resection very difficult. To overcome the limits of current diagnostic imaging techniques used for gliomas, we proposed using FTIR imaging, with a spatial resolution from 6 to 10 μm, to provide molecular information for their histological examination, based on discrimination between normal and tumor vasculature. Differentiation between normal and tumor blood vessel spectra by hierarchical cluster analysis was performed on tissue sections obtained from xenografted brain tumors of Rag-gamma mice 28 days after intracranial implantation of glioma cells, as well as for human brain tumors obtained in clinics. Classical pathological examination and immunohistochemistry were performed in parallel to the FTIR spectral imaging of brain tissues. First on the animal model, classification of FTIR spectra of blood vessels could be performed using spectral intervals based on fatty acyl (3050-2800 cm(-1)) and carbohydrate (1180-950 cm(-1)) absorptions, with the formation of two clusters corresponding to healthy and tumor parts of the tissue sections. Further data treatments on these two spectral intervals provided interpretable information about the molecular contents involved in the differentiation between normal and tumor blood vessels, the latter presenting a higher level of fatty acyl chain unsaturation and an unexpected loss of absorption from osidic residues. This classification method was further successfully tested on human glioma tissue sections. These findings demonstrate that FTIR imaging could highlight discriminant molecular markers to distinguish between normal and tumor vasculature, and help to delimitate areas of corresponding tissue.
    The Analyst 10/2010; 135(12):3052-9. · 4.23 Impact Factor
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    ABSTRACT: Carmustine-releasing wafers (Gliadel have been available and reimbursed in France since 2005. A retrospective multicenter study was conducted in 26 French Departments of Neurosurgery to analyze practices of French neurosurgeons using Gliadel, compare the adverse effects and survival with those of previous phase III trials, and assess survival in patients with newly diagnosed malignant gliomas (MG) receiving Gliadel plus radiochemotherapy with temozolomide (TMZ). A total of 163 patients who received Gliadel for MG were included in this study: 83 (51%) with newly diagnosed MG and 80 (49%) with recurrent MG. In the newly diagnosed group, 51.8% of patients received radiochemotherapy with TMZ. Adverse events (AEs) emerged in 44.6% of the population, including 6% with septic abscess. The AE rate was not statistically correlated with adjuvant use of TMZ. For the newly diagnosed group, median survival was 17 months. Total or subtotal resection appeared to have a great impact on survival (P = 0.016), as did treatment with adjuvant radiotherapy (P = 0.004). For the group with recurrent MG, median survival was 7 months. Total or subtotal resection excision appeared to have a great impact on survival (P = 0.002), as did preoperative Karnowsky Scale (PO-KPS) (P = 0.012). Survival rates for newly diagnosed patients were better than those reported in previous phase III trials. The combination of Gliadel and radiochemotherapy with TMZ was well tolerated and appeared to increase survival without increasing AEs.
    Annals of Surgical Oncology 07/2010; 17(7):1740-6. · 4.12 Impact Factor
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    ABSTRACT: Plexopathies and peripheral neuropathies appear progressively and with several years delay after radiotherapy. These lesions are observed principally after three clinical situations: supraclavicular and axillar irradiations for breast cancer, pelvic irradiations for various pathologies and limb irradiations for soft tissue sarcomas. Peripheral nerves and plexus (brachial and lumbosacral) are described as serial structures and are supposed to receive less than a given maximum dose linked to the occurrence of late injury. Literature data, mostly ancient, define the maximum tolerable dose to a threshold of 60 Gy and highlight also a great influence of fractionation and high fraction doses. For peripheral nerves, most frequent late effects are pain with significant differences of occurrence between 50 and 60 Gy. At last, associated pathologies (diabetes, vascular pathology, neuropathy...) and associated treatments have probably to be taken into account as additional factors, which may increase the risk of these late radiation complications.
    Cancer/Radiothérapie 07/2010; 14(4-5):405-10. · 1.48 Impact Factor

Publication Stats

1k Citations
264.84 Total Impact Points

Institutions

  • 2004–2011
    • Université Victor Segalen Bordeaux 2
      • Institut de Santé Publique d'Epidémiologie et de Développement (ISPED)
      Bordeaux, Aquitaine, France
  • 2001–2010
    • Institut Bergonié
      Burdeos, Aquitaine, France
  • 1986–2010
    • University of Bordeaux
      Burdeos, Aquitaine, France
  • 1989–2009
    • Centre Hospitalier Universitaire de Bordeaux
      Burdeos, Aquitaine, France
  • 2000
    • Institut Universitaire de France
      Lutetia Parisorum, Île-de-France, France
  • 1988
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
    • University of Pavia
      Ticinum, Lombardy, Italy