Nusinersen treatment in adults with severe spinal muscular atrophy: A real-life retrospective observational cohort study.

BACKGROUND AND OBJECTIVES: Spinal muscular atrophy (SMA) is a progressive neurodegenerative disease due to homozygous loss-of-function of the survival motor neuron gene SMN1 with absence of the functional SMN protein. Nusinersen, a costly intrathecally administered drug approved in 2017 in Europe, induces alternative splicing of the SMN2 gene, which then produces functional SMN protein, whose amount generally increases with the number of SMN2 gene copies. METHODS: We retrospectively collected data from consecutive wheelchair-bound adults with SMA managed at a single center in 2018-2020. The following were collected at each injection, on days 1, 14, 28, 63, 183, and 303: 32-item Motor Function Measurement (MFM) total score and D2 and D3 subscores; the Canadian Occupational Performance Measure (COPM) performance and satisfaction scores; and lung function tests. The patients were divided into two groups based on whether their MFM total score was

Gene transfer of two entry inhibitors protects CD4⁺ T cell from HIV-1 infection in humanized mice.

Targeting viral entry is the most likely gene therapy strategy to succeed in protecting the immune system from pathogenic HIV-1 infection. Here, we evaluated the efficacy of a gene transfer lentiviral vector expressing a combination of viral entry inhibitors, the C46 peptide (an inhibitor of viral fusion) and the P2-CCL5 intrakine (a modulator of CCR5 expression), to prevent CD4⁺ T-cell infection in vivo. For this, we used two different models of HIV-1-infected mice, one in which ex vivo genetically modified human T cells were grafted into immunodeficient NOD.SCID.γc⁻/⁻mice before infection and one in which genetically modified T cells were derived from CD34⁺ hematopoietic progenitors grafted few days after birth. Expression of the transgenes conferred a major selective advantage to genetically modified CD4⁺ T cells, the frequency of which could increase from 10 to 90% in the blood following HIV-1 infection. Moreover, these cells resisted HIV-1-induced depletion, contrary to non-modified cells that were depleted in the same mice. Finally, we report lower normalized viral loads in mice having received genetically modified progenitors. Altogether, our study documents that targeting viral entry in vivo is a promising avenue for the future of HIV-1 gene therapy in humans.

Mutations in SEPN1 cause congenital muscular dystrophy with spinal rigidity and restrictive respiratory syndrome.

One form of congenital muscular dystrophy, rigid spine syndrome (MIM 602771), is a rare neuromuscular disorder characterized by early rigidity of the spine and respiratory insufficiency. A locus on 1p35-36 (RSMD1) was recently found to segregate with rigid spine muscular dystrophy 1 (ref. 1). Here we refine the locus and find evidence of linkage disequilibrium associated with SEPN1, which encodes the recently described selenoprotein N (ref. 2). Our identification and analysis of mutations in SEPN1 is the first description of a selenoprotein implicated in a human disease.

Anaphylaxis to pork kidney is related to IgE antibodies specific for galactose-alpha-1,3-galactose.

BACKGROUND: Carbohydrate-specific IgE antibodies present on nonprimate mammalian proteins were incriminated recently in delayed meat anaphylaxis. The aim of this study was to explore whether anaphylaxis to mammalian kidney is also associated with galactose-α-1,3-galactose (αGal)-specific IgE. METHODS: Fourteen patients with anaphylaxis to pork or beef kidney underwent prick tests to meat and kidney. Some patients also underwent skin tests to Erbitux(®) (cetuximab). IgE antibodies to αGal, swine urine proteins, beef and pork meat, serum albumin proteins, cat, and rFel d 1 were measured by ImmunoCAP(®). The αGal levels were estimated in meats and kidney by ELISA inhibition assay. Cross-reactivity between αGal and pork kidney was studied with the ImmunoCAP(®) inhibition assay. RESULTS: Among the 14 patients, 12 presented with anaphylactic shock. Reactions occurred within 2 h from exposure in 67% of patients. Associated risk factors were observed in 10 cases, and alcohol was the main cofactor. Three patients underwent an oral challenge to pork kidney, and anaphylaxis occurred after ingestion of small quantities (1-2 g). Prick tests to kidney were positive in 54% of patients. All tested patients showed positive skin tests to Erbitux(®). All patients tested positive for IgE to αGal, with levels ranging from 0.4 to 294 kU/l. IgE binding to αGal was inhibited by raw pork kidney extract (mean, 77%; range, 55-87%), which showed a high amount of αGal determinants. CONCLUSIONS: Pork or beef kidney anaphylaxis is related to αGal IgE. Its peculiar severity could be due to an elevated content of αGal epitopes in kidney.

Selection efficiency and effective population size in Drosophila species.

A corollary of the nearly neutral theory of molecular evolution is that the efficiency of natural selection depends on effective population size. In this study, we evaluated the differences in levels of synonymous polymorphism among Drosophila species and showed that these differences can be explained by differences in effective population size. The differences can have implications for the molecular evolution of the Drosophila species, as is suggested by our results showing that the levels of codon bias and the proportion of adaptive substitutions are both higher in species with higher levels of synonymous polymorphism. Moreover, species with lower synonymous polymorphism have higher levels of nonsynonymous polymorphism and larger content of repetitive sequences in their genomes, suggesting a diminished efficiency of selection in species with smaller effective population size.

The efficiency of purifying selection in Mammals vs. Drosophila for metabolic genes.

The nearly neutral theory of molecular evolution states that the efficiency of natural selection depends on the effective population size. By using a wide range of multispecies data on nucleotide polymorphism, we have tried to ascertain whether there are any differences in the level of selective constraints of metabolic process genes between Mammals and Drosophila species. The results are consistent with a higher selective constraint in Drosophila than in Mammals, according to the expected under the nearly neutral model: purifying selection seems to be more efficient in species with a larger effective population size.

The economic costs of severe anaphylaxis in France: an inquiry carried out by the Allergy Vigilance Network.

BACKGROUND: The prevalence of severe anaphylaxis, between 1 and 3 per 10,000, has increased sharply over recent years, with a rate of lethality of 1%. The economic burden is unknown. OBJECTIVE: The aim of this study was to estimate the economic costs of anaphylaxis, including direct costs of treatment, hospitalization, preventive and long-care measures, and the indirect cost: absenteeism. METHODS: Analysis of 402 patients of anaphylaxis declared by 384 allergists was reported to the Allergy Vigilance Network. The global cost was estimated from the national data of hospital admissions: ICD-10 coding available for 2003, 2004 and 2005. RESULTS: Three work/classroom days were lost per patient. Diagnosis required oral challenge with hospitalization in 18% of cases. The estimated mean total cost was 1895 euros for food- and drug-related anaphylaxis (5610 euros for the most severe), and 4053 euros for Hymenoptera anaphylaxis. National statistics recorded 2575 patients in 2005; 22% more than in 2003. The estimated annual cost was 4,789,500 euros. The possible reasons for this being an under-estimate include: data coming only from hospitalized patients, poor identification by medical teams unfamiliar with ICD-10 codes, peri-operative anaphylaxis being insufficiently declared, rush-immunotherapy and maintenance treatments for Hymenoptera anaphylaxis. Similarly, the extra cost of cow milk substitutes, as well as insurance costs where deaths are followed by litigation were not taken into account. CONCLUSIONS: The mean cost of anaphylaxis was 1895-5610 euros in nonfatal patients. The prevalence was under-estimated because of many biases, leading to under-estimation of the national cost. Further studies would be necessary to evaluate the value of preventive strategies.

Oral desensitization in children with milk and egg allergies obtains recovery in a significant proportion of cases. A randomized study in 60 children with cow's milk allergy and 90 children with egg allergy.

BACKGROUND: Food allergy is treated by avoidance diets in order to prevent anaphylactic reactions and to cure chronic associated symptoms. However, the natural history is left unchanged. OBJECTIVE: To search for a beneficial effect of an oral desensitization protocol to allergenic foods in IgE-dependent milk or egg allergies in children. METHODS: 60 children with documented cow's milk allergy (13 months-6.5 years), and 90 children with egg allergy (12 months-8 years), were consecutively included after 6-12 months of avoidance diet, if a SBPCFC to 60 ml milk (60 ml) or to 965 mg of raw egg white was negative. They were randomized for uninterrupted avoidance or oral desensitization (group A or OD). Six months later, a new SBPCFC was performed with, up to 200 ml of milk or 7g of raw egg white. Prick tests and specific IgE levels were carried out simultaneously. RESULTS: Data were obtained for 57 children with CMA (30 A and 27 OD), and 84 children with EA (35 A and 49 OD). The two groups (AD or OD group) were similar with regard to means of ages, the size of PT wheals and the level of IgEs at baseline. MILK ALLERGY: A SBPCFC to milk was positive in 11.1% of those following OD vs. 40% after A (p < .025). The size of PT decreased after OD and increased after A (-3.4 mm vs. +0.84 mm; p < .002). EGG ALLERGY: The SBPCFC to egg was positive in 30.6% after OD vs. 48.6% after A (p < .1). After 6 months, in the OD group, the mean size of the PT and the level of specific IgE were significantly reduced compared to the A group. In the A group, the threshold of reactivity was often lower, or more serious symptoms were observed. CONCLUSION: Oral desensitization helps the egg and milk allergic children to overcome their allergies. Since the avoidance of these foods is likely to increase sensitization as well as to lower the threshold of reactivity, an active treatment is required. Further attempts to standardize the procedures of oral desensitization are expected.

[Technique of complex mammary irradiation: Mono-isocentric 3D conformational radiotherapy and helical tomotherapy]. / Techniques d'irradiation mammaire complexe : radiothérapie conformationelle tridimensionnelle mono-isocentrique et nomothérapie hélicoïdale.

PURPOSE: To evaluate the dosimetric contribution of helical tomotherapy for breast cancers compared with conformal radiotherapy in mono-isocentric technique. PATIENTS AND METHOD: For 23 patients, the dosimetric results in mono-isocentric 3D conformational radiotherapy did not satisfy the constraints either of target volumes nor organs at risk. A prospective dosimetric comparison between mono-isocentric 3D conformational radiotherapy and helical tomotherapy was therefore carried out. RESULTS: The use of helical tomotherapy showed a benefit in these 23 patients, with either an improvement in the conformity index or homogeneity, but with an increase in low doses. Of the 23 patients, two had pectus excavatum, five had past thoracic irradiation and two required bilateral irradiation. The other 14 patients had a combination of morphology and/or indication of lymph node irradiation. For these patients, helical tomotherapy was therefore preferred to mono-isocentric 3D conformational radiotherapy. CONCLUSIONS: Tomotherapy appears to provide better homogeneity and tumour coverage. This technique of irradiation may be justified in the case of morphological situations such as pectus exavatum and in complex clinical situations. In other cases, conformal radiotherapy in mono-isocentric technique remains to be favoured.

Technical knockout, a Drosophila model of mitochondrial deafness.

Mutations in mtDNA-encoded components of the mitochondrial translational apparatus are associated with diverse pathological states in humans, notably sensorineural deafness. To develop animal models of such disorders, we have manipulated the nuclear gene for mitochondrial ribosomal protein S12 in Drosophila (technical knockout, tko). The prototypic mutant tko(25t) exhibits developmental delay, bang sensitivity, impaired male courtship, and defective response to sound. On the basis of a transgenic reversion test, these phenotypes are attributable to a single substitution (L85H) at a conserved residue of the tko protein. The mutant is hypersensitive to doxycyclin, an antibiotic that selectively inhibits mitochondrial protein synthesis, and mutant larvae have greatly diminished activities of mitochondrial redox enzymes and decreased levels of mitochondrial small-subunit rRNA. A second mutation in the tko gene, Q116K, which is predicted to impair the accuracy of mitochondrial translation, results in the completely different phenotype of recessive female sterility, based on three independent transgenic insertions. We infer that the tko(25t) mutant provides a model of mitochondrial hearing impairment resulting from a quantitative deficiency of mitochondrial translational capacity.

Mutation analysis in 16 patients with mtDNA depletion.

Sixteen unrelated Southern European patients with the mitochondrial depletion syndrome (MDS) were analyzed for mutations in the TK2 and DGUOK genes. Three novel mutations were identified in TK2 (R183G, R254X, and 142insG). When we analyzed additional genes involved in the dNTPs pool, such as SLC25A19 (DNC) and NT5M (d-NT2), we did not detect mutations. The current study suggest that scanning the TK2, DGUOK, SLC25A19, and NT5M genes is likely to help about 10% of MDS families in terms of genetic counseling. Also, our findings indicate that genotype-phenotype correlations are not straightforward in MDS.

Investigation of stretching behaviour induced by the selective 5-HT6 receptor antagonist, Ro 04-6790, in rats.

1. The present study examined the effects of the selective 5-HT6 receptor antagonist 4-amino-N-(2, 6 bis-methylamino-pyrimidin-4-yl)-benzene sulphonamide (Ro 04-6790) on locomotor activity and unconditioned behaviour in male Sprague Dawley rats (230-300 g). 2. In non-quantified behavioural observations, animals treated with Ro 04-6790 (3, 10 or 30 mg kg(-1), i.p) showed no overt behavioural signs except a dose-dependent reduction in locomotor activity and a behavioural syndrome of stretching, yawning and chewing. The latter behaviour was most pronounced between 30 and 90 min following the administration of Ro 04-6790. 3. Detailed analysis of the stretching and yawning behaviour showed that Ro 04-6790 (3, 10 or 30 mg kg(-1), i.p.) dose-dependently induced stretching. The number of stretches observed following treatment with either Ro 04-6790 (10 mg kg(-1) i.p.) or Ro-04-6790 (30 mg kg(-1), i.p.) was significantly greater than that observed in saline-treated rats. The yawning behaviour, however, was not dose-dependent nor was the number of yawns in any of the drug treated groups significantly greater than in those treated with saline. 4. Pretreatment (30 min) with the non-selective muscarinic antagonists scopolamine (0.1, 0.3 or 1 mg kg(-1), i.p.) and atropine (0.3, 1 or 3 mg kg(-1), s.c.) but not methylatropine (1, 3 or 10 mg kg(-1), s.c) significantly inhibited stretching induced by Ro 04-6790 (30 mg kg(-1), i.p.). 5. The dopamine D2-like receptor antagonist, haloperidol (0.03, 0.1 or 0.3 mg kg(-1), s.c.) given at the same time as Ro 04-6790 (30 mg kg(-1), i.p.) had no effect on the stretching induced by the 5-HT6 antagonist. 6. These data suggest that systemic injection of the 5-HT6 antagonist, Ro 04-6790, produces a stretching behaviour that appears to be mediated by an increase in cholinergic neurotransmission in the CNS and which could be a useful functional correlate for 5-HT6 receptor blockade. There is no evidence for dopamine D2-like receptor involvement in this behaviour.

The effects of tamoxifen on endometrial insulin-like growth factor-1 expression.

OBJECTIVE: To determine whether modulation of insulin-like growth factor-1 and insulin-like growth factor-binding protein-1 expression underlies the uterotropic effects associated with tamoxifen therapy in postmenopausal breast cancer patients. METHODS: Using immunohistochemical techniques, we analyzed 37 endometrial specimens from biopsies (n = 18) or hysterectomies (n = 19) for Ki-67, insulin-like growth factor-1, and insulin-like growth factor-binding protein-1 expression. Specifically, five secretory- and three proliferative-phase endometrial specimens were used as controls; 20 specimens (including two endometrial adenocarcinomas) were analyzed from postmenopausal breast cancer patients treated with tamoxifen (20 mg/day) for at least 6 months; and nine endometrial adenocarcinoma specimens from patients not treated with tamoxifen were studied. Intensity of immunostaining was quantified using digitized imaging techniques. RESULTS: Insulin-like growth factor-1 and insulin-like growth factor-1-binding protein-1 were found to be expressed in normal and neoplastic endometrium of all patients, regardless of tamoxifen treatment. However, insulin-like growth factor-1 expression varied cyclically in histologically normal endometrium, was reduced in undifferentiated endometrial tumors, and was upregulated in tamoxifen-treated specimens. Insulin-like growth factor-binding protein-1 immunostaining did not vary during the menstrual cycle, but it was reduced significantly in benign tamoxifen-exposed tissue and endometrial adenocarcinomas, regardless of degree of differentiation or tamoxifen exposure. No correlation was found between the expression of insulin-like growth factor-1 and insulin-like growth factor-binding protein-1 and the proliferative indices of the tissues examined. CONCLUSION: The expression of insulin-like growth factor-1 and insulin-like growth factor-binding protein-1 in the uterus supports an autocrine and/or paracrine role for these proteins in endometrial physiology. Although further studies are needed, our investigation suggests that altered expression of insulin-like growth factor-1 and insulin-like growth factor-binding protein-1 may contribute to the uterotropic effects of tamoxifen.

Simultaneous occurrence of kaposi's sarcoma and chronic myelogenous leukemia.

We report here a 75-year-old man from South France who developed Kaposi's Sarcoma (KS) 5 months after diagnosis of Philadelphia-chromosome positive chronic myelogenous leukemia (CML). He was found positive for HHV-8 by PCR, negative for both HIV 1 and HIV 2 by serology, and had a normal CD4/CD8 ratio. Favourable evolution of both CML and KS has been obtained with vinblastine and interferon alpha treatment. The patient is currently alive in complete remission of SK and major cytogenetic remission of CML with a 48 month follow-up. Since no immune deficiency could be documented in the patient, this rare observation suggests that CML may have triggered the onset of SK through cytokine release.

Pharmacologic evaluation of the discriminative stimulus of metachlorophenylpiperazine.

A pharmacologic analysis of the discriminative stimulus of metachlorophenylpiperazine (mCPP) is reported. mCPP and m-trifluoromethylphenylpiperazine generalised, whereas 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole, 6-chloro-2-(1-piperazinyl)-pyrazine, and mesulergine partially generalised to the mCPP discriminative cue. However, although mianserin, methiothepin, ritanserin, mesulergine and N-(1-methyl-5'-indolyl)-N'-(3-pyridyl)urea hydrochloride (SB 200646) all antagonised the effect of 5-hydroxytryptamine (5-HT) on IP3 formation in the rat choroid plexus, they failed to antagonise the mCPP response in the drug discrimination studies. The 5-HT3 receptor antagonist MDL 72222 neither generalised nor antagonised the mCPP cue. These data suggest that neither the 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT5, 5-HT6, nor 5-HT7 receptors are involved. The response does appear to be mediated by a postsynaptic 5-HT receptor, however, because fenfluramine generalised to the cue. Haloperidol generalises, and amphetamine partially antagonises the mCPP discriminative cue and low doses of apomorphine partially generalises to the mCPP cue, which suggests that a decrease in dopamine neurotransmission may also be involved.

In vitro cytotoxic effects of enzymatically induced oxygen radicals in human fibroblasts: Experimental procedures and protection by radical scavengers.

Introduction of hypoxanthine and xanthine oxidase into human fibroblast cultures induces a dose-dependent cytotoxicity as a result of free-radical formation. The influence of medium, cell density and the power of recovery after free-radical attack were investigated. It appears that toxicity is higher in physiological Dulbecco phosphate buffer or Hanks' balanced salt solution than in modified Eagle medium, is inversely proportional to cell density and that damage is most often irreversible. Using this model, we studied the protective effects of a hydrosoluble flavonoid, silybin, and of a well known antioxidant, BHT (butylated hydroxytoluene). These molecules were administered before and during free-radical attack. With BHT significant protection was observed when it was added before free-radical attack (24% protection at a concentration of 10(-4)m) and before and during exposure (20% protection at a concentration of 10(-5)m). When silybin is applied during radical attack maximal activity is recorded at a concentration of 8 x 10(-4)m (45%), but the most interesting results are observed when 1 x 10(-4) and 8 x 10(-4)m are used, respectively, before and during radical exposure (63% of activity).

Cariogenic feeding habits and fluoride supplementation during infancy and early childhood.

Parents of 240 children between nine months and three years of age were interviewed using a questionnaire in order to determine cariogenic feeding habits and fluoride supplementation. Mean age of weaning from the bottle was 14.6 months. After 18 months of age, children from minority ethnic groups were more frequently bottle-fed than French-Canadian children (p < .005). Giving a bottle in bed (34.6% of cases) was more often practised by less educated mothers (p = .007) or by minority ethnic groups (p = .002), and was seen as a cariogenic factor by 31% of parents. Fluoride was given in half of cases, mainly by highly educated mothers (p = .001) and was mentioned as a preventive measure by 27% of parents. Physicians should be aware of poor parental knowledge and practices of preventive dentistry, and must discuss cariogenic feeding habits and fluoride supplementation during well-baby visits.

[Hodgkin's disease in patients infected with the human immunodeficiency virus]. / La maladie de Hodgkin chez les patients atteints du virus de l'immunodéficience humaine.

INTRODUCTION: Hodgkin's disease in patients infected by the human immunodeficiency virus (HIV) is still not part of the definition of acquired immune deficiency syndrome. Nonetheless, this entity has a particular presentation when compared to the disease occurring in immune-competent patients. CURRENT KNOWLEDGE AND KEY POINTS: Increased frequency (> 75%) of advanced anatomical stages and extranodular localizations (Ann Arbor system stages III and IV) has been outlined in HIV-infected patients. Mediastinal involvement is more unusual in immunocompromised than in immune-competent patients. The presence of B symptoms (fever, weight loss, nocturnal sweats) is very frequent. Finally, the predominance of mixed cellularity (type 3) characterizes Hodgkin's disease in immunocompromised patients. Due to either the immunodeficiency, antiretroviral treatments, poor hematological tolerance in response to chemotherapy, or to advanced anatomical stages, disease management may be hampered. Current therapeutical approaches often obtain complete remission; however, some deaths are still related to the disease progression to acquired immune deficiency syndrome. FUTURE PROSPECTS AND PROJECTS: From these observations, Hodgkin's disease management in HIV-infected patients relies on therapeutical approaches similar to those used for non infected patients, with some specific recommendations. Chemotherapy should be conducted in the shortest time in order to minimize chemotherapy-induced immunosuppression. Simultaneous use of antiretroviral treatment and reinforced opportunistic infection prophylaxis are of pivotal importance. Finally, the use of hematopoietic growth factors appears to be safe regarding viral replication, but still requires further evaluation.

[Potential indications for helical tomotherapy in breast cancers]. / Indications potentielles de la tomothérapie hélicoïdale dans les cancers du sein.

PURPOSE: To evaluate the dosimetric gain obtained in either the planning target volume or organs at risk coverage by the use of intensity-modulated radiation therapy in some particular postoperative breast cancers. PATIENTS AND METHOD: Prospective dosimetric comparison between monoisocentric conformal radiotherapy and intensity-modulated radiation therapy in nine patient files. RESULTS: Using intensity-modulated radiation therapy was shown to improve in each case, at least one conformity, homogeneity, and coverage index either for planning target volumes or for organs at risk. Intensity-modulated radiation therapy was therefore always chosen rather than conformal monoisocentric radiotherapy. CONCLUSIONS: Indications to retain intensity-modulated radiation therapy would consist of bilateral lesions, pectus excavatum, past thoracic irradiation (Hodgkin's disease) and complex volumes in obese or overweight patients.

[Conventional 2D and monoisocentric 3D techniques in breast and lymphatic irradiation: a dosimetric comparison]. / Techniques classique bidimensionnelle et mono-isocentrique tridimensionnelle dans l'irradiation du sein et des aires ganglionnaires : comparaison dosimétrique.

PURPOSE: The activity of our radiation oncology department mainly relies on breast pathology. Since July 2009, all the irradiations delivered simultaneously to the breast (CTV1), the surgical bed (CTV2), the internal mammary chain and the supra- and infraclavicular areas have been carried out using a mono-isocentric technique. This study aimed to compare dosimetric results between conventional 2D and mono-isocentric 3D techniques with or without optimization. PATIENTS AND METHODS: From January to August 2009, 20 patients with breast cancer in whom irradiation of the CTV1, CTV2, internal mammary chain and supra- and infraclavicular areas was retained, were included in a specific cohort. In each case, we have compared dosimetric results obtained with the conventional technique and with a mono-isocentric 3D technique, either with manual field in the field segmentation or with automatic segmentation (Oncentra Masterplan(®) from Nucletron(®), Optimizer(®) solution). Selected criteria were as follows: V95, V107 and mean dose (Dmean) to the target volumes, V20 and V30 to the ipsilateral lung, V35 and mean dose to the heart and maximal dose (Dmax) to the spinal cord. RESULTS: Supra- and infraclavicular areas irradiation was significantly better using the mono-isocentric 3D technique (V95 %: 89.7 % vs. 77.1 %; P=0.001) as well as dose homogeneity (Dmean: 46.3 Gy vs. 45.1 Gy; P=0.008). No statistical difference was observed for the other target volumes. Heart and spinal cord protection were better with the mono-isocentric 3D technique (respectively Dmean: 8.4Gy vs. 11.1 Gy; P<0.0001 and Dmax: 29.2 Gy vs. 35.8 Gy; P=0.0003). CONCLUSION: Mono-isocentric irradiation of the breast and lymphatic areas is a modern technique that benefits from imaging and computer progresses while being simple to carry out using standard planning system and linear accelerators. Mono-isocentric 3D irradiation with manual segmentation of the breast and the nodal areas provides a target volume irradiation comparing with conventional technique 2D and a better protection of the heart and of the spinal cord.