Hormone-free protocols for the control of reproduction and artificial insemination in goats.

The dairy goat industry is of great economic importance to certain rural areas of the European Union (EU), especially the Mediterranean region. Its sustainability, however, is severely affected by the seasonality of goat reproduction, which leads to fluctuations in the availability of final products. Classical hormone treatments based on progestagens and eCG are the main tools employed in the effort to achieve fertility outside of the normal breeding season. They are also used to induce and synchronize oestrus and ovulation in artificial insemination programs. The food safety policy of the EU is becoming ever stricter with regard to the use of hormonal treatments for reproductive purposes, pushing livestock-raising towards ever cleaner and greener production systems. Recent advances in the use of natural methods able to generate endocrine signals that induce the ovulatory process have improved our capacity to foster reproduction in the non-breeding season. When used in a fashion appropriate for the latitude at which animals live, their breed, and the management system under which they are raised, environmental (photoperiod), nutritional and sociosexual (the male effect) signals offer alternatives to classic hormonal techniques. This affords the fragile and heterogeneous goat production sector with new opportunities. This article describes the most representative advances made in the use of the male effect as a natural method of inducing ovulation during seasonal anoestrus. Its association with other methods for optimizing responses and synchronizing induced ovulation is also discussed; such associations allow it to be used as an alternative to hormonal treatment in artificial insemination programs.

[Does Alzheimer's disease exist in all primates? Alzheimer pathology in non-human primates and its pathophysiological implications (II)]. / ¿Existe la enfermedad de Alzheimer en todos los primates? Patología Alzheimer en primates no humanos y sus implicaciones fisiopatológicas (II).

INTRODUCTION: In the ageing process there are some species of non-human primates which can show some of the defining characteristics of the Alzheimer's disease (AD) of man, both in neuropathological changes and cognitive-behavioural symptoms. The study of these species is of prime importance to understand AD and develop therapies to combat this neurodegenerative disease. DEVELOPMENT: In this second part of the study, these AD features are discussed in the most important non-experimental AD models (Mouse Lemur -Microcebus murinus, Caribbean vervet -Chlorocebus aethiops, and the Rhesus and stump-tailed macaque -Macaca mulatta and M. arctoides) and experimental models (lesional, neurotoxic, pharmacological, immunological, etc.) non-human primates. In all these models cerebral amyloid neuropathology can occur in senility, although with different levels of incidence (100% in vervets;<30% in macaques). The differences between normal and pathological (Alzheimer's) senility in these species are difficult to establish due to the lack of cognitive-behavioural studies in the many groups analysed, as well as the controversy in the results of these studies when they were carried out. However, in some macaques, a correlation between a high degree of functional brain impairment and a large number of neuropathological changes ("possible AD") has been found. CONCLUSIONS: In some non-human primates, such as the macaque, the existence of a possible continuum between "normal" ageing process, "normal" ageing with no deep neuropathological and cognitive-behavioural changes, and "pathological ageing" (or "Alzheimer type ageing"), may be considered. In other cases, such as the Caribbean vervet, neuropathological changes are constant and quite marked, but its impact on cognition and behaviour does not seem to be very important. This does assume the possible existence in the human senile physiological regression of a stable phase without dementia even if neuropathological changes appeared.

[Does Alzheimer's disease exist in all primates? Alzheimer pathology in non-human primates and its pathophysiological implications (I)]. / ¿Existe la enfermedad de Alzheimer en todos los primates? Afección de Alzheimer en primates no humanos y sus implicaciones fisiopatológicas (I).

INTRODUCTION: Many publications consider that Alzheimer's disease (AD) is exclusive to the human species, and that no other animal species suffers from the disease. However, various studies have shown that some species can present with some of the defining characteristics of the human disease, including both neuropathological changes and cognitive-behavioural symptoms. DEVELOPMENT: In this work, the results published (PubMed) on senile brain changes in non-human primates of different degrees of evolution, are reviewed. The neuropathological changes associated with the accumulation of amyloid or highly phosphorylated tau protein are rare outside the primate order, but in all the sub-orders, families, genera and species of non-human primates that have been studied, some senile individuals have shown amyloid accumulation in the brain. In fact, in some species the presence of these deposits in senility is constant. Changes related to the accumulation of tau protein are always of very little significance, and have been detected only in some non-human primate species, both little evolved and highly evolved. In different species of non-human primates, some types of cognitive-behavioural changes are more common in some senile individuals when compared with both normal adult individuals and other senile individuals of the species. The importance of determining the longevity of the species in different habitats (natural habitats, new habitats, semi-captivity, captivity) is stressed in these studies. CONCLUSIONS: Morphological, histochemical and cognitive-behavioural features similar to those observed in elderly humans are present in senile non-human primates. Moreover, other characteristics seen in non-human primates could be indicative of a pathological «Alzheimer type¼ ageing.

[Role of hypofractionated radiotherapy in the treatment of prostate cancer: a review]. / Place de l'hypofractionnement dans la radiothérapie des cancers de la prostate : revue de la littérature.

BACKGROUND: Radiotherapy of prostate cancers, over the last few years, has been an alternative choice to radical prostatectomy in the case of localised cancers as well as being the preferred treatment in both advanced localised cancers and those of the elderly. A conventional course of prostate radiotherapy consisting of four to five sessions a week, lasts between 7 and 8 weeks plus about one week of preparation. MATERIALS AND METHODS: A systematic review of the scientific literature based on Pubmed, along with an exhaustive review of randomised studies presented at international congresses, have made it possible to analyse the numerous therapeutic regimens available other than the conventional normofractioned one (i.e. with doses per session ranging between 1.8 and 2.2 grays). RESULTS: Five randomised trials reported since 2005, plus several thousand patients treated by stereotaxic radiotherapy, have given rise to numerous scientific questions; these alternative hypofractioned courses (dose per fraction higher than 2.2 grays) have a potentially enhanced antitumoral efficacity along with the practical advantages of a shortened duration of radiotherapy. CONCLUSION: The aim of this analysis of the scientific literature on hypofractioning in prostate cancer radiotherapy is to gather all the scientific evidence we currently have at our disposal. Further mature results of future randomised trials will have to be examined before modifying current practice.

Spatial and temporal control of gene therapy using ionizing radiation.

Activation of transcription of the Egr-1 gene by X-rays is regulated by the promoter region of this gene. We linked the radiation-inducible promoter region of the Egr-1 gene to the gene encoding the radiosensitizing and tumoricidal cytokine, tumour necrosis factor-alpha (TNF-alpha) and used a replication-deficient adenovirus to deliver the Egr-TNF construct to human tumours growing in nude mice. Combined treatment with Ad5.Egr-TNF and 5,000 cGy (rad) resulted in increased intratumoral TNF-alpha production and increased tumour control compared with treatment with Ad5.Egr-TNF alone or with radiation alone. The increase in tumour control was achieved without an increase in normal tissue damage when compared to tissue injury from radiation alone. Control of gene transcription by ionizing radiation in vivo represents a novel method of spatial and temporal regulation of gene-based medical treatments.

Subjective voice analysis in patients with muscular tension dysphonia: comparison between clinician and patient evaluation.

BACKGROUND: This study evaluated the correlation between patient and clinician subjective voice analysis in a group of patients suffering from muscular tension dysphonia. This disease does not usually present with organic lesions, and voice analysis is crucial to evaluate it. METHODS: A retrospective study with 75 patients was performed. Correlation between grade, roughness, breathiness, asthenia and strain scale and voice handicap index-10 was analysed. Any possible influence of the type of muscular tension dysphonia on these two scales was studied. RESULTS: There are only a few studies that correlate voice handicap index-10 and the grade, roughness, breathiness, asthenia and strain scale; however, none of them are specific for patients suffering from muscular tension dysphonia. A moderate correlation (r = 0.56) was found. No influence of muscular tension dysphonia type on voice handicap index-10 score was found, but muscular tension dysphonia type 4 had worse grade, roughness, breathiness, asthenia and strain scale scores than other muscular tension dysphonia types. This could be explained if muscular tension dysphonia type 4 is considered to be the most severe form of this disease. CONCLUSION: The use of assessment scales based on the opinion of both the clinician and patient must be considered as complementary clinical tools in order to perform a complete assessment of dysphonia.

[TAFRO syndrome and cutaneous necrotizing vasculitis]. / Syndrome TAFRO et vascularite nécrosante cutanée : une association inédite.

INTRODUCTION: TAFRO syndrome is a systemic inflammatory syndrome in the spectrum of Castleman's disease, associating thrombocytopenia, anasarca, fever, renal failure and/or reticulin myelofibrosis and organomegaly. Its association with necrotizing cutaneous vasculitis has not yet been reported. CASE REPORT: A 69-year-old woman presented with weight loss, fever, anasarca, organomegaly, lymphadenopathy, anuria and extensive necrotic livedo occurring after acute diarrhea. Biology showed anemia, thrombocytopenia, renal failure, hypergammaglobulinemia, a circulating B-lymphocyte clone, hypoparathyroidism and autoimmune hypothyroidism. The skin biopsy showed small vessel vasculitis with fibrinoid necrosis. Methylprednisolone infusions associated with tocilizumab were ineffective and the patient became anuric. Rituximab and plasma exchanges associated to corticosteroids allowed remission for 2 months. Combination of rituximab, cyclophosphamide and dexamethasone resulted in a prolonged remission. CONCLUSION: We report here the first case of severe cutaneous necrotizing vasculitis in a patient suffering from TAFRO syndrome. The possible resistance to tocilizumab should be known.

Inhibition of tumor growth by elimination of granulocytes.

As observed for many types of cancers, heritable variants of ultraviolet light-induced tumors often grow more aggressively than the parental tumors. The aggressive growth of some variants is due to the loss of a T cell-recognized tumor-specific antigen; however, other variants retain such antigens. We have analyzed an antigen retention variant and found that the variant tumor cells grow at the same rate as the parental tumor cells in vitro, but grew more rapidly than the parental cells in the T cell-deficient host. The growth of the variant cells was stimulated in vitro by factors released from tumor-induced leukocytes and by several defined growth factors. In addition, the variant cancer cells actually attracted more leukocytes in vitro than the parental cells. Furthermore, elimination of granulocytes in vivo in nude mice by a specific antigranulocyte antibody inhibited the growth of the variant cancer, indicating that this tumor requires granulocytes for rapid growth.

Auditory discrimination training for tinnitus treatment: the effect of different paradigms.

Acoustic deprivation, i.e. hearing loss, is responsible for a cascade of processes resulting in reorganisation of the cortex. Tinnitus mechanisms are explained by synchronization of the neural spontaneous activity and might be related to cortical re-mapping. Auditory discrimination training (ADT) has demonstrated in both animals and humans to induce tonotopical changes in the auditory pathways through neural plasticity. We hypothesize that ADT could have some effect on tinnitus perception. The objective of this study is to compare the effect on tinnitus following two paradigms of ADT. Only patients from 20 to 60 years of age were recruited. Inclusion criteria were pure tone tinnitus of mild or moderate handicap according to the Tinnitus Handicap Inventory score (<56). ADT patients were randomized in two groups: SAME (ADT in the same frequency of tinnitus pitch, 20 patients) and NONSAME (ADT in the frequency one-octave below tinnitus pitch, 21 patients). Groups of pair of tones (70% standard tones ST, 30% deviant tones ST + 0.1-0.5 kHz) were randomly mixed for 20 min/day during 1 month. Patient had to mark when the two sounds of the pair were similar or different. Control group included 26 patients from the waiting list (WLG). Patients were also divided according to the trained frequency and the deepest hearing-impaired frequency. Outcome parameters were set up according to the answer to the question "is your tinnitus better, same, or worse with the treatment?" (RESP), the tinnitus handicap inventory (THI) and the visual analogue scale from 1 to 10 on tinnitus intensity (VAS). Tinnitus improved in 42.2% of the patients (RESP). VAS and THI scores were reduced but only THI differences were statistically significant (P = 0.003). ADT patients improved significantly compared with WLG in RESP and THI scores (P < 0.01). Training frequencies one-octave below the tinnitus pitch (NONSAME) decreased significantly THI scores compared with patients trained frequencies similar to tinnitus pitch (SAME, P = 0.035). RESP and VAS scores decreased more in NONSAME group though differences were not significant. We did not find any differences when comparing the group training the deepest hearing-impaired frequency and the group who trained other frequencies. Auditory discrimination training significantly improved tinnitus handicap compared to a waiting list group. Those patients who trained frequencies one octave below the tinnitus pitch had better outcome than those who performed the ADT with frequencies similar to the tinnitus pitch (P = 0.035).

Quadrivalent versus trivalent influenza vaccine: clinical outcomes in two influenza seasons, historical cohort study.

OBJECTIVES: The quadrivalent influenza vaccine (QIV) contains two influenza B antigens (one of each B lineage), while the trivalent vaccine (TIV) contains solely one. As a result, a mismatch between the circulating B lineage and the lineage in the TIV occurs frequently. We aimed to compare the frequency of clinically significant outcomes in a large cohort of vaccinees receiving either TIV or QIV. METHODS: Historical cohort study of all inactivated influenza vaccinees (aged 3 years and older) in a Health Maintenance Organization insuring 1.2 million individuals, over two influenza seasons in which both vaccines were provided non-selectively. Primary outcome was hospital admissions during the influenza season. Multivariate analysis was performed using logistic regression to adjust for relevant covariates. RESULTS: Our cohort included 150 518 and 168 296 vaccinees in the first (S1) and second season (S2), respectively. The two influenza seasons were characterized by high Influenza B activity. Of those vaccinated with QIV, 2074 of 49 726 (4.2%) and 6563 of 121 741 (5.4%) were hospitalized compared with 7378 of 100 792 (7.3%) and 3372 of 46 555 (7.2%) of those vaccinated with TIV (S1 and S2, respectively). After multivariate analysis adjusting for several covariates (gender, age, socioeconomic status, chronic morbidity, timing of vaccination), compared with TIV recipients, QIV vaccinees had lower odds for hospitalization (OR = 0.92, 95% CI 0.87-0.98 and OR = 0.89, 95% CI 0.85-0.93) or emergency department visit (OR = 0.91, 95% CI 0.87-0.95 and OR = 0.84, 95% CI 0.81-0.87) in S1 and S2, respectively (p < 0.001). Lower odds of mortality and influenza-like illness were also observed in S2 (OR = 0.61, 95% CI 0.50-0.75 and OR = 0.92, 95% CI 0.90-0.95, respectively). CONCLUSIONS: In seasons with relatively high influenza B activity, QIV appeared more protective than TIV in Israel.

[Indications and outlooks of radiohormonal therapy of high-risk prostate cancers]. / Indications et perspectives de l'hormonoradiothérapie des cancers de prostate à haut risque.

Prostate cancer is a sensitive adenocarcinoma, in more than 80% of cases, to chemical castration, due to its hormone dependence. Locally advanced and/or high-risk cancer is defined based on clinical stage, initial prostate specific antigen serum concentration value or high Gleason score. Hormone therapy associated with radiation therapy is the standard of management and improves local control, reduces the risk of distant metastasis and improves specific and overall survival. Duration of hormone therapy, dose level of radiation therapy alone or associated with brachytherapy are controversial data in the literature. The therapeutic choice, multidisciplinary, depends on the age and comorbidity of the patient, the prognostic criteria of the pathology and the urinary function of the patient. Current research focuses on optimizing local and distant control of these aggressive forms and incorporates neoadjuvant or adjuvant chemotherapy and also new hormone therapies.

Patterns of practice of androgen deprivation therapy combined to radiotherapy in favorable and unfavorable intermediate risk prostate cancer. Results of The PROACT Survey from the French GETUG Radiation Oncology group.

PURPOSE: The intermediate-risk (IR) prostate cancer (PCa) group is heterogeneous in terms of prognosis. For unfavorable or favorable IR PCa treated by radiotherapy, the optimal strategy remains to be defined. In routine practice, the physician's decision to propose hormonal therapy (HT) is controversial. The PROACT survey aimed to evaluate pattern and preferences of daily practice in France in this IR population. MATERIALS AND METHODS: A web questionnaire was distributed to French radiotherapy members of 91 centers of the Groupe d'Etude des Tumeurs Uro-Genitales (GETUG). The questionnaire included four sections concerning: (i) the specialists who prescribe treatments and multidisciplinary decisions (MTD) validation; (ii) the definition of IR subsets of patients; (iii) radiotherapy parameters; (iv) the pattern of practice regarding cardiovascular (CV) and (iv) metabolic evaluation. A descriptive presentation of the results was used. RESULTS: Among the 82 responses (90% of the centers), HT schedules and irradiation techniques were validated by specific board meetings in 54% and 45% of the centers, respectively. Three-fourths (76%) of the centers identified a subset of IR patients for a dedicated strategy. The majority of centers consider PSA>15 (77%) and/or Gleason 7 (4+3) (87%) for an unfavorable IR definition. Overall, 41% of the centers performed systematically a CV evaluation before HT prescription while 61% consider only CV history/status in defining the type of HT. LHRH agonists are more frequently prescribed in both favorable (70%) and unfavorable (98%) IR patients. Finally, weight (80%), metabolic profile (70%) and CV status (77%) of patients are considered for follow-up under HT. CONCLUSION: To the best of our knowledge, this is the first survey on HT practice in IR PCa. The PROACT survey indicates that three-quarters of the respondents identify subsets of IR-patients in tailoring therapy. The CV status of the patient is considered in guiding the HT decision, its duration and type of drug.

Development of a short olfactory test based on the Connecticut Test (CCCRC).

OBJECTIVE: To create a short olfactory test, Connecticut Smell Test (CST), based on the CCCRC (Connecticut Chemosensor and Clinical Research Center). DESIGN: A prospective patient-based study. SETTINGS: Smell and Taste Outpatient Clinic at the Fundación Hospital Alcorcón, Madrid, Spain. MATERIAL AND METHODS: We compared a short test based on the CCCRC with the Pocket Smell Test (PST) based on the University of Pennsylvania Smell Identification Test) UPSIT in 40 patients with nasal polyposis, in order to determine the specificity, sensitivity, positive predictive and negative predictive values. The validity index was 95% with an accuracy rate of 10%. We determined unit cost, the time required to perform the test in the outpatient office and the difficulty to perform the test. RESULTS: The sensibility was 93.3% and the specificity was 76% with a positive predictive value of 70% and a negative predictive value of 95%. The unitary cost of CST was euro0.65 when it is performed by a doctor. The unitary cost of PST is euro1.76. Our short test took 34 seconds to perform. More than 96% of the patients thought the test was easy to do. CONCLUSION: Our test is a valid, easy and quick test to be used in patients with nasal polyposis.

[Ductal carcinoma in situ: role of the boost]. / Radiothérapie des carcinomes canalaires in situ: impact du complément d'irradiation du lit tumoral.

Ductal carcinoma in situ is defined as breast cancer confined to the ducts of the breast without evidence of penetration of the basement membrane. Local treatment quality represents one of the most prognostic factors as half of recurrences are invasive diseases. The main goal of adjuvant radiotherapy after conservative surgery is to decrease local recurrences and to permit breast conservation with low treatment-induced sequelae. Several randomized trials have established the impact of 50 Gy to the whole breast in terms of local control. Nevertheless, no randomized trial is still available concerning the role of the boost in this disease. In this review, we present updated results of the literature and we detail the French multicentric randomized trial evaluating the impact of a 16 Gy boost after 50 Gy delivered to the whole breast in 25 fractions and 33 days. This protocol will start inclusions in October 2008.

[Elevation of PSA after prostate radiotherapy: rebound or biochemical recurrence?]. / Elévation du PSA après irradiation prostatique : rebond ou récidive biologique?

The fact that external beam radiotherapy and brachytherapy are now considered to be curative techniques has led to major review of the modalities of follow-up after radiotherapy for prostate cancer. The problem concerns both the diagnosis of recurrence, rapidly announced by elevation of prostatic-specific antigen (PSA), usually at a subclinical stage, and the validity of criteria of biochemical recurrence to allow comparison of various study. Physicians involved in follow-up should be aware of the potential of bounce in PSA follow-up after external beam radiotherapy or brachytherapy. The PSA bounce phenomemon was defined by a rise of PSA values (+0.1 -0.8 ng/ml) with a subsequent fall. Biochemical failure after external beam radiotherapy or brachytherapy (with or without hormonotherapy) was defined by Phoenix criteria by a rise of 2 ng/ml above an initial PSA nadir. This definition was more correlated to PSA bounce phenomenon.

Trans-electrical nerve stimulation (TENS) for somatic tinnitus.

The somatic tinnitus syndrome includes those forms of tinnitus that are associated with a somatic disorder involving the head and upper neck. It has been suggested that physiological mechanisms where interactions occur between the somatosensory and auditory systems are the etiology for that kind of tinnitus. Trans-electrical nerve stimulation (TENS) of areas of skin close to the ear increases the activation of the dorsal cochlear nucleus through the somatosensory pathway and may augment the inhibitory role of this nucleus on the CNS and thereby ameliorate tinnitus. In a prospective descriptive study of 26 patients with the probable diagnosis of somatic tinnitus we found that TENS could improve the tinnitus in 46% of the participants (23% did not hear it anymore, and in 23% its intensity was reduced). VAS scores improved from 6.5 to 6.0 after 2 weeks of treatment (p<0.01). Patients used TENS at home for 2h, once per day during 2 weeks (alternating ramped burst, 150 pps, with pulse duration of 100 micro s, amplitude 0-60 mA; average TENS intensity was 27 mA). Intermittent "typewriter" type of tinnitus was the most responsive. Somatic tinnitus without otologic disease had better response than tinnitus associated to otological causes (p=0.047).

[PSA bounce after permanent implant prostate brachytherapy may mimic a biochemical failure]. / Influence sur les résultats des rebonds du PSA après curiethérapie de prostate: étude de 295 cas avec trois ans de suivi.

PURPOSE: To assess the frequency of the PSA "bouncing" phenomenon after a significant follow-up in a series of patients treated by permanent implant brachytherapy for a prostate cancer. To look for the clinical and dosimetric parameters possibly linked to this transitory secondary PSA increase. To evaluate in which percentage of cases this bouncing could have mimicked a biochemical relapse according to the ASTRO consensus criteria. PATIENTS AND METHODS: From January 1999, to December 2001, 295 patients were treated by a permanent prostate implantation (real-time technique, with free (125)I seeds- Isoseed Bebig-) by the Institut Curie-Hôpital Cochin-Hôpital Necker Paris group. The mean follow-up is 40.3 months (9-66 months). The PSA level was regularly checked, at least every 6 months. We defined as a "bouncing" all increase in PSA, starting at 0.1 ng/ml, subsequently followed by a spontaneous (without any treatment) decrease, with return to the previous level or lower. We particularly focused on the patients fulfilling the criteria for a biochemical relapse according to the ASTRO consensus (Three successive increases in PSA). A multivariate analysis tried to identify independent factors among the usual clinical and dosimetric parameters. RESULTS: In our series, 161 patients (55%) showed a transitory PSA increase (bouncing) of at least 0.1 ng/ml; 145 patients (49%) a bouncing of 0.2 ng/ml, 93 patients (32%) a bouncing of 0.4 ng/ml and 43 patients (15%) a bouncing of at least 1 ng/ml. Mean PSA bounce was 0.8 ng/ml (0.1-4.1), and mean time to bounce was 19 months. Thirty-two patients (11% of the total number) presented three successive PSA increases with a significant (3 months) interval between the dosages, and therefore were to be considered as being in biochemical relapse according to the ASTRO consensus criteria. Actually, among those 32 patients, 18 (56%) subsequently showed a complete normalization of their PSA, without any treatment. Ten patients went on increasing their PSA, and were considered to be really in biochemical relapse. For the last 4 patients, the situation still remains ambiguous. In multivariate analysis, age<70 years (P<0.00001) and D90>200 Gy (P<0.003) were identified as independent factors for a PSA bouncing of at least 0.4 ng/ml. CONCLUSIONS: The observed rate of 32% of patients showing a PSA bouncing of at least 0.4 ng/ml in our series is in good agreement with what has been previously reported in the literature. Age<70 years and D90>200 Gy were found to be independent factors predicting for such a secondary transitory increase in PSA. Interestingly, among 32 patients fulfilling the classical criteria of the ASTRO for a biochemical relapse, 18 (56%) subsequently showed a spontaneous PSA decrease, demonstrating that the ASTRO consensus is not well adapted to the biochemical follow-up of our patients undergoing permanent implant prostate Brachytherapy.

[Progress in radiation therapy and integration in Tenon hospital (AP-HP) of new advances in routine practices of radiotherapy for non-small-cell lung cancer]. / Evolution de la radiothérapie externe et intégration à l'hôpital Tenon (AP-HP) des innovations technologiques récentes dans la pratique de la radiothérapie externe des carcinomes bronchiques non à petites cellules.

Much progress has been made in recent years in administration modalities for external radiotherapy of non-small-cell lung carcinoma. Three-dimensional conformal radiotherapy with or without intensity modulation, with respiratory gated radio-therapy (4D radiotherapy), and image-guided radiotherapy (IGRT) can be considered as a third revolution in radiation therapy after total dose fractionation and the development of megavoltage radiation therapy equipment. We describe progress in the three-dimensional radiotherapy technique and the integration of this technique in the department of Radiation Oncology at Tenon hospital (AP-HP).

[Concurrent administration of adjuvant chemotherapy and radiotherapy after breast-conservative surgery enhances late toxicities]. / La chimiothérapie concomitante de la radiothérapie augmente la toxicité tardive après chirurgie conservatrice du cancer du sein.

PURPOSE: In 1996, a multicenter randomized study comparing after breast-conservative surgery, sequential vs concurrent adjuvant chemotherapy (CT) with radiation therapy (RT) was initiated (ARCOSEIN study). Seven hundred sixteen patients were included in this trial. After a median follow-up of 6.7 (4.3-9) years, we decided to prospectively evaluate the late effects of these two strategies. PATIENTS AND METHODS: A total of 297 patients were asked to follow-up from the five larger including institutions. Seventy-two percent (214 patients) were eligible for late toxicity. After breast-conserving surgery with axillary dissection, patients were treated either with sequential treatment with CT first followed by RT (arm A) or CT administered concurrently with RT (arm B). In all patients, CT regimen combined mitoxantrone (12 mg/m(2)), 5-FU (500 mg/m(2)), and cyclophosphamide (500 mg/m(2)), 6 cycles (day 1-day 21). In arm B, patients received concurrently the first 3 cycles of CT with RT. In arm A, RT started 3 to 5 weeks after the 6th cycle of CT. Conventional RT was delivered to the whole breast using a 2 Gy-fraction protocol to a total dose of 50 Gy (+/-boost to the primary tumour bed). The assessment of toxicity was blinded to treatment and was graded by the radiation oncologist according to the LENT-SOMA scale. Skin pigmentation was also evaluated using a personal 5-points scoring system (excellent, good, moderate, poor, very poor). RESULTS: Among the 214 evaluated patients, 107 were treated in each arm. The two populations were homogeneous for patients', tumors' and treatment characteristics. Subcutaneous fibrosis (SF), telengectasia (T), skin pigmentation (SP), and breast atrophy (BA) were significantly increased in arm B. Twenty patients experienced grade superior or equal to 2 (SF) in arm B vs five in arm A (P=0.003). Twenty-five and seven patients showed grade superior or equal to 2 (T) in arm B and A, respectively (P=0.001). Forty-four and twenty patients showed grade superior or equal to 2 (BA) in arm B and A, respectively (P=0.0006). Thirty patients experienced grade superior or equal to 3 (SP) in arm B vs fifteen in arm A (P=0.02). No statistical difference was observed between the two arms concerning grade superior or equal to 2 pain, breast oedema, and lymphoedema. No deaths were caused by late toxicity. CONCLUSION: Following breast conserving surgery, the concurrent use of CT with RT is significantly associated with an increase incidence of grade 2 or greater late side effects.