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Background: In asthma, obesity status is associated with poor control and high exacerbation rates. The primary objective was to determine the effect of bariatric surgery (BS) on asthma control and exacerbations., Methods: Retrospective study with a 3-year cohort of obese patients before and after BS: a baseline period (P0) covering the 12 months before BS and P1 and P2 periods covering the first and second years after BS, respectively. Asthma control was assessed from the use of relievers, and severe exacerbation rates, i.e. use of oral corticosteroids and asthma-related hospitalizations (ARHs). P1 and P2 measures were compared with those of P0. Patients were matched with non-obese patients and compared over P0 using a generalized linear mixed model with random effects., Results: 2601 asthma patients undergoing BS were included. Of these, 2556 patients were matched with 2556 nonobese asthma patients. After BS, the risk of poor control decreased [OR = 0.26 (95 % CI: 0.21-0.32)] together with the mean exacerbation rate, with IRRs of 0.54 (95 % CI: 0.51-0.58) and 0.60 (95 % CI: 0.56-0.64) for P1 and P2, respectively, compared with P0. The incidence risk ratios (IRRs) were of 1.19 (95 % CI: 1.04-1.35) and 1.28 (95 % CI: 1.20-1.37) for poor control and severe exacerbation rates, respectively, in obese vs. nonobese asthma patients., Conclusion: In patients with asthma, obesity is a major risk factor for poor control and increased exacerbation rates, with both outcomes highly reversible for at least two years following BS., Competing Interests: Declaration of competing interest Nothing to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Treatment landscape in metastatic lung cancer has progressed quickly over the last decade, mainly due to immunotherapies and targeted therapies. This study aimed to describe change in epidemiological data of patients with metastatic lung cancer., Methods: A cohort of patients identified between 2013 and 2021 with lung cancer and a marker of metastases (ICD-10 code or reimbursement for Bevacizumab or Pemetrexed) was built from the French claims database. A trend analysis of the rate of newly-diagnosed metastatic patients and the proportion of deaths over the study period was performed using Joinpoint® software., Results: Between 2013 and 2021, 147,760 metastatic lung cancer patients were identified (men: 66.5%, median age: 66 years). A statistically significant decrease in the crude rate of newly-diagnosed metastatic patients was observed in men (-1.18% per year in average), whereas a statistically significant increase was described in women (+2.36% per year in average). A downward trend in the proportion of deaths was found for both gender (-4.37% and -5.07% per year on average, respectively)., Discussion: This study provides unpublished epidemiological data on metastatic lung cancer in France and confirms sex-differentiated trends in the rate of newly-diagnosed metastatic patients, already observed for all stages combined. A statistically significant decrease in the proportion of deaths among metastatic lung cancer patients is observed in both genders. These results underline the importance of ongoing investments in prevention and screening initiatives to reverse the incidence trends observed in women. Moreover, it highlights the criticality of therapeutic innovation in sustaining the increase in survival., (Copyright © 2024 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: The study aimed to determine the level of agreement between patients with epilepsy and their proxies when assessing psychiatric comorbidities, sleep disorders, and medication adherence using standardized questionnaires., Methods: This agreement study is an ancillary analysis of the PRERIES study, a matched case-control study exploring SUDEP risk factors. Controls aged 15 years and older, with active epilepsy or in remission for less than 5 years were recruited between 01/01/2011 and 03/31/2019. An interview was carried out by a trained psychologist on both the patient and a proxy-respondent. During these independent interviews, the following comorbidities were explored: psychiatric comorbidities using the MINI, the STAI- Y 2 and NDDI-E scales, sleep disorders with the SDQ-SA and Epworth scales and medication adherence. Level of agreement between patient and their proxy was estimated using Gwet's AC1&2., Results: Among the 107 patient-proxy dyads recruited, proxy respondents were mainly family members (65.4%) or spouses (30.8%). Exploration of present major depression showed excellent agreement at 0.81 [0.65;0.97], as well as exploration of dysthymia at 0.96 [0.61;1]. Suicidal risk evaluation had a lesser agreement at 0.77 [0.60;0.94]. Agreement on anxiety was moderate 0.5 [0.38;0.62]. For sleep disorder, SDQ-SA presented a better agreement than the Epworth questionnaire with respectively 0.73 [0.51;0.95] and 0.45 [0.26;0.63]. For medication adherence, the overall agreement rate was excellent (0.90 [0.78;1])., Conclusion: Exploration of potential risk factors through families can give valuable and relatively robust information, especially if the respondent lives with the patient, and should be retrieved, when possible, in usual clinical setting., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: To define the phenotypic and mutational spectrum of epilepsies related to DEPDC5, NPRL2 and NPRL3 genes encoding the GATOR1 complex, a negative regulator of the mTORC1 pathway METHODS: We analyzed clinical and genetic data of 73 novel probands (familial and sporadic) with epilepsy-related variants in GATOR1-encoding genes and proposed new guidelines for clinical interpretation of GATOR1 variants., Results: The GATOR1 seizure phenotype consisted mostly in focal seizures (e.g., hypermotor or frontal lobe seizures in 50%), with a mean age at onset of 4.4 years, often sleep-related and drug-resistant (54%), and associated with focal cortical dysplasia (20%). Infantile spasms were reported in 10% of the probands. Sudden unexpected death in epilepsy (SUDEP) occurred in 10% of the families. Novel classification framework of all 140 epilepsy-related GATOR1 variants (including the variants of this study) revealed that 68% are loss-of-function pathogenic, 14% are likely pathogenic, 15% are variants of uncertain significance and 3% are likely benign., Conclusion: Our data emphasize the increasingly important role of GATOR1 genes in the pathogenesis of focal epilepsies (>180 probands to date). The GATOR1 phenotypic spectrum ranges from sporadic early-onset epilepsies with cognitive impairment comorbidities to familial focal epilepsies, and SUDEP.

The melanosome pattern was characterized systematically in keratinocytes in situ in highly, moderately, and lightly pigmented human skin, classified according to the individual typological angle, a colorimetric measure of skin color phenotype. Electron microscopy of skin samples showed qualitatively and quantitatively that in highly pigmented skin, although melanosomes are mostly isolated and distributed throughout the entire epidermis, clusters are also observed in the basal layer. In moderately and lightly pigmented skin, melanosomes are concentrated in the first layer of the epidermis, isolated-but for most of them, grouped as clusters of melanocores delimited by a single membrane. Electron tomography resolving intracellular three-dimensional organization of organelles showed that clustered melanocores depict contacts with other cellular compartments, such as endoplasmic reticulum and mitochondria. Additionally, immunogold labelling showed that clusters of melanocores do not correspond to autophagosomes or melanophagosomes but that they present, similarly to melanosomes in melanocytes, features of nonacidic, nondegradative organelles. Overall, these observations suggest that melanocore clusters do not correspond to autophagic organelles but represent reservoirs or protective structures for melanosome integrity and function. These results open avenues for understanding the basis of skin pigmentation in different skin color phenotypes., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Alzheimer's disease is the most common neurodegenerative disease associated with aggregation of Aβ peptides. Aβ toxicity is mostly related to the capacity of intermediate oligomers to disrupt membrane integrity. We previously expressed Aβ 1-42 in a eukaryotic cellular system and selected synthetic variants on their sole toxicity. The most toxic mutant G37C forms stable oligomers., Methods: Different biophysical methods (Fluorescence spectroscopy, cross-linking, mass spectrometry (MS), Small Angle X-ray Scattering (SAXS), Atomic Force Microscopy (AFM), Transmission Electron Microscopy (TEM), calcein leakage) were used., Results: The oligomers are mostly populated by a 14mers resulting from the packing of homodimers. These homodimers come from the formation of a disulfide bridge between two monomers. This link stabilizes the multimers and prevents the assembly into amyloid fibrils. These oligomers affect the membrane integrity. The reduction of disulfide bonds leads to a rearrangement and redirects assembly of Aβ amyloid fibrils., Conclusion: The toxic synthetic Aβ G37C mutant can assemble into an amyloid of unusual morphology through the formation of anti-parallel β-sheets. This pathway involves the formation of oligomers resulting from the arrangement of Aβ dimers linked by covalent di-sulfide link, being these oligomers harmful for the membranes., General Significance: The capacity to produce large amount of stable oligomers without additional detergents or extrinsic cross-linkers allow further structural and biophysical studies to understand their capacity to assemble and disrupt the membranes, a key event in Alzheimer's disease., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The aim of the present research was to study vocational identity in French adolescent and emerging adult students by using a French adaptation of the Vocational Identity Status Assessment (VISA), and to analyze the links between vocational identity formation and negative and positive psychological adjustment. Participants were 1077 French students who completed self-report scales about vocational identity, depression and satisfaction with life. The French version of the VISA showed good psychometric properties and six identity statuses were derived by means of cluster analysis: achievement, foreclosure, moratorium, searching moratorium, diffused diffusion and carefree diffusion. The main findings show that diffused diffusion and moratorium represent the dark sides of identity because of their negative psychological adjustment, and that the two processes of reconsideration of commitment were differently associated with psychological adjustment. These findings demonstrate that clinical interventions should be adapted to the individual's identity profile., (Copyright © 2015 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the safety and efficacy of whole breast irradiation with a concomitant boost., Patients and Materials: This is a retrospective study of 121 patients with node negative T1-T2 breast tumors inferior to 3 cm in diameter, previously treated by conservative surgery without chemotherapy. A dose of 50 Gy was delivered to the whole breast in 2 Gy daily fractions with 5 weekly treatments. A concomitant boost to the lumpectomy site delivered a total of 10 Gy in 1 Gy fractions twice a week. This would result in an equivalent tumour bed dose (assuming an α/β of 4) of approximately 65 Gy in 2 Gy fractions., Results: Over 7 years, 121 patients were treated. The median age was 67 years (range, 46-86 years). Stage distribution was: 115 T1, 6 T2; 116 tumors had positive hormonal receptors, 6 grade SBR3. With a median follow-up of 6 years (range, 1.4-11.4 years), 5-year overall survival was 98.2% (95% confidence interval [CI] 0.95-1), disease-free survival was 100% and local recurrence-free survival 100%. The maximum acute skin toxicity by the end of treatment was grade 2. Cosmetic outcomes were good on the long term. One spontaneous rib fracture was observed 1 year after radiotherapy among 76 patients., Conclusions: The study shows that whole breast radiation therapy with a concomitant boost is safe and effective for selected patients with low risk of relapse, and gives excellent long term results. This protocol represents a good alternative to longer standard whole breast radiation therapy with sequential boost to the lumpectomy bed., (Copyright © 2014 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Refractory status epilepticus (SE) is a current daily therapeutic challenge. Electroconvulsive therapy (ECT), which is frequently used to treat psychiatric disorders, is known to raise the seizure threshold. As such, ECT could be of major interest in refractory SE. In this paper, we provide a brief overview of ECT in refractory SE. Although no placebo-controlled or open-label study has been published on the efficacy or safety of ECT in refractory SE, eight case reports have been identified. SE cessation was obtained in 80% of cases, and complete recovery was achieved in 27% of patients. Despite the heterogeneity of the ECT parameters used in these articles, we identified some common features that may be recommended for the use of ECT in refractory SE. ECT might be a viable therapeutic strategy for the most resistant and severe cases of SE, particularly after the failure of two inductions of anesthetic coma. This potential indication highlights the urgent need for clinical trials that assess the usefulness of ECT in refractory SE., (Copyright © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Periventricular nodular heterotopia, the most common form of cortical malformation in adulthood, is characterized by nodules of neurons ectopically placed along the lateral ventricles. Classically, ectopic nodules are bilateral and symmetric defining bilateral periventricular nodular heterotopia (BPNH). BPNH can lead to epilepsy and intellectual disability of variable severity. The X-linked dominant form of BPNH, related to mutations in FLNA encoding filamin A, is the major cause of BPNH, causing prenatal and neonatal lethality in males that explain the excess of affected women. However, few living males have been described with this condition. In addition, mutations in FLNA have been also exceptionally associated with unilateral nodular heterotopia. We describe here three new patients, all carrying a novel missense mutation in FLNA. Two of the patients were adult males with BPNH; both had normal cognitive development and one did not manifest any seizure until he died at age 57. The last patient was a female adult with epilepsy and focal nodules essentially located along the right ventricle. We compare the clinical and imaging data of our patients with those of previously described similar cases. The type and location of FLNA mutations leading to such atypical presentations are discussed., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Purpose: Surgical resection remains the standard treatment for patients with resectable retroperitoneal sarcomas. The aim of this study was to retrospectively analyse the outcomes of patients with primary retroperitoneal sarcoma., Patients and Methods: We analysed data of 50 patients with primary retroperitoneal sarcoma who underwent curative-intent resection from 1975 to 2008. External beam radiotherapy and chemotherapy were delivered postoperatively. Demographics, surgical, pathological variables and chemo/radiation therapy were analysed as prognosis factors., Results: There were 22 males and 28 females (mean age 54 ± 13 years). Surgery required visceral resections in 30 patients. There were 16 leiomyosarcomas, 25 liposarcomas and eight other sub-types. Twenty-one patients had clear surgical margins. Twenty-eight patients received postoperative external beam radiotherapy (median 45 Gy) and 15 received chemotherapy. At the end of the follow-up (median 55 months), local recurrence occurred in 39% (n=14) among R0/R1 resection group (n=36). Postoperative external beam radiotherapy tends to increase the time of local recurrence from surgery (27 vs. 13 months, P=0.05). The overall survival rates were 81%, 55% and 46% at 1, 3 and 5 years, respectively. Although R0 resection (P=0.01), well tumour differentiation (P=0.004) and postoperative external beam radiotherapy (P=0.02) significantly influenced overall survival in univariate analysis, only R0 resection was an independent prognostic factor in a multivariate analysis., Conclusion: We confirm the pre-eminence of radical surgery with negative margins as major prognostic factor and the benefit of postoperative radiotherapy., (Copyright © 2012 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

In December 2007, Babesia bovis was introduced to New Caledonia through the importation of cattle that had been vaccinated with a live tick fever (babesiosis and anaplasmosis) vaccine. Although the tick Rhipicephalus (Boophilus) microplus is common in New Caledonia, the territory had previously been free of tick-borne diseases of cattle. This paper describes the initial extent of the outbreak, the measures and rationale for disease control, and the progress to date of the eradication campaign. Initially, 22 properties were affected involving approximately 2300 cattle in 'high risk' zones and 1600 in adjoining 'suspect' zones. Rather than slaughtering infected herds or attempting to eliminate the tick vector, the campaign was based on quarantine of affected properties, and aggressive tick control in conjunction with 3-monthly treatments of the high risk cattle with the antiprotozoal drug imidocarb dipropionate. Subsequent surveillance by ELISA and PCR showed a progressive and dramatic decline in seroprevalence among infected herds and the absence of new infections. All 22 properties were considered to be free of Babesia within 12 months of the start of the disease control program. These results indicate that the strategy was effective in eliminating Babesia from infected herds and feasible as an eradication strategy on a moderately large scale. Unfortunately, early in the campaign, babesiosis spread to a herd of feral cattle on a property in the 'suspect' zone, and this reservoir of infection subsequently resulted in the infection (or reinfection) of cattle on several neighbouring commercial farms. The eradication campaign in New Caledonia is currently focussed on destocking the feral cattle - extensive surveillance suggests that this is the only remaining nidus of infection., (2010 Elsevier GmbH. All rights reserved.)

Unlabelled: The electrophysiological evaluation of Wolff-Parkinson-White syndrome (WPW) is recommended in children aged more than five years to detect a risk of life-threatening arrhythmia. The purposes of the study were to determine the feasibility of transesophageal EPS in a child between six and 10 years in out-patient clinic., Methods: Electrophysiological study (EPS) was indicated in 22 children, aged six to 10 years, with a manifest WPW either for no documented tachycardia (n=7), unexplained dizziness (n=2) or for a sportive authorization in 10 asymptomatic children. Two of the last children had a history of permanent tachycardia after the birth but were asymptomatic since the age of one year without drugs., Results: EPS was performed in all children. The main difficulty lied in passing the catheter through the mouth. Programmed stimulation at cycle length of 380 ms was performed in all children to avoid high rates of pacing when the conduction through the accessory pathway (AP) and normal AV system was evaluated. Isoproterenol was not required in five children, because they developed a catecholaminergic sinus tachycardia. The AP refractory period was determined in all children between 200 and 270 ms. Orthodromic reentrant tachycardia (RT) was induced in 11 children, three asymptomatic children (27%), seven complaining of tachycardia and one with syncope. Rapid antidromic tachycardia was induced in this last child with dizziness. Atrial fibrillation was never induced., Conclusions: Esophageal EPS can be performed without sedation in a young child six to 10-year-old with a shortened protocol of stimulation, which was capable to clearly evaluate the WPW-related risks.

Purpose: To study prognostic factors of obliteration and risk factors of brain radiation necrosis in order to propose an algorithm for radiosurgery prescription for cerebral arteriovenous malformations (cAVM)., Material and Methods: One hundred and seventy-nine patients were analysed. Radiosurgery delivered 6 or 10 MV X-rays by arc therapy in 84% of cases, or by fixed field in 16% of cases using two different micro-multileaf collimators (micro-MLC). Follow-up consisted of screening radiation necrosis by MRI every 6 months, and assessing local control by arteriography every 2 years. Obliteration was defined as at least 95% reduction of cAVM volume. Cox proportional hazard model was used to evaluate the local control and the appearance of radiation necrosis over time., Results: Local control rate was 82.7% with the mean follow-up of 3.1 years (0.5-11). Significant prognostic factors were: simple nidus (RR=2.8, p<0.0001), number of embolizations before radiosurgery below 4 (RR=2.9, p<0.0001), prescribed dose to the periphery of at least 18 Gy (RR=2, p=0.0002), nidus volume below8cm(3) (RR=1.9, p=0.0002), and number of table positions below six (RR=1.4, p=0.05). Radiation necrosis rate was 11.2% with a mean time to onset of 18 months. Significant predictive factors were: fixed field versus arc therapy (according to MLC RR=9.1, p<0.0001, and RR=15.1, p=0.01), age below 30 years (RR=2.5, p=0.04), depth of cAVM greater than or equal to 7 cm (RR=7.6, p=0.008), and volume of brain tissue covered by the 12 Gy isodose (V12 Gy) of at least 11 cm(3) (RR=7.8, p=0.05)., Conclusion: A radiosurgery prescription algorithm taking into account the prescribed dose to the periphery (> or = 18 Gy) and reduction of V12 Gy was elaborated from these data.

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.

Polymorphisms of the genes 5'-10'-methylenetetrahydrofolate reductase (MTHFR, 677CT and 1298AC), methionine synthase (MTR, 2756AC) and methionine synthase reductase (MTRR, 66AC) provoke variations in enzyme activity, which can lead to alterations in the metabolism of folates and in the synthesis of S-adenosyl-methionine (SAM), the most active methyl donor in the body. This could play an important role in carcinogenesis through the degree of DNA methylation and of nucleotide synthesis. In the present study, four polymorphisms were studied, two of the methylenetetrahydrofolate reductase gene, and the other two of methionine synthase and methionine synthase reductase. Our aim was to study the association between prostate carcinoma susceptibility and these polymorphisms. A hospital-based case-control study was conducted in 182 patients (mean age: 70.7+/-7.29 years) with histologically confirmed prostate carcinoma and in 205 control subjects (mean age: 70.3+/-7.82 years) diagnosed with benign prostatic hyperplasia (BPH). Genomic DNA was extracted from peripheral leukocytes. Comparison of the MTHFR CT and TT genotypes in patients and the controls revealed significant differences (0.57 vs 0.38) (OR: 2.19, 95% CI: 1.46-3.30) and (0.06 vs 0.15) (OR: 0.36, 95% CI: 0.17-0.73), respectively. No statistically significant differences were found between patients and controls with respect to the MTHFR 1298AC, the MTR 2756AC and the MTRR 66AC polymorphisms. However, among the patients, the MTR 2756 allele C was related to a high Gleason score. We conclude that the polymorphism MTHFR C677T is clearly related to prostatic carcinogenesis, on the contrary to the other polymorphisms studied, although the MTR 2756 allele C acts as a factor of tumor aggressiveness, this being found in tumors with high carcinogenic potential.

Unlabelled: Beginning 1998, a working group of specialists convened by the guidelines department (Standards, Options and Recommendations: SOR) of the National French Federation of Comprehensive Cancer Centres (FNCLCC) published then regularly updated Recommendations relative to the use of ESA in anaemic patients with cancer. This article presents a short version of the Recommendations updated in 2007., Methods: This updating process is based on the methodology developed and used in the "Standards, Options: Recommendations" programme. The methodological approach combines systematic review with the judgement of a multidisciplinary group of experts. A Recommendation is a proposal of one or several clinical attitudes intended to improve cancer patient care. There are two levels of gradation for the Recommendations: Standards and Options. Their setting takes into account the organisational context of care, the particular situation of the patient and the expression of his preferences. Before publication, the RPC-SOR are re-examined by independent reviewers selected according to the same principles as the group of expert writers., Results: New data are sufficiently important to update the latest Recommendations validated in 2003. Thus, five clinical questions were updated. The resulting modifications were either major (new Options or new Standards) or minor (increased level of evidence). It should be noted that for the clinical question--use of ESA in radiotherapy--new data are not sufficient to generate modifications in the initial Recommendations which remain valid., Conclusions: Because of the important new data published on the subject between 2003 and 2007, it appears relevant to re-examine these Recommendations according to a systematic monitoring process which should be renewed in 2 years.

Introduction: Beginning 1998, a working group of specialists convened by the guidelines department (Standards, Option and Recommendations: SOR) of the National French Federation of Comprehensive Cancer Centres (FNCLCC) published then regularly updated Recommendations relative to the use of ESA(epoetin alfa, epoetin bêta, darbepoetin) in anaemic patients with cancer. This article presents the updated Recommendations set up in 2007., Methods: This updating process is based on the methodology developed and used in the "Standards, Options: Recommendations" programme. The methodological approach combines systematic review with the judgement of a multidisciplinary group of experts. On the basis of analysis of literature, the conclusions and their level of evidence are established. Then, the conclusions accompanied by experts' judgement lead to the Recommendations. A Recommendation is a proposal of one or several clinical attitudes intended to improve cancer patient care. Before publication, the RPC-SOR are re-examined by independent reviewers selected according to the same principles as the group of expert writers., Results: New data, relative to the "use of ESA in anaemic cancer patients undergoing radiotherapy", didn't lead to update the latest Recommendations validated in 2003. However, new data relative to the "use of ESA in anaemic prophylaxis among adult patients with cancer" and to the "use of iron with ESA in cancer patients" were sufficient to generate either major or minor modifications to the initial Recommendations., Conclusions: Thus, it appears relevant to re-examine these Recommendations according to a systematic monitoring process which should be renewed in two years.

The human immunodeficiency virus type 1 (HIV-1) Vpu protein binds to the CD4 receptor and targets it to the proteasome for degradation. This process requires the recruitment of human betaTrCP, a component of the Skp1-Cullin-F box (SCF) ubiquitin ligase complex, that interacts with phosphorylated Vpu molecules. Vpu, unlike other ligands of betaTrCP, has never been reported to be degraded. We provide evidence that Vpu, itself, is ubiquitinated and targeted for degradation by the proteasome. We demonstrate that the mutant Vpu2.6, which cannot interact with betaTrCP, is stable and, unlike wild-type Vpu, is not polyubiquitinated. These results suggest that betaTrCP is involved in Vpu polyubiquitination.

It has been shown that a delay in radiotherapy (RT) initiation resulted in a higher local relapse (LR) rate. The present analysis investigated retrospectively if the RT-adjuvant therapy sequence modified local-disease-free survival (L-DFS) after breast-conserving surgery (BCS) in node-positive (N +) breast cancer patients. Among seven French Adjuvant Study Group trials, 1,831 patients were assessable: 475 received RT directly after BCS, 567 after the 3rd chemotherapy (CT) cycle, and 789 after the 6th CT cycle. In the 1,356 patients receiving CT, it consisted of FEC regimens (fluorouracil, epirubicin, cyclophosphamide) in 83.5% of patients. After a 102-month median follow-up, 214 patients (11.7%) developed LR. The 9-year L-DFS rates were 92.0%, 81.5%, and 87.4%, respectively (p < 0.0001). In the multivariate analysis, the timing of RT was not associated with a higher rate of LR, whereas tumor size and hormonotherapy were prognostic factors. In our population, there was no increase in the risk of LR when RT was delayed to deliver adjuvant CT. Prognostic factors were tumor size, and hormonotherapy. The number of CT courses could modify this risk.

During the treatments of carcinomas of the cervix, anemia is relatively frequent and its origin is complex combining often hemorrhage, iron deprivation, inflammatory reactions and infection. The frequency of the primary anemia (hemoglobin level<12 g/dl) is correlated with clinical stage and varies from one publication to another, mainly from 25% for stage I, to 33% for stage II and can approach 40% for stage III. Anemia is correlated with patient survival and it appears to be one of the most powerful prognostic factor after clinical stage and tumor size. Anemia is a bad prognostic factor related to stage and tumor size but it has not been proven to be an independent factor. Anemia increases hypoxia of cervix carcinomas, which is an independent prognostic factor for patients N0. Moreover, we know that the oxygenation of these tumors is correlated with hemoglobin levels. The normalization of Hb levels by transfusion could certainly modify the prognosis of patients anemic before treatment, or of those becoming anemic during radiotherapy treatment. For smokers, anemia is certainly more important that we can appreciate from the Hb levels only, by the presence of carboxyhemoglobin. Concomitant chemotherapies with cisplatin compounds are actually standards and they can largely increase the risk of inducing anemia, therefore more than 50% of patients will experiment it during their different treatments. Transfusion is recommended by the SOR (Standards Options and Recommendations of the Fédération nationale des centres de lutte contre le cancer) under 10 g/dl. The use of erythropoietin is a therapeutic option for Hb levels between 10 and 12 g/dl and strongly recommended after a Hb normalization by blood transfusion. For 70% of patients who respond to erythropoietin, a better control of the Hb level is obtained. The impact of this anemia on quality of life and treatments compliance justifies the use of erythropoietin, especially in cancers for which treatments induce a deep fatigue and a very bad tolerance, which could be a limiting factor.

Introduction: Between May 2002 and May 2004, eight French comprehensive cancer centres did a prospective nonrandomized study including 200 patients, 100 with cancer of the prostate and 100 with head and neck cancers. Half of each patient group was treated by IMRT and the others by RTC 3D. This clinical study was associated with an economic study and a physics study. We report here the first results., Patients and Methods: For the clinical study, the analysis of the data of the first 88 patients irradiated for a prostatic cancer shows that 39 received RTC and 49 IMRT with a mean dose of 78 Gy at the ICRU point at 2 Gy per fraction. For H&N tumours, the preliminary analysis was done on the 87 first patients with a mean follow-up of 11.5 months (2 to 25 months) and a median of 8.4 months for the IMRT groups and 13.2 months for the RTC group. The economic study was done on the first 157 patients included during the first 18 months: 71 treated by RTC (35 for H&N and 36 for prostate) and 86 treated by IMRT (38 for H&N and 48 for prostate). The assessment of the direct costs was realized by a micro-costing technique. The physical study compared dose distributions for both techniques and has created quality control recommendations., Results: Clinical studies of the acute reactions do not show any difference between groups, but we want to point out the short follow-up and the relatively high dose delivered to cancers of the prostate. The physics study demonstrates that IMRT is technically feasible in good clinical conditions with high quality assurance, a good reproducibility and precision. Dosimetric data show that IMRT could certainly spare organs at risk more than RTC for H&N tumours. The direct costs of "routine" treatments for H&N tumours were 4922 euros for IMRT versus 1899 euros for RTC and for the prostatic cancers 4911 euros for IMRT versus 2357 for RTC.

Aims of the Study: Retrospective analysis of patients treated by preoperative brachytherapy for endometrial carcinoma., Patients and Methods: From 1973 to 1994, 780 consecutive patients with a clinical stage I-II endometrial carcinoma were treated with brachytherapy followed by surgery and pelvic irradiation if necessary. Tumour was staged according to 1979 UICC classification. There were 462 T1a, 257 T1b, and 61 T2, 62% were well differentiated. Brachytherapy consisted in one low dose rate endocavitary application. Sixty grays were delivered on the reference isodose. Surgery consisted in a TAH/BSO (Piver II) and was performed 6 weeks later. Nodal pelvic irradiation was indicated in case of unfavourable pathological prognostic factors., Results: Median follow up was 122 months. Five year survival rates were: 84% for overall survival, 86% for survival without recurrence, 92.8% for local control, and 3.8% for late complications. Pronostic factors were age, stage, differentiation, grade and postoperative extension. Multivariate analysis showed only age, differentiation and postoperative extension to be independent prognostic factors., Conclusion: If for stage 1, initial surgery has now replaced preoperative brachytherapy in most cases because it allows to identify initial prognostic factors, preoperative brachytherapy remains the most interesting option for stage 2 endometrial carcinomas.

Purpose: To report preliminary results of a prospective study of intensity-modulated radiotherapy (IMRT) for head and neck squamous cell carcinoma (HNC) with bilateral irradiation of the neck., Patients and Methods: At the Alexis Vautrin Cancer Center, 23 patients have been treated with IMRT for HNC since January 2002-August 2003. The first 10 patients with a minimum follow-up of 3 months were analyzed. All tumors were oropharyngeal. There were four females and six males, with a mean age of 50 years (range 39-66). Stages were I-II in eight and III-IV in two. CTV1 was microscopic disease and N0 neck (prescribed dose : 50 Gy) and CTV2 was macroscopic disease and the volume at risk (prescribed dose: 66-70 Gy). PTV were CTV + 5 mm. Patient's immobilization consisted of a five-point head neck shoulder thermoplastic mask. Set-up verifications were done by semi-automatically matching portal images and digitized reconstructed radiographs. IMRT used dynamic multileaf collimation. Five patients (group A) received 50 Gy IMRT (two post-operative and three with a brachytherapy boost with a mean dose: 27.5 Gy), and five patients (group B) received 66-70 Gy IMRT (four post-operative). Acute and late normal tissue effects were graded according to the RTOG-EORTC radiation morbidity scoring criteria., Results: With a median follow-up of 7.4 months (range 3-18.5), no patient died or had loco-regional relapse. The displacements were <4 mm in 98% cases. CTV1 and 2 received 95% of the prescribed dose in 100% of the volume. On average the mean dose to the contralateral parotid was 25.5 Gy for group A vs. 31 Gy for group B (P = 0.09). Mean doses <26 Gy were obtained in three of five patients in group A vs. zero of five patients in group B (P = 0.04). Acute skin toxicities were grade 1 in five patients, grade 2 in four and grade 3 in one. Acute mucositis cases were grade 1 in three patients, grade 2 in five and localized grade 3 in two. At 3 months, 50% of the patients had a grade 0-1 late xerostomia., Conclusion: The 26 Gy dose limit constraint to the contralateral parotid was easier to satisfy when IMRT was prescribed at a maximum dose of 50 Gy. Acute toxicity is low. The displacements in the mask indicate that it is possible to define the PTV as CTV + 4 mm. This reduction should decrease the mean dose to the parotids. At 3 months, a 50% rate of grade 0-1 late xerostomia encourages the hope of a very low rate at 2 years.

Context: "The Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centres (FNCLCC), the twenty French cancer centres, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery., Objectives: To update the Standards, Options and Recommendations clinical practice guidelines for the use of recombinant erythropoietin (epoietin alpha and beta darbepoietin-alpha, EPO) in the management of anaemia in oncology for patient undergoing radiotherapy., Methods: The working group identified the questions requiring up-dating from the previous guideline. Medline and Embase were searched using specific search strategies from January 1999 to October 2002. Literature monitoring was performed to identify randomised clinical trials published between October 2002 to November 2003. In addition several Internet sites were searched in October 2002., Results: There is no standard attitude for use of rHuEPO in patients undergoing radiotherapy. There is no evidence to support use of rHuEPO in patients with ENT cancer receiving radiotherapy alone. In patients undergoing curative radiotherapy, it is recommended to correct anaemia under I Og/dL using transfusion rather than rHuEPO. When the haemoglobin concentration is between 12g/dL and 14g/dL initial use of rHuEPO can be an option under certain conditions for radiochemotherapy if the risk of anaemia is high with the chemotherapy regimen used. Anaemic patients should be included in clinical trials to clarify the impact of rHuEPO in terms of local control of the tumour and survival.

Unlabelled: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centres (FNCLCC), the 20 French cancer centres, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery., Objectives: To update the Standards, Options and Recommendations clinical practice guidelines for the use of recombinant erythropoietin (epoietin alpha and beta darbepoietin-alpha, EPO) in the management of anaemia in oncology. To define, on the basis of the critical appraisal of the best available evidence and expert agreement, the clinical situations in which the administration of rHuEPO is indicated, and those in which it is not indicated, except in the setting of randomised controlled trial., Methods: The working group identified the questions requiring up-dating from the previous guideline. Medline and Embase were searched using specific search strategies from January 1999 to October 2002. Literature monitoring was performed to identify randomised clinical trials published between October 2002 to November 2003. In addition several Internet sites were searched in October 2002., Results: A total of 36 new references, corresponding to 30 randomised clinical trials, were identified. The role of rHuEPO is certain when the haemoglobin concentration is below 10 g/dL, but remains uncertain when the concentration is between 10 g/dL and 12 g/dL. When the haemoglobin concentration is between 12 g/dL and 14 g/dL there is no justification to use rHuEPO to prevent anaemia, except in the setting of autologous blood transfusion programmes before major surgery. No anti-anaemic treatment is justified if the haemoglobin concentration is higher than 14 g/dL, except in the setting of a randomised clinical trial., (Copyright John Libbey Eurotext 2003.)

Purpose: To retrospectively assess the efficacy of post-mastectomy re-irradiation for local relapse of breast cancer., Patients and Methods: Twenty patients, initially treated by conservative surgery and radiotherapy (50 Gy in 25 fractions over 5 weeks) were treated from 1998 to 2001 for a local relapse by salvage mastectomy and re-irradiation (either electron or photon beams). Mean age was 53 years (31-71). Reasons for re-irradiation were that the local relapses were inflammatory (4 pts), multifocal (5 pts), cutaneous (5 pts), involved the nipple (3 pts) or because the surgical margins (either muscle or skin) were involved (3 pts). The median dose of re-irradiation was 45 Gy (33-65) in 15 fractions over 33 days. Mean follow-up was 48 months (5-97)., Results: Fifteen patients remained free of a second local recurrence and 10 were still alive, without metastasis. Neither the dose of re-irradiation nor the irradiated surfaces were prognostic factors of local control (P = 0.877 and P = 0.424). Five patients developed radiation-induced pneumonitis without functional respiratory impairment. The incidence of pneumonitis seemed to be related to the biological dose of re-irradiation (P = 0.037). Other late complications occurred such as pigmentation changes (12 pts), telangiectasia (8 pts), chondritis (2 pts), parietal fibrosis (7 pts), rib fractures (4 pts), severe pain (11 pts) and lymphedema (2 pts). The increase in biological equivalent dose was highly statistically linked with the occurrence of disabling pain (P = 0.0123)., Conclusion: Parietal re-irradiation achieves good and lasting local control with an acceptable rate of acute complications but with a risk of disabling late sequelae such as severe pain.

The STIC 2001 and STIC 2002 projects intend to allow the implementation and the assessment of Intensity Modulated Radiation Therapy in France. IMRT is an innovative technique in which the high-dose radiation volume conforms to an accurately defined target volume with less morbidity to the surrounding normal tissues. The main medical objectives of the projects are (1) to improve the therapeutic index while decreasing acute toxicity and late sequelae (mainly xerostomia and acute mucite for head and neck tumors), which allows an increase in the radiation dose to the tumor and then a better tumor control; (2) to propose a salvage treatment to patients who locally recurred in previously irradiated sites; (3) to determine the optimal treatment guidelines for a safe use of the technique in clinical routine. Our projects also aim at comparing IMRT and 3D conformal treatments on the one hand (STIC 2001), and IMRT and conventional treatments on the other hand (STIC 2002), with regard to costs. As a matter of fact, the use of IMRT is presently limited in France because its implementation requires high investment and personnel costs. The seventeen French Regional Cancer Centres involved in the two projects intend to study the additional cost of the use IMRT in comparison with the use of standard techniques, which appears to be a step for a wide use of this technique in France. Each of the studies is two-year prospective, and includes patients with head and neck tumors treated with a curative intend (post operative or exclusive treatments for STIC 2002 and STIC 2002), and patients with a prostate cancer (STIC 2001).

Hyperthermia between 40 and 45 degrees C is now recognized to radiosensitive tumors locally increasing local control. The more recent technological progress show the possibility of heating at depth while controlling temperature by opened NMR. In Germany and Netherland, hyperthermia is a standard treatment for cervix carcinomas and for some sarcomas. Many on going clinical trials has been recently opened and a European network of excellence "Eurotherm" is proposed. More recently thermo-sensitive liposomes has been proposed in the US for carrying and targeting not only chemotherapeutics agents but also gene therapies. In France, these deep heating techniques are not applied. Today, only microwave superficial hyperthermia, thermo ablation using either radiofrequencies or high focussed ultrasound, and loco regional heating by intraperitoneal perfusion or by external circulation for tumors of the extremities, are in clinical evaluation. Is appears suitable to define clinical French teams, that could evaluate the clinical use of deep heating by the more recent developed techniques.

A review of the activity and techniques of total body irradiation (TBI) in France in the last 20 years is presented. In order to have on overall view of the activity and techniques of total body irradiation in France, the group of cancer centre radiation oncologists sent a questionnaire to all the cancer centres or public hospitals radiotherapy departments dealing with this treatment. Thirty-six questionnaires were sent and thirty-one departments answered. Three departments do not offer this treatment. Five departments did not answer. Results, therefore, concern the activity of the 28 departments that agreed to give detailed and clear answers. A total of 10 630 TBIs have been documented, 850 to 900 TBI have been done each year since 1995. Single fraction TBIs are used in only five centres and are being progressively abandoned. For multiple-fraction TBIs, the techniques described here are the ones used in 1999, at the time the questionnaires were sent. A majority (98%) of the teams used linear accelerators. The collected data are synthesised in tables. Nowadays, single fraction TBIs are only indicated in exceptional cases. Most of the TBIs are fractionated in six twice-daily fractions with pulmonary shielding to limit the dose between 6 and 11 Gy depending on departments' protocols and pathologies.

Purpose: Breast cancer rarely occurs in very young women, its diagnosis and management could sometimes be difficult. Our aim is to analyse the epidemiological and clinicopathological features of a group of very young women and especially to evaluate the results of therapeutic strategy., Methods: We report a retrospective study conducted at the department of radiotherapy in Alexis-Vautrin Centre, concerning 30 patients aged < or = 30 years in whom a diagnosis of invasive breast carcinoma was made between 1986 and 2001., Results: Six patients had familial history of breast cancer. Palpable tumor was found in 90% of cases, the average size was 3.5 cm. Eleven patients presented with stage I, 11 presented with stage II, 6 presented with stage III and 2 presented with stage IV. Five cancers were diagnosed after pregnancy (average tumor size = 5.8 cm). Eleven patients received neoadjuvant chemotherapy and 23 (82%) of 28 operable cases of invasive malignancy underwent breast conservative surgery (BCS). We found an invasive ductal carcinoma with grade III in 13/27 cases and a nodal involvement in a half of cases, 11 patients of 26 had no expression of oestrogen receptor. The average follow-up was 5 years: six patients (20%) recurred locally (all of them were initially treated by BCS), four patients developed a contralateral breast cancer and three developed a second malignancy. Ten patients died of their metastatic disease. The 5-year overall survival rate was 78%., Conclusion: Our results are consistent with those of the published reports and suggest that very young women with breast cancer have a poorer prognosis compared with the older ones. They should receive, according to their prognostic factors, an appropriate regional, systemic and hormonal therapy.

Acute mucositis is common after radiotherapy for head and neck cancers. During the past 3 decades, there was a gradual evolution in the treatment modalities for locally advanced carcinomas (concomitant radio-chemotherapy, accelerated radiotherapy). These new strategies are accompanied by an increase in early mucosal reactions. At the present time, there is no widely accepted prophylaxis or effective treatment. Many traditional remedies or new agents seem ineffective (Sucralfate, Chlorhexidine, GM-CSF, Silver nitrate, Prostaglandin, anti-oxidants, Benzydamine hydrochloride), while others seem promising (Povidone-iodine, nonabsorbable antibiotic lozenges and antifungals, local GM-CSF, Glutamide, Low-energy laser, corticosteroïds). Radioprotectors are controversial and should be only used in experimental protocols and not in routine practice. However, some recommendations can be proposed: general prevention and global care before cancer therapy should be systematic (oral hygiene, dental and periodontal treatment, advice to avoid the use of tobacco and alcohol); frequent oral rinsing with a bland mouthwash (Povidone-iodine or others) should be used at the start of treatment because there are significant modifications of the oral microflora increased by a disturbed salivary flow; these mouthwashes could be associated with nonabsorbable antibiotic lozenges or antifungal topicals (bicarbonates, Amphotéricine B); Systematic percutaneous fluoroscopic gastrostomy should be decided before any aggressive treatments (concomitant radio-chemotherapy, accelerated radiotherapy); pain should be controlled; finally, the radiation technique should be optimized (mucosal-sparing block, conformal radiotherapy and intensity-modulated radiation therapy).

Intensity modulated radiation therapy (IMRT) is an advanced method of conformal radiotherapy. It permits optimal dose distribution to the target volume while preserving surrounding normal tissues. IMRT, with a multileaf collimator, can be realised in two different ways: either the segmented mode, which consists of combining small elementary static field, or the dynamic mode, which consists of moving the leaves while irradiating. The purpose of this work was to study these two methods of modulation on a Varian linear accelerator equipped with a collimator consisting of 40 pairs of one-centimetre-wide leaves. The measurements, obtained by using a diode array, showed that the quality of the irradiation in the dynamic mode does not depend on either the dose rate or the duration of the irradiation. In the segmented mode, weak magnitude segments are preferable, but increase the errors in the delivered dose. Comparisons of various profiles showed that the measured profiles are consistent with those programmed. Both modes seem to be equivalent for step-shaped profiles. In the case of profiles with constant slope, the segmentation generated by the segmented method deteriorates the profile. Even though the choice of technique is strongly dependent on the material available, the dynamic mode presents greater flexibility of use and has been chosen in our institution for IMRT.

The objectives of this prospective study was to define the comparative ability of stress myocardial scintigraphy and dobutamine stress echocardiography to demonstrate post-MI myocardial viability, assessed on the functional recovery in terms of improvement of global and segmental kinetics by cardiac gamma-angiography after revascularization. 18 patients (11 anterior MI, 7 lateral or inferior MI) and 162 segments were analysed semiquantitatively. All patients with persistent significant stenosis underwent secondary revascularization of the artery responsible for myocardial infarction. The prevalence of viability was high, as only 34% of segments initially presented a segmental kinetic abnormality and contraction was improved at 6 months in 54% of cases. Stress scintigraphy and dobutamine echocardiography detected viability with a sensitivity of 96% and 70%, a specificity of 88% and 82%, a positive predictive value of 89% and 77% and a negative predictive value of 95% and 76%, respectively. Only the wall score index with low-dose dobutamine was correlated with the ejection fraction at 6 months. Stress echocardiography is a more reliable predictor of the degree of functional recovery after revascularization. Scintigraphy visualizes much more extensive abnormalities than echocardiography. This often corresponds to ischaemic territories with normal contraction under baseline conditions and low doses of dobutamine. It therefore seems preferable both examinations for optimal assessment of thrombolized patients following myocardial infarction.

The outcome of head and neck malignancies is closely related to the achievement of local tumor control. The occurrence of severe late complications is the consequence of the anatomic vicinity between dose-limiting normal tissues and the tumor, thus reducing the curative potential of radiotherapy. Conformal radiotherapy is presently actively investigated as a way to improve the dose distribution in head and neck malignancies (especially when originating from the nasopharynx or the sinuses) while protecting healthy organs. Such an approach requires a chain of sophisticated procedures, including efficient quality assurance programs, in order to achieve the proper degree of safety. The relatively limited clinical studies published to-date have already confirmed the advantage of conformal radiotherapy in terms of dose delivery. The development of beam intensity modulation is likely to further contribute to the improvement of the therapeutic ratio.

Context: The <> (SOR), started in 1993, are a collaborative project between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcomes for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary experts group, with feedback from specialists in cancer care delivery. The initial guidelines are being updated in case of new evidence., Objectives: To update the clinical practice guideline [39] with definitions of new Standards, Options and Recommendations for the use of recombinant human erythropoietin (rHuEPO) in oncology., Methods: Data have been identified by literature search using Medline, Current Contents, Embase, Cancerlit (march 1996-march 1999). The main end points considered were hemoglobin level, haematocrit, quality of life, transfusion requirements, incidence and length of hospital stays, efficacy of cancer treatment, safety and costs. Once the guideline was updated and defined, the document was submitted to 42 reviewers for peer review, and to the medical committees of the 20 French Cancer Centres for review and agreement., Results: The new key recommendations are: 1) The use of recombinant human erythropoietin in oncology is an alternative to treat chemotherapy-induced anemia when the chemotherapeutic regimen contains platinum; 2) Cancer-induced anemia reduces patients' quality of life. Treatment of anemia by transfusions of erythropoietin may improve quality of life; 3) We recommend assessment of haemoglobin levels during radiation therapy and the possible use of erythropoietin to optimise the efficacy of radiation therapy; 4) Erythropoietin is effective in others pathologies (multiple myeloma, non-Hodgkin lymphoma, non-platinum based chemotherapy.) and also in pediatric patients but the risk/benefit ratio for anemia therapy (i.e. transfusion or erythropoietin therapy) must be analysed for each individual; 5) We recommend an economic analysis of the need of erythropoietin within the context of the french health care system.

Purpose: In a retrospective analysis, our aim was to evaluate the immediate tolerance and the early and late complications of abdomino-pelvic radiotherapy in the Centre Alexis-Vautrin (France)., Patients and Methods: From 1st January 1983 to 31st December 1993, 117 patients were treated at Centre Alexis Vautrin in Nancy for epithelial ovarian cancer by abdominal and/or pelvic irradiation after surgery. They were aged from 24 to 85 with a median of 56 years. There were ten patients with stage I (9%), 28 patients with stage II (24%), 60 patients with stage III (61%) and 19 patients with stage IV (16%) disease. Results of surgery were determined as follows: satisfactory with absence of tumoral residuum in 26% cases (30 patients) and with residuum inferior to 20 mm in 46% cases (52 patients; incomplete in 26% cases (31 patients) either because of residuum superior in 20 mm and/or incomplete surgery; and not evaluable in 3% cases (four patients). Seventy-seven patients were sent to the Centre for postoperative treatment (66% patients of the series), 48 of them (62.4%) after non-satisfactory surgery, 29 after satisfactory surgery (37.6%). Chemotherapy was administered to only 104 patients (89% cases), and contained platinum salts and cyclophosphamid for 87% of these patients. Fourteen patients (12%) received a single irradiation dose after surgery: three in stage I, three with poor evaluation of the disease in the initial stage, three with medical contraindications to chemotherapy treatment, six with contraindications due to advanced age (?? Makes 15 ). Histologically, 46% of patients had a serous adenocarcinoma, 9% a mucinous adenocarcinoma, 11% an endometrioid adenocarcinoma, 2% a clear cell adenocarcinoma, 1% an undifferentiated adenocarcinoma, and 31% an epithelial carcinoma without any other indication. The histological grade which was recently introduced was rarely indicated. Complementary radiotherapeutic treatment consisted of pelvic irradiation for 14 patients (12%), abdomino-pelvic irradiation for 63 patients (54%), and total abdominal irradiation with a pelvic boost for 40 patients (34%)., Results: The immediate tolerance to irradiation can be considered as globally satisfactory since 9% of the patients (ten cases) had no problems and 64% of the patients developed a minor intolerance easily controlled by symptomatic treatments. There were also digestive complications: nausea, vomiting and diarrhea for 66% of the patients (50 cases); to a lesser extent, 20% of the cases experienced associated digestive and hematological complications (15 patients); 9% isolated hematological troubles such as anemia (seven patients); 4% digestive complications (three patients) and 1% hematological and urinary digestive troubles (one patients). Late irradiation sequelae were evaluated for 89 patients with a follow-up lasting from 4 months to 11 years. Sixty-six patients had no sequelae, eleven patients had minor tolerability problems--mainly digestive for more than half of them. Five patients presented severe complications, including hematological problems such as chronic thrombopenia in two cases, urinary-problems in two other cases, and one patient presented with a case of histologically proven malabsorption. Two patients presented major problems; one case of radic cystitis and one of radic bowel. Two patients died of iatrogenic causes: one of induced leukemia, the other of treatment-induced digestive and renal complications. The overall survival rate was 30% at 5 years and 22% at 10 years. It was 90% at 5 and 10 years for stage I patients, 60% at 5 years and 30% at 10 years for stage II patients, 22% at 5 years and 8% at 10 years for stage III patients, and finally 10% at 5 years for stage IV patients., Conclusion: In this retrospective analysis of 117 epithelial ovarian cancers, treated over 10 years and which all received pelvic and/or abdominal irradiation, we can conclude that this treatment is globally well tolerated and that it yields a

Purpose: From 1975 to 1996, 98 patients with infiltrative vesical carcinomas were treated at the Centre Alexis Vautrin by conservative surgery and interstitial brachytherapy (192lr). The mean follow-up was about eight years. From this retrospective non randomized study, we tried to determine the tolerance to this treatment., Materials and Methods: There were 86 men and 12 women. The mean age was 63 years. We found three pTis tumors, 28 stage pT1 tumors, 38 stage pT2 tumors, 24 stage pT3A tumors, four stage pT3B tumors and one stage Tx tumors. The therapeutic scheme consisted of pelvic radiation therapy (3 fractions of 3,5 Gy) immediately followed by lymphadenectomy (for stage pT3 tumors) and by cystotomy or partial cystectomy during which we inserted brachytherapy plastic tubes. The delivered dose was 50 Gy for superficially infiltrative tumors and 30 Gy for deeply infiltrative tumors; at the lowest dose, the treatment ended with external beam irradiation., Results: At 5 years the control rate was 72%, the specific survival 80% and the global survival 71%. Twenty-nine patients had a local recurrence. Of these, seven underwent total cystectomy. Thirty-seven patients developed 43 complications; 35 were intravesical, 10 (28%) were estimated to be higher than grade 2 because of technical problems that led us to modify the technique., Conclusion: It is essential to develop close collaboration between surgeons and brachytherapists, to select patients and to use a rigorous technique. Interstitial brachytherapy for infiltrative vesical carcinomas thus yields both high local control and satisfying results in regard to patient's well-being.

Unlabelled: The "Standards, Options and Recommendations" (SOR), started in 1993, are a collaborative project between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcomes for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary experts group, with feedback from specialists in cancer care delivery., Objectives: To develop a clinical practice guideline with definitions of Standards, Options and Recommendations for the use of recombinant human erythropoietin (rHuEPO) in oncology., Methods: Data have been identified by literature search using Medline (up to march 1996) and Current Contents (up to october 1996) and personal references lists. The main end points considered were hemoglobin level, haematocrit, quality of life, transfusion requirements, incidence and length of hospital stays, efficacy of cancer treatment, safety and costs. Once the guideline was defined, the document was submitted to 39 reviewers for peer review, and to the medical committees of the 20 French Cancer Centres for review and agreement., Results: The key recommendations are: 1) the use of recombinant human erythropoietin in oncology is validated for chemotherapy-induced anemia when the chemotherapeutic regimen contains platinum. In other cases, we recommend to suggest patients participating in prospective clinical trials; 2) for chemotherapy (platinum based)-induced anemia, the benefits/risks ratio for anemia therapy (i.e. transfusion or erythropoietin therapy) must be analysed for each individual patient; 3) we recommend participation in studies to identify predictive factors for non-response to erythropoietin therapy to select non-responding patients; 4) to investigate the clinical benefit of erythropoietin therapy for anemia due to intensive cytotoxic chemotherapy and radiation therapy, we recommend to suggest patients participating in large multicentre phase III trials; 5) at the present time, there is insufficient evidence to recommend the use of erythropoietin therapy in children.

From 1977 to 1991, we treated 361 carcinomas of the velotonsillar region, either by brachytherapy alone (18 cases), or by an association of external radiotherapy and brachytherapy (343 patients). The latter was performed using a special technique with iridium wires in plastic tubes with afterloading. The primary was the tonsil in 128 patients, the soft palate in 134 patients. We numbered also 9 posterior pillars, 63 anterior pillars and 27 velotonsillar sulcus. According to the UICC staging system (28), we classified the patients in 90 T1, 141 T2, 119 T3, 2 T4, 9 Tx with 230 N0, 93 N1, 9 N2, 20 N3 and 9 Nx. The results at 5 and 10 years show respectively: local control (LC) 80% and 75%, locoregional control 75% and 70%, global survival 53% and 28%, specific survival 63% and 52%. The univariate study shows at 5 years a better local control for T1-T2 (87%) than for T3 (67%) with p = 0.00004. The locoregional control is better for N0 (80%) than for N+ (66%) with p = 0.002, this is the same for global survival (59% versus 42%, p = 0.002). The two groups were individualised according to the primary. Inside each of these groups, the prognosis is identical for different localisations, which allows to put them together. We can therefore distinguish a group A which includes the tonsil, the soft palate and posterior pillar. This group has a better prognosis (controls and survivals) than group B (anterior pillar and velotonsillar sulcus) (p < 0.002). The tumours extended to the mobile tongue, the base of the tongue or the velotonsillar sulcus have a poorer prognosis than those without propagation or with an upwards propagation (p < 0.002). The statistical study of radiobiological factors that can influence the tissular repair shows that there are less recurrences if the duration of treatment is inferior to 55 days and if the interval between external irradiation and brachytherapy is inferior to 20 days. A sufficient safety margin seems also necessary for a good local control. The dose rate within the limits used does not seem to influence the local control and the total dose delivered to the tumour, but this is not surprising since the highest doses are given to the tumours with the smallest regression during external irradiation. The multivariate study for local control shows that the most significant factors are the T, the tumoral localisation and the total duration of treatment. For complications (classified in 4 stages), the dose rate is the most significant factor.

Unlabelled: Radiation therapy has considerably evolved in 1 century. After the revolution due to cobalt in the beginning of the sixties, we are now entering the 2nd revolution in three fields in external radiotherapy., Methodology: the development of quality assurance programmes gives the guarantee that the treatment is done as it is prescribed. Technology: recent developments allow conformal radiation therapy which permits to increase the dose without increasing side effects. Biology: the implementation of predictive assays will permit to choose the best modality of treatment for each patient. In brachytherapy, the use of high dose rate radioactive sources increases indications in locations not yet accessible. Pulse dose rate brachytherapy increases radio-protection and will make optimization possible in complex volumes. In the future, indications of curative radiotherapy will probably increase in regard to earlier diagnosis of many cancers and to increase of efficacy of general treatments on metastatic disease.

The study bears on 672 infiltrating carcinomas of the cervix treated from 1977 until the end of 1991, by a radiosurgical combination (311 patients) or by exclusive irradiation (361 patients). The radiosurgical series includes mostly stages IB and II and patients under 50 years because of the therapeutic protocol. Most of the patients aged over 50 years and all stages III were treated by exclusive irradiation. External beam irradiation was most often performed in 4 fields by linear accelerator of 12 and 25 MeV. Uterovaginal brachytherapy used the technique of molds. In 55 cases, a complementary interstitial brachytherapy was applied on residual node. A computer dosimetry was made for each patient with calculation of the doses delivered to organs at risk and to node areas (points of calculation ICRU n degrees 38). The results at 5 years are as follows for the total series: locoregional control (LRC) 79%, specific survival (SS) 73%, overall survival 70%. For stage I, the LRC of the radiosurgical series is 92%, that of the series of exclusive irradiation 87% (no significant difference, neither for SS if we consider the tumoral size); For stage II, the LRC is 70% in the radiosurgical series and 79% in the series of exclusive irradiation. There is no difference if proximal stage II is compared. Conversely, for distal stage II, the difference is very significant in favour of exclusive irradiation (LRC 31%/77%, SS 26%/70%, p < 0.006). If we consider the results according to age, the difference for distal stage II comes mostly from patients under 50 years and especially those aged 40 years or under. For stage III, the LRC is 61% for patients over 50 years and 34% for those aged 50 years or under (p = 0.006). As the nodes, the results of surgical pieces and lymphadenectomy are studied. The patients under 40 years in stages II and III present more metastases than others (p = 0.003). Among the therapeutic factors, the dose rate and the treatment duration were particularly studied. A detailed study of the complications is made for the radiosurgical series as for the series of exclusive irradiation according to the French Italian glossary of complications as well as a study of the factors inducing them.

Thymomas is a rare disease. Staging systems and surgical adjuvant treatments remain controversial. We retrospectively reviewed the outcome and the prognostic factors in a series of 149 patients with non metastatic thymomas treated in ten French cancer centers between 1979 and 1990. Patients were staged according to the "GETT" classification derived from that of Masaoka. There were 13 stage I patients, 46 stage II, 58 stage III and 32 stage IV. Surgery consisted of complete resection in 63 patients, partial resection in 31 patients and biopsy alone in 55 patients. All patients received postoperative radiation therapy and 74 were given postoperative chemotherapy. Median follow-up was 7.7 years. Local control was obtained in 117 patients (78.5%) and was influenced by the extent of surgery (p < 0.0001). Metastases occurred in 26 patients. Seven patients developed grade 3-4 pulmonary and heart complications. One patient developed a malignant lymphoma after 24 cycles of chemotherapy. Disease-free survival (DFS) rates were of five years 92%, 75%, 60%, 39% and 48% in stage I, II, IIIA, IIIB and IVA patients, respectively. After complete resection, partial resection and biopsy alone, these rates were 74%, 60% and 38%, respectively. With a multivariate analysis, DFS rates were influenced by the extent of surgery (p < 0.001) and by chemotherapy (p < 0.001). Three other factors could predict a worse DFS: young age (p < 0.006), stages III-IV (p < 0.04) and mediastinal symptoms (p < 0.001), "GETT" staging correlated well with local control and survival. After complete resection, a 50 Gy postoperative radiation therapy can be recommended in patients with invasive thymomas. Despite a 65% local control rate after partial resection or biopsy alone in this series, a higher dose of radiation (> 60 Gy) must be evaluated. Despite the benefit of the chemotherapy in this retrospective and multicentric study, the role of this treatment remains to be assessed.

Between November 1991 and June 1992, 50 patients suspected of pulmonary embolism (SP > 20%) underwent Doppler echocardiography, venous Doppler ultrasonography and pulmonary angiography. Pulmonary embolism was confirmed by pulmonary angiography in all patients but 3 (2 pts: mean pulmonary pressure > 50 mmHg and 1 pt: mobile thrombus between the infundibulum and the main pulmonary artery). Two groups were identified on the basis of Miller's index: Group 1: "non-massive" pulmonary embolism, Miller < 60% (n = 18); Group 2: "massive" pulmonary embolism, Miller > or = 60% (n = 29). The patient with thrombus in the main pulmonary artery and the two with high pulmonary pressures were included in Group 2. Venous Doppler ultrasonography was performed in 96% (n = 48) of patients, including 90% within the first 24 hours. No distinction could be drawn between the two groups on the basis of venous Doppler ultrasonography findings. A majority of patients had thrombosis of main collecting vessels (Group 1 = 75%, Group 2 = 78%) and 10% of patients had no venous thrombosis of the lower limbs. Doppler echocardiography was performed in all patients, including 94% (n = 47) within the first 24 hours. Dilatation of the left ventricle as well as analysis of septal contraction was evaluable in all patients except one of Group 2, because of poor technical quality and of artificial pacing. A RV/LV ratio > 0.60 was found in 97% (30/31) of patients of Group 2 as compared with 39% (7/18) in Group 1.(ABSTRACT TRUNCATED AT 250 WORDS)