ANALYSE DE MARQUEURS INTERMEDIAIRES POUR L'ESTIMATION DU RISQUE VASCULAIRE AU COURS DE NOUVELLES APPROCHES THERAPEUTIQUES (GASTROPLASTIE POUR OBESITE SEVERE ET TRAITEMENT SUBSTITUTIF DU DEFICTIT EN HORMONE DE CROISSANCE DE L'ADULTE)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Perception des essais cliniques par les patients et les investigateurs : enquête à l'hôpital Neuro-Cardiologique de Lyon

Objectif : Ce travail présente une première enquête conduite auprès de patients et d'investigateurs français, pour évaluer leurs motivations, les bénéfices et contraintes liées à leur participation à l'essai. Méthode : Vingt investigateurs et 37 patients ont été interrogés via un questionnaire. Résultats : La principale motivation du patient est l'altruisme contrairement à l'investigateur qui recherche prioritairement un bénéfice pour son patient. Après participation, le patient souligne sa satisfaction d'avoir pu aider la médecine. L'amélioration de son propre état de santé semble secondaire. Le risque principal lié à l'essai est celui d'être inclus dans le bras placebo. L'investigateur estime quant à lui avoir pu acquérir un savoir faire. Les contraintes sont essentiellement logistiques. Par ailleurs, il existe une divergence de perception d'un même essai entre le patient et l'investigateur, ce dernier surestimant généralement les contraintes de l'essai pour le patient. Conclusion : La connaissance des ces éléments est utile pour améliorer le recrutement des patients qui s'avère encore difficile en France

Perception des essais cliniques par les patients et les investigateurs : revue bibliographique (1

Objectif - Méthode : L'objectif de ce travail bibliographique (base de données Medline, période 1966-2005) est de recenser les motivations des patients et des investigateurs, avant participation à un essai clinique et leurs perceptions, en cours ou après participation. Résultats : Sur 79 publications (3 françaises), 27 enquêtes anglo-saxonnes ont été menées auprès de patients et d'investigateurs. Leurs principales attentes sont respectivement l'altruisme et la recherche d'un bénéfice direct pour le patient. Après participation, si le patient souligne le réconfort psychologique reçu, l'investigateur est satisfait d'avoir fait accéder son patient à un nouveau traitement. L'investigateur évoque surtout des contraintes logistiques, tandis que le patient dénonce le principe de randomisation et l'inconfort lié aux multiples examens. Enfin, toutes les attentes de l'investigateur semblent satisfaites, contrairement à celles du patient. Conclusion : La connaissance de la perception de l'essai clinique par ces acteurs est indispensable aux professionnels de santé, notamment pour améliorer le recrutement

Practical dosimetry of peptide receptor radionuclide therapy with (90)Y-labeled somatostatin analogs.

The challenge for internal therapy is to deliver the highest possible dose to the tumor while sparing normal organs from damage. Currently, the potential risk of kidney and red marrow toxicity limits the amount of radioactivity that may be administered. An accurate dosimetry method that would provide reliable dose estimates to these critical organs and to tumors before therapy would allow the clinician to plan a specific therapeutic regimen and also select those patients who would benefit the most from treatment. The dosimetry for (90)Y-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotide is usually based on quantitative imaging at different time points that provides information on activity retention in organs over time and on stylized models representing average individuals. Because the therapeutic agent labeled with (90)Y is not suitable for quantitative imaging, the peptide surrogate labeled with the positron emitter (86)Y can be considered the most appropriate tracer for measuring distribution and retention of the radiopharmaceutical over time. Dose calculations in target organs are generally performed using the MIRDOSE program, in which S values from source to target are integrated. Significant improvement of dose estimates may be achieved by introducing patient-specific adjustments to the standard models. The use of individual kidney volumes assessed by CT instead of the use of a fixed volume for males and females may significantly improve the determination of kidney radiation doses. The use of actual CT-derived tumor volumes has also shown a dose-efficacy relationship. Additional improvements in this field include the validation and use of an (111)In surrogate to avoid the complexity of (86)Y use and the consideration of radiobiologic parameters, such as fractionation effects and the specific biologic efficacy of internally deposited radiation, which are probably underestimated using currently available methods

Patient-specific Dosimetry in predicting renal toxicity with Y-90-DOTATOC: Relevance of kidney volume and dose rate in finding a dose-effect relationship

Nephrotoxicity is the major limiting factor during therapy with the radiolabeled somatostatin analog Y-90-1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA)-D-Phe(1)-Tyr(3)-octreotide (DOTATOC). Pretherapeutic assessment of kidney absorbed dose could help to minimize the risk of renal toxicity. The aim of this study was to evaluate the contribution of patient-specific adjustments to the standard dosimetric models, such as the renal volume and dose rate, for estimating renal absorbed dose during therapy with Y-90-DOTATOC. In particular, we investigated the correlation between dose estimates and effect on renal function after therapy. Methods: Eighteen patients with neuroendocrine tumors (9 men and 9 women; median age, 59 y) underwent treatment with 90Y-DOTATOC (8.1-22.9 GBq) after pretherapeutic biodistribution study with Y-86-DOTATOC. Kidney uptake and residence times were measured and the absorbed dose (KAD) was computed using either the MIRDOSE3.1 software assuming a standard kidney volume (KAD(StdVol)) or the MIRD Pamphlet 19 values and the actual kidney cortex volume determined by pretherapeutic CT (KAD(CTVol). For each patient, the biologic effective dose (BED) was calculated according to the linear quadratic model to take into account the effect of dose rate and fractionation. Renal function was evaluated every 6 mo by serum creatinine and creatinine clearance (CLR) during a median follow-up of 35.5 mo (range, 18-65 mo). The individual rate of decline of renal function was expressed as CLR loss per year. Results: KAD(CTVol) ranged between 19.4 and 39.6 Gy (mean, 28.9 +/- 5.34 Gy). BED, obtained from KAD(CTVol), ranged between 27.7 and 59.3 Gy (mean, 40.4 +/- 10.6 Gy). The CLR loss per year ranged from 0% to 56.4%. In 12 of 18 patients, CLR loss per year was 20% received a BED >45 Gy. Patients who were treated with low fractionation were those with the highest rate of renal function impairment. Conclusion: Radiation nephrotoxicity after 90Y-DOTATOC therapy is dose dependent. Individual renal volume, dose rate, and fractionation play important roles in an accurate dosimetry estimation that enables prediction of risk of renal function impairment

Patient-specific dosimetry in predicting renal toxicity with (90)Y-DOTATOC: relevance of kidney volume and dose rate in finding a dose-effect relationship.

Nephrotoxicity is the major limiting factor during therapy with the radiolabeled somatostatin analog (90)Y-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-d-Phe(1)-Tyr(3)-octreotide (DOTATOC). Pretherapeutic assessment of kidney absorbed dose could help to minimize the risk of renal toxicity. The aim of this study was to evaluate the contribution of patient-specific adjustments to the standard dosimetric models, such as the renal volume and dose rate, for estimating renal absorbed dose during therapy with (90)Y-DOTATOC. In particular, we investigated the correlation between dose estimates and effect on renal function after therapy. METHODS: Eighteen patients with neuroendocrine tumors (9 men and 9 women; median age, 59 y) underwent treatment with (90)Y-DOTATOC (8.1-22.9 GBq) after pretherapeutic biodistribution study with (86)Y-DOTATOC. Kidney uptake and residence times were measured and the absorbed dose (KAD) was computed using either the MIRDOSE3.1 software assuming a standard kidney volume (KAD(StdVol)) or the MIRD Pamphlet 19 values and the actual kidney cortex volume determined by pretherapeutic CT (KAD(CTVol)). For each patient, the biologic effective dose (BED) was calculated according to the linear quadratic model to take into account the effect of dose rate and fractionation. Renal function was evaluated every 6 mo by serum creatinine and creatinine clearance (CLR) during a median follow-up of 35.5 mo (range, 18-65 mo). The individual rate of decline of renal function was expressed as CLR loss per year. RESULTS: KAD(CTVol) ranged between 19.4 and 39.6 Gy (mean, 28.9 +/- 5.34 Gy). BED, obtained from KAD(CTVol), ranged between 27.7 and 59.3 Gy (mean, 40.4 +/- 10.6 Gy). The CLR loss per year ranged from 0% to 56.4%. In 12 of 18 patients, CLR loss per year was 20% received a BED >45 Gy. Patients who were treated with low fractionation were those with the highest rate of renal function impairment. Conclusion: Radiation nephrotoxicity after (90)Y-DOTATOC therapy is dose dependent. Individual renal volume, dose rate, and fractionation play important roles in an accurate dosimetry estimation that enables prediction of risk of renal function impairment

Post-surgical management of non-functioning pituitary adenoma

Post-surgical surveillance of non-functioning pituitary adenoma (NFPA) is based on magnetic resonance imaging (MRI) at 3 or 6 months then 1 year. When there is no adenomatous residue, annual surveillance is recommended for 5 years and then at 7, 10 and 15 years. In case of residue or doubtful MRI, prolonged annual surveillance monitors any progression. Reintervention is indicated if complete residue resection is feasible, or for symptomatic optic pathway compression, to create a safety margin between the tumor and the optic pathways ahead of complementary radiation therapy (RT), or in case of post-RT progression. In case of residue, unless the tumor displays elevated growth potential, it is usually recommended to postpone RT until progression is manifest, as efficacy is comparable whether treatment is immediate or postponed. The efficacy of the various RT techniques in terms of tumor volume control is likewise comparable. RT-induced hypopituitarism is frequent, whatever the technique. The choice thus depends basically on residue characteristics: size, delineation, and proximity to neighboring radiation-sensitive structures. Reduced rates of vascular complications and secondary brain tumor can be hoped for with one-dose or hypofractionated stereotactic RT, but there has been insufficient follow-up to provide evidence. Somatostatin analogs and dopaminergic agonists have yet to demonstrate sufficient efficacy. Temozolomide is an option in aggressive NFPA resistant to surgery and RT.Après chirurgie, la surveillance des adénomes hypophysaires non fonctionnels (AHNF) repose sur l’imagerie par résonance magnétique (IRM) réalisée 3, voire 6 mois, puis un an après l’intervention chirurgicale. En l’absence de reliquat adénomateux, une surveillance annuelle est recommandée pendant 5 ans, puis 7, 10 et 15 ans après la chirurgie. En cas de reliquat ou d’image douteuse, une surveillance annuelle prolongée précisera l’évolutivité éventuelle de la lésion. Une seconde intervention chirurgicale est justifiée en cas de possibilité d’exérèse complète d’un reliquat, de compression symptomatique des voies optiques, afin de garder une distance de sécurité entre la tumeur et les voies optiques avant irradiation complémentaire ou en cas de progression tumorale après radiothérapie. En présence d’un reliquat, il est le plus souvent justifié (sauf si la tumeur manifeste un potentiel de croissance élevé) de différer la radiothérapie au moment où ce reliquat évolue, son efficacité étant comparable que le traitement soit réalisé d’emblée ou différé. L’efficacité des différentes techniques de radiothérapie sur le contrôle du volume tumoral est comparable. L’hypopituitarisme radio-induit est fréquent, quelle que soit la technique utilisée. Le choix dépendra donc essentiellement des caractéristiques du reliquat (taille, limites, proximité des structures radio-sensibles avoisinantes). Avec les radiothérapies stéréotaxiques en dose unique ou hypo-fractionnées, on espère une fréquence moindre des complications vasculaires et des rares tumeurs cérébrales secondaires ; mais le recul reste insuffisant. Les analogues de la somatostatine et les agonistes dopaminergiques n’ont pas fait la preuve jusqu’alors d’une efficacité suffisante. Le témozolamide peut être discuté chez les patients présentant des AHNF agressifs après chirurgie et radiothérapie