The Experts below are selected from a list of 126 Experts worldwide ranked by ideXlab platform
J Castelli - One of the best experts on this subject based on the ideXlab platform.
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intensity modulated radiotherapy for prostate cancer with seminal vesicle involvement t3b a multicentric retrospective analysis
PLOS ONE, 2019Co-Authors: F Goupy, S Supiot, D Pasquier, I Latorzeff, Ulrike Schick, Erik Monpetit, G Martinage, C Herve, Bernadette Le Proust, J CastelliAbstract:Objectives No study has reported clinical results of external-beam radiotherapy specifically for T3b prostate cancer. The possibility of escalating the Dose to the involved seminal vesicles (ISV) while respecting the Dose constraints in the organs at risk is thus so far not clearly demonstrated. The objective of the study was to analyze the Dose distribution and the clinical outcome in a large series of patients who received IMRT for T3b prostate cancer. Materials and methods This retrospective analysis included all patients who received IMRT and androgen deprivation therapy for T3b prostate cancer, between 2008 and 2017, in six French institutions, with available MRI images and dosimetric data. Results A total of 276 T3b patients were included. The median follow-up was 26 months. The median (range) prescribed Doses (Gy) to the prostate and to the ISV were 77 (70–80) and 76 (46–80), respectively. The Dose constraint recommendations were exceeded in less than 12% of patients for the rectum and the bladder. The 5-year risks of biochemical and clinical recurrences and cancer-specific death were 24.8%, 21.7%, and 10.3%, respectively. The 5-year risks of local, pelvic lymph node, and metastatic recurrences were 6.4%, 11.3%, and 15%, respectively. The number of involved lymph nodes (≤ 2 or ≥ 3) on MRI was the only significant prognostic factor in clinical recurrence (HR 9.86) and death (HR 2.78). Grade ≥ 2 acute and 5-year late toxicity rates were 13.2% and 12% for digestive toxicity, and 34% and 31.5% for urinary toxicity, respectively. The Dose to the pelvic lymph node and the age were predictive of late digestive toxicity. Conclusion IMRT for T3b prostate cancer allows delivery of a Curative Dose in the ISV, with a moderate digestive toxicity but a higher urinary toxicity. Lymph node involvement increases the risk of recurrence and death.
F Goupy - One of the best experts on this subject based on the ideXlab platform.
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intensity modulated radiotherapy for prostate cancer with seminal vesicle involvement t3b a multicentric retrospective analysis
PLOS ONE, 2019Co-Authors: F Goupy, S Supiot, D Pasquier, I Latorzeff, Ulrike Schick, Erik Monpetit, G Martinage, C Herve, Bernadette Le Proust, J CastelliAbstract:Objectives No study has reported clinical results of external-beam radiotherapy specifically for T3b prostate cancer. The possibility of escalating the Dose to the involved seminal vesicles (ISV) while respecting the Dose constraints in the organs at risk is thus so far not clearly demonstrated. The objective of the study was to analyze the Dose distribution and the clinical outcome in a large series of patients who received IMRT for T3b prostate cancer. Materials and methods This retrospective analysis included all patients who received IMRT and androgen deprivation therapy for T3b prostate cancer, between 2008 and 2017, in six French institutions, with available MRI images and dosimetric data. Results A total of 276 T3b patients were included. The median follow-up was 26 months. The median (range) prescribed Doses (Gy) to the prostate and to the ISV were 77 (70–80) and 76 (46–80), respectively. The Dose constraint recommendations were exceeded in less than 12% of patients for the rectum and the bladder. The 5-year risks of biochemical and clinical recurrences and cancer-specific death were 24.8%, 21.7%, and 10.3%, respectively. The 5-year risks of local, pelvic lymph node, and metastatic recurrences were 6.4%, 11.3%, and 15%, respectively. The number of involved lymph nodes (≤ 2 or ≥ 3) on MRI was the only significant prognostic factor in clinical recurrence (HR 9.86) and death (HR 2.78). Grade ≥ 2 acute and 5-year late toxicity rates were 13.2% and 12% for digestive toxicity, and 34% and 31.5% for urinary toxicity, respectively. The Dose to the pelvic lymph node and the age were predictive of late digestive toxicity. Conclusion IMRT for T3b prostate cancer allows delivery of a Curative Dose in the ISV, with a moderate digestive toxicity but a higher urinary toxicity. Lymph node involvement increases the risk of recurrence and death.
Virginie Siguret - One of the best experts on this subject based on the ideXlab platform.
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safety profile of tinzaparin administered once daily at a standard Curative Dose in two hundred very elderly patients
Drug Safety, 2002Co-Authors: Eric Pautas, Isabelle Gouin, Oliver Bellot, J P Andreux, Virginie SiguretAbstract:Objectives: Too few very elderly patients with an age-related renal impairment are included in clinical trials. We conducted a study in order to evaluate the safety profile of tinzaparin, a low molecular weight heparin (LMWH), given at a Curative Dose (175 IU/kg once daily) in very elderly patients treated for up to 30 days.
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elderly patients treated with tinzaparin innohep administered once daily 175 anti xa iu kg anti xa and anti iia activities over 10 days
Thrombosis and Haemostasis, 2000Co-Authors: Virginie Siguret, Eric Pautas, J P Andreux, M Fevrier, C Wipff, B Durandgasselin, M Laurent, M Durso, Pascale GaussemAbstract:Since low molecular weight heparins (LMWH) are partly eliminated by renal excretion, their pharmacodynamic profile may be modified in very elderly patients with age-related renal impairment. The aim of this prospective study was to determine whether tinzaparin (Innohep) 175 anti-Xa IU/kg administered subcutaneously once daily over 10 days does accumulate in hospital patients greater than 70 years of age. Plasma anti-Xa and anti-IIa amidolytic levels and APTT were determined prior to the first injection (day 0), and then, at peak level i.e. 5 h after the second injection (day 2) and subsequently on days 5, 7 and 10. Thirty consecutive inpatients (6 men, 24 women) requiring LMWHs at a Curative Dose for acute thromboembolic disease were included. Patients' characteristics (mean +/- SD) were: age 87.0+/-5.9 years (range 71-96), body weight 62.7+/-14.6 kg (range 38-90) and creatinine clearance 40.6+/-15.3 mL/min (range 20-72). The mean actual Dose of tinzaparin delivered was 174.8 anti-Xa IU/kg. Since no patient had an anti-Xa activity above 1.5 IU/mL, the Dose of tinzaparin remained fixed over 10 days. Anti-Xa and anti-IIa peak levels measured on day 2 were 0.66+/-0.20 IU/mL (range 0.26-1.04) and 0.33+/-0.10 IU/mL (range 0.18-0.55), respectively. Ex vivo anti-Xa/anti-IIa ratios were close to 2.1. APTT ratios (patient/control) were strongly correlated with anti-IIa activity (p <0.01). There was no progressive increase of the anti-Xa and anti-IIa activities after repeated administration of tinzaparin over the 10 day treatment period. No correlation was found between anti-Xa and anti-IIa activities and age, weight, or creatinine clearance. No major bleeding occurred during the study and only one minor haematoma at the injection site was reported. No thrombo-embolic complication or death occurred. Tinzaparin may thus be administered safely at a treatment Dose (175 anti-Xa IU/kg) in older patients with age-related renal impairment. Neither Dose adjustment, nor serial anti-Xa activity monitoring seems to be required in patients with creatinine clearance above 20 mL/min during the first ten day treatment.
Nicholas J White - One of the best experts on this subject based on the ideXlab platform.
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oral artesunate Dose response relationship in acute falciparum malaria
Antimicrobial Agents and Chemotherapy, 2002Co-Authors: Brian Angus, Itaporn Thaiaporn, Kenechanh Chanthapadith, Yupin Suputtamongkol, Nicholas J WhiteAbstract:The combination of an oral artemisinin derivative (usually artesunate) and mefloquine has become standard treatment for multidrug-resistant falciparum malaria in several parts of Southeast Asia. The Doses of artesunate used in monotherapy and combination treatment have largely been derived empirically. In order to characterize the in vivo Dose-response relationship for artesunate and thus rationalize dosing, 47 adult patients with acute uncomplicated falciparum malaria and parasitemia > or = 1% were randomized to receive a single oral Dose of artesunate varying between 0 and 250 mg together with a Curative Dose of oral mefloquine. Acceleration of parasite clearance was used as the pharmacodynamic variable. An inhibitory sigmoidal maximum effect (Emax) pharmacodynamic model typical of a Dose-response curve was fitted to the relationship between Dose and shortening of parasite clearance time (PCT). The Emax was estimated as 28.6 oral h, and the 50% effective concentration was 1.6 mg/kg of body weight. These results imply that there is no reduction in PCTs with the use of single Doses of artesunate higher than 2 mg/kg, and this therefore reflects the average lower limit of the maximally effective Dose.
Tatsuaki Kanai - One of the best experts on this subject based on the ideXlab platform.
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probabilistic Dose distribution from interfractional motion in carbon ion radiation therapy for prostate cancer shows rectum sparing with moderate target coverage degradation
PLOS ONE, 2018Co-Authors: Daniel Bridges, Hidemasa Kawamura, Tatsuaki KanaiAbstract:Purpose This observational study investigates the influence of interfractional motion on clinical target volume (CTV) coverage, planning target volume (PTV) margins, and rectum tissue sparing in carbon ion radiation therapy (CIRT). It reports Dose coverage to target structures and organs at risk in the presence of interfractional motion, investigates rectal tissue sparing, and provides recommendations for lowering the rate of toxicity. We also propose probabilistic DVH based on cone-beam computed tomography (CBCT) table shifts from photon therapy for consideration in bone-matching CIRT treatment planning to represent probable Dose to our CIRT patient population. Methods At Gunma University Hospital intensity-modulated x-ray therapy (IMXT, aka IMRT) prostate cancer patients are positioned on a table which is shifted twice based on CBCT to align bones and then align prostate tissue to isocenter. These shifts thereby contain interfractional motion. A total of 1306 such table shifts from 85 patients were collected. Normal probability distributions were fit to the difference between bone-matching and prostate-matching CBCT-to-planning CT table shifts (i.e. interfractional motion). Between 2011 and 2016 CIRT prostate patients were treated with three beams to PTV1 (lateral-opposing and anterior) one per day for 9 fractions and two beams for a boost PTV2 (lateral-opposing) one per day for 7 fractions for a prescribed total of 57.6 Gy(RBE) as follows: PTV1 extends the prostate contour by 10/10, 5/10, 6/6 mm in the right/left, posterior/anterior, and superior/inferior directions, respectively, and the proximal seminal vesicles contour by 5 mm superiorly and inferiorly, 3 mm right and left. PTV2 reduces PTV1 posteriorly along a straight line to exclude the rectum and reduces the superior and inferior margins by 6 mm. Probable interfractional motion for 40 patients was simulated using each patient’s own beam data as follows: The previously fit normal probability distributions were randomly sampled 2000 times per patient, and the five beams were shifted and summed with the same relative weighting as in the 16-fraction regimen. The resulting Dose distribution was then scaled back down by 16/2000 to match the prescribed number of fractions. We then analyzed the resulting Doses to contoured structures. Results Probable Dose to rectum is substantially less than planned: For example, mean+-standard deviation D2% for planned and probable DVH is 51+-1.9 and 45+-2.4, respectively. Cumulative DVH show mean CTV fraction receiving a given probable Dose is less than the mean fraction receiving the corresponding planned Dose for Doses larger than 52 Gy(RBE), up to 19% less at 57.4 Gy(RBE). Our PTV1 margins generally cover 95% of interfractional motion but seminal vesicles and inferior prostate receive less Dose than planned due to insufficient PTV2 margins. Conclusion Assuming rigidly shifting interfractional motion around the prostate region and neglecting minor changes in soft tissue stopping power, interfractional motion resulted in target underdosing but better tissue sparing in all cases. Given our low rates of relapse and recurrence, it appears less Curative Dose is needed than previously thought or else current planning target margins may be excessive: Planning target volumes should be reconsidered with the adoption of Dose verification methods. Our probable Dose distributions quantify expected Dose for future Dose verification studies.
