Microdosimetry in low energy proton beam at therapeutic-equivalent fluence rate with silicon 3D-cylindrical microdetectors

In this work we show the first microdosimetry measurements on a low energy proton beam with therapeutic-equivalent fluence rates by using the second generation of 3D-cylindrical microdetectors. The sensors belong to an improved version of a novel silicon-based 3D-microdetector design with electrodes etched inside silicon, which were manufactured at the National Microelectronics Centre (IMB-CNM, CSIC) in Spain. A new microtechnology has been employed using quasi-toroid electrodes of 25μm diameter and a depth of 20μm within the silicon bulk, resulting in a well-defined cylindrical radiation sensitive volume. These detectors were tested at the 18 MeV proton beamline of the cyclotron at the National Accelerator Centre (CNA, Spain). They were assembled into an in-house low-noise readout electronics to assess their performance at a therapeutic-equivalent fluence rate. Microdosimetry spectra of lineal energy were recorded at several proton energies starting from 18 MeV by adding 50μm thick tungsten foils gradually at the exit-window of the cyclotron external beamline, which corresponds to different depths along the Bragg curve. The experimentalyF¯values in silicon cover from (5.7 ± 0.9) to (8.5 ± 0.4) keV μm-1in the entrance to (27.4 ± 2.3) keV μm-1in the distal edge. Pulse height energy spectra were crosschecked with Monte Carlo simulations and an excellent agreement was obtained. This work demonstrates the capability of the second generation 3D-microdetectors to assess accurate microdosimetric distributions at fluence rates as high as those used in clinical centers in proton therapy

Blood Adv

Real-world data are essential to complement clinical trial (CT) data, but major challenges remain, like data quality. REal world dAta in LYmphoma and Survival in Adults (REALYSA) is a prospective non-interventional multicentric cohort started in 2018 (NCT03869619) including patients newly diagnosed with lymphoma in France. Herein is a proof-of-concept analysis on first-line DLBCL patients to (i) evaluate the capacity of the cohort to provide robust data through a multi-step validation process; (ii) assess the consistency of the results; (iii) conduct an exploratory transportability assessment of two recent phase 3 CT (POLARIX, SENIOR). The analysis population comprised DLBCL patients included before March 31st 2021, who received immunochemotherapy. 645 patients were included, for whom 3589 queries were generated, resulting in high data completeness (<4% missing data). Median age was 66 years (19-98) with mostly advanced-stage disease (472; 73%) and high international prognostic index (IPI) score (IPI 2-5, 486; 76%). Treatments were mostly R-CHOP (482; 75%) and R-miniCHOP (86; 13%). Estimated 1-year EFS and OS were 77.9% (95% CI: 73.8-81.4) and 90.0% (95% CI: 86.5-92.5), respectively (median follow-up: 9.9 months). Regarding transportability, when applying trials' main inclusion criteria (age, PS, IPI), outcomes seemed comparable between REALYSA patients and standard arms of POLARIX (1-year PFS 79.8% (95% CI, 75.9-83.6) vs. 79.8% (95% CI, 73.9-84.4)) and SENIOR (1-year EFS à 64.5% (95% CI: 47.8-77.0) vs. 60.0% (95% CI: 50.8-68.1)). With its rigorous data validation process, REALYSA program provides high-quality RWD, thus constituting a platform for numerous scientific purposes

An open-label randomized controlled trial of low-dose corticosteroid plus enteric-coated mycophenolate sodium versus standard corticosteroid treatment for minimal change nephrotic syndrome in adults (MSN Study).

International audienceFirst-line therapy of minimal change nephrotic syndrome (MCNS) in adults is extrapolated largely from pediatric studies and consists of high-dose oral corticosteroids. We assessed whether a low corticosteroid dose combined with mycophenolate sodium was superior to a standard oral corticosteroid regimen. We enrolled 116 adults with MCNS in an open-label randomized controlled trial involving 32 French centers. Participants randomly assigned to the test group (n=58) received low-dose prednisone (0.5 mg/kg/day, maximum 40 mg/day) plus enteric-coated mycophenolate sodium 720 mg twice daily for 24 weeks; those who did not achieve complete remission after week 8 were eligible for a second-line regimen (increase in the prednisone dose to 1 mg/kg/day with or without Cyclosporine). Participants randomly assigned to the control group (n=58) received conventional high-dose prednisone (1 mg/kg/day, maximum 80 mg/day) for 24 weeks. The primary endpoint of complete remission after four weeks of treatment was ascertained in 109 participants, with no significant difference between the test and control groups. Secondary outcomes, including remission after 8 and 24 weeks of treatment, did not differ between the two groups. During 52 weeks of follow-up, MCNS relapsed in 15 participants (23.1%) who had achieved the primary outcome. Median time to relapse was similar in the test and control groups (7.1 and 5.1 months, respectively), as was the incidence of serious adverse events. Five participants died from hemorrhage (n=2) or septic shock (n=3), including 2 participants in the test group and 3 in the control group. Thus, in adult patients, treatment with low-dose prednisone plus enteric-coated mycophenolate sodium was not superior to a standard high-dose prednisone regimen to induce complete remission of MCNS