Stacked magnetic resonators for MRI RF coils decoupling

International audienceParallel transmission is a very promising method to tackle B 1 + field inhomogeneities at ultrahigh field in magnetic resonant imaging (MRI). This technique is however limited by the mutual coupling between the radiating elements. Here we propose to solve this problem by designing a passive magneto-electric resonator that we here refer to as stacked magnetic resonator (SMR). By combining numerical and experimental methodologies, we prove that this passive solution allows an efficient decoupling of active elements of a phased-array coil. We demonstrate the ability of this technique to significantly reduce by more than 10 dB the coupling preserving the quality of images compared to ideally isolated linear resonators on a spherical salty agar gel phantom in a 7 T MRI scanner

Bevacizumab, olaparib, and durvalumab in patients with relapsed ovarian cancer: a phase II clinical trial from the GINECO group

International audienceAbstract Most patients with advanced ovarian cancer (AOC) ultimately relapse after platinum-based chemotherapy. Combining bevacizumab, olaparib, and durvalumab likely drives synergistic activity. This open-label phase 2 study (NCT04015739) aimed to assess activity and safety of this triple combination in female patients with relapsed high-grade AOC following prior platinum-based therapy. Patients were treated with olaparib (300 mg orally, twice daily), the bevacizumab biosimilar FKB238 (15 mg/kg intravenously, once-every-3-weeks), and durvalumab (1.12 g intravenously, once-every-3-weeks) in nine French centers. The primary endpoint was the non-progression rate at 3 months for platinum-resistant relapse or 6 months for platinum-sensitive relapse per RECIST 1.1 and irRECIST. Secondary endpoints were CA-125 decline with CA-125 ELIMination rate constant K (KELIM-B) per CA-125 longitudinal kinetics over 100 days, progression free survival and overall survival, tumor response, and safety. Non-progression rates were 69.8% (90%CI 55.9%-80.0%) at 3 months for platinum-resistant relapse patients (N = 41), meeting the prespecified endpoint, and 43.8% (90%CI 29.0%-57.4%) at 6 months for platinum-sensitive relapse (N = 33), not meeting the prespecified endpoint. Median progression-free survival was 4.1 months (95%CI 3.5–5.9) and 4.9 months (95%CI 2.9–7.0) respectively. Favorable KELIM-B was associated with better survival. No toxic deaths or major safety signals were observed. Here we show that further investigation of this triple combination may be considered in AOC patients with platinum-resistant relapse

A new paradigm in managing advanced ovarian cancer: differentiating patients requiring neoadjuvant treatment from primary cytoreduction

International audienceOur study aims to evaluate the comparability of primary debulking surgery (PDS) and neoadjuvant chemotherapy (NACT) patients. This single-center retrospective study includes all patients treated for advanced stages high-grade serous ovarian carcinomas (HGSOC) between 2007 and 2017. Preoperative characteristics and postoperative outcomes were compared after a propensity score matching analysis. Of the 221 patients included, 38% underwent PDS, and 62% received NACT. There was no age difference at diagnosis; however, CA125 levels, PCI score levels, and rates of stage IV were higher in the NACT group. There were no differences concerning the rate and the severity of complications (p = 0.29). The propensity score distribution showed a broad distinction between PDS patients and NACT patients with no significant overlap. Survival analyses demonstrate, after a median follow-up of 66.5 months, an overall survival (OS) of 105.9 and progression-free survival (PFS) of 29.2 months in the PDS group, compared to OS of 52.8 and PFS of 18.9 months in the NACT group. Advanced HGSOC is a heterogeneous population, in which inoperable patients should be differentiated from PDS patients based on many factors, primarily tumor burden

Clinical activity and safety of the anti-PD-1 monoclonal antibody dostarlimab for patients with recurrent or advanced dMMR endometrial cancer

International audienceThis document provides a short summary of the GARNET trial which was published in JAMA Oncology in October 2020. At the end of this document, there are links to websites where you can find more information about this study. The trial enrolled adult participants with advanced solid tumors. This report is restricted to patients with a particular type of endometrial cancer that has a deficient mismatch repair (dMMR) status. Patients received a trial treatment called dostarlimab (also known by the brand name Jemperli). In the US, dostarlimab is approved as a single therapy in adult patients with dMMR recurrent or advanced endometrial cancer that has progressed on or after platinum-based chemotherapy. In the EU, dostarlimab is approved as a single therapy in adult patients with recurrent or advanced dMMR/microsatellite instability–high (MSI-H) endometrial cancer that has progressed on or after treatment with a platinum-containing regimen. The GARNET trial looked at dostarlimab given intravenously to patients with dMMR endometrial cancer from 7 countries. The trial showed that dostarlimab was successful in shrinking the tumor in 42% of these patients. In general, the percentage of participants who experienced medical problems (referred to as side effects) was low and within expectations for this type of treatment. ClinicalTrials.gov NCT number: NCT02715284

Clinical Activity and Safety of the Anti–Programmed Death 1 Monoclonal Antibody Dostarlimab for Patients With Recurrent or Advanced Mismatch Repair–Deficient Endometrial Cancer

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Kerker Effect in Ultrahigh-Field Magnetic Resonance Imaging

International audienceUltrahigh-field (UHF) magnetic resonance imaging (MRI) systems are getting a lot of attention as they ensure high intrinsic signal-to-noise ratio resulting in higher spatial and temporal resolutions as well as better contrast. This promises improved clinical results with regard to morphological as well as functional and metabolic capabilities. Traditionally, MRI relies on volume coils (birdcage) able to deliver a homogeneous radio frequency field exciting the nuclei magnetic spin. However, this strategy is hindered at UHF because of the rf field inhomogeneities yielded by the increased Larmor frequency. A standard approach consists of inserting passive dielectric elements within the volume coil in order to locally enhance the rf field and mitigate these inhomogeneities. However, the lack of control over their electromagnetic properties prevents the development of optimal solutions. Here, a single meta-atom is used to achieve efficient and tunable rf field control in UHF MRI. We demonstrate theoretically and experimentally a full overlap between the electric dipolar and magnetic dipolar resonances of the meta-atom. This interaction is precisely tuned to reach the so-called Kerker scattering conditions when illuminated in the near field by a birdcage coil. At these conditions, a strong enhancement or suppression of the rf field is achieved in the vicinity of the meta-atom within the MRI volume coil

Enhancement of transmit and receive efficiencies with hybridized meta-atom in 7T head coil

International audienceBackground B1 homogeneity in 7T MRI remains an important challenge in order to fully benefit from the signal enhancement due to the stronger magnetization available in ultra-high field scanners. High-dielectric constant pads have been proposed and optimized for passive shimming purposes [1-3]. Common formulations of dielectric pads for 7T applications are based on BaTiO 3 mixed with water. They present some drawbacks such as performance decay over time and toxicity. While previous studies tackled directly the formulation problem introducing new dielectric materials and solvent [4], we adopted a new approach based on metamaterials [5]. We demonstrated that the hybridization of four parallel metallic wires arranged on a square unit cell provides the ability to control radiofrequency field inside a 7T head birdcage. In the present work, we show that these hybridized meta-atom (HMA) can be used to improve MRI acquisition in the presence of a head receive array routinely used for in vivo MRI protocol

Passive RF shimming for 7T head coil with hybridized meta-atom: In vivo investigation

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First-in-human first-in-class phase I trial of murlentamab, an anti-Mullerian-hormone receptor II (AMHRII) monoclonal antibody acting through tumor-associated macrophage (TAM) engagement, as single agent and in combination with carboplatin (C) and paclitaxel (P) in AMHRII-expressing advanced/metastatic gynecological cancer patients (pts)

International audience2521 Background: Membranous expression of AMHRII is found in ~70% of gynecological tumors. Murlentamab (M) binds with high affinity both AMHRII (at cell membrane) and CD16 (on macrophage, via its low fucose Fc). M reprograms TAMs, restoring their antitumoral functions (phagocytosis) resulting in cytotoxic T cell reactivation. Methods: Pts with advanced/metastatic AMHRII-expressing ovarian, cervical or endometrial cancer with measurable disease and performance status ≤ 1 received M as single agent (SA) in 8 dose escalating and 2 expansion cohorts. Combination with CP was studied in 2 escalating cohorts. Safety, recommended dose determination, antitumor activity, pharmacodynamics (PD) effects (circulating immune cells and tumor microenvironment (TME) from paired biopsies) were assessed. Results: 68 heavily pretreated (median 4 prior lines) pts received M for 0.5 to 11 months (mo) (59 pts M SA and 9 pts M + CP). No dose limiting toxicity was reported. Most common toxicity was G1-2 asthenia (29 %). Eight pts (12%) had G ≥ 3 reversible toxicities (asthenia, nausea/vomiting, anorexia, arthralgia). No antidrug antibody was detected. One partial response (PR) was achieved with M SA in a granulosa pt. In CP combination, 4/9 pts (44%) responded to treatment (1 Complete Response and 3 PRs). Overall, 22/67 (33%) pts were progression-free at 4 mos. Among 17 pts treated ≥ 6 mos, 6/9 (67%) granulosa pts with M SA and 4/5 (80%) endometrium and cervix with CP combination had a longer PFS than under previous regimen. PD blood assessment of 25 pts treated with M SA showed an increase in classical monocytes, and T cells and neutrophils activation. Changes in TME under M will be presented. Conclusions: Murlentamab was very well tolerated, demonstrated immune PD effects and showed hints of antitumor activity. These results together with its innovative immunological mode of action support development of M in AMHRII-expressing cancers, in combination with chemotherapy or other immune oncology drugs. Clinical trial information: NCT02978755