Institut Gustave Roussy

RET fusions appear in 1%-2% of non-small cell lung cancers (NSCLCs). The results from the ARROW study (ClinicalTrials.gov identifier: NCT03037385) supported US Food and Drug Administration approval of pralsetinib, an oral selective RET inhibitor, for metastatic RET-altered NSCLC and RET fusion-positive thyroid cancers. ARROW was a phase I/II open-label study of pralsetinib 400 mg once daily in RET fusion-positive NSCLCs. Coprimary end points were overall response rate (ORR) and safety. Key secondary end points included duration of response, progression-free survival, and overall survival (OS). At data lock (May 20, 2024), 281 patients initiated pralsetinib (median treatment duration, 15.0 months). ORR (measurable disease patients; n = 259) was 78% (95% CI, 69 to 86) for treatment-naïve patients and 63% (95% CI, 54 to 71) for prior platinum-based chemotherapy patients. Median OS was 44.3 months (95% CI, 30.9 to 53.1), 50.1 months (95% CI, 28.3 to not reached) in treatment-naïve patients, and 39.7 months (95% CI, 27.8 to 53.2) in prior platinum patients. Common grade ≥3 treatment-related adverse events were anemia (21%), hypertension (15%), and decreased neutrophils (13%). Three treatment-related deaths occurred (pneumonia, n = 2; interstitial lung disease and rhabdomyolysis, n = 1 each). Safety was consistent with previous ARROW reports; no hypersensitivity was reported in patients receiving prior immunotherapies. Pralsetinib produced robust, durable responses with manageable safety in treatment-naïve and previously treated patients with RET fusion-positive NSCLCs, confirming previous findings with longer follow-up.

CHRONOS is a multicenter, retrospective, cohort study involving acute graft-versus-host disease (aGvHD) adult patients with gastrointestinal (GI) symptoms, steroid- and ruxolitinib refractory, who initiated third-line therapy between 30 May 2019 and 30 September 2024. Primary endpoints were all-organ overall response rate (ORR) and GI-specific ORR (GI-ORR) around 28 days after treatment initiation. Secondary endpoints included duration of response, real-world progression-free survival (rwPFS) of underlying malignancy, and overall survival (OS). Fifty-nine patients from 16 sites in Europe were included. On Day 28, ORR was 36% (95% CI: 24-49%), GI-ORR was 37% (95% CI: 25-51%); 29% (95% CI: 11-49%) of responders lost response within 30 days, and 52% (95% CI: 29-72%) within 90 days. Median rwPFS and median OS were both 86 days (95% CI: 54-128 days). Median OS was higher in responders than in non-responders (186 versus 45 days). Over the 12-month follow-up period, 41 patients died, mainly due to aGvHD progression (n = 25), and infectious complications (n = 9). Within 3 months, Grade ≥ 2 infectious events occurred in 51% of patients; Grade 3-4 thrombocytopenia and neutropenia in 64% and 32%, respectively. These findings demonstrate limited effectiveness of third-line therapy in this cohort of steroid- and ruxolitinib-refractory aGvHD patients with GI symptoms.

Objective.This study aims to implement and evaluate a source modeling method for Monte Carlo (MC) simulation of computed tomography (CT) systems in the absence of manufacturer data. This work enables simulation of realistic CT x-ray sources by integrating experimental measurements, particularly x-ray spectrometry, and to assess its applicability to single-energy CT scanners.Approach.An experimental method was implemented combining x-ray spectra using a CdTe spectrometer and a bowtie filter attenuation profile measured with an ionization chamber, and compared to manufacturer data. Two source models with different levels of complexity were created for GATE 10 simulations. First, a basic model single-spectrum (SS) using one energy spectrum measured on the beam axis combined with the attenuation profile was considered. Multi-spectra (MS) model incorporated additional spectra off-axis. For comparison, the SS model was used with manufacturer's data. These source models were evaluated by comparing simulations and measurements of half-value layers (HVLs) of aluminum at three voltages (80 kV, 120 kV and 140 kV), as well as CT dose index (CTDI) values measured on both head and body phantoms.Main results.HVL of SS and MS models showed a better agreement with measurements, yielding a mean difference of 4%. CTDI values derived from simulations based on MS source outperformed the other sources, with differences inferior to 7% with measurements. SS results had good agreement with measurements (<10%), but underestimated dose evaluation in some cases by up to 16%. The Manufacturer source showed the largest discrepancies, especially at 140 kV.Significance.This work highlighted that modeling spectral variations across the x-ray beam significantly improves CT source model. The proposed framework offers a replacement for manufacturer data when not available and participates in the foundation for using MC methods to support the integration of new CT systems.

Deep and continuous sedation addresses the refractory suffering of patients expected to die in the short term. This practice creates a distinctive experience for both healthcare professionals and relatives. The objective of this study was to describe their psychological adjustment after caring for cancer patients for whom deep sedation was implemented. APSY-SED is a multicenter, prospective, longitudinal study using mixed methods. This report focuses on quantitative data collected during the initial (T1) phase, at the onset of sedation. Relatives completed questionnaires assessing attachment style (RSQ), anxiety and depression (STAI-S, BDI-II), and satisfaction with end-of-life care (CANHELP). Healthcare professionals completed a job satisfaction questionnaire (Karasek questionnaire). The sample included 52 relatives and 46 healthcare professionals from five French hospitals. Satisfaction with needs negatively predicted depression (β = -2.68, P = 0.007). Anxiety was predicted by total CanHelp (β = 4.13, P = 0.004), but reduced by satisfaction with involvement (β = -1.84, P = 0.035) and relationship with doctors and nurses (β = -1.77, P = 0.008). ANOVA showed higher satisfaction when sedation was patient-initiated (P = 0.015). Among professionals, 19.6% reported job strain; job latitude was high (M = 76.83, SD = 7.57). These findings underscore the need for targeted emotional support for anxious relatives and highlight the protective role of satisfactory end-of-life care in mitigating depressive symptoms. Clear protocols and communication may help preserve high job satisfaction among healthcare professionals. Further longitudinal and qualitative research is necessary to clarify how these factors evolve over time within continuous deep sedation contexts.