Hôtel-Dieu de Québec

Objective.High dose rate brachytherapy (BT) is a widely adopted modality for cancer treatment. However, it is not free from error and uncertainty.In-vivodosimetry (IVD) is the only technique that confirms correct dose delivery. This study details and validates a calibration method for plastic scintillation detector (PSD), bypassing dose gradient and positioning issues in BT calibration.Approach.The PRB-0057 PSD (Medscint, Québec, Canada), a1×1mm scintillating fiber coupled to a 20 m Eska GH-4001 clear optical fiber (Mitsubishi Rayon, Japan) of the same diameter, was calibrated and connected to the Hyperscint-RP200 research platform for optical signal collection. Hyperspectral calibration was performed at a LINAC with a kV and a 6 MV beam, enabling the independent stem effect removal. For validation, BT measurements with aSk=29447U iridium-192 Flexisource (Elekta Brachy, Veenendaal, The Netherlands) were performed in a motorized IBA-Blue-Phantom2water tank. Dose rates were measured at 10 Hz along the source's vertical/transverse axis at a fixed transverse distance of1.2±0.05cm in 0.2 cm steps. Calibration accuracy was evaluated using relative differences (RDs) between measured and TG-43U1 dose rates, converted to inverse-square equivalent positional errors. A detailed uncertainty budget was established to the measurement setup.Main results.Comparison agreed with RDs around 2.5% at 1.2 cm, corresponding to inverse-square positional uncertainties of<0.15mm. At greater distances, up to 8 cm, RDs increase to about 5%, corresponding to inverse-square positional uncertainties up to 3 mm, mainly due to reduced light-yield. Uncertainties found to depend on the source-detector distance, ranging from 3.92% to6.42% (k=1)over the range of explored distances.Significance.Results confirm the effectiveness of a 6 MV external beam PSD calibration to be used in time-resolved IVD. Uncertainties close to the source are consistent with the Afterloader and IBA motorized unit reproducibility and are mainly dominated by reduced detector response at larger distances. Our study further underlined the intrinsic limitation of IVD in the face of known uncertainties.

To describe a series of doxycycline-induced fixed drug eruptions (FDE) observed in sexual health clinics, in a context of increasing doxycycline use for sexually transmitted infection (STI) management and prophylaxis in France. We conducted a retrospective case series, combined with a doxycycline prescription audit and a sexual health clinician survey. Thirteen male patients (mean age: 32.5 years) were diagnosed with doxycycline-induced FDE. Most were MSM (men who have sex with men, 84.6%) and received doxycycline for STI treatment (92.3%). Lesions were mainly genital (85%) and often misdiagnosed as ulcerative STIs. Doxycycline prescriptions increased by 345% between 2018 and 2024. When performed, allergy workups confirmed the diagnosis in 60% of cases. The sharp rise in doxycycline use for STI prophylaxis coincides with the identification of multiple FDE cases. Enhanced dermatological awareness is needed within antimicrobial stewardship programs to ensure safer implementation of doxycycline-based prevention strategies.

Reference materials are essential for the validation, verification, and implementation of clinical assays. Seracare has developed the Seraseq line-commercial reference standards for non-invasive prenatal testing (NIPT)-which are designed to simulate maternal plasma containing cell-free DNA (cfDNA). This study aims to evaluate the performance of Seraseq reference materials compared to natural maternal plasma, particularly assessing their quality and reliability as reference standards in NIPT workflows, both with and without size selection to enrich fetal fraction. We analyzed six replicates from eight different Seraseq genotypes. cfDNA was extracted, prepared into sequencing libraries, and sequenced following the same protocols used for natural plasma samples. Size-selection was also applied to enrich shorter cfDNA fragments. The key performance metrics included cfDNA yield and integrity, library preparation efficiency, sequencing quality, fetal fraction estimation, and detection of aneuploidies and sex chromosome abnormalities. cfDNA quantity and quality from Seraseq materials were comparable to natural plasma. The materials yielded consistent library concentrations. Sequencing showed reliable detection of all targeted aneuploidies except the microdeletion del22q11, even with elevated fetal fraction. Size-selection increased fetal fraction and improved Z-scores for aneuploidy detection across all genotypes. Fragment size profiles exhibited slight but consistent deviations from natural plasma, notably after size selection. Seraseq reference materials closely mimic the cfDNA characteristics of maternal plasma and perform reliably across multiple testing dimensions. While they may present slight differences in fragment size periodicity, these did not affect analytical performance. These materials are therefore suitable for validating and monitoring NIPT workflows.

Observational studies have demonstrated that aspirin and/or PTSG2 inhibitor (e.g., celecoxib) use, before or after colon cancer (CC) diagnosis, is associated with a lower risk of recurrence. However, a randomized trial of adjuvant celecoxib therapy in stage III CC did not show improved survival compared to placebo treatment. We therefore hypothesized that immune microenvironment features may identify patient subgroups with stronger survival benefits from anti-inflammatory celecoxib treatment. Drawing from an NCI-Intergroup trial (Cancer and Leukemia Group B [now Alliance for Clinical Trials in Oncology]/SWOG 80702) for patients with stage III resected CC that compared 3 versus 6 months of adjuvant fluorouracil, leucovorin, and oxaliplatin ± 3 years of celecoxib, we conducted tissue-based tumor microenvironment profiling on 1,098 resected tumors using a custom 9-plex, T-cell multiplex immunofluorescence assay coupled with digital image analysis and supervised machine learning. The Kaplan-Meier method was used to describe disease-free survival, based on T cell density, and log-rank testing was performed. Cox proportional hazards models were used to examine unadjusted and adjusted associations between T cell density and disease-free survival (DFS). Two-sided P values ≤0.05 were considered statistically significant. We found that higher CD3+ T cell density was associated with longer DFS with an adjusted hazard ratio (HR) of 0.69 (95% confidence interval [CI] 0.52-0.91) for patients with densities in the highest tertile as compared the lowest tertile (P=0.01). T cell subset analysis showed that stromal regulatory T helper cells (HR 0.42 comparing highest to lowest tertile, CI 0.31-0.58, P&amp;lt;0.001) and stromal memory cytotoxic T cells (HR 0.55 comparing highest to lowest tertile, CI 0.42-0.74, P&amp;lt;0.001) were most strongly associated with longer DFS. Compared to the placebo group, adjuvant celecoxib use associated with improved DFS for patients with low but not high stromal CD3+ T cell density (adjusted HRs of 0.45 [CI 0.31-0.65] for lowest tertile and 1.13 [CI 0.73-1.74] for highest tertile; Pinteraction=0.01). This association was also seen when the analysis was restricted to microsatellite stable tumors (HR 0.50 [CI 0.32-0.80] for lowest density tertile and 1.50 [CI 0.87-2.59] for highest density tertile; Pinteraction=0.01). T cell subset analysis showed that DFS benefit for celecoxib use most strongly associated with stromal memory helper T cell density (HR 0.38 [CI 0.26-0.56] for lowest density tertile and 1.26 [CI 0.80-1.97] for highest density tertile; Pinteraction&amp;lt;0.001). Together, these results show that while higher T cell infiltration is associated with improved DFS, lower T cell infiltration is associated with improved DFS for patients treated with celecoxib. This unexpected finding may inform immunomodulatory treatment strategies for CC. Citation Format: Yasutoshi Takashima, Chao Ma, Qian Shi, Andressa Dias Costa, Tyler Twombly, Juha P. Väyrynen, Melissa Zhao, Ardaman Shergill, Pankaj Kumar, Felix Couture, Philip Kuebler, Smitha Krishnamurthi, Benjamin Tan, Eileen M. O'Reilly, Anthony F. Shields, Shuji Ogino, Charles S. Fuchs, Jeffrey A. Meyerhardt, Jonathan A. Nowak. Prognostic and predictive role of T cell infiltration in stage III colon cancer (CC) treated with celecoxib: CALGB/SWOG 80702 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5858.

Klinefelter syndrome (KS) is a sex chromosome-related genetic disease that commonly affects male subjects with infertility. Small testes, gynecomastia, infertility, and possible developmental abnormalities are symptoms of this condition. According to recent studies, people with KS also may have other neurologic problems, particularly tremors resembling essential tremors. Our review attempts to explore the features of tremors and their treatment in individuals with KS using case studies and previously published research. A PubMed/Medline search was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines using the following MeSH terms: ("Tremor") AND ("Klinefelter syndrome") OR ("Tremor") AND ("associated") AND ("Klinefelter syndrome") OR ("Tremor") AND ("hypogonadism"). The review included 24 articles. The average age at tremor onset was 15.59 years, and the most prevalent tremor types (31.91% of cases) were a combination of postural and kinetic/intention tremors. Overall, 40% of patients exhibited some improvement; 10% showed significant improvement, and 50% showed no impact when antitremor medications were administered. Testosterone replacement therapy is not a suitable option for this symptom because the effects of testosterone treatment on tremors are inconsistent. In each of the three described cases, tremors were significantly relieved after deep brain stimulation (DBS) surgery of the ventral intermediate nucleus (VIM). We also report a case of a man aged 54 years with KS who was unable to perform his regular tasks owing to severe tremors. His tremor was well managed with bilateral DBS of the thalamic VIM nucleus. Tremors are a potentially disabling associated manifestation of KS. The available literature on the management of tremors in patients with KS is limited. Surgical VIM-DBS has shown promising results in managing medication-refractory tremors in patients with KS, with an acceptable safety profile. Further research is needed to determine the causes of tremors in KS and to optimize treatment.

IntroductionOur translational study aims to identify prognostic and actionable biomarkers in early-staged cervical cancer from Senticol III cohort.MethodsTumoral slides of the first 150 randomized patients were analyzed based on SEDLIS criteria, TIL’s infiltration, PD-L1 expression and HPV status. Sequencing of tumor DNA was carried out using an in-house targeted next-generation sequencing panel of 571 genes. Relapse-free survival (RFS) was defined as the time between randomization and relapse of any type. We performed univariate and multivariate analysis to compare distributions of categorical variables.ResultsThe sequencing quality control criteria were met for 135 samples. PIK3CA was the most commonly altered gene (17%). Loss-of-function variants in KMT2-family genes were found in 16% of samples, and in 6% for ARID1A. There were 6 relapses, of which 4 were considered as low-risk based on SEDLIS criteria. KMT2C (p=0,018) and ARID1A (p < 0,001) pathogen variants were significantly associated with RFS. On multivariate analysis, alteration of ARID1A was independently associated with relapse. We found 32% of genomic alterations actionable for a target therapy.Conclusion/ImplicationsGenes involved in chromatin remodeling (ARID1A and KMT2C) are prognostic biomarkers of clinical interest in ESCC. On multivariate analysis, only alteration of ARID1A remains an independent biomarker predictive of relapse. Actionable molecular alterations were identified in 32% of the patients, highlighting the relevance of personalized therapeutic approaches including epidrugs in ESCC.