Maria Sklodowska-Curie National Research Institute of Oncology

Dermatologic toxicities represent a broad and heterogeneous group of immune-related adverse events (irAEs) in patients with melanoma treated with immunotherapy, ranging from mild, transient, and self-limiting reactions to severe and potentially life-threatening conditions. Certain dermatologic toxicities have been shown to reflect immune system activation and may influence decisions on treatment continuation. The objective of this study was to comprehensively analyse real-world evidence in order to characterise the frequency, time to onset, and spectrum of dermatologic toxicities in patients with melanoma treated with immunotherapy. A systematic literature search was conducted in the PubMed and EBSCO (MEDLINE Complete) databases to identify relevant reports published between January 2014 and December 2024. Case reports and letters describing skin toxicities in adult patients with melanoma undergoing immunotherapy were included. A total of 18 patients with melanoma who had experienced dermatologic immune-related adverse events (d-irAEs) were identified. Breslow thickness ranged from 0.85 to 5.1 mm. The most frequently administered treatment was anti-PD-1 monotherapy. All reported cases involved metastatic disease (18/18, 100

Sunitinib, a multitargeted tyrosine kinase inhibitor, is used in advanced clear cell renal cell carcinoma (ccRCC). Corrected QT interval (QTc) prolongation is a recognized cardiovascular toxicity of this therapy. To evaluate the incidence, timing, and severity of QTc prolongation in real-world advanced ccRCC patients treated with first-line sunitinib, compare Bazett’s and Fridericia’s correction formulas, and identify risk factors. This retrospective single-center cohort study included 67 patients between January 2019 and June 2022. QTc was calculated manually using Bazett’s and Fridericia’s formulas and graded per Common Terminology Criteria for Adverse Events (CTCAE) v5.0. The incidence, timing, and severity of QTc prolongation were assessed based on the highest recorded QTc value. Statistical analyses compared QTc values between formulas and evaluated potential clinical predictors of QTc prolongation. The median treatment duration was 1.4 years (IQR 0.72–2.99). QTc prolongation ≥ 450ms occurred in 44.8

Accurate size estimation of large (≥ 20 mm) colorectal laterally spreading tumors (LSTs) is essential for procedural planning, risk stratification, and predicting technical difficulty. Yet, the reliability of visual LST size assessment among endoscopists has not been systematically evaluated. 46 LSTs were recorded during colonoscopy. Twenty-four international expert endoscopists independently reviewed de-identified videos and provided visual estimates for (1) maximal diameter, (2) oral–anal axis, (3) left–right axis, and (4) percentage of colonic circumference involved. Each lesion was assessed twice in randomized order. Fleiss’s kappa, Krippendorff’s alpha, and intraclass correlation coefficients (ICC) were used to evaluate inter- and intra-rater agreement. A total of 1104 measurements were collected. Inter-endoscopist kappa agreement for maximal diameter was poor (κ = 0.16), with similarly poor agreement for the oral–anal (κ = 0.15) and left–right axes (κ = 0.14). The percentage of circumferential involvement demonstrated moderate reproducibility (ICC 0.74 and 0.70 across rounds). Subgroup analyses showed consistently poor agreement for larger lesions for diameter-based methods, whereas circumferential percentage estimation ranged from poor to good depending on LST size and morphology. Intra-endoscopist agreement for diameter- and axis-based approaches showed wide variability (κ range 0.01–0.67), while circumferential estimates achieved good to excellent agreement for most endoscopists. Visual estimation of large colorectal LST size is highly variable among expert endoscopists. Maximal diameter and axial lengths demonstrate poor inter- and intra-observer reliability. Circumferential extent is the most reproducible descriptor and may be the preferred approach for reporting LST size in clinical practice and research.

LBA4 Background: ESR1 mutations ( ESR1 m) constitutively activate the estrogen receptor (ER) and are the most common mechanism of acquired resistance to aromatase inhibitor (AI) + CDK4/6i. Molecular monitoring by ctDNA analysis can detect the emergence of ESR1 m during 1L AI + CDK4/6i. Camizestrant, the next-generation selective ER degrader (SERD) and complete ER antagonist, has shown anti-tumor activity in pts with and without detectable ESR1 m. SERENA-6 is the first global registrational Phase 3 trial assessing a ctDNA-guided approach to detect the emergence of ESR1 m during 1L AI + CDK4/6i to inform a switch in therapy ahead of disease progression. Methods: Pts with HR+/HER2– ABC who had received ≥6 months of 1L AI (anastrozole/letrozole) + CDK4/6i (abemaciclib/palbociclib/ribociclib) were enrolled and had ctDNA tested for ESR1 m every 2–3 months, coinciding with routine imaging. At ESR1 m detection, pts without evidence of disease progression were randomized 1:1 to switch to camizestrant (75 mg) with continued CDK4/6i (type and dose maintained) + placebo for AI vs continuing AI + CDK4/6i + placebo for camizestrant. The primary endpoint was investigator-assessed PFS (per RECIST v1.1). Prespecified interim analysis data cutoff was Nov 28, 2024. Results: 3,256 eligible pts were surveilled for ESR1 m using ctDNA until 315 eligible pts were randomized to switch to camizestrant (n=157) or continue with AI (n=158). All pts remained on the same CDK4/6i. ~50% of randomized pts had ESR1 m detected at the first ctDNA test. Baseline characteristics were well balanced between treatments. After 171 PFS events, hazard ratio for PFS was 0.44 (95% CI 0.31–0.60, p<0.00001; median PFS 16.0 vs 9.2 months). PFS benefit was consistent across subgroups. PFS rate at 12 months was 60.7% (95% CI 51.1–69.0) vs 33.4% (95% CI 24.9–42.2) and at 24 months was 29.7% (95% CI 19.0–41.2) vs 5.4% (95% CI 0.7–18.2). PFS2 hazard ratio was 0.52 (95% CI 0.33–0.81; 27% maturity). OS is immature (12%). Camizestrant + CDK4/6i was well tolerated with safety consistent with the known profiles of camizestrant, and of each CDK4/6i. Rates of treatment discontinuation due to adverse events were 1.3% for camizestrant and 1.9% for AI. Conclusions: Camizestrant + CDK4/6i guided by emergence of ESR1 m during 1L AI + CDK4/6i in pts with HR+/HER2– ABC resulted in a statistically significant and clinically meaningful improvement in PFS. SERENA-6 is the first global Phase 3 trial to demonstrate clinical utility of using ctDNA to detect and treat emerging resistance, ahead of disease progression. These findings represent a potential new treatment strategy to optimize and improve 1L patient outcomes. Clinical trial information: NCT04964934 .

Purpose To evaluate the diagnostic accuracy of three proton magnetic resonance spectroscopy (1H-MRS) strategies-short echo (TE 30 ms), intermediate echo (TE 97 ms), and MEGA-PRESS-for detecting the oncometabolite 2-hydroxyglutarate (2HG) to non-invasively determine isocitrate dehydrogenase (IDH) mutation status in adult-type diffuse gliomas. Methods A cohort of 152 patients with adult-type diffuse gliomas (84 IDH-mutant, 68 IDH-wild-type) underwent preoperative 3T MRI incorporating standard morphological sequences and 1H-MRS acquisitions. Spectra were evaluated to assess the presence of a 2HG peak. Diagnostic performance was analysed independently for each method and collectively for a subgroup of patients receiving all three sequences. Results The intermediate echo (TE 97 ms) method demonstrated 100% specificity and 51.2% sensitivity, while the short echo (TE 30 ms) sequence achieved 97% specificity and 88.9% sensitivity. The MEGA-PRESS method yielded 86.7% specificity and 72.2% sensitivity but was limited by a high non-diagnostic rate (17.5%) due to artifact susceptibility. When combined, the spectroscopy methods achieved 100% sensitivity, 85.7% specificity, and 93.7% overall accuracy in detecting 2HG. Conclusion Conventional PRESS sequences (TE 30 ms and TE 97 ms) outperform MEGA-PRESS for the routine clinical detection of 2HG due to higher technical reliability. An optimized conventional PRESS protocol offers a robust, highly accurate, and non-invasive preoperative tool for identifying glioma genotypes and predicting tumour phenotypes.