Angiologica (Italy)

Abstract Background: Current data support that metastatic hormone receptor-positive (HR+) and HER2-positive (HER2+) breast cancer offers distinct treatment options targeting both the hormone receptor and the HER2-pathway. This might lead to increased treatment efficacy with the potential of omitting chemotherapy in these patients. The aim of the randomized multicenter phase III DETECT V trial was to analyze the efficacy of chemotherapy free and CDK4/6 inhibitor containing treatment strategies compared to current standard treatment. Methods: Between 09/2015 and 11/2022, 271 patients with HER2+ and HR+ MBC in the 1st-3rd line setting were randomized 1:1 to receive trastuzumab and pertuzumab combined with either endocrine therapy or chemotherapy followed by maintenance therapy with dual HER2 targeted and endocrine therapy. Chemotherapy and the endocrine agents could be chosen from a variety of available regimens according to physicians’ choice. In January 2019, the protocol was amended with the addition of the CDK4/6 inhibitor ribociclib to both treatment arms. The primary objective of DETECT V was to compare tolerability between the treatment arms, and secondary objectives comprised the comparison of overall survival (OS), progression-free survival (PFS) and safety, as well as the evaluation of the effect of adding ribociclib to both treatment arms. Here we report results of the final efficacy analyses as based on the modified ITT set of 262 patients (9 patients did not receive any study treatment and were excluded). Of these, 120 patients were recruited before the addition of ribociclib (59 and 61 patients in the chemotherapy-free and chemotherapy-containing treatment arm, respectively), and 142 patients were recruited after the addition of ribociclib (73 and 69 patients in the chemotherapy-free and chemotherapy-containing treatment arm, respectively). Results: Median patient age was 60 years, 202 (77.1%) of patients were in the first line setting and 137 (52.3%) patients had a metastasis-free interval (from primary diagnosis) exceeding 12 months. The overall comparison between all patients receiving chemotherapy-free and chemotherapy-containing treatment showed no significant difference with regard to OS and PFS (median OS not reached vs 46.1 months, HR 0.98, 95% CI 0.60 - 1.59, p = 0.93; median PFS 19.5 vs 23.0 months, HR 1.15, 95% CI 0.82 - 1.62, p = 0.42). However, both OS and PFS were significantly improved by the (non-randomized) addition of ribociclib (OS: median OS not reached vs 46.1 months, HR 0.43, 95% CI 0.26 - 0.72, p = 0.001; PFS: median PFS 29.7 vs 15.6 months, HR 0.48, 95% CI 0.34 - 0.67, p < 0.001). A separate analysis for the two treatment arms showed that the addition of ribociclib to chemotherapy-containing treatment significantly improved both OS (median OS not reached vs 38.7 months, HR 0.30, 95% CI 0.14 - 0.64, p = 0.002) and PFS (median PFS 33.1 vs 15.4 months, HR 0.35, 95% CI 0.21 - 0.59, p < 0.001), while the addition of ribociclib to chemotherapy-free treatment significantly improved PFS (median PFS 27.2 vs 15.6 months, HR 0.61, 95% CI 0.38 - 0.98, p = 0.040) but not OS (median OS not reached in both groups, HR 0.60, 95% CI 0.30 - 1.23, p = 0.163). An exploratory cross-cohort comparison revealed significantly improved outcome for patients receiving chemotherapy-free treatment plus ribociclib vs chemotherapy-containing treatment without ribociclib (OS: median OS not reached vs 38.7 months, HR 0.48, 95% CI 0.24 - 0.94, p = 0.033; PFS: median PFS 27.2 vs 15.4 months, HR 0.53, 95% CI 0.33 - 0.85, p = 0.008). Conclusion: Our results suggest that chemotherapy-free treatment for patients with HER2+ and HR+ MBC may be a valuable and effective treatment alternative, and may improve survival with the addition of ribociclib. Citation Format: W. Janni, T. Fehm, V. Müller, J. Blohmer, A. De Gregorio, T. Decker, A. Hartkopf, N. Ditsch, M. Schmidt, P. Wimberger, T. Engler, M. Banys-Paluchowski, P. A. Fasching, B. Rack, A. Schneeweiss, K. Pantel, T. W. Friedl, F. Schochter, J. Huober. Efficacy Analysis of the Randomized Phase III DETECT V trial: Treatment De-escalation by Omission of Chemotherapy and the Effect of Adding Ribociclib in HER2-positive and Hormone-receptor Positive Metastatic Breast Cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr RF4-02.

ABSTRACT Objective: To compare posterior decompression techniques in degenerative cervical myelopathy (DCM) and evaluate their clinical outcomes. Methods: A retrospective observational study was conducted on patients with DCM who underwent posterior cervical decompression surgery between 2012 and 2022. Variables analyzed included surgical time, intraoperative blood loss, and hospital stay. Results: A total of 32 patients were included. Open surgery had a surgical time of 176.6 ± 45.3 minutes, blood loss of 300.5 ± 236.3 ml, and a hospital stay of 4.5 ± 4.4 days. Minimally invasive surgery had a surgical time of 161.5 ± 72 minutes, blood loss of 93.8 ± 69.5 ml, and a hospital stay of 1.8 ± 1 day. Conclusions: Minimally invasive decompression resulted in shorter surgical time, reduced blood loss, and shorter hospital stay compared to open surgery. Further research is needed to determine its impact on functional outcomes. Level of Evidence II; Retrospectivef Study.

Aim Evaluation of epicardial fat thickness (EFT) and concentrations of biochemical markers in overweight patients after coronary artery bypass grafting (CABG) at different stages of the rehabilitation period.Material and methods The study included 155 patients aged 35 to 65 years with left main coronary artery disease who underwent CABG. Patients were divided into 3 groups. The main group (Group 1) consisted of 85 overweight (OW) patients (48 men and 37 women) after CABG (CABG+OW+) with body mass index (BMI) 28.0 ± 0.9 kg/m2). Group 2 included 70 patients (39 men and 31 women) with normal body weight (BMI 23.3 ± 1.1 kg/m2) after CABG (CABG+OW-). The control group (Group 3) consisted of 30 healthy age-matched volunteers without acute or chronic disease (BMI 20.4±0.7 kg/m2).Results A trend toward increased EFT and concentrations of acid-soluble blood fraction (ASBF) and deoxyribonucleic acid (DNA) in blood was observed in Group 1 at the third stage of rehabilitation. Concentrations of neutrophil extracellular traps (NETs) were significantly (p<0.05) higher in Group 1 at all stages of rehabilitation, with a trend toward an increase at the third stage of rehabilitation compared to Group 2.Conclusion In OW patients after CABG, the EFT and the DNA concentration were significantly increased 1.8 times (p<0.05), the ASFB was 2.1 times higher, and the NET concentration was 1.9 times higher than in patients with normal body weight. In OW patients after CABG, the EFT and the concentrations of cell-free nucleic acids (ASBF, DNA) and NETs were significantly increased (p<0.05) at the third stage of rehabilitation compared to patients with normal body weight. Strong direct correlations were found between EFT and ASBF (r=0.705; p<0.001) at the second stage of rehabilitation and between EFT and DNA (r=0.825; p<0.001) at the third stage of rehabilitation.

This systematic review and meta-analysis compared the diagnostic performance of MRI, [ 18 F]FDG-PET/CT, and [ 18 F]FDG-PET/MRI in detecting focal bone lesions and bone marrow infiltration in the initial staging of patients with multiple myeloma (MM) who underwent both MRI and [ 18 F]FDG-PET/CT or [ 18 F]FDG-PET/MRI studies. A systematic literature search was conducted across PubMed, Embase, and Cochrane databases, including studies comparing the performance of MRI (WB-MRI or spine/pelvis MRI), [ 18 F]FDG-PET/CT, and/or [ 18 F]FDG-PET/MRI in the same patients for MM initial staging. Pooled sensitivities and concordance between imaging modalities were analyzed using R (package META-R). Heterogeneity and bias were assessed with the QUADAS-C tool. Twenty studies (published between 2007 and 2025) using the international MM diagnostic criteria as a reference standard met the inclusion criteria. Of these, 13 (n=742) compared per-patient sensitivity of [ 18 F]FDG-PET/CT and MRI, and 4 (n=224) compared MRI and [ 18 F]FDG-PET/MRI. Pooled sensitivities were 0.807 (95% CI: 0.74-0.86) for [ 18 F]FDG-PET/CT (with significant heterogeneity) versus 0.914 (95% CI: 0.88-0.94) for MRI (0.906 for spine/pelvis MRI and 0.920 for WB-MRI) ( P <0.001 for meta-regression analysis). Using contingency tables, 83% (599/721) of included patients had concordant [ 18 F]FDG-PET/CT and MRI results, while 14% (101/721) patients had negative [ 18 F]FDG-PET/CT and positive MRI with significant differences between the 2 techniques for the paired sample analysis ( P <0.001). The pooled sensitivity of the 4 studies including [ 18 F]FDG-PET/MRI was 0.944 (95% CI: 0.88-0.98). Consensus definitions for specificity in MM imaging should be standardized across studies. This systematic review and comparative meta-analysis demonstrates superior sensitivity of WB-MRI compared with [ 18 F]FDG-PET/CT for initial staging of MM patients. Future international guidelines might prioritize MRI and [ 18 F]FDG-PET/MRI for staging of MM patients. PROSPERO CRD42024564937.

Metastatic castration-resistant prostate cancer (mCRPC) patients with BRCA1/2 mutations show significant responses to poly-ADP ribose polymerase inhibitors (PARPi), while the efficacy of these agents in patients with homologous recombination repair (HRR) gene alterations other than BRCA remains unclear. This meta-analysis aimed at assessing the efficacy of PARPi in mCRPC harboring alterations in four rare HRR genes (i.e. CDK12, PALB2, ATM, and CHEK2). Five randomised phase III trials (PROfound, PROpel, MAGNITUDE, TALAPRO-2, TRITON3) were selected through searching the Medline/PubMed, Cochrane Library, and ASCO Meeting abstracts. Data extraction followed the PRISMA statement. The primary endpoints, radiographic progression-free survival (rPFS) and overall survival (OS) with the relative 95% CI, were calculated using fixed- or random-effects methods, depending on the studies' heterogeneity. RevMan software for meta-analysis (v.5.2.3) was used. PARPi significantly improved rPFS in mCRPC patients with CDK12 alterations (hazard ratio (HR) = 0.65; p = 0.02) without OS benefit. In patients with ATM, CHEK2, or PALB2 alterations, no significant benefit was observed in rPFS or OS. Due to the low incidence of these rare mutations, we grouped them into gene panels, revealing a significant rPFS advantage when CDK12+PALB2 (HR = 0.63; p = 0.009) were combined, and a similar benefit when including CHEK2 in the gene panel (HR = 0.69; p = 0.01). CDK12 alterations could be considered as a predictive biomarker of rPFS benefit with PARPi. A gene panel grouping CDK12 and PALB2 with or without CHEK2 mutations could also enable prediction of rPFS benefit with PARPi.

Crohn's disease (CD) is a complex, chronic inflammatory bowel disease characterized by unpredictable flare-ups and periods of remission. Despite advances in treatment, CD remains a significant health burden, leading to substantial direct healthcare costs and out-of-pocket expenses for patients, especially in the first-year post-diagnosis. The impact of CD on patients' quality of life is profound, with significant reductions in physical, emotional, and social well-being. Despite advancements in therapeutic options, including biologics, immunomodulators, and small molecules, many patients struggle to achieve or maintain remission, leading to a considerable therapeutic ceiling. This has led to an increased focus on novel and emerging treatments. This context underscores the importance of exploring advanced and innovative treatment options for managing refractory CD. By examining the latest approaches, including immunomodulators, combination therapies, stem cell therapies, and emerging treatments like fecal microbiota transplantation and dietary interventions, there is an opportunity to gain a comprehensive understanding of how best to address and manage refractory cases of CD.

Sarcoidosis is an inflammatory disease characterized by immune cell–rich granulomas that form in multiple organs. In this issue of the JCI, Sati and colleagues used scRNA-seq and spatial transcriptomics of skin samples from patients with sarcoidosis and non-sarcoidosis granulomatous disease to identify upregulation of a stromal-immune CXCL12/CXCR4 axis and accumulation of type 1 innate lymphoid cells (ILC1s) in sarcoidosis. The accumulation of ILC1s in skin and blood was specific to patients with sarcoidosis and not observed in other granulomatous diseases. The authors used a mouse model of lung granuloma to show that ILCs contribute to granuloma formation and that blockade of CXCR4 reduced the formation of granulomas, providing a proof of concept that sarcoidosis may be treated by CXCR4 blockade to prevent the progression of disease in patients. These results suggest ILC1s could serve as a diagnostic biomarker in sarcoidosis and a potential therapeutic target.

Primary tumor (PT) sidedness is an established prognostic marker in metastatic colorectal cancer (mCRC) and has a predictive impact on the efficacy of anti-epidermal growth factor receptor (anti-EGFR) antibody [monoclonal antibody (mAb)] in patients with RAS wild-type mCRC. This investigation focuses on patients with BRAFV600E-mutated (BRAFmt) mCRC and examines the efficacy of anti-EGFR mAbs in relation to primary tumor sidedness (PTS). This pooled analysis was carried out using individual patient data from five randomized studies in the first-line setting of mCRC. The population of interest was limited to patients with BRAFmt mCRC and known PTS. For analysis, treatment was stratified into two groups: those treated with anti-EGFR mAbs and those without. Dichotomous variables, such as overall response rate and objective response rate (ORR), were compared using chi-square or Fisher's exact test. Time-to-event endpoints [progression-free survival (PFS) and overall survival (OS)] were analyzed using the Kaplan-Meier method, log-rank test, and Cox regression. An interaction test was carried out via Cox regression. A total of 102 patients with BRAFmt mCRC were identified. The type of targeted therapy (anti-EGFR-based versus non-anti-EGFR) did not significantly impact the outcome. However, in patients with left-sided primary tumors, anti-EGFR mAb-based treatment, compared with non-anti-EGFR, was associated with a higher ORR (58% versus 34%; P < 0.01), trended toward improved PFS [hazard ratio (HR) 0.62; 95% confidence interval (CI) 0.34-1.13; P= 0.12], and demonstrated prolonged OS (HR 0.38; 95% CI 0.20-0.72; P < 0.01). In patients with right-sided primary tumors, anti-EGFR-based therapy had no effect on ORR (33% versus 36%; P > 0.99), induced inferior PFS (HR 1.97; 95% CI 1.12-3.47; P= 0.02), and trended toward a worse OS (HR 1.76; 95% CI 0.99-3.13; P= 0.05). This analysis suggests that PTS has predictive value for the efficacy of anti-EGFR mAb in the first-line treatment of BRAFmt mCRC.