MD Anderson Cancer Center Madrid

Avelumab, pembrolizumab, and enfortumab vedotin (EV) demonstrated efficacy in mUC following platinum-based chemotherapy. However, real-world data in patients with urothelial carcinoma with squamous differentiation (UCSD) are limited. The aim of this study is to assess the real-world clinical outcomes of avelumab, pembrolizumab, or EV in mUCSD patients. The ARON-2EV study is a retrospective, international, multicenter analysis in patients with mUC treated with avelumab, pembrolizumab, or EV across 79 centers in 21 countries. Patients were divided into three cohorts: 1 (avelumab), 2 (pembrolizumab), and 3 (EV). Primary endpoints were overall survival (OS) and time on treatment (ToT). Secondary objectives included evaluating clinical factors associated with outcomes and exploring the impact of UCSD histology on response to therapy. Statistical methods included Kaplan-Meier estimates, log-rank tests, Fisher's exact and chi-square tests, and Pearson's correlation coefficients. A total of 1918 patients, 1696 with advanced pure UC (pUC) and 222 with mUCSD (36 in cohort 1, 111 in cohort 2, and 75 in cohort 3), were included. Median OS was shorter in patients with UCSD compared to patients with pUC histology in the three cohorts (1: 13.0 vs 26.8months, HR 2.66,p = 0.003; 2: 10.2 vs 18.5months, HR 1.52,p = 0.008; and 3: 7.6 vs 13.1months, HR 1.68,p = 0.011). Median ToT was shorter in patients with UCSD compared to patients with pUC histology in cohort 1 (3.5 vs 5.6months, HR 1.57,p = 0.044) and 3 (7.6 vs 13.6months, HR 1.83,p = 0.005) but not in cohort 2 (3.7 vs 4.7months, HR 1.19,p = 0.177). Response to therapy was negatively correlated with UCSD histology in cohorts 2 (correlation coefficient 0.094,p = 0.008) and 3 (correlation coefficient 0.107,p = 0.021), while response to avelumab was not correlated with UCSD (correlation coefficient 0.072,p = 0.263). UCSD is a histology with a poor prognosis and response to treatments compared to pUC. Treatments activity and effectiveness in divergent differentiations should be addressed in dedicated prospective studies. NCT05290038.

Although patients with early-onset colorectal cancer (EOCRC) share characteristics with the general colorectal cancer population, they also exhibit distinct features. Parameters such as sarcopenia, myosteatosis, and overall body composition play a crucial role in disease progression. This study aimed to assess the impact of body composition on oncological prognosis. Patients were recruited from the Humanitas Research Hospital (Milan, Italy) and the Spanish Early-Onset Colorectal Cancer Consortium (SECOC) prospective multicenter study. Preoperative computed tomography scans were analyzed between January 2019 and December 2023. Skeletal muscle mass index, visceral adipose tissue cross-sectional area, and intermuscular and intramuscular adipose tissues at the level of the transverse processes of the third lumbar vertebra (L3) were measured. Sarcopenia, obesity, and myosteatosis were defined according to sex-specific and body mass index cutoff points. After analyzing 197 patients, the mean age at diagnosis was 42.16±6.1years. According to the colorectal tumor characteristics, 64% of the tumors were located in the colon (n =126). After analysis of radiological body characteristics, the prevalence of sarcopenia was 61.9% and myosteatosis was 40.1%. Overall and disease-free survival analysis identified, among other factors, psoas muscle index [hazard ratio (HR) 0.67, 95% CI 0.53-0.85], sarcopenia (HR 2.09, 95% CI 1.06-4.14), and myosteatosis (HR 2.29, 95% CI 1.25-4.19) as independent factors implicated in oncological prognosis. EOCRC patients showed a high prevalence of sarcopenia and myosteatosis, similar to that described in elderly cohorts. This deficiency in muscle quality and quantity was a risk factor for recurrence and mortality during the follow-up of their neoplasia.

Accurate prediction of time-to-event outcomes, commonly known as survival analysis, is vital in high-stakes domains such as healthcare and business, where timely and trustworthy insights can have profound implications. Traditional survival analysis methods either provide predictions without clear explanations or offer interpretability without a mechanism to integrate expert insights. In many real-world scenarios, decision-makers require models that are both transparent and capable of interactively incorporating domain knowledge to refine predictions. The key challenge we address is how to simultaneously achieve accurate time-to-event forecasting, clear interpretability, and interactive integration of expert feedback. We propose the Interpretable and Interactive Deep Discrete-Time Survival Analysis framework, an approach that is both data-driven and knowledge-driven. Furthermore, it embeds expert knowledge into the model, dynamically aligns feature contributions with evolving risk patterns, and actively engages experts to guide the learning process interactively. This interactive strategy not only enhances predictive performance but also produces explanations that clearly reflect the critical factors identified by domain experts. Extensive evaluations on diverse clinical and business datasets demonstrate that our method captures feature importance and yields robust and reliable predictions that stand in contrast to conventional black-box models. These results indicate that bridging interpretability with interactive expert engagement can significantly improve decision support systems. By integrating accurate forecasting with human-aligned, interactive explanations, our framework offers a promising direction for developing more transparent and trusted models across a wide range of disciplines.

BackgroundMost patients with prostate cancer experience symptomatic skeletal events, leading to increased morbidity and mortality. BMAs have been approved since 2007 and recommended in mCRPC to prevent SSEs in patients with bone metastases or high-risk of osteoporotic fracture. Herein, we sought to assess real-world trends of BMA administration in patients with mCRPC.MethodsWe used the de-identified nationwide Flatiron Health electronic health record-derived database to extract patient-level data. Eligibility: patients with mCRPC with available date of mCRPC diagnosis and information on receipt of BMA. Patients were categorized into 2 cohorts based on BMA receipt. Treatment trends of BMA by year of mCRPC diagnosis were summarized using frequency and percentages. Baseline characteristics at mCRPC diagnosis (age, race-ethnicity, practice type, insurance) were compared using the Wilcoxon rank-sum and chi-squared tests.ResultsOf 24,105 patients with metastatic prostate cancer, 14,112 with mCRPC were eligible and included. A total of 7,990 (56.6%) received BMA while 6,122 (43.4%) did not. BMA receipt cohort: median age was 75 (IQR 67-81), the majority were White (61%), treated in community practice (87%) and had a commercial health plan (80%). BMA non-receipt cohort: median age was 75 (IQR 68-82), the majority were White (61%), treated in community practice (78%), and had a commercial health plan (76%). Use of BMA decreased over time from 56% in 2013 to 46% in 2024 (Table 1).ConclusionsDespite recommendations to use BMAs in patients with mCRPC and bone metastasis or high-risk of fracture, our findings reveal a low utilization rate of BMAs in mCRPC with a notable decline over time. This highlights the need to incorporate BMAs in clinical practice.Table 1Trends of BMA usage over time (2013-2024).Year, n (%)2013 N = 5492014 N = 10352015 N = 12232016 N = 13452017 N = 14412018 N = 13462019 N = 14692020 N = 13802021 N = 13522022 N = 13932023 N = 11962024 N = 383BMA receipt316 (56%)674 (65%)792 (65%)837 (62%)886 (61%)766 (57%)816 (56%)766 (56%)692 (51%)713 (51%)556 (46%)176 (46%)Denosumab190 (60.1%)450 (66.8%)557 (70.3%)599 (71.6%)606 (68.4%)533 (70%)526 (64.5%)488 (63.7%)410 (59.2%)414 (58.1%)290 (52.2%)94 (53%)Zoledronic acid120 (38%)220 (32.6%)228 (28.7%)233 (27.8%)270 (30.5%)225 (29%)281 (34.4%)273 (35.6%)277 (40%)295 (41.4%)258 (46.4%)82 (47%)Teriparatide/other bisph.6 (1.9%)4 (0.6%)7 (1%)5 (0.6%)10 (1.1%)8 (1%)9 (1.1%)5 (0.7%)5 (0.7%)4 (0.5%)8 (1.4%)0

SummaryInherited thrombocytopenia (IT) with germline variants in RUNX1, ETV6 or ANKRD26 carries a high risk (10%–45%) of developing haematological malignancy (IT‐HM). We evaluated the clinical, platelet and molecular characteristics in 37 patients with RUNX1‐related thrombocytopenia (RT), 9 with ETV6‐RT and 20 with ANRKD26‐RT. Genetic diagnosis was delayed by about 20 years from the identification of thrombocytopenia. Bleeding tendency was present in 25%–30% of RUNX1‐RT and ANKRD26‐RT patients. Platelet aggregation was impaired in 90% of all patients, while reduced activation and granule secretion were heterogeneous. Most RUNX1‐RT patients had low glycoprotein Ia (GPIa) levels, which may be a useful disease biomarker. Sixteen distinct genetic variants in RUNX1, four in ETV6 and four in ANKRD26 were identified in patients. The clinical profile showed immune, skin, gastrointestinal and other comorbidities in many patients. One third of the cases developed a malignancy: This included eight RUNX1‐RT patients with myelodysplastic syndrome (MDS), five with acute myeloid leukaemia (AML), and one with chronic myeloid leukaemia (CML) Ph+. One patient with ETV6‐RT subsequently developed B‐cell acute lymphoblastic leukaemia (B‐ALL) during childhood. Three cases with ANKRD26‐RT demonstrated a multifaceted clinical presentation, including B‐ALL Ph+, MDS and breast cancer. The high incidence of HM development highlights the importance of early diagnosis in life.

BackgroundPembrolizumab plus lenvatinib is a treatment option for metastatic Renal Cell Carcinoma (mRCC). In the ARON-1 study we investigated we the real-world experiences gained from the use of this combination for mRCC.MethodsWe retrospectively investigated real-world clinical outcomes of mRCC patients receiving pembrolizumab plus lenvatinib within the ARON-1 study. Overall survival (OS) was calculated from the start of pembrolizumab plus lenvatinib to death for any cause. Progression-Free Survival (PFS) was defined as the time from the start of pembrolizumab to progression or death from any cause. Duration of response (DoR) was defined as the time from the start of pembrolizumab to disease progression or death, whichever occurred first, in patients who achieved complete remission (CR) or partial response (PR). Overall Response Rate (ORR) was defined as the proportion of patients who achieve a CR or PR per RECIST criteria. Adverse events were retrospectively collected from electronic and paper charts and categorized by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.ResultsOverall, we included 202 mRCC patients treated with pembrolizumab plus lenvatinib. The median follow-up time was 15.1 months. The median OS was not reached (NR), with a median PFS of 25.6 months and an Overall Response Rate (ORR) of 59%. The median Duration of Response (DoR) was 26.2 months. G3-G4 adverse events (AEs) were observed in 92 patients (46%), with hypertension being the most common AE (13%).ConclusionsPembrolizumab plus lenvatinib is an effective and tolerable treatment for mRCC also in the real-world setting.