Antibody–drug conjugates (ADCs) are complex molecules composed of a monoclonal antibody, a linker and a cytotoxic payload. Their design enables the selective delivery of cytotoxic agents to tumoral cells through antibody binding to a tumor-expressed antigen, followed by internalization, intracellular degradation and payload release, ultimately enabling the cytotoxic drug to exert its antitumor activity. ADCs have been evaluated in phase II and III trials in previously treated advanced non-small cell lung cancer (NSCLC), both in oncogene-addicted and in non-oncogene-addicted tumors, addressing resistance to standard therapies. Ongoing clinical trials are now expanding their use both in the first-line setting for advanced disease and in earlier disease stages. This narrative review summarizes the currently available data for ADC treatment in NSCLC, highlighting the need for improved patient selection to maximize benefit while limiting toxicity, incorporating clinical characteristics, pharmacogenomics and optimal treatment sequencing in the equation. Moreover, the understanding of resistance mechanisms and the development and validation of predictive biomarkers will be of utmost relevance to inform clinical practice.
CONTEXT:The likelihood of remission in patients with autoimmune hyperthyroidism (AH) depends on several prognostic factors. The free T3 (FT3)/free T4 (FT4) ratio has been suggested as a potential marker of disease severity and prognosis. OBJECTIVE:To evaluate the prognostic value of the FT3/FT4 ratio in predicting the likelihood of relapse in patients with AH. METHODS:This retrospective cohort study included 80 patients with AH diagnosed between 2000 and 2021. Clinical and biochemical data were collected at diagnosis and during follow-up to assess the likelihood of remission in patients attempting to discontinue antithyroid drug (ATD) therapy. Receiver operating characteristic analysis and logistic regression were used to identify predictors of relapse. RESULTS:Of the 48 patients who discontinued ATD therapy, 24 (50%) relapsed, predominantly within 12 months. The FT3/FT4 ratio was significantly higher in patients who relapsed both at diagnosis (median 0.46 vs 0.36; P .001) and at ATD withdrawal (median 0.43 vs 0.33; P < .001). An FT3/FT4 ratio ≥0.42 at diagnosis predicted relapse with 83% sensitivity and 66% specificity. In a multivariate analysis, FT3/FT4 ratio ≥0.42 at diagnosis (odds ratio 7.18; P .012) and the presence of orbitopathy were identified as independent predictors of relapse. Longer time to FT3 normalization (P .02) and orbitopathy were associated with relapse in univariate analyses (P .039). CONCLUSION:The FT3/FT4 ratio, measured both at diagnosis and before ATD withdrawal, is a significant predictor of relapse in AH. This parameter may represent a useful tool for guiding decisions about treatment duration and withdrawal.
Background Muscle-invasive and metastatic urothelial carcinoma of urinary bladder (UCUB) is associated with poor overall survival. However, individual years of life lost (YLL) according to detailed patient and disease characteristics have never been quantified. Patients and Methods Within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2021), muscle-invasive organ-confined (OC, T2N0M0), non-organ-confined (NOC, T3-4 and/or N1-3 M0), and metastatic (anyT, anyN, M1) UCUB patients aged 40-75 years were included. Relying on Social Security Administration (SSA) life tables, a 1:1 age, sex, and year of diagnosis matched control (Monte Carlo simulation) was simulated for each patient. Kaplan-Meier method was used to calculate average YLL truncated at the age of 75 years between SEER cases and SSA simulated controls. Results A total of 30,519 patients were included: 14,754 (48.3%) OC, 10,330 (33.8%) NOC, and 5435 (17.8%) metastatic. Compared with simulated population controls, average YLL was 3.7, 6.0, and 9.1 years for OC, NOC, and metastatic disease, respectively. YLL was most pronounced among patients diagnosed at younger ages (40-55 years: 9.2, 14.1, and 18.0 years for OC, NOC, and metastatic, respectively), decreasing with advancing age at diagnosis. Less pronounced YLL observations were recorded in most contemporary years (2017-2021: 2.7, 4.4, and 7.9 years for OC, NOC, and metastatic, respectively) across all stages compared with earlier periods. No clinically meaningful differences in YLL were observed between sexes. (male OC: 3.6, NOC: 5.9, metastatic: 9.0; female OC: 4.1, NOC: 6.6, metastatic: 9.5). Conclusions UCUB is associated with substantial YLL, particularly in metastatic and younger patients. However, an YLL decrease over time was observed.
To identify a tumor-mean absorbed dose (Dmean) that can predict response to Yttrium-90 resin-microsphere transarterial radioembolization (TARE) in patients with hepatocellular carcinoma (HCC) and evaluate its efficacy and safety. Patients with HCC eligible for TARE in two centers between January 2020 and May 2024 were retrospectively analyzed. Clinical, radiological, and procedural data were collected. Objective response rate (ORR) on lesion, complete response (CR), overall response, time-to-local progression (TLP), and time-to-progression (TTP) were evaluated on contrast-enhanced CT at 3 and 6 months according to mRECIST. The optimal Dmean of ORR on the target lesion and of CR was identified with ROC analysis at 3-months. Fischer’s test compared ORR, Kaplan–Meier survival outcomes, and Cox regression was used for uni-and multivariable analyses. Seventy-six lesions in 64 patients (mean age 71.3 ± 9.6; 54 men) were evaluated. Median follow-up was 15.0 months (IQR 8.0–24.3). Mean tumor diameter was 55.2 (± 31.8) mm. CR on target lesion at 3-months was achieved in 42 lesions. Mean TLP and OS were 27.6 ± 2.5 and 36.2 ± 2.9 months, respectively. The calculated Dmean for ORR was 296.74 Gy (specificity 100, PPV 100
Distinguishing Glioblastoma (GBM) recurrence from radiation-induced injury, including radiation necrosis (RN), remains a major clinical challenge in neuro-oncology. Because angiogenesis reflects dynamic vascular remodeling, we investigated whether longitudinal assessment of circulating angiogenic mediators, particularly the Angiopoietin-1 to Angiopoietin-2 ratio (Ang-1/Ang-2), could improve discrimination between disease progression and RN. In this prospective observational study, 42 patients with newly diagnosed GBM underwent peripheral blood (serum) sampling at index surgery and at reoperation. Circulating angiogenic and inflammatory mediators were quantified using a multiplex bead-based assay. Imaging findings were integrated with histopathological confirmation at reoperation (n = 21). Baseline Ang-1/Ang-2 ratios were lower (median 3) in patients whose first post-treatment event was RN (n = 11) than in those developing tumor recurrence (median 7, p = 0.028). Higher Ang-1/Ang-2 were associated with reduced RN risk (HR 0.75, p = 0.031). Longitudinally, Ang-1 levels declined following chemoradiotherapy (median change − 9235 pg/mL; p = 0.002), resulting in reduced Ang-1/Ang-2 (p = 0.004). At reoperation, recurrent tumors exhibited higher peripheral Ang-1/Ang-2 than RN (median 2.36 vs. 1.48; p = 0.023). Correlation network analyses of peripheral mediators revealed dense, synchronized signaling in RN and modular network organization with reduced global synchronization in recurrence. The addition of Ang-1/Ang-2 provided a possible incremental explanatory value over advanced imaging alone (ROC 0.94 vs. 0.73; p = 0.055). Peripheral assessment of the Ang-1/Ang-2 ratio may capture a compressed systemic signal reflecting the underlying vascular state beyond the blood-brain barrier. By encoding the balance between vascular stabilization and destabilization within the angiopoietin-Tie2 axis, this ratio provides biologically meaningful information and represents a mechanistically grounded biomarker.
