Pathology

Standardized p53‑IHC shows substantial reproducibility and affects Barrett's diagnoses

In a nationwide Dutch consultation cohort (1,146 cases, 1,704 biopsy levels), p53‑IHC concordance with an expert panel was moderate-to-substantial (κ = 0.61). Interobserver agreement among 13 trained pathologists was substantial (Fleiss' κ = 0.65). About 24.2% of p53‑IHC assessments were reclassified versus referring hospitals, and p53‑IHC prompted diagnostic shifts between NDBE, IND, and LGD. The authors conclude standardized p53‑IHC interpretation is reliable and clinically meaningful for routine Barrett's workflows. 1

First‑line ICI regimen efficacy in advanced NSCLC varies by histology

This network meta‑analysis of 41 phase 3 RCTs (23,871 patients) found ICI regimen rankings differ between non‑squamous and squamous NSCLC. Toripalimab plus chemotherapy ranked best in non‑squamous disease (SUCRA = 0.97) but worst in squamous disease (SUCRA = 0.09). PD‑L1 subgroups showed different optimal regimens, implying PD‑L1 alone may be insufficient to guide first‑line selection. Authors recommend accounting for histological subtype when selecting first‑line ICI combinations. 2

Basket and umbrella trials are promising but methodologically demanding in pediatrics

This systematic review screened 1,867 records and included 28 studies addressing pediatric basket and umbrella designs. Basket designs were more common, especially in early‑phase oncology and rare diseases, and are efficient for biomarker‑defined groups. The review emphasizes the need for robust statistical plans, Bayesian methods when appropriate, and clear regulatory alignment. Authors caution these designs require careful inference methods and cannot replace rigorous confirmatory trials without proper safeguards. 3