Longitudinal Analysis Reveals Dynamic Changes in Histopathologic Features in Responders to Neoadjuvant Treatment in a Stage III BRAF-Mutant Melanoma Cohort
Details
Publication Year 2025-04-14,Volume 38,Issue #8,Page 100776
Journal Title
Modern Pathology
Publication Type
Online publication before print
Abstract
Despite advances in systemic therapies, cutaneous melanoma remains a highly deadly disease. Patients with high-risk stage III melanoma have a significant likelihood of recurrence following surgery. Although adjuvant immunotherapy has been the standard of care, recent evidence demonstrates that neoadjuvant immunotherapy is more effective for higher-risk stage III patients, showing superior survival outcomes compared with adjuvant immunotherapy. This has led to an immediate paradigm shift in clinical practice toward neoadjuvant therapy for this cohort. The NeoTrio clinical trial assessed the efficacy of sequential or combination BRAF-targeted therapy with anti-programmed cell death-1 in the neoadjuvant setting. However, research on longitudinal histopathologic changes during this treatment period remains limited. Analysis of hematoxylin and eosin slides from 60 patients across 4 matched neoadjuvant timepoints revealed dynamic changes in a number of treatment response features. Females achieved significantly higher rates of major pathologic response (P = .002) and displayed higher levels of inflammatory fibrosis (P = .04) and hyalinized fibrosis (P = .01). The presence of tertiary lymphoid structures (P = .013) and plasma cells (P = .02) at resection was significantly associated with response. Combination scoring of histopathologic features (composite score and the immune-related pathologic response [irPR] score) was significantly associated with response early during the neoadjuvant period (composite score at week 2 on-treatment, P = .03; high irPR score at week 2 on-treatment, P = .01). A high irPR score at week 2 on-treatment was also found to be significantly associated with a lower chance of recurrence at this early neoadjuvant timepoint (P = .02). Other features associated with a lower likelihood of recurrence included increased hyalinized fibrosis (P = .015) and the presence of extensive lymphocyte density score (P = .01), tertiary lymphoid structures (P = .03), and plasma cells (P = .01). This study deepens our understanding of treatment response markers and their dynamic changes during neoadjuvant therapy. It underscores the significance of these features, particularly given their early emergence and strong associations with response and recurrence.
Keywords
BRAF mutation; dabrafenib; immunotherapy; melanoma; targeted therapy; trametinib
Department(s)
Medical Oncology
Terms of Use/Rights Notice
Refer to copyright notice on published article.


Creation Date: 2025-05-22 04:29:26
Last Modified: 2025-05-22 04:29:54

© 2025 The Walter and Eliza Hall Institute of Medical Research. Access to this website is subject to our Privacy Policy and Terms of Use

An error has occurred. This application may no longer respond until reloaded. Reload 🗙