Immune-Adjusted Nodal Risk Classification After Neoadjuvant Immunotherapy for Resectable Head and Neck Cutaneous...

Area of Science:

• Oncology
• Immunotherapy
• Surgical Pathology

Background:

• Conventional nodal staging may not accurately reflect outcomes after neoadjuvant immunotherapy for head and neck cutaneous squamous cell carcinoma (HNcSCC).
• There is a need for improved risk stratification methods that account for post-treatment biological changes.

Purpose of the Study:

• To develop and validate an immune-adjusted nodal risk classification for resectable HNcSCC treated with neoadjuvant immunotherapy.
• To compare the prognostic performance of the new classification against conventional staging methods (ypN stage and iN-core).

Main Methods:

• Retrospective analysis of 82 HNcSCC patients treated with neoadjuvant immunotherapy and surgery.
• Development of the iN-risk classification integrating residual viable nodal burden, residual extranodal extension (rENE), and nodal pathological response.
• Comparison of disease-free survival (DFS) and overall survival (OS) between risk groups and with conventional staging.

Main Results:

• The iN-risk classification identified three distinct risk groups (iN-low, iN-intermediate, iN-high) with significantly different 3-year DFS rates (91.2%, 70.8%, 25.9%; P < 0.001).
• iN-high disease was independently associated with inferior DFS (HR 13.42) and OS (HR 20.86) compared to iN-low disease.
• The iN-risk model demonstrated superior prognostic accuracy (higher C-indexes) for DFS and OS compared to conventional staging.

Conclusions:

• An immune-adjusted nodal risk classification incorporating residual nodal disease, rENE, and nodal response offers improved risk stratification for HNcSCC patients post-neoadjuvant immunotherapy.
• This novel classification may aid in personalizing treatment strategies and predicting outcomes more accurately.