Decoding anterior tongue carcinoma beyond TNM: Indian multi-centric, real-world data on molecular profiling and immunity in relation to clinical outcome—A divide, dive deep, and conquer approach.

Abstract

e18054 Background: Anterior tongue cancer is predominant in Asia, particularly India. Locally advanced anterior tongue cancer exhibits poor outcomes, with recurrence rates exceeding 50% within two years despite standard treatment. The current head and neck cancer guidelines are largely based on Western data, which has limited anterior tongue cancer-specific insights. Our study seeks to risk-stratify tongue cancer using clinical and pathological parameters and further evaluate genomic and immune correlates with clinical outcomes. This represents a pioneering effort in addressing this unmet need. Methods: A prospective study was conducted on 100 anterior tongue cancer cases (2021–2024) following ethical committee approval. Patients were stratified into 4 risk groups. NGS based 500-gene molecular profiling and IHC based immune markers were assessed ,correlating them with 2 year disease-free survival (DFS). Group A: Depth of invasion (DOI) < 5 mm; No adverse features. Group B: DOI > 5 mm; Positive LVI or PNI; Lymph node-negative. Group C: Tumor classified as T3/T4 or lymph node-positive; Treated with neoadjuvant chemotherapy [C1] or chemoimmunotherapy [C2]. Group D: Tumor classified as T3/T4 or lymph node-positive; Underwent upfront surgery followed by adjuvant therapy. Results: 2 year DFS: 100%,85%,50%-85% and 70% in Group A,B,C1-C2 and D. Genomic Insights: The most frequent mutation was p53 , followed by TERT and NOTCH . Notably, recurrence rate was 83% in TERT mutant cases. Immune Correlates: PD-L1 positivity was observed in 80% of tumors and 90% were immune cell infiltration positive [HOT]. Group-Specific Observations: Group A: Early Tongue cancer without any adverse features had 100% 2 year DFS. Group B: This subgroup received adjuvant radiation as optional recommendation, 2 failures in this group accounting to a drop in DFS to 85% was in the subset that received no adjuvant radiation. Group C: NACT yielded 40% response, 30% stable disease, and 30% progression . High PD-L1 positivity suggested potential for chemo-immunotherapy, using which, the response rate improved to 90%,showing promise in this cohort. Group D: High-risk features (T4, N2, LVI, PNI) reduced DFS from 70% to 20%, emphasizing the need for intensified neoadjuvant strategies which potentially could be chemoimmunotherapy. Conclusions: Our study highlights that 80% of anterior tongue cancers are PD-L1 positive, and improved response to chemo immunotherapy, emphasizing the need for immunotherapy-based approaches in locally advanced cases. Genomic markers such as TERT and p53 are linked to poor prognosis, necessitating treatment intensification. Thus with existing inferior outcomes to standard therapy, tailor made treatment intensification is a mandate in anterior tongue carcinomas. Clinical trial information: CTRI/2024/12/078690 .