A Complete Response to Immunotherapy in a Patient with Locally Advanced Squamous Cell Lung Cancer Harboring a Novel TMEM178B::BRAF Fusion: A Case Report.

Background: The development of advanced genomic sequencing techniques now makes it possible to identify novel biomarkers and guide the design of targeted therapeutic strategies. For advanced squamous non-small cell lung cancer (NSCLC), V-Raf murine sarcoma viral oncogene homolog B1 (BRAF) fusions have not been evaluated as a therapeutic target. However, agents that block the pathway activated by these fusions have shown efficacy in other solid tumors, such as melanoma, astrocytoma, acinar carcinoma of the pancreas, and papillary thyroid tumors. Case Report: Here, we present the case of a patient with locally advanced squamous NSCLC and minimal smoking history who was found to harbor a TMEM178B::BRAF fusion. Following curative-intent chemoradiotherapy (CRT) and subsequent maintenance immunotherapy, the patient achieved a complete radiological response at 12 months, accompanied by a marked improvement in both quality of life and overall clinical status. Conclusions: The findings in this patient underscore the importance of extending molecular genetic studies to patients with squamous histology who lack toxic habits or known risk factors. Gene alterations such as BRAF rearrangements may not only predict the response to immunotherapy-based treatments but also represent a promising avenue for the development of new therapeutic strategies.