Squamous Cell Carcinoma, NOS

This multicenter retrospective Japanese study compared afatinib and osimertinib as first-line treatments for advanced or recurrent non-small cell lung cancer (NSCLC) harboring uncommon EGFR mutations. Weighted analyses revealed no significant differences in time to treatment failure or overall survival between the two EGFR-TKIs. While afatinib was associated with higher response rates and more frequent adverse events requiring dose reduction, subgroup analyses suggested differential treatment effects based on mutation subtype. Furthermore, subsequent immune checkpoint inhibitor-based regimens showed limited additional benefit.

This retrospective study compared the clinicopathological features of stage I-II oral squamous cell carcinoma (OSCC) in adolescents and young adults (AYAs) versus older patients. OSCCs in AYAs are more frequently located on the tongue and exhibit distinct histological patterns, including an abnormal TP53 immunophenotype. Although AYAs demonstrate significantly better overall and disease-free survival, a depth of invasion (DOI) greater than 5 mm is a major prognostic indicator for distant metastasis and poorer survival within this group. Other factors such as clinical stage, tumor thickness, and tumor budding may also predict the risk of postoperative lymph node metastasis. Tested molecular markers did not provide robust prognostic stratification.

This study investigated the TP53 mutation landscape in oral squamous cell carcinoma (OSCC) and its association with patient survival. Using next-generation sequencing on 124 samples, pathogenic TP53 mutations were detected in 65% of patients, encompassing 75 distinct variant patterns. Patients harboring these mutations exhibited significantly shorter cancer-specific survival, particularly those with advanced-stage (III/IV) disease. Truncating or splice mutations were associated with an even worse prognosis. These findings highlight the importance of TP53-based molecular classification for developing novel precision strategies against OSCC.

This study investigates histologic transformation to lung squamous cell carcinoma (LUSC) in EGFR-mutant lung adenocarcinoma (LUAD) patients, an underrecognized resistance mechanism. Multiomic analyses revealed that patients with transforming or adenosquamous (LUAS) phenotypes experienced shorter overall survival on first-line osimertinib. Inactivation of the retinoblastoma (Rb) pathway, particularly via CDKN2A/B deletions, was identified as a key driver of this transformation. Furthermore, MET pathway upregulation was observed, and combined EGFR and MET inhibition demonstrated efficacy in preclinical models. These findings suggest novel strategies to counteract this aggressive form of resistance.