Presenter(s)
S. Choi1,2, V. Lee3, E. C. Dee4, A. L. Ong King5, J. J. Kang6, Y. Yu4, S. M. McBride4, M. Wu7, T. J. Ow8, A. Ho7, C. Pickering9, R. J. Wong8, N. Riaz4, and N. Y. Lee4; 1Case Western Reserve University School of Medicine, Cleveland, OH, 2Memorial Sloan Kettering Cancer Center, New York City, NY, 3Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT, 4Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 5Department of Dermatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, 6Memorial Sloan Kettering Cancer Center, New Haven, CT, 7Memorial Sloan Kettering Cancer Center, New York, NY, 8Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, 9Yale School of Medicine, New Haven, CT
Purpose/Objective(s):
Preclinical studies have demonstrated that loss-of-function mutations in CASP8 increase invasiveness in head and neck squamous cell carcinoma (HNSCC) cell lines. However, the association between CASP8 mutations and clinically relevant invasive features such as bone invasion has not been well characterized. We evaluated whether oncogenic CASP8 mutations are associated with bone invasion in patients with oral cavity carcinoma (OCC) using institutional genomic and clinical data.Materials/Methods:
Patients with OCC and available next-generation sequencing data were identified from an institutional database. CASP8 mutation status was annotated using OncoKB, and oncogenic mutations were analyzed. Detailed chart review was performed to determine the presence of bone invasion based on pathologic findings. Multivariable logistic regression was used to assess the association between oncogenic CASP8 mutations and bone invasion, adjusting for gender and race. Statistical significance was defined as p < 0.05.Results:
A total of 89 patients with OCC were included. The median age was 63 years (interquartile range [IQR] 56–73), and 53 patients (59.6%) were male. The cohort was predominantly White (75.3%), with 19.1% Asian and 2.2% Black patients. Oncogenic CASP8 mutations, as defined by OncoKB, were identified in 10 patients (11.2%). Bone invasion was present in 21 patients (23.6%) overall and occurred more frequently in tumors harboring oncogenic CASP8 mutations (50.0%) compared with CASP8 wild-type tumors (50.0% vs 20.3%). On multivariable logistic regression adjusting for gender and race, oncogenic CASP8 mutation status was significantly associated with bone invasion (odds ratio [OR] 5.04, 95% confidence interval [CI] 1.15–24.17, p = 0.033).Conclusion:
Oncogenic CASP8 mutations are significantly associated with bone invasion in OCC, supporting prior preclinical evidence linking CASP8 loss to increased tumor invasiveness in HNSCC. Identification of CASP8 mutations may help identify tumors at higher risk for osseous involvement, with potential implications for surgical planning and earlier consideration of adjuvant radiotherapy. These findings highlight the role of genomic markers in predicting locally aggressive disease and guiding multidisciplinary management.