Histological heterogeneity of SLFN11 expression and its association with response to carboplatin plus paclitaxel therapy in salivary gland cancer.

BACKGROUND: Schlafen family member 11 (SLFN11) has emerged as a potential biomarker of sensitivity to DNA-damaging agents, including platinum compounds. However, its expression profile and clinical significance in salivary gland cancer (SGC) remain poorly understood. This study investigated the histological distribution of SLFN11 expression and its association with response to carboplatin plus paclitaxel (CBDCA+PTX) therapy in SGC. METHODS: SLFN11 expression was assessed by immunohistochemistry using an H-score-based method. Associations between SLFN11 expression and histological grade or subtype were evaluated. In addition, treatment outcomes were analyzed in patients who received CBDCA+PTX as first-line systemic therapy for recurrent or metastatic disease. Objective response rate (ORR) was assessed according to RECIST version 1.1, and progression-free survival (PFS) was estimated using the Kaplan-Meier method. RESULTS: SLFN11 expression demonstrated significant heterogeneity among histological subtypes and was enriched in high-grade tumors, particularly salivary duct carcinoma and squamous cell carcinoma. Seventeen patients treated with CBDCA+PTX were included in the efficacy analysis. In the overall cohort, ORR was numerically higher in the SLFN11-high group than in the SLFN11-low group (60% vs. 29%; odds ratio, 3.75). A similar tendency was observed in the non-adenoid cystic carcinoma (non-AdCC) subgroup (75% vs. 50%; odds ratio, 3.00). In contrast, PFS did not differ by SLFN11 expression status. CONCLUSIONS: SLFN11 expression varies substantially across histological subtypes of SGC and is enriched in high-grade tumors. SLFN11-high tumors showed higher response rates to CBDCA+PTX therapy, suggesting that SLFN11 may be associated with initial tumor response to platinum-containing chemotherapy, although this finding is exploratory and hypothesis-generating.