225MO - Clinical, pathologic and immune-related features of radiation-associated oral cavity squamous cell carcinoma: A matched cohort study

Background

Post-radiation (RT) oral squamous cell carcinoma (OCSCC) is a common second malignancy in patients with nasopharyngeal carcinoma, often with a lethal outcome. We conducted a retrospective comparative analysis on the clinicopathologic features of post-RT OCSCC with demographic-matched sporadic OCSCC to shed light on their distinctive clinical behaviors.

Methods

Consecutive patients with OCSCC in our institution from 2000-2020 were identified. Post-RT OCSCC were matched with sporadic OCSCC in a 1:2 fashion using age, sex, year of diagnosis and anatomic sub-sites. Clinical records and pathology slides were reviewed retrospectively. Tumor samples were subjected to immunohistochemical staining for Ki67, FOXP3, PD-1, PD-L1, MSH6 and PMS2 and quantitative mRNA expression analysis of 31 immune-related genes to investigate any differences in host immune response across two groups.

Results

Sixty post-RT OCSCC and 113 sporadic OCSCC were included. Post-RT OCSCC had a higher proportion of N0 diseases than sporadic OCSCC. Adverse pathologic features were more frequently observed in post-RT OCSCC, including perineural invasion, worse pattern of invasion-5 and tumor budding ≥5. With a median follow-up duration of 10.2 years, the relapse-free survival (RFS) and overall survival (OS) were lower in patients with post-RT than sporadic OCSCC (10-year RFS, 29.6% vs 52.4%, p=0.035; 10-year OS, 30.5% vs 52.3%, p=0.031). OCSCC-specific survival was similar (10-year, 68.8% vs 67.1%, p=0.91). All relapses in patients with post-RT OCSCC were loco-regional, whereas 34% of relapses in patients with sporadic OCSCC were distant. Patients with post-RT OCSCC had excess mortality due to pneumonia and cerebrovascular events. Compared with sporadic OCSCC, post-RT OCSCC had higher gene expression of CD4 and TGF-β, and higher PD-1 expression on IHC.

Conclusions

Post-RT OCSCC has distinct clinic-pathologic characteristics and relapse patterns from sporadic OCSCC which could be attributable to limited treatment options, more aggressive biologic phenotype and different host immune response. Further exploration of the role of immune checkpoint therapy may be justified given the high proportion of PD-1 in post-RT OCSCC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Hospital Authority, Hong Kong.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.