Whether receipt of radiation itself versus having persistent baseline genetic and environmental (read: smoking) risk factors leads to second primary head and neck cancers remains controversial. Nonetheless, cancers arising in a previously irradiated field are bad news, both due to uniquely bad biology and limited safe treatment options. This retrospective matched cohort study compared post-radiaiton (n=60) versus de novo (n=113) squamous cell carcinoma of the oral cavity to demonstrate the former had more adverse pathologic features as expected but also higher immune cell expression of PD-1 and higher expression of TGF-β in the tumor microenvironment. This suggests immune checkpoint inhibition, or maybe even a novel dual-targeted agent, may prove of particular benefit in addressing the challenges of definitively managing a second head and neck primary oral cavity cancer in a previously irradiated field. | Chow, JAMA Netw Open 2023
