In what situations, if any, would you add chemotherapy to adjuvant radiotherapy in patients with resected head and neck cancer without ENE or positive magrin?

I would only consider adding Chemotherapy to radiation if at least 3 intermediate risk factors (as mentioned in the question) are present post-operatively in an HPV negative patient. Obviously, each such patient is discussed in the tumor board prior to such recommendation.

In our multi-D tumor board, we do not routinely recommend concurrent radiation and chemotherapy in the post-op situation for patients who do not have positive margins or ENE.

Rarely, if we encounter patients with large or multiple level 4 nodes, we may have a discussion about the addition of chemo.

As this is an unanswered question, we are actively trying to enroll in post-op trials such as EA3132: Phase II Randomized Trial of Radiotherapy with or without Cisplatin for Surgically Resected Squamous Cell Carcinoma of the Head and Neck (SCCHN) with TP53 Sequencing.