The current study reports the results of an open label pilot study evaluating a novel treatment protocol for patients with locally advanced head and neck cancer. Patients received induction chemotherapy and those who had a clinical complete response to induction chemotherapy were offered trans-oral nidusectomy for the primary lesion and neck node dissection. If a pathologic complete response was achieved, patients were then observed. Patients not achieving a clinical or pathologic complete response to induction therapy were subsequently treated with chemoradiation.