Patients with HPV+ oropharyngeal carcinoma were enrolled on an institutional review board–approved prospective study of which de-escalation based on imaging response was done for node(s) only. Pretreatment 18F-fluorodeoxyglucose and dynamic 18F-FMISO (fluoromisonidazole) positron emission tomography (PET) scans were performed. For patients with pretreatment hypoxia on18F-FMISO PET (defined as a >1.2 tumor to muscle standard uptake value ratio), a repeat scan was done 1 week after chemoradiation. Patients without pretreatment hypoxia or with resolution of hypoxia on repeat scan received a 10-Gy dose reduction to metastatic lymph node(s). The 2-year local, regional, distant metastasis–free, and overall survival rates were estimated using the Kaplan-Meier product-limit method. A subset of patients had biopsy of a hypoxic node done under image guidance.
Thirty-three HPV+ OPC patients were enrolled in this pilot study. One hundred percent showed pretreatment hypoxia (at primary site and/or node[s]), and among these, 48% resolved (at primary site and/or node[s]); 30% met criteria and received 10-Gy reduction to the lymph node(s). At the median follow-up of 32 months (range, 21-61 months), the 2-year locoregional control rate was 100%. One patient failed distantly with persistence of hypoxia on 18F-FMISO PET. The 2-year distant metastasis–free rate was 97%. The 2-year OS rate was 100%. Hypoxia on imaging was confirmed pathologically.
Hypoxia is present in HPV+ tumors but resolves within 1 week of treatment in 48% of cases either at the primary site and/or lymph node(s). Our 100% locoregional control rate suggests that intratreatment functional imaging used to selectively de-escalate node(s) to 60 Gy was confirmed safe using our stringent imaging criteria. Intratreatment functional imaging warrants further study to determine its ultimate role in de-escalation treatment strategies.