The use of imaging midtreatment for human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma may guide the use of deintensified chemoradiotherapy, according to a phase II study from the University of Michigan presented by Regan et al at the 2024 Multidisciplinary Head and Neck Cancers Symposium (Abstract 16).
“FDG-PET [fludeoxyglucose/positron-emission tomography] may be a reliable biomarker to selectively de-escalate radiation dose” in early-stage HPV-positive disease, improving toxicity while preserving oncologic outcomes, said Samuel Regan, MD, a resident in the Department of Radiation Oncology at the University of Michigan. “There were few locoregional recurrences,” he noted.
About the Study
The study enrolled 89 patients with stage I to II HPV-associated oropharyngeal tumors that were FDG-PET–avid. All patients had a radiation plan for 70 Gy to gross disease and 56 Gy to elective nodal regions, to be given concurrently with carboplatin and paclitaxel. A midtreatment PET scan was planned to assess response, and these imaging results determined additional treatment. Patients with a ≥ 50% reduction in metabolic tumor volume stopped treatment at 54 Gy and the others completed the entire course of 70 Gy. The primary endpoint was noninferiority of 2-year locoregional recurrence in the entire cohort, compared to an institutional historic control.
Primary Endpoint Met
Of the 84 patients who underwent a midtreatment FDG-PET and evaluation for de-escalation of radiotherapy, 48 continued to standard therapy and 36 met the criteria for de-escalation. The only significant difference in patient characteristics was higher baseline weight in the standard treatment group (median = 208 pounds vs 186 pounds, P = .011). Median follow-up was 32 months.
The trial met its primary endpoint, demonstrating a 2-year locoregional recurrence rate for the entire cohort of 6.8%, and, by cohort, 4.6% among patients treated throughout with 70 Gy and 9.4% for those de-escalated to 54 Gy. “Importantly, these rates represent only two and three locoregional failures each, respectively, and with broad, overlapping confidence intervals precludes any definitive comparison of these two different cohorts,” Dr. Regan said.
The 2-year progression-free survival rate was 87% with 70 Gy, with salvage therapy leaving the majority of these eight patients without evidence of disease, a few still on therapy, and one disease-related death in the conventional treatment group.
Weight Loss and Swallowing Metrics
In general, de-escalation ameliorated toxicity related to radiotherapy. Median weight loss from baseline to 3 months postradiotherapy was 23 pounds in the standard group and 11 pounds in the de-escalated group (P < .001), and percentage lost was 12.6% and 6.0%, respectively (P < .001). A feeding tube was required by 16% and 11% of patients, respectively (P = .5), and there was no appreciable change in penetration-aspiration scale from baseline in either group.
The University of Washington Quality of Life (UWQOL) Total and Pain Subscale scores as well as the FACT-HN Total and Cancer Subscales significantly improved at 1 month—above the minimal clinically important difference threshold (0.5 standard deviations)—in the de-escalated cohort. Most patients in both cohorts returned to baseline at 1 year.
Better patient selection by using multimodality imaging and companion biomarkers—perhaps circulating tumor HPV DNA—may also improve the efficacy of de-intensification, Dr. Regan added.
Disclosure: For full disclosures of the study authors, visit astro.confex.com.
