De-Escalation Strategy Appears Feasible in HPV+ Oropharyngeal Cancer

HPV-positive oropharyngeal cancer patients undergoing concurrent chemoradiotherapy were still able to achieve good clinical outcomes, and with minimal toxicity, with reduced radiation to elective treatment regions, a single-institution study found.

The de-escalation strategy was associated with a 24-month locoregional control rate of 97.0%, a distant metastasis-free survival of 95.2%, and overall survival of 95.1% in a cohort of nearly 300 patients with HPV-positive oropharyngeal cancer, reported Nancy Lee, MD, and colleagues from Memorial Sloan Kettering Cancer Center in New York City.

“With longer term follow-up data to validate the results, this regimen can be safely adapted for treating a wide range of patients with HPV-associated oropharyngeal carcinoma undergoing primary concurrent chemoradiotherapy,” they wrote in JAMA Oncology.

As pointed out by Lee’s group, the commonly used subclinical dose of 50 to 60 Gy “was based on historical radiobiological data from limited imaging capability for detecting occult metastasis.”

For their study, the investigators aimed to evaluate a de-escalation strategy established at Sloan Kettering, in which HPV-positive oropharyngeal cancer patients undergoing concurrent chemoradiotherapy received a lower dose to elective nodal and subclinical regions, while sparing selected negative neck, retropharyngeal, level Ib, and level V nodal basins.

Their cohort study included 276 patients (median age 61 years, 89.5% male) consecutively treated with concurrent chemoradiotherapy from 2017 to 2019. They received a reduced radiotherapy volume and dose of 30 Gy to the elective treatment regions over 15 fractions, followed by a cone down of 40 Gy in 20 fractions to gross disease for a total dose of 70 Gy.

About a third had cT3-cT4 disease, 23.5% had cN2-cN3 disease, and 93.8% had a primary site at either the base of the tongue or the tonsil. Three-fourths received high-dose cisplatin, with 62.3% able to complete a cumulative dose of 300 mg/m².

“In 87 patients (31.5%), indeterminate nodes or areas immediately adjacent to the gross disease were treated with a dose of 50 Gy,” Lee and her colleagues reported. “Most patients who received an intermediate dose of 50 Gy were treated within the first year after implementing the new dosing regimen before physicians gradually became more comfortable treating the entire elective regions with 30 Gy.”

In some cases, the higher dose related to “other small areas of concern per the treating physician’s discretion, and this flexibility in dosing has worked well for treatment planning while still keeping most of the elective regions dosed to 30 Gy,” they added.

During a follow-up of 26 months, eight patients (2.9%) developed a locoregional recurrence — seven at the primary site and/or gross disease in nodes that received a full 70 Gy dose, and one who had persistent gross disease in a node that was not previously identified and received only 30 Gy.

Just 17 patients (6.2%) required a feeding tube during treatment (median 5 months of feeding tube dependence).

Patient-reported quality-of-life scores, as determined by the Gothenburg Trismus Questionnaire, showed that facial pain scores were substantially better at 24 months than at baseline, while muscular tension scores were worse and scores for jaw-related problems and eating limitation were comparable to baseline.

In a commentary accompanying the study, Philip Schaner, MD, PhD, of Dartmouth-Hitchcock Medical Center in Hanover, New Hampshire, and Ravi Chandra, MD, PhD, of Oregon Health & Science University in Portland, wrote that while the results are encouraging, “the concept of substantially reducing elective dosing should be further integrated into prospective trial design.”

In addition, they noted that it is still unclear how to select the best option among the many de-escalation strategies that are being investigated (including tailored systemic therapies, or use of biomarkers or imaging), and that more data are needed to determine which patients are best suited for which strategies, and who would benefit from differing degrees of treatment deintensification.

The authors acknowledged some limitations to the study, including the fact that it was a single-institution, non-randomized, retrospective cohort study.