De-escalated radiation safe, effective for HPV-positive oropharyngeal cancer
Aggressive de-escalation of radiation therapy conferred locoregional control comparable with historical data among patients with HPV-positive oropharyngeal squamous cell carcinoma, according to results of a phase 2 trial presented at the American Society for Radiation Oncology Annual Meeting.
De-escalated treatment also led to fewer side effects, improved swallowing function and no negative impact on quality of life.
“Multiple research groups are currently exploring incremental reductions in radiation dose for HPV oropharyngeal cancer,” Daniel Ma, MD, assistant professor of radiation oncology at Mayo Clinic in Rochester, Minnesota, said during a press conference. “We explored a more aggressive course, cutting the radiation by half, from the standard dose of 60 Gy to 30 Gy.”
Data suggest that by the year 2030, half of oropharyngeal malignancies will be HPV related. Cure rates for HPV-positive oropharyngeal cancer are high. However, standard treatment can lead to serious and life-altering side effects, which need to be minimized.
The analysis included data from 80 patients (median age, 60.5 years; men, n = 73) with no evidence of residual disease after surgery, a minimal smoking history, and stage III or stage IV disease.
Patients received a total dose of 30 Gy (n = 37) or 36 Gy (n = 43) radiation therapy twice daily for 2 weeks, which is 50% less than the standard dose of 60 Gy to 66 Gy. Patients also received two courses of 15 mg/m2 docetaxel on days 1 and 8.
Two-year locoregional control served as the primary endpoint.
Other research groups are investigating de-escalated treatment using a radiation dose of 15% less than standard.
“[There are] two thoughts we had in deescalating doses to 30 Gy,” Ma said. “Number one, the use of 30 Gy for HPV-related malignancies isn’t new. We’ve had a reasonable experience with it before.
“The second point is more controversial,” Ma added. “... Even though it seems scary to go down from 60 Gy to 30 Gy, we thought it was safer because of our salvage option.”
Median follow-up was 23.6 months (range, 12-46).
At 2 years, two patients experienced local recurrence and one patient experienced nodal recurrence for a locoregional control rate of 96.3%.
In addition, four distant recurrences occurred, for a 2-year PFS rate of 91.3%. Researchers compared this rate with the 2-year PFS of 86.4% for HPV-related cancer in the RTOG 0234 trial.
One percent of patients experienced grade 2 or worse adverse events at 1-year follow-up and 10% had by 2-year follow-up. All grade 3 or higher events occurred by 3 months and resolved by 6 months.
Conversely, 55% of patients in RTOG 0234 experienced grade 2 or worse events.
According to the Modified Barium Swallow Impairment Profile, ability to swallow improved slightly at 1 year following radiation therapy compared with baseline (47.4 ± 5.2 vs. 48.6 ± 4.8; P = .03). No patient required a feeding tube during treatment.
Researchers used various scales to determine impact on quality of life. Patients reported worse salivary flow after treatment on the University of Michigan Xerostomia Quality-of-Life Scale (70.3 ± 6.7 vs. 64.8 ± 8.8; P < .0001). None of the other quality-of-life scales declined significantly.
“De-escalated therapy led to significant improved side effects and quality of life. These data will need to be validated in a randomized setting,” Ma said, adding that a phase 3 trial is planned. – by Melinda Stevens
Disclosures: Ma reports no relevant financial disclosures. One other researcher reports a consultant role with UpToDate and royalties from Elsevier.