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De-escalated radiation safe, effective for HPV-positive oropharyngeal cancer
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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.
Perspective
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Paul Harari, MD, FASTRO
This is an exciting area very dear to my heart, having spent 30 years as a specialist in this area. HPV-associated head and neck cancer is a relatively new entity worldwide. It has only been known for the last 10 to 15 years that this is, in fact, a distinct tumor type. The molecular profile and genetic landscape is very distinct from HPV-negative cancer. It requires and warrants different treatment approaches. This is one of many approaches — as Ma and colleagues alluded to — of being able to de-escalate treatment for HPV-associated cancers. It is a challenging business because when you have a high cure rate, you don’t want to lower it. If we can maintain equivalent cure rates and diminish the side effect profile, then this is a powerful advance for patients.
There is no surprise this would lower the side effect profile. You will see a profoundly diminished side effect profile, but the more intense question for the designer of the phase 3 clinical trial is: Can you safely maintain the cure rate? This phase 2 trial opens the window for that phase 3 trial. The early look researchers have provided is quite safe and encouraging. Nevertheless, it is phase 2 and requires validation in a larger cohort in a randomized fashion. We wait with anticipation and high interest for this study to advance de-escalation in treatment for HPV-associated head and neck cancers.
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Richard Bakst, MD
Most head and neck cancers used to be driven by alcohol and tobacco, and those tended to be aggressive. Now there is this wave of the HPV epidemic, no longer driven by tobacco and alcohol. What we have appreciated clinically with HPV-positive disease is that patients likely do better. Treatment has been guided by older studies of patients from an era where cancer was driven by tobacco and alcohol. Because HPV-positive patients do better, we have started to ask whether they need as much therapy as someone with cancer driven by alcohol and tobacco.
These results suggest that the doses required to treat this disease are likely lower than the doses required to cure people in the era of tobacco- and alcohol-driven cancers. Although this study used a unique radiation regimen that isn’t used day to day, the bottom line is that their outcomes were comparable with other studies, suggesting there is room to safely lower the dose of radiation in these patients and to potentially limit toxicities without compromising curability.
Although this still needs to go to a phase 3 trial, the data add to the growing list that suggests we are safely moving in the direction of treatment deintensification. This study also pushes the boundary as to how low we can go on dose. This is one of the lowest dose regimens I’ve seen used.
This is not something everyone is going to start using. This is more food for thought to design appropriate treatments for this population. The overall feeling is that we can probably lower the radiation dose. It doesn’t mean everyone should get the low dose, but we are safely, slowly and surely moving in that direction.
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