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Reduced Radiation Effective for Many HPV-Associated Throat Cancers

Samson, Kurt

doi: 10.1097/01.COT.0000527181.72655.4b
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SAN DIEGO—It may be possible to treat HPV-associated throat cancer with a significantly reduced dose of radiation than the current standard of care, results of a phase II clinical trial indicate.

Half the current dose of 60 Gray (Gy) after surgery was found to be sufficiently effective in treating many patients with oropharyngeal squamous cell carcinoma (OPSCC) linked to HPV, according to data presented at the American Society for Radiation Oncology Annual Meeting (Abstract LBA-14).

Radiation therapy at doses of 30 Gy to 36 Gy provided cancer control in patients and reduced the severity of side effects, noted Daniel Ma, MD, lead author of the study and Assistant Professor of Radiation Oncology at the Mayo Clinic in Rochester, Minn., in a press briefing.

“Patients in the trial received half the standard radiation dose but achieved equally high cure rates 2 years after treatment, with improved quality of life and lowered treatment costs.”

HPV-related OPSCC responds more readily to chemotherapy and radiation therapy and, therefore, has a high cure rate, but treating throat and neck regions often results in grade 2 or greater side effects, often difficulties in swallowing and salivation.

Over the past 10 years, the incidence and prevalence of HPV-related oropharyngeal cancer have risen dramatically, outpacing the growth of most other types of cancer, said Ma.

In the U.S., HPV accounts for about 70 percent of all new cases of oropharyngeal cancer, and almost half of all adults have been infected with the virus, according to the CDC. About 39,800 HPV-associated cancers occur each year, with an estimated 23,300 in women and about 16,500 men infected.

Cervical cancer is the most common HPV-associated cancer among women, while oropharyngeal cancers are the most common in men. If current epidemiologic trends continue, HPV infection will account for half of all forms of head and neck cancer by 2030, Ma noted. Moreover, because the average OPSCC patient is younger and will live longer with permanent treatment side effects, it is important to find ways to reduce treatment's impact, he explained.

Between 1988 and 2004, the rates of HPV-associated OPSCC more than doubled, while the rates of HPV-negative disease—which is typically caused by smoking and alcohol consumption—dropped by half.

“The profile of the typical oropharynx cancer patient has changed, which means that our approach to treating this disease needs to change as well,” Ma said.

“Several research groups are pursuing an incremental approach to de-escalating treatment, such as using 15 percent less radiation dose. Our trial took a different approach—testing whether we could cut the dose by half. Our findings indicate that this more aggressive approach toward treatment reduction can be viable for appropriately selected patients.”

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Methods, Results

The study involved some 80 patients with stage III or IV HPV-related OPSCC who had a minimal smoking history and no evidence of residual disease following surgery, with a median follow-up of 2 years after de-escalated dosing from 60 Gy to 30 Gy.

The rate of tumor control in the oropharynx and surrounding region was 95 percent and only three patients experienced a local recurrence at 2 years. One additional patient had a regional recurrence. Disease-free survival (DFS) at 2 years was 89 percent.

By comparison, results from the RTOG 0234 clinical trial reported a 2-year DFS rate of 86.4 percent. RTOG 0234 was a phase II randomized trial of surgery followed by chemoradiotherapy plus C225, or cetuximab, in 234 patients with advanced SCC of the head and neck and high-risk pathology.

Only 1 percent of patients reported grade 2 or higher side effects at 1 year, but 10 percent experienced such side effects at 2 years. Other studies of adjuvant radiation for OPSCC have generally found rates of late grade 2 or higher side effects in more than 50 percent of patients. In RTOG 0234, the rate was 55 percent.

No grade 3 or greater toxicity was reported at either 1 or 2 years in the current study. A total of 18 percent of patients reported cumulative grade 3+ toxicity within 3 months of treatment; however, all instances resolved by 6 months.

Patients in the study demonstrated an improved ability to swallow at 1 year compared to pre-treatment, and none required a feeding tube. Quality of life largely improved or remained unchanged following treatment, except for dry mouth. Patients reported somewhat worse salivary flow on one scale, but none of the other quality-of-life scales declined significantly.

“Side effects with dose-reduced treatment were dramatically less than what we usually see in treatment of adjuvant radiation therapy for oropharynx cancer,” stated Ma. “The shorter course of treatment also has practical value for patients. If a patient has 20 twice-daily sessions instead of 30 daily treatment sessions, their financial cost is reduced by a third, and time away from work or family is reduced by a third—but the likelihood of cure remains the same.”

While the results are promising, Ma emphasized that findings from a randomized study directly comparing the dose-reduced treatment with traditional treatment are needed before the new approach can be adopted widely.

“This treatment approach should be considered investigational until confirmed in a phase III study, such as the ongoing multi-institutional DART-HPV trial that is currently open for patient accrual,” he said.

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Commentary

ASTRO President Paul Harari, MD, FASTRO, Chairman of the Department of Human Oncology at the University of Wisconsin, Madison, commented on the findings.

“I don't think any of us would have been surprised that this approach would lower the side-effect profile,” he said. “When you give 30-36 Gy to a head-and-neck cancer patient versus 70 Gy, you are going to see markedly, profoundly diminished side-effect profiles.”

Harari, who moderated the panel discussion, said that this is a special area of study for him because he has spent 30 years as a head and neck cancer specialist.

“HPV oropharyngeal cancer is a relatively new entity worldwide. Only in the last 10-12 years has there been recognition that this is in fact a distinct tumor type. The molecular profile and genetic landscape of HPV-associated head and neck cancer is very different from HPV-negative cancer, and it requires and warrants different treatment approaches.”

Harari, a lead investigator for the RTOG-0234 trial, said the new study is one of many experimental approaches to de-intensify or de-escalate treatment for such cancers.

“It's a challenging business because, when you have a high cure rate for a tumor, the last thing that you want to do is lower that cure rate. But when you have a high cure rate and high toxicity with traditional treatment—and make no mistake about it, this is a toxic treatment—if we can maintain equivalent cure rates and diminish the side effect profile, this is a powerful advance for patients and providers.”

Kurt Samson is a contributing writer.

Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
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