SAN DIEGO – In low- and middle-income countries with high incidence and mortality from head and neck cancer, resources remain limited. Patients often can’t travel far for treatment or afford to stay near a treatment center for the length of time required for conventionally fractionated radiotherapy.
in these settings.
The phase 3 randomized HYPNO trial, conducted in 10 low- and middle-income countries, revealed that the hypofractionated regimen shortened total treatment time by a median of 11.5 days and was noninferior to conventional fractionation for tumor control and safety.
The primary trial results were presented by Søren Bentzen, PhD, DMSc, at the annual meeting of the American Society for Radiation Oncology.
“It was Usain Bolt who said, ‘I train for 4 years to run 9 seconds,’ and that was the feeling that I had when we did the noninferiority test,” said Dr. Bentzen, from the University of Maryland School of Medicine in Baltimore. “We had not looked at the data while the data were being accumulated, and guess what? It actually turned out that we had noninferiority with respect to both locoregional control and the late effects.”
In the HYPNO trial, Dr. Bentzen and colleagues wanted to determine whether a streamlined approach to the treatment of patients in low- and middle-income countries could improve access to care and still achieve strong outcomes.
The investigators used mathematical modeling to devise a strategy to reduce the number of fractions and put this hypothesis to the test in a pragmatic trial.
Patients from Uruguay, Brazil, Argentina, Cuba, South Africa, India, Pakistan, Thailand, Indonesia, and the Philippines were enrolled. After stratification by performance status, tumor subsite, institution, and previous treatment with chemotherapy, the 792 patients in the trial were randomly assigned in a 1:1 ratio to receive either 66 Gy in 33 fractions 6 days each week over 5.5 weeks, or 55 Gy in 20 fractions 5 days per week over 4 weeks. In both groups, weekly cisplatin was optional.
Compliance with the regimens was high in both arms, with 95% of patients assigned to conventional fractionation and 99% assigned to hypofractionation receiving the total planned doses.
At 3 years’ follow-up, the rates of locoregional control were 50.7% in the hypofractionation arm and 51.2% in the conventional fractionation arm (P = .40). No significant differences between the groups have emerged over 5 years, Dr. Bentzen said.
Rates of late toxicities of grade 3 or greater at 3 years’ follow-up were similar between the groups, at 18.8% in the hypofractionation arm and 20.2% in the conventional fractionation arm (P = .68).
Three-year overall survival rates also did not differ between the groups – 54.1% in the hypofractionation arm vs. 55.5% in the conventional arm (P = .62) – nor did rates of progression-free survival – 44.0% vs. 45.3%.
“Head and neck cancer caused by factors other than the human papillomavirus (HPV) remains a significant burden especially in lower- and middle-income countries,” Dr. Bentzen said in a press release. “This is a trial that directly informs how you can effectively deliver radiation therapy to patients in a resource-scarce environment.”
Beth Beadle, MD, PhD, the invited discussant at a media briefing where Dr. Bentzen summarized the findings, said, “I think this trial is going to change practice in low- and middle-income countries and will improve access to care.”
Although the approach used in the HYPNO trial will likely allow more patients to receive treatment and will save lives in countries with limited resources, the strategy likely won’t apply to U.S. practice, noted Dr. Beadle, a professor of radiation oncology at Stanford University, California.
“The one thing I do caution, and that Dr. Bentzen brought up, is that this is a very different population than the one that we see in the United States now,” Dr. Beadle said. “In fact, it’s very challenging to find a similar patient population to even serve as a comparison in the modern era and modern techniques.”
The HYPNO trial was sponsored by the International Atomic Energy Agency. Dr. Bentzen and Dr. Beadle have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.