Short-Course Radiotherapy May Reduce Resource Burden of Head and Neck Cancer Treatment in Low- and Middle-Income Countries
Resource-sparing hypofractionated radiation therapy could offer an invaluable alternative for treating head and neck cancer, especially for patients in low- and middle-income countries, according to data presented during the Plenary Session at the 2023 American Society for Radiation Oncology (ASTRO) Annual Meeting.1
Results of the phase III HYPNO trial, which investigated the use of hypofractionation to treat locally advanced head and neck squamous cell carcinoma, showed similar effectiveness and side-effect profile compared with traditional normofractionation methods. Rates of 3-year locoregional tumor control and grade 3 or greater late adverse events with hypofractionation were both within 0.5% of normofractionation—a noninferiority result that favors shorter radiation treatment.
These findings could have significant implications for health-care systems in regions with limited access to extensive radiation therapy, the study authors reported. “Head and neck cancer caused by factors other than the human papillomavirus remains a significant burden, especially in lower- and middle-income countries,” said lead author Søren M. Bentzen, PhD, DMSc, FASTRO, Professor of Radiation Oncology and Director of the Division of Biostatistics and Bioinformatics in the Department of Epidemiology and Public Health at the University of Maryland School of Medicine, Baltimore. “This is a trial that directly informs how you can effectively deliver radiation therapy to patients in a resource-scarce environment.”
“This is a trial that directly informs how you can effectively deliver radiation therapy to patients in a resource-scarce environment.”— Søren M. Bentzen, PhD, DMSc, FASTRO
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As Dr. Bentzen reported, approximately 70% of the 10 million cancer-related deaths worldwide occur in low- and middle-income countries. Head and neck squamous cell carcinoma, which is linked to smoking and tobacco chewing, remains the sixth most common cancer in the world (4.5% of new cases) but affects low- and middle-income countries disproportionately. In India, for example, the disease constitutes 30% of incident cancers.
“Patients in low- and middle-income countries have limited access to radiation therapy and to surgery,” Dr. Bentzen explained. “Reducing the number of radiation doses/fractions would allow more patients to be treated.”
HYPNO Trial Design
Based on mathematic models that analyzed outcomes of published randomized controlled trials, Dr. Bentzen and colleagues hypothesized that a 20-fraction, 4-week schedule could provide noninferior outcomes for both tumor control and late adverse events compared with a “standard” 33-fraction, 5.5-week schedule.
The stratified, randomized controlled open-label noninferiority phase III trial enrolled 792 patients with locally advanced head and neck cancer (primarily stage III and IV), across 12 centers in 10 low- to middle-income countries. Patients were randomly assigned to receive either hypofractionation (55 Gy in 20 fractions, with 5 fractions per week over 4.0 weeks) or conventional normofractionation (66 Gy in 33 fractions, with 6 fractions per week over 5.5 weeks) with or without weekly cisplatin.
Hypofractionation Noninferior to Conventional Fractionation
Results of the study showed that resource-sparing hypofractionation with or without cisplatin was noninferior to accelerated radiation therapy with respect to the primary outcome. After 3 years, patients who received the accelerated treatment had roughly the same level of locoregional tumor control (test for noninferiority within a 10% margin, P = .041) and late-term side effects (test for noninferiority within a 10% margin, P = .004) as those who received the longer treatment.
The overall survival and progression-free survival rates at 3 years after treatment were also not significantly different between groups (overall survival = 54.1% with hypofractionated treatment vs 55.5% with conventional treatment, P = .62; progression-free survival = 44.0% vs 45.3%, P = .42).
“There’s basically no difference in the -proportion of patients who are free from locoregional recurrence at a given point, and this is true for grade 3 or more adverse events as well,” said Dr. Bentzen. “In fact, the number of serious adverse events is lower in the hypofractionated arm.”
- Results of a large randomized controlled trial have shown that resource-sparing hypofractionated radiation therapy with or without cisplatin is as effective as accelerated radiation therapy in the control of locally advanced head and neck squamous cell carcinoma.
- This research, conducted primarily in low- and middle-income countries, could have significant implications for health-care systems in regions where access to radiation therapy is limited.
According to Dr. Bentzen, accelerating radiation treatment is a complex problem because delivering too high a dose or too many doses too quickly can cause side effects that impact a person’s quality of life. Conversely, not delivering enough radiation may allow the cancer to return.
“There is actually a sweet spot where you get exactly the right balance among the total dose, the total treatment time, and the dose you deliver in each fraction,” he explained. “The net result is that you hit the tumor hard enough to get good control, but you don’t affect the normal tissue more than you would with the standard treatment.”
Dr. Bentzen and his team are completing additional subgroup analyses to confirm the accelerated regimen is effective for a wide variety of patient types.
DISCLOSURE: This study was supported by funding from the International Atomic Energy Agency. Dr. Bentzen reported no conflicts of interest.
1. Bentzen SM, Rosenblatt E, Gupta T, et al: Randomized controlled trial of hypofractionated vs normofractionated accelerated radiation therapy with or without cisplatin for locally advanced head and neck squamous cell carcinoma (HYPNO). 2023 ASTRO Annual Meeting. Abstract LBA02. Presented October 2, 2023.
Beth Beadle, MD, PhD
Abstract discussant Beth Beadle, MD, PhD, Professor and Director of Head and Neck Radiation Oncology at Stanford University, underscored the significance of the HYPNO trial in advancing global cancer care, especially in underprivileged settings.
“This trial could lead to ...