We now have three large noninferiority trials with different eligibility criteria and different regimens. All three have found that moderate hypofractionation is not worse than conventional fractionation.— W. Robert Lee, MD
Formal discussant W. Robert Lee, MD, of Duke University School of Medicine, Durham, North Carolina, placed himself firmly in the camp supporting hypofractionation as a new standard of care. “We now have three large noninferiority trials with different eligibility criteria and different regimens. All three have found that moderate hypofractionation is not worse than conventional fractionation,” Dr. Lee stated. “In my view, moderate hypofractionation is tested and proven.”
The devil is in the details, Dr. Lee explained. The word “hypofractionation” can refer to moderate hypofractionation, as was used in the current trial, or extreme hypofractionation (delivered in larger fractions over 1–2 weeks), which is still being tested and has not yet been proved to be noninferior to conventional radiation therapy.
“Around 2006, when experts proposed that the biology of prostate cancer favored hypofractionation, the debate became very emotional. Four randomized trials were designed to test the hypothesis that hypofractionation was superior to conventional radiation therapy, and these trials showed remarkable consistency. None proves superiority of hypofractionation,” Dr. Lee told listeners.
Three Studies Confirm Noninferiority
“Some people have suggested that lack of superiority means equivalence, but this audience is too wise for that conclusion. You need a noninferiority study to make this sort of inference. Now we have three noninferiority studies with a total of more than 5,000 patients establishing noninferiority of moderate hypofractionation,” he continued.
RTOG 0415 compared moderately fractionated vs conventional radiation therapy in low-risk patients not treated with androgen-deprivation therapy.1 CHHiP compared two different moderately hypofractionated schedules with conventional radiation therapy in intermediate-risk disease.2 “The current study presented [today] also showed noninferiority in intermediate-risk patients,” he added.
Turning to cost considerations, Dr. Lee told listeners: “Focusing only on efficacy is fiscally unsustainable for our health-care system. The ASCO value framework includes cost. As a radiation oncologist, I believe we must play our part and also focus on the cost of our therapies. Moderate hypofractionation does reduce cost compared with conventional radiation therapy.”
Extreme hypofractionated therapy, however, is still under study. “We don’t want to adopt a therapy that has not been vetted and proven,” he closed. ■
Disclosure: Dr. Lee reported no potential conflicts of interest.
1. Lee WR, Dignam JJ, Amin M, et al: NRG Oncology RTOG 0415: A randomized phase III non-inferiority study comparing two fractionated schedules in patients with low-risk prostate cancer. 2016 Genitourinary Cancers Symposium. Abstract 01.
2. Dearnaley D, Syndikus I, Mussop H, et al: Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5-year outcomes of the randomised, non-inferiority, phase 3 CHHiP trial. Lancet Oncol. June 20, 2016 (early release online).