There has been some question as to whether the toxicity of delivering very high doses of external beam radiation per treatment (or fraction) in fewer fractions (called “extreme hypofractionation” or SBRT) would be high compared to conventional dose rates per fraction. While SBRT practitioners have reported very low toxicity rates (see table in this link), there has always been some doubt because there may have been some bias in how patients were selected in the various studies.
The HYPO-RT-PC trial was the first trial ever to randomly assign patients to one kind of radiation or the other. Between 2005 and 2015, they enrolled 1200 intermediate-risk patients in Scandinavia to receive either:
- Conventional fractionation: 78 Gy in 39 fractions
- SBRT: 42.7 Gy in 7 fractions
The biologically effective dose is 19% higher for SBRT in terms of cancer control. The biologically effective doses are equivalent in terms of toxicity.
There were a few differences from some US practices:
- “Intermediate risk” was defined as one or two of the following 3 risk factors:
- Stage T1c-T3a (T3a is a high risk factor in the commonly used US definition)
- PSA> 10 ng/ml (PSA> 20 ng/ml is a high risk factor in the commonly used US definition)
- Gleason score ≥7 (Gleason scores greater than 7 are a high risk factor in the commonly used US definition)
- 80% of the men were treated with a technology called 3D-CRT, which is seldom used for external beam therapy anymore at major tertiary care centers. It is never used for SBRT in the US because it is considered not precise enough, and too toxic.
- SBRT is usually delivered in 4 or 5 fractions in the US. CyberKnife and VMAT are the most common technologies in use, and use of sophisticated image guidance throughout each treatment is a common practice.
The toxicity results are based on 866 patients who had 2-year follow-up results. There were some differences in acute toxicity:
- Acute urinary toxicity was 27.6% for the SBRT group and 22.8% for the conventional fractionation group, but the difference was not statistically significant.
- Acute rectal toxicity was 9.4% for the SBRT group and 5.3% for the conventional fractionation group. The difference was statistically significant, but narrowed by 3 or 6 months.
Neither physician-reported toxicity nor patient-reported late-term toxicity differed by the fractionation schedule they received. By two years:
- Late-term urinary side effects were reported by 5.4% of the SBRT group and 4.6% of the conventional fractionation group. The difference was not statistically significant.
- Late term rectal side effects were reported by 2.2% of the SBRT group and 3.7% of the conventional fractionation group. The difference was not statistically significant.
- Impotence was reported by 34% of both groups, up from 16% at baseline.
- Patient-reported bother from urinary, rectal and sexual side effects were not different.
Given their use of the largely outmoded 3D-CRT technology, it was not surprising that acute toxicity would be elevated. I’m frankly surprised that late-term toxicity was not higher for SBRT.
They plan to present their findings on oncological outcomes at a future time.