Toxicity higher with hypofractionation in Dutch radiotherapy trial using 3D-CRT


A Dutch research group has published the toxicity outcomes of a randomized clinical trial (HYPRO) designed to test whether a hypofractionated external beam (EBRT) regimen compared to conventional fractionation. They will report on the oncological outcomes at a later date.

Between 2007 and 2010, Aluwini et al. enrolled and treated 782 patients with intermediate- and high-risk prostate cancer at four Dutch centers. About half were treated with the hypofractionated regimen, half with conventional dosing as follows:

  • Hypofractionation: 19 fractions of 3.4 Gy each
  • Conventional fractionation: 39 fractions of 2.0 Gy each

Both groups were treated with conformal EBRT (3D-CRT), not with intensity-modulated radiation therapy (IMRT) or stereotactic body radiation therapy (SBRT). The relative biologically effective dose was 16 percent higher for the hypofractionated 3D-CRT regimen.

After a median follow-up of 60 months, the 3-year late-term toxicity outcomes were as follows:

  • Genitourinary toxicity, grade 2 or higher:
    • 41 percent for the hypofractionated group
    • 39 percent for the conventionally fractionated group
    • Hazard ratio: 1.16 (non-inferiority threshold: 1.11)
  • Genitourinary toxicity, grade 3 or higher:
    • 19 percent for the hypofractionated group
    • 13 percent for the conventionally fractionated group
  • Gastrointestinal toxicity, grade 2 or higher:
    • 22 percent for the hypofractionated group
    • 18 percent for the conventionally fractionated group
    • Hazard ratio: 1.19 (non-inferiority threshold: 1.13)
  • Gastrointestinal toxicity, grade 3 or higher:
    • 3 percent for the hypofractionated group
    • 3 percent for the conventionally fractionated group

Because the toxicity difference slightly exceeded the pre-established thresholds, the authors conclude that the hypofractionated regimen was not non-inferior to the conventionally fractionated regimen in terms of late term toxicity.

Because the hypofractionated regimen was a higher biologically effective dose, we might expect toxicity to be somewhat higher. Several recent major trials showed that hypofractionated IMRT was non-inferior to conventional fractionation in terms of both oncological control and late-term toxicity (see this link and this one and this one). The lesson we learn from this study is that hypofractionation delivered using 3D-CRT does carry an increased risk of toxicity. To avoid that, it is important to use well-planned IMRT-based or SBRT-based regimens. 3D-CRT is probably not the optimal platform for such treatment.

Editorial note: This commentary was written for The “New” Prostate Cancer InfoLink by Allen Edel.

5 Responses

  1. Imaging Associated with This Study?

    Allen, thanks for your article.

    If you have access to the paper, does it indicate whether advanced imaging was used to plan and execute the treatments? I don’t associate advanced imaging with an older technology like 3D-conformal, but I suppose you could combine the two technologies, and my impression is that care in the Netherlands in recent years would be pretty good.

    If advanced imaging were not used, that could explain why a higher fraction dose that was slightly (or more) off target could result in inferior results.

  2. Jim,

    I don’t know what kind of imaging or immobilization was used. I doubt that advanced image guidance would much improve toxicity because of the wide treatment area used with 3D-CRT.

  3. Allen,

    Can we say that 3D-CRT using process VMAT is equivalent to the IMRT?

  4. Thanks.

  5. VMAT (Volumetric Modulated Arc Therapy) is a kind of IMRT that deposits radiation along an arc. It is intensity-modulated, not 3D-CRT.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google+ photo

You are commenting using your Google+ account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

This site uses Akismet to reduce spam. Learn how your comment data is processed.

%d bloggers like this: