The theoretical tissue-sparing effects of PBRT on non-cancerous tissues


Proponents of proton beam radiation therapy (PBRT) have long touted its theoretical, healthy, tissue-sparing effects. However, there has (to date) never been a completed, randomized clinical trial comparing PBRT to modern photon-based radiation treatment (intensity-modulated radiation therapy or IMRT) that would demonstrate whether such an effect actually exists in clinical practice. Previous, retrospective cohort and database studies have failed to demonstrate significant differences in urinary and rectal toxicity.

Fang et al., from the University of Pennsylvania, have recently reported data from a case-matched study of PBRT vs IMRT toxicity:

  • 91 case-matched pairs were identified from a pool of 394 patients treated between 2010 and 2012.
  • Pairs were matched by risk group, age, and prior (pre-treatment) gastrointestinal and genitourinary disorders.

Both sets of men received 79.2 Gy of radiation, whether by PBRT or IMRT. Bladder and rectal dosimetry were significantly better for PBRT as compared to IMRT.

The authors report the following results:

  • Average (median) follow-up was
    • 47 months (range, 5 to 65 months) for patients who received IMRT
    • 29 months (range, 5 to 50 months) for those who received PBRT
  • There were no significant differences in
    • Acute urinary toxicity of Grade ≥ 2
    • Acute rectal toxicity of Grade ≥ 2
    • Late urinary toxicity of Grade ≥ 2
    • Late rectal toxicity of of Grade ≥ 2

The authors did not, however, measure differences that may have occurred in erectile and/or sexual function.

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

9 Responses

  1. How does “no significant differences” equal “significantly better”?

  2. I guess it depends how you define significant.

    PBRT was clearly better on 3 of 4 measures and slightly worse on the 4th.

  3. So why is PBRT big business, right now? Why do countries invest so much in an instrument that has not yet demonstrably done or demonstrably not done, what was originally claimed? wouldn’t it be more cost-effective to study one dedicated set-up? When the doctors here had to decide between EBRT and PBRT for me, they chose the former. I assume because I was T2c, the affected volume (I forget the technical term) was considered to be too large, for a highly directed beam of protons that hit a smaller region. I should have asked.

  4. Dear Doug:

    Numerical “betterness” and statistically significant “betterness” are meaningfully different, as I know you well understand. I’d also note that this paper is coauthored by a couple of leaders in the PBRT community.

    Dear Rob:

    The fact that the accuracy of the dosimetry was greater for PBRT than it was for IMRT but that the risk for side effects was not statistically different is exactly the point.

  5. Dear George:

    PBRT has been proven to be more effective than other forms of radiotherapy for some types of cancer. As yet, however, such evidence is missing for the treatment of prostate cancer … but some people simply have faith that higher technology treatment simply “must” be better, whether there is real evidence or not.

  6. Thanks Doug and Sitemaster, but I’m still a little confused. Doug, will you please elaborate? Which three? I only find two — bladder and rectal dosimetry.

  7. Dear Sitemaster,

    Thank you. I thought PBRT had not yet proven its worth in any sense, for any sort of cancer.

  8. Rob:

    “Dosimetry” refers to the accuracy with which specific levels of radiation are delivered to targeted areas of the body (i.e., to the prostate and surrounding tissues like the bladder and rectum in this case). Fang et al. state that relevant variables were much better for PBRT than for IMRT in this study, and that these differences were statistically significant (P ≤ 0.01).

    The rates of occurrence of toxic effects of Grade 2 or higher were lower with PBRT for acute gastrointestinal toxicity (OR = 0.27; P = 0.09), acute genitourinary toxicity (OR = 0.69; P = 0.36), and late genitourinary toxicity (HR = 0.56; P = 0.22), but were higher for late gastrointestinal toxicity (HR = 1.24; P = 0.62). However, none of these measures were statistically significant because the P value was always higher than 0.05, implying that this could have occurred by random chance.

    The advocates for PBRT, based on the theory that PBRT delivers radiation therapy more accurately than IMRT, would have expected the dosimetry results reported, but they would also have hoped that the risk for side effects would be significantly better with PBRT too.

    Doug has (correctly) pointed out that they were numerically better for three of the four types of side effect. My point is that in no case is the difference statistically significant. I would also note that the IMRT patients seem to have been followed, on average, for about 18 months longer than the PBRT patients, which would (theoretically) increase the chance of observation of “late” side effects of all types in the IMRT patients compared to the PBRT patients.

    The study’s authors conclude simply that “the risks of acute and late GI/GU toxicities did not differ significantly after adjustment for confounders and predictive factors.”

  9. Much thanks, Sitemaster. I think I’ve got it, and you’ve helped me understand (indirectly) an advantage of low-dose brachytherapy. Clearly, the meal is still a la carte.

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