One large “zap” for painful bone metastases is enough

In 2011, the American Society for Radiation Oncology (ASTRO) issued a consensus statement as part of its “Choosing Wisely” campaign that found that 30 Gy in 10 fractions (treatments), 20 Gy in 5 fractions, and 8 Gy in 1 fraction all gave equivalent pain relief. The detailed guidelines are here. They did note, however, that repeat treatments were sometimes necessary.

A retrospective study this year at the Mayo Clinic found that local control of prostate cancer bone metastases was much improved (from 47 percent to 87 percent for 3-year local control) by increasing the radiation single dose from 8 Gy to ≥ 18 Gy. (However, the higher dose did not significantly affect the biochemical failure or distant failure rate.)

Now, Nguyen et al. report the results of the first prospective, randomized clinical trial. The trial was conducted at M. D. Anderson Cancer Center from 2014 to 2018 among 160 people with painful bone metastases from any of a variety of cancer types.

  • Half received 12 Gy in a single fraction for ≥ 4 cm bone lesions, or 16 Gy in a single fraction for < 4 cm bone lesions (single fraction cohort — SF cohort)
  • Half received 30 Gy in 10 fractions (multi-fraction cohort — MF cohort)
  • Treated bone metastases were predominantly non-spinal
  • Up to three bone metastases were treated at a time

At all follow-up times (2 weeks, 3 months, 6 months, and 9 months):

  • Pain palliation (complete + partial) was significantly better among the SF cohort
    • At 9 months, pain palliation was 77 percent for the SF vs 46 percent for the MF cohort
  • In the SF cohort, those who got the 16 Gy dose had three times better pain palliation vs those who got the 12 Gy dose.
  • Local control at 2 years was 100 percent for patients in the SF cohort vs 76 percent for patients in the MF cohort.
  • Median survival was not significantly different
  • No significant differences in toxicity (nausea, vomiting, fatigue, dermatitis, and fracture)
  • No significant differences in quality of life

This Phase II study was too small to be definitive, especially for cancer-type subgroups. However, the patient should ask any radiation oncologist who plans to give more than a single fraction to explain his recommendation. (It is entirely possible that the location of the bone metastasis calls for a lower dose rate.) Moreover, the single fraction dose of 16 Gy or 18 Gy seems optimal for both pain palliation and local control. BUT … The patient should not expect this palliative treatment to increase survival.

Editorial note: This commentary was written by Allen Edel for The “New” Prostate Cancer InfoLink. Allen wishes to thanks to Dr. Valerae Lewis of the M. D. Anderson Cancer Center for allowing him to review the full text of the article by Nguyen et al.

7 Responses

  1. While there are clear advantages to a single dose for this small cohort, I do wonder how it compares to the more conventional spot radiation protocol of two or three treatments (unknown dosage) that we have frequently encountered in our support function. I can only recall a couple of guys who have such long multi-fraction doses for spot RT ….

    I am also confused by the dosage: “12 Gy for ≥ 4-cm lesions or 16 Gy for < 4-cm lesions”

    Lesions greater than 4 cm get a 25% lower dose than lesions less than 4 cm? This seems the wrong way around and clearly explains why the larger dose for the smaller lesion is three times as effective … or am I missing something?

  2. Hi Rick.

    As the dose is delivered to a wider area, the potential for toxicity increases. A 4 cm tumor is quite large for prostate cancer. Remember that the Gray is a unit of absorbed energy of ionizing radiation per kilogram. So, for example, a dose of just 3-5 Gy over the entire body would be lethal.

    The point of the study is that there is no advantage to fractionating for pain palliation. Based on observational studies, there was an open question as to whether multiple fractions were necessary. The answer, based on this RCT, is that no, only a single fraction of adequate dose (16-18 Gy) actually does a better job.

  3. Tx for the enlightenment, Allen … but I still find it confusing. That less can be more for a wider area makes sense, but not to the point of being inverse. Why is the larger dose to a smaller area not more damaging to surrounding tissue.

    Is there a lay explanation I can read anywhere?

  4. Please correct the commentary as there was no assessment at 6 months, only at 2 weeks, 3 months and 9 months.

  5. Rick:

    If you ablate a small tumor, the collateral damage is limited to a smaller area than if you ablate a larger tumor. This is the theory behind HIFU. They completely ablate a small focus of cancer, rather than treat the entire prostate with non-ablative radiation. The hope is that toxicity (to the bladder, rectum, and neurovascular bundles will be less because of the limited area of treatment even though the energy absorbed per kilogram is much greater.

  6. artglassbygerry:

    The table on p. 875 shows pain response at 2 weeks, 1 month, 3 months, 6 months, and 9 months.

  7. Thanks again, Allen … I think I follow what you are saying — but this may best be left to the back of a napkin next time we break bread!

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