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% 3-year local control to 87% 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 MD Anderson 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)
• Half received 30 Gy in 10 fractions (Multi-Fraction Cohort - MF)
• 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
• At 9 months, pain palliation was 77% for the SF vs 46% for the MF
• In the Single Fraction Cohort, those who got the 16 Gy dose had 3 times better pain palliation vs those who got the 12 Gy dose.
• Local control at 2 years was 100% for SF vs 76% for MF
• 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 challenge an radiation oncologist who plans to give more than a single fraction to explain his recommendation. (It is entirely possible the 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. The patient should not expect this D3alliative treatment to increase survival.

Spine metastases

Spinal metastases may respond to radiation differently from other bone metastases. Ryu et al. reported the results of the NRG Oncology/RTOG 0631 randomized clinical trial. They tried to obtain proof that SBRT (16-18 Gy in one dose) was superior to IMRT in one dose (8 Gy) in terms of pain response. After 3 months, 61% of those treated with IMRT had a significant pain improvement vs 41% of those treated with SBRT. After 1 year, there was no difference in pain scores. After 2 years, there was no difference in spinal fractures or compression. 

There is conflicting data from other institutions. Sprave et al. at Heidelberg reported better pain response at 6 months (but not at 3 months) with SBRT (24 Gy in 1 fraction) vs 3DCRT (30 Gy in 10 fractions). Sahgal et al. in a Canadian/Australian multi-institutional trial, found there was a better pain response with SBRT (24 Gy in 2 fractions) compared to IMRT (20 Gy in 5 fractions). After 3 months, significant pain improvement was 35% for SBRT vs 14% for IMRT.

note: thanks to Valerae Lewis for allowing me to review the full text