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Top Line: The most common (read: usually only) side effect to anticipate from most palliative radiation treatments to uncomplicated painful bone mets is a transient pain flare.
The Study: A landmark trial in 2015 demonstrated a significant decrease in incidence of pain flare with 8 mg of oral dex for 5 days starting the day of receipt of 8 Gy x 1. Here’s a strikingly similar double-blind study enrolling around the same time that prospectively randomized 295 patients receiving 8 Gy x 1 or 4 Gy x 5-6 for painful bone mets to one of three arms starting on day 1 of radiation:  dex 8 mg x 4 days,  dex 8 mg x 1 day → placebo x 3 days,  placebo x 4 days. The primary endpoint again was incidence of pain flare, defined as a 25% increase in opioid intake and/or a 2+ increase on a 0-10 pain scale that—and now this is important—had to return to baseline within 14 days or else it was considered pain progression. The incidence of pain flare was  38%,  27%, and  39%. However, single-dose versus 4 days of dex had slightly higher rates of pain progression such that rates of pain flare or progression was  52%,  50% and  63%. All of this is to say, there wasn’t a significant improvement with prophylactic dex. What 4 days of dex did achieve was less pain flare on days 2-5 (52% of all pain flares) than arms  73% and  88%, which may be important if someone is struggling to lie on the table for 5 days of treatment. Though in that situation you might ask yourself: is single-fraction not an option..?
TBL: A second large phase 3 trial failed to confirm a significant advantage in pain flare prevention with prophylactic dex given with conventional palliative radiation for painful bone mets. | van der Linden, Int J Radiat Oncol Biol Phys 2020