Reply to F. Fiorica et al and D. Vordermark
Authors: Aileen B. Chen, Deborah Schrag
Journal: Journal of Clinical Oncology (2013)

Fiorica and Berretta 1 responded to our recently published article, 2 highlighting several key arguments in the ongoing debate over the appropriate dose and fractionation for palliative radiation therapy for bone metastases.They correctly note that evaluation of treatment effect from palliative radiation can be difficult and subjective.Although randomized studies in bone metastases showed equivalence in pain relief from single versus multiple fractions, it is possible that an outcome that was not evaluated (eg, bone remineralization) could differ or that longer follow-up could reveal greater differences in pain relief or late effects.Despite these uncertainties, on the basis of the best available evidence, short-course radiation therapy should be considered standard of care in most patients with uncomplicated bone metastases, although additional study may be warranted to identify those patients more likely to benefit from longer courses of radiation or the best treatment for more complicated bone metastases.Even though some patients may benefit from longer courses of radiation, we have not yet identified who those patients should be, and the 6% rate of single-fraction radiation to bone metastases observed in the Cancer Care Outcomes and Surveillance Study data seems far lower than what the randomized literature would suggest is appropriate.Fiorica and Berretta also comment that it is difficult to identify which patients need radiation as a pure palliative approach and which patients may experience longer survival, which might impact the dose and fractionation of radiation chosen.For example, radiobiologic principles suggest that shorter fractionation schemes may be associated with more frequent and severe late effects. 3However, clinical data from randomized studies have not borne this out, and in the opinion of the American Society for Radiation Oncology Task Force on bone metastases, "Numerous prospective, randomized trials have failed to show any significant difference in long-term toxicity between a single 8-Gy fraction and more prolonged RT [radiation therapy] courses for uncomplicated, painful bone metastases.No additional studies are suggested to confirm this recommendation." 4(p969) Another frequent concern that is raised is the higher retreatment rates observed with single-fraction versus multifraction regimens. [5]6][7] Although it is true that the observed rates of retreatment were higher in the singlefraction groups, patients may find it worthwhile to accept a 10% to 15% greater risk of retreatment 8 to avoid longer radiation therapy courses in the majority who will never require it.In addition, it is unclear to what extent this difference results from a greater comfort level with retreatment among radiation oncologists after single-fraction radiation versus objectively higher rates of pain recurrence.In patients surviving longer than 1 year, the Dutch Bone Metastasis Study did not find a significant difference in duration of response or progression rates, although some might argue that the doses compared (8 Gy ϫ 1 Gy v 4 Gy ϫ 6) were not sufficiently different to expect a difference in outcome. 9