Benefit–Harm Balance May Favour Single-Fraction Radiation For Bone Metastasis

Research compares the efficacy and toxicity of single-fraction versus multi-fraction repeat radiation for painful bone metastases

medwireNews: The results of a randomised controlled clinical trial support the use of single-fraction radiotherapy for some patients undergoing repeat radiation for painful bone metastases.

In an intention-to-treat analysis, 28% of 425 patients given a single 8 Gy fraction reported a significant reduction in pain at the 2-month check-up compared with 32% of 425 patients given 20 Gy in multiple fractions, indicating non-inferiority for the single fraction regimen.

Single-fraction treatment did not meet the non-inferiority criteria in per protocol analysis, however, with just 45% of 258 patients achieving an overall pain response to radiotherapy compared with 51% of 263 patients given multi-fraction radiotherapy, report Edward Chow, from Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada, and co-authors.

But single-fraction radiotherapy was associated with significantly less acute toxicity at the 2-week check than the multi-fraction regimen. In particular, lack of appetite was reported by 56% of assessed patients who were given 8 Gy compared with 66% of assessed patients who were given 20 Gy, and diarrhoea by 23% and 31%, respectively.

Patients given 8 Gy did show a trend towards an increased risk of pathological fractures (7 vs 5%) and spinal cord or cauda equine compression (2 vs <1%) compared with those given 20 Gy, but the researchers note that these differences were not significant and the total number of affected patients was “very small”.

They add: “[D]ue to the realistic assumption that this population of patients will have important treatment limitations due to metastatic cancer, it is likely they would find a single treatment more convenient.”

Median survival in the 8 Gy and 20 Gy patient groups was comparable, at 9.3 and 9.7 months, respectively, with a corresponding 53% and 52% of patients alive after a median of 12.2 months of follow-up. Twelve percent of patients overall died within 2 months.

Writing in The Lancet Oncology, the team therefore concludes that the per protocol analysis means “[i]t is possible that a small proportion of patients might gain more benefit from multiple fraction treatment, but this schedule should be considered in view of the potential costs of greater acute toxicity, and probably greater inconvenience to patients.”

In an accompanying Comment, Carsten Nieder, from Nordland Hospital in Bodø, Norway, writes that decision making for palliative repeat radiation “remains complex” because most patients appear to benefit from a single fraction and the possible “trade-offs” between efficacy, convenience and toxicity.

“Death within 3 months was not uncommon, supporting use of single fractions for all patients with an unfavourable outlook,” he suggests, noting that other factors not assessed in the current study may influence treatment efficacy, such as tumour volume or lesion type.

“Notwithstanding, this study showed that re-irradiation is beneficial, even in patients without response to initial radiotherapy,” Carsten Nieder concludes.


Chow E, van der Linden YM, Roos D, et al. Single versus multiple fractions of repeat radiation for painful bone metastases: a randomised, controlled, non-inferiority trial. Lancet Oncol 2013 Dec 20. pii: S1470-2045(13)70556-4. doi: 10.1016/S1470-2045(13)70556-4. [Epub ahead of print].

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