Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic pain due to bone metastases (Trans-Tasman Radiation Oncology Group, TROG 96.05)

Abstract

Background and purpose Despite numerous randomized trials investigating radiotherapy (RT) fractionation schedules for painful bone metastases, there are very few data on RT for bone metastases causing pain with a neuropathic component. The Trans-Tasman Radiation Oncology Group undertook a randomized trial comparing the efficacy of a single 8 Gy (8/1) with 20 Gy in 5 fractions (20/5) for this type of pain. Materials and methods Eligible patients had radiological evidence of bone metastases from a known malignancy with no change in systemic therapy within 6 weeks before or anticipated within 4 weeks after RT, no other metastases along the distribution of the neuropathic pain and no clinical or radiological evidence of cord/cauda equina compression. All patients gave written informed consent. Primary endpoints were pain response within 2 months of commencement of RT and time to treatment failure (TTF). The hypothesis was that 8/1 is at least as effective as 20/5 and the planned sample size was 270 patients. Results Between February 1996 and December 2002, 272 patients were randomized (8/1:20/5=137:135) from 15 centres (Australia 11, New Zealand 3, UK 1). The commonest primary cancers were lung (31%), prostate (29%) and breast (8%); index sites were spine (89%), rib (9%), other (2%); 72% of patients were males and the median age was 67 (range 29–89). The median overall survival (95% CI) for all randomized patients was 4.8 mo (4.2–5.7 mo). The intention-to-treat overall response rates (95% CI) for 8/1 vs 20/5 were 53% (45–62%) vs 61% (53–70%), P=0.18. Corresponding figures for complete response were 26% (18–34%) vs 27% (19–35%), P=0.89. The estimated median TTFs (95% CI) were 2.4 mo (2.0–3.3 mo) vs 3.7 mo (3.1–5.9 mo) respectively. The hazard ratio (95% CI) for the comparison of TTF curves was 1.35 (0.99–1.85), log-rank P=0.056. There were no statistically significant differences in the rates of re-treatment, cord compression or pathological fracture by arm. Conclusions 8/1 was not shown to be as effective as 20/5, nor was it statistically significantly worse. Outcomes were generally poorer for 8/1, although the quantitative differences were relatively small.