Radiation therapy (RT) is effective in partially or completely relieving pain in a majority of patients with bone metastases, although a transient worsening of pain may occur in some patients . This typically occurs in the first few days after RT, and the flare in pain generally lasts one to two days.
Surgical fixation may be indicated prior to external beam RT (EBRT) to decrease pain and facilitate rehabilitation in symptomatic bone metastases causing a pathologic fracture involving the long bones or other weight-bearing bones. In other cases, prophylactic fixation to prevent pathologic fractures may be recommended prior to EBRT. Patients with inoperable fractures and those who are physically debilitated may achieve pain relief from palliative EBRT alone.
Single-dose versus fractionated treatment
Guidelines from the American Society for Radiation Oncology (ASTRO), based upon a systematic review of the literature, support treatment with a single fraction of radiation using a dose of 8 Gy to provide palliation for relief of pain from bone metastases . This approach is more convenient and cost effective compared with fractionated schedules.
In this review, retreatment was necessary in approximately 20% of patients treated with a single fraction compared with 8% in those initially managed with a fractionated regimen . There was no evidence that the use of a single-fraction regimen was associated with an increase in acute or late toxicity.
The effectiveness of a single fraction of 8 Gy compared with longer fractionated courses is illustrated by the three largest randomized trials:
- In a Dutch multicenter trial, 1171 patients with painful bone metastases were randomly assigned to 8 Gy in a single dose or 24 Gy in six fractions [5,6]. The palliative benefit was similar in both groups (overall pain relief in 72 and 69% of patients, respectively), as was the time to response (median three weeks in both groups). There was no difference in treatment-related toxicity. However, retreatment was required by significantly more patients treated with a single fraction (25 versus 7%).
- In the Radiation Therapy Oncology Group (RTOG) trial 9714, 949 patients with prostate or breast cancer and painful bone metastases were randomly assigned to 8 Gy in a single fraction or 30 Gy in 10 fractions . Patients with evidence of cauda equina syndrome or epidural spinal cord compression were excluded. There were no significant differences in the rates for complete and partial pain relief (overall 66% in each group), the use of narcotics, or the incidence of subsequent pathologic fractures. However, patients treated with a single fraction were twice as likely to require retreatment (18 versus 9%).
- A British trial randomly assigned 765 patients with painful bone metastases to 8 Gy as a single fraction, 20 Gy in five fractions, or 30 Gy in 10 fractions . With median 12 month follow-up, there were no differences in any of the pain end points among the three groups (78% overall response rate with either single dose or multidose schedules); there was no difference in time to response between the regimens (median less than one month in those responding). Patients treated with a single fraction were twice as likely to require reirradiation of the same site, but the majority could be successfully retreated with a single fraction.
Dose of radiation
A systematic review of the literature that looked at different doses of radiation administered as a single fraction concluded that a dose of 8 Gy was more effective than lower doses in providing pain relief .
- As an example, in a multicenter trial, 651 patients with painful bone metastases were randomly assigned to treatment with either 8 Gy or 4 Gy as a single dose . The main tumor types represented in the trial were breast, lung, and prostate cancer (35, 35, and 17%, respectively). The overall response rate was higher at 4, 8, and 52 weeks with the 8 Gy dose of radiation (83 versus 71, 91 versus 83, and 93 versus 82%, respectively). The retreatment rate was significantly lower in those given 8 Gy (14 versus 22%).
Reirradiation may be a useful option for patients with painful bone metastases if the initial treatment fails to adequately relieve bone pain or there is a subsequent relapse after an initial response. A meta-analysis of seven studies that included 2694 patients who were initially treated with RT for painful bone metastases found that reirradiation was subsequently used in 527 (20%) . Retreatment produced some benefit in terms of pain relief in 58% (95% CI, 49-67%).
There are only limited data on the optimal schedule and dose for patients in whom reirradiation is indicated. The most extensive data come from a trial in which 850 patients were randomly assigned to either a single fraction of 8 Gy or 20 Gy divided in eight fractions of 2.5 Gy .
- Overall, 521 patients (61%) received the assigned treatment and were assessable for a pain response two months after completion of reirradiation. Within the per protocol subset, there was no statistically significant difference in pain response (28% of those given a single 8 Gy fraction versus 32% of those given the 20 Gy in eight fractions); this difference was within the predetermined non-inferiority limits. There was no statistically significant difference in the incidence of pathologic fractures or spinal cord compression, although there was a trend toward a decreased incidence in those given the longer schedule.
- Acute toxicity was significantly higher in the 20 Gy arm one week after treatment in terms of loss of appetite, incidence of vomiting, diarrhea, and skin reddening. There was no difference in patient-reported global quality of life two months after treatment.