External-beam Radiation Therapy for Skeletal Metastases
External-beam Radiation Therapy for Skeletal Metastases
For palliation of pain, the optimal prescription for radiation therapy has long been debated. An abundance of data from multiple randomized clinical trials and meta-analyses has demonstrated that prolonged fractionated radiation therapy is not superior to a shorter treatment course. An early randomized study from the Radiation Therapy Oncology Group (RTOG) between 1974 and 1980 included 266 patients with solitary metastasis who were randomly assigned to treatment with 40.5 Gy in 15 fractions or 20 Gy in 5 fractions; another 750 patients with multiple metastases were randomly assigned to 30 Gy in 10 fractions, 15 Gy in 5 fractions, 20 Gy in 5 fractions, or 25 Gy in 5 fractions. Quantitative measurement of pain was the endpoint. Overall, 83% of the patients achieved partial pain relief and 54% of the patients obtained complete pain relief. There were no significant differences between the treatment assignment in either the single- or multiple-metastases groups. The median duration of minimal pain relief was 20 weeks and that of complete pain relief was 12 weeks. Some pain relief was experienced within the first 4 weeks in most patients who reported pain relief, but in about half of the patients, complete pain relief was reported at least 4 weeks after the start of treatment.
Rades et al retrospectively reported on 1,304 patients with spinal metastasis irradiated with several schedules: 8 Gy in 1 fraction, 20 Gy in 5 fractions, 30 Gy in 10 fractions, 37.5 Gy in 15 fractions, and 40 Gy in 20 fractions. Motor function improved in 26% to 31%, and posttreatment ambulatory rates were 63% to 74% in the different radiotherapy schedule groups, without significant differences among them. However, in-field recurrences were significantly more common after 8 Gy in 1 fraction and 20 Gy in 5 fractions (approximately 12% in these groups) than with the other radiotherapy schedules (approximately 4%). Myelopathy was not observed in any radiotherapy schedule group, with a median follow-up of 14 months.
Randomized trials of different radiotherapy schedules for painful skeletal metastases have similarly observed that 8 Gy in 1 fraction initially is equally efficacious as more protracted schedules with a higher total dose; however, the patients who received 8 Gy in 1 fraction had inferior long-term control of pain and were more likely to require reirradiation.
Hartsell et al led an RTOG study from 1998 to 2001 that randomized 898 patients with bone metastasis from prostate cancer and breast cancer to receive 8 Gy in 1 fraction vs 30 Gy in 10 fractions. The Brief Pain Inventory assessment was available for 66% of the patients. The complete response rate was 15% in the 8-Gy group compared with 18% in the 30-Gy group; the partial response rate was 50% in the 8-Gy group compared with 48% in the 30-Gy group (P = .06). At 3 months, about one-third of the patients in each group no longer required narcotic medications. Approximately 5% of patients in each group had a pathological fracture in the treatment field. Although there is no statistical difference in the risk of fracture, there is a greater need for re-treatment following single-fraction treatment; the 3-year re-treatment rate was 18% vs 9% (P < .001). Grades 2–4 acute toxicity occurred more frequently in the 30-Gy group than in the 8-Gy group (17% vs 10%; P = .002); the incidence of late toxicity did not differ (4% in both groups).
Outcomes With Different Conventional Radiotherapy Schedules
For palliation of pain, the optimal prescription for radiation therapy has long been debated. An abundance of data from multiple randomized clinical trials and meta-analyses has demonstrated that prolonged fractionated radiation therapy is not superior to a shorter treatment course. An early randomized study from the Radiation Therapy Oncology Group (RTOG) between 1974 and 1980 included 266 patients with solitary metastasis who were randomly assigned to treatment with 40.5 Gy in 15 fractions or 20 Gy in 5 fractions; another 750 patients with multiple metastases were randomly assigned to 30 Gy in 10 fractions, 15 Gy in 5 fractions, 20 Gy in 5 fractions, or 25 Gy in 5 fractions. Quantitative measurement of pain was the endpoint. Overall, 83% of the patients achieved partial pain relief and 54% of the patients obtained complete pain relief. There were no significant differences between the treatment assignment in either the single- or multiple-metastases groups. The median duration of minimal pain relief was 20 weeks and that of complete pain relief was 12 weeks. Some pain relief was experienced within the first 4 weeks in most patients who reported pain relief, but in about half of the patients, complete pain relief was reported at least 4 weeks after the start of treatment.
Rades et al retrospectively reported on 1,304 patients with spinal metastasis irradiated with several schedules: 8 Gy in 1 fraction, 20 Gy in 5 fractions, 30 Gy in 10 fractions, 37.5 Gy in 15 fractions, and 40 Gy in 20 fractions. Motor function improved in 26% to 31%, and posttreatment ambulatory rates were 63% to 74% in the different radiotherapy schedule groups, without significant differences among them. However, in-field recurrences were significantly more common after 8 Gy in 1 fraction and 20 Gy in 5 fractions (approximately 12% in these groups) than with the other radiotherapy schedules (approximately 4%). Myelopathy was not observed in any radiotherapy schedule group, with a median follow-up of 14 months.
Randomized trials of different radiotherapy schedules for painful skeletal metastases have similarly observed that 8 Gy in 1 fraction initially is equally efficacious as more protracted schedules with a higher total dose; however, the patients who received 8 Gy in 1 fraction had inferior long-term control of pain and were more likely to require reirradiation.
Hartsell et al led an RTOG study from 1998 to 2001 that randomized 898 patients with bone metastasis from prostate cancer and breast cancer to receive 8 Gy in 1 fraction vs 30 Gy in 10 fractions. The Brief Pain Inventory assessment was available for 66% of the patients. The complete response rate was 15% in the 8-Gy group compared with 18% in the 30-Gy group; the partial response rate was 50% in the 8-Gy group compared with 48% in the 30-Gy group (P = .06). At 3 months, about one-third of the patients in each group no longer required narcotic medications. Approximately 5% of patients in each group had a pathological fracture in the treatment field. Although there is no statistical difference in the risk of fracture, there is a greater need for re-treatment following single-fraction treatment; the 3-year re-treatment rate was 18% vs 9% (P < .001). Grades 2–4 acute toxicity occurred more frequently in the 30-Gy group than in the 8-Gy group (17% vs 10%; P = .002); the incidence of late toxicity did not differ (4% in both groups).
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