8 Gy single fraction radiotherapy for the treatment of metastatic skeletal pain: randomised comparison with a multifraction schedule over 12 months of patient follow-up. Bone Pain Trial Working Party. Randomized prospective clinical study of small, large and twice-a-day fraction radiotherapy for painful bone metastases. Prospective randomised trial of single and multifraction radiotherapy schedules in the treatment of painful bony metastases. Randomized trial of single dose versus fractionated palliative radiotherapy of bone metastases. Pain relief and quality of life following radiotherapy for bone metastases: a randomised trial of two fractionation schedules. A randomized trial of a single treatment versus conventional fractionation in the palliative radiotherapy of painful bone metastases. [A randomized trial of single and multifraction radiation therapy for bone metastasis: a preliminary report]. Rapid course radiation therapy vs. more standard treatment: a randomized trial for bone metastases. The effect of a single fraction compared to multiple fractions on painful bone metastases: a global analysis of the Dutch Bone Metastasis Study.
To compare a single fraction of 8 Gy with a course of multifraction radiotherapy in terms of long-term benefits and short-term side effects in patients with painful skeletal metastases.
                Seven hundred and sixty-five patients with painful skeletal metastases requiring palliative radiotherapy were entered into a prospective randomised clinical trial comparing 8 Gy single fraction with a multifraction regimen (20 Gy/5 fractions or 30 Gy/10 fractions). Patients recorded pain severity and analgesic requirements on self-assessment questionnaires before treatment, at 2 weeks and at 1, 2, 3, 4, 5, 6, 8, 10 and 12 months after radiotherapy. Pain relief was the primary endpoint of treatment benefit. Short-term side-effects were compared in a subset of 133 consecutive patients who graded nausea, vomiting and antiemetic usage prior to treatment and at daily intervals from days I to 14.
                Overall survival at 12 months was 44%, with no statistically significant difference apparent between randomised groups. There were no differences in the time to first improvement in pain, time to complete pain relief or in time to first increase in pain at any time up to 12 months from randomisation, nor in the class of analgesic used. Retreatment was twice as common after 8 Gy than after multifraction radiotherapy, although retreatment for residual or recurrent pain did not reflect a difference between randomised groups in the probability of pain relief. The difference in the rate of retreatment is thought to reflect a greater readiness to prescribe radiotherapy after a single fraction, not a greater need. There were no significant differences in the incidence of nausea, vomiting, spinal cord compression or pathological fracture between the two groups.
                A single fraction of 8 Gy is as safe and effective as a multifraction regimen for the palliation of metastatic bone pain for at least 12 months. The greater convenience and lower cost make 8 Gy single fraction the treatment of choice for the majority of patients. A prospective randomized clinical trial comparing small, large and twice-a-day fraction for the relief of painful bone metastases was performed from 1981 to 1986 at Tokyo Women's Medical College Hospital. Eighty patients with painful bone metastases (92 sites) were divided into three radiation methods which were conventional fraction scheme of 5 times/week at 2 Gy/day for a total of 30 Gy/15 fractions (Group I, TDF: 49), 2 times/week at 4.5 Gy/day for a total of 22.5 Gy/5 fractions (Group II, TDF: 50) and 3 times/week at 2 Gy/day twice a day at a minimum interval of 6 h for a total of 20 Gy/10 fractions (Group III). Pain was assessed using a score and response rate was 76% in Group I, 75% in Group II and 78% in Group III which were not statistically significant mutually. Group II and III regimes were found to have an earlier shorter onset of pain relief than Group I, but the dose of onset of pain relief was almost the same. Our data suggested that individualization of radiotherapy schedules based on to assess the patient's condition and the expected quality of life and to consider radiation site and size of field, was more important than the fractionation regime in the treatment of painful bone metastases. A prospective randomised trial comparing a single fraction of 8 Gy with 30 Gy in 10 daily fractions for the relief of metastatic bone pain was performed. In 28 months, 288 patients were randomised. Pain was assessed using a questionnaire completed by the patient at home on a daily basis. No difference was found in the speed of onset or duration of pain relief between the two treatment regimes, and pain relief was independent of the histology of the primary tumour. Data in the literature suggest that for painful bone metastases a single dose is as effective as fractionated radiotherapy. In the present multicentre prospective trial, the effects of 8 Gy x1 and 5 Gy x4 were compared.
                A total of 241 patients were randomized to 8 Gy (122 patients) or 20 Gy (119 patients). The primary tumour was in the breast in 39% of patients, in the prostate in 34% of patients, in the lung in 13% of patients and in other locations in 14% of patients. Outcome measures were pain relief as measured by VAS and in half of the patients also by a five-point categorical pain scale, global quality of life (QoL) and analgesic consumption. Evaluation was performed before and 4, 8, 12 and 20 weeks after treatment.
                A total of 239 patients were evaluable for response. The two groups did not differ with respect to age, sex, primary tumour, metastasis localization, analgesic consumption (type and dose), performance status, prior systemic treatment, degree of pain and QoL. The treatment was completed as planned in 98% of patients. The degree of pain relief did not differ between the two treatment groups. At 4 weeks the difference in pain relief was 6% (95% CI 7, 20%) and at 8 weeks the difference was 13% (95% CI 3, 28%). Neither was there any significant difference in the duration of pain relief, the number of new painful sites and the need for reirradiation and toxicity was minor.
                The present randomized study showed that a single fraction of 8 Gy was as effective as 5 Gy x4 in relieving pain from bone metastasis. The optimum dose and fractionation schedule for the palliative irradiation of painful bone metastases is controversial.
                To compare the efficacy, side-effects and effect on quality of life of two commonly used radiotherapy schedules in the management of painful bone metastases.
                In a prospective trial, 280 patients were randomised to receive either a single 10 Gy treatment or a course of 22.5 Gy in five daily fractions for the relief of localised metastatic bone pain.
                Response rates have been calculated from 240 assessable treated sites of pain. The overall response rates were 83.7% (single treatment) and 89.2% (five fractions). The complete response rates were 38.8% (single treatment) and 42.3% (five fractions). The median duration of pain control was 13.5 weeks (single treatment) and 14.0 weeks (five fractions). None of these differences was statistically significant. There were no differences between the groups in the effect of treatment on a variety of quality of life parameters.
                It is concluded that a single 10 Gy treatment is as effective as a course of 22.5 Gy in five fractions in the management of painful bone metastases. In a randomized prospective trial of radiotherapy in 29 patients. Comparing 24 Gy in six fractions is two to three weeks with a single treatment of 8 Gy in the palliative treatment of bone metastasis no differences could be detected in daily subjective pain scores for one month or monthly objective scores for six months. Of the single treatment group 25% required retreatment. Daily subjective record of nausea/vomiting, diarrhoea, skin reaction and lethargy for one month showed no difference between the two groups. Palliative radiotherapy for metastatic bone pain using a single treatment is recommended. From April, 1989 through January, 1990, a randomized trial was conducted to investigate the efficacy of single fraction radiation treatment (8, 10, 12, 15Gy) compared to a multifraction dose schedule (5Gy x 4, 5Gy x 5, 5Gy x 6) as a therapy for a bone metastasis. Both subjective and objective pain scores were used to measure the therapeutic results. A total of 31 patients participated in the trial and, for analysis, 27 of these patients were follow-up for more than 8 weeks after the start of the radiation therapy. The following statistics resulted. Of the single fraction series, symptomatic pain relief was obtained in 86% of the patients (12/14 treatment areas), and of the multifraction series, 92% (12/13). Further, a complete response was achieved in 57% (8/14) of the single fraction patients and 31% (4/13) of the multifraction patients, respectively. Between the two treatment regimens, no difference was found in the incidence of pain relief, speed of onset, or acute morbidity. Finally, no severe morbidity was seen in either arm. In a prospective randomized trial we examined whether radiotherapy of painful bone metastases can be shortened using larger single doses without impairing effectivity.
                One hundred patients with painful bone metastases having no prior surgical intervention or treatment with x-ray therapy and had a median follow-up of 12 months were analyzed. The primary tumor was located in the breast in 43%, in the lung in 24%, and in the prostate in 14%. The most frequent sites of metastases were the pelvis (31%), the vertebral column (30%), and the ribs (20%). Further percentages of sites were: lower extremity 11%, upper extremity 6%, and skull 2%. Fifty-one patients received a short course radiotherapy with a total dose of 20 Gy in 1 week (daily dose 4 Gy), and 49 patients received 30 Gy in 3 weeks (daily dose 2 Gy).
                There were no significant differences in frequency, duration of pain relief, improvement of mobility, recalcification, frequency of pathologic fractures nor survival. There was a light trend favoring 30 Gy in frequency of pain relief and recalcification. Survival was mostly influenced by primary tumor site, Karnofsky performance status, and possibly by the response to radiotherapy (pain relief).
                Because of the very short life expectancy of patients with metastatic bone disease, we now use 20 Gy in 1 week as our standard to reduce hospital stay. To answer the question whether a single fraction of radiotherapy that is considered more convenient to the patient is as effective as a dose of multiple fractions for palliation of painful bone metastases. Patients: 1171 patients were randomised to receive either 8 Gy x 1 (n = 585) or 4 Gy x 6 (n = 586). The primary tumour was in the breast in 39% of the patients, in the prostate in 23%, in the lung in 25% and in other locations in 13%. Bone metastases were located in the spine (30%), pelvis (36%), femur (10%), ribs (8%), humerus (6%) and other sites (10%).
                Questionnaires were mailed to collect information on pain, analgesics consumption, quality of life and side effects during treatment. The main endpoint was pain measured on a pain scale from 0 (no pain at all) to 10 (worst imaginable pain). Costs per treatment schedule were estimated.
                On average, patients participated in the study for 4 months. Median survival was 7 months. Response was defined as a decrease of at least two points as compared to the initial pain score. The difference in response between the two treatment groups proved not significant and stayed well within the margin of 10%. Overall, 71% experienced a response at some time during the first year. An analysis of repeated measures confirmed that the two treatment schedules were equivalent in terms of palliation. With regard to pain medication, quality of life and side effects no differences between the two treatment groups were found. The total number of retreatments was 188 (16%). This number was 147 (25%) in the 8 Gy x 1 irradiation group and 41 (7%) in the 4 Gy x 6 group. It was shown that the level of pain was an important reason to retreat. There were also indications that doctors were more willing to retreat patients in the single fraction group because time to retreatment was substantially shorter in this group and the preceding pain score was lower. Unexpectedly, more pathological fractures were observed in the single fraction group, but the absolute percentage was low. In a cost-analysis, the costs of the 4 Gy x 6 and the 8 Gy x 1 treatment schedules were calculated at 2305 and 1734 Euro respectively. Including the costs of retreatment reduced this 25% cost difference to only 8%. The saving of radiotherapy capacity, however, was considered the major economic advantage of the single dose schedule.
                The global analysis of the Dutch study indicates the equality of a single fraction as compared to a 6 fraction treatment in patients with painful bone metastases provided that 4 times more retreatments are accepted in the single dose group. This equality is also shown in long term survivors. A more detailed analysis of the study is in progress.
Single fraction radiotherapy was as effective as multifraction radiotherapy in relieving metastatic bone pain. However, the retreatment rate and pathological fracture rates were higher after single fraction radiotherapy. Studies with quality of life and health economic end points are warranted to find out the optimal treatment option.