› Forums › Cutaneous Melanoma Community › Painful bone metastases – repeat radiation trial
- This topic is empty.
- Post
-
- January 6, 2014 at 6:31 pm
Single vs Multiple Fractions of Repeat Radiation for Painful Bone Metastases
Lancet Oncol 2013 Dec 23;[EPub Ahead of Print], E Chow, YM van der Linden, D Roos, WF Hartsell, P Hoskin, JSY Wu, MD Brundage, A Nabid, CJA Tissing-Tan, B Oei, S Babington, WF Demas, CF Wilson, RM Meyer, BE Chen, RKS Wong
Research · January 02, 2014TAKE-HOME MESSAGE
- In an attempt to determine the benefit of repeat palliative radiotherapy to previously radiated painful bone metastasis, investigators randomized patients to 8 Gy in a single fraction or 20 Gy in multiple fractions and evaluated pain response at 2 months. Although the results are confounded by a high rate of not assessable patients in both arms, single-fraction radiation therapy appeared to be non-inferior and less toxic to multiple fractions.
- While this trial appears to support a less intensive palliative radiation treatment, improved trial adherence in future explorations will help in firmly defining future treatment protocols.
– Chris Tully, MD
ABSTRACT
Background
Although repeat radiation treatment has been shown to palliate pain in patients with bone metastases from multiple primary origin sites, data for the best possible dose fractionation schedules are lacking. We aimed to assess two dose fractionation schedules in patients with painful bone metastases needing repeat radiation therapy.
Methods
We did a multicentre, non-blinded, randomised, controlled trial in nine countries worldwide. We enrolled patients 18 years or older who had radiologically confirmed, painful (ie, pain measured as ≥2 points using the Brief Pain Inventory) bone metastases, had received previous radiation therapy, and were taking a stable dose and schedule of pain-relieving drugs (if prescribed). Patients were randomly assigned (1:1) to receive either 8 Gy in a single fraction or 20 Gy in multiple fractions by a central computer-generated allocation sequence using dynamic minimisation to conceal assignment, stratified by previous radiation fraction schedule, response to initial radiation, and treatment centre. Patients, caregivers, and investigators were not masked to treatment allocation. The primary endpoint was overall pain response at 2 months, which was defined as the sum of complete and partial pain responses to treatment, assessed using both Brief Pain Inventory scores and changes in analgesic consumption. Analysis was done by intention to treat.
Findings
Between Jan 7, 2004, and May 24, 2012, we randomly assigned 425 patients to each treatment group. 19 (4%) patients in the 8 Gy group and 12 (3%) in the 20 Gy group were found to be ineligible after randomisation, and 140 (33%) and 132 (31%) patients, respectively, were not assessable at 2 months and were counted as missing data in the intention-to-treat analysis. In the intention-to-treat population, 118 (28%) patients allocated to 8 Gy treatment and 135 (32%) allocated to 20 Gy treatment had an overall pain response to treatment (p=0·21; response difference of 4·00% [upper limit of the 95% CI 9·2, less than the prespecified non-inferiority margin of 10%]). In the per-protocol population, 116 (45%) of 258 patients and 134 (51%) of 263 patients, respectively, had an overall pain response to treatment (p=0·17; response difference 6·00% [upper limit of the 95% CI 13·2, greater than the prespecified non-inferiority margin of 10%]). The most frequently reported acute radiation-related toxicities at 14 days were lack of appetite (201 [56%] of 358 assessable patients who received 8 Gy vs 229 [66%] of 349 assessable patients who received 20 Gy; p=0·011) and diarrhoea (81 [23%] of 357 vs 108 [31%] of 349; p=0·018). Pathological fractures occurred in 30 (7%) of 425 patients assigned to 8 Gy and 20 (5%) of 425 assigned to 20 Gy (odds ratio [OR] 1·54, 95% CI 0·85–2·75; p=0·15), and spinal cord or cauda equina compressions were reported in seven (2%) of 425 versus two (<1%) of 425, respectively (OR 3·54, 95% CI 0·73–17·15; p=0·094).
Interpretation
In patients with painful bone metastases requiring repeat radiation therapy, treatment with 8 Gy in a single fraction seems to be non-inferior and less toxic than 20 Gy in multiple fractions; however, as findings were not robust in a per-protocol analysis, trade-offs between efficacy and toxicity might exist.
The Lancet OncologySingle Versus Multiple Fractions of Repeat Radiation for Painful Bone Metastases: A Randomised, Controlled, Non-Inferiority Trial
Lancet Oncol 2013 Dec 23;[EPub Ahead of Print], E Chow, YM van der Linden, D Roos, WF Hartsell, P Hoskin, JSY Wu, MD Brundage, A Nabid, CJA Tissing-Tan, B Oei, S Babington, WF Demas, CF Wilson, RM Meyer, BE Chen, RKS Wong
Tagged: caregiver, cutaneous melanoma
- You must be logged in to reply to this topic.
Commentary by
Painful bone metastases remain one of the most feared and difficult consequences of advanced cancer. Radiation therapy provides relief of pain, and evidence has accumulated that a single fraction of 8 Gy can yield similar results to multiple smaller fractions over 1 to 2 weeks designed to deliver 20 Gy. Less is known about the benefit of single fraction vs multiple fractions when re-radiating lesions that either failed to respond to the first radiation or became painful again. Chow and colleagues performed a multicenter trial over several years designed to answer that question. They found that, in general, a single 8 Gy fraction yielded a noninferior result in terms of the primary endpoint of pain reduction compared with multiple fractions. However, the study was hampered by a high dropout rate and large number of patients who did not complete the pain assessment at the appropriate time. These complications were not unexpected as the trial dealt with a very advanced population. It was, therefore, gratifying to see that quality of life improved for the majority of patients in both arms after re-irradiation.
These results support the use of a convenient, single day/dose of 8 Gy when a bony lesion requires re-irradiation for pain control. Such an approach could be useful for palliation even in patients not receiving active cancer therapy and those on hospice care, given the significant improvement in pain, symptoms, and quality of life seen in many patients.