Bone metastases are common among patients with solid primary tumors of the breast, prostate, lung, and other organs; up to 85% of patients with advanced breast or prostate cancer will experience the metastatic spread of their cancer to bones.1 The effects of bone metastases on a patient’s quality of life depend on tumor size, location of the tumor, and involvement of adjacent tissue. Bone tumors can be very painful and resistant to pain-management medication, and frequently weaken bone, causing complications and functional impairments (skeletal-related events [SREs]; eg, bone fractures, spinal compression).2
Palliative radiotherapy can alleviate pain and delay SREs. Targeted (denosumab) or systemic osteoclast-inhibiting bisphosphonate (eg, zoledronate) therapies are also frequently undertaken to delay or prevent SREs. Traditional treatment options also include conventional pain medications, chemotherapy and hormone therapy, corticosteroids, or bone-seeking radiopharmaceuticals.1 In 2012, the US Food and Drug Administration also approved palliative MRI-guided focused ultrasound ablation of painful bone metastases, and microwave ablation is currently under clinical development. These modalities hold promise as important treatment options, particularly for patients whose bone tumors are radioresistant.
Single-fraction (8 Gy) radiotherapy is the standard first-line palliative treatment for patients with uncomplicated bone pain.2-4 Retreatment is more frequently necessary after single-dose treatments, however, it affects up to 42% of patients.2
Now, results from an international randomized trial have shown that single-fraction 8-Gy radiotherapy effectively relieves overall pain at 2 months, and is less toxic than a multiple-fraction 20-Gy regimen, when delivered at least 4 weeks after first-line radiotherapy.5 The study included patients without spinal cord compression, pathologic bone fractures, or impending fractures requiring surgical fixation.5 Pain was assessed using the Brief Pain Inventory and patients’ use of pain medication.
The study “showed that re-irradiation is beneficial, even in patients without response to initial radiotherapy,” wrote oncologist Carsten Nieder, MD, of Nordland Hospital in Norway, in an accompanying commentary.2
However, only 521 (61%) of the 850 participants could be assessed at 2 months, the study authors cautioned.5 Fatigue, vomiting, and diarrhea were less frequent among patients who underwent the single-fraction 8-Gy treatment compared with those who underwent multiple-fraction 20-Gy radiotherapy.5
Trends toward increased fractures within radiation fields and spinal compression among patients in the single-fraction group did not reach statistical significance.5 Further analysis is needed to determine the influence of bisphosphonate therapy on radiotherapy outcomes.2,5
“In the meantime, decision-making remains complex because many, but not all, patients seem to be adequately treated with single fractions, and trade-offs between efficacy and inconvenience or toxicity might exist,” noted Dr. Nieder.2
But for now, at least, the best available evidence supports a single-fraction 8 Gy radiotherapy regimen for both first-line and repeat palliation in most patients suffering painful metastatic bone tumors.
- Rubini G, Nicoletti A, Rubini D, Asabella AN. Radiometabolic treatment of bone-metastasizing cancer: from 186-Rhenium to 223-Radium. Cancer Biother Radiopharm. 2014;29(1):1-11.
- Nieder C. Repeat palliative radiotherapy for painful bone metastases. Lancet Oncol. 2014;15(2):126-128.
- Lutz S, Berk L, Chang E, et al. Palliative radiotherapy for bone metastases: an ASTRO evidence-based guideline. Int J Rad Oncol Biol Physics. 2011;79(4):965-976.
- Dennis K, Mahhani L, Zeng L, et al. Single fraction conventional external beam radiation therapy for bone metastases: a systematic review of randomised controlled trials. Radiother Oncol. 2013;106(1):5-14.
- Chow E, van der Linden Y, Roos D, et al. Single versus multiple fractions of repeat radiation for painful bone metastases: a randomised, controlled, non-inferiority trial. Lancet Oncol. 2014;15(2):164-171.