116Radiotherapy dose fractionation Third edition
Localised bone pain in established metastatic disease
Background
Uncomplicated local bone pain responds well with response rates of 70–80% after
localised external beam treatment. Since response may take 4–6 weeks to achieve, it is
recommended that consideration be given to the patient’s prognosis before treatment. A
number of large randomised controlled trials have been undertaken to explore the optimal
dose. Three reviews have been completed using the Cochrane methodology. On the basis
of this information, the recommended fractionation is a single dose of 8 Gray (Gy) (Level
1a).
1–4
Bone metastases may give rise to pain with neuropathic features rather than simple bone
pain. One randomised controlled trial specically addressed this question, comparing
single-dose 8 Gy to multifraction treatment, for most patients 20 Gy in ve fractions.
No major advantage for the multifraction arm was identied, and the recommendation
therefore is that these patients should also receive a single dose of 8 Gy.
5
Recommendation
For the initial therapy of pain from bone metastases:
8 Gy single dose (Grade A)
The types of evidence and the grading of recommendations used within this review are based on
those proposed by the Oxford Centre for Evidence-based Medicine.
4
Bone metastases in oligometastatic disease
In the context of oligometastatic disease, stereotactic body radiotherapy (SBRT) can
achieve local control rates of 80% and treatment has been shown to be well tolerated, with
low rates of spinal cord myelopathy (see section 20).
Retreatment
Retreatment should be considered in patients still having clinically signicant pain after 4–6
weeks despite optimal analgesic. After a single dose, around 25% of patients may need
re-treatment at some point.
6
Limited evidence suggests that response rates are similar to
those after primary treatment.
7
There are no data to guide optimal dose fractionation for
retreatment; a randomised trial compared 8 Gy single dose with 20 Gy in ve fractions (eight
fractions over the spinal cord) and showed no signicant dierence (Level 1b).
4,8
Both may
be considered acceptable treatments for re-irradiation.
Recommendations
For the re-irradiation of bone metastases:
8 Gy single dose (Grade B)
20 Gy in 5 daily fractions (or 8 fractions over the spinal cord) over 1 week (Grade B)
The types of evidence and the grading of recommendations used within this review are based on
those proposed by the Oxford Centre for Evidence-based Medicine.
4
18.
Bone metastases
117Radiotherapy dose fractionation Third edition
Scattered bone pain
For metastatic bone pain at several sites despite adequate analgesia, wide-eld or
hemibody external beam radiotherapy (EBRT) may be eective. Appropriate pre-
medication, such as dexamethasone and a 5HT3 antagonist is advised to reduce radiation-
induced nausea and vomiting. There are no randomised data to compare such treatment
to isotope therapy, but case–control comparisons suggest that all are equally eective.
However, EBRT is associated with more toxicity in terms of gastrointestinal and bone
marrow side-eects.
9
A large international study tested two, four and ve fraction regimens,
but there is no evidence to suggest that any of these are superior to giving the treatment in a
single-dose (Level 4).
4,10
Recommendation
For patients with scattered bone pain:
Upper hemibody 6 Gy single dose (Grade C)
Lower hemibody 8 Gy single dose (Grade C)
The types of evidence and the grading of recommendations used within this review are based on
those proposed by the Oxford Centre for Evidence-based Medicine.
4
Pathological fracture
Prophylaxis
Bone metastases with high risk of pathological fracture can be identied from their
radiological appearances. Suggested parameters include: those with > 50% cortical
destruction, >3 centimetre (cm) maximum diameter, axial cortical involvement >3 cm and
multifocal lytic disease.
11
Surgical xation should be considered.
If radiotherapy is to be used, there is no consensus on the best fractionation in this setting.
Higher risk lesions were in general excluded from fractionation trials. Common practice
would be for these patients to receive a fractionated regimen such as 20 Gy in ve fractions
or 8 Gy single dose (Level 5).
4
Recommendation
To prevent pathological fracture:
8 Gy single dose (Level 4) or
20 Gy in 5 fractions over 1 week (Level 4)
The types of evidence and the grading of recommendations used within this review are based on
those proposed by the Oxford Centre for Evidence-based Medicine.
4
118Radiotherapy dose fractionation Third edition
Established fracture
Bones such as ribs, vertebrae and pelvic and shoulder girdle bones are not amenable
to surgical xation and can be treated with local radiotherapy. There is no consensus on
optimal fractionation.
Recommendation
For inoperable pathological fractures:
8 Gy single dose (Grade D) or
20 Gy in 5 fractions over 1 week (Grade D)
The types of evidence and the grading of recommendations used within this review are based on
those proposed by the Oxford Centre for Evidence-based Medicine.
4
Postoperative radiotherapy
After internal xation of a fracture or prophylactic pinning of a high-risk lesion, postoperative
radiotherapy is often recommended. There is limited literature to support its ecacy and no
consensus on dose. Treatment should be considered for all patients with persisting bone
pain after surgery. In cases where treatment is given with the aim of enabling bone healing
and long-term rehabilitation, consideration should be given to performance status and
predicted survival.
Recommendations
Postoperative radiotherapy after xation of bone metastases:
8 Gy single dose (Grade D) or
20 Gy in 5 fractions over 1 week (Grade D)
The types of evidence and the grading of recommendations used within this review are based on
those proposed by the Oxford Centre for Evidence-based Medicine.
4
119Radiotherapy dose fractionation Third edition
1. McQuay H, Carroll D, Moore RA. Radiotherapy for painful bone metastases: a systematic review. Clin
Oncol 1997; 9(3): 150–154.
2. Wu JS, Wong R, Johnston M et al. Meta-analysis of dose-fractionation radiotherapy trials for the
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3. Sze WM, Shelley MD, Held I, Wilt TJ, Mason MD. Palliation of metastatic bone pain: single fraction
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4. www.cebm.net/oxford-centre-evidence-based-medicine-levels-evidence-march-2009
(last accessed 30/9/16)
5. Roos DE, Turner SL, O’Brien PC et al. Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of
radiotherapy for neuropathic pain due to bone metastases. Radiother Oncol 2005; 75(1): 54–63.
6. van der Linden YM, Lok YJ, Steenland E et al. Single fraction radiotherapy is ecacious: a further
analysis of the Dutch Study controlling for the inuence of retreatment. Int J Radiat Oncol Biol Phys
2004; 59(2): 528–537.
7. Mithal NP, Needham PR, Hoskin PJ. Retreatment with radiotherapy for painful bone metastases. Int J of
Rad Oncol Biol Phys 1994; 29(5): 1011–1014.
8. Chow E, van der Linden YM, Roos D et al. Single versus multiple fractions of repeat radiations for
painful bone metastases: a randomised, controlled, non-inferiority trial. Lancet Oncol 2014; 15(2):
164–171.
9. Dearnaley DP, Bayley RJ, A’Hern RP, Gadd J, zivanovic MM, Lewington VJ. Palliation of bone
metastases in prostate cancer. Hemibody irradiation or strontium-89. Clin Oncol (R Coll Radiol) 1992;
4(2): 101–107.
10. Salazar OM, Sandhu T, da Motta NW et al. Fractionated half-body irradiation (HBI) for the rapid
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International Atomic Energy Agency (IAEA). Int J Radiat Oncol Biol Phys 2001; 50(3): 765–775.
11. van der Linden YM, Kroon HM, Dijkstra SP et al. Simple radiographic parameter predicts fracturing in
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