Single-Fraction SBRT vs Multifraction RT for Nonspine Bone Metastases NCT02163226
ForPainful, predominantly nonspine bone mets, life expectancy >3 mo, no prior RT
TL;DR3-mo ITT pain response 38% vs 21% (P=.05) with 12-16 Gy single-fraction SBRT vs 30 Gy/10; 2-yr local PFS 100% vs 75.6%.
Dose, not single fraction per se, carries the pain signal: 3-mo ITT response was 62% (13 of 21) with 16 Gy vs 30% (18 of 60) with 12 Gy, and 12 Gy tracked 30 Gy/10 at 9 mo (13.3% vs 15.2%). Because 16 Gy went to smaller lesions, the dose choice remains hypothesis-level.
In a pt with a painful nonspine bone met, good performance status and longer expected survival, this supports single-fraction SBRT as a reasonable alternative to 30 Gy/10; it does not test SBRT against an 8 Gy single fraction or extend to spine lesions, cord compression or pathologic fracture.
Dose carries the pain signal: 3-mo ITT response was 62% (13 of 21) with 16 Gy vs 30% (18 of 60) with 12 Gy, and 12 Gy tracked 30 Gy/10 at 9 mo. Local failure was 0% with SBRT at 24 mo, but 16 Gy went to smaller lesions, so the dose pick is hypothesis-level.
14 details 2 trials watching
Phase 2, nonblinded, randomized noninferiority trial at one institution, 1:1, N=160 (81 SBRT, 79 MFRT). Stratified by tumor size, bone site and number of sites irradiated. Enrolled September 2014 to June 2018.
Pathologic cancer diagnosis, painful bone mets (score ≥2 of 10), age ≥18, life expectancy >3 mo; up to 3 fields allowed. Excluded prior RT to the site, untreated cord compression, pathologic fracture at the site, and recent radioisotope.
SBRT 12 or 16 Gy x1 by lesion size (4 cm cutoff) vs 30 Gy in 10 fx. PTV = GTV + 5 mm, no CTV; 2D/3D, IMRT or VMAT delivery. Prophylactic 7-day low-dose dexamethasone recommended for SBRT only.
Primary: pain response by international consensus criteria (pain score plus MED), noninferiority margin 10%. Secondary: MDASI QoL, CTCAE toxicity, local control, OS.
No toxicity differences between arms. G3 fatigue 9.9% vs 5.1% (P=.37), fracture 1.2% vs 0% (P=.99); MDASI scores improved in both arms without a difference.
Prior randomized trials found no pain difference between single and multifraction conventional courses, with more retreatment after 8 Gy. RTOG 9714 and the Dutch Bone Metastasis Study are the conventional-dose trials behind that equivalence. This trial escalates the single fraction but never tests it against 8 Gy.
Dexamethasone given asymmetrically to SBRT pts confounds early pain response. The 16 vs 12 Gy contrast is non-randomized and tracks lesion size. Five SBRT pts did not receive treatment due to insurance denial, and median OS of 6.7 mo leaves few pts at risk for late local failure.
The ITT data support noninferiority and a local-control advantage for SBRT; the superiority read depends on per-protocol denominators. The live question is 16 Gy vs 8 Gy in pts selected for longer survival, which needs a phase 3.
| Analysis · timepoint | SBRT | MFRT | P |
|---|---|---|---|
| ITT · 1 mo | 44% (n=36) | 30% (n=24) | .18 |
| ITT · 3 mo | 38% (n=31) | 21% (n=17) | .05 |
| Per-protocol · 2 wk | 34 of 55 (62%) | 19 of 52 (36%) | .01 |
| Per-protocol · 3 mo | 31 of 43 (72%) | 17 of 35 (49%) | .03 |
| Per-protocol · 9 mo | 17 of 22 (77%) | 12 of 26 (46%) | .04 |
| Timepoint | 16 Gy x1 | 12 Gy x1 | 30 Gy/10 | P |
|---|---|---|---|---|
| 3 mo | 62% (13 of 21) | 30% (18 of 60) | 21% (17 of 79) | .003 |
| 9 mo | 42.9% (9 of 21) | 13.3% (8 of 60) | 15.2% (12 of 79) | .005 |
| Endpoint | SBRT | MFRT | P |
|---|---|---|---|
| 1-yr local PFS | 100% | 90.5% | .01 (curve) |
| 2-yr local PFS | 100% | 75.6% | .01 (curve) |
| 24-mo cumulative local failure | 0% | 9.7% | .02 |
| 2-yr reirradiation | 0% | 5.3% | .10 |
CONSORT flow
Single-institution randomized phase 2 with one-sided alpha 0.20; superiority signals are per-protocol amid heavy attrition, comparator 30 Gy/10 rather than 8 Gy. Authors call for phase 3.
- Does 16 Gy SBRT beat 8 Gy single fraction for pain?
- Phase 3 confirmation of SBRT pain response in nonspine bone mets recruiting A Phase III Randomized Trial Comparing Stereotactic Body Radiation Therapy (SBRT) vs Conventional Palliative Radiation Therapy for Painful Bone Metastases Phase 3n=220 · primary completion 2027-06 · phase 3 SBRT dose levels vs conventional palliative RTrecruiting Stereotactic Body Radiotherapy vs Conventional Palliative Radiotherapy for Painful Non-Spine Bone Metastases Phase 3n=230 · primary completion 2027-07 · phase 3 SBRT vs conventional RT, non-spine pain relief
- Which pts live long enough to gain from SBRT local control?
📚 Sources · 📄 1 paper
The longer read
The trial answers a narrower question than its headline suggests. The comparator is 30 Gy in 10 fractions, a regimen that prior randomized work had already shown to be no better for pain than a short single-fraction course, which mostly costs more retreatment. RTOG 9714 and the Dutch Bone Metastasis Study are the conventional-dose trials behind that equivalence. So this result is best read as escalated single-fraction SBRT against a protracted conventional course, not against the single-fraction standard most departments default to. Whether 16 Gy beats 8 Gy, the decision that actually sits in front of a palliative clinic, is untested here.
Within that frame the signal runs in one direction. The ITT pain response difference at 3 months (38% vs 21%, P=.05), the local-control separation (2-yr local PFS 100% vs 75.6%) and the narcotic-escalation HR of 0.26 all favour SBRT. But the trial was powered for noninferiority with a one-sided alpha of 0.20, a permissive phase 2 threshold, and the superiority language rests mostly on per-protocol comparisons that analyzed 44 of 81 and 35 of 79 pts at 3 months. Pts who die early or deteriorate leave per-protocol denominators, and if that attrition differs by arm in ways linked to pain, the gap can widen without any treatment effect. The ITT figures are the ones to carry into a tumor board.
Two design features push the pain endpoint toward SBRT independent of dose. Prophylactic dexamethasone was recommended for the SBRT arm only, and steroids blunt early pain and flare; the 2-week per-protocol separation is exactly where that would show. The dose subset is also confounded, since 16 Gy went to the smaller lesions, so the 16 vs 12 Gy contrast mixes dose with tumour size. The finding that 12 Gy pain response at 9 months sat close to 30 Gy/10 (13.3% vs 15.2%) is the cautionary half of that subset and deserves as much weight as the 16 Gy result.
Local control is the cleaner secondary. Zero local failures with SBRT against a rising cumulative incidence with MFRT is coherent with the BED gap, but events were few (HR 0.18, 95% CI 0.02-1.47) and median OS was 6.7 months in both arms, so most pts did not live long enough for local failure to matter. That tension defines who the result applies to: a durable local benefit is plausible in the minority with long expected survival, and those pts were a small share of this cohort despite the life-expectancy entry criterion.
For an RT reader, the trial supports SBRT as a reasonable option for selected nonspine lesions in pts with good performance status and longer expected survival, and it argues that the confirmatory phase 3 should be run against 8 Gy rather than 30 Gy/10. It does not establish superiority for pain, and its single-institution design with size-assigned dosing makes the preference for 16 Gy a hypothesis rather than a finding.