Hepatobiliary
Randomised evidence that SBRT is the added variable, in an arm-to-arm design where sorafenib is common to both, but read against a systemic backbone the field has since replaced.
RTOG 1112 NCT01730937
ForLocally advanced HCC unsuitable for local-regional therapy, 74% macrovascular invasion
15.8 vs 12.3 mo
HR 0.77, 90% CI 0.59-1.01, 1-sided P=.06 (did not meet)
TL;DRmOS 15.8 vs 12.3mo, HR 0.77 (90% CI 0.59-1.01), 1-sided P=.06; adjusted HR 0.72, P=.04; PFS HR 0.55.
The PFS signal is where SBRT earns its place: 9.2 vs 5.5 mo, HR 0.55 (95% CI 0.40-0.75), in a cohort 74% macrovascular-invasion positive, at 27.5 to 50 Gy in 5 fx with no excess G3+ toxicity (47% vs 42%, P=.52). That moves the add-SBRT-to-systemic decision in vascular-invasion HCC, even with sorafenib as the backbone.
In locally advanced HCC with macrovascular invasion who are unsuitable for or refractory to local-regional therapy, this supports adding 5-fraction SBRT to first-line systemic therapy; it does not address SBRT layered onto current IO-based regimens.
Personalized SBRT at 27.5 to 50 Gy in 5 fractions produced mPFS 9.2 vs 5.5 mo, HR 0.55 (95% CI 0.40-0.75), in a cohort 74% macrovascular-invasion positive, with G3+ toxicity indistinguishable from systemic therapy alone (47% vs 42%, P=.52). That is the case for offering liver SBRT alongside systemic therapy in vascular-invasion HCC.
The systemic backbone was fixed at sorafenib in both arms, so the OS and PFS deltas reflect the addition of RT, not drug choice. The open question for a med onc is sequencing: whether the HR 0.55 PFS gain persists on an IO-based first-line backbone, which is untested here.
10 details 5 trials watching
Multicenter phase 3 RCT, 1:1, stratified by performance status, liver function, degree of metastases and macrovascular invasion. 193 randomized, 177 eligible; accrual April 2013 to March 2021, stopped early once standard-of-care systemic therapy changed.
HCC unsuitable for or refractory to standard local-regional therapies and candidates for first-line systemic therapy. 150 of 177 (84.7%) male, median age 66 (IQR 60-72), macrovascular invasion in 131 (74.0%).
Personalized SBRT, 27.5 to 50 Gy in 5 fractions, delivered before sorafenib. The dose range is individualized rather than fixed, so the prescription reflects liver reserve and target geometry, not a single protocol dose.
Sorafenib in both arms; the experimental arm added SBRT first. The systemic backbone is identical, so the difference is attributable to radiation.
Primary: overall survival. Secondary: progression-free survival, adverse events, quality of life. The primary OS comparison was tested 1-sided with 90% CIs.
OS 15.8 vs 12.3 mo, HR 0.77 (90% CI 0.59-1.01), 1-sided P=.06; adjusted for stratification factors HR 0.72 (95% CI 0.52-0.99), 2-sided P=.04. PFS 9.2 vs 5.5 mo, HR 0.55 (95% CI 0.40-0.75), P<.001.
| Measure | Sorafenib | SBRT + sorafenib | P |
|---|---|---|---|
| Tx-related G3+ AE | 37 of 88 (42%) | 39 of 83 (47%) | P=.52 |
| Tx-related deaths | 2 | 1 | n/a |
| Improved QoL at 6 mo | 2 of 20 (10%) | 6 of 17 (35%) | n/a |
Treatment-related G3+ AEs 47% (39 of 83) with SBRT vs 42% (37 of 88) with sorafenib alone, P=.52. Treatment-related deaths: 2 sorafenib (unspecified, liver failure), 1 SBRT arm (lung infection).
The sorafenib comparator is the SHARP-era standard, and 1L HCC has since moved to IO-based combinations, which is why accrual closed. No randomised trial has yet tested SBRT against, or added to, those current regimens.
Early closure leaves the OS test underpowered, and the 2-sided P=.04 comes from the stratification-adjusted model rather than the primary unadjusted analysis. QoL was assessed in only 20 and 17 evaluable pts at 6 months, too few to weigh against the toxicity comparison.
The consistency between an OS HR of 0.77 and a PFS HR of 0.55 in a 74% macrovascular-invasion cohort argues the local effect is real and that OS dilution reflects competing liver and systemic events, not absence of benefit. What it does not settle is whether that local effect survives on top of a systemic backbone that already controls disease better than sorafenib did.
CONSORT flow
Randomised phase 3, prespecified OS primary, but 1-sided P=.06 misses and accrual closed early; comparator arm is sorafenib, now superseded.
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