Hepatobiliary
2026-08-08
BEACON-HCC
ForHCC across all stages, North American practice context
TL;DRNew North American HCC allocation framework; expert decisions 96.6% concordant with BEACON vs 72.4% with BCLC 2025 across 29 cases.
First major allocation framework to place EBRT/SBRT alongside TARE as a first-line locoregional option rather than a BCLC afterthought, extending to Class 1D (Vp1-2) and Class 3B (Vp3/4). The panel's own citation base for Class 3B is RTOG1112, which showed only a trend (p=0.06) for SBRT vs sorafenib, so the elevation runs ahead of randomised evidence.
For a cirrhotic patient with unifocal HCC not eligible for resection or transplant, this framework treats SBRT as a legitimate first-line ablative option rather than a fallback; it does not apply to Class 4A, where the panel explicitly withholds EBRT outside symptom palliation.
SBRT enters the allocation boxes as a first-line locoregional option across Classes 1A through 3A, not a salvage line, which changes referral expectations at tumor board. No dose or fractionation is specified anywhere in the framework, and the Class 3B citation is RTOG1112 at p=0.06, so the elevation runs ahead of randomised evidence.
The framework pushes back on reflexive systemic therapy for macrovascular invasion: Class 1D (Vp1-2) is routed to local or surgical options, and adjuvant therapy after complete response is explicitly not recommended. Systemic therapy stays the cornerstone only for Class 3B, 4A, and 4B.
Resection is preferred without CSPH, transplant with it, and both extend beyond early stage after downstaging response. Class 3B carries a cited RCT showing resection after neoadjuvant radiation beat up-front resection, and Vp1-2 patients with deep durable responses become transplant candidates rather than automatic exclusions.
9 details 4 trials watching
Modified Delphi consensus, 20 North American multidisciplinary experts, iterative discussion and voting over two rounds. Followed by a 29-case pilot concordance exercise against external experts.
Framework spans the full HCC spectrum, from unifocal ≤3 cm (Class 1A) to distant metastases (Class 4B). Class assignment keys on tumor burden, Vp level of portal invasion, and poor prognostic features (>8 cm, AFP >1000 ng/mL, poor differentiation).
EBRT including SBRT is named a first-line locoregional option in Classes 1A through 3A, on par with TARE, RFA/MWA, and TACE. No dose or fractionation is specified anywhere in the framework: the stated rationale is ablative dose delivered selectively to limit radiation-induced liver injury. In Class 4A, EBRT is not routinely indicated outside palliation of symptomatic disease.
Expert decisions matched BEACON in 28 of 29 cases (96.6%) vs 72.4% for BCLC 2025. The single discordant case was combination systemic plus locoregional therapy for vascular invasion reaching the right atrium.
| BEACON class | BCLC 2025 | AJCC v8 | Adaptation from BCLC |
|---|---|---|---|
| Class 1A | Very early (0) or early (A) | Stage 1A or 1B | Aligned; framework elevates SBRT and TARE |
| Class 1B | Early (A) | Stage 1B | Aligned |
| Class 1C | Early (A) | Stage 2 | Aligned |
| Class 1D | Advanced (C) | Stage 2 | Macrovascular invasion may suit local or surgical therapy: TARE, SBRT, resection |
| Class 2 | Early (A) | Stage 1A or 1B | Aligned; framework elevates SBRT and TARE |
| Class 3A | Intermediate (B) or advanced (C) | Stage 3A | Aligned; framework elevates SBRT and TARE |
| Class 3B | Advanced (C) | Stage 3B or 4A | Macrovascular invasion may be amenable to local therapy in selected cases |
| Class 4A | Intermediate (B) | Stage 3A | Extensive intrahepatic spread treated as systemic process |
| Class 4B | Advanced (C) | Stage 4B | Stage and treatment framework aligned |
BCLC keeps radiation outside its core allocation algorithm; BEACON moves it in. The supporting evidence the panel cites is uneven: DOSISPHERE (ORR 71 vs 36%, OS 26.6 vs 10.7 mo) for personalized-dosimetry TARE is randomised, while the SBRT case in Class 3B rests on RTOG1112, which reached only p=0.06 for OS vs sorafenib.
The 72.4% BCLC comparator was scored by BEACON's own authors against cases the same group selected, and 29 cases cannot exercise nine classes evenly. Round-1 per-class agreement is unreadable from the source table because vote counts and class labels arrived unpaired.
The framework's real claim is that intrahepatic burden and Vp level, not BCLC's stage buckets, should drive allocation, and that radiation-based modalities are burden-appropriate rather than stage-restricted. Whether that improves outcomes is untested: validation against empiric clinical data is deferred to the HCC-Live Consortium.
Delphi consensus framework, not an efficacy study. Concordance figures measure opinion against opinion. Elevates EBRT/TARE to first-line locoregional status in a formal allocation system.
- Head-to-head SBRT vs TARE for liver-confined HCC n=146 · primary completion 2028-12 · randomised phase 2 TARE vs SBRT, =3 HCC lesionsrecruiting Comparison of SBRT and SIRT With Combination IO for Locally-advanced, Unresectable HCCs (BIIRTH) Phase 2/3n=106 · primary completion 2034-03 · TACE-SBRT vs Y90 SIRT, PFS primary
- Does BEACON allocation improve survival vs BCLC allocation
- Optimal sequencing of ICI with locoregional therapy active Durvalumab/Tremelimumab in Neoadjuvant and Adjuvant Setting in Patients With HCC Treated by by Percutaneous Ablation Procedure Phase 2n=30 · primary completion 2027-09 · durva/treme before and after percutaneous ablationrecruiting Using Radiotherapy and Immunotherapy to Treat Advanced Liver Cancer Before Transplant Phase 1/2n=48 · primary completion 2031-06 · Y90/SBRT plus atezo-bev, transplant conversion
📚 Sources · 📄 1 paper
Abstract
2026-07-01
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.
- Does SBRT benefit persist on IO-based first-line systemic therapy recruiting Testing Immunotherapy With or Without Stereotactic Body Radiation Therapy in Patients With Advanced Liver Cancer, HELIO-RT Trial Phase 3n=226 · primary completion 2029-03 · phase 3 IO +/- SBRT in advanced HCC
- Optimal sequencing of SBRT relative to systemic therapy start not yet Second-line Systemic Therapy Combined with SBRT for HCC with Oligoprogression After Standard First-line Systemic Treatment Phase 2n=70 · primary completion 2026-10 · SBRT added at oligoprogression on 2nd-linerecruiting SBRT Plus Systemic Therapy vs Systemic Therapy Alone in BCLC C Hepatocellular Carcinoma Phase 2n=184 · primary completion 2027-11 · SBRT + systemic vs systemic alone, BCLC C, OS 1°
- Which macrovascular-invasion subgroups gain most from SBRT recruiting Atezolizumab Plus Bevacizumab Alone or Combined with External Beam Radiotherapy for HCC with Macrovascular Invasion Phase 2n=138 · primary completion 2026-03 · atezo/bev +/- EBRT to the invaded vesselrecruiting Using Radiotherapy and Immunotherapy to Treat Advanced Liver Cancer Before Transplant Phase 1/2n=48 · primary completion 2031-06 · Vp1-3 only, SBRT + atezo/bev to transplant
📚 Sources · 📄 1 paper
Abstract
2026-05-18 ESTRO Congress 2026
Multinational HCC EBRT IPD Cohort
ForVery early / early-stage HCC (BCLC-0 or A), incl. treatment-naive
TL;DRMedian OS 6.8y BCLC-0 and 4.6y BCLC-A across 4,913 EBRT-treated HCC pts, comparable to resection and ablation.
The modifiable RT variable in the Cox model is ablative dose, which was associated with reduced mortality, so the transferable read is that dose, not simply delivering EBRT, tracks with the outcome. Fractionation and dose thresholds are not given in the abstract. This is the citation for putting EBRT on the BCLC-0/A allocation discussion.
In BCLC-0 or A HCC where resection, transplant, or ablation is not feasible or is declined, this supports discussing ablative-dose EBRT as a locoregional option; it does not establish EBRT over resection or ablation in a pt eligible for either.
Ablative dose was the modifiable variable associated with reduced mortality, so the transferable read is dose, not simply offering EBRT. Dose thresholds, fractionation, and modality mix are not given in the source abstract. This is the citation for putting EBRT into the BCLC-0/A allocation discussion at tumor board.
Child-Pugh B or C, performance status, and tumor burden drove mortality in the multivariable model, which is the gating frame for who gets locoregional therapy at all. For the med onc coordinating a BCLC-0/A pt, EBRT enters the locoregional menu alongside ablation rather than as a last resort.
Median OS of 6.8 y (BCLC-0) and 4.6 y (BCLC-A) in EBRT-treated pts is a cross-literature benchmark against resection and ablation, not a head-to-head. It bears on referral for the medically inoperable or anatomically difficult pt, and does not establish EBRT over resection in a fully resectable candidate.
9 details 2 trials watching
Systematic review of EBRT publications meeting prespecified HCC technical standards (search date December 15, 2022), with corresponding authors invited to contribute individual patient data. Kaplan-Meier OS and RMST stratified by BCLC stage and treatment status; random-effects Cox for covariates. No comparator arm.
4,913 pts treated with EBRT, median follow-up 5.0 years, multinational. Analyses split by BCLC stage and by treatment-naive vs treatment-experienced; the headline read sits in BCLC-0 and BCLC-A.
EBRT delivered per each contributing series, gated by the prespecified technical standards rather than one protocol. Ablative dose was associated with a reduced risk of death; specific dose levels, fractionation, and modality mix are not given in the source abstract.
Overall survival by Kaplan-Meier and restricted mean survival time, stratified by BCLC stage and treatment status. Covariate associations from multivariable random-effects Cox modeling.
Median OS 6.8 y (95% CI 5.7-8.7) for BCLC-0 and 4.6 y (95% CI 4.1-5.1) for BCLC-A. Treatment-naive: not reached (95% CI 8.6-NR) for BCLC-0, 5.4 y (95% CI 4.5-6.7) for BCLC-A.
| Cohort | BCLC-0 | BCLC-A |
|---|---|---|
| All pts | 6.8 y (95% CI 5.7-8.7) | 4.6 y (95% CI 4.1-5.1) |
| Treatment-naive | NR (95% CI 8.6-NR) | 5.4 y (95% CI 4.5-6.7) |
The authors frame these medians as comparable with resection, thermal ablation, and other ablative locoregional therapies, a cross-study benchmark rather than a randomised comparison. EBRT's exclusion from BCLC has rested on the absence of OS evidence, which is the gap this cohort is built to fill.
IPD came only from authors who published and agreed to share, so contributing centers are self-selected and unmeasured selection at the patient level (who was routed to EBRT rather than resection) is unrecoverable. More recent year of treatment predicting survival mixes technique gains with stage migration and modern systemic salvage over a multi-decade accrual window.
The claim is an allocation claim, not an efficacy claim: EBRT belongs in the BCLC decision tree as an option to be weighed. It does not settle sequencing against ablation in a pt eligible for both, and the ablative-dose signal makes the quality of the RT, not its mere availability, the operative variable.
Largest EBRT IPD cohort argues for a BCLC allocation change, but it is pooled non-randomised data with no head-to-head comparator against resection or ablation.
- Ablative dose threshold and fractionation driving the survival association
- EBRT vs thermal ablation head-to-head in early HCC recruiting Stereotactic Radiosurgery Versus Radiofrequency Ablation for Primary Liver Cancer Phase 2n=130 · primary completion 2025-01 · phase 2 SBRT vs RFA, inoperable primary liver caactive Stereotactic Body Radiotherapy Versus Radiofrequency Ablation for Unresectable, Small (≤ 3 cm) HCC Phase NAn=178 · primary completion 2026-12 · randomised SBRT vs RFA, unresectable HCC <=3cm
- Selection differences between EBRT-treated and resected early-stage pts