What is the recommended dose of Stereotactic Body Radiation Therapy (SBRT) for a patient with liver metastases (liver mets)?

SBRT Dose for Liver Metastases

For liver metastases, deliver 60 Gy in 3 fractions (BED10 ≥100 Gy) to maximize local control and overall survival, as this represents the established standard dose with proven efficacy and acceptable toxicity. 1, 2, 3

Recommended Dosing Regimen

The optimal SBRT dose is 60 Gy delivered in 3 fractions over 3-14 days, which achieves a BED10 of 180 Gy. 2, 3 This dose was established through Phase I/II trials and has become the standard approach for liver metastases. 3

• The National Comprehensive Cancer Network specifically recommends 60 Gy in 3 fractions for liver metastases, emphasizing adequate normal liver volume preservation and strict adherence to gastrointestinal dose constraints. 1
• Alternative fractionation schemes of 30-50 Gy in 3-5 fractions may be used when normal organ constraints cannot be met with the standard regimen, but these lower doses compromise outcomes. 4

Evidence Supporting High-Dose SBRT

Higher doses (BED10 ≥100 Gy) demonstrate significantly superior outcomes compared to lower doses:

• Local control: 2-year local control rates are 77.2% with BED10 ≥100 Gy versus 59.6% with BED10 <100 Gy. 5
• Overall survival: Median OS is 27 months with BED10 ≥100 Gy versus 15 months with BED10 <100 Gy (p <0.0001). 5
• A moderate correlation (0.47) exists between SBRT biologically effective dose and local control, while the correlation between dose and OS at 2 years is poor (0.29). 5

High-dose SBRT (>100 Gy BED98%) achieves 90% 2-year local control compared to 60% with lower doses (≤100 Gy BED98%), without increasing toxicity. 6 In multivariable analysis, dose group (HR 3.61, p=0.017) and tumor volume (HR 1.01, p=0.005) were the only significant predictors of local control. 6

Patient Selection Criteria

SBRT should be offered to patients with oligometastases (1-5 lesions, mostly 1-2) who are not surgical candidates, following systemic therapy. 5

Liver Function Requirements:

• Child-Pugh Class A: Primary candidates with established safety data; standard dosing applies. 5, 1, 4
• Child-Pugh Class B: Can be treated but require dose modifications and strict dose constraint adherence. 5, 1, 4
• Child-Pugh Class C: Absolute contraindication due to poor prognosis and lack of established safety. 5, 1, 4, 7

Tumor Characteristics:

• Maximum tumor diameter <6 cm is the traditional cutoff, though no strict size limit exists if sufficient uninvolved liver volume remains and dose constraints can be met. 4, 2, 3
• Smaller tumor volumes (<40 cm³) correlate with improved outcomes: median OS 25 months versus 15 months (p=0.0014) and better local control (52 versus 39 months). 8
• At least 700 mL of normal liver must receive <15 Gy total dose. 2, 3

Critical Dose Constraints

Mean liver dose should be kept at 15-20 Gy depending on baseline liver function, with stricter constraints for compromised hepatic reserve. 7

• Ensure adequate uninvolved liver volume preservation with strict adherence to liver radiation dose constraints. 4
• Gastrointestinal structures require strict dose constraints to minimize toxicity risk. 1, 7
• For lesions abutting critical structures (diaphragm, stomach, bowel), hydrodissection techniques can enable safe treatment in some instances. 4, 7

Expected Outcomes

With 60 Gy in 3 fractions, expect:

• 1-year local control: 67% 5
• 2-year local control: 59% 5
• 18-month actuarial local control: 93% 2
• 1-year overall survival: 67% 5
• 2-year overall survival: 57% 5
• Median overall survival: 22 months (varies by primary tumor: colorectal 27 months, breast 21 months, gynecological 25 months, lung 10 months, pancreatic 6 months). 8

Safety Profile

Toxicities are mostly mild to moderate with the standard 60 Gy/3 fraction regimen:

• Pooled grade 1-2 liver toxicity: 30.7% 5
• Pooled grade 3-4 liver toxicity: 8.7% 5
• Liver failure: 0.6% 5
• Treatment-related deaths: 0.004% 5
• Acute liver toxicity up to 90%, usually mild-moderate 5
• No grade ≥3 toxicity reported in some series using lower doses 9
• Grade 3 toxicity occurred in only 7% versus 2% when comparing ≤100 Gy to >100 Gy BED98% groups (p=0.23), demonstrating that higher doses do not increase severe toxicity. 6

Common Pitfalls to Avoid

• Never use conventional low-dose palliative radiation (8 Gy in 1 fraction) for liver metastases in patients with reasonable life expectancy, as this achieves suboptimal local control rates below 50% at 1 year for bulky tumors. 1, 7
• Do not treat patients with Child-Pugh C cirrhosis with liver SBRT due to unacceptable risk. 5, 1, 4, 7
• Avoid doses below BED10 of 100 Gy when technically feasible, as this significantly compromises local control and overall survival. 5, 8, 6
• Ensure multidisciplinary team management including expertise in medical oncology, radiation oncology, hepatobiliary surgery, and radiology. 5
• Verify adequate time interval (typically 6 weeks or less) between treatments to reduce toxicity in reirradiation settings. 1