What is the role of Stereotactic Body Radiation Therapy (SBRT) in treating gallbladder cancer?

SBRT for Gallbladder Cancer

SBRT is not a standard treatment for gallbladder cancer and lacks guideline support, but may be considered as adjuvant therapy in highly selected cases after extensive liver resection when conventional chemoradiation tolerance is limited by liver toxicity. 1

Current Evidence Landscape

The available evidence for SBRT in gallbladder cancer is extremely limited, consisting primarily of case reports rather than systematic studies or guidelines. The evidence base is substantially stronger for cholangiocarcinoma, which shares anatomic proximity and some treatment principles with gallbladder cancer.

Gallbladder-Specific Evidence

• A single case report demonstrates the potential therapeutic role of adjuvant SBRT for gallbladder cancer after extensive liver resection, particularly when conventional chemoradiation tolerance is limited by liver toxicity. 1

• Surgical resection remains the only curative treatment for gallbladder cancer, with locoregional failure being a significant problem even after liver resection. 1

• Multiple studies have shown benefit for adjuvant radiation in high-risk gallbladder cancer patients, though no Level I evidence exists. 1

Extrapolation from Cholangiocarcinoma Evidence

Given the anatomic proximity and similar biliary tract origin, cholangiocarcinoma data provides the most relevant framework for considering SBRT in gallbladder cancer:

Guideline-Based Recommendations for Biliary Tract Cancers

• The French Association for the Study of the Liver recommends SBRT for unique intrahepatic cholangiocarcinoma lesions less than 5 cm when surgical resection is not possible. 2

• SBRT dosing of 30-50 Gy in 3-5 fractions is recommended for hepatobiliary tumors, with exact dose determined by ability to meet normal organ constraints and underlying liver function. 2, 3

• Most tumors regardless of location may be amenable to SBRT if sufficient uninvolved liver exists and dose constraints can be respected. 2, 3

Clinical Outcomes from Cholangiocarcinoma Studies

• In cholangiocarcinoma, SBRT achieves 1-year overall survival of 45-59% and 2-year overall survival of 20-35%, with median survival of 10-15.7 months. 4, 5, 6

• Local control rates with SBRT in cholangiocarcinoma are 78-85% at 1 year and 47-72% at 2 years. 4, 5, 6

• SBRT produces similar or superior results compared to standard chemotherapy or chemoradiation in cholangiocarcinoma, with acceptable treatment-related toxicities. 4, 7

Patient Selection Criteria

When considering SBRT for gallbladder cancer, apply the following selection framework:

• Patients with Child-Pugh A liver function are the most appropriate candidates; carefully selected Child-Pugh B patients may be considered with dose modifications. 8, 2

• Child-Pugh C cirrhosis is an absolute contraindication, as safety has not been established in this population. 8, 2

• Lesions should ideally be less than 5 cm, though there is no strict size limit if sufficient uninvolved liver exists and dose constraints can be respected. 2, 3

• Total bilirubin level >3 mg/mL should be considered a relative contraindication unless segmental treatment can be performed. 8

Technical Considerations

Dose and Fractionation

• Standard SBRT dosing is 30-50 Gy in 3-5 fractions, with the median prescribed dose being 40-45 Gy in 3 fractions based on cholangiocarcinoma data. 2, 5, 6

• Dose modifications may be required for patients with Child-Pugh B cirrhosis, with strict adherence to dose constraints. 8, 2

Planning Requirements

• Respiratory motion management is essential for tumors near the diaphragm, requiring 4D-CT imaging to capture full respiratory excursion. 3

• Hydrodissection techniques can enable safe treatment of lesions abutting critical structures including the diaphragm, stomach, or bowel. 2, 3

• Ensure sufficient uninvolved liver volume and strict adherence to liver radiation dose constraints. 2, 3

Integration with Systemic Therapy

• SBRT should be combined with systemic chemotherapy, particularly gemcitabine plus cisplatin, which remains the standard first-line systemic therapy for biliary tract cancers. 2

• First-line cisplatin-gemcitabine with durvalumab or pembrolizumab provides better overall survival than chemotherapy alone in advanced biliary tract cancers. 2

Safety Profile

• Treatment-related toxicity is generally acceptable and manageable, with 77% experiencing grade 1-2 toxicity (most commonly fatigue or pain) and 10-16% experiencing grade ≥3 toxicity in cholangiocarcinoma series. 5, 6

• Treatment-related deaths are rare, with only one reported in systematic reviews of cholangiocarcinoma SBRT. 4

Critical Pitfalls to Avoid

• Do not use SBRT without multidisciplinary tumor board confirmation of unresectability, as surgical resection remains the preferred curative treatment when feasible. 2, 1

• Avoid conventional low-dose palliative radiation when ablative SBRT is feasible, as this achieves suboptimal local control. 2

• Do not attempt SBRT in patients with lesions abutting critical structures without appropriate planning or hydrodissection techniques. 2

• Ensure adequate liver function assessment before treatment, as post-treatment liver failure risk increases with baseline hepatic dysfunction. 8, 2

Clinical Algorithm for Decision-Making

1. Confirm unresectability through multidisciplinary evaluation 2, 1
2. Assess liver function (Child-Pugh classification) 8, 2
3. Evaluate tumor size, location, and proximity to critical structures 2, 3
4. Determine if dose constraints can be met with adequate uninvolved liver volume 2, 3
5. Consider hydrodissection for tumors abutting critical structures 2, 3
6. Integrate with systemic chemotherapy (gemcitabine-cisplatin ± immunotherapy) 2
7. Use 30-50 Gy in 3-5 fractions with strict normal tissue constraints 2, 3