What is the role of Stereotactic Body Radiation Therapy (SBRT) in locally advanced Cholangiocarcinoma?

Role of SBRT in Locally Advanced Cholangiocarcinoma

SBRT should be considered as a definitive treatment option for patients with unresectable locally advanced cholangiocarcinoma, particularly for solitary intrahepatic lesions less than 5 cm, where it achieves local control rates of approximately 78-85% at 1 year with acceptable toxicity. 1, 2

Primary Treatment Indications

SBRT is recommended for unique intrahepatic cholangiocarcinoma lesions less than 5 cm when surgical resection is not possible. 1 This represents the optimal patient population based on guideline recommendations from the French Association for the Study of the Liver, which provides expert opinion with strong agreement for this indication.

For hilar (perihilar) cholangiocarcinoma, SBRT demonstrates promising efficacy with 2-year local control rates of 47-78%, though conventional chemoradiotherapy is not routinely recommended outside of clinical trials. 3, 4, 5

Clinical Outcomes Supporting SBRT Use

Survival Benefits

• Median overall survival ranges from 15-17 months for unresectable disease treated with SBRT, with 1-year survival rates of 58-59% and 2-year survival rates of 33-35%. 2, 4
• For hilar cholangiocarcinoma specifically, SBRT plus gemcitabine achieved 2-year survival of 80% and 4-year survival of 30% in one series. 5
• SBRT appears comparable or superior to standard chemotherapy alone, with one study showing SBRT significantly superior to both chemoradiation and trans-arterial-radio-embolization in terms of overall survival. 6

Local Control

• Pooled 1-year local control is 83.4% across multiple studies, substantially better than conventional approaches. 2
• Actuarial local control rates range from 78-85% at 1 year and 47% at 2 years. 4, 6, 7
• Median time to progression is 16.8 months, with 1-year freedom from progression of 67%. 4

Treatment Specifications

Dosing Regimens

The most commonly used SBRT dose is 30-40 Gy delivered in 3-5 fractions, typically given over consecutive days. 4, 5, 7 Specific protocols include:

• 30 Gy in 3 fractions for hilar cholangiocarcinoma 5
• Median dose of 40 Gy in 5 fractions for mixed extrahepatic/intrahepatic disease 4
• 45 Gy in 3-5 fractions as reported in systematic reviews 6

Combination with Systemic Therapy

SBRT should be combined with systemic chemotherapy, particularly gemcitabine plus cisplatin, which remains the standard first-line systemic therapy. 1, 3 The combination of SBRT with gemcitabine has shown particular promise in hilar cholangiocarcinoma, achieving high local control with minimal toxicity. 5

Safety Profile

Toxicity is generally acceptable and manageable, with most patients experiencing grade 1-2 acute toxicity. 2, 4

• 77% of patients experience grade 1-2 acute toxicity, most commonly fatigue or pain 4
• Grade ≥3 toxicity occurs in approximately 12-16% of patients 4, 7
• Specific grade 3 toxicities include duodenal ulceration, cholangitis, and liver abscess 7
• Treatment-related mortality is rare, with only one death reported across systematic reviews 2

Clinical Context and Limitations

Conventional chemoradiotherapy is not recommended for unresectable intrahepatic or perihilar cholangiocarcinoma outside of therapeutic trials. 1 This makes SBRT particularly valuable as it provides a non-invasive, short-duration treatment option with superior local control compared to conventional radiation approaches.

SBRT is frequently used as salvage therapy, with 28.6-66.7% of patients having received previous systemic or local treatments before SBRT. 6 This demonstrates its utility even in previously treated patients.

Role in Transplant Protocols

For patients eligible for orthotopic liver transplantation, SBRT can serve as effective neoadjuvant therapy, with median overall survival of 31.3 months in transplant patients compared to 15.7 months in non-transplant patients. 4

Critical Pitfalls to Avoid

• Do not use SBRT for patients with Child-Pugh C cirrhosis, as safety has not been established in this population with very poor prognosis 3
• Avoid conventional low-dose palliative radiation (8 Gy in 1 fraction) for cholangiocarcinoma, as this achieves suboptimal local control 3
• Ensure lesions are not abutting critical structures (bile ducts, stomach, bowel) without appropriate planning, though hydrodissection techniques can enable safe treatment in some cases 3
• Recognize that evidence quality is limited, with most studies showing moderate to serious risk of bias and no randomized controlled trials available 2

Treatment Algorithm

1. Confirm unresectability through multidisciplinary tumor board evaluation
2. Assess tumor characteristics: solitary lesions <5 cm are ideal candidates 1
3. Initiate or continue systemic chemotherapy with gemcitabine plus cisplatin 1, 3
4. Deliver SBRT at 30-45 Gy in 3-5 fractions 4, 5, 6
5. Continue systemic therapy post-SBRT as clinically indicated
6. Monitor for local control every 3 months with imaging 7