What curative‑intent stereotactic body radiotherapy (SBRT) dose schedule is recommended for an unresectable or medically inoperable cholangiocarcinoma patient?

SBRT Dose Recommendations for Unresectable Cholangiocarcinoma

For unresectable or medically inoperable cholangiocarcinoma, the recommended SBRT dose is 30-50 Gy delivered in 3-5 fractions, with most evidence supporting 45 Gy in 3 fractions for peripheral lesions and 40-45 Gy in 5 fractions for centrally located tumors near critical structures. 1, 2, 3

Dose Selection Algorithm

Peripheral intrahepatic lesions (<5 cm):

• Primary recommendation: 45 Gy in 3 fractions (15 Gy per fraction) 4, 2
• This achieves a biological effective dose (BED) of approximately 112.5 Gy₁₀, which exceeds the threshold for optimal local control 5, 6
• The French Association for the Study of the Liver specifically endorses SBRT for unique intrahepatic lesions <5 cm when surgery is not feasible 1

Centrally located or hilar cholangiocarcinoma:

• Primary recommendation: 40-45 Gy in 5 fractions (8-9 Gy per fraction) 3
• Hypofractionated radiotherapy with 15 fractions can be considered for more centrally located disease to reduce gastrointestinal toxicity 7
• The median dose of 40 Gy in 5 fractions achieved 1-year overall survival of 59% and 2-year local control of 47% 3

Dose escalation considerations:

• Target a BED₁₀ ≥75 Gy for improved outcomes 5
• Studies using equivalent dose in 2 Gy fractions (EQD2) ≥71.3 Gy₂ achieved pooled 1-year local control of 81.8% versus 74.7% for lower doses 6
• The most common effective regimen of 45 Gy in 3 fractions delivers an EQD2 of approximately 78.75 Gy₂ 4, 2

Critical Patient Selection Criteria

Anatomic requirements:

• Lesions must be ≤5 cm for optimal outcomes 1
• Ensure adequate distance from duodenum, stomach, and bowel to meet dose constraints 1, 4
• Hydrodissection techniques can enable treatment of lesions abutting critical structures 1

Liver function requirements:

• Child-Pugh A liver function is required; limited data exist for Child-Pugh B 1
• Absolute contraindication: Child-Pugh C cirrhosis 1
• Ensure sufficient uninvolved liver volume to meet dose constraints 1

Integration with Systemic Therapy

Standard first-line approach:

• Combine SBRT with cisplatin-gemcitabine plus immunotherapy (durvalumab or pembrolizumab) 1
• This combination provides superior overall survival compared to chemotherapy alone 1
• SBRT can be delivered during first-line immunotherapy-chemotherapy for oligometastatic disease 1

Expected Outcomes

Local control:

• 1-year local control: 78-79% 2, 6
• 2-year local control: 30-47% 5, 3
• Actuarial local control rates of 61.5% at 1 year and 30.8% at 2 years with median dose 45 Gy in 5 fractions 5

Survival:

• Median overall survival: 12.6-17 months 2, 5, 3
• 1-year overall survival: 50-59% 5, 3
• 2-year overall survival: 14-33% 5, 3
• For BED >75 Gy₁₀: 1-year survival 58.3% and 2-year survival 33.3% versus 20% and 0% for lower doses 5

Critical Toxicity Management

Gastrointestinal toxicity (dose-limiting):

• Most common severe toxicity: duodenal/pyloric ulceration (occurring in up to 22% of patients) 4
• Duodenal stenosis occurred in 11% in one series 4
• Grade ≥3 acute toxicity: <10%; late toxicity: 10-20% 6
• Key pitfall: Maximum dose to 1 cm³ of duodenum correlates with severe ulceration risk 4

Liver toxicity:

• Radiation-induced liver disease is rare when proper dose constraints are followed 5
• Other toxicities include cholangitis and liver abscess (12% grade III toxicity overall) 2

Common Pitfalls to Avoid

1. Never use conventional low-dose palliative radiation (8 Gy in 1 fraction) for cholangiocarcinoma, as this achieves suboptimal local control 1

2. Do not proceed without multidisciplinary tumor board confirmation of unresectability 1

3. Avoid SBRT in Child-Pugh C patients due to unacceptable toxicity risk 1

4. Do not ignore duodenal dose constraints - the difference in maximum dose to 1 cm³ of duodenum reaches statistical significance for severe toxicity 4

5. Ensure adequate respiratory motion management for lesions abutting the diaphragm 1

6. Do not use SBRT as monotherapy - always combine with systemic chemotherapy, particularly gemcitabine-cisplatin with immunotherapy 1