What is the role of Stereotactic Body Radiation Therapy (SBRT) in managing unresectable cholangiocarcinoma?

Role of Stereotactic Body Radiation Therapy in Unresectable Cholangiocarcinoma

Stereotactic body radiation therapy (SBRT) may be considered for unresectable intrahepatic cholangiocarcinoma lesions less than 5 cm when surgical resection is not possible, but conventional chemoradiotherapy should probably not be used outside of clinical trials. 1

Guideline-Based Recommendations

Intrahepatic Cholangiocarcinoma (iCCA)

• SBRT may be considered for unique iCCA lesions <5 cm if surgical resection is not possible according to the 2024 French Association for the Study of the Liver guidelines (expert opinion with strong agreement). 1
• Conventional chemoradiotherapy (CRT) is probably not recommended for patients with unresectable iCCA outside of therapeutic trial settings (GRADE 2−). 1
• Several trials and meta-analyses suggest SBRT may provide benefits including improved local control, overall survival, and acceptable toxicity in iCCA. 1

Perihilar Cholangiocarcinoma (pCCA)

• Conventional CRT is probably not recommended for unresectable pCCA outside of clinical trials (GRADE 2−). 1
• Interventional radiology approaches are not recommended for pCCA (GRADE 1−). 1

Clinical Outcomes from Research Evidence

Efficacy Data

• Median overall survival ranges from 10.6 to 17 months across multiple studies of SBRT for unresectable cholangiocarcinoma. 2, 3, 4, 5
• One-year local control rates range from 74.7% to 81.8%, with higher rates achieved when equivalent dose in 2 Gy fractions (EQD2) ≥71.3 Gy is used. 6
• One-year overall survival rates are approximately 53.8% to 59%, with two-year survival rates of 32-33%. 2, 3, 6
• Response rates (by modified RECIST criteria) reach 46.4% with disease control rates of 89.3%. 3

Dosing Protocols

• The most commonly used SBRT dose is 40-45 Gy delivered in 3-5 fractions, prescribed to the 70-92% isodose line. 2, 3, 4, 5
• Median prescription doses range from 30-54 Gy in 3-5 fractions across published series. 3, 4, 6
• Higher biological effective doses (EQD2 ≥71.3 Gy) correlate with improved local control. 6

Toxicity Profile and Critical Caveats

Gastrointestinal Toxicity

• Duodenal and gastric ulceration represent the most significant toxicity concern, occurring in 10-20% of patients as late effects. 5, 6
• Acute grade ≥3 toxicity occurs in less than 10% of patients, while late grade ≥3 toxicity occurs in 10-20%. 6
• In one series, 16% of patients experienced grade ≥3 toxicity, including duodenal ulceration, cholangitis, and liver abscess. 2, 4
• Duodenal radiation exposure directly correlates with toxicity risk—maximum dose to 1 cm³ of duodenum shows statistically significant association with moderate to high-grade gastrointestinal toxicity. 5

Common Acute Effects

• Most patients (77%) experience grade 1-2 acute toxicity, most commonly fatigue or pain. 2
• Cholangitis and liver abscess can occur as complications. 4

Patient Selection Criteria

Ideal Candidates

• Solitary intrahepatic lesions <5 cm represent the best candidates based on guideline recommendations. 1
• Patients with solitary lesions, CA19-9 ≤37 U/mL, and earlier TNM stage have significantly better outcomes. 3
• Unresectable disease without extrahepatic metastases. 2, 3, 4

Poor Candidates

• Tumors in close proximity to duodenum or stomach require extreme caution due to high risk of ulceration and stenosis. 5
• Patients with multiple lesions, elevated CA19-9 (>600 U/mL), and advanced TNM stage have worse prognosis. 3
• Perihilar tumors have higher rates of duodenal complications given anatomic proximity. 5

Special Considerations

Neoadjuvant Setting

• SBRT combined with chemotherapy as neoadjuvant therapy prior to orthotopic liver transplantation shows promising results, with median overall survival of 31.3 months in transplanted patients. 2
• This represents a substantial improvement over SBRT alone for unresectable disease. 2

Comparison to Conventional Approaches

• SBRT outcomes appear comparable to conventionally fractionated chemoradiotherapy with or without brachytherapy boost, but with practical advantages of shorter treatment duration. 5
• The median overall survival of 15-17 months with SBRT compares favorably to historical controls with conventional radiation (11-15 months). 1, 2, 4

Integration with Systemic Therapy

• SBRT is typically used in combination with systemic chemotherapy at the discretion of the medical oncologist. 4
• Standard first-line systemic therapy remains cisplatin-gemcitabine with or without immunotherapy. 1