What is the best treatment approach for a patient with a 4 cm liver lesion in segments 5 and 8 arising from the fundus of the gallbladder, considering Stereotactic Body Radiation Therapy (SBRT) as an option?

Treatment Approach for 4 cm Liver Lesion in Segments 5 and 8 Arising from Gallbladder Fundus

Critical First Step: Establish Diagnosis and Resectability

This lesion requires urgent multidisciplinary evaluation to determine if this represents gallbladder cancer with direct liver invasion versus primary hepatocellular carcinoma (HCC), as the treatment paradigm differs fundamentally between these diagnoses. 1

If Gallbladder Cancer with Liver Invasion:

Surgical resection with en bloc hepatectomy (segments 4b/5) and lymphadenectomy remains the only potentially curative option and should be pursued if technically feasible with adequate future liver remnant. 1

• Resection is indicated for solitary masses without major vascular invasion, requiring at least 30-40% adequate future liver remnant with preserved vascular and biliary inflow/outflow 1
• Portal vein embolization should be considered preoperatively if future liver remnant is marginal 1

If unresectable, SBRT represents a reasonable locoregional option for this 4 cm lesion, particularly given the location in segments 5 and 8 which are peripheral and away from critical structures. 1, 2

• SBRT dosing of 30-50 Gy in 3-5 fractions is appropriate, depending on ability to meet normal organ constraints and underlying liver function 2
• 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 achieves 2-year local control rates of 47-78% for hilar cholangiocarcinoma and should be combined with systemic chemotherapy (gemcitabine plus cisplatin with durvalumab or pembrolizumab) 2

Critical caveat: Lesions arising from the gallbladder fundus and abutting the liver require extreme caution with thermal ablation (RFA/microwave) due to risk of gallbladder perforation and bile peritonitis. 1

If Primary HCC:

For a 4 cm HCC in segments 5 and 8, treatment selection depends on liver function (Child-Pugh class), resectability, and transplant candidacy. 1

Algorithm for HCC Treatment Selection:

1. Child-Pugh A with resectable disease:

   • Surgical resection is preferred if adequate future liver remnant (≥30-40%) and no major vascular invasion 1
   • Consider liver transplantation if patient meets or is near UNOS criteria (single lesion <5 cm) 1

2. Unresectable or inoperable 4 cm HCC:

   • Combination therapy with microwave ablation (MWA) and/or arterially directed therapies is recommended for tumors 3-5 cm when tumor location is favorable and liver function is adequate 1
   • SBRT should be considered as alternative when ablation/embolization have failed or are contraindicated 1
   • SBRT achieves 96% 2-year local control for HCC and 100% for lesions ≤4 cm 3

3. SBRT-specific considerations for HCC:

   • Delivers 46.8 Gy ± 3.7 in 4-6 fractions with excellent local control (96% at 2 years) and 82.3% overall survival at 2 years 3
   • No grade >2 treatment toxicity observed in retrospective series 3
   • High conformal HDR radioablation achieves tumor control rates >90% after 12 months in ≤5 cm tumors 1
   • However, RFA demonstrated better survival than SBRT in small tumors ≤3 cm in comparative trials 1

Location-Specific Advantages for SBRT in Segments 5 and 8:

The peripheral location in segments 5 and 8 makes this lesion particularly suitable for SBRT, as it avoids the limitations of thermal ablation near the gallbladder. 1, 2

• SBRT is not limited by adjacency to gallbladder, exophytic growth, or central location, unlike thermal ablation 1
• Segments 5 and 8 are sufficiently distant from major bile ducts and hilum to allow safe dose delivery 2
• Hydrodissection techniques can enable safe treatment if the lesion abuts the diaphragm 2

Contraindications and Pitfalls:

Do not proceed with SBRT if:

• Child-Pugh class C cirrhosis (safety not established, very poor prognosis) 1, 2, 4
• Bilirubin >3 mg/dL unless segmental treatment possible 1
• Insufficient uninvolved liver volume to meet dose constraints 2

For Child-Pugh B patients, SBRT requires dose modifications and strict adherence to liver dose constraints but can be safely performed. 2, 4

Integration with Systemic Therapy:

If gallbladder cancer/cholangiocarcinoma: Combine SBRT with cisplatin-gemcitabine plus immunotherapy (durvalumab or pembrolizumab), which provides superior overall survival compared to chemotherapy alone. 2

If HCC with extensive disease: Consider sorafenib or lenvatinib as systemic therapy, with SBRT reserved for oligometastatic control. 1

Monitoring and Follow-up:

• FDG-PET/CT provides superior assessment of treatment response compared to anatomic imaging alone for cholangiocarcinoma 5
• For HCC, multiphase enhanced CT using European Association for Study of the Liver criteria better estimates response than RECIST 6
• Non-enhancement reflecting tumor necrosis is an early indicator of response, with best non-enhancement percentage observed at 12 months 6