Can diaphragmatic pleurisy occur within the first week after high‑dose stereotactic body radiotherapy (SBRT) to the liver dome for cholangiocarcinoma in an adult patient, and what monitoring and management should be provided?

Diaphragmatic Pleurisy After Hepatic SBRT for Cholangiocarcinoma

Diaphragmatic pleurisy can occur within the first week after high-dose SBRT to the liver dome for cholangiocarcinoma, and you should anticipate this as an expected acute toxicity requiring symptomatic management with NSAIDs and close monitoring for progression to more severe complications.

Acute Toxicity Timeline and Mechanism

Early-onset pleuritic chest pain within the first week after SBRT to liver dome lesions represents acute inflammatory response from radiation exposure to the diaphragm and adjacent pleural surfaces. This differs from the delayed toxicities (radioembolization-induced liver disease at 4-8 weeks or late hepatotoxicity at 6+ months) seen with other liver-directed therapies 1.

Expected Acute Toxicities in First Week

The most common Grade ≥2 early toxicities after hepatic SBRT include:

• Grade 2 nausea and vomiting (reported in 50% of patients) 2
• Gastrointestinal pain (Grade 2 in 20% of patients) 2
• Pleuritic chest pain when treating liver dome lesions abutting the diaphragm

These acute symptoms are typically transient and manageable 2, 3.

Critical Monitoring Protocol

Week 1 Assessment

• Daily symptom assessment for escalating chest pain, dyspnea, or fever
• Distinguish pleurisy from more serious complications: biliary stenosis, duodenal ulceration, or early liver failure 2
• Monitor for fever suggesting cholangitis or liver abscess (Grade 3 toxicity occurring in 12% of patients) 3

Red Flags Requiring Urgent Evaluation

• Persistent fever (>38.5°C) suggesting cholangitis or abscess formation 3
• Severe abdominal pain that could indicate duodenal ulceration (Grade 3 toxicity) 2, 3
• Jaundice or rising bilirubin suggesting biliary obstruction or early liver failure 2
• Respiratory compromise beyond expected pleuritic pain

Management Algorithm

First-Line Symptomatic Management

1. NSAIDs for pleuritic pain (unless contraindicated by liver function)
2. Antiemetics for nausea (expected in 50% of patients) 2
3. Reassurance that transient symptoms are expected with liver dome SBRT

Escalation Criteria

If symptoms persist beyond 7-10 days or worsen:

• CT imaging to exclude pleural effusion, pneumonitis, or hepatic complications
• Laboratory assessment: CBC, comprehensive metabolic panel, bilirubin, CA19-9
• Consider infectious workup if fever develops (cholangitis occurs as Grade 3 toxicity) 3

Technical Planning Considerations to Minimize Risk

For future patients with liver dome lesions:

Respiratory Motion Management

• 4D-CT imaging to capture full respiratory excursion for diaphragm-adjacent tumors 4, 5
• Respiratory gating or abdominal compression to minimize diaphragm dose 4

Dose Constraints

• Standard SBRT dosing: 30-50 Gy in 3-5 fractions 6, 4, 7
• Most common regimen: 45 Gy in 3 fractions for peripheral lesions 4, 3, 8
• Modified fractionation: 40-45 Gy in 5 fractions for centrally located tumors near critical structures 4

Hydrodissection Technique

• Consider hydrodissection when lesions directly abut the diaphragm to create separation and reduce dose 6, 4, 5

Expected Clinical Course

Local Control and Survival

• 100% local control at median 14-month follow-up in one series 2
• 79% actuarial local control at median 38-month follow-up 3
• Median overall survival: 14-17 months 9, 3
• 1-year survival: 57-83% 2, 8

Late Toxicity Risk

Late Grade ≥2 toxicities occur but are less common than acute symptoms:

• Grade 2 gastrointestinal pain (30% of patients) 2
• Grade 3 biliary stenosis (10% of patients) 2
• Grade 5 liver failure (rare, 10% in one series) 2

Integration with Systemic Therapy

SBRT must be combined with systemic chemotherapy—never delivered as monotherapy 4:

• First-line regimen: cisplatin-gemcitabine plus durvalumab or pembrolizumab 6, 4, 5
• Timing: SBRT can be administered concurrently with first-line chemo-immunotherapy for oligometastatic disease 4

Common Pitfalls to Avoid

• Do not dismiss early chest pain as insignificant—monitor for progression to Grade 3+ toxicity 2, 3
• Do not use conventional low-dose palliative radiation (8 Gy × 1) for cholangiocarcinoma—this provides suboptimal local control 6, 4
• Do not treat Child-Pugh C patients with SBRT—this is an absolute contraindication 6, 4, 5
• Do not overlook respiratory motion for liver dome lesions—inadequate motion management increases diaphragm dose 4, 5