Indications for Radiotherapy in Primary Liver Cancer (Hepatocellular Carcinoma & Intrahepatic Cholangiocarcinoma)

1. Overview

Modern conformal external beam radiotherapy (EBRT) and intra-arterial radionuclide techniques have expanded the role of radiation in liver malignancies once considered poorly radioresponsive. Appropriate patient selection balances potential for local control or symptom relief against hepatic reserve and competing treatment modalities (resection, ablation, TACE, systemic therapy, transplant).

2. Prerequisites & Baseline Assessment

| Domain | Key Elements |
|——–|————–|
| Diagnosis | Multiphasic CT or MRI with characteristic enhancement or histology |
| Liver Function | Child-Pugh class (A preferred; cautious in B; generally avoid in decompensated C unless palliative) |
| Performance Status | ECOG 0–2 (occasionally 3 if symptom-directed palliative) |
| Tumor Burden | Number, size, vascular invasion, extrahepatic disease |
| Portal Hypertension | Platelets, spleen size, varices assessment |
| Prior Locoregional Therapy | TACE, ablation, Y-90 history impacts planning |

3. Indication Tiers

| Tier | Category | Typical Clinical Scenario | Radiotherapy Objective |
|——|———-|—————————|———————–|
| A (Definitive / Potentially Disease-Modifying) | Unresectable but liver-confined HCC (≤5–6 cm solitary or oligolesions) | Not surgical candidate due to location or function | Achieve ablative local control (SBRT) |
| A | Portal vein tumor thrombus (segmental, lobar, main) | PVTT limiting systemic/locoregional therapy | Thrombus regression, improve portal flow |
| A | Intrahepatic cholangiocarcinoma (unresectable) | Localized disease unsuitable for surgery | Prolong local control, bridge to transplant (selected) |
| B (Adjunct / Bridging) | Bridge or downstage to transplant | Waitlist management, reduce dropout | Maintain or shrink disease burden |
| B | Consolidation after incomplete TACE/ablation | Residual enhancing nodule | Sterilize residual disease |
| B | Oligoprogressive lesion during systemic therapy | Single site progression on otherwise controlled disease | Sustain systemic regimen efficacy |
| C (Palliative / Symptom-directed) | Painful bone metastasis | Osseous lesion causing pain or impending fracture | Analgesia, structural stabilization (with ortho) |
| C | Adrenal metastasis (symptomatic) | Unresectable, hormonal or mass effect | Local control, symptom palliation |
| C | Abdominal lymph node metastasis | Symptomatic mass effect or progression | Control nodal disease, relieve compression |
| C | Vascular/biliary obstruction | Hilar mass causing jaundice (post drainage) | Reduce obstruction recurrence |

4. Specific Clinical Scenarios

4.1 Unresectable Liver-Confined HCC

• Often multifactorial unresectability: inadequate future liver remnant, proximity to major vessels, poor functional reserve.
• SBRT or hypofractionated IMRT achieves high local control in lesions unsuitable for ablation (subdiaphragmatic, adjacent to vessels causing heat-sink effect).

4.2 Portal Vein Tumor Thrombus (PVTT)

| Aspect | Detail |
|——–|——-|
| Rationale | PVTT worsens prognosis; limits TACE; risk of intrahepatic dissemination |
| RT Role | Shrink/regress thrombus → enable TACE/systemic therapy, reduce portal hypertension |
| Evidence (Illustrative) | Retrospective cohorts show response rates ~20–40% with improved 1-year survival in responders |

4.3 Residual/Recurrence After Locoregional Therapy

• Enhancing residue post-TACE or ablation can be targeted with focal RT to escalate BED while sparing previously treated parenchyma.
• Dose painting techniques (IMRT/SBRT) tailor differential dosing.

4.4 Intrahepatic Cholangiocarcinoma (ICC)

• Unresectable ICC may derive survival benefit from higher dose RT (BED escalation) ± systemic chemotherapy.
• Motion management critical due to central location near biliary tree.

4.5 Extrahepatic Symptomatic Metastases

| Site | RT Aim | Typical Regimen |
|——|——-|—————-|
| Bone | Analgesia | 8 Gy ×1; 20 Gy ×5; 30 Gy ×10; SBRT for oligometastatic control |
| Adrenal | Local control / endocrine symptom relief | SBRT 40–50 Gy / 5 fx |
| Lymph Node (abdominal) | Palliate compression, maintain biliary/vascular patency | 30–45 Gy conventional or SBRT boost |

5. Contraindications & Cautions

| Scenario | Concern | Approach |
|———-|——–|———|
| Child-Pugh C (decompensated) | High risk RILD, decompensation | Restrict to symptom-directed low dose or avoid |
| Diffuse multifocal involvement (>70% liver) | Excess normal liver exposure | Consider systemic ± selective intra-arterial therapy |
| Uncontrolled ascites / encephalopathy | Poor tolerance | Optimize medical management first |
| Severe thrombocytopenia (<40–50k) | Bleeding risk, impaired tolerance | Correct/co-manage before RT |
| Active uncontrolled infection | Treatment interruption risk | Treat infection prior to initiation |

6. Integration with Other Modalities

| Combination | Purpose | Sequencing Notes |
|————|——–|——————|
| RT + TACE | Enhance local control for large lesions | RT after TACE once liver enzymes normalize |
| RT + Y-90 (Selective Internal RT) | Multifocal + dominant lesion strategy | Stage therapies; cumulative liver dose modeling |
| RT + Systemic (TKI/IO) | Potential synergy (immunomodulation) | Monitor hepatic, immune toxicity (e.g., LFTs q2–4 weeks) |
| RT + Ablation | Hybrid for multiple or perilous locations | Ablate small peripheral; RT central/vascular-adjacent |

7. Response & Follow-Up

| Time Point | Assessment | Criteria |
|———–|———–|———|
| 6–12 weeks post-RT | MRI/CT (arterial + portal phases) | mRECIST: absence of arterial enhancement = response |
| Every 3–4 months (year 1–2) | Imaging + AFP | Detect new lesions/progression |
| Liver function monitoring | LFTs, Child-Pugh recalculation | Identify early toxicity |

8. Toxicity Considerations (Summary)

| Toxicity | Notes | Mitigation |
|———-|——-|———–|
| Classic RILD | Anicteric hepatomegaly, ascites (weeks–months) | Mean liver dose constraints; spare ≥700 cc |
| Non-classic RILD | Jaundice, elevated transaminases (cirrhotics) | Dose adaptation in Child-Pugh B |
| GI Ulceration | Central or hilar lesions near stomach/duodenum | Fractionation adjustment, OAR contour diligence |
| Biliary strictures | High-dose near ductal system | Limit dose, consider MR-guidance |
| Fatigue | Common, transient | Supportive care |

9. Practical Planning Pearls

• Employ 4D-CT or breath-hold to reduce PTV margins and spare uninvolved liver.
• Use biological effective dose (BED10 ≥80–100 Gy) for ablative intent if liver constraints met.
• Prioritize sparing of functional liver subsegments (functional imaging emerging: SPECT, DCE MRI, gadoxetic uptake mapping).
• Recalculate Child-Pugh at each on-treatment visit for early decompensation detection.

10. Emerging/Investigational Areas

| Area | Potential Impact |
|——|——————|
| MR-guided adaptive RT | Margin reduction; real-time motion compensation |
| Radiomics-based risk prediction | Personalized dose, toxicity forecasting |
| Immunoradiotherapy sequencing trials | Enhanced systemic control beyond field |
| Proton/Carbon ion therapy | Lower integral dose for large targets |
| Functional liver avoidance planning | Preserve future systemic/locoregional options |

11. Key Takeaways

• Radiotherapy plays a versatile role: ablative, bridging, consolidative, and palliative in HCC/ICC when matched to patient hepatic reserve and target geometry.
• Portal vein tumor thrombus, residual post-TACE disease, and unresectable but localized lesions are high-yield indications.
• Child-Pugh class, target proximity to critical GI structures, and prior locoregional treatments govern feasibility and dosing.
• Multimodality sequencing and vigilant follow-up optimize outcomes while minimizing hepatic and GI toxicity.

Disclaimer: Educational synthesis; adhere to institutional protocols and contemporary guidelines.