Table 2. Comparison of EBRT modalities for HCC treatment.
| 2DCRT | 3DCRT | IMRT | SBRT | PBT | |
|---|---|---|---|---|---|
| Planning | Bony landmarks defined by X-ray [6], minimal CT required [15] | CT required [15] | 4D-CT/MRI/PET [15] | CT/MRI/PET | CT/MRI/PET |
| Radiation beam and beam modifiers | Photons or electrons±wedge filters; coplanar beams [15] | Photons, wedges, a field in the field, compensators; several coplanar and noncoplanar beams[15] | Use of multiple modulated beamlets, Photons+IMRT, Multiple noncoplanar beams or arcs [15]; s-IMRT: Step-and-shoot and sliding window techniques; VMAT: Rotational IMRT using conventional MLCs; h-IMRT: Rotational IMRT using helical tomotherapy |
Photon-based technique including radiation beams used in 3DCRT and IMRT; performed using conventional linear accelerators | Proton-based; Uses patient- and field-specific collimators, compensators, particle accelerators [46] |
| Total dose | <30–35 Gy [14] | 45–60 Gy [14,55] | 40–100 Gy [57] (customized based on GTV, ITV, PTV, CTV) | Typically 24–60 Gy [58] (determined by tumor size and OAR) | 72.6Gy/22 fractions or 66Gy/10 fractions [48] |
| Side effects and toxicity | Highest toxicity [59]; Higher collateral dose deposition; Lowest survival and higher risk of adverse effects compared to other modalities [59] |
Low toxicity [16] | No significant difference compared to 3DCRT [18,19]; Improved precision and conformality, reduced collateral dose deposition [6]; Low RILD; but higher risk of RILD for Larger tumors [17] |
Low toxicity [5,37,43] | Low toxicity to liver and OARs [47,49], reduced toxicity compared to other modalities |
| Procedure-related | Non-invasive | Non-invasive | Non-invasive | Non-invasive More complex planning than 3DCRT, More expensive than 2D/3DCRT [6] |
Non-invasive |
| Costs to patient | Cheapest [6]; Minimal imaging, infrastructure, and training required [6] |
Inexpensive [6]; More extended treatment regimen than 2DCRT (multiple weeks) [6] |
More costly with more advanced imaging requirements; More extended treatment regimen (multiple weeks), more expensive than 2D/3DCRT [6] |
More costly with more advanced imaging requirements | Larger space required, more costly, limited availability, more extended treatment regimen (multiple weeks) [6] |
| Technical | Inadequate identification of volume (GTV, CTV, ITV) and OAR [15] | Planning requires multiple CT images [15] but better delineation of surrounding tissue than 2DCRT and collateral dose deposition; Permits targeted therapy [16]; Can compute CTV, GTV, OAR, and plan properly; Can combine stereotactic technology |
Better tumor coverage More complex planning |
Higher fractional doses delivered; Irradiation delivered in fewer fractions; Requires patient immobility and multi-image guidance |
The dosimetric advantage compared to photon-based EBRT: Localized deposition of dose following the Bragg peak; Higher line energy transfer [44]; Increased tumor targeting, suitable in cirrhotic patients [60] Requires precise positioning of dose gradients as slight differences can lead to under/over dosage due to finite range of protons; |
| Efficacy and utility | Utility in resource-poor setting and emergency setting | Can treat several lesions in a single course [16]; Higher likelihood of producing a response in deeper lesions inaccessible to percutaneous procedures [16] |
Improved mOS, ORR, PFS, 1-year survival rate, and LCR than 3DCRT [18,19] | Reduced efficacy with tissue heterogeneity |
2DCRT: Two-dimensional conventional radiotherapy; 3DCRT: Three-dimensional conformal radiotherapy; BED: Biologically effective dose10; CI: Conformity index; CP: Child-Pugh classification; CT: Computerized tomography; CTV: Clinical target volume; EBRT: External beam radiation therapy; GIT: Gastrointestinal tract; GTV: Gross tumor volume; HI: Homogeneity index;
h-IMRT: Helical IMRT; IMRT: Intensity-modulated radiotherapy; ITV: Internal target volume; IVCTT: Inferior vena cava tumor thrombosis; LCR: Local control rate; MRI: Magnetic resonance imaging; MLC: Multi-leaf collimator; MVI: Macroscopic vascular invasion; OAR: Critical organs at risk; ORR: Objective response rate; OS: Overall survival; PFS: Progression-free survival;
PBT: Proton beam therapy; PVTT: Portal vein tumor thrombus; RILD: Radiation-induced liver damage; SBRT: Stereotactic body radiation therapy; s-IMRT: Static IMRT; VMAT: Volumetric modulated arc therapy