Purpose: To quantify the detrimental impact of respiratory motion on the critical “peak-and-valley” dose distribution in lattice radiotherapy (LRT) for liver tumors, to thereby evaluate the necessity of motion management.
Methods: This study assessed the data of 24 patients with liver cancer who underwent free-breathing 4D-CT simulation, for which a 2×2×2 vertices LRT tree was constructed. Volumetric Modulated Arc Therapy (VMAT) plans were generated based on the results of free-breathing CT. The delivered dose distribution under respiratory motion was then simulated by dividing the planned dose into 10 equal subcomponents, applying phase-specific isocenter shifts derived from 4D-CT displacement measurements, and summing the deformed doses. The metrics analyzed included the vertex dose deviation, valley-to-peak dose ratio (VPDR), and low-dose bath volumes.
Results: The analysis revealed a mean 3D respiratory motion error of 8.59 mm, with predominant displacement in the superior-inferior (SI) direction (6.78±3.15 mm). Respiratory motion significantly degraded the LRT dose distributions; specifically, the vertices mean dose (Dmean) decreased from 50.19 Gy to 42.26 Gy, while the maximum dose (Dmax) from 58.94 Gy to 52.63 Gy. Crucially, the VPDR increased in all directions, with the most pronounced increase observed in the SI direction (0.14±0.04 to 0.18±0.06, representing a 28.6% increase), escalating exponentially when motion error exceeded 8 mm. Increases in the left-right (LR) (0.41 to 0.44, increasing 7.3%) and antero-posterior (AP) (0.41 to 0.45, increasing 9.8%) directions were comparatively smaller. The motion also paradoxically altered the low-dose regions; while the absolute V40%, V20%, and V10% volumes decreased by approximately 10 cm3 in the delivered plan, normalization to match the prescription coverage revealed significant increases in these volumes (minimum increases: V40% by 3.59 cm3, V20% by 15.85 cm3 and V10% by 92.29 cm3).
Conclusion: Respiratory motion severely degrades essential spatial fractionation during liver LRT, particularly when exceeding 8 mm and occurring predominantly in the SI direction. This motion reduces peak vertex doses, increases the VPDR (homogenizing the dose distribution), and disrupts the low-dose bath volumes critical for normal tissue sparing and the bystander effect.
| [1] |
Vilarinho S, Taddei T. Therapeutic strategies for hepatocellular carcinoma: new advances and challenges. Curr Treat Options Gastroenterol. 2015;13(2):219-234.
|
| [2] |
Gupta N, Jonnalagadda S. Curbside Consultation in GI Cancer for the Gastroenterologist: 49 Clinical Questions. Gastroenterology. 2012, 142(2):410-411.
|
| [3] |
Ahmed MM, Wu X, Mohiuddin M, et al. Optimizing GRID and Lattice Spatially Fractionated Radiation Therapy: Innovative Strategies for Radioresistant and Bulky Tumor Management. Semin Radiat Oncol. 2024;34(3):310-322.
|
| [4] |
Prezado Y, Lamirault C, Larcher T, et al. On the significance of peak dose in normal tissue toxicity in spatially fractionated radiotherapy: The case of proton minibeam radiation therapy. Radiother Oncol. 2025;205:110769.
|
| [5] |
Carvalho HA, Villar RC. Radiotherapy and immune response: the systemic effects of a local treatment. Clinics (Sao Paulo). 2018;73(suppl 1):e557s.
|
| [6] |
Kraus KM, Winter J, Zhang Y, et al. Treatment Planning Study for Microbeam Radiotherapy Using Clinical Patient Data. Cancers (Basel). 2022;14(3):685.
|
| [7] |
Lee PY, Huang BS, Lee SH, et al. An investigation into the impact of volumetric rescanning and fractionation treatment on dose homogeneity in liver cancer proton therapy. J Radiat Res. 2024;65(1):100-108.
|
| [8] |
Jeong H, Lee SB, Yoo SH, et al. Compensation method for respiratory motion in proton treatment planning for mobile liver cancer. J Appl Clin Med Phys. 2013;14(2):4055.
|
| [9] |
Yeo UA, Taylor ML, Supple JR, et al. Evaluation of dosimetric misrepresentations from 3D conventional planning of liver SBRT using 4D deformable dose integration. J Appl Clin Med Phys. 2014;15(6):4978.
|
| [10] |
Katano A, Noyama T, Morishima K, et al. Dosimetric Comparison Study Between Free Breathing and Breath Hold Techniques in Patients Treated by Liver-Directed Stereotactic Body Radiation Therapy. Cureus. 2023;15(6):e40382.
|
| [11] |
Sarudis S, Karlsson A, Nyman J, et al. Dosimetric effects of respiratory motion during stereotactic body radiation therapy of lung tumors. Acta Oncol. 2022;61(8):1004-1011.
|
| [12] |
Liu L, Fei Z, Li J, et al. Impact of respiratory motion on dose distribution in SIB-SBRT for lung cancer. J Appl Clin Med Phys. 2025;4:e70136.
|
| [13] |
Tsai YL, Wu CJ, Shaw S, et al. Quantitative analysis of respiration-induced motion of each liver segment with helical computed tomography and 4-dimensional computed tomography. Radiat Oncol. 2018;13(1):59.
|
| [14] |
Couinaud C. Le foie: études anatomiques et chirurgicales. Paris, France: Masson; 1957.
|
| [15] |
Wu X, Perez NC, Zheng Y, et al. The Technical and Clinical Implementation of LATTICE Radiation Therapy (LRT). Radiat Res. 2020;194(6):737-746.
|
| [16] |
At B, Velayudham R. Assessing dosimetric advancements in spatially fractionated radiotherapy: From grids to lattices. Med Dosim. 2024;49(3):206-214.
|
| [17] |
Zhang H, Wu X, Zhang X, et al. Photon GRID Radiation Therapy: A Physics and Dosimetry White Paper from the Radiosurgery Society (RSS) GRID/LATTICE, Microbeam and FLASH Radiotherapy Working Group. Radiat Res. 2020;194(6):665-677.
|
| [18] |
Ferini G, Valenti V, Tripoli A, et al. Lattice or Oxygen-Guided Radiotherapy: What If They Converge? Possible Future Directions in the Era of Immunotherapy. Cancers (Basel). 2021;13(13):3290.
|
| [19] |
Naqvi SA, Mohiuddin MM, Ha JK, Regine WF. Effects of tumor motion in GRID therapy. Med Phys. 2008;35(10):4435-4442.
|
| [20] |
Yang Y, Kang M, Huang S, et al. Impact of respiratory motion on proton pencil beam scanning FLASH radiotherapy: anin silicoand phantom measurement study. Phys Med Biol. 2023;68(8):10.
|
| [21] |
Liu X, Liu Z, Wang D, et al. Effects of low dose radiation on immune cells subsets and cytokines in mice. Toxicol Res (Camb). 2020;9(3):249-262.
|
| [22] |
Munoz-Schuffenegger P, Ng S, Dawson LA. Radiation-Induced Liver Toxicity. Semin Radiat Oncol. 2017;27(4):350-357.
|
| [23] |
Subramanian N, Čolić A, Santiago Franco M, et al. Superior Anti-Tumor Response After Microbeam and Minibeam Radiation Therapy in a Lung Cancer Mouse Model. Cancers (Basel). 2025;17(1):114.
|
| [24] |
Nizin PS. Electronic equilibrium and primary dose in collimated photon beams. Med Phys. 1993;20(6):1721-1729.
|
| [25] |
Grams MP, Mateus CQ, Mashayekhi M, et al. Minibeam Radiation Therapy Treatment (MBRT): Commissioning and First Clinical Implementation. Int J Radiat Oncol Biol Phys. 2024;120(5): 1423-1434.
|
| [26] |
Turna M, Küçükmorkoç E, Rzazade R, et al. Feasibility and tolerability of breath-hold in liver stereotactic body radiotherapy with surface guided radiotherapy. Tech Innov Patient Support Radiat Oncol. 2023;28:100223.
|
| [27] |
Li W, Ye X, Huang Y, et al. An integrated ultrasound imaging and abdominal compression device for respiratory motion management in radiation therapy. Med Phys. 2022;49(10):6334-6345.
|
| [28] |
Iizuka Y, Hiraoka M, Kokubo M, et al. Dynamic tumor-tracking stereotactic body radiotherapy with real-time monitoring of liver tumors using a gimbal-mounted linac: A multi-institutional phase II study. Clin Transl Radiat Oncol. 2023; 39: 100591.
|
| [29] |
Ehrbar S, Jöhl A, Kühni M, et al. ELPHA: Dynamically deformable liver phantom for real-time motion-adaptive radiotherapy treatments. Med Phys. 2019;46(2):839-850.
|
| [30] |
Prezado Y. Divide and conquer: spatially fractionated radiation therapy. Expert Rev Mol Med, 2022,24:e3.
|
RIGHTS & PERMISSIONS
2025 The Author(s). Precision Radiation Oncology published by John Wiley & Sons Australia, Ltd on behalf of Shandong Cancer Hospital & Institute.
PDF
