Fundamental Physical Principles and Clinical Applications of Proton Therapy: A Comprehensive Review

Authors

  • Crownbirth Ebipade Eki
    Delta State University, Abraka
  • Anita Franklin Akpolile
    Delta State University,  Abraka
  • Godwin Kparobo Agbajor
    Delta State University,  Abraka

Keywords:

Proton therapy, Bragg peak, Stopping power, Linear Energy Transfer, Pencil Beam Scanning, Radiobiological Effectiveness, FLASH radiotherapy

Abstract

Proton therapy is an advanced modality in external beam radiotherapy that exploits the unique depth-dose distribution of accelerated protons to achieve improved tumor targeting compared with conventional photon-based techniques in selected anatomical geometries. This review synthesizes the fundamental physical principles underlying proton therapy, including proton-matter interactions, stopping power, linear energy transfer (LET), the Bragg peak, and the generation of the spread-out Bragg peak (SOBP). Accelerator technologies such as cyclotrons and synchrotrons, beam delivery methods including passive scattering and pencil beam scanning, and treatment planning approaches incorporating proton computed tomography and range verification are examined. The radiobiological effectiveness of protons is discussed alongside emerging evidence for FLASH proton therapy, which delivers ultra-high dose rates (>40 Gy/s) currently under early-stage clinical investigation. Clinical applications are supported by Level I evidence from randomized controlled trials (e.g., the 2025 Lancet trial demonstrating 90.9% versus 81.0% five-year overall survival for oropharyngeal cancer), Level II evidence from prospective cohort studies, and Level III evidence from meta-analyses showing reduced toxicity and secondary malignancy risks in pediatric cancers and central nervous system tumors. Despite challenges such as range uncertainty and high facility costs, proton therapy continues to evolve as a component of precision oncology in appropriately selected patients. This review underscores how fundamental physics principles translate into measurable clinical benefits when applied to specific tumor sites and patient populations.

Author Biographies

Crownbirth Ebipade Eki

Department of Physics, Delta State University, Abraka, Delta State.

Anita Franklin Akpolile

Department of Physics, Delta State University,  Abraka, Delta State.

Senior Lecturer

Godwin Kparobo Agbajor

Department of Physics, Delta State University,  Abraka, Delta State

Dimensions

Alme, J., Barnaföldi, G. G., Barthel, R., Bös, N., Dahbi, Z., Drecoll, J., & Wysocki, S. (2020). A high-granularity digital tracking calorimeter optimized for proton CT. Frontiers in Physics, 8, 568243. https://doi.org/10.3389/fphy.2020.568243 DOI: https://doi.org/10.3389/fphy.2020.568243

Alruhaimi, S. A., Tarkhan, W. H., & Hussien, A. H. (2025). Study of the electronic stopping power of proton in different materials according to the Bohr and Bethe theories. Open Engineering, 15(1), 20240060. DOI: https://doi.org/10.1515/eng-2024-0060

Amin, S., Amin, P., & Lin, C. (2025). Proton beam radiation therapy and the overall survival of adult and pediatric patients diagnosed with central nervous system tumors. BMC cancer, 25(1), 1187. https://doi.org/10.1186/s12885-025-14582-2 DOI: https://doi.org/10.1186/s12885-025-14582-2

Asadi, A. (2022). Comparative dosimetric evaluation of passive scattering proton therapy and pencil beam scanning proton therapy using Monte Carlo simulations. Journal of Instrumentation, 17, P09008. https://doi.org/10.1088/1748-0221/17/09/P09008 DOI: https://doi.org/10.1088/1748-0221/17/09/P09008

Attix, F. H. (2008). Introduction to radiological physics and radiation dosimetry. John Wiley & Sons.

Atun, R., Jaffray, D. A., Barton, M. B., Bray, F., Baumann, M., Vikram, B., & Gospodarowicz, M. (2015). Expanding global access to radiotherapy. The lancet oncology, 16(10), 1153-1186. DOI: https://doi.org/10.1016/S1470-2045(15)00222-3

Battistoni, G., Toppi, M., & Patera, V. (2021). Measuring the impact of nuclear interaction in particle therapy and in radio protection in space: the FOOT experiment. Frontiers in Physics, 8, 568242. DOI: https://doi.org/10.3389/fphy.2020.568242

Brodin, N. P., Kabarriti, R., Schechter, C. B., Pankuch, M., Gondi, V., Kalnicki, S., & Tomé, W. A. (2021). Individualized quality of life benefit and cost-effectiveness estimates of proton therapy for patients with oropharyngeal cancer. Radiation Oncology, 16(1), 19. https://doi.org/10.1186/s13014-021-01745-1 DOI: https://doi.org/10.1186/s13014-021-01745-1

Brown, J. S., Amend, S. R., Austin, R. H., Gatenby, R. A., Hammarlund, E. U., & Pienta, K. J. (2023). Updating the definition of cancer. Molecular Cancer Research, 21(11), 1142–1147. DOI: https://doi.org/10.1158/1541-7786.MCR-23-0411

Byun, H. K., Han, M. C., Yang, K., Kim, J. S., Yoo, G. S., Koom, W. S., & Kim, Y. B. (2021). Physical and biological characteristics of particle therapy for oncologists. Cancer Research and Treatment, 53(4), 611–624. https://doi.org/10.4143/crt.2021.066 DOI: https://doi.org/10.4143/crt.2021.066

Cengel, K. A., Kim, M. M., Diffenderfer, E. S., & Busch, T. M. (2024). FLASH radiotherapy: What can FLASH's ultra-high dose rate offer to the treatment of patients with sarcoma? Seminars in Radiation Oncology, 34(2), 218–228. https://doi.org/10.1016/j.semradonc.2024.02.001 DOI: https://doi.org/10.1016/j.semradonc.2024.02.001

Chen, Z., Dominello, M. M., Joiner, M. C., & Burmeister, J. W. (2023). Proton versus photon radiation therapy: A clinical review. Frontiers in Oncology, 13, 1133909. DOI: https://doi.org/10.3389/fonc.2023.1133909

Chin, M., Ullah, M. N., Innes, D., & Levin, C. (2025). Ultra-high spatial resolution clinical positron emission tomography (PET) systems. Applied Sciences, 15(9), 5207. https://doi.org/10.3390/app15095207 DOI: https://doi.org/10.3390/app15095207

Choi, J. I., Hardy-Abeloos, C., Lozano, A., Hanlon, A., Vargas, C., Maduro, J. H., & Mutter, R. W. (2024). PTCOG international survey of practice patterns and trends in utilization of proton therapy for breast cancer. Clinical and Translational Radiation Oncology, 48, 100847. DOI: https://doi.org/10.1016/j.ctro.2024.100847

Collings, E. W., Norman, H. X. Q., & Steinberg, A. (2022). Accelerators, gantries, magnets and imaging systems for proton and ion therapy. Frontiers in Oncology, 11, 737837. https://doi.org/10.3389/fonc.2021.737837

Corrao, G., Marvaso, G., Mastroleo, F., Biffi, A., Pellegrini, G., Minari, S., & Jereczek-Fossa, B. A. (2024). Photon vs proton hypofractionation in prostate cancer: A systematic review and meta-analysis. Radiotherapy and Oncology, 195, 110264. DOI: https://doi.org/10.1016/j.radonc.2024.110264

Cox, A. M. G., Hattam, L., Kyprianou, A. E., & Pryer, T. (2024). A Bayesian inverse approach to proton therapy dose delivery verification. Proceedings of the Royal Society A, 480(2284), 20230836. https://doi.org/10.1098/rspa.2023.0836 DOI: https://doi.org/10.1098/rspa.2023.0836

Crossley, A., Habermann, K., Horton, E., Koskela, J., Kyprianou, A. E., & Osman, S. (2025). Jump stochastic differential equations for the characterization of the Bragg peak in proton beam radiotherapy. Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences, 481(2310). DOI: https://doi.org/10.1098/rspa.2024.0687

Dalalas, D., Papadopoulos, A., Kyriakou, I., Stewart, R. D., Karaiskos, P., & Emfietzoglou, D. (2024). Relative Biological Effectiveness (RBE) of Monoenergetic Protons: Comparison of Empirical and Biophysical Models. Applied Sciences, 14(24), 11981. https://doi.org/10.3390/app142411981 DOI: https://doi.org/10.3390/app142411981

Das, A., Gaikwad, U., Krishnan, G., Rajendran, A., Patil, S., Subramaniam, P., & Jalali, R. (2023). Successful implementation of image-guided, intensity-modulated proton therapy with pencil-beam scanning in medulloblastoma. Diagnostics, 13(21), 3378. https://doi.org/10.3390/diagnostics13213378 DOI: https://doi.org/10.3390/diagnostics13213378

Daugherty, E. C., Zhang, Y., Xiao, Z., Mascia, A. E., Sertorio, M., Woo, J., & Perentesis, J. P. (2024). FLASH radiotherapy for the treatment of symptomatic bone metastases in the thorax (FAST-02): protocol for a prospective study of a novel radiotherapy approach. Radiation Oncology, 19(1), 34. DOI: https://doi.org/10.1186/s13014-024-02419-4

Di, Y., Meng, L., Wang, Y., & Li, J. (2026). Advances in FLASH radiation therapy: A review on biological foundations and clinical prospects. Translational oncology, 65, 102676. Advance online publication. https://doi.org/10.1016/j.tranon.2026.102676 DOI: https://doi.org/10.1016/j.tranon.2026.102676

Dueholm Vestergaard, C., Vindelev Elstrøm, U., Paul Muren, L., Ren, J., Nørrevang, O., Jensen, K., & Trier Taasti, V. (2025). Erratum to "Proton dose calculation on cone-beam computed tomography using unsupervised 3D deep learning networks" [Phys Imaging Radiat Oncol. 2024 Oct 26; 32:100658. Physics and Imaging in Radiation Oncology, 36, 100849. https://doi.org/10.1016/j.phro.2025.100849 DOI: https://doi.org/10.1016/j.phro.2025.100849

Eaton, B. R., MacDonald, S. M., Yock, T. I., & Tarbell, N. J. (2015). Secondary malignancy risk following proton radiation therapy. Frontiers in Oncology, 5, 261. https://doi.org/10.3389/fonc.2015.00261 DOI: https://doi.org/10.3389/fonc.2015.00261

Frank, S. J., Busse, P. M., Lee, J. J., Rosenthal, D. I., Hernandez, M., Swanson, D. M., Garden, A. S., Gunn, G. B., Patel, S. H., Snider, J. W., Ma, D. J., Molitoris, J. K., Lee, N. Y., Parvathaneni, U., McDonald, M. W., Kalman, N. S., Lin, A., Mohammed, N., Henson, C., Hyde, C., University of Texas MD Anderson Cancer Center Clinical Trial Consortium (2026). Proton versus photon radiotherapy for patients with oropharyngeal cancer in the USA: a multicentre, randomised, open-label, non-inferiority phase 3 trial. Lancet (London, England), 407(10524), 174–184. https://doi.org/10.1016/S0140-6736(25)01962-2 DOI: https://doi.org/10.1016/S0140-6736(25)01962-2

Gao, R., Diallo, M., Liu, H., Magliari, A., Sackett, J., Verbakel, W., Meyers, S., Mcbeth, R., Zarepisheh, M., Arberet, S., Kraus, M., Ghesu, F. C., & Kamen, A. (2025). Automating RT planning at scale: High quality data for AI training (arXiv: 2501.11803v4). ArXiv. https://arxiv.org/abs/2501.11803

Glatzer, S. (2025). Advancing Deep Learning for Automated Treatment Planning in Adaptive Radiotherapy (Doctoral dissertation, Technische Universität Wien).

Hälg, R. A., & Schneider, U. (2020). Neutron dose and its measurement in proton therapy: Current state of knowledge. British Journal of Radiology, 93(1107), 20190412. DOI: https://doi.org/10.1259/bjr.20190412

Hazem, R. (2023). Interaction of proton beam with human tissues in proton therapy. In Proton Therapy—Technological Advances and Future Direction. IntechOpen. DOI: https://doi.org/10.5772/intechopen.1003186

He, J., Liu, Y., Zhang, X., Li, B., Yang, L., Wang, H., & Wang, L. (2024). Comparison of proton therapy and photon therapy for early-stage non-small cell lung cancer: a meta-analysis. Biomarker Research, 12(1), 90. DOI: https://doi.org/10.1186/s40364-024-00642-5

Helm, A., & Fournier, C. (2023). High-LET charged particles: Radiobiology and application for new approaches in radiotherapy. Strahlentherapie und Onkologie, 199(12), 1225–1241. DOI: https://doi.org/10.1007/s00066-023-02158-7

Horendeck, D., Walsh, K. D., Hirakawa, H., Fujimori, A., Kitamura, H., & Kato, T. A. (2021). High LET-like radiation tracks at the distal side of accelerated proton Bragg peak. Frontiers in Oncology, 11, 690042. https://doi.org/10.3389/fonc.2021.690042 DOI: https://doi.org/10.3389/fonc.2021.690042

Huang, D., Frank, S. J., Verma, V., & colleagues. (2021). Cost-effectiveness models of proton therapy for head and neck: Evaluating quality and methods to date. International Journal of Particle Therapy, 8, 339–353. DOI: https://doi.org/10.14338/IJPT-20-00058.1

International Atomic Energy Agency. (2023). what are particle accelerators? IAEA. https://www.iaea.org/newscenter/news/what-are-particle-accelerators

Janson, M., Glimelius, L., Fredriksson, A., Traneus, E., & Engwall, E. (2024). Treatment planning of scanned proton beams in RayStation. Medical Dosimetry, 49(1), 2-12. DOI: https://doi.org/10.1016/j.meddos.2023.10.009

Kahalley, L. S., Ris, M. D., Mahajan, A., Okcu, M. F., Chintagumpala, M., Paulino, A. C., Brown, A., McGregor, L., Gundy, P., Hockenberry, M., & O'Neil, S. (2019). Prospective, longitudinal comparison of neurocognitive change in pediatric brain tumor patients treated with proton radiotherapy versus surgery only. Neuro-Oncology, 21(7), 809–818. https://doi.org/10.1093/neuonc/noz041 DOI: https://doi.org/10.1093/neuonc/noz041

Kiss-Miki, R., Obeidat, M., Máté, V., Teutsch, B., Agócs, G., Kiss-Dala, S., Hegyi, P., Kovács, J., Párniczky, A., Tuboly, E., and Garami, M. (2025). Proton or photon? Comparison of survival and toxicity of two radiotherapy modalities among pediatric brain cancer patients: A systematic review and meta-analysis. PLOS ONE, 20(2), e0318194. https://doi.org/10.1371/journal.pone.0318194 DOI: https://doi.org/10.1371/journal.pone.0318194

Kristensen, L., Poulsen, P. R., Kanouta, E., Rohrer, S., Ankjærgaard, C., Andersen, C. E., & Sørensen, B. S. (2024). Spread-out Bragg peak FLASH: Quantifying normal tissue toxicity in a murine model. Frontiers in Oncology, 14, 1427667. DOI: https://doi.org/10.3389/fonc.2024.1427667

Kutuva, A. R., Caudell, J. J., Yamoah, K., Enderling, H., & Zahid, M. U. (2023). Mathematical modeling of radiotherapy: Impact of model selection on estimating minimum radiation dose for tumor control. Frontiers in Oncology, 13, 1130966. https://doi.org/10.3389/fonc.2023.1130966 DOI: https://doi.org/10.3389/fonc.2023.1130966

Lane, S. A., Slater, J. M., & Yang, G. Y. (2023). Image-guided proton therapy: A comprehensive review. Cancers, 15(9), 2555. https://doi.org/10.3390/cancers15092555 DOI: https://doi.org/10.3390/cancers15092555

Lastrucci, A., Wandael, Y., Ricci, R., Maccioni, G., & Giansanti, D. (2024). The integration of deep learning in radiotherapy: Exploring challenges, opportunities, and future directions through an umbrella review. Diagnostics, 14(9), 939. https://doi.org/10.3390/diagnostics14090939 DOI: https://doi.org/10.3390/diagnostics14090939

Lee, S. H., Chao, P. J., Wu, Z. J., Wu, J. J., Shiau, J., Shih, H. H., & Lee, T. F. (2025). Ensemble RBE Modeling in Proton Therapy: A Meta-Synthesis Framework for Dose Assessment in the Brainstem and Spinal Cord. Cancer Control, 32, 10732748251355396. DOI: https://doi.org/10.1177/10732748251355396

Lomax, A. J. (2020). Myths and realities of range uncertainty. British Journal of Radiology, 93(1107), 20190582. https://doi.org/10.1259/bjr.20190582 DOI: https://doi.org/10.1259/bjr.20190582

Mascia, A. E., Daugherty, E. C., Zhang, Y., Lee, E., Xiao, Z., Sertorio, M., & Breneman, J. C. (2023). Proton FLASH radiotherapy for the treatment of symptomatic bone metastases: the FAST-01 nonrandomized trial. JAMA oncology, 9(1), 62-69. DOI: https://doi.org/10.1001/jamaoncol.2022.5843

McIntyre, M., Wilson, P., Gorayski, P., & Bezak, E. (2023). A systematic review of LET-guided treatment plan optimisation in proton therapy: Identifying the current state and future needs. Cancers, 15(17), 4268. DOI: https://doi.org/10.3390/cancers15174268

Mee, T., Kirkby, N. F., Defourny, N. N., Kirkby, K. J., & Burnet, N. G. (2023). The use of radiotherapy, surgery and chemotherapy in the curative treatment of cancers: A population-based study. British Journal of Radiology, 96(1152), 20230334. https://doi.org/10.1259/bjr.20230334 DOI: https://doi.org/10.1259/bjr.20230334

Miao, Y., Zheng, T., Zhang, Q., Li, X., Wang, H., Chen, J., & Zhang, J. (2025). Efficacy and safety of proton radiotherapy in treating choroidal melanoma: A systematic review and meta-analysis. Radiation Oncology, 20, 7. https://doi.org/10.1186/s13014-024-02580-w DOI: https://doi.org/10.1186/s13014-024-02580-w

Moglioni, M., Kraan, A. C., Baroni, G., Battistoni, G., Belcari, N., Berti, A., & Bisogni, M. G. (2022). In-vivo range verification analysis with in-beam PET data for patients treated with proton therapy at CNAO. Frontiers in Oncology, 12, 929949. https://doi.org/10.3389/fonc.2022.929949 DOI: https://doi.org/10.3389/fonc.2022.929949

Mohamed, N., Lee, A., & Lee, N. Y. (2022). Proton beam radiation therapy treatment for head and neck cancer. Precision Radiation Oncology, 6, 59–68. DOI: https://doi.org/10.1002/pro6.1135

Mohammed, M. I. (2024). Theoretical study of energy loss of proton in human tissues. Ibn Al Haitham Journal for Pure and Applied Sciences, 37(4), 162–173. https://doi.org/10.30526/37.4.3636

Mohan, R. (2022). A review of proton therapy—Current status and future trends. Frontiers in Oncology, 12, 959819.

Nácher, E., Briz, J. A., Nerio, A. N., Perea, A., Távora, V. G., Tengblad, O., & Borge, M. J. G. (2024). Characterization of a novel proton-CT scanner based on silicon and LaBr₃ (Ce) detectors. European Physical Journal Plus, 139, 404. https://doi.org/10.t1140/epjp/s13360-024-05203-1 DOI: https://doi.org/10.1140/epjp/s13360-024-05203-1

Natelauri, E., Pkhaladze, M., & Atskvereli, M. (2024). Radiobiology of proton therapy and its clinical implications. IntechOpen. https://doi.org/10.5772/intechopen.1003188 DOI: https://doi.org/10.5772/intechopen.1003188

Newhauser, W. D., & Zhang, R. (2015). The physics of proton therapy. Physics in Medicine and Biology, 60(8), R155–R209. https://doi.org/10.1088/0031-9155/60/8/R155 DOI: https://doi.org/10.1088/0031-9155/60/8/R155

Nien, H. H., Wang, L. Y., Liao, L. J., Lin, P. Y., Wu, C. Y., Shueng, P. W., ... & Hsieh, C. H. (2022). Advances in image-guided radiotherapy in the treatment of oral cavity cancer. Cancers, 14, 4630. https://doi.org/10.3390/cancers14194630 DOI: https://doi.org/10.3390/cancers14194630

Overgaard, C. B., Reaz, F., Ankjærgaard, C., Andersen, C. E., Sitarz, M., Johansen, J. G., & Bassler, N. (2024). The proton RBE and the distal edge effect for acute and late normal tissue damage in vivo. Radiotherapy and Oncology. https://doi.org/10.1016/j.radonc.2024.110668 DOI: https://doi.org/10.1016/j.radonc.2024.110668

Paganetti, H. (2014). Relative biological effectiveness (RBE) values for proton beam therapy: Variations as a function of biological endpoint, dose, and linear energy transfer. Physics in Medicine & Biology, 59(22), R419–R472. https://doi.org/10.1088/0031-9155/59/22/R419 DOI: https://doi.org/10.1088/0031-9155/59/22/R419

Paganetti, H. (2018). Proton relative biological effectiveness—Uncertainties and opportunities. International Journal of Particle Therapy, 5(1), 2–14. https://doi.org/10.14338/IJPT-18-00009.1 DOI: https://doi.org/10.14338/IJPT-18-00011.1

Paganetti, H. (2020). Proton therapy physics (2nd Ed.). CRC Press.

Paganetti, H. (2021). Mechanisms and review of clinical evidence for variations in relative biological effectiveness in proton therapy. International Journal of Radiation Oncology, Biology, Physics. https://doi.org/10.1016/j.ijrobp.2021.08.015 DOI: https://doi.org/10.1016/j.ijrobp.2021.08.015

Pardo-Montero, J., Pombar, M., Gómez-Caamaño, A., Giordanengo, S., & González-Crespo, I. (2023). Variation of the relative biological effectiveness with fractionation in proton therapy: Analysis of prostate cancer response. arXiv. https://arxiv.org/abs/2303.09485 DOI: https://doi.org/10.1002/mp.16783

Patel, T., Johar, P., Kanisetti, V., Talacheru, S., Avinash, V., Das, A., & Gadad, B. S. (2025). Long-term neurocognitive and behavioral outcomes in survivors of pediatric brain tumors: a systematic review. Frontiers in neuroscience, 19, 1587059. DOI: https://doi.org/10.3389/fnins.2025.1587059

Perotti Bernardini, G., Galapon, A., Guterres Marmitt, G., Free, J., van Ooijen, P., Langendijk, J., & Both, S. (2025). Proton radiography interpretation with artificial intelligence for treatment deviation detection in proton therapy. Physics and Imaging in Radiation Oncology, 36, 100872. https://doi.org/10.1016/j.phro.2025.100872 DOI: https://doi.org/10.1016/j.phro.2025.100872

Podgoršak, E. B. (2006). Radiation physics for medical physicists. Berlin, Heidelberg: Springer Berlin Heidelberg.

Saito, T., Chhabra, A. M., Chen, Y. L., Li, X., Wang, H., Zhang, J., & Hernandez, M. (2024). Proton beam therapy for skull base chordoma: A systematic review and meta-analysis. Cancers, 16(2), 312. https://doi.org/10.3390/cancers16020312 DOI: https://doi.org/10.3390/cancers16142569

Sami, M., Yousuf, M., Hashmi, Q., Ahmad, M., Ghilman, M., & Shareef, H. (2024). Proton Radiation Therapy for Head and Neck Cancers. Cureus, 16(10), e70752. https://doi.org/10.7759/cureus.70752 DOI: https://doi.org/10.7759/cureus.70752

Seeman, J., Schulte, D., Delahaye, J. P., Ross, M., Stapnes, S., Grudiev, A., & Guiducci, S. (2020). Design and principles of linear accelerators and colliders. In S. Myers and H. Schopper (Eds.), Particle Physics Reference Library (pp. 295–336). Springer. https://doi.org/10.1007/978-3-030-34245-6_7 DOI: https://doi.org/10.1007/978-3-030-34245-6_7

Tay, R., Syed, A., Nesbit, M., & Kuncic, Z. (2021). Converging proton minibeams with magnetic fields for enhanced therapeutic index in proton therapy. Frontiers in Oncology, 11, 737837. https://doi.org/10.3389/fonc.2021.737837 DOI: https://doi.org/10.3389/fonc.2021.737837

Verma, V., Mishra, M. V., & Mehta, M. P. (2016). A systematic review of the cost and cost‐effectiveness studies of proton radiotherapy. Cancer, 122(10), 1483-1501. DOI: https://doi.org/10.1002/cncr.29882

Wang, Q., Chen, W., Liu, X., Zhang, Y., Li, J., & Wang, J. (2024). Automating proton PBS treatment planning for head and neck cancers using policy gradient-based deep reinforcement learning. arXiv. https://arxiv.org/abs/2409.11576

Werner, T., Kulessa, T., Bangert, M., & Debus, J. (2025). Range straggling in proton therapy: Clinical implications and mitigation strategies. Medical Physics.

Wildman, V. L., Wynne, J. F., Momin, S., Kesarwala, A. H., & Yang, X. (2025). Recent advances in applying machine learning to proton radiotherapy. Biomedical physics & engineering express, 11(4), 042005. https://doi.org/10.1088/2057-1976/adeb90 DOI: https://doi.org/10.1088/2057-1976/adeb90

Wilson, R. R. (1946). Radiological use of fast protons. Radiology, 47(5), 487–491. DOI: https://doi.org/10.1148/47.5.487

Wohlfahrt, P., Möhler, C., Richter, C., & Greilich, S. (2018). Evaluation of stopping-power prediction by dual and single energy computed tomography in an anthropomorphic ground-truth phantom. International Journal of Radiation Oncology, 100(1), 244–253. https://doi.org/10.1016/j.ijrobp.2017.09.025 DOI: https://doi.org/10.1016/j.ijrobp.2017.09.025

Xiao, M., Liu, B., Peng, J., Li, M., & Xie, S. (2024). Comparison of cyclotron and synchrotron in particle therapy. Visualized Cancer Medicine, 5, Article 7. https://doi.org/10.1051/vcm/2024008 DOI: https://doi.org/10.1051/vcm/2024008

Yang, W., Liu, X., Zhang, Y., Chen, J., Li, H., Wang, Q., & Zhou, P. (2025). Proton beam therapy for a patient with prostatic rhabdomyosarcoma: A case report and review of the literature. Frontiers in Oncology, 15, 1490098. https://doi.org/10.3389/fonc.2025.1490098 DOI: https://doi.org/10.3389/fonc.2025.1490098

Yang, Z., Li, H., Li, Y., Li, Y., Chang, Y., Li, Q., & Zhang, X. (2019). Statistical evaluation of worst-case robust optimization intensity-modulated proton therapy plans using an exhaustive sampling approach. Radiation Oncology, 14(1), 129. https://doi.org/10.1186/s13014-019-1335-8 DOI: https://doi.org/10.1186/s13014-019-1335-8

Young, H. D., and Freedman, R. A. (2020). University physics with modern physics (15th Ed.). Pearson.

Young, S., Phaterpekar, K., Tsang, D. S., Boldt, G., & Bauman, G. S. (2023). Proton radiotherapy for the management of medulloblastoma: A systematic review of clinical outcomes. Advances in Radiation Oncology, 8(2), 101154. https://doi.org/10.1016/j.adro.2023.101154 DOI: https://doi.org/10.1016/j.adro.2023.101189

Zając-Grabiec, A., Biesaga, B., Krzyżowska, M., Drosik-Rutowicz, K., & Miszczyk, J. (2025). Non-cancer effects after proton beam therapy for pediatric tumors: A narrative review. Frontiers in Oncology, 15, 1554765. https://doi.org/10.3389/fonc.2025.1554765 DOI: https://doi.org/10.3389/fonc.2025.1554765

Zhang, M. Z., Li, D. M., Shen, L. R., Zhang, H. R., Chen, Z. L., Du, H. W., & Zhao, Z. T. (2023). SAPT: a synchrotron-based proton therapy facility in Shanghai. Nuclear Science and Techniques, 34(10), 148. DOI: https://doi.org/10.1007/s41365-023-01293-1

Zhang, Q., Yang, W., Tan, L., Guo, X., Wang, T., Zhu, P., & Hou, J. (2026). Advances in proton therapy technology and global clinical applications. Frontiers in Oncology, 16, 1718677. DOI: https://doi.org/10.3389/fonc.2026.1718677

Zhou, P., Du, Y., Zhang, Y., Zhu, M., Li, T., Tian, W., & Xiao, Z. (2023). Efficacy and safety in proton therapy and photon therapy for patients with esophageal cancer: a meta-analysis. JAMA network open, 6(8), e2328136 DOI: https://doi.org/10.1001/jamanetworkopen.2023.28136

Published

2026-04-08

How to Cite

Eki, C. E., Akpolile, A. F., & Agbajor, G. K. (2026). Fundamental Physical Principles and Clinical Applications of Proton Therapy: A Comprehensive Review. Nigerian Journal of Theoretical and Environmental Physics, 4(1), 74-91. https://doi.org/10.62292/njtep.v4i1.2026.115

Issue

Vol. 4 No. 1 (2026): Nigerian Journal of Theoretical and Environmental Physics - Vol. 4 No. 1

Section

Review Article
Copyright & Licensing

How to Cite

Eki, C. E., Akpolile, A. F., & Agbajor, G. K. (2026). Fundamental Physical Principles and Clinical Applications of Proton Therapy: A Comprehensive Review. Nigerian Journal of Theoretical and Environmental Physics, 4(1), 74-91. https://doi.org/10.62292/njtep.v4i1.2026.115

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