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| Fig. 1: Illustration of the yellow line of a proton beam field-shaping aperture, firing at a tumor in the brain. Illustration was generated by overlaying the computer-simulated radiation deposition onto a CT scan. Location of the tumor is circled out in red, and is very closed to critical structures like the eyes, optic nerves, and brain stem colored in pale green and blue. More radiation is deposited (red color) in the tumor than in healthy tissue. (Courtesy of the National Cancer Institute) |
Radiation therapy with photons (X-rays) is the most commonly adopted treatment method to combat tumors, with 50% of all cancer patients receiving radiation therapy. [1] Compared to the photon and electron beams, proton beams scatter through much smaller angles due to their greater mass. Hence, proton beams have a sharper lateral distribution than the electron or photon beams. This is very advantageous in the treatment of tumors in close vicinity of critical normal structures, for example, tumors of the brain, eye, and spine. [2] However, it is important to note that PBT is not the best option for all types of treatment. There are both benefits and limitations. For example, due to the Bragg peak, a phenomenon unique to protons which will be expanded upon later, PBT is best for its precision in treating clearly defined, metastatic tumors. However, if radiation treatment for larger or less well-defined areas is required, photon or electron radiation or chemotherapy might serve as a better option for the patient. [3]
The Bragg peak is the distinguishing property for protons in beam therapy. The rate of energy loss due to ionization and excitation caused by a charged particle traveling in a medium is proportional to the square of the particle charge and inversely proportional to the square of its velocity. The further a particle deposits itself into a medium, the rate of energy loss reaches maximum. For a mono-energetic proton beam, there is a slow increase in dose with depth initially, followed by a sharp increase near the end of the deposition. This sharp increase or peak in dose deposition at the end of particle trajectory is called the Bragg peak. Compared to a photon beam, the Bragg peak from exhibited in a proton beam is very sharp and is able to be tuned to release most of its energy precisely at the location or depth the tumor is located. Fig. 1 is an example of proton beam hitting a brain tumor, overlayed onto a CT scan.
The two main types of proton delivery systems are: passive beam scattering and dynamic spot scanning system. For passive beam scattering, the depth-dose distribution is a Bragg peak with a width of approximately 0.6 cm at the 90% level. It is only suitable for targets with very little extent in depth, such as the pituitary gland. [3] For dynamic spot scanning system, the beam shape is like a narrow pencil, called the "pencil beam", enters the treatment nozzle and is magnetically scanned across the target cross section. The depth of the spot can be varied by adjusting the energy of the protons, leaving room for flexibility to achieve intended dose pattern. However, dynamic spot scanning system is very sensitive to organ motion. It works well to immobilized tumors, such as those located in the head and neck, spinal cord, lower pelvis, with a movement of less than 5 mm. [3]
The feasibility and advantages of PBT in pediatric cancer has been confirmed by multiple studies, A phase II clinical study published in 2016 reported the long-term results of PBT in 59 patients (aged 3-21 years) with medulloblastoma. [4] PBT was found to be more optimal than photon therapy due to the reduced symptoms: no late toxicities of the heart, lungs, and digestive tract side effects, and no second primary tumor occurred. [5]
A recent meta-analysis compared the effectiveness of PBT and photon therapy for chordoma. [5,6] The estimated 10-year overall survival rates of the PBT group reached 60%, which was significantly higher than that of the conventional photon therapy (21%). [5] Traditionally, surgery has been the preferred treatment of chordoma and chondrosarcoma. However, the cancers are located in the skull base and are close to cranial nerves and blood vessels, making the surgery critically risky. Photon radiation therapy is non-intrusive; however, it is also a less desirable option. This is because the radiation dosage is significantly limited to avoid damaging structures surrounding the tumors, such as the brain stem, temporal lobe and optic nerve which are extremely sensitive to dose. Proton beam can achieve higher precision and can thus increase the dosage while better protecting surrounding tissue, making PBT a preferable option when treating radio-resistant chordomas and chondrosarcomas for many decades.
As of August 2018, there were approximately 70 proton centers in operation in the world, and 45 were under construction, compared to more than 8,000 sites for radiation therapy worldwide. [5,7] Why are there significantly fewer proton beam sites than photon and electron radiation sites? Currently, very large accelerators, such as cyclotrons and synchrotrons, are required to generate the proton beam used in radiotherapy, making it less accessible for commercial mass production. There are recent attempts to reduce the size of the accelerators and or to improve the performance of PBT. Two examples are high-gradient electrostatic accelerators and laser- plasma particle accelerators. [2]
© Tiffany Wang. The author warrants that the work is the author's own and that Stanford University provided no input other than typesetting and referencing guidelines. The author grants permission to copy, distribute and display this work in unaltered form, with attribution to the author, for noncommercial purposes only. All other rights, including commercial rights, are reserved to the author.
[1] J. R. Hughes and J. L. Parsons, "FLASH Radiotherapy: Current Knowledge and Future Insights Using Proton-Beam Therapy," Int. J. Mol. Sci. 21, 6492 (2020).
[2] J. P. Gibbons, Khan's The Physics of Radiation Therapy, 6th Ed. (Wolters Kluwer, 2020).
[3] H. Liu and J. Y. Chang, "Proton therapy in clinical practice," Chin. J. Cancer. 30(5), 315 (2011).
[4] T. I. Yock et al., "Long-Term Toxic Effects of Proton Radiotherapy for Paediatric Medulloblastoma: A Phase 2 Single-Arm Study," Lancet Oncol. 17, 287 (2016).
[5] M. Hu et al., "Proton Beam Therapy For Cancer in the Era of Precision Medicine," J. Hematol. Oncol. 11, 136 (2018).
[6] J. Zhou et al., "Comparison of the Effectiveness of Radiotherapy with Photons and Particles for Chordoma After Surgery: A Meta-Analysis," World Neurosurg. 117, 46 (2018).
[7] E. Zubizarreta, J. Van Dyk, and Y, Lievens, "Analysis of Global Radiotherapy Needs and Costs by Geographic Region and Income Level," Clin. Oncol. 29, 84 (2017).