Proton Beam Therapy (For CNS Tumors)

  • Divya Yerramilli
  • Marc R. Bussière
  • Jay S. Loeffler
  • Helen A. ShihEmail author


For CNS tumors, proton beam therapy is a unique modality of radiation that offers several physical advantages as compared to traditional photon radiation. Protons have superior dose conformality and therefore significantly reduce normal tissue exposure to low dose radiation. This improved dosimetry translates into improved clinical outcomes for some indications of radiation therapy, and these scenarios will be further explored in this chapter. However, there are certain limitations to proton therapy, including the high capital costs and the lack of robust data on clinical applications. The true clinical benefit of proton therapy remains an active area of investigation, and ongoing studies to measure the potential reduction of treatment-related adverse effects will help to elucidate these controversies. In this chapter, the evolution, potential applications, and limitations of proton therapy will be described. Important treatment considerations, treatment planning, and quality assurance guidelines are also defined.


Protons CNS tumors Radiation techniques Treatment planning Quality assurance 


  1. 1.
    Khan FM, Gibbons JP. Chapter 27: Proton beam therapy. In: Khan’s the physics of radiation therapy. Philadelphia, PA: Lippincott Williams & Wilkins; 2014. p. 527–40.Google Scholar
  2. 2.
    Urie MM, Sisterson JM, Koehler AM, et al. Proton beam penumbra: effects of separation between patient and beam modifying devices. Med Phys. 1986;13(5):734–41.Google Scholar
  3. 3.
    Koehler AM, Preston WM. Protons in radiation therapy: comparative dose distributions for protons, photons, and electrons. Radiology. 1972;104(1):191–5.Google Scholar
  4. 4.
    Wilson RR. Radiological use of fast protons. Radiology. 1946;47(5):487–91.Google Scholar
  5. 5.
    Gridley DS, Grover RS, Loredo LN, et al. Proton-beam therapy for tumors of the CNS. Expert Rev Neurother. 2010;10(2):319–30.Google Scholar
  6. 6.
    Teh BS, Woo SY, Butler EB. Intensity modulated radiation therapy (IMRT): a new promising technology in radiation oncology. Oncologist. 1999;4(6):433–42.Google Scholar
  7. 7.
    Shumway DA, Griffith KA, Pierce LJ, et al. Wide variation in the diffusion of a new technology: practice-based trends in intensity-modulated radiation therapy (IMRT) use in the state of Michigan, with implications for IMRT use nationally. J Oncol Pract. 2015;11(3):e373–9.Google Scholar
  8. 8.
    Suit H, Chu W. History of charged particle radiotherapy. In: De Laney TF, Kooy HM, editors. Proton and charged particle radiotherapy. Philadelphia, PA: Lippincott Williams & Wilkins; 2008. p. 1–8.Google Scholar
  9. 9.
    Urano M, Verhey LJ, Goitein M, et al. Relative biological effectiveness of modulated proton beams in various murine tissues. Int J Radiat Oncol Biol Phys. 1984;10(4):509–14.Google Scholar
  10. 10.
    Paganetti H, Niemierko A, Ancukiewicz M, et al. Relative biological effectiveness (RBE) values for proton beam therapy. Int J Radiat Oncol Biol Phys. 2002;53(2):407–21.Google Scholar
  11. 11.
    Paganetti H. Relative biological effectiveness (RBE) values for proton beam therapy. Variations as a function of biological endpoint, dose, and linear energy transfer. Phys Med Biol. 2014;59(22):R419.Google Scholar
  12. 12.
    Paganetti H, Jiang H, Parodi K, et al. Clinical implementation of full Monte Carlo dose calculation in proton beam therapy. Phys Med Biol. 2008;53(17):4825.Google Scholar
  13. 13.
    Cox JD, Stetz J, Pajak TF. Toxicity criteria of the radiation therapy oncology group (RTOG) and the European organization for research and treatment of cancer (EORTC). Int J Radiat Oncol Biol Phys. 1995;31(5):1341–6.Google Scholar
  14. 14.
    Cardis E, Gilbert ES, Carpenter L, et al. Effects of low doses and low dose rates of external ionizing radiation: cancer mortality among nuclear industry workers in three countries. Radiat Res. 1995;142(2):117–32.Google Scholar
  15. 15.
    Lowe XR, Bhattacharya S, Marchetti F, et al. Early brain response to low-dose radiation exposure involves molecular networks and pathways associated with cognitive functions, advanced aging and Alzheimer’s disease. Radiat Res. 2009;171(1):53–65.Google Scholar
  16. 16.
    Lawrence YR, Li XA, El Naqa I, et al. Radiation dose–volume effects in the brain. Int J Radiat Oncol Biol Phys. 2010;76(3):S20–7.Google Scholar
  17. 17.
    Jagsi R, DeLaney TF, Donelan K, et al. Real-time rationing of scarce resources: The Northeast Proton Therapy Center experience. J Clin Oncol. 2004;22(11):2246–50.Google Scholar
  18. 18.
    Bekelman JE, Asch DA, Tochner Z, et al. Principles and reality of proton therapy treatment allocation. Int J Radiat Oncol Biol Phys. 2014;89(3):499–508.Google Scholar
  19. 19.
    Al-Mefty O, Kersh JE, Routh A, et al. The long-term side effects of radiation therapy for benign brain tumors in adults. J Neurosurg. 1990;73(4):502–12.Google Scholar
  20. 20.
    Schulz-Ertner D, Tsujii H. Particle radiation therapy using proton and heavier ion beams. J Clin Oncol. 2007;25(8):953–64.Google Scholar
  21. 21.
    Seifert V, Stolke D, Mehdorn HM, et al. Clinical and radiological evaluation of long-term results of stereotactic proton beam radiosurgery in patients with cerebral arteriovenous malformations. J Neurosurg. 1994;81(5):683–9.Google Scholar
  22. 22.
    Silander H, Pellettieri L, Enblad P, et al. Fractionated, stereotactic proton beam treatment of cerebral arteriovenous malformations. Acta Neurol Scand. 2004;109(2):85–90.Google Scholar
  23. 23.
    Vernimmen FJ, Slabbert JP, Wilson JA, et al. Stereotactic proton beam therapy for intracranial arteriovenous malformations. Int J Radiat Oncol Biol Phys. 2005;62(1):44–52.Google Scholar
  24. 24.
    Weber DC, Chan AW, Bussiere MR, et al. Proton beam radiosurgery for vestibular schwannoma: tumor control and cranial nerve toxicity. Neurosurgery. 2003;53(3):577–88.Google Scholar
  25. 25.
    Lunsford LD, Niranjan A, Flickinger JC, et al. Radiosurgery of vestibular schwannomas: summary of experience in 829 cases. J Neurosurg. 2005;102(Suppl):195–9.Google Scholar
  26. 26.
    Loeffler JS, Shih HA. Radiation therapy in the management of pituitary adenomas. J Clin Endocrinol Metabol. 2011;96(7):1992–2003.Google Scholar
  27. 27.
    Ronson BB, Schulte RW, Han KP, et al. Fractionated proton beam irradiation of pituitary adenomas. Int J Radiat Oncol Biol Phys. 2006;64(2):425–34.Google Scholar
  28. 28.
    Hug EB, DeVries A, Thornton AF, et al. Management of atypical and malignant meningiomas: role of high-dose, 3D-conformal radiation therapy. J Neuro-Oncol. 2000;48(2):151–60.Google Scholar
  29. 29.
    Arvold ND, Niemierko A, Broussard GP, et al. Projected second tumor risk and dose to neurocognitive structures after proton versus photon radiotherapy for benign meningioma. Int J Radiat Oncol Biol Phys. 2012;83(4):e495–500.Google Scholar
  30. 30.
    Blomquist E, Bjelkengren G, Glimelius B. The potential of proton beam radiation therapy in intracranial and ocular tumours. Acta Oncol. 2005;44(8):862–70.Google Scholar
  31. 31.
    Shih HA, Sherman JC, Nachtigall LB, et al. Proton therapy for low-grade gliomas: results from a prospective trial. Cancer. 2015;121(10):1712–9.Google Scholar
  32. 32.
    Fitzek MM, Thornton AF, Rabinov JD, et al. Accelerated fractionated proton/photon irradiation to 90 cobalt gray equivalent for glioblastoma multiforme: results of a phase II prospective trial. J Neurosurg. 1999;91(2):251–60.Google Scholar
  33. 33.
    Deraniyagala RL, Yeung D, Mendenhall WM, et al. Proton therapy for skull base chordomas: an outcome study from the University of Florida Proton Therapy Institute. J Neurol Surg B Skull Base. 2014;75(01):053–7.Google Scholar
  34. 34.
    Weber DC, Malyapa R, Albertini F, et al. Long term outcomes of patients with skull-base low-grade chondrosarcoma and chordoma patients treated with pencil beam scanning proton therapy. Radiother Oncol. 2016;120(1):169–74.Google Scholar
  35. 35.
    Sikuade MJ, Salvi S, Rundle PA, et al. Outcomes of treatment with stereotactic radiosurgery or proton beam therapy for choroidal melanoma. Eye. 2015;29(9):1194–8.Google Scholar
  36. 36.
    Polishchuk AL, Mishra KK, Weinberg V, et al. Temporal evolution and dose-volume histogram predictors of visual acuity after proton beam radiation therapy of uveal melanoma. Int J Radiat Oncol Biol Phys. 2017;97(1):91–7.Google Scholar
  37. 37.
    Mizumoto M, Okumura T, Ishikawa E, et al. Reirradiation for recurrent malignant brain tumor with radiotherapy or proton beam therapy. Strahlenther Onkol. 2013;189(8):656–63.Google Scholar
  38. 38.
    McDonald MW, Linton OR, Shah MV. Proton therapy for reirradiation of progressive or recurrent chordoma. Int J Radiat Oncol Biol Phys. 2013;87(5):1107–14.Google Scholar
  39. 39.
    Mehta M. Randomized phase II trial of hypofractionated dose-escalated photon IMRT or proton beam therapy versus conventional photon irradiation with concomitant and adjuvant temozolomide in patients with newly diagnosed glioblastoma. In: [Internet]. Bethesda (MD): National Library of Medicine (US). 2015. Available from: NLM Identifier: NCT02179086.
  40. 40.
    Abramson Cancer Center at the University of Pennsylvania. Proton radiation for meningiomas and hemangiopericytomas. In: [Internet]. Bethesda (MD): National Library of Medicine (US). 2015. Available from: NLM Identifier: NCT01117844.
  41. 41.
    Olsen DR, Bruland ØS, Frykholm G, et al. Proton therapy–a systematic review of clinical effectiveness. Radiother Oncol. 2007;83(2):123–32.Google Scholar
  42. 42.
    Lodge M, Pijls-Johannesma M, Stirk L, et al. A systematic literature review of the clinical and cost-effectiveness of hadron therapy in cancer. Radiother Oncol. 2007;83(2):110–22.Google Scholar
  43. 43.
    Glimelius B, Montelius A. Proton beam therapy–do we need the randomised trials and can we do them? Radiother Oncol. 2007;83(2):105–9.Google Scholar
  44. 44.
    Winey B, Daartz J, Dankers F, et al. Immobilization precision of a modified GTC frame. J Appl Clin Med Phys. 2012;13(3):12.Google Scholar
  45. 45.
    Bussière MR, Adams JA. Treatment planning for conformal proton radiation therapy. Technol Cancer Res Treat. 2003;2(5):389–99.Google Scholar
  46. 46.
    Engelsman M, Rosenthal SJ, Michaud SL, et al. Intra and interfractional patient motion for a variety of immobilization devices. Med Phys. 2005;32(11):3468–74.Google Scholar
  47. 47.
    Chen CC, Chapman P, Petit J, et al. Proton radiosurgery in neurosurgery. Neurosurg Focus. 2007;23(6):E4.Google Scholar
  48. 48.
    Schneider U, Pedroni E, Lomax A. The calibration of CT Hounsfield units for radiotherapy treatment planning. Phys Med Biol. 1996;41(1):111.Google Scholar
  49. 49.
    Gottschalk B. Passive beam scattering. In: De Laney TF, Kooy HM, editors. Proton and charged particle radiotherapy. Philadelphia, PA: Lippincott Williams & Wilkins; 2008. p. 33–9.Google Scholar
  50. 50.
    Pedroni E. Pencil beam scanning. In: De Laney TF, Kooy HM, editors. Proton and charged particle radiotherapy. Philadelphia, PA: Lippincott Williams & Wilkins; 2008. p. 33–9.Google Scholar
  51. 51.
    Pedroni E, Scheib S, Böhringer T, et al. Experimental characterization and physical modelling of the dose distribution of scanned proton pencil beams. Phys Med Biol. 2005;50(3):541.Google Scholar
  52. 52.
    Bussiere M, Loeffler J, Chapman P, et al. Techniques of radiosurgery. Chapter 254. Proton radiosurgery. In: Youmans WH, editor. Neurological surgery. Amsterdam: Elsevier; 2016.Google Scholar
  53. 53.
    De Laney TF, Kooy HM, editors. Proton and charged particle radiotherapy. Philadelphia, PA: Lippincott Williams & Wilkins; 2008.Google Scholar
  54. 54.
    Yock T, Schneider R, Friedmann A, et al. Proton radiotherapy for orbital rhabdomyosarcoma: clinical outcome and a dosimetric comparison with photons. Int J Radiat Oncol Biol Phys. 2005;63(4):1161–8.Google Scholar
  55. 55.
    Boehling NS, Grosshans DR, Bluett JB, et al. Dosimetric comparison of three-dimensional conformal proton radiotherapy, intensity-modulated proton therapy, and intensity-modulated radiotherapy for treatment of pediatric craniopharyngiomas. Int J Radiat Oncol Biol Phys. 2012;82(2):643–52.Google Scholar
  56. 56.
    Verhey LJ, Smith V, Serago CF, et al. Comparison of radiosurgery treatment modalities based on physical dose distributions. Int J Radiat Oncol Biol Phys. 1998;40(2):497–505.Google Scholar
  57. 57.
    Phillips MH, Frankel KA, Lyman JT, et al. Comparison of different radiation types and irradiation geometries in stereotactic radiosurgery. Int J Radiat Oncol Biol Phys. 1990;18(1):211–20.Google Scholar
  58. 58.
    Bolsi A, Fogliata A, Cozzi L, et al. Radiotherapy of small intracranial tumours with different advanced techniques using photon and proton beams: a treatment planning study. Radiother Oncol. 2003;68(1):1–14.Google Scholar
  59. 59.
    Tayama R, Fujita Y, Tadokoro M, et al. Measurement of neutron dose distribution for a passive scattering nozzle at the Proton Medical Research Center (PMRC). Nucl Instrum Methods Phys Res, Sect A. 2006;564(1):532–6.Google Scholar
  60. 60.
    Vynckier S, Bonnett DE, Jones DTL. Supplement to the code of practice for clinical proton dosimetry. Radiother Oncol. 1994;32(2):174–9.Google Scholar
  61. 61.
    Lu HM. Proton therapy: operations and physics QA at MGH. Presented at AAPM, 2013.Google Scholar
  62. 62.
    Sahoo N. Quality assurance implementation in proton therapy centers. Presented at AAPM, 2013.Google Scholar
  63. 63.
    American College of Radiology. ACR-AAPM technical standard for the performance of proton beam radiation therapy. Accessed 15 Feb 2017.
  64. 64.
    American College of Radiology. ACR practice parameter for 3D external beam radiation planning and conformal therapy. 2016. Accessed 15 Feb 2017.
  65. 65.
    American College of Radiology. ACR technical standard for medical physics performance monitoring of image-guided radiation therapy (IGRT). 2014. Accessed 15 Feb 2017.
  66. 66.
    American College of Radiology. ACR–ASTRO practice parameter for image-guided radiation therapy (IGRT) CSC/BOC. 2014. Accessed 15 Feb 2017.
  67. 67.
    American College of Radiology. ACR practice parameter for intensity modulated radiation therapy (IMRT). 2016. Accessed 15 Feb 2017.
  68. 68.
    American College of Radiology. ACR practice parameter for the performance of brain stereotactic radiosurgery. 2016. Accessed 15 Feb 2017.
  69. 69.
    American College of Radiology. ACR–ASTRO practice parameter for the performance of stereotactic body radiation therapy. 2014. Accessed 15 Feb 2017.
  70. 70.
    American College of Radiology. ACR technical standard for the performance of radiation oncology physics for external beam therapy. Accessed 15 Feb 2017.Google Scholar
  71. 71.
    Goitein M, Jermann M. The relative costs of proton and X-ray radiation therapy. Clin Oncol. 2003;15(1):S37–50.CrossRefGoogle Scholar
  72. 72.
    Lievens Y, Pijls-Johannesma M. Health economic controversy and cost-effectiveness of proton therapy. Semin Radiat Oncol. 2013;23(2):134–41.Google Scholar
  73. 73.
    Zietman AL. The titanic and the iceberg: prostate proton therapy and health care economics. J Clin Oncol. 2007;25(24):3565–6.Google Scholar
  74. 74.
    Konski A, Speier W, Hanlon A, et al. Is proton beam therapy cost effective in the treatment of adenocarcinoma of the prostate? J Clin Oncol. 2007;25(24):3603–8.CrossRefPubMedGoogle Scholar
  75. 75.
    Lundkvist J, Ekman M, Ericsson SR, et al. Proton therapy of cancer: potential clinical advantages and cost-effectiveness. Acta Oncol. 2005;44(8):850–61.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Divya Yerramilli
    • 1
  • Marc R. Bussière
    • 2
  • Jay S. Loeffler
    • 2
  • Helen A. Shih
    • 2
    Email author
  1. 1.Harvard Radiation Oncology Program, Department of Radiation OncologyMassachusetts General HospitalBostonUSA
  2. 2.Department of Radiation OncologyMassachusetts General HospitalBostonUSA

Personalised recommendations