• Logo
  • SBMUJournals

Proton Therapy in Neurosurgery: A Historical Review and Future Perspective Based on Currently Available New Generation Systems

Parisa Azimi, Amir Movafeghi




Purpose: To evaluate of Proton therapy (PT) for neurosurgery patients and is also to explain the need for this system in Iran.

Methods: A literature review was conducted (1984–2016). The strategy included a combination of keywords including proton therapy, neck, neurosurgery, brain, head, tumor, spine, arteriovenous malformation (AVMs), cervical and spine in database of PubMed. New generation PT systems were assessed. Findings are summarized, with a focus on the application of PT in neurosurgery. Finally, the future of PT is discussed.

Results: A total of 1329 citations were screened. In all, 60 articles were included. The synthesis of the data showed two applications of PT in neurosurgery, including: (a) the use in head disease such as AVMs, acromegaly, medulloblastoma, primitive neuroectodermal tumors, papillary tumors of the pineal region, low-grade astrocytoma, head and neck adenoid cystic carcinoma, meningioma, mesenchymal tumors, pediatric cranial tumors, squamous cell carcinoma of the head, craniospinal, and skull base chordomas and chondrosarcomas; (b) the apply in the spinal disease as chordoma or chondrosarcoma of the cervical, sacrum, thoracic and lumbar spine, ependymomas, tumor locations included cervical, thoracic, lumbar, S1-S2, and S3 or below. In addition, the combination of a gantry and cyclotron with new proton therapy systems, results in a lower cost.

Conclusion: PT may be associated with better outcomes for selected patients with malignant diseases of the head and spine. The findings suggest that there exists a need for at least one center to treat the patient demand in Iran.


Proton therapy; neurosurgery; Iran


Businesswire.com. Research and Markets: US Proton Therapy Market Analysis to 2017. USA, c2012 [cited 2012 Dec 19]. Available from:

http://www.businesswire.com/news /home /20121219005533/en/Research-Markets-Proton-Therapy-Market-Analysis-2017

PTCOG: Particle Therapy Co-Operative Group. A non-profit organisation for those interested in proton, light ion and heavy charged particle radiotherapy, c2013, [cited 2013]. Available from: http://www.ptcog.ch.

Buildingbetterhealthcare.co.uk. The future is proton therapy. UK, c2014 [cited 2014 Jan 23]. Available from: http://www.buildingbetterhealthcare.co.uk/technical/article_ page/The_ future_is_proton_therapy/95018

DeLaney TF. Proton therapy in the clinic. Front Radiat Ther Oncol. 2011;43:465-85.

Zhu X, Fakhri GE. Proton Therapy Verification with PET Imaging. Theranostics. 2013; 3 (10) :731-740. doi:10.7150/thno.5162.

Durante M, Loeffler JS. Charged particles in radiation oncology. Nat Rev Clin Oncol. 2010 Jan;7(1):37-43.

Proton-cancer-treatment.com. Prague, Czech Republic: Proton Therapy Around the World. c2016 [cited 2016 Jul 4]. Available from: http://www.proton-cancer-treatment.com/proton-therapy/proton-therapy-around-the-world/

Raju MR. Proton radiobiology, radiosurgery and radiotherapy. Int J Radiat Biol. 1995 Mar;67(3):237-59.

Pronovasolutions.com. Maryville, USA: Pronova SC 360, c2016 [cited 2016 Jul 8], Available from: http://pronovasolutions.com/home/.

National Cancer Control Programs, Iran, c2014, Available from:http://www.ircancer.ir.

Mevion.com, Littleton, USA: Mevion Medical Systems, Mevion 250 Locations. c2016 [cited 2016 Jul 6], Available from: http://www.mevion.com/locations

Verma V, Mishra MV, Mehta MP. A systematic review of the cost and cost-effectiveness studies of proton radiotherapy 2016 May 15;122(10):1483-501.

Winn HR. Youmans Neurological Surgery. 6th ed. Philadelphia, PA, WB Saunders Company; Chapter 254 Proton Radiosurgery p 2617-2621, 2011

iba-protontherapy.com. Louvain-la-Neuve Belgium: IBA Group, IBA Proton Therapy Centers around the World. c2016 [cited 2016 Jul 5], Available from: www.iba-protontherapy.com/proton-therapy-centers.

Klein EE. New Developments in Proton Therapy Delivery Systems. Symposium on the Promises and Perils of Proton Radiotherapy, AAPM, 2011.

Hitachi.com, Twinsburg, Ohio: Hitachi Medical Systems, Inc. Global Locations, c2016 [cited 2016 Jul 6], Available from: http://www.hitachi.com/businesses/healthcare/products-support/pbt/contents02.html.

Proton-therapy-today.com. Proton Therapy Today: the online magazine for proton therapy. c2016 [updated 2014 Sep 10, cited 2016 Jul 5], Available from: http://www.proton-therapy-today.com/category/stories/proton-therapy-centers/.

University of Tsukuba Hospital. Proton Beam Therapy Center, Patients Catalogue. Japan. c2016 [cited 2016 Jul 2], Available from: www.pmrc.tsukuba.ac.jp/en/pdf/TSUKUBA_pmrc_brochure_en.pdf.

Varian.com. Palo Alto, California: Varian Medical Systems, Inc. Varian ProBeam® c2016 [cited 2016 Jul 6]. Available from: https://www.varian.com/oncology/solutions/proton-therapy

Umezawa M. HITACHI Proton Beam Therapy System. Particle Beam Therapy Symposium. 55th AAPM Annual Meeting, Aug.3 2013.

Mitsubishielectric.com. Tokyo, Japan. Particle Therapy Facilities c2016 [cited 2016 Jul 5], Available from: http://www.mitsubishielectric.com/bu/particlebeam/installations/installations.html.

Stein BM, Hilal SK, Mohr JP, Wilson CB. Proton therapy for arteriovenous malformations of the brain. N Engl J Med. 1984;310(10):656-7.

Tseĭtlina MA, Kizhaev EV, Luchin EI, Agapov AV, Gaevskiĭ VN, Gulidov IA, et al. Proton three-demensional conformal radiosurgery of arteriovenous malformation of the brain. Zh Vopr Neirokhir Im N N Burdenko. 2013;77(4):43-50.

Walcott BP, Hattangadi-Gluth JA, Stapleton CJ, Ogilvy CS, Chapman PH, Loeffler JS. Proton beam stereotactic radiosurgery for pediatric cerebral arteriovenous malformations. Neurosurgery. 2014 Apr;74(4):367-73

Hattangadi JA, Chapman PH, Bussière MR, Niemierko A, Ogilvy CS, Rowell A, et al: Planned two-fraction proton beam stereotactic radiosurgery for high-risk inoperable cerebral arteriovenous malformations. Int J Radiat Oncol Biol Phys. 2012;83(2):533-41.

Nakai Y, Ito Y, Sato M, Nakamura K, Shiigai M, Takigawa T, et al. Multimodality treatment for cerebral arteriovenous malformations: complementary role of proton beam radiotherapy. Neurol Med Chir (Tokyo). 2012;52(12):859-64.

Petit JH, Biller BM, Coen JJ, Swearingen B, Ancukiewicz M, Bussiere M, et al. Proton stereotactic radiosurgery in management of persistent acromegaly. Endocr Pract. 2007;13(7):726-34.

Timmermann B, Lomax AJ, Nobile L, Grotzer MA, Weiss M, Kortmann RD, et al. Novel technique of craniospinal axis proton therapy with the spot-scanning system: avoidance of patching multiple fields and optimized ventral dose distribution. Strahlenther Onkol. 2007;183(12):685-8.

Mu X, Björk-Eriksson T, Nill S, Oelfke U, Johansson KA, Gagliardi G, et al: Does electron and proton therapy reduce the risk of radiation induced cancer after spinal irradiation for childhood medulloblastoma? A comparative treatment planning study. Acta Oncol. 2005;44(6):554-62.

Eaton BR, Esiashvili N, Kim S, Weyman EA, Thornton LT, Mazewski C, et al. Clinical Outcomes Among Children With Standard-Risk Medulloblastoma Treated With Proton and Photon Radiation Therapy: A Comparison of Disease Control and Overall Survival. Int J Radiat Oncol Biol Phys. 2016;94(1):133-8.

Giantsoudi D, Sethi RV, Yeap BY, Eaton BR, Ebb DH, Caruso PA, et al. Incidence of CNS Injury for a Cohort of 111 Patients Treated With Proton Therapy for Medulloblastoma: LET and RBE Associations for Areas of Injury. Int J Radiat Oncol Biol Phys. 2016 May 1;95(1):287-96.

Moeller BJ, Chintagumpala M, Philip JJ, Grosshans DR, McAleer MF, Woo SY, et al. Low early ototoxicity rates for pediatric medulloblastoma patients treated with proton radiotherapy. Radiat Oncol. 2011; 6:58.

Miralbell R, Lomax A, Bortfeld T, Rouzaud M, Carrie C. Potential role of proton therapy in the treatment of pediatric medulloblastoma/primitive neuroectodermal tumors: reduction of the supratentorial target volume. Int J Radiat Oncol Biol Phys. 1997;38(3):477-84.

Stokkevåg CH, Engeseth GM, Ytre-Hauge KS, Röhrich D, Odland OH, Muren LP, et al. Estimated risk of radiation-induced cancer following paediatric cranio-spinal irradiation with electron, photon and proton therapy. Acta Oncol. 2014;53(8):1048-57.

Abela L, Rushing EJ, Ares C, Scheer I, Bozinov O, Boltshauser E, et al: Pediatric papillary tumors of the pineal region: to observe or to treat following gross total resection? Childs Nerv Syst. 2013; 29(2):307-10.

Hug EB, Muenter MW, Archambeau JO, DeVries A, Liwnicz B, Loredo LN, et al. Conformal proton radiation therapy for pediatric low-grade astrocytomas. Strahlenther Onkol. 2002;178(1):10-7.

Bhattasali O, Holliday E, Kies MS, Hanna E, Garden AS, Rosenthal DI, et al. Definitive proton radiation therapy and concurrent cisplatin for unresectable head and neck adenoid cystic carcinoma: A series of 9 cases and a critical review of the literature. Head Neck. 2016 Apr;38 Suppl 1:E1472-80.

Linton OR, Moore MG, Brigance JS, Summerlin DJ, McDonald MW: Proton therapy for head and neck adenoid cystic carcinoma: initial clinical outcomes. Head Neck. 2015;37(1):117-24.

Frank SJ, Cox JD, Gillin M, Mohan R, Garden AS, Rosenthal DI, et al. Multifield optimization intensity modulated proton therapy for head and neck tumors: a translation to practice. Int J Radiat Oncol Biol Phys. 2014;89(4):846-53.

Arvold ND, Niemierko A, Broussard GP, Adams J, Fullerton B, Loeffler JS, 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.

Noel G, Habrand JL, Helfre S, Mammar H, Kalifa C, Ferrand R, et al: Proton beam therapy in the management of central nervous system tumors in childhood: the preliminary experience of the Centre de Protonthérapie d'Orsay. Med Pediatr Oncol. 2003;40(5):309-15.

Habrand JL, Mammar H, Ferrand R, Pontvert D, Bondiau PY, Kalifa C, et al. Proton beam therapy (PT) in the management of CNS tumors in childhood. Strahlenther Onkol. 1999;175 Suppl 2:91-4.

Carabe A, España S, Grassberger C, Paganetti H. Clinical consequences of relative biological effectiveness variations in proton radiotherapy of the prostate, brain and liver. Phys Med Biol. 2013; 58(7):2103-17.

Kuhlthau KA, Pulsifer MB, Yeap BY, Rivera Morales D, Delahaye J, Hill KS, et al. Prospective study of health-related quality of life for children with brain tumors treated with proton radiotherapy.J Clin Oncol. 2012; 30(17):2079-86.

Hug EB, Sweeney RA, Nurre PM, Holloway KC, Slater JD, Munzenrider JE. Proton radiotherapy in management of pediatric base of skull tumors. Int J Radiat Oncol Biol Phys. 2002;52(4):1017-24.

McAllister B, Archambeau JO, Nguyen MC, Slater JD, Loredo L, Schulte R, et al. Proton therapy for pediatric cranial tumors: preliminary report on treatment and disease-related morbidities. Int J Radiat Oncol Biol Phys. 1997;39(2):455-60.

Stromberger C, Cozzi L, Budach V, Fogliata A, Ghadjar P, Wlodarczyk W, et al. Unilateral and bilateral neck SIB for head and neck cancer patients : Intensity-modulated proton therapy, tomotherapy, and RapidArc. Strahlenther Onkol. 2016 Apr;192(4):232-239.

Jakobi A, Bandurska-Luque A, Stützer K, Haase R, Löck S, Wack LJ, et al. Identification of Patient Benefit From Proton Therapy for Advanced Head and Neck Cancer Patients Based on Individual and Subgroup Normal Tissue Complication Probability Analysis. Int J Radiat Oncol Biol Phys. 2015;92(5):1165-74.

Barten DL, Tol JP, Dahele M, Slotman BJ, Verbakel WF. Comparison of organ-at-risk sparing and plan robustness for spot-scanning proton therapy and volumetric modulated arc photon therapy in head-and-neck cancer. Med Phys. 2015;42(11):6589-98.

Munck Af Rosenschold P, Engelholm SA, Brodin PN, Jørgensen M, Grosshans DR, Zhu RX, et al. A Retrospective Evaluation of the Benefit of Referring Pediatric Cancer Patients to an External Proton Therapy Center. Pediatr Blood Cancer. 2016;63(2):262-9.

Habrand JL, Schneider R, Alapetite C, Feuvret L, Petras S, Datchary J, et al. Proton therapy in pediatric skull base and cervical canal low-grade bone malignancies. Int J Radiat Oncol Biol Phys. 2008;71(3):672-5.

Weber DC, Badiyan S, Malyapa R, Albertini F, Bolsi A, Lomax AJ, et al. Long-term outcomes and prognostic factors of skull-base chondrosarcoma patients treated with pencil-beam scanning proton therapy at the Paul Scherrer Institute. Neuro Oncol. 2016;18(2):236-43

Feuvret L, Bracci S, Calugaru V, Bolle S, Mammar H, De Marzi L, et al. Efficacy and Safety of Adjuvant Proton Therapy Combined With Surgery for Chondrosarcoma of the Skull Base: A Retrospective, Population-Based Study. Int J Radiat Oncol Biol Phys. 2016 May 1;95(1):312-21.

Weber DC, Rutz HP, Pedroni ES, Bolsi A, Timmermann B, Verwey J, et al. Results of spot-scanning proton radiation therapy for chordoma and chondrosarcoma of the skull base: the Paul Scherrer Institut experience. Int J Radiat Oncol Biol Phys. 2005;63(2):401-9.

Hug EB, Loredo LN, Slater JD, DeVries A, Grove RI, Schaefer RA, et al. Proton radiation therapy for chordomas and chondrosarcomas of the skull base. J Neurosurg. 1999;91(3):432-9.

Santoni R, Liebsch N, Finkelstein DM, Hug E, Hanssens P, Goitein M, et al. Temporal lobe (TL) damage following surgery and high-dose photon and proton irradiation in 96 patients affected by chordomas and chondrosarcomas of the base of the skull. Int J Radiat Oncol Biol Phys. 1998;41(1):59-68.

Debus J, Hug EB, Liebsch NJ, O'Farrel D, Finkelstein D, Efird J, et al. Brainstem tolerance to conformal radiotherapy of skull base tumors. Int J Radiat Oncol Biol Phys. 1997;39(5):967-75.

Austin-Seymour M, Munzenrider J, Linggood R, Goitein M, Verhey L, Urie M, et al. Fractionated proton radiation therapy of cranial and intracranial tumors. Am J Clin Oncol. 1990;13(4):327-30.

Austin-Seymour M, Munzenrider J, Goitein M, Verhey L, Urie M, Gentry R, et al. Fractionated proton radiation therapy of chordoma and low-grade chondrosarcoma of the base of the skull. J Neurosurg. 1989;70(1):13-7.

Noel G, Habrand JL, Jauffret E, de Crevoisier R, Dederke S, Mammar H, et al. Radiation therapy for chordoma and chondrosarcoma of the skull base and the cervical spine. Prognostic factors and patterns of failure. Strahlenther Onkol 2003;179:241–8.

Benk V, Liebsch NJ, Munzenrider JE, Efird J, McManus P, Suit H. Base of skull and cervical spine chordomas in children treated by high-dose irradiation. Int J Radiat Oncol Biol Phys. 1995;31(3):577-81.

Fagundes MA, Hug EB, Liebsch NJ, Daly W, Efird J, Munzenrider JE. Radiation therapy for chordomas of the base of skull and cervical spine: patterns of failure and outcome after relapse. Int J Radiat Oncol Biol Phys. 1995;33(3):579-84.

Yasuda M, Bresson D, Chibbaro S, Cornelius JF, Polivka M, Feuvret L, et al. Chordomas of the skull base and cervical spine: clinical outcomes associated with a multimodal surgical resection combined with proton-beam radiation in 40 patients. Neurosurg Rev. 2012; 35(2):171-82.

Engelsman M, DeLaney TF, Hong TS. Proton radiotherapy: the biological effect of treating alternating subsets of fields for different treatment fractions. Int J Radiat Oncol Biol Phys. 2011; 79(2):616-22.

Munzenrider JE, Austin-Seymour M, Blitzer PJ, Gentry R, Goitein M, Gragoudas ES, et al. Proton therapy at Harvard. Strahlentherapie. 1985;161(12):756-63.

Orecchia R, Vitolo V, Fiore MR, Fossati P, Iannalfi A, Vischioni B, et al. Proton beam radiotherapy: report of the first ten patients treated at the "Centro Nazionale di Adroterapia Oncologica (CNAO)" for skull base and spine tumours. Radiol Med. 2014;119(4):277-82.

Choi GH, Yang MS, Yoon DH, Shin HC, Kim KN, Yi S, et al. Pediatric cervical chordoma: report of two cases and a review of the current literature. Childs Nerv Syst. 2010; 26(6):835-40.

de Ribaupierre S, Vernet O, Beck-Popovic M, Meagher-Villemure K, Rilliet B. Cervical nerve root synovial sarcoma in a child with chromosomal (X;18) translocation. Case report and review of the literature. Pediatr Neurosurg. 2007;43(5):382-5.

Holliday EB, Mitra HS, Somerson JS, Rhines LD, Mahajan A, Brown PD, et al. Postoperative proton therapy for chordomas and chondrosarcomas of the spine: adjuvant versus salvage radiation therapy. Spine (Phila Pa 1976). 2015;40(8):544-9.

Staab A, Rutz HP, Ares C, Timmermann B, Schneider R, Bolsi A, et al. Spot-scanning-based proton therapy for extracranial chordoma. Int J Radiat Oncol Biol Phys. 2011; 81(4):e489-96.

Yadav P, Paliwal BR, Kozak K. Dosimetric comparison of photon and proton treatment techniques for chondrosarcoma of thoracic spine. Med Dosim. 2013;38(3):233-7.

Matsumoto K, Nakamura K, Shioyama Y, Sasaki T, Ohga S, Yamaguchi T, et al. Treatment Planning Comparison for Carbon Ion Radiotherapy, Proton Therapy and Intensity-modulated Radiotherapy for Spinal Sarcoma. Anticancer Res. 2015;35(7):4083-9.

DeLaney TF, Liebsch NJ, Pedlow FX, Adams J, Dean S, Yeap BY, et al. Phase II study of high-dose photon/proton radiotherapy in the management of spine sarcomas. Int J Radiat Oncol Biol Phys. 2009;74(3):732-9.

Hill-Kayser C, Kirk M. Brainstem-sparing craniospinal irradiation delivered with pencil beam scanning proton therapy. Pediatr Blood Cancer. 2015;62(4):718-20.

Amsbaugh MJ, Grosshans DR, McAleer MF, Zhu R, Wages C, Crawford CN, et al. Proton therapy for spinal ependymomas: planning, acute toxicities, and preliminary outcomes. Int J Radiat Oncol Biol Phys. 2012;83(5):1419-24.

Ray GL, Buchsbaum JC, McMullen KP, Simoneaux RV, Hines M, Douglas JG, et al. Definitive treatment of leptomeningeal spinal metastases in children. Pediatr Blood Cancer. 2013;60(11):1839-41.

Delaney TF, Liebsch NJ, Pedlow FX, Adams J, Weyman EA, Yeap BY, et al. Long-term results of Phase II study of high dose photon/proton radiotherapy in the management of spine chordomas, chondrosarcomas, and other sarcomas. J Surg Oncol. 2014 Apr 19. [Epub ahead of print].

Chen YL, Liebsch N, Kobayashi W, Goldberg S, Kirsch D, Calkins G, et al: Definitive high-dose photon/proton radiotherapy for unresected mobile spine and sacral chordomas. Spine 2013;38(15):E930-6.

Knopf AC, Parodi K, Paganetti H, Bortfeld T, Daartz J, Engelsman M, et al. Accuracy of proton beam range verification using post-treatment positron emission tomography/computed tomography as function of treatment site. Int J Radiat Oncol Biol Phys. 2011; 79(1):297-304.

Newhauser WD, Fontenot JD, Mahajan A, Kornguth D, Stovall M, Zheng Y, et al. The risk of developing a second cancer after receiving craniospinal proton irradiation. Phys Med Biol. 2009;54(8):2277-91.

Krejcarek SC, Grant PE, Henson JW, Tarbell NJ, Yock TI. Physiologic and radiographic evidence of the distal edge of the proton beam in craniospinal irradiation. Int J Radiat Oncol Biol Phys. 2007;68(3):646-9.

Stoker JB, Grant J, Zhu XR, Pidikiti R, Mahajan A, Grosshans DR. Intensity modulated proton therapy for craniospinal irradiation: organ-at-risk exposure and a low-gradient junctioning technique. Int J Radiat Oncol Biol Phys. 2014;90(3):637-44.

Parodi K, Paganetti H, Shih HA, Michaud S, Loeffler JS, DeLaney TF, et al. Patient study of in vivo verification of beam delivery and range, using positron emission tomography and computed tomography imaging after proton therapy. Int J Radiat Oncol Biol Phys. 2007;68(3):920-34.

Rutz HP, Weber DC, Goitein G, Ares C, Bolsi A, Lomax AJ, et al. Postoperative spot-scanning proton radiation therapy for chordoma and chondrosarcoma in children and adolescents: initial experience at paul scherrer institute. Int J Radiat Oncol Biol Phys. 2008;71(1):220-225.

Kjellberg RN: Stereotactic Bragg peak proton beam radiosurgery for cerebral arteriovenous malformations. Ann Clin Res. 1986;18 Suppl 47:17-19.

Suit HD, Goitein M, Munzenrider JE, Verhey L, Davis KR, Koehler A, et al. Definitive radiation therapy for chordoma and chondrosarcoma of base of skull and cervical spine. J Neurosurg. 1982;56 (3):377-385.

Hug EB, Fitzek MM, Liebsch NJ, Munzenrider JE. Locally challenging osteo- and chondrogenic tumors of the axial skeleton: results of combined proton and photon radiation therapy using three-dimensional treatment planning. Int J Radiat Oncol Biol Phys. 1995;31(3):467-476.

Al-Mefty O, Borba LAB. Skull base chordomas: a management challenge. J Neurosurg. 1997;86(2):182-189.

McAllister B, Archambeau JO, Nguyen MC, Slater JD, Loredo L, Schulte R, et al. Proton therapy for pediatric cranial tumors: preliminary report on treatment and disease-related morbidities. Int J Radiat Oncol Biol Phys. 1997;39(2):455-460.

Gudjonsson O, Blomquist E, Nyberg G, Pellettieri L, Montelius A, Grusell E, et al. Stereotactic irradiation of skull base meningiomas with high energy protons. Acta Neurochir (Wien). 1999;141(9):933-940.

Wenkel E, Thornton AF, Finkelstein D, Adams J, Lyons S, De La Monte S, et al. Benign meningioma: partially resected, biopsied, and recurrent intracranial tumors treated with combined proton and photon radiotherapy. Int J Radiat Oncol Biol Phys. 2000;48(5):1363.

Vernimmen FJ, Harris JK, Wilson JA, Melvill R, Smit BJ, Slabbert JP. Stereotactic proton beam therapy of skull base meningiomas. Int J Radiat Oncol Biol Phys. 2001;49(1):99-105.

Allen AM, Pawlicki T, Dong L, Fourkal E, Buyyounouski M, Cengel K. An evidence based review of proton beam therapy: the report of ASTRO's emerging technology committee. Radiother Oncol. 2012;103(1):8-11.

Amichetti M1, Cianchetti M, Amelio D, Enrici RM, Minniti G. Proton therapy in chordoma of the base of the skull: a systematic review. Neurosurg Rev. 2009;32(4):403-16.

Amichetti M, Amelio D, Cianchetti M, Enrici RM, Minniti G. A systematic review of proton therapy in the treatment of chondrosarcoma of the skull base. Neurosurg Rev. 2010;33(2):155-65.

National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Head and neck cancers. Version 1.2015. Available from: http://pic1.cmt.com.cn/newspic/files/NCCN

McDonald MW, Linton OR, Shah MV. Proton therapy for reirradiation of progressive or recurrent chordoma. Int J Radiat Oncol Biol Phys 2013; 87(5):1107–1114.

Yock T, DeLaney TF, Esty B, Tarbell NJ. Pediatric tumors. In: Delaney TF, Kooy HM, editors. Philadelphia: Proton and charged particle radiotherapy. 1st ed. Lipincott Williams & Wilkins; 2008.

Miralbell R, Lomax A, Cella L, Schneider U. Potential reduction of the incidence of radiation-induced second cancers by using proton beams in the treatment of pediatric tumors. Int J Radiat Oncol Biol Phys. 2002;54(3):824-9.

Newhauser WD, Fontenot JD, Mahajan A, Kornguth D, Stovall M, Zheng Y, et al. The risk of developing a second cancer after receiving craniospinal proton irradiation. Phys Med Biol. 2009;54(8):2277-91.

Merchant TE. Proton beam therapy in pediatric oncology. Cancer J. 2009;15(4):298-305.

Eaton BR, Yock T. The use of proton therapy in the treatment of benign or low-grade pediatric brain tumors. Cancer J. 2014;20(6):403-8.

Merchant TE, Farr JB. Proton beam therapy: a fad or a new standard of care. Curr Opin Pediatr. 2014;26(1):3-8.

Esteves SC, Nadalin W, Piske RL, Benabou S, Souza Ed, Oliveira AC. Radiosurgery with a linear accelerator in cerebral arteriovenous malformations. Rev Ass Med Bras 2008; 54(2): 2: 167-172.

Friedman WA, Bova FJ, Mendenhall WM. Lenear accelerator radiosurgery for arteriovenous malformations: the relationship of size to outcome. J Neurosurg. 1995;82(2):180-9.

Ray GL, Buchsbaum JC, McMullen KP, Simoneaux RV, Hines M, Douglas JG, et al. Definitive treatment of leptomeningeal spinal metastases in children. Pediatr Blood Cancer. 2013;60(11):1839-1841.

Terasawa T1, Dvorak T, Ip S, Raman G, Lau J, Trikalinos TA. Systematic review: charged-particle radiation therapy for cancer. Ann Intern Med. 2009;151(8):556-65.

Brada M, Pijls-Johannesma M, De Ruysscher D. Current clinical evidence for proton therapy. Cancer J. 2009;15(4):319-24.

Lodge M, Pijls-Johannesma M, Stirk L, Munro AJ, De Ruysscher D, Jefferson T. A systematic literature review of the clinical and cost-effectiveness of hadron therapy in cancer. Radiother Oncol. 2007;83(2):110-22.

Olsen DR, Bruland OS, Frykholm G, Norderhaug IN: Proton therapy - a systematic review of clinical effectiveness. Radiother Oncol. 2007;83(2):123-32.

Elnahal SM, Kerstiens J, Helsper RS, Zietman AL, Johnstone PA. Proton beam radiotherapy and accountable care: the challenges ahead [serial online]. Int J Radiat Oncol Biol Phys. 2013;85(4):e165-e172.

Kerstjens J, Johnstone PA. Proton therapy expansion under current United States reimbursement models. Int J Radiat Oncol Biol Phys. 2014;89(2):235-240.

Lievens Y, Pijls-Johannesma M. Health economic controversy and costeffectiveness of proton therapy. Semin Radiat Oncol. 2013;23(2):134-141.

Chen AB. Comparative effectiveness research in radiation oncology: assessing technology. Semin Radiat Oncol. 2014;24(1):25-34.

Vega RM, Kim J, Bussière M, Hattangadi J, Hollander A, Michalski J, et al. Cost-Effectiveness of Proton Therapy Compared to Photon Therapy in the Management of Pediatric Medulloblastoma. 2013 American Society for Radiation Oncology (ASTRO) 55th Annual Meeting News Briefing, Tuesday, September 24, 2013

Bindra RS, Wolden SL. Advances in Radiation Therapy in Pediatric Neuro-oncology. J Child Neurol. 2016;31(4):506-16.

Cheng Q, Roelofs E, Ramaekers BL, Eekers D, van Soest J, Lustberg T, et al. Development and evaluation of an online three-level proton vs photon decision support prototype for head and neck cancer - Comparison of dose, toxicity and cost-effectiveness. Radiother Oncol. 2016 Feb;118(2):281-5.

www.appliedradiationoncology.com, Buchsbaum JC. Pediatric proton therapy in 2015: Indications, applications and considerations. Applied radiation oncology.

Available from: http://cdn.agilitycms.com/applied-radiation-oncology/PDFs/issues/ARO_09-15_Buchsbaum.pdf

Newhauser WD, Zhang R. The physics of proton therapy. Phys Med Biol. 2015;60(8):R155-209.

Sakurai H, Robert Lee W, Orton CG. Point/counterpoint: we do not need randomized clinical trials to demonstrate the superiority of proton therapy. Med Phys. 2012;39(4):1685-7.

Combs SE, Laperriere N, Brada M. Clinical controversies: proton radiation therapy for brain and skull base tumors. Semin Radiat Oncol. 2013;23(2):120-6.

DOI: https://doi.org/10.22037/icnj.v3i2.13324


  • There are currently no refbacks.