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Proton beam therapy for skull base chordomas: a systematic review of tumor control rates and survival rates

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Abstract

The management of base of skull (BS) chordomas is a neurosurgical conundrum owing to their close proximity to the critical neurovascular structures. Surgical resection is the gold standard treatment followed by adjuvant radiotherapy which includes photon therapy, proton beam therapy (PBT), gamma knife radiosurgery, etc. PBT has become an unparalleled therapeutic modality in the management of BS chordomas. The aim of this systematic review was to assess the outcomes in BS chordoma patients who received PBT as a primary or adjuvant therapy. PubMed and Cochrane databases were screened till May 2022. Following the PRISMA guidelines, studies were reviewed thoroughly, and the data of the included study was extracted. Statistical analysis was performed using the SAS 9.4 with P value < .05 considered as significant. Sixteen studies with 752 patients were included. The majority of the patients were adults (> 18 years) with a male:female ratio of 1.2. The most common clinical features were cranial nerve (3rd, 6th, or 12th) palsy and hearing impairment. Ninety-five percent of the patients underwent surgical resection before PBT. The mean PBT dose received was 74.02 cGe (cobalt gray equivalent). Eighty percent of the patients showed a positive response to the therapy defined in terms of tumor regression. Five-year local control (LC), overall survival (OS), and progression-free survival (PFS) were calculated as 76.6%, 79.6%, and 89%, respectively. Statistical analysis revealed none of the factors had any significant association with 5-year LC. PBT is a growing therapeutic technique that has revolutionized the treatment of BS chordomas.

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References

  1. McMaster ML, Goldstein AM, Bromley CM, Ishibe N, Parry DM (2001) Chordoma: incidence and survival patterns in the United States, 1973–1995. Cancer Causes Control 12(1):1–11. https://doi.org/10.1023/a:1008947301735

    Article  CAS  PubMed  Google Scholar 

  2. Healey JH, Lane JM (1989) Chordoma: a critical review of diagnosis and treatment. Orthop Clin North Am 20(3):417–426

    CAS  PubMed  Google Scholar 

  3. Tenny S, Varacallo M. Chordoma. [Updated 2022 Feb 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430846/

  4. Koutourousiou M, Snyderman CH, Fernandez-Miranda J, Gardner PA (2011) Skull base chordomas. Otolaryngol Clin North Am 44(5):1155–1171. https://doi.org/10.1016/j.otc.2011.06.002

    Article  PubMed  Google Scholar 

  5. Wang L, Wu Z, Tian K et al (2017) Clinical features and surgical outcomes of patients with skull base chordoma: a retrospective analysis of 238 patients. J Neurosurg 127(6):1257–1267. https://doi.org/10.3171/2016.9.JNS16559

    Article  PubMed  Google Scholar 

  6. Kishimoto R, Omatsu T, Hasegawa A, Imai R, Kandatsu S, Kamada T (2012) Imaging characteristics of metastatic chordoma. Jpn J Radiol 30(6):509–516. https://doi.org/10.1007/s11604-012-0086-3

    Article  PubMed  Google Scholar 

  7. Habrand JL, Datchary J, Bolle S et al (2016) Chordoma in children: case-report and review of literature. Rep Pract Oncol Radiother 21(1):1–7. https://doi.org/10.1016/j.rpor.2015.10.007

    Article  PubMed  Google Scholar 

  8. Mobley BC, McKenney JK, Bangs CD et al (2010) Loss of SMARCB1/INI1 expression in poorly differentiated chordomas. Acta Neuropathol 120(6):745–753. https://doi.org/10.1007/s00401-010-0767-x

    Article  CAS  PubMed  Google Scholar 

  9. Yadav R, Sharma MC, Malgulwar PB et al (2014) Prognostic value of MIB-1, p53, epidermal growth factor receptor, and INI1 in childhood chordomas. Neuro Oncol 16(3):372–381. https://doi.org/10.1093/neuonc/not228

    Article  CAS  PubMed  Google Scholar 

  10. al-Mefty O, Borba LA (1997) Skull base chordomas: a management challenge. J Neurosurg 86(2):182–189. https://doi.org/10.3171/jns.1997.86.2.0182

    Article  CAS  PubMed  Google Scholar 

  11. Stacchiotti S, Sommer J, Chordoma Global Consensus Group (2015) Building a global consensus approach to chordoma: a position paper from the medical and patient community. Lancet Oncol 16(2):e71–e83. https://doi.org/10.1016/S1470-2045(14)71190-8

    Article  PubMed  Google Scholar 

  12. Weber DC, Rutz HP, Pedroni ES et al (2005) 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 63(2):401–409. https://doi.org/10.1016/j.ijrobp.2005.02.023

    Article  PubMed  Google Scholar 

  13. Hoch BL, Nielsen GP, Liebsch NJ, Rosenberg AE (2006) Base of skull chordomas in children and adolescents: a clinicopathologic study of 73 cases. Am J Surg Pathol 30(7):811–818. https://doi.org/10.1097/01.pas.0000209828.39477.ab

    Article  PubMed  Google Scholar 

  14. Rutz HP, Weber DC, Goitein G et al (2008) 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 71(1):220–225. https://doi.org/10.1016/j.ijrobp.2007.09.014

    Article  PubMed  Google Scholar 

  15. Pehlivan B, Ares C, Lomax AJ et al (2012) Temporal lobe toxicity analysis after proton radiation therapy for skull base tumors. Int J Radiat Oncol Biol Phys 83(5):1432–1440. https://doi.org/10.1016/j.ijrobp.2011.10.042

    Article  PubMed  Google Scholar 

  16. Korchi AM, Garibotto V, Lovblad KO, Haller S, Weber DC (2013) Radiologic patterns of necrosis after proton therapy of skull base tumors. Can J Neurol Sci 40(6):800–806. https://doi.org/10.1017/s0317167100015924

    Article  PubMed  Google Scholar 

  17. Deraniyagala RL, Yeung D, Mendenhall WM et al (2014) Proton therapy for skull base chordomas: an outcome study from the University of Florida proton therapy institute. J Neurol Surg B Skull Base 75(1):53–57. https://doi.org/10.1055/s-0033-1354579

    Article  PubMed  Google Scholar 

  18. McDonald MW, Linton OR, Moore MG, Ting JY, Cohen-Gadol AA, Shah MV (2016) Influence of residual tumor volume and radiation dose coverage in outcomes for clival chordoma. Int J Radiat Oncol Biol Phys 95(1):304–311. https://doi.org/10.1016/j.ijrobp.2015.08.011

    Article  PubMed  Google Scholar 

  19. Weber DC, Malyapa R, Albertini F et al (2016) Long term outcomes of patients with skull-base low-grade chondrosarcoma and chordoma patients treated with pencil beam scanning proton therapy. Radiother Oncol 120(1):169–174. https://doi.org/10.1016/j.radonc.2016.05.011

    Article  PubMed  Google Scholar 

  20. Tsitouras V, Wang S, Dirks P et al (2016) Management and outcome of chordomas in the pediatric population: the Hospital for Sick Children experience and review of the literature. J Clin Neurosci 34:169–176. https://doi.org/10.1016/j.jocn.2016.06.003

    Article  PubMed  Google Scholar 

  21. Ramm-Pettersen J, Frič R, Berg-Johnsen J (2017) Long-term follow-up after endoscopic trans-sphenoidal surgery or initial observation in clivus chordomas. Acta Neurochir (Wien) 159(10):1849–1855. https://doi.org/10.1007/s00701-017-3236-7

    Article  Google Scholar 

  22. Gatfield ER, Noble DJ, Barnett GC et al (2018) Tumour volume and dose influence outcome after surgery and high-dose photon radiotherapy for chordoma and chondrosarcoma of the skull base and spine. Clin Oncol (R Coll Radiol) 30(4):243–253. https://doi.org/10.1016/j.clon.2018.01.002

    Article  CAS  Google Scholar 

  23. Takagi M, Demizu Y, Nagano F et al (2018) Treatment outcomes of proton or carbon ion therapy for skull base chordoma: a retrospective study. Radiat Oncol 13(1):232. https://doi.org/10.1186/s13014-018-1173-0

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Hottinger AL, Bojaxhiu B, Ahlhelm F et al (2020) Prognostic impact of the “Sekhar grading system for cranial chordomas” in patients treated with pencil beam scanning proton therapy: an institutional analysis. Radiat Oncol 15(1):96. https://doi.org/10.1186/s13014-020-01547-x

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Iannalfi A, D’Ippolito E, Riva G et al (2021) 2020 Proton and carbon ion radiotherapy in skull base chordomas: a prospective study based on a dual particle and a patient-customized treatment strategy [published correction appears in Neuro Oncol. Neuro Oncol 22(9):1348–1358. https://doi.org/10.1093/neuonc/noaa067

    Article  CAS  Google Scholar 

  26. Basler L, Poel R, Schröder C et al (2020) Dosimetric analysis of local failures in skull-base chordoma and chondrosarcoma following pencil beam scanning proton therapy. Radiat Oncol 15(1):266. https://doi.org/10.1186/s13014-020-01711-3

    Article  PubMed Central  PubMed  Google Scholar 

  27. Metcalfe C, Muzaffar J, Kulendra K et al (2021) Chordomas and chondrosarcomas of the skull base: treatment and outcome analysis in a consecutive case series of 24 patients. World J Surg Oncol 19(1):68. https://doi.org/10.1186/s12957-021-02178-6

    Article  PubMed Central  PubMed  Google Scholar 

  28. Rutkowski MJ, Birk HS, Wood MD et al (2017) Metastatic clival chordoma: a case report of multiple extraneural metastases following resection and proton beam radiotherapy in a 5-year old boy. J Neurosurg Pediatr 19(5):531–537. https://doi.org/10.3171/2017.1.PEDS16549

    Article  PubMed  Google Scholar 

  29. Forsyth PA, Cascino TL, Shaw EG et al (1993) Intracranial chordomas: a clinicopathological and prognostic study of 51 cases. J Neurosurg 78(5):741–747. https://doi.org/10.3171/jns.1993.78.5.0741

    Article  CAS  PubMed  Google Scholar 

  30. Tamura T, Sato T, Kishida Y et al (2015) Outcome of clival chordomas after skull base surgeries with mean follow-up of 10 years. Fukushima J Med Sci 61(2):131–140. https://doi.org/10.5387/fms.2015-12

    Article  PubMed Central  PubMed  Google Scholar 

  31. Choi D, Gleeson M (2010) Surgery for chordomas of the craniocervical junction: lessons learned. Skull Base 20(1):41–45. https://doi.org/10.1055/s-0029-1242984

    Article  PubMed Central  PubMed  Google Scholar 

  32. Colli BO, Al-Mefty O (2001) Chordomas of the skull base: follow-up review and prognostic factors. Neurosurg Focus 10(3):E1. https://doi.org/10.3171/foc.2001.10.3.2

    Article  CAS  PubMed  Google Scholar 

  33. Gay E, Sekhar LN, Rubinstein E et al (1995) Chordomas and chondrosarcomas of the cranial base: results and follow-up of 60 patients. Neurosurgery 36(5):887–897. https://doi.org/10.1227/00006123-199505000-00001

    Article  CAS  PubMed  Google Scholar 

  34. Carpentier A, Polivka M, Blanquet A, Lot G, George B (2002) Suboccipital and cervical chordomas: the value of aggressive treatment at first presentation of the disease. J Neurosurg 97(5):1070–1077. https://doi.org/10.3171/jns.2002.97.5.1070

    Article  PubMed  Google Scholar 

  35. Munzenrider JE, Liebsch NJ (1999) Proton therapy for tumors of the skull base. Strahlenther Onkol 175(Suppl 2):57–63. https://doi.org/10.1007/BF03038890

    Article  PubMed  Google Scholar 

  36. Suit H, Goldberg S, Niemierko A et al (2003) Proton beams to replace photon beams in radical dose treatments. Acta Oncol 42(8):800–808. https://doi.org/10.1080/02841860310017676

    Article  PubMed  Google Scholar 

  37. Amichetti M, Cianchetti M, Amelio D, Enrici RM, Minniti G (2009) Proton therapy in chordoma of the base of the skull: a systematic review. Neurosurg Rev 32(4):403–416. https://doi.org/10.1007/s10143-009-0194-4

    Article  PubMed  Google Scholar 

  38. Matloob SA, Nasir HA, Choi D (2016) Proton beam therapy in the management of skull base chordomas: systematic review of indications, outcomes, and implications for neurosurgeons. Br J Neurosurg 30(4):382–387. https://doi.org/10.1080/02688697.2016.1181154

    Article  PubMed  Google Scholar 

  39. Alahmari M, Temel Y (2019) Skull base chordoma treated with proton therapy: a systematic review. Surg Neurol Int. 10:96. Published 2019 Jun 7. https://doi.org/10.25259/SNI-213-2019

  40. Di Maio S, Temkin N, Ramanathan D, Sekhar LN (2011) Current comprehensive management of cranial base chordomas: 10-year meta-analysis of observational studies. J Neurosurg 115(6):1094–1105. https://doi.org/10.3171/2011.7.JNS11355

    Article  PubMed  Google Scholar 

  41. Engelsman M, Schwarz M, Dong L (2013) Physics controversies in proton therapy. Semin Radiat Oncol 23(2):88–96. https://doi.org/10.1016/j.semradonc.2012.11.003

    Article  PubMed  Google Scholar 

  42. Jiang S, Wang J, Li H et al (2016) Novel hybrid scattering- and scanning-beam proton therapy approach. Int J Part Ther 3(1):37–50. https://doi.org/10.14338/IJPT-15-00014.1

    Article  PubMed Central  PubMed  Google Scholar 

  43. Grosshans DR, Zhu XR, Melancon A et al (2014) Spot scanning proton therapy for malignancies of the base of skull: treatment planning, acute toxicities, and preliminary clinical outcomes. Int J Radiat Oncol Biol Phys 90(3):540–546. https://doi.org/10.1016/j.ijrobp.2014.07.005

    Article  PubMed  Google Scholar 

  44. Ares C, Hug EB, Lomax AJ et al (2009) Effectiveness and safety of spot scanning proton radiation therapy for chordomas and chondrosarcomas of the skull base: first long-term report. Int J Radiat Oncol Biol Phys 75(4):1111–1118. https://doi.org/10.1016/j.ijrobp.2008.12.055

    Article  PubMed  Google Scholar 

  45. Benk V, Liebsch NJ, Munzenrider JE, Efird J, McManus P, Suit H (1995) Base of skull and cervical spine chordomas in children treated by high-dose irradiation. Int J Radiat Oncol Biol Phys 31(3):577–581. https://doi.org/10.1016/0360-3016(94)00395-2

    Article  CAS  PubMed  Google Scholar 

  46. Austin AM, Douglass MJJ, Nguyen GT, Penfold SN (2017) A radiobiological Markov simulation tool for aiding decision making in proton therapy referral. Phys Med 44:72–82. https://doi.org/10.1016/j.ejmp.2017.11.013

    Article  PubMed  Google Scholar 

  47. Schultz C, Goffi-Gomez MV, Pecora Liberman PH, Pellizzon AC, Carvalho AL (2010) Hearing loss and complaint in patients with head and neck cancer treated with radiotherapy. Arch Otolaryngol Head Neck Surg 136(11):1065–1069. https://doi.org/10.1001/archoto.2010.180

    Article  PubMed  Google Scholar 

  48. Austin AM, Douglass MJJ, Nguyen GT et al (2019) Cost-effectiveness of proton therapy in treating base of skull chordoma. Australas Phys Eng Sci Med 42(4):1091–1098. https://doi.org/10.1007/s13246-019-00810-0

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. University College of Medical Sciences and GTB Hospital, Delhi, India

    Bhavya Pahwa

  2. Department of Preventive Medicine, Loma Linda University, Loma Linda, CA, USA

    Khalid Medani

  3. Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, USA

    Victor M. Lu & Turki Elarjani

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  1. Bhavya Pahwa
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  2. Khalid Medani
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  3. Victor M. Lu
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  4. Turki Elarjani
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All authors contributed to the study conception and design. Material preparation and data collection and analysis were performed by Bhavya Pahwa, Khalid Medani, and Victor M Lu. The first draft of the manuscript was written by Bhavya Pahwa and Turki Elarjani, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Turki Elarjani.

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Pahwa, B., Medani, K., Lu, V.M. et al. Proton beam therapy for skull base chordomas: a systematic review of tumor control rates and survival rates. Neurosurg Rev 45, 3551–3563 (2022). https://doi.org/10.1007/s10143-022-01880-7

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