Top

Journal of Neuro-Oncology

Published in:

01-11-2019 | Glioblastoma | Topic Review

Carbon ion radiotherapy in the treatment of gliomas: a review

Authors: Timothy D. Malouff, Jennifer L. Peterson, Anita Mahajan, Daniel M. Trifiletti

Published in: Journal of Neuro-Oncology | Issue 2/2019

Abstract

Introduction

Gliomas are among the most common primary brain malignancies, with a poor prognosis for high grade gliomas despite aggressive therapy. Carbon ions, which exhibit favorable biological and physical characteristics, have recently been studied in intracranial malignancies as a way to escalate dose to the tumor while minimizing dose to normal tissue.

Methods

Pubmed/Medline, SCOPUS, EMBASE, CINAHL and the Cochrane database were systematically reviewed using the search terms “carbon ion” and “glioma” or “glioblastoma” in August 2019. Out of 332 articles screened, 43 were included in this analysis.

Results

This comprehensive review describes the pertinent physics and radiation biology studies relevant to the treatment of gliomas with carbon ions and summarizes the important clinical studies for both high and low grade gliomas. Studies investigating carbon ions as both definitive radiotherapy and as a boost to traditional radiotherapy are reviewed. The use of carbon ion radiotherapy in the setting of recurrent disease is also described.

Conclusions

Carbon ion radiotherapy is both efficacious and safe based on early clinical studies. Current trials, including the CLEOPATRA and CINDERLLA trials, hope to define the role of carbon ion radiotherapy in the treatment of gliomas.

Adeberg S, Harrabi SB, Verma V, Bernhardt D, Grau N, Debus J, Rieken S (2017) Treatment of meningioma and glioma with protons and carbon ions. Radiat Oncol 12(1):193. https://doi.org/10.1186/s13014-017-0924-7 CrossRefPubMedPubMedCentral

Maucort-Boulch D, Baron MH, Pommier P, Weber DC, Mizoe JE, Rochat J, Boissel JP, Balosso J, Tsujii H, Amsallem E (2010) Rationale for carbon ion therapy in high-grade glioma based on a review and a meta-analysis of neutron beam trials. Cancer Radiother 14(1):34–41. https://doi.org/10.1016/j.canrad.2009.08.141 CrossRefPubMed

Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996. https://doi.org/10.1056/NEJMoa043330 CrossRefPubMed

Cantrell JN, Waddle MR, Rotman M, Peterson JL, Ruiz-Garcia H, Heckman MG, Quinones-Hinojosa A, Rosenfeld SS, Brown PD, Trifiletti DM (2019) Progress toward long-term survivors of glioblastoma. Mayo Clin Proc 94(7):1278–1286. https://doi.org/10.1016/j.mayocp.2018.11.031 CrossRefPubMed

Rackwitz T, Debus J (2019) Clinical applications of proton and carbon ion therapy. Semin Oncol. https://doi.org/10.1053/j.seminoncol.2019.07.005 CrossRefPubMed

Mohamad O, Sishc BJ, Saha J, Pompos A, Rahimi A, Story MD, Davis AJ, Kim DWN (2017) Carbon ion radiotherapy: a review of clinical experiences and preclinical research, with an emphasis on DNA damage/repair. Cancers 9(6):66. https://doi.org/10.3390/cancers9060066 CrossRefPubMedCentral

Chiblak S, Campos B, Gal Z, Tang Z, Unterberg A, Debus J, Herold-Mende C, Abdollahi A (2012) Photon vs. proton vs. carbon irradiation of glioma initiating cells. Int J Radiat Oncol Biol Phys 84(3):S677.CrossRef

Suzuki M, Kase Y, Kanai T, Ando K (1998) Correlation between cell death and induction of non-rejoining PCC breaks by carbon-ion beams. Adv Space Res 22(4):561–568CrossRefPubMed

Lopez Perez R, Nicolay NH, Wolf JC, Frister M, Schmezer P, Weber KJ, Huber PE (2019) DNA damage response of clinical carbon ion versus photon radiation in human glioblastoma cells. Radiother Oncol 133:77–86. https://doi.org/10.1016/j.radonc.2018.12.028 CrossRefPubMed

10.

Ferrandon S, Magne N, Battiston-Montagne P, Hau-Desbat NH, Diaz O, Beuve M, Constanzo J, Chargari C, Poncet D, Chautard E, Ardail D, Alphonse G, Rodriguez-Lafrasse C (2015) Cellular and molecular portrait of eleven human glioblastoma cell lines under photon and carbon ion irradiation. Cancer Lett 360(1):10–16. https://doi.org/10.1016/j.canlet.2015.01.025 CrossRefPubMed

11.

Morini J, Babini G, Barbieri S, Baiocco G, Ciocca M, Ivaldi GB, Liotta M, Molinelli S, Tabarelli de Fatis P, Ottolenghi A (2019) A comparison between X-ray and carbon ion irradiation in human neural stem cells. Radiat Prot Dosim 183(1–2):102–106. https://doi.org/10.1093/rpd/ncy231 CrossRef

12.

Jinno-Oue A, Shimizu N, Hamada N, Wada S, Tanaka A, Shinagawa M, Ohtsuki T, Mori T, Saha MN, Hoque AS, Islam S, Kogure K, Funayama T, Kobayashi Y, Hoshino H (2010) Irradiation with carbon ion beams induces apoptosis, autophagy, and cellular senescence in a human glioma-derived cell line. Int J Radiat Oncol Biol Phys 76(1):229–241. https://doi.org/10.1016/j.ijrobp.2009.08.054 CrossRefPubMed

13.

Oishi T, Sasaki A, Hamada N, Ishiuchi S, Funayama T, Sakashita T, Kobayashi Y, Nakano T, Nakazato Y (2008) Proliferation and cell death of human glioblastoma cells after carbon-ion beam exposure: morphologic and morphometric analyses. Neuropathology 28(4):408–416. https://doi.org/10.1111/j.1440-1789.2008.00899.x CrossRefPubMed

14.

Zhang L, Yan J, Liu Y, Zhao Q, Di C, Chao S, Jie L, Liu Y, Zhang H (2017) Contribution of caspase-independent pathway to apoptosis in malignant glioma induced by carbon ion beams. Oncol Rep 37(5):2994–3000. https://doi.org/10.3892/or.2017.5529 CrossRefPubMed

15.

Alphonse G, Maalouf M, Battiston-Montagne P, Ardail D, Beuve M, Rousson R, Taucher-Scholz G, Fournier C, Rodriguez-Lafrasse C (2013) p53-independent early and late apoptosis is mediated by ceramide after exposure of tumor cells to photon or carbon ion irradiation. BMC Cancer 13:151. https://doi.org/10.1186/1471-2407-13-151 CrossRefPubMedPubMedCentral

16.

Isono M, Yoshida Y, Takahashi A, Oike T, Shibata A, Kubota Y, Kanai T, Ohno T, Nakano T (2015) Carbon-ion beams effectively induce growth inhibition and apoptosis in human neural stem cells compared with glioblastoma A172 cells. J Radiat Res 56(5):856–861. https://doi.org/10.1093/jrr/rrv033 CrossRefPubMedPubMedCentral

17.

Schlaff CD, Krauze A, Belard A, O'Connell JJ, Camphausen KA (2014) Bringing the heavy: carbon ion therapy in the radiobiological and clinical context. Radiat Oncol 9(1):88. https://doi.org/10.1186/1748-717X-9-88 CrossRefPubMedPubMedCentral

18.

Liu Y, Liu Y, Sun C, Gan L, Zhang L, Mao A, Du Y, Zhou R, Zhang H (2015) Correction: carbon ion radiation inhibits glioma and endothelial cell migration induced by secreted VEGF. PLoS ONE 10(8):e0135508. https://doi.org/10.1371/journal.pone.0135508 CrossRefPubMedPubMedCentral

19.

Liu Y, Liu Y, Sun C, Gan L, Zhang L, Mao A, Du Y, Zhou R, Zhang H (2014) Carbon ion radiation inhibits glioma and endothelial cell migration induced by secreted VEGF. PLoS ONE 9(6):e98448. https://doi.org/10.1371/journal.pone.0098448 CrossRefPubMedPubMedCentral

20.

Stahler C, Roth J, Cordes N, Taucher-Scholz G, Mueller-Klieser W (2013) Impact of carbon ion irradiation on epidermal growth factor receptor signaling and glioma cell migration in comparison to conventional photon irradiation. Int J Radiat Biol 89(6):454–461. https://doi.org/10.3109/09553002.2013.766769 CrossRefPubMed

21.

Rieken S, Habermehl D, Wuerth L, Brons S, Mohr A, Lindel K, Weber K, Haberer T, Debus J, Combs SE (2012) Carbon ion irradiation inhibits glioma cell migration through downregulation of integrin expression. Int J Radiat Oncol Biol Phys 83(1):394–399. https://doi.org/10.1016/j.ijrobp.2011.06.2004 CrossRefPubMed

22.

Rieken S, Habermehl D, Wurth L, Mohr A, Lindel K, Weber K, Haberer T, Debus J, Combs SE Carbon ion irradiation with or without the addition of cilengitide is an effective inhibitor of integrine-mediated tumor cell migration. In: 9th Meeting of the European Association of NeuroOncology, Maastricht, Netherlands, September 16–19, 2010 2010.

23.

Eke I, Storch K, Kastner I, Vehlow A, Faethe C, Mueller-Klieser W, Taucher-Scholz G, Temme A, Schackert G, Cordes N (2012) Three-dimensional invasion of human glioblastoma cells remains unchanged by X-ray and carbon ion irradiation in vitro. Int J Radiat Oncol Biol Phys 84(4):e515–523. https://doi.org/10.1016/j.ijrobp.2012.06.012 CrossRefPubMed

24.

Hasegawa M, Asakawa I, Katayama E, Inoue E, Tamamoto T, Okada H, Kato S, Murakami T, Ishiuchi S, Nakano T (2011) IAP and NF-kappaB activation induced by carbon ion beams in human radioresistant glioblastoma cells with mutant-type p53 in vivo. Int J radiat Oncol Biol Phys 81(12):S724–S725CrossRef

25.

Facoetti A, Nano R (2014) Glioblastoma stem cells radioresistance: Evaluation of the potential benefits from carbon ion irradiation. In: 9th International Conference of Anticancer Research, Sithonia Greece, October 6–10, 2014 2014.

26.

Chiblak S, Tang Z, Campos B, Gal Z, Unterberg A, Debus J, Herold-Mende C, Abdollahi A (2016) Radiosensitivity of patient-derived glioma stem cell 3-dimensional cultures to photon, proton, and carbon irradiation. Int J Radiat Oncol Biol Phys 95(1):112–119. https://doi.org/10.1016/j.ijrobp.2015.06.015 CrossRefPubMed

27.

Takahashi M, Fujimori A (2014) Carbon ion beam is more effective to induce cell death in sphere-type A172 human glioblastoma cells compared with X-rays. Int J Radiat Biol 90(12):1125–1132. https://doi.org/10.3109/09553002.2014.927933 CrossRefPubMed

28.

Matsumoto H, Hayashi S, Hatashita M, Shioura H, Ohtsubo T, Kitai R, Ohnishi T, Yukawa O, Furusawa Y, Kano E (2000) Induction of radioresistance to accelerated carbon-ion beams in recipient cells by nitric oxide excreted from irradiated donor cells of human glioblastoma. Int J Radiat Biol 76(12):1649–1657CrossRefPubMed

29.

Combs SE, Bohl J, Elsasser T, Weber KJ, Schulz-Ertner D, Debus J, Weyrather WK (2009) Radiobiological evaluation and correlation with the local effect model (LEM) of carbon ion radiation therapy and temozolomide in glioblastoma cell lines. Int J Radiat Biol 85(2):126–137. https://doi.org/10.1080/09553000802641151 CrossRefPubMed

30.

Harrabi S, Combs SE, Brons S, Haberer T, Debus J, Weber KJ (2013) Temozolomide in combination with carbon ion or photon irradiation in glioblastoma multiforme cell lines—does scheduling matter? Int J Radiat Biol 89(9):692–697. https://doi.org/10.3109/09553002.2013.791406 CrossRefPubMed

31.

Schlaich F, Brons S, Haberer T, Debus J, Combs SE, Weber KJ (2013) Comparison of the effects of photon versus carbon ion irradiation when combined with chemotherapy in vitro. Radiat Oncol 8:260. https://doi.org/10.1186/1748-717X-8-260 CrossRefPubMedPubMedCentral

32.

Combs SE, Zipp L, Rieken S, Habermehl D, Brons S, Winter M, Haberer T, Debus J, Weber KJ (2012) In vitro evaluation of photon and carbon ion radiotherapy in combination with chemotherapy in glioblastoma cells. Radiat Oncol 7:9. https://doi.org/10.1186/1748-717X-7-9 CrossRefPubMedPubMedCentral

33.

Combs SE, Kessel K, Habermehl D, Haberer T, Jakel O, Debus J (2013) Proton and carbon ion radiotherapy for primary brain tumors and tumors of the skull base. Acta Oncol 52(7):1504–1509. https://doi.org/10.3109/0284186X.2013.818255 CrossRefPubMed

34.

Rieken S, Habermehl D, Haberer T, Jaekel O, Debus J, Combs SE (2012) Proton and carbon ion radiotherapy for primary brain tumors delivered with active raster scanning at the Heidelberg Ion Therapy Center (HIT): early treatment results and study concepts. Radiat Oncol 7:41. https://doi.org/10.1186/1748-717X-7-41 CrossRefPubMedPubMedCentral

35.

Rieken S, Habermehl D, Nikoghosyan A, Jensen A, Haberer T, Jakel O, Munter MW, Welzel T, Debus J, Combs SE (2011) Assessment of early toxicity and response in patients treated with proton and carbon ion therapy at the Heidelberg ion therapy center using the raster scanning technique. Int J Radiat Oncol Biol Phys 81(5):e793–801. https://doi.org/10.1016/j.ijrobp.2010.12.018 CrossRefPubMed

36.

Mizoe JE, Tsujii H, Hasegawa A, Yanagi T, Takagi R, Kamada T, Tsuji H, Takakura K, Organizing Committee of the Central Nervous System Tumor Working G (2007) Phase I/II clinical trial of carbon ion radiotherapy for malignant gliomas: combined X-ray radiotherapy, chemotherapy, and carbon ion radiotherapy. Int J Radiat Oncol Biol Phys 69(2):390–396. https://doi.org/10.1016/j.ijrobp.2007.03.003 CrossRef

37.

Wang X, Zhang Q, Zhang H, Gao J, Ran J, Li Q, Liu R, Wei S, Luo H, Wei X, Liu Z, Sun S, Xu L The preliminary results of carbon ion radiotherapy in 60 patients. In: ESTRO 35, Turin, Italy, April 29-May 3, 2016 2016.

38.

Hadziahmetovic M, Shirai K, Chakravarti A (2011) Recent advancements in multimodality treatment of gliomas. Future Oncol 7(10):1169–1183. https://doi.org/10.2217/fon.11.102 CrossRefPubMed

39.

Combs SE, Bruckner T, Mizoe JE, Kamada T, Tsujii H, Kieser M, Debus J (2013) Comparison of carbon ion radiotherapy to photon radiation alone or in combination with temozolomide in patients with high-grade gliomas: explorative hypothesis-generating retrospective analysis. Radiother Oncol 108(1):132–135. https://doi.org/10.1016/j.radonc.2013.06.026 CrossRefPubMed

40.

Combs SE, Kieser M, Rieken S, Habermehl D, Jakel O, Haberer T, Nikoghosyan A, Haselmann R, Unterberg A, Wick W, Debus J (2010) Randomized phase II study evaluating a carbon ion boost applied after combined radiochemotherapy with temozolomide versus a proton boost after radiochemotherapy with temozolomide in patients with primary glioblastoma: the CLEOPATRA trial. BMC Cancer 10:478. https://doi.org/10.1186/1471-2407-10-478 CrossRefPubMedPubMedCentral

41.

clinicaltrials.gov (2019) Carbon ion radiotherapy for primary glaioma (CLEOPATRA); NCT01165671. https://clinicaltrials.gov/ct2/show/NCT01165671?term=CLEOPATRA&rank=1.

42.

Kong L, Gao J, Hu J, Lu R, Yang J, Qiu X, Hu W, Lu JJ (2019) Carbon ion radiotherapy boost in the treatment of glioblastoma: a randomized phase I/III clinical trial. Cancer Commun 39(1):5. https://doi.org/10.1186/s40880-019-0351-2 CrossRef

43.

Combs SE, Ellerbrock M, Haberer T, Habermehl D, Hoess A, Jakel O, Jensen A, Klemm S, Munter M, Naumann J, Nikoghosyan A, Oertel S, Parodi K, Rieken S, Debus J (2010) Heidelberg ion therapy center (HIT): initial clinical experience in the first 80 patients. Acta Oncol 49(7):1132–1140. https://doi.org/10.3109/0284186X.2010.498432 CrossRefPubMed

44.

Hasegawa A, Mizoe JE, Tsujii H, Kamada T, Jingu K, Iwadate Y, Nakazato Y, Matsutani M, Takakura K, Organizing Committee of the Central Nervous System Tumor Working G (2012) Experience with carbon ion radiotherapy for WHO Grade 2 diffuse astrocytomas. Int J Radiat Oncol Biol Phys 83(1):100–106. https://doi.org/10.1016/j.ijrobp.2011.06.1952 CrossRef

45.

Combs SE, Burkholder I, Edler L, Rieken S, Habermehl D, Jakel O, Haberer T, Haselmann R, Unterberg A, Wick W, Debus J (2010) Randomised phase I/II study to evaluate carbon ion radiotherapy versus fractionated stereotactic radiotherapy in patients with recurrent or progressive gliomas: the CINDERELLA trial. BMC Cancer 10:533. https://doi.org/10.1186/1471-2407-10-533 CrossRefPubMedPubMedCentral

46.

Mahasittiwat P, Mizoe JE, Hasegawa A, Ishikawa H, Yoshikawa K, Mizuno H, Yanagi T, Takagi R, Pattaranutaporn P, Tsujii H (2008) l-[METHYL-(11)C] methionine positron emission tomography for target delineation in malignant gliomas: impact on results of carbon ion radiotherapy. Int J Radiat Oncol Biol Phys 70(2):515–522. https://doi.org/10.1016/j.ijrobp.2007.06.071 CrossRefPubMed

47.

Debus C, Waltenberger M, Floca R, Afshar-Oromieh A, Bougatf N, Adeberg S, Heiland S, Bendszus M, Wick W, Rieken S, Haberkorn U, Debus J, Knoll M, Abdollahi A (2018) Impact of (18)F-FET PET on target volume definition and tumor progression of recurrent high grade glioma treated with carbon-ion radiotherapy. Sci Rep 8(1):7201. https://doi.org/10.1038/s41598-018-25350-7 CrossRefPubMedPubMedCentral

48.

Bauer J, Unholtz D, Sommerer F, Kurz C, Haberer T, Herfarth K, Welzel T, Combs SE, Debus J, Parodi K (2013) Implementation and initial clinical experience of offline PET/CT-based verification of scanned carbon ion treatment. Radiother Oncol 107(2):218–226. https://doi.org/10.1016/j.radonc.2013.02.018 CrossRefPubMed

49.

Nischwitz SP, Bauer J, Welzel T, Rief H, Jakel O, Haberer T, Frey K, Debus J, Parodi K, Combs SE, Rieken S (2015) Clinical implementation and range evaluation of in vivo PET dosimetry for particle irradiation in patients with primary glioma. Radiother Oncol 115(2):179–185. https://doi.org/10.1016/j.radonc.2015.03.022 CrossRefPubMed

50.

Niyazi M, Brada M, Chalmers AJ, Combs SE, Erridge SC, Fiorentino A, Grosu AL, Lagerwaard FJ, Minniti G, Mirimanoff RO, Ricardi U, Short SC, Weber DC, Belka C (2016) ESTRO-ACROP guideline "target delineation of glioblastomas". Radiother Oncol 118(1):35–42. https://doi.org/10.1016/j.radonc.2015.12.003 CrossRefPubMed

Title: Carbon ion radiotherapy in the treatment of gliomas: a review
Authors: Timothy D. Malouff
Jennifer L. Peterson
Anita Mahajan
Daniel M. Trifiletti
Publication date: 01-11-2019
Publisher: Springer US
Keywords: Glioblastoma
Glioma
Glioma
Glioblastoma
Radiotherapy
Glioblastoma
Glioma
Published in: Journal of Neuro-Oncology / Issue 2/2019
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-019-03303-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Carbon ion radiotherapy in the treatment of gliomas: a review

Abstract

Introduction

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 2/2019

Actionable FGFR1 and BRAF mutations in adult circumscribed gliomas

Risk factors for intraoperative stimulation-related seizures during awake surgery: an analysis of 109 consecutive patients

Communicating hydrocephalus after radiosurgery for vestibular schwannomas: does technique matter? A systematic review and meta-analysis

Cognitive functioning and predictors thereof in patients with 1–10 brain metastases selected for stereotactic radiosurgery

Oligodendroglioma confers higher risk of radiation necrosis

Cerebrospinal fluid VEGF levels and angiogenic capacity as potential prognostic markers in patients with gliomas: a pilot study