Skip to main content
Top
Published in: Journal of Neuro-Oncology 3/2020

01-05-2020 | Radiotherapy | Topic Review

Carbon ion radiotherapy for skull base chordomas and chondrosarcomas: a systematic review and meta-analysis of local control, survival, and toxicity outcomes

Authors: Victor M. Lu, Kyle P. O’Connor, Anita Mahajan, Matthew L. Carlson, Jamie J. Van Gompel

Published in: Journal of Neuro-Oncology | Issue 3/2020

Login to get access

Abstract

Background

Carbon ion radiotherapy (CIRT) is an emerging radiation therapy to treat skull base chordomas and chondrosarcomas. To date, its use is limited to a few centers around the world, and there has been no attempt to systematically evaluate survival and toxicity outcomes reported in the literature. Correspondingly, the aim of this study was to qualitatively and quantitatively assess these outcomes.

Methods

A systematic search of seven electronic databases from inception to November 2019 was conducted following PRISMA guidelines. Articles were screened against pre-specified criteria. Outcomes were then pooled by random-effects meta-analyses of proportions.

Results

A total of nine studies provided unique metadata for assessment, with six originating from Heidelberg, Germany. The surveyed cohort size was 632 patients, with 389 (62%) chordomas and 243 (38%) chondrosarcomas of the skull base. Across all studies, median cohort age at therapy and female proportion were 46 years and 51% respectively. Estimates of local control incidence at 1-, 5-, and 10-years in chordoma-only studies were 99%, 80%, and 56%, and in chondrosarcoma-only studies were 99%, 89%, and 88%. Estimates of overall survival probability at 1-, 5-, and 10-years in chordoma-only studies were 100%, 94%, and 78%, and in chondrosarcoma-only studies were 99%, 95%, and 79%. The incidence of early and late toxicity (Grade ≥ 3) ranged from 0 to 4% across all study groups.

Conclusions

The emerging use of CIRT to treat skull base chordomas and chondrosarcomas appear promising with regard to tumor control, overall survival, and risk profile of early and late toxicity. The current literature suffers from the fact only a few centers in the world currently employ this technology.
Appendix
Available only for authorised users
Literature
3.
go back to reference Heffelfinger MJ, Dahlin DC, MacCarty CS, Beabout JW (1973) Chordomas and cartilaginous tumors at the skull base. Cancer 32(2):410–420CrossRef Heffelfinger MJ, Dahlin DC, MacCarty CS, Beabout JW (1973) Chordomas and cartilaginous tumors at the skull base. Cancer 32(2):410–420CrossRef
10.
go back to reference Schulz-Ertner D, Haberer T, Jakel O, Thilmann C, Kramer M, Enghardt W, Kraft G, Wannenmacher M, Debus J (2002) Radiotherapy for chordomas and low-grade chondrosarcomas of the skull base with carbon ions. Int J Radiat Oncol Biol Phys 53(1):36–42CrossRef Schulz-Ertner D, Haberer T, Jakel O, Thilmann C, Kramer M, Enghardt W, Kraft G, Wannenmacher M, Debus J (2002) Radiotherapy for chordomas and low-grade chondrosarcomas of the skull base with carbon ions. Int J Radiat Oncol Biol Phys 53(1):36–42CrossRef
24.
go back to reference Moher D, Liberati A, Tetzlaff J, Althman D (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PloS Med 6(7):e1000097CrossRef Moher D, Liberati A, Tetzlaff J, Althman D (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PloS Med 6(7):e1000097CrossRef
27.
go back to reference Higgins JPT, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. Br Med J 327(7414):557–560CrossRef Higgins JPT, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. Br Med J 327(7414):557–560CrossRef
28.
go back to reference Atkins D, Best D, Briss PA, Eccles M, Falck-Ytter Y, Flottorp S, Guyatt GH, Harbour RT, Haugh MC, Henry D, Hill S, Jaeschke R, Leng G, Liberati A, Magrini N, Mason J, Middleton P, Mrukowicz J, O'Connell D, Oxman AD, Phillips B, Schunemann HJ, Edejer T, Varonen H, Vist GE, Williams JW Jr, Zaza S (2004) Grading quality of evidence and strength of recommendations. BMJ (Clin Res ed) 328(7454):1490. https://doi.org/10.1136/bmj.328.7454.1490 CrossRef Atkins D, Best D, Briss PA, Eccles M, Falck-Ytter Y, Flottorp S, Guyatt GH, Harbour RT, Haugh MC, Henry D, Hill S, Jaeschke R, Leng G, Liberati A, Magrini N, Mason J, Middleton P, Mrukowicz J, O'Connell D, Oxman AD, Phillips B, Schunemann HJ, Edejer T, Varonen H, Vist GE, Williams JW Jr, Zaza S (2004) Grading quality of evidence and strength of recommendations. BMJ (Clin Res ed) 328(7454):1490. https://​doi.​org/​10.​1136/​bmj.​328.​7454.​1490 CrossRef
29.
go back to reference Wells G, Shea B, O’connell D, Peterson J, Welch V, Losos M, Tugwell P (2016) The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa Hospital Research Institute, Ottawa. 2009. Available in March Wells G, Shea B, O’connell D, Peterson J, Welch V, Losos M, Tugwell P (2016) The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa Hospital Research Institute, Ottawa. 2009. Available in March
31.
go back to reference Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50(4):1088–1101CrossRef Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50(4):1088–1101CrossRef
32.
go back to reference Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ (Clin Res ed) 315(7109):629–634CrossRef Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ (Clin Res ed) 315(7109):629–634CrossRef
33.
go back to reference Duval S, Tweedie R (2000) Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 56(2):455–463CrossRef Duval S, Tweedie R (2000) Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 56(2):455–463CrossRef
34.
go back to reference Mattke M, Vogt K, Bougatf N, Welzel T, Oelmann-Avendano J, Hauswald H, Jensen A, Ellerbrock M, Jäkel O, Haberer T, Herfarth K, Debus J, Uhl M (2018) High control rates of proton- and carbon-ion-beam treatment with intensity-modulated active raster scanning in 101 patients with skull base chondrosarcoma at the Heidelberg Ion Beam Therapy Center. Cancer 124(9):2036–2044. https://doi.org/10.1002/cncr.31298 CrossRefPubMed Mattke M, Vogt K, Bougatf N, Welzel T, Oelmann-Avendano J, Hauswald H, Jensen A, Ellerbrock M, Jäkel O, Haberer T, Herfarth K, Debus J, Uhl M (2018) High control rates of proton- and carbon-ion-beam treatment with intensity-modulated active raster scanning in 101 patients with skull base chondrosarcoma at the Heidelberg Ion Beam Therapy Center. Cancer 124(9):2036–2044. https://​doi.​org/​10.​1002/​cncr.​31298 CrossRefPubMed
35.
36.
go back to reference Uhl M, Mattke M, Welzel T, Roeder F, Oelmann J, Habl G, Jensen A, Ellerbrock M, Jäkel O, Haberer T, Herfarth K, Debus J (2014) Highly effective treatment of skull base chordoma with carbon ion irradiation using a raster scan technique in 155 patients: first long-term results. Cancer 120(21):3410–3417. https://doi.org/10.1002/cncr.28877 CrossRefPubMed Uhl M, Mattke M, Welzel T, Roeder F, Oelmann J, Habl G, Jensen A, Ellerbrock M, Jäkel O, Haberer T, Herfarth K, Debus J (2014) Highly effective treatment of skull base chordoma with carbon ion irradiation using a raster scan technique in 155 patients: first long-term results. Cancer 120(21):3410–3417. https://​doi.​org/​10.​1002/​cncr.​28877 CrossRefPubMed
37.
go back to reference Rieken S, Habermehl D, Nikoghosyan A, Jensen A, Haberer T, Jäkel O, Münter 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–e801. https://doi.org/10.1016/j.ijrobp.2010.12.018 CrossRefPubMed Rieken S, Habermehl D, Nikoghosyan A, Jensen A, Haberer T, Jäkel O, Münter 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–e801. https://​doi.​org/​10.​1016/​j.​ijrobp.​2010.​12.​018 CrossRefPubMed
43.
go back to reference Weber DC, Murray F, Combescure C, Calugaru V, Alapetite C, Albertini F, Bolle S, Goudjil F, Pica A, Walser M, Mammar H, Bachtiary B, Lomax T, Noël G, Dendale R, Feuvret L (2018) Long term outcome of skull-base chondrosarcoma patients treated with high-dose proton therapy with or without conventional radiation therapy. Radiother Oncol 129(3):520–526. https://doi.org/10.1016/j.radonc.2018.06.040 CrossRefPubMed Weber DC, Murray F, Combescure C, Calugaru V, Alapetite C, Albertini F, Bolle S, Goudjil F, Pica A, Walser M, Mammar H, Bachtiary B, Lomax T, Noël G, Dendale R, Feuvret L (2018) Long term outcome of skull-base chondrosarcoma patients treated with high-dose proton therapy with or without conventional radiation therapy. Radiother Oncol 129(3):520–526. https://​doi.​org/​10.​1016/​j.​radonc.​2018.​06.​040 CrossRefPubMed
Metadata
Title
Carbon ion radiotherapy for skull base chordomas and chondrosarcomas: a systematic review and meta-analysis of local control, survival, and toxicity outcomes
Authors
Victor M. Lu
Kyle P. O’Connor
Anita Mahajan
Matthew L. Carlson
Jamie J. Van Gompel
Publication date
01-05-2020
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 3/2020
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-020-03464-1

Other articles of this Issue 3/2020

Journal of Neuro-Oncology 3/2020 Go to the issue