Advertisement

A multi-institutional analysis of clinical outcomes and patterns of care of 1p/19q codeleted oligodendrogliomas treated with adjuvant or salvage radiation therapy

  • Alexander J. Lin
  • Liam T. Kane
  • Jason K. Molitoris
  • Deborah R. Smith
  • Sonika Dahiya
  • Shahed N. Badiyan
  • Tony J. C. Wang
  • Tim J. Kruser
  • Jiayi HuangEmail author
Clinical Study

Abstract

Purpose

Practice patterns vary for adjuvant treatment of 1p/19q-codeleted oligodendroglioma patients. This study evaluates the outcomes of adjuvant (aRT) versus salvage radiation therapy (sRT) in a multi-institutional cohort.

Methods

Oligodendroglioma patients with confirmed 1p/19q codeletion who were treated with RT with or without chemotherapy from 2000 to 2017 at four tertiary centers were retrospectively reviewed. Overall survival (OS), post-RT progression-free survival (PFS), freedom-from-RT (FFRT), and radiation necrosis (RN) rates were determined using Kaplan–Meier analyses. OS1/PFS1 were defined from the initial surgery. OS2/PFS2 were defined from the RT start-date. Multivariable analyses (MVAs) of prognostic factors for OS and PFS were performed with Cox regression.

Results

One hundred eighty-six patients were identified: 124(67%) received aRT and 62(33%) received sRT; of sRT patients, 58% were observed after surgery while 42% received chemotherapy without aRT. The median time from initial diagnosis to sRT was 61 months, and 74% had reoperations before sRT. sRT had longer OS1 than aRT (94% vs. 69% at 10 years, p = 0.03) and PFS1 (10-year PFS of 80% vs. 68%, p = 0.03), though sRT was not associated with significantly different OS1/PFS1 on MVAs. Chemotherapy did not delay sRT compared to observation and had worse PFS2 (42% vs. 79% at 5 years, p = 0.08). Higher RT dose was not associated with improved clinical outcomes but was associated with higher symptomatic RN rate (15% vs. 0% at 2 years, p = 0.003).

Conclusions

Delaying RT for selected oligodendroglioma patients appears safe. Adjuvant chemotherapy does not delay sRT longer than observation and may be associated with worse PFS after RT.

Keywords

1p/19q codeletion Oligodendroglioma Radiation therapy Observation Chemotherapy 

Notes

Author contributions

All authors contributed to the experimental design, analysis, and interpretation of the data. All authors were involved in the writing of the manuscript at draft and revision stages, and have read and approved the final version.

Funding

None.

Compliance with ethical standards

Conflict of interest

S.B. had speaker's honoraria from Varian Medical Systems for topics outside this work. T.W. reports personal fees and non-financial support from AbbVie, non-financial support from Merck, personal fees from AstraZeneca, personal fees from Doximity, non-financial support from Novocure, personal fees and non-financial support from Elekta and personal fees from Wolters Kluwer, outside the submitted work. T.K. reports personal fees from AbbVie, AstraZeneca, and Varian Medical Systems, all outside the submitted work. J.H. reports research support from Pfizer and Cantex, personal fees from Viewray, outside the submitted work.

Supplementary material

11060_2019_3344_MOESM1_ESM.docx (17 kb)
Supplementary file1 (DOCX 16 kb)

References

  1. 1.
    Weller M, Van Den BM, Tonn JC et al (2018) Review european association for neuro-oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas. Lancet Oncol 18:e315–e329CrossRefGoogle Scholar
  2. 2.
    Wick W, Roth P, Hartmann C et al (2016) Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide. Neuro Oncol 18:1529–1537PubMedPubMedCentralGoogle Scholar
  3. 3.
    Schiff D, Van den Bent M, Vogelbaum MA et al (2019) Recent developments and future directions in adult lower-grade gliomas: society for neuro-oncology (SNO) and European Association of Neuro-Oncology (EANO) consensus. Neuro Oncol 21:837–853CrossRefGoogle Scholar
  4. 4.
    Cairncross G, Wang M, Shaw E et al (2013) Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. J Clin Oncol 31:337–343CrossRefGoogle Scholar
  5. 5.
    Van Den Bent MJ, Brandes AA, Taphoorn MJB et al (2013) Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. J Clin Oncol 31:344–350CrossRefGoogle Scholar
  6. 6.
    Buckner JC, Shaw EG, Pugh SL et al (2016) Radiation plus procarbazine, CCNU, and vincristine in low-grade glioma. N Engl J Med 374:1344–1355CrossRefGoogle Scholar
  7. 7.
    The Cancer Genome Atlas Research Network (2015) Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med 372:2481–2498CrossRefGoogle Scholar
  8. 8.
    Soffietti R, Baumert BG, Bello L et al (2010) Guidelines on management of low-grade gliomas: report of an EFNS-EANO task force. Eur J Neurol 17:1124–1133CrossRefGoogle Scholar
  9. 9.
    Wahl M, Phillips JJ, Molinaro AM et al (2017) Chemotherapy for adult low-grade gliomas: clinical outcomes by molecular subtype in a phase II study of adjuvant temozolomide. Neuro Oncol 19:242–251PubMedGoogle Scholar
  10. 10.
    Rudà R, Soffietti R (2017) Controversies in management of low-grade gliomas in light of new data from clinical trials. Neuro Oncol 19:143–144CrossRefGoogle Scholar
  11. 11.
    Acharya S, Robinson CG, Michalski JM et al (2018) Association of 1p/19q codeletion and radiation necrosis in adult cranial gliomas after proton or photon therapy. Int J Radiat Oncol Biol Phys 101:334–343CrossRefGoogle Scholar
  12. 12.
    Van Den Bent MJ, Afra D, De Witte O et al (2005) Long-term efficacy of early versus delayed radiotherapy for low-grade astrocytoma and oligodendroglioma in adults: the EORTC 22845 randomised trial. Lancet 366:985–990CrossRefGoogle Scholar
  13. 13.
    Shaw E, Berkey B, Coons S et al (2008) Recurrence following neurosurgeon-determined gross-total resection of adult supratentorial low-grade glioma: results of a prospective clinical trial. J Neurosurg 109:835–841CrossRefGoogle Scholar
  14. 14.
    Brown PD, Buckner JC, Uhm JH et al (2003) The neurocognitive effects of radiation in adult low-grade glioma patients. Neuro Oncol 5:161–167CrossRefGoogle Scholar
  15. 15.
    Johnson BE, Mazor T, Hong C et al (2014) Mutational analysis reveals the origin and therapy-driven evolution of recurrent glioma. Science 343:189–194CrossRefGoogle Scholar
  16. 16.
    Speirs CK, Simpson JR, Robinson CG et al (2015) Impact of 1p/19q codeletion and histology on outcomes of Anaplastic gliomas treated with radiation therapy and temozolomide. Int J Radiat Oncol Biol Phys 91:268–276CrossRefGoogle Scholar
  17. 17.
    Karim ABMF, Maat B, Hatlevoll R et al (1996) A randomized trial on dose-response in radiation therapy of low-grade cerebral glioma: European Organization for Research and Treatment of Cancer (EORTC) study 22844. Int J Radiat Oncol Biol Phys 36:549–556CrossRefGoogle Scholar
  18. 18.
    Shaw E, Arusell R, Scheithauer B et al (2002) Prospective randomized trial of low-versus high-dose radiation therapy in adults with supratentorial low-grade glioma: initial report of a North Central Cancer Treatment Group/Radiation Therapy Oncology Group/Eastern Cooperative Oncology Group Study. J Clin Oncol 20:2267–2276CrossRefGoogle Scholar
  19. 19.
    Horbinski C, Nikiforova MN, Hobbs J et al (2012) The importance of 10q status in an outcomes-based comparison between 1p/19q fluorescence in situ hybridization and polymerase chain reaction-based microsatellite loss of heterozygosity analysis of oligodendrogliomas. J Neuropathol Exp Neurol 71:73–82CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Alexander J. Lin
    • 1
  • Liam T. Kane
    • 2
  • Jason K. Molitoris
    • 3
  • Deborah R. Smith
    • 4
  • Sonika Dahiya
    • 5
  • Shahed N. Badiyan
    • 1
  • Tony J. C. Wang
    • 4
  • Tim J. Kruser
    • 2
  • Jiayi Huang
    • 1
    Email author
  1. 1.Department of Radiation Oncology, Center for Advanced MedicineWashington University School of MedicineSt. LouisUSA
  2. 2.Department of Radiation OncologyNorthwestern UniversityChicagoUSA
  3. 3.Department of Radiation OncologyUniversity of MarylandBaltimoreUSA
  4. 4.Department of Radiation OncologyColumbia UniversityNew YorkUSA
  5. 5.Department of Pathology and ImmunologyWashington University School of MedicineSt. LouisUSA

Personalised recommendations