Journal of Neuro-Oncology

, Volume 145, Issue 1, pp 75–83 | Cite as

Receipt of brachytherapy is an independent predictor of survival in glioblastoma in the Surveillance, Epidemiology, and End Results database

  • Jiri BartekJr
  • Ali A. Alattar
  • Sanjay Dhawan
  • Jun Ma
  • Tomoyuki Koga
  • Peter Nakaji
  • Kathryn E. Dusenbery
  • Clark C. ChenEmail author
Clinical Study



There has been a resurgence of interest in brachytherapy as a treatment for glioblastoma, with several currently ongoing clinical trials. To provide a foundation for the analysis of these trials, we analyze the Surveillance, Epidemiology, and End Results (SEER) database to determine whether receipt of brachytherapy conveys a survival benefit independent of traditional prognostic factors.

Materials and methods

We identified 60,456 glioblastoma patients, of whom 362 underwent brachytherapy. We grouped patients based on receipt of brachytherapy and compared clinical and demographic variables between groups using Student’s t-test and Pearson’s chi-squared test. We assessed survival using Kaplan–Meier curves and Cox proportional hazards models.


Median overall survival was 16 months in patients who received brachytherapy compared to 9 months in those who did not (log-rank p < 0.001). Patients who underwent brachytherapy tended to be younger (p < 0.001), suffered from smaller tumors (< 4 cm, p < 0.001), and were more likely to have undergone gross total resection (GTR, p < 0.001). In univariable Cox models, these variables were independently associated with improved overall survival. Additionally, improved survival was associated with known receipt of chemotherapy (HR 0.459, p < 0.001), external beam radiation (HR 0.447, p < 0.001), and brachytherapy (HR 0.637, p < 0.001). The association between brachytherapy and improved survival remained robust (HR 0.859, p = 0.031) in a multivariable model that adjusted for patient age, tumor size, tumor location, GTR, receipt of chemotherapy, and receipt of external beam radiation.


Our SEER analysis indicates that brachytherapy is associated with improved survival in glioblastoma after controlling for age, tumor size/location, extent of resection, chemotherapy, and external beam radiation.


Brachytherapy Glioblastoma Surveillance, Epidemiology, and End Results (SEER) Survival 




Compliance with ethical standards

Conflict of interest

All authors declare no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the Ethical Standards of the Institutional and/or National Research Committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.


  1. 1.
    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, European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Group, National Cancer Institute of Canada Clinical Trials Group (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996. CrossRefPubMedGoogle Scholar
  2. 2.
    Gaspar LE, Fisher BJ, Macdonald DR, LeBer DV, Halperin EC, Schold SC Jr, Cairncross JG (1992) Supratentorial malignant glioma: patterns of recurrence and implications for external beam local treatment. Int J Radiat Oncol Biol Phys 24(1):55–57CrossRefPubMedGoogle Scholar
  3. 3.
    Adkison JB, Thomadsen B, Howard SP (2008) Systemic iodine 125 activity after GliaSite brachytherapy: safety considerations. Brachytherapy 7(1):43–46. CrossRefPubMedGoogle Scholar
  4. 4.
    Bernstein M, Laperriere N, Leung P, McKenzie S (1990) Interstitial brachytherapy for malignant brain tumors: preliminary results. Neurosurgery 26(3):371–379; discussion 379–380CrossRefPubMedGoogle Scholar
  5. 5.
    Bernstein M, Laperriere N, Glen J, Leung P, Thomason C, Landon AE (1994) Brachytherapy for recurrent malignant astrocytoma. Int J Radiat Oncol Biol Phys 30(5):1213–1217CrossRefPubMedGoogle Scholar
  6. 6.
    Gutin PH, Leibel SA, Wara WM, Choucair A, Levin VA, Philips TL, Silver P, Da Silva V, Edwards MS, Davis RL et al (1987) Recurrent malignant gliomas: survival following interstitial brachytherapy with high-activity iodine-125 sources. J Neurosurg 67(6):864–873. CrossRefPubMedGoogle Scholar
  7. 7.
    Gutin PH, Hosobuchi Y, Phillips TL, Stupar TA (1981) Stereotactic interstitial irradiation for the treatment of brain tumors. Cancer Treat Rep 65(Suppl 2):103–106PubMedGoogle Scholar
  8. 8.
    Gutin PH, Phillips TL, Wara WM, Leibel SA, Hosobuchi Y, Levin VA, Weaver KA, Lamb S (1984) Brachytherapy of recurrent malignant brain tumors with removable high-activity iodine-125 sources. J Neurosurg 60(1):61–68. CrossRefPubMedGoogle Scholar
  9. 9.
    Gutin PH, Prados MD, Phillips TL, Wara WM, Larson DA, Leibel SA, Sneed PK, Levin VA, Weaver KA, Silver P et al (1991) External irradiation followed by an interstitial high activity iodine-125 implant “boost” in the initial treatment of malignant gliomas: NCOG Study 6G–82-2. Int J Radiat Oncol Biol Phys 21(3):601–606CrossRefPubMedGoogle Scholar
  10. 10.
    Hitchon PW, VanGilder JC, Wen BC, Jani S (1992) Brachytherapy for malignant recurrent and untreated gliomas. Stereotact Funct Neurosurg 59(1–4):174–178. CrossRefPubMedGoogle Scholar
  11. 11.
    Hosobuchi Y, Phillips TL, Stupar TA, Gutin PH (1980) Interstitial brachytherapy of primary brain tumors. Preliminary report J Neurosurg 53(5):613–617. CrossRefPubMedGoogle Scholar
  12. 12.
    Kickingereder P, Hamisch C, Suchorska B, Galldiks N, Visser-Vandewalle V, Goldbrunner R, Kocher M, Treuer H, Voges J, Ruge MI (2014) Low-dose rate stereotactic iodine-125 brachytherapy for the treatment of inoperable primary and recurrent glioblastoma: single-center experience with 201 cases. J Neurooncol 120(3):615–623. CrossRefPubMedGoogle Scholar
  13. 13.
    Laperriere NJ, Leung PM, McKenzie S, Milosevic M, Wong S, Glen J, Pintilie M, Bernstein M (1998) Randomized study of brachytherapy in the initial management of patients with malignant astrocytoma. Int J Radiat Oncol Biol Phys 41(5):1005–1011CrossRefPubMedGoogle Scholar
  14. 14.
    Loeffler JS, Alexander E III, Hochberg FH, Wen PY, Morris JH, Schoene WC, Siddon RL, Morse RH, Black PM (1990) Clinical patterns of failure following stereotactic interstitial irradiation for malignant gliomas. Int J Radiat Oncol Biol Phys 19(6):1455–1462CrossRefPubMedGoogle Scholar
  15. 15.
    Lucas GL, Luxton G, Cohen D, Petrovich Z, Langholz B, Apuzzo ML, Sapozink MD (1991) Treatment results of stereotactic interstitial brachytherapy for primary and metastatic brain tumors. Int J Radiat Oncol Biol Phys 21(3):715–721CrossRefPubMedGoogle Scholar
  16. 16.
    Malkin MG (1994) Interstitial brachytherapy of malignant gliomas: the Memorial Sloan-Kettering Cancer Center experience. Recent Results Cancer Res 135:117–125CrossRefPubMedGoogle Scholar
  17. 17.
    Prados MD, Gutin PH, Phillips TL, Wara WM, Sneed PK, Larson DA, Lamb SA, Ham B, Malec MK, Wilson CB (1992) Interstitial brachytherapy for newly diagnosed patients with malignant gliomas: the UCSF experience. Int J Radiat Oncol Biol Phys 24(4):593–597CrossRefPubMedGoogle Scholar
  18. 18.
    Selker RG, Shapiro WR, Burger P, Blackwood MS, Arena VC, Gilder JC, Malkin MG, Mealey Jr JJ, Neal JH, Olson J, Robertson JT, Barnett GH, Bloomfield S, Albright R, Hochberg FH, Hiesiger E, Green S, Brain Tumor Cooperative Group (2002) The Brain Tumor Cooperative Group NIH Trial 87–01: a randomized comparison of surgery, external radiotherapy, and carmustine versus surgery, interstitial radiotherapy boost, external radiation therapy, and carmustine. Neurosurgery 51(2):343–355; discussion 355–347CrossRefPubMedGoogle Scholar
  19. 19.
    Sneed PK, Prados MD, McDermott MW, Larson DA, Malec MK, Lamborn KR, Davis RL, Weaver KA, Wara WM, Phillips TL et al (1995) Large effect of age on the survival of patients with glioblastoma treated with radiotherapy and brachytherapy boost. Neurosurgery 36(5):898–903; discussion 903–894CrossRefPubMedGoogle Scholar
  20. 20.
    Waters JD, Rose B, Gonda DD, Scanderbeg DJ, Russell M, Alksne JF, Murphy K, Carter BS, Lawson J, Chen CC (2013) Immediate post-operative brachytherapy prior to irradiation and temozolomide for newly diagnosed glioblastoma. J Neurooncol 113(3):467–477. CrossRefPubMedGoogle Scholar
  21. 21.
    Welsh J, Sanan A, Gabayan AJ, Green SB, Lustig R, Burri S, Kwong E, Stea B (2007) GliaSite brachytherapy boost as part of initial treatment of glioblastoma multiforme: a retrospective multi-institutional pilot study. Int J Radiat Oncol Biol Phys 68(1):159–165. CrossRefPubMedGoogle Scholar
  22. 22.
    Youssef E, Nakaji P, Thomas T, McBride H, Fram E, Brachman D (2017) SCDT-36. Novel modular, permanently implanted collagen-based device for intraoperative brachytherapy in patients with central nervous system tumors. Neuro-oncology 19(Suppl. 6):vi272CrossRefPubMedCentralGoogle Scholar
  23. 23.
    Barbarite E, Sick JT, Berchmans E, Bregy A, Shah AH, Elsayyad N, Komotar RJ (2017) The role of brachytherapy in the treatment of glioblastoma multiforme. Neurosurg Rev 40(2):195–211. CrossRefPubMedGoogle Scholar
  24. 24.
    Gutin PH, Phillips TL, Hosobuchi Y, Wara WM, MacKay AR, Weaver KA, Lamb S, Hurst S (1981) Permanent and removable implants for the brachytherapy of brain tumors. Int J Radiat Oncol Biol Phys 7(10):1371–1381CrossRefPubMedGoogle Scholar
  25. 25.
    Carroll KT, Bryant AK, Hirshman B, Alattar AA, Joshi R, Gabel B, Carter BS, Harismendy O, Vaida F, Chen CC (2018) Interaction between the contributions of tumor location, tumor grade, and patient age to the survival benefit associated with gross total resection. World Neurosurg 111:e790–e798. CrossRefPubMedGoogle Scholar
  26. 26.
    SEER Program and Staging Manual 2018. Radiation NAACCR Item#:1360. NAACCR Name: RX Summ-Radiation (2018)Google Scholar
  27. 27.
    Alattar AA, Carroll KT, Bryant AK, Hirshman B, Joshi R, Carter BS, Harismendy O, Chen CC (2019) Prognostic importance of age, tumor location, and tumor grade in Grade II astrocytomas: an integrated analysis of the Cancer Genome Atlas and the Surveillance, Epidemiology, and End Results database. World Neurosurg 121:e411–e418. CrossRefPubMedGoogle Scholar
  28. 28.
    Ribas A, Hamid O, Daud A, Hodi FS, Wolchok JD, Kefford R, Joshua AM, Patnaik A, Hwu WJ, Weber JS, Gangadhar TC, Hersey P, Dronca R, Joseph RW, Zarour H, Chmielowski B, Lawrence DP, Algazi A, Rizvi NA, Hoffner B, Mateus C, Gergich K, Lindia JA, Giannotti M, Li XN, Ebbinghaus S, Kang SP, Robert C (2016) Association of pembrolizumab with tumor response and survival among patients with advanced melanoma. JAMA 315(15):1600–1609. CrossRefPubMedGoogle Scholar
  29. 29.
    Siddiqi SN, Provias J, Laperriere N, Bernstein M (1997) Effects of iodine-125 brachytherapy on the proliferative capacity and histopathological features of glioblastoma recurring after initial therapy. Neurosurgery 40(5):910–917; discussion 917–918CrossRefPubMedGoogle Scholar
  30. 30.
    Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352(10):997–1003. CrossRefPubMedGoogle Scholar
  31. 31.
    Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, Miller CR, Ding L, Golub T, Mesirov JP, Alexe G, Lawrence M, O’Kelly M, Tamayo P, Weir BA, Gabriel S, Winckler W, Gupta S, Jakkula L, Feiler HS, Hodgson JG, James CD, Sarkaria JN, Brennan C, Kahn A, Spellman PT, Wilson RK, Speed TP, Gray JW, Meyerson M, Getz G, Perou CM, Hayes DN, Cancer Genome Atlas Research Network (2010) Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17(1):98–110. CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Noone AM, Lund JL, Mariotto A, Cronin K, McNeel T, Deapen D, Warren JL (2016) Comparison of SEER treatment data with Medicare claims. Med Care 54(9):e55–e64. CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Stupp R, Taillibert S, Kanner A, Read W, Steinberg D, Lhermitte B, Toms S, Idbaih A, Ahluwalia MS, Fink K, Di Meco F, Lieberman F, Zhu JJ, Stragliotto G, Tran D, Brem S, Hottinger A, Kirson ED, Lavy-Shahaf G, Weinberg U, Kim CY, Paek SH, Nicholas G, Bruna J, Hirte H, Weller M, Palti Y, Hegi ME, Ram Z (2017) Effect of tumor-treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: a randomized clinical trial. JAMA 318(23):2306–2316. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Department of Medicine and the Department of Clinical NeuroscienceKarolinska InstitutetStockholmSweden
  2. 2.Department of NeurosurgeryKarolinska University HospitalStockholmSweden
  3. 3.Department of NeurosurgeryRigshospitaletCopenhagenDenmark
  4. 4.Faculty of Health SciencesUCSDSan DiegoUSA
  5. 5.Department of NeurosurgeryUniversity of MinnesotaMinneapolisUSA
  6. 6.Barrow Brain and SpinePhoenixUSA
  7. 7.Department of Radiation OncologyUniversity of MinnesotaMinneapolisUSA
  8. 8.Department of NeurosurgeryUniversity of MinnesotaMinneapolisUSA

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