Journal of Neuro-Oncology

, Volume 102, Issue 3, pp 471–475 | Cite as

Repeated treatments with bevacizumab for recurrent radiation necrosis in patients with malignant brain tumors: a report of 2 cases

  • Motomasa Furuse
  • Shinji Kawabata
  • Toshihiko Kuroiwa
  • Shin-Ichi MiyatakeEmail author
Case Report


Bevacizumab is expected to constitute a new treatment modality for radiation necrosis. In the present cases, we observed a recurrence of radiation necrosis after temporary improvement by bevacizumab treatment. Re-treatment with bevacizumab controlled the necrosis again. A 39-year-old male and a 57-year-old female were diagnosed with glioblastoma and lung cancer metastasis, respectively. The former patient underwent partial resection of the glioblastoma, followed by boron neutron capture therapy (BNCT) and 30 Gy of fractionated X-ray radiotherapy. Eleven months after BNCT, he suffered from left hemiparesis and convulsions with enlargement of a perifocal edema. The latter patient underwent stereotactic radiosurgery twice for the same tumor. Three months after the second radiosurgery, she had an uncontrollable convulsion and right hemiplegia with a massive perifocal edema. Both lesions were suggested to be radiation necroses by positron emission tomography using amino acids as a tracer. Neither patient responded to corticosteroids, anticoagulants, or vitamin E. They underwent treatment with 5 mg/kg bevacizumab biweekly, for a total of 6 cycles. The size of the perifocal edema was clearly reduced in response to the treatments. The neurological status of the patients improved concomitant with therapy. However, the clinical status of both patients was aggravated several months after the bevacizumab was stopped, and the perifocal edemas enlarged again. The patients underwent a second treatment with bevacizumab, and the perifocal edemas again decreased. Although radiation necrosis may recur several months after bevacizumab treatment, repeated bevacizumab treatments also appear to be effective.


Bevacizumab Boron neutron capture therapy Brain edema Glioblastoma, metastatic brain tumor Radiation necrosis 



This work was partly supported by a Grant-in-Aid for Scientific Research (B) (19390385 to S.I.M.) from the Japanese Ministry of Education, Science and Culture and in part by the Takeda Science Foundation for Osaka Medical College.


  1. 1.
    Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335–2342PubMedCrossRefGoogle Scholar
  2. 2.
    Sander A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355:2542–2550CrossRefGoogle Scholar
  3. 3.
    Escudier B, Pluzanska A, Koralewski P, Ravaud A, Bracarda S, Szczlik C, Chevreau C, Filipek M, Melichar B, Bajetta E, Gorbunova V, Bay JO, Bodrogi I, Jagiello-Gruszfeld A, Moore N, AVOREN Trial Investigators (2007) Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomized, double-blind phase III trial. Lancet 370:2103–2111PubMedCrossRefGoogle Scholar
  4. 4.
    Miller KD, Chap LI, Holmes FA, Cobleigh MA, Marcom PK, Fehrenbacher L, Dickler M, Overmoyer BA, Reimann JD, Sing AP, Langmuir V, Rugo HS (2005) Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol 23:792–799PubMedCrossRefGoogle Scholar
  5. 5.
    Vredenburgh JJ, Desjardins A, Herndon JE IId, Marcello J, Reardon DA, Quinn JA, Rich JN, Sathornsumetee S, Gururangan S, Sampson J, Wagner M, Bailey L, Bigner DD, Friedman AH, Friedman HS (2007) Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol 25:4722–4729PubMedCrossRefGoogle Scholar
  6. 6.
    Gonzalez J, Kumar AJ, Conrad CA, Levin VA (2007) Effect of bevacizumab on radiation necrosis of the brain. Int J Radiat Oncol Biol Phys 67:323–326PubMedCrossRefGoogle Scholar
  7. 7.
    Torcuator R, Zuniga R, Mohan YS, Rock J, Doyle T, Anderson J, Gutierrez J, Ryu S, Jain R, Rosenblum M, Mikkelsen T (2009) Initial experience with bevacizumab treatment for biopsy confirmed cerebral radiation necrosis. J Neurooncol 94:63–68PubMedCrossRefGoogle Scholar
  8. 8.
    Levin VA, Bidaut L, Hou P, Kumar AJ, Wefel JS, Bekele N, Prabhu S, Loghin M, Gilbert MR, Jackson EF (2010) Randomized double-blind placebo-controlled trial of bevacizumab therapy for radiation necrosis of the central nervous system. Int J Radiat Oncol Biol Phys. doi: 10.1016/j.ijrobp.2009.12.061
  9. 9.
    Miyashita M, Miyatake S, Imahori Y, Yokoyama K, Kawabata S, Kajimoto Y, Shibata MA, Otsuki Y, Kirihata M, Ono K, Kuroiwa T (2008) Evaluation of fluoride-labeled boronophenylalanine-PET imaging for the study of radiation effects in patients with glioblastomas. J Neurooncol 89:239–246PubMedCrossRefGoogle Scholar
  10. 10.
    Miyatake S, Kawabata S, Nonoguchi N, Yokoyama K, Kuroiwa T, Matsui H, Ono K (2009) Pseudoprogression in boron neutron capture therapy for malignant gliomas and meningiomas. Neurooncology 11:430–436Google Scholar
  11. 11.
    Miyatake S, Kawabata S, Kajimoto Y, Aoki A, Yokoyama K, Yamada M, Kuroiwa T, Tsuji M, Imahori Y, Kirihata M, Sakurai Y, Masunaga S, Nagata K, Maruhashi A, Ono K (2005) Modified boron neutron capture therapy for malignant gliomas performed using epithermal neutron and two boron compounds with different accumulation mechanisms: an efficacy study based on findings on neuroimages. J Neurosurg 103:1000–1009PubMedCrossRefGoogle Scholar
  12. 12.
    Kawabata S, Miyatake SI, Kuroiwa T, Yokoyama K, Doi A, Iida K, Miyata S, Nonoguchi N, Michiue H, Takahashi M, Inomata T, Imahori Y, Kirihata M, Sakurai Y, Maruhashi A, Kumada H, Ono K (2009) Boron neutron capture therapy for newly diagnosed glioblastoma. J Radiat Res (Tokyo) 50:51–60Google Scholar
  13. 13.
    Fitzek MM, Thornton AF, Rabinov JD, Lev MH, Pardo FS, Munzenrider JE, Okunieff P, Bussiere M, Braun I, Hochberg FH, Hedley-Whyte ET, Liebsch NJ, Harsh GR IV (1999) Accelerated fractionated proton/photon irradiation to 90 cobalt gray equivalent for glioblastoma multiforme: results of a phase II prospective trial. J Neurosurg 91:251–260PubMedCrossRefGoogle Scholar
  14. 14.
    Iuchi T, Hatano K, Narita Y, Kodama T, Yamaki T, Osato K (2006) Hypofractionated high-dose irradiation for the treatment of malignant astrocytomas using simultaneous integrated boost technique by IMRT. Int J Radiat Oncol Biol Phys 64:1317–1324PubMedCrossRefGoogle Scholar
  15. 15.
    Delanian S, Balla-Mekias S, Lefaix JL (1999) Striking regression of chronic radiotherapy damage in a clinical trial of combined pentoxifylline and tocopherol. J Clin Oncol 17:3283–3290PubMedGoogle Scholar
  16. 16.
    Glantz MJ, Burger PC, Friedman AH, Radtke RA, Massey EW, Schold SC Jr (1994) Treatment of radiation-induced nervous system injury with heparin and warfarin. Neurology 44:2020–2027PubMedGoogle Scholar
  17. 17.
    Rizzoli HV, Pagnanelli DM (1984) Treatment of delayed radiation necrosis of the brain. A clinical observation. J Neurosurg 60:589–594PubMedCrossRefGoogle Scholar
  18. 18.
    Shaw PJ, Bates D (1984) Conservative treatment of delayed cerebral radiation necrosis. J Neurol Neurosurg Psychiatry 47:1338–1341PubMedCrossRefGoogle Scholar
  19. 19.
    Tandon N, Vollmer DG, New PZ, Hevezi JM, Herman T, Kagan-Hallet K, West GA (2001) Fulminant radiation-induced necrosis after stereotactic radiation therapy to the posterior fossa. Case report and review of the literature. J Neurosurg 95:507–512PubMedCrossRefGoogle Scholar
  20. 20.
    Coderre JA, Morris GM, Micca PL, Hopewell JW, Verhagen I, Kleiboer BJ, van der Kogel AJ (2006) Late effects of radiation on the central nervous system: role of vascular endothelial damage and glial stem cell survival. Radiat Res 166:495–503PubMedCrossRefGoogle Scholar
  21. 21.
    Kimura T, Sako K, Tohyama Y, Aizawa S, Yoshida H, Aburano T, Tanaka K, Tanaka T (2003) Diagnosis and treatment of progressive space-occupying radiation necrosis following stereotactic radiosurgery for brain metastasis: value of proton magnetic resonance spectroscopy. Acta Neurochir (Wien) 145:557–564CrossRefGoogle Scholar
  22. 22.
    Midgley R, Kerr D (2005) Bevacizumab—current status and future directions. Ann Oncol 16:999–1004PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Motomasa Furuse
    • 1
  • Shinji Kawabata
    • 1
  • Toshihiko Kuroiwa
    • 1
  • Shin-Ichi Miyatake
    • 1
    Email author
  1. 1.Department of NeurosurgeryOsaka Medical CollegeTakatsukiJapan

Personalised recommendations