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