Significant antitumor response of disseminated glioblastoma to bevacizumab resulting in long-term clinical remission in a patient with encephalocraniocutaneous lipomatosis: A case report

Abstract

The prognosis of recurrent and disseminated glioblastoma is very poor. Bevacizumab is an effective established therapy for recurrent glioblastoma following treatment with radiotherapy plus temozolomide. However, the efficacy of bevacizumab is limited to prolonging progression-free survival, without significant prolongation of the overall survival. We herein report a case of glioblastoma in a 32-year-old female patient with encephalocraniocutaneous lipomatosis (ECCL) that had disseminated following surgical resection and subsequent treatment with temozolomide and radiation therapy. The disseminated tumors disappeared completely after five courses of bevacizumab therapy. Surprisingly, the patient has remained in clinical remission for >2.5 years after dissemination by continuing this therapy. To the best of our knowledge, this is the first case of long-time clinical remission following glioblastoma dissemination and treatment with bevacizumab. In the present case, bevacizumab exerted an atypically strong antitumor effect against disseminated glioblastoma after multidisciplinary treatments had already been applied. Moreover, this is the first report of ECCL associated with a malignant brain tumor.

Methylome analysis and whole-exome sequencing reveal that brain tumors associated with encephalocraniocutaneous lipomatosis are midline pilocytic astrocytomas

“…These activating hotspot mutations are identified in affected tissues, but not in the peripheral blood of ECCL patients, and are likely the result of post-zygotic constitutional mosaicism promoting locally constitutive activation of the RAS-MAPK pathway [ 1 ]. The same FGFR1 mutations occur in subgroups of sporadic low-grade gliomas (LGG) [ 7 , 10 , 12 ] indicating probable intersection between ECCL and tumorigenesis, possibility further substantiated by reports of brain tumors in nine ECCL cases with wide-ranging histopathological subtypes [ 1 – 3 , 5 , 6 , 8 , 9 , 13 ].…”

Combining therapy with recombinant human endostatin and cytotoxic agents for recurrent disseminated glioblastoma: a retrospective study

“…In addition, this study did not focus on one chemotherapy regimen and fail to provide an effective therapeutic approach [17]. Most of the other published studies were case reports [18][19][20]. Okita Y reported a case of leptomeningeal dissemination of recurrent glioblastoma that achieved transient neurological and radiological improvement after chemotherapy with TMZ and bevacizumab (PFS = 2.3 months) and died 5 months after diagnosis of dissemination [18].…”

“…However, the younger age (32-year-old) might influence the survival. Moreover, the biological differences between this particular glioblastoma in patient with encephalocraniocutaneous lipomatosis and common glioblastoma remain unknown [20].…”

Encephalocraniocutaneous Lipomatosis (Haberland Syndrome or Fishman Syndrome)

“…132 Concerning brain tumors, apart from surgical approach, a recent case report of an adult female affected by glioblastoma and ECCL reported the efficacy of bevacizumab in the long time clinical remission of the disseminated glioblastoma. 133…”