Multidisciplinary Therapy Managed Recurrent Glioblastoma in a BRAF-V600E Mutant Pregnant Female: A Case Report and Review of the Literature

Abstract

Background: Glioblastoma (GBM) is the most malignant intracranial tumor in adults. However, the overall management of GBM in pregnancy is rarely reported. How to balance the therapeutic benefits to the mother and risks to the fetus remains hugely challenging for clinicians. The application of specific targeting therapy combined with conventional treatment sheds light on a longer lifetime for the patients suffering from GBM. Case Presentation: We present a pregnant female at 20 weeks gestation diagnosed with GBM. Surgical resection was initially performed without adjuvant therapy, and the tumor recurred de novo 2 months later. A secondary craniotomy and cesarean section were performed simultaneously at 32 weeks gestation, both the patient and infant were survived. She was subsequently treated with traditional chemo-radiotherapy. No other identified genetic alterations indicating an optimistic prognosis were detected except for BRAF V600E mutation. Thus, the BRAF inhibitor was placed on her with achieving a good clinical outcome of more than 2-year survival without recurrence. Conclusion: Personalized multidisciplinary therapy should be considered when GBMs occur in pregnancy. Response to the therapy in this presenting case suggests that BRAF V600E mutation is a favorable biomarker for GBM. The mortality of GBM might be reduced through genetic testing and targeted treatment. However, more studies must be conducted to confirm our observation.

Keywords: BRAF V600E; glioblastoma (GBM); multidisciplinary therapy (MDT); pregnancy; vemurafenib.

Figure 1

Main medical imaging and histopathology information of the pregnant GBM patient. (A) MRI images of the primary GBM prior to the first right parietal craniotomy that demonstrated a heterogeneous cystic and solid mass in the right parietal lobe with marked surrounding edema and a shift of the midline structures to the left side (01/11/2017). (B) MRI images on the 3rd day after the first right parietal craniotomy that demonstrated a total resection of the mass, the marked surrounding edema and a shift of the midline structures to the left side remained (01/21/2017). (C) Histopathological features of the primary GBM. Hematoxylin and eosin (H & E) staining of the primary revealed the hyper-cellular astrocytic neoplasm. The features such as mitotic activity, microvascular proliferation, and pseudopalisading presented. The histopathological features indicated the primary tumor to be GBM. (D) Emergency CT scan when the patient was diagnosed with a recurrent tumor, prior to the second right parietal craniotomy which demonstrated a huge fresh mass of low density in the right parietal lobe surrounded by extensive edema, accompanied with a shift of midline structure and distortion of the right lateral ventricle (03/28/2017). (E) MRI images on the 3rd day after the second right parietal craniotomy which demonstrated a total resection of the recurrent tumor, the marked surrounding edema and a shift of the midline structures to the left side still remained (03/30/2018). (F) Histopathological features of the recurrent GBM. Hematoxylin and eosin (H & E) staining of the primary revealed the similar histopathological features with the primary tumor. (G) MRI images of the latest follow-up after multidisciplinary therapy (12/08/2018). The images demonstrated no signs of recurrence and smaller volume of the surrounding edema. The region of the tumor transformed into a capsule without enhancement. The disease remained stable.

Figure 2

Overview of the patient's course of disease, treatment regimen and genetic analysis.