Treatment of adult brainstem glioma with combined antiangiogenic therapy: a case report and literature review

Figures & data

Figure 1 Brain MRI scans.

Notes: MRI before treatment (A–D): (A) axial T2W shows a hyperintense signal alteration in the right side of the pons; (B) axial T1W post-contrast; (C) sagittal T1W post- contrast; and (B and C) increased enhancement within the tumor. (D) 3D-ASL CBF shows increased CBF value in the right pons. MRI after treatment (E–H): (E) axial T2W shows a decreased hyperintense signal in the right side of the pons compared to pretreatment; (F) axial T1W post-contrast; (G) sagittal T1W post-contrast; and (F and G) disappeared right pontine lesion. (H) 3D-ASL CBF shows decreased CBF value in the right pons compared to pretreatment.

Abbreviations: 3D-ASL, three-dimensional arterial spin labelling; CBF, cerebral blood flow; T1W, T1 weighted; T2W, T2 weighted.

Figure 2 Histopathologic and immunohistochemical examinations of the biopsy tissue.

Notes: (A) H&E stain showed features of anaplastic astrocytoma (WHO grade III) with increased cellularity, nuclear atypia, and mitotic activity. (B) MiB1 (Ki-67) immunohistochemistry showed high proliferative activity with 60% positive cells. (C) GFAP immunohistochemistry. (D) Oligo-2 immunohistochemistry. (E) VEGFR-1 immunohistochemistry. (F) VEGFR-2 immunohistochemistry. (G) CD117 (c-kit). (H) H3K27M immunohistochemistry. Staining was positive for GFAP, oligo-2, VEGFR1, and VEGFR2 and negative for c-kit and H3K27M. Magnification 400×.

Abbreviation: VEGFR, vascular endothelial growth factor receptor.

Table 1 Results of molecular tests

Item	Result
MGMT promoter methylation	Positive
Loss of heterozygosity of chromosome 1p	Positive
Loss of heterozygosity of chromosome 19q	Negative
IDH1 R132 mutation	Negative
IDH2 R172 mutation	Negative
TERT C228T mutation	Negative
TERT C250T mutation	Negative
BRAF V600E mutation	Negative
H3F3A K27M mutation	Negative
HIST1H3B K27M mutation	Negative

Table 2 Survival data of histologically diagnosed brainstem gliomas in adults

References	Tumor histology	No. of patients	Therapy	mPFS (months)	mOS (months)
Kesari et al (2008)^Citation8 n=101a	WHO grade I WHO grade II WHO grade III WHO grade IV	16 15 12 3	Radiation, chemotherapy (PCV, lomustine, vincristine, carboplatin, carmustine, temozolomide, irinotecan)	44 48 10 10	83 168 17 16
Babu et al (2013)^Citation12 n=7	AA GB	3 4	Radiotherapy and concurrent temozolomide, other salvage chemotherapy	6.7 (AA + GB)	13.5 (AA + GB)
Babu et al (2014)^Citation13 n=34	AA GB	22 12	Radiotherapy, temozolomide, other salvage chemotherapy, and/or bevacizumab	NA NA	77 12.1
Hundsberger et al (2014)^Citation11 n=21	LG-BSG HG-BSG	8 13	Radiotherapy and/or chemotherapy, supportive care	24.1 5.8	30.5 11.5
Dey et al (2014)^Citation14 n=240	AA GB	75 165	Radiation, data regarding chemotherapy, and other treatment regimens NA	NA NA	12 6
Reithmeier et al (2014)^Citation4 n=104b	WHO grade I WHO grade II WHO grade III WHO grade IV	16 31 42 14	Radiation, chemotherapy, interstitial radiosurgery (with I-125 seeds), combined radiation and chemotherapy, supportive care	NA NA NA NA	NA 26.2 12.9 9.8
Theeler et al (2015)^Citation15 n=143a	DA AA GB	4 18 21	Radiation, chemotherapy (temozolomide, cytotoxic chemotherapy, and/or bevacizumab)	NA NA NA	77 21.1 14.8

Notes:

a The study contained patients who were diagnosed radiologically.

b In one patient, grading was not performed.

Abbreviations: AA, anaplastic astrocytoma; DA, diffuse astrocytoma; GB, glioblastoma; HG-BSG, high-grade brainstem glioma; LG-BSG, low-grade brainstem glioma; mOS, median overall survival; mPFS, median progression-free survival; NA, not available; PCV, procarbazine, lomustine, and vincristine.

Table 3 Case reports of adult BSG treated with antiangiogenic agents

References	Patient’s age (years), gender	Tumor location	Histology	Therapy	PFS
Torcuator et al (2009)^Citation20	43, female	Pons	NA (progressive diffuse BSG diagnosed by MRI)	Initial: radiotherapy (54 Gy) TMZ irinotecan and bevacizumab	From bevacizumab: 1+ year
Raza et al (2009)^Citation21	Adult (age and sex not mentioned)	Pons and medulla	NA (malignant infiltrative diffuse BSG diagnosed by MRI)	Initial: radiotherapy TMZ bevacizumab	From bevacizumab: 30+ months
Blesa et al (2012)^Citation22	38, male	Brainstem	Glioblastoma multiforme WHO grade IV	Initial: radiotherapy (60 Gy) TMZ changed to: irinotecan Salvage: bevacizumab cetuximab	From initial: 8 months From irinotecan: 0 month From bevacizumab: 20 months
Reithmeier et al (2013)^Citation23	32, female	Medulla oblongata	Astrocytoma WHO grade II	Initial: radiotherapy (54 Gy) Salvage: intensified TMZ, bevacizumab	From initial: 4 months From bevacizumab: 97+ weeks
	36, female	Cerebellar peduncle with infiltration of the brain stem	Initial: glioma WHO grade II Recurrence: malignant astrocytoma WHO grade III	Initial: interstitial radiosurgery of iodine-125 seeds Salvage: radiotherapy (60 Gy) TMZ carmustine bevacizumab	From initial: 20 months From bevacizumab: 35 weeks
	39, male	Pontine tegmentum	Anaplastic astrocytoma WHO grade III	Initial: radiotherapy (54 Gy) Salvage: TMZ lomustine bevacizumab	From initial: 4 months From bevacizumab: 39 weeks
	36, male	Medulla	Diffuse astrocytoma WHO grade II	Initial: radiotherapy (60 Gy) Salvage: TMZ bevacizumab (concomitant)	From initial: 12 months From bevacizumab: 4 months
	49, female	Right medulla	Anaplastic astrocytoma WHO grade III	Initial: TMZ (concomitant) Changed to: carboplatin etoposide interferon-b Salvage: bevacizumab	From initial: 0 month in progression From bevacizumab: 10 months
	21, male	Right pons	NA (radiologically diagnosed)	Initial: radiotherapy (60 Gy) Salvage: TMZ bevacizumab	From bevacizumab: 6 months
	59, male 66, male	Right pons Right pons	NA (radiologically diagnosed) NA (radiologically diagnosed)	Initial: TMZ bevacizumab Salvage: radiotherapy (60 Gy) Initial: radiotherapy (60 Gy) TMZ bevacizumab	From bevacizumab: 9 months in progression From bevacizumab: 8 months

Abbreviations: BSG, brainstem glioma; NA, not available; PFS, progression-free survival; TMZ, temozolomide.

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