Extensive brainstem infiltration, not mass effect, is a common feature of end-stage cerebral glioblastomas

Abstract

Background Progress in extending the survival of glioblastoma (GBM) patients has been slow. A better understanding of why patient survival remains poor is critical to developing new strategies. Postmortem studies on GBM can shed light on why patients are dying. Methods The brains of 33 GBM patients were autopsied and examined for gross and microscopic abnormalities. Clinical-pathologic correlations were accomplished through detailed chart reviews. Data were compared with older published autopsy GBM studies that predated newer treatment strategies, such as more extensive surgical resection and adjuvant temozolomide. Results In older GBM autopsy series, mass effect was observed in 72% of brains, with herniation in 50% of all cases. Infiltration of tumor into the brainstem was noted in only 21% of those older cases. In the current series, only 10 of 33 (30%) GBMs showed mass effect (P = 0.0003), and only 1 (3%) showed herniation (P < 0.0001). However, extensive GBM infiltration of the brainstem was present in 22 cases (67%, P < 0.0001), with accompanying destruction of the pons and white matter tracts. There was a direct correlation between longer median patient survival and the presence of brainstem infiltration (16.1 mo in brainstem-invaded cases vs 9.0 mo in cases lacking extensive brainstem involvement; P = 0.0003). Conclusions With improving care, severe mass effect appears to be less common in GBM patients today, whereas dissemination, including life-threatening brainstem invasion, is now more pronounced. This has major implications regarding preclinical GBM models, as well as the design of clinical trials aimed at further improving patient survival.

Double Recombinant Vaccinia Virus: A Candidate Drug against Human Glioblastoma

“…Treating the resection cavity with the virus or intravenous virus administration after surgery can reduce the risk of relapse by inhibiting the growth of GSCs. It is known that a population of GSCs is capable of self-renewal, proliferation, and invasion, and can cause local recurrence around the surgical site and/or non-local recurrence in the remainder [31,32]. Possible combinatorial therapy is used to reduce the risk of relapse.…”

Disappearance of MMR-deficient subclones after controlled IL-12 and PD-1 inhibition in a glioma patient

“…Third, the extensive infiltration of tumors into the brainstem is consistent with our previous study of end-stage gliomas, particularly those with a protracted disease course. 15 …”

Engineering Three-Dimensional Tumor Models to Study Glioma Cancer Stem Cells and Tumor Microenvironment

“…The role of cadherins in glioma progression is not well-understood yet. However, the interaction between CSCs and other cellular components of the TME, such as those forming the white matter tracts that glioma cells used to migrate through or ECs from the BBB, has recently acquired great relevance (Drumm et al, 2019 ). Although previous studies reported differing results regarding the concentration level of cadherins and glioma cell invasion capacity, it was finally clear that rather than the concentration of cadherins available, the most important factor determining migration and invasiveness in GBM cell lines was the instability and disorganization of cadherin-mediated junctions (Barami et al, 2006 ).…”