Surgical impact on brain tumor invasion: A physical perspective

Malignant brain tumors such as gliomas expand through proliferation and invasion within the confines of the bony skull, hence in a mechanically constraint area. That is, the brain tissue's mechanical 'reserve' rooms, i.e. the interstitial space, the cerebrospinal fluid filled ventricles and the vascular system can only temporarily compensate, through fluid shifts, any sudden or even gradual increase in intracranial pressure (ICP) as it relates to e.g. an intracerebral hemorrhage or a tumor. Once the point of decompensation is reached (Figure 1) any even miniscule increase in volume will trigger a massive, life-threatening increase in ICP [1] that generally leads to surgical intervention in an attempt to resect some of this pressure-raising volume.Standard treatment for highly aggressive gliomas (anaplastic astrocytomas and glioblastomas (GBM)) has therefore changed little over the years and still consists of gross surgical resection followed by adjuvant radiotherapy and chemotherapy (e.g., [2]). The problem is that the already spatially disseminated tumor cannot be visualized at the single cell level with current clinical imaging modalities, let alone be removed completely. Hence, after a period of temporary betterment, the tumor almost always returns, primarily locally, i.e., at the surgical edge, in conjunction with widespread tissue invasion that at some point prohibits further cytoreductive therapy. Therefore, regardless of any treatment, the grim outcome overall did not change in decades with most GBM patients succumbing to the disease within 1–2 years after diagnosis (e.g., [3]). New approaches are therefore desperately needed and, as always, the development of innovative strategies starts with a better understanding of the current limitations. Here, we discuss, from a pure theoretical and simple mechanistic perspective, if the first line approach of surgical debulking has any impact on the characteristic invasive behaviour of these cancer systems post-extirpa