Modification of loco-regional microenvironment in brain tumors by spinal cord stimulation. Implications for radio-chemotherapy

Abstract

The effectiveness of radiotherapy and chemotherapy in high grade gliomas (HGG) depends on tumor micro-environment. We summarize our experience of the influence of spinal cord stimulation (SCS) on this micro-environment. Patients with HGG (n = 26) were assessed pre- and post-SCS, using: (1) Doppler in middle cerebral arteries (MCA) and (2) in common carotid arteries (CCA); (3) tumor blood-flow using single photon emission computed tomography (SPECT); (4) tumor-pO(2) (mmHg) using polarographic probes (eight tumor areas from five patients); and (5) tumor glucose metabolism using (18)F-fluoro-2-deoxyglucose ((18)FDG) positron emission tomography ((18)FDG-PET). Pre-SCS: tumor blood-flow was lower (P < 0.001) than peri-tumor areas and healthy contra-lateral areas. Tumor-pO(2) was lower (P < 0.042) than healthy tissue. Tumor glucose metabolism was higher than peri-tumor areas (P = 0.017) and healthy contra-lateral areas (P = 0.048). Post-SCS: there were increases in: MCA blood-flow (P ≤ 0.002), CCA blood-flow (P ≤ 0.013), tumor blood-flow (P = 0.033), tumor glucose metabolism (P = 0.027) and tumor-pO(2) (P = 0.022). The percentage of hypoxic values decreased (P = 0.007). SCS can modify tumor micro-environment. The potential usefulness of SCS in improving the effectiveness of radio-chemotherapy in HGG needs to be evaluated.

Spinal Cord Stimulation as Adjuvant During Chemotherapy and Reirradiation Treatment of Recurrent High-Grade Gliomas

“…5 Using the polarographic probe technique to directly measure brain tissue pO 2 we had also described that SCS can increase tumor oxygenation and decrease tumor hypoxia. 6 We propose that the encouraging results of the present study could be related to the modification of those parameters by SCS; an increase in tumor blood flow could improve chemotherapy delivery and tumor oxygenation and, hence, decrease tumor hypoxia. These effects might be even more relevant if reirradiation is administered at higher doses per fraction, that is, more sensitive to the hypoxia-mediated radioresistance, as occurs for stereotactic radiosurgery or hypofractionated SRT.…”

“…6 The current report shows our preliminary observations regarding the use of SCS during the deployment of chemotherapy, and reirradiation, for the treatment of recurrent HGG.…”

“…26 Further details are described in an updated review by Visocchi et al 27 Spinal cord stimulation was not associated with increased toxicity to the scheduled radiotherapy, 6 temozolomide, or bevacizumab. Indeed, there was a significant decrease in the patient's corticosteroid requirement, and an increase in performance status.…”

“…We have previously described that cervical spinal cord stimulation (SCS) can modify tumor microenvironment in HGG by increasing tumor blood flow, oxygenation, and metabolism 5,6 as well as by decreasing tumor hypoxia. 6 The current report shows our preliminary observations regarding the use of SCS during the deployment of chemotherapy, and reirradiation, for the treatment of recurrent HGG.…”

Neuromodulation of Vegetative State through Spinal Cord Stimulation: Where Are We Now and Where Are We Going?

“…SCS has been shown to augment CBF and speculated to protect the brain from focal ischemia in a large series of experiments, both on animals and on humans [47,48,49,50,51,52,53], and has been proposed for the treatment of several cerebral low-perfusion syndromes [54,55,56,57,58,59,60,61,62,63,64,65,66,67]. However, there is not yet an ultimate scientific explanation; moreover, a clear understanding of the mechanisms elicited by SCS is still lacking [4,53,68].…”