Spinal cord stimulation as adjuvant during chemotherapy and reirradiation treatment of recurrent high-grade gliomas.

AIMS: Relapsed high-grade gliomas (HGGs) have poor prognoses and there is no standard treatment. HGGs have ischemia/hypoxia associated and, as such, drugs and oxygen have low access, with increased resistance to chemotherapy and radiotherapy. Tumor hypoxia modification can improve outcomes and overall survival in some patients with these tumors. In previous works, we have described that cervical spinal cord stimulation can modify tumor microenvironment in HGG by increasing tumor blood flow, oxygenation, and metabolism. The aim of this current, preliminary, nonrandomized, study was to assess the clinical effect of spinal cord stimulation during brain reirradiation and chemotherapy deployed for the treatment of recurrent HGG; the hypothesis being that an improvement in oxygenated blood supply would facilitate enhanced delivery of the scheduled therapy. MATERIALS AND METHODS: Seven patients had spinal cord stimulation applied during the scheduled reirradiation and chemotherapy for the treatment of recurrent HGG (6 anaplastic gliomas and 1 glioblastoma). Median dose of previous irradiation was 60 Gy (range = 56-72 Gy) and median dose of reirradiation was 46 Gy (range = 40-46 Gy). Primary end point of the study was overall survival (OS) following confirmation of HGG relapse. RESULTS: From the time of diagnosis of last tumor relapse before reirradiation, median OS was 39 months (95% CI = 0-93) for the overall study group: 39 months (95% CI = 9-69) for those with anaplastic gliomas and 16 months for the patient with glioblastoma. Posttreatment, doses of corticosteroids was significantly decreased (P = .026) and performance status significantly improved (P = .046). CONCLUSIONS: Spinal cord stimulation during reirradiation and chemotherapy is feasible and well tolerated. In our study, spinal cord stimulation was associated with clinical improvement and longer survival than previously reported in recurrent anaplastic gliomas. Spinal cord stimulation as adjuvant during chemotherapy and reirradiation in relapsed HGGs merits further research.

Increased locoregional blood flow in brain tumors after cervical spinal cord stimulation.

OBJECT: Patients with high-grade gliomas have poor prognoses following standard treatment. Generally, malignant brain tumors have a decreased blood flow that results in increased resistance to radiation and reduced delivery of chemotherapeutic agents and oxygen. The aim of the present study was to assess the effect of spinal cord stimulation (SCS) on locoregional blood flow in high-grade tumors in the brain. METHODS: Fifteen patients (11 with Grade III and four with Grade IV brain tumors) had SCS devices inserted prior to scheduled radiotherapy. Both before and after SCS, the patients underwent the following procedures: 1) single-photon emission computerized tomography (SPECT) scanning; 2) middle cerebral artery (MCA) blood flow velocity measurements (centimeters/second) with the aid of transcranial Doppler (TCD) ultrasonography; and 3) common carotid artery (CCA) blood flow volume quantification (milliliters/minute) based on time-domain processing by using color Doppler ultrasonography. The indices demonstrated on SPECT scanning before SCS were significantly lower (p < 0.001) in tumor sites compared with those in peritumoral sites (32%) and healthy contralateral areas (41%). Poststimulation results revealed the following: 1) a mean increase of 15% in tumor blood flow in 75% of patients (p = 0.033), as demonstrated on SPECT scanning: 2) a mean increase of greater than 18% in systolic and diastolic blood flow velocities in both tumorous and healthy MCAs in all but one patient (p < 0.002), as exhibited on TCD ultrasonography; and 3) a mean increase of greater than 60% in blood flow volume in tumorous and healthy CCAs in all patients (p < 0.013), as revealed on color Doppler ultrasonography studies. CONCLUSIONS: Preliminary data show that SCS can modify locoregional blood flow in high-grade malignant tumors in the brain, thus indicating that SCS could be used to improve blood flow, oxygenation, and drug delivery to such tumors and could be a useful adjuvant in chemoradiotherapy.

Increase of brain tumor oxygenation during cervical spinal cord stimulation. Report of three cases.

Malignant brain tumors have been shown to decrease O2 and blood flow resulting in hypoxia and low perfusion that in turn reduce radiation sensitivity and access by chemotherapeutic agents. Spinal cord stimulation (SCS) is a procedure that has been used quite successfully in the treatment of pain and ischemic syndromes. In the present study the authors applied the method and, with polarographic probes inserted in the tumor sites, measured the changes in tissue oxygenation and hypoxia in two separate tumor areas in three patients with high-grade astrocytomas. The results of the SCS indicated that overall tumor oxygenation increased by 90% (from 13.2+/-9.4 mm Hg to 25.1+/-9.6 mm Hg; p = 0.013); the percentage of moderately hypoxic values (< 10 mm Hg) decreased by 55% (from 48.6+/-20.1% to 22+/-13.3%; p = 0.026); and the percentage of considerably hypoxic values (< 5 mm Hg) decreased by 45% (from 28+/-20.3% to 15.5+/-15%; p = 0.018). In this report the authors describe a potential novel application of SCS, and the preliminary results suggest that tumor tissue oxygenation and hypoxia are significantly improved as a result. If these findings are confirmed, the method may be applicable as an adjuvant to radiotherapy and chemotherapy regimens.