Electrical spinal cord stimulation during radiotherapy and temozolomide in high grade gliomas. A phase II report

11510 Background: Ischemia-hypoxia in high grade gliomas (HGG) turns tumor cells more aggressive and more resistant to radiotherapy (RT) and temozolomide (TMZ). Higher glucose metabolism pre-treatment has been correlated with better response to TMZ using 18-FDG-PET. In preliminary works, we have reported that electrical spinal cord stimulation (SCS) can modify loco-regional oxygenation, blood flow and metabolism in HGG. The aim of this study was to evaluate tumor response and toxicity in HGG using SCS during RT plus TMZ. Methods: 10 patients (males/females: 8/2; median age: 51 years (30–68)) were enrolled in this trial. Tumors were 6 glioblastomas and 4 relapsed anaplastic gliomas. Diagnosis was after complete resection (1), subtotal resection (6), biopsy (1) or MRI + PET (2 relapsed HGG). Tetrapolar electrode for SCS was percutaneously inserted on the posterior surface of the cervical spinal cord at C2-C4 level. RT was at 2 Gy/fraction, 5 fractions/week, total dose 60 Gy (40 Gy in previously irradiated tumors). TMZ was administered at 75 mg/m2 daily during RT, followed by at least 6 cycles of adjuvant TMZ at 200 mg/m2. Tumor response was evaluated by CT and PET. Results: After concurrent RT+TMZ, CT showed: 5 partial response (PR), 3 complete response (CR), 2 stable disease (SD). After 6 adjuvant cycles of TMZ, CT (median 10 months after surgery) showed: 4 PR, 3 CR, 3 progression disease (PD). PET showed post-surgical residual tumor in the 9 evaluated patients. After 6 cycles of TMZ, PET showed: 4 CR, 2 PR (they obtained delayed CR after 12 and 18 cycles of TMZ), PD n = 2, and two patients without PET assessment (1 with PR in CT, and 1 without tumor in CT). For the study group median overall survival (OS) was 22 months (95% CI = 14–30) and for glioblastomas 16 months (95% CI = 6–26). For relapsed anaplastic gliomas mean OS was 37 months (95% CI = 22–52). One patient did not finish scheduled adjuvant TMZ and only one patient experienced hematological toxicity with neutropenia G-I and thrombopenia G-III. Conclusions: Electrical SCS during RT+TMZ did not increase toxicity. Preliminary data about tumor response and OS seem to be encouraging and they support further research. Supported by Grants: FUNCIS 03/09 and ISCiii, RTICCC C03/10. No significant financial relationships to disclose.

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

Integrative Cancer Therapies ◽

10.1177/1534735414550037 ◽

2014 ◽

Vol 13 (6) ◽

pp. 513-519 ◽

Cited By ~ 1

Author(s):

Bernardino Clavo ◽

Francisco Robaina ◽

Ignacio J. Jorge ◽

Raquel Cabrera ◽

Eugenio Ruiz-Egea ◽

...

Keyword(s):

Spinal Cord ◽

Overall Survival ◽

Spinal Cord Stimulation ◽

Cervical Spinal Cord ◽

Performance Status ◽

Tumor Hypoxia ◽

High Grade ◽

Median Dose ◽

Anaplastic Gliomas ◽

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.

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An analysis of two different schedules of radiochemotherapy with concomitant temozolomide in high grade gliomas

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.2035 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 2035-2035 ◽

Cited By ~ 1

Author(s):

G. R. D’Agostino ◽

M. Balducci ◽

C. Anile ◽

S. Manfrida ◽

G. Di Lella ◽

...

Keyword(s):

Overall Survival ◽

Statistical Significance ◽

Residual Tumor ◽

Hematological Toxicity ◽

High Grade ◽

Safe Alternative ◽

Neurological Toxicity ◽

Tumor Bed ◽

Historical Series ◽

High Grade Gliomas

2035 Background: We compared two different schedules of temozolomide (TMZ) concomitant therapy in terms of toxicity and outcome. Methods: 70 patients (median age 61 years, range 27–80) affected by high grade gliomas were treated with concomitant chemoradiation. Conformal radiotherapy (5,940 cGy, 180 cGy/day; CTV2: tumor bed + residual tumor if present + oedema, 3,960 cGy; CTV1: tumor bed + residual tumor if present + margins, 1,980 cGy) was associated with one of the following TMZ schedules: TMZ1: (75 mg/m2 × 5 days, first and last week of radiotherapy); TMZ2 (75 mg/m2, 7 days/week, from the first to the last day of radiotherapy); Toxicities were graded according to RTOG criteria. Survival analysis based on the Kaplan-Meier model. Results: From October, 2000 to March, 2006, 54 patients high grade gliomas were evaluated. 41 patients (29 GBL, 70.7%; 12 AA, 29.3%) were treated between October 2003 and March 2006 with TMZ2, and compared to an historical series of 29 patients (25 GBL, 86.2%; 4 AA, 13.%) treated in our Institution before 2003 with TMZ1. All patients received adjuvant chemotherapy with TMZ for 6 cycles or until disease progression. Hematological toxicity was mild in both group, whereas neurological toxicity (seizures) was higher in TMZ2 group, with a grade > 2 toxicity registered in 11/41 pts (26.8%) compared to 1/29 of the TMZ1 group (3.5%), even if this difference failed to achieve statistical significance (p=0.06). The overall survival did not significantly differ among the 2 schedules (p=0.60). In fact, at a median follow-up of 21 months (range 3- 68), median survival time was 21 months and 19 months, for TMZ1 and TMZ2 groups, respectively, with a 1-year and 2-year overall survival of 73.1% in the TMZ1 group and 75.3% in the TMZ2 group, respectively. Conclusions: In our experience, the concomitant administration of TMZ at the daily dose of 75 mg/m2 given continuously or only in the first and the last week of radiotherapy obtained comparable results in terms of outcome, with a heavier neurological toxicity when given 7 days per week, from the first to the last day of radiotherapy. These data suggest that, in selected cases, the TMZ1 schedule can be considered as a safe, alternative strategy, which does not impact significantly on patient outcome, compared to the standard TMZ2. No significant financial relationships to disclose.

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Increase of brain tumor oxygenation during cervical spinal cord stimulation

Journal of Neurosurgery Spine ◽

10.3171/spi.2002.96.1.0094 ◽

2002 ◽

Vol 96 (1) ◽

pp. 94-100 ◽

Cited By ~ 6

Author(s):

Bernardino Clavo ◽

Francisco Robaina ◽

Jesús Morera ◽

Eugenio Ruiz-Egea ◽

Juan L. Pérez ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Stimulation ◽

Tumor Tissue ◽

Tissue Oxygenation ◽

Cervical Spinal Cord ◽

Radiation Sensitivity ◽

Chemotherapeutic Agents ◽

Tumor Oxygenation ◽

High Grade ◽

Content Type

✓ 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.

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