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

2014 ◽  
Vol 13 (6) ◽  
pp. 513-519 ◽  
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.

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

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 11510-11510 ◽  
Author(s):  
B. Clavo ◽  
F. Robaina ◽  
A. Cabezon ◽  
I. J. Jorge ◽  
P. Ponce ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Stimulation ◽  
Tumor Response ◽  
Cervical Spinal Cord ◽  
Residual Tumor ◽  
Hematological Toxicity ◽  
Subtotal Resection ◽  
High Grade ◽  
Anaplastic Gliomas ◽  
High Grade Gliomas

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.

Increase of brain tumor oxygenation during cervical spinal cord stimulation

2002 ◽  
Vol 96 (1) ◽  
pp. 94-100 ◽  
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.

scholarly journals Safety and efficacy of Hypofractionated stereotactic radiosurgery for high-grade Gliomas at first recurrence: a single-center experience

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yun Guan ◽  
Ji Xiong ◽  
Mingyuan Pan ◽  
Wenyin Shi ◽  
Jing Li ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adverse Events ◽  
Stereotactic Radiosurgery ◽  
Performance Status ◽  
Target Volume ◽  
Salvage Treatment ◽  
High Grade ◽  
High Grade Gliomas ◽  
Grade 3 ◽  
Hypofractionated Stereotactic Radiosurgery

Abstract Background The optimal treatment for recurrent high-grade gliomas (rHGGs) remains uncertain. This study aimed to investigate the efficacy and safety of hypofractionated stereotactic radiosurgery (HSRS) as a first-line salvage treatment for in-field recurrence of high-grade gliomas. Methods Between January 2016 and October 2019, 70 patients with rHGG who underwent HSRS were retrospectively analysed. The primary endpoint was overall survival (OS), and secondary endpoints included both progression-free survival (PFS) and adverse events, which were assessed according to Common Toxicity Criteria Adverse Events (CTCAE) version 5. The prognostic value of key clinical features (age, performance status, planning target volume, dose, use of bevacizumab) was evaluated. Results A total of 70 patients were included in the study. Forty patients were male and 30 were female. Forty-nine had an initial diagnosis of glioblastoma (GBM), and the rest (21) were confirmed to be WHO grade 3 gliomas. The median planning target volume (PTV) was 16.68 cm3 (0.81–121.96 cm3). The median prescribed dose was 24 Gy (12–30 Gy) in 4 fractions (2–6 fractions). The median baseline of Karnofsky Performance Status (KPS) was 70 (40–90). With a median follow-up of 12.1 months, the median overall survival after salvage treatment was 17.6 months (19.5 and 14.6 months for grade 3 and 4 gliomas, respectively; p = .039). No grade 3 or higher toxicities was recorded. Multivariate analysis showed that concurrent bevacizumab with radiosurgery and KPS > 70 were favourable prognostic factors for grade 4 patients with HGG. Conclusions Salvage HSRS showed a favourable outcome and acceptable toxicity for rHGG. A prospective phase II study (NCT04197492) is ongoing to further investigate the value of hypofractionated stereotactic radiosurgery (HSRS) in rHGG.

scholarly journals Safety and Efficacy of Hypofractionated Stereotactic Radiosurgery for High-Grade Gliomas at First Recurrence: A Single-Center Experience

2020 ◽  
Author(s):  
Yun Guan ◽  
Ji Xiong ◽  
Mingyuan Pan ◽  
Wenyin Shi ◽  
Jing Li ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adverse Events ◽  
Performance Status ◽  
Target Volume ◽  
Salvage Treatment ◽  
High Grade ◽  
Cyberknife Radiosurgery ◽  
High Grade Gliomas ◽  
Grade 3 ◽  
Hypofractionated Stereotactic Radiosurgery

Abstract Background: The optimal treatment for recurrent high-grade gliomas (rHGG) remains uncertain. This study aimed to investigate the efficacy and safety of CyberKnife radiosurgery as a salvage treatment for in field recurrence of high-grade gliomas at first time.Methods: Between January 2016 and October 2019, seventy patients with rHGG undergone CyberKnife radiosurgery were retrospectively analyzed. The primary endpoint was overall survival (OS), and secondary endpoints included both progression-free survival (PFS) and adverse events which was according to Common Toxicity Criteria Adverse Events (CTCAE) version 5. The prognostic value of key clinical features (age, performance status, planning target volume, dose, use of bevacizumab) were evaluated.Results: A total of 70 patients were included in the study. Forty patients were male and 30 were female. Forty-nine had an initial diagnosis of glioblastoma (GBM), and the rest (21) were confirmed to be WHO grade 3 gliomas. The median planning target volume (PTV) was 16.68 cm3 (0.81 – 121.96 cm3). The median prescribed dose was 24 Gy (12-30 Gy) in 4 fractions (2-6 fractions). Median baseline of Karnofsky Performance Status (KPS) is 70 (40 - 90). With a median follow-up of 12.1 months, the median overall survival after salvage treatment was 17.6 months (19.5 and 14.6 months for grade 3 and 4 gliomas respectively; p = .039). No grade 3 or higher toxicities was recorded. Multivariate analysis showed that concurrent bevacizumab with radiosurgery and KPS>70 were favorable prognostic factors for grade 4 patients with HGG.Conclusions: Salvage CyberKnife radiosurgery showed a favorable outcome and acceptable toxicity for rHGG. A prospective phase II study (NCT04197492) is ongoing to further investigate the value of hypofractionated stereotactic radiosurgery (HSRS) in rHGG.

Cervical Spinal Cord Stimulation for the Vegetative State: A Preliminary Result of 12 Cases

2018 ◽  
Vol 22 (3) ◽  
pp. 347-354 ◽  
Author(s):  
Yangyang Xu ◽  
Peng Li ◽  
Shizhen Zhang ◽  
Yi Wang ◽  
Xiaoyan Zhao ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Stimulation ◽  
Cervical Spinal Cord ◽  
Vegetative State

scholarly journals Cerebral blood flow increase in cancer patients by applying cervical spinal cord stimulation

Neurocirugía ◽  
2007 ◽  
Vol 18 (1) ◽  
Author(s):  
B. Clavo ◽  
F. Robaina ◽  
L. Catalá ◽  
M. Lloret ◽  
B. Pinar ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cancer Patients ◽  
Spinal Cord Stimulation ◽  
Cervical Spinal Cord ◽  
Blood Flow Increase

OS03.4.A Irradiation of the subventricular and subgranular zone and overall survival in high-grade glioma patients

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii6-ii6
Author(s):  
D Bruil ◽  
S David ◽  
S Nagtegaal ◽  
J Verhoeff
Keyword(s):  
Overall Survival ◽  
Confidence Interval ◽  
High Grade Glioma ◽  
Radiotherapy Planning ◽  
Intracranial Volume ◽  
High Grade ◽  
Subgranular Zone ◽  
Median Dose ◽  
Repair Capacity ◽  
The Mean

Abstract BACKGROUND Previous research has shown that neural stem cells (NSCs) in the subventricular zone (SVZ) may support the growth of glioma by recruiting new cells to the tumor. NSCs are located in the SVZ as well as in the subgranular zone (SGZ) of the hippocampus, the two neurogenic niches of the brain. This might indicate that irradiation of the SVZ and SGZ, and thereby damaging NSCs, reduces tumor growth and improves overall survival (OS). However, irradiation may also inhibit the repair capacity of healthy brain tissue by these neurogenic niches. Therefore, we investigated the effects of SVZ and SGZ irradiation dose on OS, in a cohort of high-grade glioma patients. MATERIAL AND METHODS We have retrospectively selected 221 patients (2014–2020) with WHO grade III and IV gliomas that underwent radiotherapy. Next to clinical baseline characteristics, T1 weighted MRI- and CT-images were collected. The SVZ and SGZ regions on the individual T1 images were delineated via non-linear registration of brain atlases. SVZ labels were created in 0.5mm isotropic MNI T1 and T2 templates, while SGZ atlas labels were available via the Hippocampus and Subfields CoBrA atlas. Next, the mean dose from the acquired SVZ and SGZ labels were extracted. The relationship between SVZ doses, SGZ doses and OS were examined using the Cox proportional hazards model and the Kaplan-Meier method (using the Log Rank test for significance). RESULTS For the mean dose in the SVZ, the hazard ratio (HR) was 1.024 per Gy (P = 0.002, [95% confidence interval, 1.009–1.040]) and the mean SGZ dose had a HR of 1.021 per Gy (P&lt; 0.001, [95% confidence interval, 1.012–1.031]). These results were then corrected for the following covariates: sex, age, total intracranial volume and extent of surgery. This resulted in a HR of 1.031 per Gy (P = 0,001, [95% confidence interval, 1.014–1.050]) for the mean SVZ dose, and a HR of 1.025 per Gy (P&lt; 0.001, [95% confidence interval, 1.015–1.036]) for the mean SGZ dose. Patients whose SVZ received greater than the median SVZ dose (= 31.3 Gy) showed a significant decrease in OS compared to patients who received less than the median dose (10.7 months vs 13.5 months median OS, P = 0.001). Patients whose SGZ received greater than the median SGZ dose (= 31.9) showed a significant decrease in OS compared to patients who received less than the median dose (10.7 months vs 15.1 months median OS, P&lt; 0.001). CONCLUSION Here, we present a large cohort of high-grade glioma patients, in which we show a statistically significant decrease in overall survival with increasing radiation dose on the SGZ and SVZ. This correlation suggests that both neurogenic niches might need to be spared during radiotherapy treatment to improve overall survival even in high-grade glioma patients. Modern radiotherapy planning and delivery options are available to implement this.

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