Expression of CD40 Correlates Negatively with Overall and Progression-Free Survival of Low- and High-Grade Gliomas

Abstract BACKGROUND: Magnetic resonance-guided laser-interstitial thermotherapy (MR-LITT) is a minimally invasive technique that shows promise in neuro-oncology because of its superiority in delivering precise minimally invasive thermal energy with minimal collateral damage. OBJECTIVE: In this analysis, we investigate initial data on the use of MR-LITT in the treatment of newly diagnosed high-grade gliomas. METHODS: With the use of the PubMed, OVID, and Google-scholar database systems, a comprehensive search of the English literature was performed. Eighty-five articles were identified plus 1 that is pending publication. Four articles were accounted for in this review, including 25 patients with newly diagnosed high-grade gliomas who underwent MR-LITT treatment. We evaluated safety, progression-free survival, and overall survival. RESULTS: Twenty-five patients with a mean age of 53.8 years underwent LITT treatments. On average, 82.9% of the pretreatment lesion volume was ablated. The average tumor volume treated was 16.5 cm3. The mean follow-up time was 7.6 months. Median overall survival was found to be 14.2 months (range 0.1-23 months). The median progression-free survival was 5.1 months (range 2.4-23 months); however, these data are limited by the relatively short follow-up of the patients reviewed and small sample size of only 25 patients. There was 1 (3.4%) major perioperative complication, which was a central nervous system infection. CONCLUSION: MR-LITT is a promising technology for the treatment of small, yet difficult-to-treat newly diagnosed high-grade gliomas. This study demonstrates that MR-LITT is safe, and future randomized studies are needed to evaluate its role as a treatment adjunct for newly diagnosed high-grade gliomas.

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Serum levels of GFAP and EGFR in primary and recurrent high-grade gliomas: correlation to tumor volume, molecular markers, and progression-free survival

Journal of Neuro-Oncology ◽

10.1007/s11060-015-1829-7 ◽

2015 ◽

Vol 124 (2) ◽

pp. 237-245 ◽

Cited By ~ 18

Author(s):

Aida Kiviniemi ◽

Maria Gardberg ◽

Janek Frantzén ◽

Riitta Parkkola ◽

Ville Vuorinen ◽

...

Keyword(s):

Molecular Markers ◽

Tumor Volume ◽

Progression Free Survival ◽

Serum Levels ◽

High Grade ◽

Free Survival ◽

High Grade Gliomas

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Comparison of 5-aminolevulinic acid and sodium fluorescein for intraoperative tumor visualization in patients with high-grade gliomas: a single-center retrospective study

Journal of Neurosurgery ◽

10.3171/2019.6.jns191531 ◽

2020 ◽

Vol 133 (5) ◽

pp. 1324-1331 ◽

Cited By ~ 2

Author(s):

Rasmus W. Hansen ◽

Christian B. Pedersen ◽

Bo Halle ◽

Anders R. Korshoej ◽

Mette K. Schulz ◽

...

Keyword(s):

Overall Survival ◽

Tumor Volume ◽

Fluorescent Dyes ◽

Aminolevulinic Acid ◽

Progression Free Survival ◽

Extent Of Resection ◽

Sodium Fluorescein ◽

High Grade ◽

Free Survival ◽

High Grade Gliomas

OBJECTIVEMaximal safe resection is an important surgical goal in the treatment for high-grade gliomas. Fluorescent dyes help the surgeon to distinguish malignant tissue from healthy. The aims of this study were 1) to compare the 2 fluorescent dyes 5-aminolevulinic acid (5-ALA) and sodium fluorescein (fluorescein) regarding extent of resection, progression-free survival, and overall survival; and 2) to assess the influence of other risk factors on clinical outcome and screen for potential disadvantages of the dyes.METHODSA total of 209 patients with high-grade gliomas were included in this retrospective study. Resections were performed in the period from 2012 to 2017 using 5-ALA or fluorescein. Extent of resection was assessed as the difference in tumor volume between early postoperative and preoperative MRI studies. Tumor progression–free survival and overall survival were analyzed using an adjusted Cox proportional hazards model.RESULTSOne hundred fifty-eight patients were operated on with 5-ALA and 51 with fluorescein. The median duration of follow-up was 46.7 and 21.2 months, respectively. Covariables were evenly distributed. There was no statistically significant difference in volumetrically assessed median extent of resection (96.9% for 5-ALA vs 97.4% for fluorescein, p = 0.46) or the percentage of patients with residual tumor volume less than 0.175 cm3 (29.5% for 5-ALA vs 36.2% for fluorescein, p = 0.39). The median overall survival was 14.8 months for the 5-ALA group and 19.7 months for the fluorescein group (p = 0.06). The median adjusted progression-free survival was 8.7 months for the 5-ALA group and 9.2 months for the fluorescein group (p = 0.03).CONCLUSIONSFluorescein can be used as a viable alternative to 5-ALA for intraoperative fluorescent guidance in brain tumor surgery. Comparative, prospective, and randomized studies are much needed.

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The role of laser interstitial thermal therapy in enhancing progression‐free survival of difficult‐to‐access high‐grade gliomas: a multicenter study

Cancer Medicine ◽

10.1002/cam4.266 ◽

2014 ◽

Vol 3 (4) ◽

pp. 971-979 ◽

Cited By ~ 128

Author(s):

Alireza M. Mohammadi ◽

Ammar H. Hawasli ◽

Analiz Rodriguez ◽

Jason L. Schroeder ◽

Adrian W. Laxton ◽

...

Keyword(s):

Multicenter Study ◽

Progression Free Survival ◽

Thermal Therapy ◽

High Grade ◽

Free Survival ◽

Laser Interstitial Thermal Therapy ◽

High Grade Gliomas

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The impact of surgery in high grade gliomas - a literature review

Romanian Neurosurgery ◽

10.1515/romneu-2015-0040 ◽

2015 ◽

Vol 29 (3) ◽

pp. 295-308

Author(s):

Adriana Baritchii ◽

A. Gubian ◽

St.I. Florian

Keyword(s):

Malignant Gliomas ◽

Progression Free Survival ◽

Extent Of Resection ◽

Cortical Mapping ◽

High Grade ◽

Free Survival ◽

Mortality And Morbidity ◽

High Grade Gliomas ◽

The Impact ◽

Related Mortality

Abstract Malignant gliomas are aggressive brain cancers. After many decades of intensive research they represent a major cause of cancer related mortality and morbidity. Management of malignant gliomas is very difficult. None of the current treatments are curative. High grade gliomas are optimally treated with surgery followed by radiotherapy and chemotherapy. The impact of surgery on progression free survival and overall survival was a constant preoccupation and debate for decades among neurosurgeons. Different studies published in the last 25 years have provided evidence that the extent of resection of high grade gliomas can influence time to progression and median survival, although so far there is no class I prospective randomized trial to fully answer this question. Some of the most important studies are reviewed here. The modern neurosurgery relay on some tools that proved to be very helpful in guiding the surgeon to achieve the maximal tumoral cytoreduction with minimum impact on the brain’s eloquent areas. iMRI has been proved to be safe and became an important tool during tumor surgery, used alone or in conjuction with other important techniques: intraoperative neurophysiology, awake cortical mapping, 5-ALA fluorescence etc. Although so far the prognostic of high grade gliomas is still disappointing, further understanding of the biology of these tumors and a patient-tailored treatment could be the keys of finding a cure in the future.

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Outcomes of Salvage Fractionated Reirradiation Combined With Bevacizumab for Recurrent High-grade Gliomas That Progressed After Treatment With Bevacizumab

10.21203/rs.3.rs-147697/v1 ◽

2021 ◽

Author(s):

Hajime Yonezawa ◽

Makoto Ohno ◽

Hiroshi Igaki ◽

Yasuji Miyakita ◽

Masamichi Takahashi ◽

...

Keyword(s):

Gastrointestinal Haemorrhage ◽

Progression Free Survival ◽

High Grade Glioma ◽

High Grade ◽

Mutation Status ◽

Free Survival ◽

Not Otherwise Specified ◽

Radiological Response ◽

High Grade Gliomas ◽

Grade 3

Abstract Background: This study evaluated the outcomes of reirradiation combined with bevacizumab (Bev) for patients with recurrent high-grade gliomas that progressed after treatment with Bev.Methods: Between January 2015 and September 2019, 14 patients who experienced progression after Bev treatment were treated with reirradiation consisting of 25 Gy in five fractions combined with Bev (ReRT/Bev). The isocitrate dehydrogenase (IDH) 1/2 mutation status was analysed by pyrosequencing. Results: The diagnoses of 14 patients at the time of reirradiation included six cases of glioblastoma (GBM) with IDH-wildtype, four cases of GBM with IDH-mutant, one case of anaplastic astrocytoma (AA) with IDH-wildtype, one case of AA with IDH-mutant, and one case of GBM not otherwise specified (NOS), and one case of radiologically diagnosed brainstem glioma. The median overall survival (OS) and progression-free survival (PFS) times with ReRT/Bev were 6.1 months and 3.8 months, respectively. The 6-month OS and PFS rates were 54.5% and 15.7%, respectively. The median OS and PFS did not differ significantly between patients with IDH-wildtype (N=7) and IDH-mutant (N=5) (OS: 7.3 [wildtype] vs 6.0 [mutant] months, p = 0.64; PFS: 3.8 [wildtype] vs 3.7 [mutant] months, p = 0.56). The median OS and PFS did not differ significantly between patients with a diagnosis of GBM (N=6) and those with a diagnosis of non-GBM (N=7) (OS: 9.3 [GBM] vs 6.0 [non-GBM] months, p = 0.19; PFS: 4.0 [GBM] vs 3.8 [non-GBM] months, p = 0.31). Four patients (28.6%) achieved a complete or partial radiological response and three patients (21.4%) experienced improvement after ReRT/Bev. Tumor recurrences were observed in 12 patients, including 3 (21.4%) in-field recurrence; 5 (35.7%) marginal recurrence, 3 (21.4%) out-field recurrence, and 1 (7.1%) had in-field and out-field recurrence. Grade 3/4 toxicities included leukopenia in four patients (28.6%), hypertension in three (21.4%), proteinuria in one (7.1%), and gastrointestinal haemorrhage in one (7.1%) with ReRT/Bev. Conclusions: ReRT/Bev for patients with high-grade glioma who experienced progression after Bev was effective and involved acceptable toxicities.

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Irinotecan and bevacizumab in progressive primary brain tumors: The Cleveland Clinic experience

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.2077 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 2077-2077 ◽

Cited By ~ 2

Author(s):

T. Kang ◽

T. Jin ◽

D. Peereboom

Keyword(s):

Overall Survival ◽

Cleveland Clinic ◽

Progression Free Survival ◽

Median Number ◽

High Grade ◽

Free Survival ◽

Intention To Treat ◽

Kaplan Meier ◽

High Grade Gliomas ◽

Chemotherapy Patients

2077 Background: High-grade gliomas are generally resistant to modern chemotherapy. In the case of glioblastoma multiforme, median overall survival has been less than 12 months and progression free survival of less than 4 months. For patients with recurrent GBMs, the 6 month progression free survival is 15–20%. The combination of irinotecan and bevacizumab is an active regimen in the treatment of this disease. Herein we report the experiences with this regimen at our institution with the objective of identifying a therapy with a better outcome than historical results. Methods: Single institutional, retrospective review of 27 patients with recurrent or progressive high grade gliomas treated at the Cleveland Clinic Brain Tumor Institute from 7/2005 through 10/2006. Patients had progressed on at least one prior chemotherapy. Patients with prior irinotecan or bevacizumab were excluded. Patients were analyzed on an intention-to-treat basis, and outcomes estimated by the Kaplan-Meier method. Results: The median age of the group was 46 years (range 5–69). The median number of prior therapies was 2 (range 1–10). Twenty of 27 patients have progressed (74%), and 11 of 27 patients have died (41%). Kaplan-Meier estimates for outcomes are summarized in the table . Progression-free survival at 6 months is 46 %, with median of 5.1 months. Overall survival at 6 months is 84%, with median of 12.6 months. In 7 patients, treatment was terminated early prior to progression. Significant toxicities include: one patient who developed hematuria, one patient with deep venous thrombosis and one patient who experienced intracranial hemorrhage. Conclusions: Our experience suggests that the combination of irinotecan and bevacizumab improves the 6-month progression-free survival when compared to historical figures. The rate of severe toxicities is consistent with prior reports and mandates careful selection of patients. Further randomized, phase 3 studies should be done to validate these results. [Table: see text] No significant financial relationships to disclose.

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Current FDA-Approved Therapies for High-Grade Malignant Gliomas

Biomedicines ◽

10.3390/biomedicines9030324 ◽

2021 ◽

Vol 9 (3) ◽

pp. 324

Author(s):

Jacob P. Fisher ◽

David C. Adamson

Keyword(s):

Controlled Trial ◽

Malignant Gliomas ◽

Progression Free Survival ◽

Standard Of Care ◽

High Grade ◽

Tumor Treatment ◽

Free Survival ◽

Randomized Controlled ◽

Significant Survival ◽

One Year

The standard of care (SOC) for high-grade gliomas (HGG) is maximally safe surgical resection, followed by concurrent radiation therapy (RT) and temozolomide (TMZ) for 6 weeks, then adjuvant TMZ for 6 months. Before this SOC was established, glioblastoma (GBM) patients typically lived for less than one year after diagnosis, and no adjuvant chemotherapy had demonstrated significant survival benefits compared with radiation alone. In 2005, the Stupp et al. randomized controlled trial (RCT) on newly diagnosed GBM patients concluded that RT plus TMZ compared to RT alone significantly improved overall survival (OS) (14.6 vs. 12.1 months) and progression-free survival (PFS) at 6 months (PFS6) (53.9% vs. 36.4%). Outside of TMZ, there are four drugs and one device FDA-approved for the treatment of HGGs: lomustine, intravenous carmustine, carmustine wafer implants, bevacizumab (BVZ), and tumor treatment fields (TTFields). These treatments are now mainly used to treat recurrent HGGs and symptoms. TTFields is the only treatment that has been shown to improve OS (20.5 vs. 15.6 months) and PFS6 (56% vs. 37%) in comparison to the current SOC. TTFields is the newest addition to this list of FDA-approved treatments, but has not been universally accepted yet as part of SOC.

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