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Daily bibliographic review of the Neurosurgery Department Hospital General Universitario de Alicante, Spain

Biopsy versus resection in the management of malignant gliomas: a systematic review and meta-analysis

J Neurosurg 112:1020–1032, 2010. DOI: 10.3171/2009.7.JNS09758

The aim of this study was to answer the question whether quality of life and progression-free and overall survival are increased in adults with supratentorial malignant glioma who are treated with cytoreductive resection as compared with those who only undergo biopsy.

Methods. A literature search of the electronic databases MEDLINE, EMBASE, and CENTRAL was performed to identify relevant studies published before May 2008. Hand-searching of reference lists of the identified studies and relevant review articles was also performed. A study was considered eligible, regardless of study design (prospective or retrospective), if: 1) quality of life and/or progression-free and/or overall survival was compared among adult patients undergoing biopsy or resection, and 2) patient age and Karnofsky Performance Scale scores were not significantly different among the 2 groups compared.

Results. One randomized controlled trial and 4 retrospective studies (involving a total of 1111 patients) were found eligible for this systematic review. A meta-analysis of the eligible studies demonstrated a significant increase in overall survival in the patients treated with resection instead of biopsy (hazard ratio 0.61, 95% CI 0.52–0.71, p < 0.0001, fixed-effect model). Although statistical pooling was not feasible, the available data suggest that quality of life was increased in patients treated with resection rather than biopsy, while there did not seem to be any significant difference in progression-free survival between the 2 groups.

Conclusions. Based on the best available evidence, it appears that cytoreductive resection in adults with supratentorial malignant glioma is associated with improved overall survival as compared with biopsy. However, well designed prospective studies are needed for more solid conclusions to be drawn.

Combination of Intracranial Temozolomide With Intracranial Carmustine Improves Survival When Compared With Either Treatment Alone in a Rodent Glioma Model

Neurosurgery:March 2010 – Volume 66 – Issue 3 – p 530–537.doi: 10.1227/01.NEU.0000365263.14725.39

BACKGROUND: Local delivery of temozolomide (TMZ) through polymers is superior to oral administration in a rodent glioma model.

OBJECTIVE: We hypothesized that the observed clinical synergy of orally administered TMZ and carmustine (BCNU) wafers would translate into even greater effectiveness with the local delivery of BCNU and TMZ and the addition of radiotherapy in animal models of malignant glioma.

METHODS: TMZ and BCNU were incorporated into biodegradable polymers that were implanted in F344 rats bearing established intracranial tumors. We used 2 different rodent glioma models: the 9L gliosarcoma and the F98 glioma.

RESULTS: In the 9L rodent glioma model, groups treated with the combination of local TMZ, local BCNU, and radiation therapy (XRT) had 75% long-term survivors (defined as animals alive 120 days after tumor implantation), which was superior to the combination of local TMZ and local BCNU (median survival, 95 days; long-term survival, 25%) and the combination of oral TMZ, local BCNU, and XRT (median survival, 62 days; long-term survival, 12.5%). To simulate the effect of this treatment in chemoresistant gliomas, a second rodent model was used with the F98 glioma, a cell line relatively resistant to alkylating agents. F98 glioma cells express high levels of alkyltransferase, an enzyme that deactivates alkylating agents and is the major mechanism of resistance of gliomas. The triple therapy showed a significant improvement in survival when compared with controls (P = .0004), BCNU (P = .0043), oral TMZ (P = .0026), local TMZ (P = .0105), and the combinations of either BCNU and XRT (P = .0378) or oral TMZ and BCNU (P = .0154).

CONCLUSION: The survival of tumor-bearing animals in the 9L and F98 glioma models was improved with the local delivery of BCNU and TMZ combined with XRT when compared with either treatment alone or oral TMZ, local BCNU, and XRT.

Primary Intramedullary Tumors of the Spinal Cord

SPINE Volume 34, Number 22S, pp S69 –S77, 2009

Study Design. Clinically based systematic review.

Objective. To define optimal clinical care for primary intramedullary spinal cord tumors using a systematic re- view with expert opinion.

Methods. Focused questions on the treatment of primary intramedullary spinal cord tumors were refined by a panel of spine oncology surgeons, medical and radiation oncologist. Keyword were searched through Medline database and pertinent abstracts and manuscripts obtained. The quality of literature was rated as high, moderate, low, or very low. Using the GRADE evidence based review system the proposed questions were answered using the literature review and expert opinion. These treatment recommendations were then rated as either strong or weak based on the quality of evidence and clinical expertise.

Results. The literature searches revealed low and very low quality evidence with no prospective or randomized studies. The MEDLINE search engine returned 9000 articles which was restricted to articles about human subjects and written in the English language. The subsequent search resulted in a return of: “spinal cord tumor” (5053), “ependymoma” (580), “astrocytoma” (420), and “glioma” (235) articles. Seventeen articles referenced timing of surgical intervention and symptomatology for intramedullary spinal cord tumors. One hundred fifty-eight chemotherapy and 183 radiation therapy articles for intramedullary spinal cord tumors were reviewed.

Conclusion. The most important factor in determining the IMSCT patient’s long-term neurologic and functional outcome after surgery is the patient’s preoperative neurologic status. However, this must be taken in the context of the underlying tumor histology. Therefore, resection is reserved for progressive neurologic decline and serial monitoring for asymptomatic individuals. Adjuvant therapy is an option for high grade astrocytomas (WHO grades 3–4).


Bevacizumab Alone and in Combination With Irinotecan in Recurrent Glioblastoma

Journal of Clinical Oncology. DOI:10.1200/JCO.2008.19.8721

Purpose

We evaluated the efficacy of bevacizumab (Avastin TM), alone and in combination with irinotecan, in patients with recurrent glioblastoma in a phase II, multicenter, open-label, noncomparative trial.

Patients and Methods

One hundred sixty-seven patients were randomly assigned to receive bevacizumab 10 mg/kg alone or in combination with irinotecan 340 mg/m2 or 125 mg/m2 (with or without concomitant enzyme-inducing antiepileptic drugs, respectively) once every 2 weeks. Primary end points were 6-month progression-free survival and objective response rate, as determined by independent radiology review. Secondary end points included safety and overall survival.

Results

In the bevacizumab-alone and the bevacizumab-plus-irinotecan groups, estimated 6-month progression-free survival rates were 42.6% and 50.3%, respectively; objective response rates were 28.2% and 37.8%, respectively; and median overall survival times were 9.2 months and 8.7 months, respectively. There was a trend for patients who were taking corticosteroids at baseline to take stable or decreasing doses over time. Of the patients treated with bevacizumab alone or bevacizumab plus irinotecan, 46.4% and 65.8%, respectively, experienced grade  3 adverse events, the most common of which were hypertension (8.3%) and convulsion (6.0%) in the bevacizumab-alone group and convulsion (13.9%), neutropenia (8.9%), and fatigue (8.9%) in the bevacizumab-plus-irinotecan group. Intracranial hemorrhage was noted in two patients (2.4%) in the bevacizumab-alone group (grade 1) and in three patients (3.8%) patients in the bevacizumabplus-irinotecan group (grades 1, 2, and 4, respectively).

Conclusion

Bevacizumab, alone or in combination with irinotecan, was well tolerated and active in recurrent glioblastoma.

Biopsy versus resection in the management of malignant gliomas

DOI: 10.3171/2009.7.JNS09758

The aim of this study was to answer the question whether quality of life and progression-free and overall survival are increased in adults with supratentorial malignant glioma who are treated with cytoreductive resection as compared with those who only undergo biopsy.

Methods. A literature search of the electronic databases MEDLINE, EMBASE, and CENTRAL was performed to identify relevant studies published before May 2008. Hand-searching of reference lists of the identified studies and relevant review articles was also performed. A study was considered eligible, regardless of study design (prospective or retrospective), if: 1) quality of life and/or progression-free and/or overall survival was compared among adult patients undergoing biopsy or resection, and 2) patient age and Karnofsky Performance Scale scores were not significantly different among the 2 groups compared.

Results. One randomized controlled trial and 4 retrospective studies (involving a total of 1111 patients) were found eligible for this systematic review. A meta-analysis of the eligible studies demonstrated a significant increase in overall survival in the patients treated with resection instead of biopsy (hazard ratio 0.61, 95% CI 0.52–0.71, p <0.0001, fixed-effect model). Although statistical pooling was not feasible, the available data suggest that quality of life was increased in patients treated with resection rather than biopsy, while there did not seem to be any significant difference in progression-free survival between the 2 groups.

Conclusions. Based on the best available evidence, it appears that cytoreductive resection in adults with supratentorial malignant glioma is associated with improved overall survival as compared with biopsy. However, welldesigned prospective studies are needed for more solid conclusions to be drawn.

Cell phones and brain tumors: a review including the long-term epidemiologic data

Vini G. Khurana, PhD, FRACS, Charles Teo, MBBS, FRACS, Michael Kundi, PhD, Lennart Hardell, MD, PhD, Michael Carlberg, MSc.

Surgical Neurology Volume 72, Issue 3, Pages 205-214 (September 2009) doi:10.1016/j.surneu.2009.01.019


The debate regarding the health effects of low-intensity electromagnetic radiation from sources such as power lines, base stations, and cell phones has recently been reignited. In the present review, the authors attempt to address the following question: is there epidemiologic evidence for an association between long-term cell phone usage and the risk of developing a brain tumor? Included with this meta-analysis of the long-term epidemiologic data are a brief overview of cell phone technology and discussion of laboratory data, biological mechanisms, and brain tumor incidence.

In order to be included in the present meta-analysis, studies were required to have met all of the following criteria: (i) publication in a peer-reviewed journal; (ii) inclusion of participants using cell phones for ≥10 years (ie, minimum 10-year “latency”); and (iii) incorporation of a “laterality” analysis of long-term users (ie, analysis of the side of the brain tumor relative to the side of the head preferred for cell phone usage). This is a meta-analysis incorporating all 11 long-term epidemiologic studies in this field.

The results indicate that using a cell phone for ≥10 years approximately doubles the risk of being diagnosed with a brain tumor on the same (“ipsilateral”) side of the head as that preferred for cell phone use. The data achieve statistical significance for glioma and acoustic neuroma but not for meningioma.

Conclusion

The authors conclude that there is adequate epidemiologic evidence to suggest a link between prolonged cell phone usage and the development of an ipsilateral brain tumor.


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