Survival statistics show hard fight when malignant brain tumors appear at multiple sites
LOS ANGELES (Aug. 24, 2012) – When aggressive, malignant tumors appear in more than one location in the brain, patient survival tends to be significantly shorter than when the disease starts as a single tumor, even though patients in both groups undergo virtually identical treatments, according to research at Cedars-Sinai Medical Center’s Maxine Dunitz Neurosurgical Research Institute.
“We’ve known that certain independent factors, such as age at diagnosis, amount of residual tumor after surgery, and the patient’s functional status are useful in predicting outcomes in patients with glioblastoma multiforme, but multifocal disease at time of onset has rarely been examined in this context. Two small previous studies were contradictory. Our study appears to confirm observations that disease in patients with more than one lesion is particularly challenging and that these patients tend to have worse outcomes. Matched survival analysis demonstrated that multifocal disease is a strong and negative independent prognostic factor,” said Chirag G. Patil, MD, director of the Center for Neurosurgical Outcomes Research in the Department of Neurosurgeryat Cedars-Sinai Medical Center.
The researchers compared outcomes of 47 patients who had multiple tumors with 47 who had a single lesion, matching them for age, functional impairment scores, extent of tumor removal and radiation therapy and chemotherapy. Median overall survival for the multifocal group was six months, compared to 11 months for those in the single tumor group.
Patil, first author of an article in the Aug. 24 Journal of Neurosurgery, noted that a comparatively large percentage of tumors in the multifocal group appeared to be “treatment resistant,” continuing to grow even after patients underwent radiation therapy.
Unlike earlier studies, nearly all of these patients were diagnosed and treated during the “temozolomide era,” beginning in 2005 when this drug joined radiation therapy as the mainstay of glioblastoma treatment. Even so, 11 of the 47 patients in the multifocal group did not receive temozolomide because, the researchers suggest, disease progression is so quick that many patients are unable to start or complete standard therapies.
Patil said researchers believe cells of multifocal tumors may have an increased ability to migrate in the brain and invade normal tissue, leading to more rapid patient decline; recent advances in therapies for glioblastomas have not improved survival in these patients.
“A thorough investigation of the unique biology of these tumors and their invasive and migratory mechanisms is needed so we may develop a new generation of targeted therapies,” said Patil, who received a Cedars-Sinai grant that will fund the study of genetic and biological differences between single tumors and those originating at multiple sites.
Glioblastoma multiforme is the most common and aggressive malignant tumor occurring in the brain, and patients typically survive 15 months when undergoing standard treatments. Other single-tumor patients in the larger pool from which those in this study were derived, had median survival of 16 months. The shorter 11-month survival of study patients is believed to result from the matching process: Because many of those with multiple-site tumors could not undergo complete tumor removal, their corresponding single-site patients had tumors with locations or characteristics that made them appropriate for biopsy only.
Citation: Journal of Neurosurgery, Aug. 24, 2012, “Prognosis of Patients with Multifocal Glioblastoma: A Case-Controlled Study.”
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Introducing the Metastatic Brain & Spine Tumor Clinic
at Cedars-Sinai Medical Center
The goal of the Metastatic Brain & Spine Tumor Clinic is to provide compassionate, cutting edge, evidence-based-care to patients with brain and spine metastases. With our systematic approach to the diagnosis, treatment and follow-up of these complicated patients, we focus on maximizing their quality of life and optimizing their clinical outcomes. We pride ourselves on clear and frequent communication with our referring oncologists and physicians. All new consultations are seen within a few days and urgent consults can be seen within 24 hours.
The Metastatic Tumor Clinic will be staffed by Stanford-trained neurosurgeon and brain tumor specialist, Chirag G. Patil M.D., and one of the most experienced spine tumor experts,John Liu, M.D. With the approval of the referring oncologist, specialists from radiation oncology and neuro-oncology will be available for consultation during the same visit. All care will be coordinated and delivered WITH the full consent of the referring oncologist.
With our promise of outstanding care and communication, you can rest assured that your patient's brain and spine metastases are being optimally managed.
Please contact our New Patient Schedulers on our dedicated doctor's line at 310-423-METS (6387).
Thank you and we hope to work with you closely in the near future.
Chirag G. Patil, M.D.
IMPORTANT WARNING: This message is intended for the use of the person or entity to which it is addressed and may contain information that is privileged and confidential, the disclosure of which is governed by applicable law. If the reader of this message is not the intended recipient, or the employee or agent responsible for delivering it to the intended recipient, you are hereby notified that any dissemination, distribution or copying of this information is STRICTLY PROHIBITED. If you have received this message in error, please notify us immediately by calling (310) 423-6428 and destroy the related message. Thank You for your cooperation. IMPORTANT WARNING: This message is intended for the use of the person or entity to which it is addressed and may contain information that is privileged and confidential, the disclosure of which is governed by applicable law. If the reader of this message is not the intended recipient, or the employee or agent responsible for delivering it to the intended recipient, you are hereby notified that any dissemination, distribution or copying of this information is STRICTLY PROHIBITED.
If you have received this message in error, please notify us immediately by calling (310) 423-6428 and destroy the related message. Thank You for your cooperation.
-- Chirag G. Patil M.D. Department of Neurosurgery Cedars-Sinai Medical Center
Department of Neurosurgery, Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, 8631 West Third Street, Suite 800E, Los Angeles, California, USA, 90048.
Historically, whole brain radiation therapy (WBRT) has been the main treatment for brain metastases. Stereotactic radiosurgery (SRS) delivers high dose focused radiation and is being increasingly utilized to treat brain metastases. The benefit of adding radiosurgery to WBRT is unclear.
To assess the efficacy of WBRT plus radiosurgery versus WBRT alone in the treatment of of brain metastases.
We searched the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2009), MEDLINE (1966 to 2009), EMBASE (1980 to 2009) and CancerLit (1975 to 2009) in order to identify trials for inclusion in this review.
The review was restricted to randomised controlled trials (RCTs) that compared use of radiosurgery and WBRT versus WBRT alone for upfront treatment of adult patients with newly diagnosed metastases (single or multiple) in the brain resulting from any primary, extracranial cancer
DATA COLLECTION AND ANALYSIS:
The Generic Inverse Variance method, random effects model in RevMan 5 was used for the meta-analysis.
A meta-analysis of two trials with a total of 358 participants, found no statistically significant difference in overall survival (OS) between WBRT plus radiosurgery and WBRT alone groups (HR = 0.82, 95% CI 0.65 to 1.02). For patients with one brain metastasis median survival was significantly longer in WBRT plus SRS group (6.5 months) versus WBRT group (4.9 months, P = 0.04). Patients in the WBRT plus radiosurgery group had decreased local failure compared to patients who received WBRT alone (HR = 0.27, 95% CI 0.14 to 0.52). Furthermore, a statistically significant improvement in performance status scores and decrease in steroid use was seen in the WBRT plus SRS group. Unchanged or improved KPS at 6 months was seen in 43% of patients in the combined therapy group versus only 28% in WBRT group (P = 0.03). Overall, risk of bias in the included studies was unclear.
Given the unclear risk of bias in the included studies, the results of this analysis have to be interpreted with caution. Analysis of all included patients, SRS plus WBRT, did not show a survival benefit over WBRT alone. However, performance status and local control were significantly better in the SRS plus WBRT group. Furthermore, significantly longer OS was reported in the combined treatment group for RPA Class I patients as well as patients with single metastasis.
-- Chirag G. Patil M.D. Department of Neurosurgery Cedars-Sinai Medical Center
The goal of the Metastatic Brain & Spine Tumor Clinic is to provide compassionate, cutting edge, evidence-based-care to patients with brain and spine metastases. With our systematic approach to the diagnosis, treatment and follow-up of these complicated patients, we focus on maximizing their quality of life and optimize their clinical outcomes. This is a interdisciplinary clinic where we have not only neurosurgeons but also specialists from radiation oncology and neuro-oncology that can evaluate patients during the same visit. The Clinic will be staffed by Stanford trained neurosurgeon, Chirag G. Patil M.D. who specializes in the care of Metastatic Brain Tumor patients together with one of most experienced Spine Tumor experts, John Liu MD. All new consultations are seen within a few days and urgent consults can be seen within 24 hours. For an appointment, please call 310-423-7900 and then press 1 to be connected immediately to a new patient scheduler.