- Department of Neurological Surgery, University of Washington School of Medicine, Seattle WA, USA
- Department of Medical Oncology, Sanford Roger Maris Cancer Center,Fargo ND, USA
- Department of Medical Oncology, University of North Dakota School of Medicine, Grand Forks ND, USA
Correspondence Address:
Daniel L. Silbergeld
Department of Neurological Surgery, University of Washington School of Medicine, Seattle WA, USA
DOI:10.4103/2152-7806.111300
Copyright: © 2013 Levitt MR This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.How to cite this article: Levitt MR, Levitt R, Silbergeld DL. Controversies in the management of brain metastases. Surg Neurol Int 02-May-2013;4:
How to cite this URL: Levitt MR, Levitt R, Silbergeld DL. Controversies in the management of brain metastases. Surg Neurol Int 02-May-2013;4:. Available from: http://sni.wpengine.com/surgicalint_articles/controversies-in-the-management-of-brain-metastases/
Abstract
The multidisciplinary management of brain metastases has generated substantial controversy as treatment has diversified in recent years. Debate about the type, role, and timing of different diagnostic and therapeutic strategies has promoted rigorous scientific research into efficacy. However, much still remains unanswered in the treatment of this difficult disease process. This manuscript seeks to highlight some of the controversies identified in previous sections of this supplement, including prognosis, pathology, radiation and surgical treatment, neuroimaging, and the biochemical underpinnings of brain metastases. By recognizing what is yet unanswered, we hope to identify areas in which further research may yield promising results.
Keywords: Brain metastases, biomarkers, chemotherapy, neuroimaging, stereotactic radiosurgery, whole-brain radiation therapy
INTRODUCTION
The rapid development of multimodal treatments for brain metastases has generated controversy both in practice and in the published literature.[
More than just an advanced stage of systemic cancer, the presence of brain metastases is a harbinger of worsened systemic prognosis. More than two-thirds of cancer patients diagnosed with brain metastases die of systemic disease progression, rather than the brain metastases themselves.[
The National Comprehensive Cancer Network (NCCN) attempts to standardize diagnostic and treatment algorithms for oncological care in the United States. Algorithms for oligometastases (1-3 metastases), multiple metastases (>3), and leptomeningeal metastases have been developed for both initial and recurrent treatment.[
PROGNOSIS
Multiple factors must be taken into account when determining the prognosis of patients with brain metastases, since prognosis influences treatment decision-making. The most important of these include age, functional status (usually measured by Karnofsky Performance Score [KPS], systemic disease status (including disease burden and progression despite systemic treatment), primary site,[
As stated earlier, institutional biases can impact the prognostic estimations of practitioners in specific practice settings, and some indices that employ more subjective grading criteria (such as the Rotterdam scoring system,[
PATHOLOGY
The primary histological subtype of brain metastases is an essential factor in the prognosis and treatment of brain metastases. However, recent advancements in immunohistochemical testing and tumor biomarkers have led some practitioners to reconsider “traditional” treatment paradigms for certain tumor subtypes. For instance, breast cancer biomarkers, which carry significant prognostic and therapeutic implications (such as hormone and HER2 receptor status and p53- and Ki-67 proliferative indices), can vary between primary tumor and brain metastases.[
Prophylactic chemotherapy in the prevention of brain metastases is more controversial. Some oncologists have proposed prophylactic lapatinib for patients with established extracranial metastases or who are at high risk for brain metastases, though this strategy is unproven.[
WHOLE-BRAIN RADIOTHERAPY
Whole-brain radiotherapy (WBRT) is an established treatment for brain metastases, and evolving techniques have improved progression-free and overall survival in many patients.[
Late cognitive changes have also been associated with WBRT, and have often been considered a significant drawback to the survival benefit conferred by this treatment.[
SURGERY
Surgical treatment for brain metastases has been established as useful tool in certain patient scenarios, especially when limited to a single metastatic lesion in patients with good KPS and controlled extracranial disease. While some cases necessitate urgent surgical intervention (such as hemorrhagic metastases with pending herniation, large posterior fossa metastases with secondary hydrocephalus and brainstem compression), for other cases surgery is contraindicated (multiple metastases not easily accessible with one surgical approach, inoperable locations of metastases, significant medical comorbidities, etc.). It is the large number of cases that fall between these two extremes where treatment becomes controversial. Debate still exists regarding the superiority of surgery versus stereotactic radiosurgery (SRS),[
NEUROIMAGING
The rapid adoption of advanced neuroimaging has improved the diagnosis and surveillance of brain metastases in recent years. However, determination of the classic diagnostic conundrum of whether a solitary enhancing brain mass represents metastases or primary glial neoplasm remains elusive, as both entities can appear identical on even high-resolution contrast-enhanced MRI. MR-spectroscopy[
SEED AND SOIL
The CNS is considered fertile “soil” for the “seed” of metastatic disease.[
CONCLUSION
The treatment of brain metastases remains challenging despite recent advancements in surgery, radiation oncology, and chemotherapeutics. Because most patients with brain metastases succumb to systemic disease progression, treatment of brain metastases does not often provide increased overall survival. In other words, as long as the CNS disease is treated, systemic disease will usually be the primary “driver.”
Advancements in neuroimaging, biomarker pathology, genetics, and treatment delivery will continue improve patient outcomes and quality of life, through the generation of new questions and controversies for which further study is developed. The most effective overall treatments require a multidisciplinary team of oncologists, neuro-oncologsts, neurosurgeons, and radiation oncologists. In combination with ancillary support staff, a multidimensional approach will ensure the best tailored therapy for each patient's individual situation, affording patient's clarity of goals, a wider array of options, and sustained hope.
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