Emerging Subspecialties in Neurology: Neuro-oncology
A developing subspecialty with many opportunities
Brian Vaillant, MD,
Sheng-Han Kuo, MD and
John de Groot, MD
From the Department of Neuro-oncology (B.V., J.d.G.), The University of Texas M.D. Anderson Cancer Center; and the Department of Neurology (S.-H.K.), Baylor College of Medicine, Houston, TX.
Address correspondence and reprint requests to Dr. John de Groot, Department of Neuro-oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX jdegroot{at}mdanderson.org.
Neuro-oncology is a unique, developing neurologic subspecialtythat combines many aspects of neurology with those of cancerbiology. The neuro-oncologist is expert in both the diagnosisand management of primary brain tumors and neurologic complicationsof cancer. A career in neuro-oncology presents opportunitiesto utilize a multidisciplinary team approach and the applicationof cutting-edge technology toward patient treatment while providingcompassionate patient care.
Neuro-oncology can trace its modern origins to the 1970s, whenthe first therapeutic trials were begun. The treatment and managementof primary brain tumors is now a rapidly evolving field. TheWorld Health Organization recognizes approximately 100 differenttypes of primary and secondary brain tumors.1,2 Glioblastoma,which is the most common and aggressive type of primary braintumor, has an incidence of 4 to 5 cases per 100,000. For patientswith glioblastoma, life expectancies are measured in monthsrather than years, with median survival after diagnosis of only12 to 14 months. In the past, surgical resection and radiationtherapy were the main treatment options offered to these patients.In the last several years, studies have shown that chemotherapyprovides a significant clinical benefit for patients with malignantbrain tumors.3 More recently, molecular markers that predictresponse to treatment are beginning to be identified in glioblastoma.4Clinical trials that incorporate biologic endpoints and correlativestudies are improving our understanding of the mechanisms ofdisease and tumor response to treatment. This greater knowledgewill lead to the development of more effective agents and individualizedtreatments based on specific tumor profiles. In addition toglioblastoma, the neuro-oncologist manages less common tumors,including other types of glioma, germ cell tumors, meningiomas,medulloblastomas, and primary CNS lymphomas, and becomes familiarwith the cancers' different biologic and molecular profiles,and treatment approaches. Despite the often poor prognosis ofpatients with brain and spinal tumors, long-term successes arepossible. Patient care focuses not only on improving survivalbut also on preserving quality of life for these patients andproviding support for their families.
The neuro-oncologist also specializes in the care of patientswith challenging neurologic complications associated with systemiccancers. A common complication of systemic cancer is metastasisto the brain. It is the most common type of brain tumor, withup to 170,000 cases a year in the United States. The neuro-oncologistis proficient in the management of seizures, cerebral edema,stroke, peripheral nerve disorders, and demyelinating disease,which often present unique diagnostic dilemmas and require complexmanagement decisions in patients with cancer. Altered mentalstatus is a common reason for neurologic consultation, and hospitalizedpatients with cancer usually have multiple causes of delirium,which requires a detailed history and neurologic examinationto determine the accurate diagnosis.5 Neuro-oncologists sharpentheir skills in lesion localization by observing neurologicdeficits in the presurgical and postsurgical setting. This acumenis also vitally important in identifying the early signs andsymptoms of spinal and leptomeningeal metastasis. Radiationtherapy and chemotherapy can produce a variety of complicationsinvolving the nervous system, including strokes, seizures, demyelination,and focal necrosis. The challenging and complex nature of patientcare makes neuro-oncology an interesting and exciting subspecialty.
Neuro-oncologists plays a unique role by coordinating the careof each patient in collaboration with a wide variety of specialists,including neurosurgeons, radiation oncologists, neuropathologists,psychiatrists, and rehabilitation physicians. In this role,the neuro-oncologist has broad knowledge of these other specialtiesand the role they play in patient management. In academic settings,tumor boards are a core teaching venue and foster camaraderieand collaboration between neuro-oncologists and other subspecialtygroups in an effort to develop optimal treatment plans for individualpatients. Additionally, neuro-oncologists work closely withmedical oncologists in coordinating care of patients with systemiccancers and brain metastases. Advances in neuro-oncology willrequire teamwork among clinicians and clinical and translationalresearch programs so that the expertise from the myriad of fieldsinvolved can be integrated into the development of cohesivepatient-oriented treatment plans. Opportunities exist for neuro-oncologiststo collaborate with other physicians on cooperative cancer groupand multi-institutional clinical trials. Effective communicationskills are essential in neuro-oncology, especially because thisneurologic subspecialty includes the discussion of complex medicalissues and terminal diagnoses.
With the explosion of our understanding of the molecular biologyof cancer, neuro-oncology offers numerous opportunities forclinician-scientists to participate in the development and clinicaltesting of novel molecularly targeted agents. Glioblastoma islikely a heterogenous disease,6 and thus not all types shouldbe treated uniformly. With the proper training, a neuro-oncologistcan utilize tools from cellular and molecular biology to designand evaluate the next generation of clinical trials. In thefuture, neuro-oncologists will integrate newly identified molecularbiomarkers into clinical trials in an effort to develop individualizedpatient treatments. Biologic agents targeting proangiogenicfactors, such as the vascular endothelial growth factor, andkinases, such as Src, epidermal growth factor receptor, andPI3 kinase, are promising treatment options as adjuncts to cytotoxicchemotherapies. The future holds promise that one day the molecularprofile of a patient's tumor may predict tumor response to therapyand guide management decisions. The Cancer Genome Atlas project(http://cancergenome.nih.gov/) is systematically exploring thegenomic changes involved in selected human cancers includingglioblastoma, and the information it provides on molecular derangementsin glioblastoma may be used to discover new targets for therapy.Neuro-oncologists will spearhead the future integration of thesemolecular discoveries into clinical trials in the effort todevelop more effective treatments for brain tumors.
Another rapidly developing area of focus in neuro-oncology isthe use of noninvasive methods of detecting tumor proliferation,invasion, and angiogenesis within the brain. Dynamic contrast-enhancedMRI, which can assess aspects of the tumor vasculature, andPET, which can be used to evaluate tumor proliferation, hypoxia,and metabolism, are two of the many exciting advances in neuroradiologythat may help change the way in which patients with gliomasare treated in the future. Functional MRI studies such as bloodoxygenation level–dependent MRI and intraoperative MRIallow the neurosurgeon to precisely excise brain tumors withminimal injury to normal brain tissue, helping to maximize surgicalresection and patient outcome7 while simultaneously preventingdevastating neurologic sequelae. In the future, neurogeneticistsand epidemiologists will assist in the determination of a patient'spharmacogenetic profile to predict response to, and toxicityfrom, specific treatments. Neuro-oncology is based on a multidisciplinaryapproach that seeks to incorporate these novel technologies,making it an exciting and rapidly evolving field.
At the resident level, there are several ways to gain exposureto neuro-oncology. If a neuro-oncology service exists in theresident's neurology department, then one could easily spendtime with that service. However, some neurology departmentsmay not have such a service. The interested resident could doan away rotation at an outside institution with a neuro-oncologyservice. Alternatively, the American Academy of Neurology (AAN)offers the Consortium of Neurology Residents and Fellows MentorshipProgram, which allows one-on-one guidance and counseling totrainees interested in subspecialties such as neuro-oncology(http://www.aam.com/education/mentors/).
Neuro-oncology offers multiple training opportunities for fellowsto prepare for a career in either clinical practice or academicneuro-oncology. Pediatric and adult neurologists, as well asmedical oncologists, may choose to subspecialize in neuro-oncologyby completing various training programs. The Society for Neuro-oncologylists almost 300 neurology-trained, about 100 medical oncology–trained,and slightly greater than 100 pediatrics-trained physiciansin its membership. One- and 2-year programs offer specializedtraining in the management of primary brain tumors, brain metastasis,and the neurologic complications of systemic cancers. Typically,in the first year of a 2-year program, the candidate is dedicatedto clinical neuro-oncology training; however, in the secondyear, the candidate may pursue clinical or basic science researchinterests in conjunction with more independent patient caremanagement training. Fellows also will become comfortable administeringintrathecal chemotherapy via lumbar puncture or Ommaya reservoirand managing related complications. Core curriculum guidelineshave been established by the United Council for Neurologic Subspecialties(UCNS), which recently established an accreditation mechanismfor neuro-oncology fellowship programs (http://www.ucns.org).The UCNS has also defined the eligibility criteria for subspecialtycertification in neuro-oncology. Interested trainees can findlistings of current fellowships on the AAN Web site (http://www.aan.com).Currently, more than 15 neuro-oncology training programs arelisted in the AAN section on fellowship training programs (http://www.aan.com/education/fellowships/index.cfm),each offering one to four positions per year. Additional resourcesand information about the field of neuro-oncology can be foundon the Society for Neuro-oncology Web site (http://www.soc-neuro-onc.org).
As with other neurology subspecialties, applicants should identifythe training programs in neuro-oncology that are best suitedto their particular interests. Some programs concentrate onpreparing the fellow to practice clinical neuro-oncology, whileothers focus on training the fellow for a career in academics.Programs can provide specialized training in molecular and stemcell biology, novel targeted therapies, functional neuroimaging,biomarker development, and patient care research, which includesthe areas of neurocognitive outcomes and quality of life. Otherprograms may provide additional training in pediatric oncology,radiation oncology, and palliative care. Combined training inmultiple subspecialties will prepare the neuro-oncology traineefor the challenges frequently encountered in the field.
Multiple career tracks are available to aspiring neuro-oncologists.Some neuro-oncologists choose a private clinical practice ina major metropolitan area, typically with some general or cancerneurology patients integrated into the practice. Given the relativerarity of primary brain tumors, neuro-oncology practice is notsuited for rural areas. Many neuro-oncologists choose an academicsetting because it provides a wide patient base, easy accessto diverse CNS tumor subspecialties, and facile integrationof clinical and translational as well as basic research. Inaddition to supporting basic research related to neuro-oncology,many academic centers provide numerous opportunities for neuro-oncologiststo concentrate on clinical trial development and the translationof new ideas from the laboratory to the clinical setting. Opportunitiesexist to integrate electrophysiology expertise with a careerin neuro-oncology. Intraoperative monitoring is frequently usedin tumor surgeries of the brain and spine, and neuro-oncologistsfrequently utilize EEG and EMG/nerve conduction studies in theclinical evaluation and management of their patients. Additionalprocedures such as intrathecal administration of chemotherapyvia lumbar puncture and Ommaya reservoir are frequently performedin the clinic for patients with leptomeningeal metastasis. Finally,one could consider employment in the biotechnology or pharmaceuticalindustry. Although there are no readily available data on jobsin industry, many medical oncologists and neurologists havehad successful careers in this setting. Currently, there isa need for formally trained neuro-oncologists across the country;for example, at the time of this writing, 15 academic job listingswere posted on the Society for Neuro-oncology Web site.
The future of neuro-oncology is promising and offers an excitingopportunity to advance the treatment of patients with braintumors and neurologic complications of cancer. The goal to personalizecancer therapy based on an individual patient's tumor drivesresearch into the genetic and epigenetic factors that are importantto tumor cell growth and survival and those that predict treatmentresponse. Newer agents targeting growth factor signaling, angiogenesis,and cell cycle pathways are expanding treatment options forpatients with brain tumors. Neuro-oncology provides an excellentopportunity to work as a neurologist with an expertise in oncology.Because of the small number of neuro-oncologists in the nation,they are a close-knit, collegial group, with many employmentopportunities available to them. Subspecialization in neuro-oncologyallows the neurologist to treat challenging diseases affectingthe nervous system while simultaneously expanding the boundariesand defining the future of a young field.
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