ONCOLOGY BOARD REVIEW MANUAL STATEMENT OF EDITORIAL PURPOSE Metastatic Brain Tumors The Hospital Physician Oncology Board Review Manual is a study guide for fellows and practicing physicians preparing for board examinations in oncology. Each manual reviews a topic essential Series Editor: to the current practice of oncology. Arthur T. Skarin, MD, FACP, FCCP Distinguished Physician, Dana-Farber Cancer Institute, PUBLISHING STAFF Harvard Medical School, Boston, MA PRESIDENT, GROUP PUBLISHER Contributors: Bruce M. White Jai Grewal, MD Co-Medical Director, Long Island Brain Tumor Center at SENIOR EDITOR NSPC, Lake Success, NY Robert Litchkofski Harpreet Kaur Grewal, MD University of Texas Health Sciences Center at Houston, EXECUTIVE VICE PRESIDENT Houston, TX Barbara T. White Santosh Kesari, MD, PhD Director, Neuro-Oncology Program, Translational Neuro- EXECUTIVE DIRECTOR Oncology Laboratories, Neurotoxicity Treatment Center, OF OPERATIONS Jean M. Gaul Moores Cancer Center, University of California San Diego Health System, La Jolla, CA Table of Contents Introduction .............................2 Case Presentation .........................3 NOTE FROM THE PUBLISHER: This publication has been developed with­ Conclusion .............................12 out involvement of or review by the Amer­ Board Review Questions ...................12 ican Board of Internal Medicine. References .............................13 www.turner-white.com Oncology Volume 10, Part 4 1 Metastatic Brain Tumors ONCOLOGY BOARD REVIEW MANUAL Metastatic Brain Tumors Jai Grewal, MD, Harpreet Kaur Grewal, MD, and Santosh Kesari, MD, PhD INTRODUCTION Brain metastases can present with a variety of symptoms (Figure 2), including focal neurological Systemic cancer can affect the central nervous deficits, headache, and seizures. The sudden onset system in several different ways, including direct of symptoms may be related to intracranial hemor- tumor metastasis and indirect remote effects. Intra- rhage associated with brain metastases. Given its cranial metastasis can involve the skull, dura, and relatively high incidence, lung cancer is the most leptomeninges (arachnoid and pia mater), as well common type of brain metastases to result in in- as the brain parenchyma. Of these, parenchymal tracranial hemorrhage. However, other cancer pri- brain metastases are the most common and have maries have, relative to their incidence, a very high been found in as many as 24% of cancer patients propensity to spontaneously develop tumor-associ- in autopsy studies.1 It has been reported that ated intracranial hemorrhage; they are melanoma, metastatic brain tumors outnumber primary brain renal cell carcinoma, choriocarcinoma, thyroid, and tumors 10 to 1.2 germ cell. Ultimately, any brain metastasis has the Metastasis to the brain generally occurs by he- potential for spontaneous hemorrhage. matogenous dissemination, with tumor cells having Often, the presentation of brain metastasis oc- a propensity to lodge and grow at the gray-white curs in a patient with established malignancy, in junction. The distribution of brain metastases is which case a clinical and radiological diagnosis proportionate to the cerebral blood flow, with 80% is usually sufficient. Magnetic resonance imaging occurring in the supratentorial region, 15% in the (MRI) with gadolinium contrast is preferred over cerebellum, and 5% in the brainstem.1 Unlike pri- computed tomography (CT) alone due to greater mary brain tumors, such as glioblastoma, brain sensitivity in identifying additional lesions. For ex- metastases do not typically involve the corpus ample, in approximately one-third of cases present- callosum or infiltrate across the midline. The most ing with a single metastasis on CT, MRI will lead to common primary histologies include lung, breast, the discovery of additional metastases (Figure 3).4 melanoma, renal, and colon cancer, and tumors of Occasionally, brain metastasis can occur as the unknown primary (Figure 1).3 presenting feature in a patient not known to have Copyright 2013, Turner White Communications, Inc., Strafford Avenue, Suite 220, Wayne, PA 19087-3391, www.turner-white.com. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, mechanical, electronic, photocopying, recording, or otherwise, without the prior written permission of Turner White Communications. The preparation and distribution of this publication are sup- ported by sponsorship subject to written agreements that stipulate and ensure the editorial independence of Turner White Communications. Turner White Communications retains full control over the design and production of all published materials, including selection of topics and preparation of editorial content. The authors are solely responsible for substantive content. Statements expressed reflect the views of the authors and not necessarily the opinions or policies of Turner White Communications. Turner White Communications accepts no responsibility for statements made by authors and will not be liable for any errors of omission or inaccuracies. Information contained within this publication should not be used as a substitute for clinical judgment. 2 Hospital Physician Board Review Manual www.turner-white.com Metastatic Brain Tumors Unknown Other 2% 10% GYN 5% GU 7% Lung 40% GI 7% Melanoma 10% Breast 19% Figure 1. Malignancies most commonly associated with brain metastasis. GI = gastrointestinal; GU = genitourinary; Gyn = gyne- cologic. (Data from Posner.3) cancer. A thorough assessment is essential in iden- 5-fluorouracil. There are no other sites of meta- tifying the associated systemic malignancy and in static disease at diagnosis. determining which site of disease is safest for tissue Eight months after her diagnosis, she develops diagnosis. In the differential diagnosis, conditions right-sided headaches. She has an excellent per- apart from metastatic disease need to be consid- formance status. CT of the brain without contrast ered (Table 1). reveals a right parietal hypodensity with significant mass effect. MRI with gadolinium contrast does CASE PRESENTATION not reveal any additional lesions (Figure 4). There is no evidence of any active extracranial disease. INITIAL PRESENTATION AND EVALUATION A 54-year-old woman presents with a left • What are important prognostic factors in breast mass and is treated with a lumpec- brain metastasis? tomy and axillary lymph node dissection. Her tumor is negative for hormonal receptors (estro- PROGNOSIS gen receptor, progesterone receptor) and is also Several factors have been validated as important negative for HER2/neu (human epidermal growth prognostic factors in patients with brain metastasis. factor receptor 2). She has positive lymph nodes These include age, performance status, and extent and receives local radiation therapy and 8 cycles of extracranial disease. These factors have been of adjuvant cyclophosphamide, methotrexate, and used to stratify patients into several prognostic www.turner-white.com Oncology Volume 10, Part 4 3 Metastatic Brain Tumors Headache 49 Cognitive 32 Weakness 30 Gait 21 Seizures 18 Speech 12 Vision 6 Percentage Figure 2. Common presenting symptoms of brain metastasis. (Data from Posner.3) ed: number of brain metastases. Known as graded prognostic assessment (GPA), this system scores patients from 0 to 4, with 4 corresponding to the most favorable prognosis.6 The most recent update found that significant prognostic factors differed for each of the following tumor types: non–small cell lung cancer (NSCLC), breast cancer, melanoma, renal cell carcinoma, and gastrointestinal cancers.7 In this analysis, patients with a low GPA score (0 to 1) tended to have a poor survival (of approximately Figure 3. (A) Computed tomography of the brain reveals a sin- 3 months) in all histologies examined. In addition, gle brain metastasis (arrow). (B) Magnetic resonance imaging performance status was found to be an important with contrast reveals a second small site of metastasis in the contralateral hemisphere (arrow). prognostic factor in all groups. With regard to breast cancer, there is emerging data that patients with hormone receptor–negative breast cancer may have increased risk of brain me- categories, known as RPA (recursive partitioning tastasis.8 Elevated serum lactate dehydrogenase analysis) classes.5 Discrete differences in survival (LDH) also has been suggested as a predictor for have been demonstrated based upon this clas- developing brain metastasis.9 The role of HER2/ sification (Table 2). Poor performance status sug- neu receptor status is unclear,10 but the prognosis gests a poor outcome (RPA class 3) regardless of of patients with brain metastasis in the setting of the other factors. The patient in this case is in the HER2-positive disease may be more favorable most favorable group, RPA class 1. due to better control of extracranial disease with Recently these prognostic categories were updat- trastuzumab.11 Features of breast cancer which ed and a fourth prognostic element was incorporat- may increase risk for developing brain metastasis 4 Hospital Physician Board Review Manual www.turner-white.com Metastatic Brain Tumors Table 1. Differential Diagnosis of Brain Metastasis Disease Process Example Demyelinating disease Multiple sclerosis Infection Cerebral abscess Primary brain tumor Glioblastoma Inflammatory/autoimmune Neurosarcoidosis Vascular Hemorrhagic stroke Idiopathic Radiation necrosis Figure 4. Right parietal