Cancer, Brain Metastasis


Article Author:
Mark Amsbaugh


Article Editor:
Catherine Kim


Editors In Chief:
Yvonne Carter
Jason Wallen


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Frank Smeeks
Kristina Soman-Faulkner
Trevor Nezwek
Radia Jamil
Patrick Le
Sobhan Daneshfar
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
3/13/2019 4:14:29 PM

Introduction

Brain metastases are a common complication of cancer and the most common type of brain tumor. Anywhere from 10% to 26% of patients who die from their cancer will develop brain metastases[1]. While few cancers that metastasize to the brain can be cured using conventional therapies, long-term survival and palliation are possible with minimal adverse effects to patients. Increasingly, neuro-cognition and quality of life are being recognized as an important endpoint for patients as survival continues to increase.

Etiology

Primary cancers such as lung, breast, and melanoma are most likely to metastasize to the brain. Small-cell lung cancer has a high propensity to spread to the brain such that prophylactic treatment (cranial irradiation) is considered the standard of care. Other malignancies such as prostate and head and neck cancers rarely result in brain metastases. It can be difficult to predict which patients will develop brain metastases other than by using tumor type and subtype.

Epidemiology

Brain metastases are the most common type of intracranial tumor. In the United States, an estimated 98,000 to 170,000 cases occur each year. The incidence of brain metastases is increasingly likely as a result of several factors[2]. Patients with a systemic metastatic disease have a longer survival with new systemic therapies (including immunotherapy) that have recently seen more widespread use. Furthermore, the growing use of sensitive MRI techniques has contributed to better detection of small asymptomatic brain metastases.

Pathophysiology

Metastatic cancer passes through the bloodstream and enters the central nervous system through a breakdown of the blood-brain barrier. Clonal cells then proliferate, causing local invasion, displacement, inflammation, and edema. Distribution throughout the central nervous system is more common in areas of high blood flow; however, different histological subtypes tend to have different distributions of location within the brain[3].

History and Physical

A detailed history and physical should be performed, focusing on symptoms, duration, and intensity. Focused questions about headaches, blurry vision, and nausea should be asked. A complete neurologic examination should be performed. This examination should include assessment of strength, sensation, coordination, reflexes, cerebellar function, proprioception, cranial nerve function, speech, thought, vision, and memory. An ophthalmic examination should be performed to evaluate for papilledema. Additional information including age, performance status, and status of systemic cancer burden should be gathered to understand the disease course and guide future therapeutic intervention.

Evaluation

A head CT allows for a quick examination, although fine-slice MR of the brain with contrast is the gold standard for neuroimaging in cases of suspected brain metastases. MR allows for a determination of the number and anatomical location of tumors and degree of associated edema. Basic laboratory assessment including CBC, metabolic panel, and liver function test should be performed.

Treatment / Management

The first step in the management of newly diagnosed brain metastases is the treatment of intracranial edema. Oral or intravenous steroids (such as dexamethasone) are commonly used. A loading dose of 10 mg intravenous (IV) dexamethasone followed by 4 mg IV every six hours is one dosing regimen. After the initial clinical response, which can occur rapidly, the dose may be tapered to avoid many of the adverse effects of long-term high dose steroid administration.

Following initiation of steroids, definitive management may be initiated. Treatment options include surgical resection (for limited brain metastases in patients with good performance status and surgically accessible lesions), whole brain radiotherapy, and stereotactic radiosurgery. Whole brain radiotherapy is given by daily radiotherapy treatments (usual 10 to 15) targeting the whole brain. Radiosurgery is a more precise form of radiotherapy which delivers a large dose only to the area of the brain metastasis, usually in a single fraction. Each of these treatments has distinct advantages as well as a unique side effect profile. A multidisciplinary treatment team of a neurosurgeon, radiation oncologist, and neuro-oncologist should participate in the formulation of the treatment plan together with the patient.

The historical standard in patients with good performance status has been surgical resection. Local recurrence following surgical resection remains high, with one trial recently reporting a 12-month freedom from local recurrence of 43% following surgical resection and observation[4]. Local control can be improved with post-operative radiosurgery or whole brain radiotherapy [4][5]. Postoperative therapy should remain an individualized treatment recommendation, taking into account the number of non-resected metastases, tumor histology, follow up, and patient preference. Whole brain radiotherapy following surgical resection of brain metastases can increase intracranial control compared to postoperative stereotactic radiosurgery but results in poorer neuro-cognitive outcomes[5].

For patients either not eligible for surgical resection of brain metastases or who elect for non-surgical therapy, stereotactic radiosurgery offers an excellent option for controlling a limited number of intracranial metastases. Although first used in combination with whole brain radiotherapy as a way to intensify local treatment, stereotactic radiosurgery is now commonly used as a stand-alone therapy. While ultimate control of brain metastases varies with dose and lesion size [6], lesions less than one centimeter have high local control with single fraction radiosurgery [7]. For larger lesions, multi-fraction treatments are sometimes employed [8]. Stereotactic radiosurgery is considered standard for patients with one to four brain metastases, but emerging data indicate it may be an acceptable treatment for patients with up to ten brain metastases [9].

For patients with poor performance status or many brain metastases, the standard of care is whole brain radiotherapy. Whole brain radiotherapy provides control of individual brain metastases as well as reduces the risk of failure in the brain at a new site. These benefits must be weighed against its potential neurocognitive side effects which occur for many patients to varying degree. Emerging data suggest that for patients with extremely poor performance status, whole brain radiotherapy may have a minimal benefit over steroids alone [10]. Therefore, in the management of brain metastases, treatment decision will need to be made on an individual patient level, taking in to account the goals of treatment in a particular situation as well as the acceptable side effect profile.

Enhancing Healthcare Team Outcomes

The management of patients with brain metastases is best done with a multidisciplinary team that includes an oncologist, neurologist, radiation therapist, palliative care specialist, pain consultant, anesthesia and a neurosurgeon. Most of these patients are frail and have a reduced life expectancy; hence the need for aggressive measures is not warranted. A team approach should discuss the best approach taking into account patient status, comorbidity and life span. Many of these patients simply benefit from palliation and pain control.[11][12]


  • Image 419 Not availableImage 419 Not available
    Contributed by Scott Dulebohn, MD
Attributed To: Contributed by Scott Dulebohn, MD

Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Cancer, Brain Metastasis - Questions

Take a quiz of the questions on this article.

Take Quiz
Which of the following malignancies rarely spreads to the brain?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which tumor in adults is most likely to metastasize to the brain?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following metastatic tumors to the brain is most likely to result in an intracranial bleed?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A middle-aged man with a 4-week history of severe headaches has a contrast CT scan which reveals several small, circular, hypodense lesions with a ring-like contrast enhancement. Which of the following is the most likely diagnosis?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 66-year-old woman with a history of breast cancer one year ago which was treated with surgery now presents with headaches. Exam shows a slight right facial droop, pronator drift on the left, and slight left hyperreflexia. What test is likely to reveal her diagnosis?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following is the MOST common tumor to metastasize to the brain in which a primary tumor is not known at the time of presentation?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which metastatic brain malignancy is associated with the worst prognosis?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 57-year-old female with a history of breast cancer resected 15 months ago presents with a 1-week history of numbness of the left hand and foot with nausea and vomiting. For the past few hours, she has had increasing pain in the right retro-orbital area. The pain is worse with bending forward and is throbbing. The patient has left lower facial droop and absence of double simultaneous tactile stimulation. What should be done next?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
What is the most common etiology of multiple brain metastases with no known primary?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
What is the most common cause of brain metastasis?

(Move Mouse on Image to Enlarge)
  • Image 4769 Not availableImage 4769 Not available
    Contributed by Wikimedia Commons,"Medical gallery of Mikael Häggström 2014" (Public Domain)
Attributed To: Contributed by Wikimedia Commons,"Medical gallery of Mikael Häggström 2014" (Public Domain)



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
What is the most common type of intracranial tumor?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Cancer, Brain Metastasis - References

References

Post-operative stereotactic radiosurgery versus observation for completely resected brain metastases: a single-centre, randomised, controlled, phase 3 trial., Mahajan A,Ahmed S,McAleer MF,Weinberg JS,Li J,Brown P,Settle S,Prabhu SS,Lang FF,Levine N,McGovern S,Sulman E,McCutcheon IE,Azeem S,Cahill D,Tatsui C,Heimberger AB,Ferguson S,Ghia A,Demonte F,Raza S,Guha-Thakurta N,Yang J,Sawaya R,Hess KR,Rao G,, The Lancet. Oncology, 2017 Aug     [PubMed]
Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC·3): a multicentre, randomised, controlled, phase 3 trial., Brown PD,Ballman KV,Cerhan JH,Anderson SK,Carrero XW,Whitton AC,Greenspoon J,Parney IF,Laack NNI,Ashman JB,Bahary JP,Hadjipanayis CG,Urbanic JJ,Barker FG 2nd,Farace E,Khuntia D,Giannini C,Buckner JC,Galanis E,Roberge D,, The Lancet. Oncology, 2017 Aug     [PubMed]
Epidemiology of brain metastases., Nayak L,Lee EQ,Wen PY,, Current oncology reports, 2012 Feb     [PubMed]
Brain metastases admissions in Sweden between 1987 and 2006., Smedby KE,Brandt L,Bäcklund ML,Blomqvist P,, British journal of cancer, 2009 Dec 1     [PubMed]
A Dose-Volume Response Model for Brain Metastases Treated With Frameless Single-Fraction Robotic Radiosurgery: Seeking to Better Predict Response to Treatment., Amsbaugh MJ,Yusuf MB,Gaskins J,Dragun AE,Dunlap N,Guan T,Woo S,, Technology in cancer research & treatment, 2017 Jun     [PubMed]
The role of tumor size in the radiosurgical management of patients with ambiguous brain metastases., Chang EL,Hassenbusch SJ 3rd,Shiu AS,Lang FF,Allen PK,Sawaya R,Maor MH,, Neurosurgery, 2003 Aug     [PubMed]
A Multi-institutional Prospective Observational Study of Stereotactic Radiosurgery for Patients With Multiple Brain Metastases (JLGK0901 Study Update): Irradiation-related Complications and Long-term Maintenance of Mini-Mental State Examination Scores., Yamamoto M,Serizawa T,Higuchi Y,Sato Y,Kawagishi J,Yamanaka K,Shuto T,Akabane A,Jokura H,Yomo S,Nagano O,Aoyama H,, International journal of radiation oncology, biology, physics, 2017 Sep 1     [PubMed]
Quattrocchi CC,Errante Y,Gaudino C,Mallio CA,Giona A,Santini D,Tonini G,Zobel BB, Spatial brain distribution of intra-axial metastatic lesions in breast and lung cancer patients. Journal of neuro-oncology. 2012 Oct;     [PubMed]
Minniti G,Scaringi C,Paolini S,Lanzetta G,Romano A,Cicone F,Osti M,Enrici RM,Esposito V, Single-Fraction Versus Multifraction (3 × 9 Gy) Stereotactic Radiosurgery for Large (>2 cm) Brain Metastases: A Comparative Analysis of Local Control and Risk of Radiation-Induced Brain Necrosis. International journal of radiation oncology, biology, physics. 2016 Jul 15;     [PubMed]
Mulvenna P,Nankivell M,Barton R,Faivre-Finn C,Wilson P,McColl E,Moore B,Brisbane I,Ardron D,Holt T,Morgan S,Lee C,Waite K,Bayman N,Pugh C,Sydes B,Stephens R,Parmar MK,Langley RE, Dexamethasone and supportive care with or without whole brain radiotherapy in treating patients with non-small cell lung cancer with brain metastases unsuitable for resection or stereotactic radiotherapy (QUARTZ): results from a phase 3, non-inferiority, randomised trial. Lancet (London, England). 2016 Oct 22;     [PubMed]
Matsuo S,Amano T,Kawauchi S,Nakamizo A, Multiple Brain Metastases from Pancreatic Adenocarcinoma Manifesting with Simultaneous Intratumoral Hemorrhages. World neurosurgery. 2019 Mar;     [PubMed]
Rastogi K,Bhaskar S,Gupta S,Jain S,Singh D,Kumar P, Palliation of Brain Metastases: Analysis of Prognostic Factors Affecting Overall Survival. Indian journal of palliative care. 2018 Jul-Sep;     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Surgery-Thoracic. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Surgery-Thoracic, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Surgery-Thoracic, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Surgery-Thoracic. When it is time for the Surgery-Thoracic board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Surgery-Thoracic.