Radiosurgery Practice Guideline Initiative …

1 1 Radiosurgery Practice Guideline InitiativeStereotactic Radiosurgery for Patients with Metastatic Brain TumorsRadiosurgery Practice Guideline Report # 5-08 ORIGINAL Guideline : May 2008 MOST RECENT LITERATURE SEARCH: May 2008 This Practice Guideline , together with a report on Metastatic Brain Tumor Management is anoriginal Guideline approved by The International Radiosurgery Association and issued in IRSA (International Radiosurgery Association) Radiosurgery Practice Guideline Initiative aims to improve outcomes forbrain metastases Radiosurgery by assisting physicians and clinicians in applying research evidence to clinical decisions whilepromoting the responsible use of health care Guideline is copyrighted by IRSA (2008) and may not be reproduced without the written permission of IRSA. IRSA reserves the right to revoke copyright authorization at any time without Guideline is not intended as a substitute for professional medical advice and does not address specific treatments orconditions for any patient.

2 Those consulting this Guideline are to seek qualified consultation utilizing information specific totheir medical situation. Further, IRSA does not warrant any instrument or equipment nor make any representations concerningits fitness for use in any particular instance nor any other warranties WORDS brain metastases WBRT stereotactic Radiosurgery Gamma Knife linear acceleratorKEY WORDS Bragg peak proton therapy irradiationMetastatic Brain TumorsConsensus StatementObjectiveTo develop a consensus-based Radiosurgery practiceguideline for brain metastases treatment recommendationsto be used by medical and public health professionals whodiagnose and manage patients with brain metastatic working group included physicians and physicists fromthe staff of major medical centers that provide first author (AN) conducted a literature search inconjunction with the preparation of this document anddevelopment of other clinical guidelines .

3 The literatureidentified was reviewed and opinions were sought fromexperts in the diagnosis and management of brain metastasesincluding members of the working ProcessThe initial draft of the consensus statement was a synthesisof research information obtained in the evidence gatheringprocess. Members of the working group provided formalwritten comments that were incorporated into the preliminarydraft of the statement. No significant disagreements final statement incorporates extensive relevant evidenceobtained by the literature search in conjunction with the finalconsensus recommendations supported by all working CompositionThe Radiosurgery guidelines group is comprised ofneurosurgeons, neuro-oncologists, radiation and medicaloncologists and physicists. Community representatives didnot participate in the development of this of Group Members: Ajay Niranjan, , , Neurosurgeon, Chair; L. Dade Lunsford, ,Neurosurgeon; Richard L.

4 Weiner, , Neurosurgeon; GailL. Rosseau, , Neurosurgeon; Gene H. Barnett, , , Neurosurgeon; Massaki Yamamoto, ; Lawrence S. Chin, , ,Neurosurgeon; Paul J. Miller, , Radiation Oncologist;Andrew E. Sloan, , Neurosurgeon; Burton L. Speiser, , Radiation Oncologist; Sandra S. Vermeulen, ,Radiation Oncologist; Harish Thakrar, , RadiationOncologist; Frank Lieberman, , Neuro-Oncologist;David Schiff, , Neuro-Oncologist; Sammie R. Coy, , Medical Physicist; Tonya K. Ledbetter, , ,Editor; Rebecca L. Emerick, , , , recommendations are made regarding targetpopulation, treatment alternatives, interventions and practicesand additional research needs. Appropriate use ofradiosurgery for patients with brain metastases Guideline is intended to provide the scientific foundationand initial framework for patients who have been diagnosedwith brain metastases. The assessment and recommendationsprovided herein represent the best professional judgment ofthe working group at this time, based on clinical researchdata and expertise currently available.

5 The conclusions andrecommendations will be regularly reassessed as newinformation becomes RadiosurgeryBrain stereotactic Radiosurgery (SRS) involves the use ofprecisely directed, closed skull, single session radiation tocreate a desired radiobiologic response within the brain targetwith acceptable minimal effects on surrounding structuresor tissues. In the case of brain metastases, highly conformal,precisely focused radiation is delivered to the metastatictumor in a single session under the direct supervision of aradiosurgery team. At Centers of Excellence, theradiosurgery team includes a neurosurgeon, a radiationoncologist, a physicist and a registered of Brain MetastasesEpidemiologic FeaturesMetastatic brain tumors are the most common intracranialneoplasms in adults and are a significant cause of morbidityand mortality. They outnumber primary brain tumors by aratio of 10 Approximately million individuals werediagnosed with cancer in 2005 2006.

6 Conservativeestimates suggest that 100,000 170,000 new cases of brainmetastases are diagnosed every year in the United States( ).59,108 Between 20% and 40% of all patients withmetastatic cancer will have brain metastases at estimate of the incidence rate of metastatic brain tumorsvaries from 11 per 100, ,127 In two large populationcohorts of patients who were diagnosed with colorectal, lung,breast or kidney carcinoma or melanoma, brain metastaseswere diagnosed in of ,108 The incidencevaried by primary tumor site. The cumulative incidence wasestimated at in patients with lung carcinoma, in patients with renal carcinoma, inpatients with melanoma, in patients with breastcarcinoma, and in patients with majority of patients who develop brain metastases havea known primary cancer (metachronous presentation). Noprimary systemic site of cancer is detected in 5 10% ofpatients with brain ,95 Patients with a history oflung cancer have the shortest latency period between thetime of initial diagnosis and the diagnosis of brain metastases(median, 6 9 months).

7 For renal cell carcinoma, the intervalis approximately one year. Patients with breast, melanomaand colon cancer experience spread of their disease to thebrain at a median latency of approximately two Therate of breast cancer metastases to the brain may be higheramong patients treated with trastuzumab (Herceptin ).7 Thismay be due to the preference for the brain by HER-2-positivetumor cells, poor penetration of the CNS by the drug orimproved extracranial control resulting in improved survivaland late tumor spread to the detection rate of brain metastases appears to beincreasing. This increase has been variably attributed toimprovements in systemic therapy leading to longer survival,an aging patient population, and the ability of magneticresonance imaging (MRI) to detect small Themajority of brain metastases are multiple, although thereported percentage of patients with solitary or multiplelesions may vary with the imaging modality used to makethe diagnosis.

8 In the CT (computed tomography) era 50%of lesions were thought to be solitary at the time of In an analysis of the Radiation TherapyOncology Group (RTOG) database of brain metastasespatients, 19% of patients presented with a single brainmetastasis on MRI, and 50% of patients had 1 3 brainmetastases. Melanoma has the greatest tendency to producemultiple lesions (75% of patients). Multiple lesions are alsofrequent in metastases from colon, breast and lung cell metastases are more likely to be for gender follows that of the primary cancer is the most common source of metastases inmale patients, while breast cancer is the most common sourcein female patients. As the frequency of lung cancer in womenincreases, it may become the most common primary tumorto metastasize to the brain in women as of brain metastases based on age parallels that ofprimary systemic tumors. Brain metastases are most commonin the fifth to seventh decades of life.

9 Sarcomas and germcell tumors are the most common solid tumors to metastasizeto the brain in spread to the brain through blood circulationoccurs primarily via arterial circulation and less often viathe Batson venous plexus (pelvic and GI tumors).129 Arterialblood must pass through the lungs before entering the brainand larger clumps of tumor cells are filtered out in lungcapillaries. Many emboli traveling to the brain via the arterialroute originate either from a primary lung tumor or ametastatic site in the lung; however, single tumor cells maypass through the capillaries of the lung. The metastatic cellsthen get trapped in gray-white junction or watershed areas,because of the change in the size of the blood vessels inthese Less than of deposited cells ultimatelyform metastatic Once the metastatic tumor embolusreaches 1 mm in size, tumor-induced angiogenesis increasesvascular permeability and disrupts the blood-brain barrier(BBB).

10 14 New capillary endothelial cells in metastatic brain3tumors display morphological and functional characteristicsassociated with the blood vessels of the primary FindingsIntracranial metastases can be categorized by location asskull, dura, leptomeninges and parenchymal brainmetastases. Lesions of the brain and leptomeninges accountfor 80% of intracranial metastases. The majority of brainmetastases (approximately 80%) are located in the cerebralhemispheres. The cerebellum (10 15%) and brainstem (2 3%) are less frequently Most metastases areround, well-demarcated lesions located at the junction ofgray and white matter. Metastatic lesions in the brain displacesurrounding brain parenchyma as they grow. Somemetastases have a miliary type of distribution throughoutthe parenchyma. Leaky tumor vessels result in an extensivezone of edema surrounding the tumor. Cystic degeneration,necrosis and areas of hemorrhage are often seen. Specifictumors may have a more characteristic gross metastatic lesions of melanoma, choriocarcinoma andrenal cell carcinoma often develop Edema of the adjacent brain parenchyma isoften prominent and sometimes disproportionate to the smallsize of the Meningeal carcinomatosis may occurin patients with lung and breast carcinoma, malignantmelanoma, and less commonly, with lymphoma, leukemiaand other FeaturesThe histopathologic features of metastatic lesions are usuallysimilar to those of the primary tumor from which theyoriginate.