brain metastases on MRIb,c
No known history of cancer
Known history of cancer
• Contrast-enhanced CT chest/abdomen/
pelvis
• Consider whole body PET/CT
• Other tests as indicated
No other readily accessible tumor for biopsy
Biopsy or resect tumor found outside CNS to confirm cancer diagnosis
See Clinical Presentation and Treatment (LTD-2) Surgeryd to confirm diagnosis of
CNS metastases:
• Resection for management of mass effect or symptoms
• Consider resection for
treatment of patients with newly diagnosed or stable systemic disease or reasonable systemic treatment optionse
• Biopsy if resection not planned
Consider surgery for brain metastasesd,f:
• Resection for management of mass effect or symptoms
• Resection for treatment of patients with newly diagnosed or stable systemic disease or reasonable systemic treatment optionse
• Biopsy if concern exists about diagnosis of CNS lesions and resection is not planned
aSee Principles of Brain and Spine Tumor Imaging (BRAIN-A).
bConsider a multidisciplinary review in treatment planning, especially once pathology is available. See Principles of Brain and Spine Tumor Management (BRAIN-E).
c"Limited" brain metastases defines a group of patients for whom SRS is equally effective and offers significant cognitive protection compared with WBRT. The definition of "limited" brain metastases in terms of number of metastases or total intracranial disease volume is evolving and may depend on the specific clinical situation. (Yamamoto M, Serizawa T, Shuto T, et al. Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol 2014;15:387-395.)
dSee Principles of Brain Tumor Surgery (BRAIN-B).
eFor secondary CNS lymphoma, treatment may include systemic treatment, whole-brain or focal RT, or combination.
fThe decision to resect a tumor may depend on the need to establish histologic diagnosis, the size of the lesion, its location, and institutional expertise. For example, smaller (<2 cm), deep, asymptomatic lesions may be considered for treatment with SRS versus larger (>2 cm), symptomatic lesions that may be more appropriate for surgery. (Ewend MG, Morris DE, Carey LA, Ladha AM, Brem S.
Guidelines for the initial management of metastatic brain tumors: role of surgery, radiosurgery, and radiation therapy. J Natl Compr Cancer Netw 2008;6:505-513.)
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
Version 5.2020 , 04/15/21 © 2021 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
Limited Brain Metastases
LTD-2
eFor secondary CNS lymphoma, treatment may include systemic treatment, whole-brain or focal RT, or combination.
gIf an active agent exists (eg, cytotoxic, targeted, or immune modulating), trial of systemic therapy with good CNS penetration may be considered in select patients (eg, for patients with small asymptomatic brain metastases from melanoma or ALK rearrangement-positive NSCLC or EGFR-mutated NSCLC); it is reasonable to hold on treating with radiation to see if systemic therapy can control the brain metastases. Consultation with a radiation oncologist and close MRI surveillance is strongly recommended. There are no data from prospective clinical trials comparing the two strategies to assess what the impact of delayed radiation would be in terms of survival or in delay of neurologic deficit development.
hSee Principles of Brain and Spinal Cord Tumor Systemic Therapy (BRAIN-D).
iSee Principles of Brain and Spinal Cord Tumor Radiation Therapy (BRAIN-C).
jSRS is preferred when safe, especially for low tumor volume, to both the resection cavity and any other non- resected brain metastases. WBRT is generally not recommended but may be appropriate in some rare clinical circumstances.
kFor brain metastases not managed with resection, SRS + WBRT is generally not recomended but may be appropriate in some rare clinical circumstances. Brown 2016 showed that for tumors <3 cm, SRS + WBRT improved local control compared with SRS alone, but did not significantly improve survival, and was associated with greater cognitive decline and poorer quality of life. (Brown PD, Jaeckle K, Ballman KV, et al. Effect of radiosurgery alone vs radiosurgery with whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases: a randomized clinical trial. JAMA 2016;316:401-409.)
lHippocampal avoidance preferred. See BRAIN-C.
CLINICAL PRESENTATION TREATMENTg,h
Disseminated systemic disease with poor systemic treatment optionse
Newly diagnosed or stable systemic disease or
Reasonable systemic treatment options existe,h
WBRTg,i
orSRS in select patientsi
orConsider palliative/best supportive care
SRS (preferred)g,i,j or WBRTi,k,l
See Follow-up and Recurrence (LTD-3)
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
Version 5.2020 , 04/15/21 © 2021 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
Limited Brain Metastases
LTD-3
FOLLOW-UPa RECURRENCE TREATMENT
Brain MRIa every 2–3m mo for 1–2 y then every 4–6 mo indefinitelyq
Recurrent disease;
local siten
Recurrent disease;
distant brain
± local recurrence
Previous surgery only
Previous WBRT or Prior SRS
Limited brain metastasesc
Extensive brain metastases
Surgery followed by SRS or RT to the surgical bedi
or Single-dose or fractionated stereotactic RTi
or WBRTi,l for large volumes orConsider systemic therapyh
Surgery followed by SRS or RT to the surgical bedi
orSingle-dose (category 2B) or fractionated stereotactic RTi,p
or Consider systemic therapyh
Surgery followed by SRS or RT to the surgical bedi
orSingle-dose or fractionated stereotactic RTi
orWBRTi,l for large volumes if not previously administered
or Consider systemic therapyh
WBRTi if not previously administered or Consider systemic therapyh
If relapses, see LTD-4 Brain MRIa
every 2–3m mo for 1–2 y then every 4–6 mo indefinitelyq
aSee Principles of Brain and Spine Tumor Imaging (BRAIN-A).
c"Limited" brain metastases defines a group of patients for whom SRS is equally effective and offers significant cognitive protection compared with WBRT. The definition of "limited" brain metastases in terms of number of metastases or total intracranial disease volume is evolving and may depend on the specific clinical situation. (Yamamoto M, Serizawa T, Shuto T, et al. Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol 2014;15:387-395.)
hSee Principles of Brain and Spinal Cord Tumor Systemic Therapy (BRAIN-D).
iSee Principles of Brain and Spinal Cord Tumor Radiation Therapy (BRAIN-C).
lHippocampal avoidance preferred. See BRAIN-C.
mMRI every 2 months (instead of 3 mo) for those patients treated with SRS alone.
nAfter SRS, recurrence on MRI can be confounded by treatment effects; consider tumor tissue sampling if there is a high index of suspicion of recurrence.
pIf patient had previous SRS with a good response >6 mo, then reconsider SRS if imaging supports active tumor and not necrosis.
qImaging to evaluate emergent signs/symptoms is appropriate at any time.
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
Version 5.2020 , 04/15/21 © 2021 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
Limited Brain Metastases
LTD-4
dSee Principles of Brain Tumor Surgery (BRAIN-B).
iSee Principles of Brain and Spinal Cord Tumor Radiation Therapy (BRAIN-C).
hSee Principles of Brain and Spinal Cord Tumor Systemic Therapy (BRAIN-D).
RECURRENCE TREATMENT
Systemic disease progression, with limited systemic treatment options and poor PS
No prior WBRT
Prior WBRT
WBRTi
orSRS in select patientsi
orPalliative/best supportive care
Reirradiation,i if prior positive response to RT or SRS in select patientsi
or Palliative/best supportive care Stable systemic
disease or reasonable systemic
treatment options
Surgeryd orSRSi
orWBRT if no prior WBRTi orSystemic therapyh
Relapse
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
Version 5.2020 , 04/15/21 © 2021 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
Limited Brain Metastases
MU-1
aSee Principles of Brain and Spine Tumor Imaging (BRAIN-A).
bConsider a multidisciplinary review in treatment planning, especially once pathology is available. See Principles of Brain and Spine Tumor Management (BRAIN-E).
cIncludes all cases that do not fit the definition of "limited brain metastases" on LTD-1.
dSee Principles of Brain Tumor Surgery (BRAIN-B).
eSee Principles of Brain and Spinal Cord Tumor Radiation Therapy (BRAIN-C).
fSRS can be considered for patients with good performance and low overall tumor volume and/or radioresistant tumors such as melanoma. (Yamamoto M, Serizawa T, Shuto T, et al. Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol 2014;15:387-395.)
gIf an active agent exists (eg, cytotoxic, targeted, or immune modulating), trial of systemic therapy with good CNS penetration may be considered in select patients (eg, for patients with small asymptomatic brain metastases from melanoma or ALK rearrangement-positive NSCLC or EGFR-mutated NSCLC); it is reasonable to hold on treating with radiation to see if systemic therapy can control the brain metastases. Consultation with a radiation oncologist and close MRI surveillance is strongly recommended. There are no data from prospective clinical trials comparing the two strategies to assess what the impact of delayed radiation would be in terms of survival or in delay of neurologic deficit development.
hSee Principles of Brain and Spinal Cord Tumor Systemic Therapy (BRAIN-D).
CLINICAL
PRESENTATIONa WORKUP PRIMARY
TREATMENTe