EANO-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up of patients with brain metastasis from solid tumours
- Study type
- Clinical guideline
- Study name
- EANO-ESMO Brain Metastases 2021
- Design
- Joint clinical guideline of the European Association of Neuro-Oncology (EANO) and the European Society for Medical Oncology (ESMO); EANO levels of evidence based on EFNS criteria and ESMO levels based on an adapted version of the IDSA-USPHS system (each recommendation has two grades)
- Source
- Ann Oncol · 2021
In plain words
This joint guideline from two respected European societies explains which treatment is suitable when cancer (for example lung, breast or melanoma) spreads to the brain. The key messages: if there are few lesions (1 to 4, and sometimes up to 10 small ones), precise radiosurgery is better than whole-brain radiotherapy because it better protects memory and thinking; a single large lesion may be removed by surgery and its site then treated with radiosurgery; and in some cancers (such as lung cancer with an EGFR or ALK mutation, or melanoma) new targeted drugs or immunotherapy can shrink the brain lesions themselves. Steroids are recommended only when there are symptoms, and anti-seizure medicine only after a seizure has happened.
Key guideline recommendations
- EANO: I, A; ESMO: I, A
Stereotactic radiosurgery (SRS) is recommended for patients with a limited number (1 to 4) of brain metastases.
- EANO: II, B; ESMO: II, B
SRS can be considered for patients with more brain metastases (5 to 10) with a cumulative tumour volume below 15 mL.
- EANO: I, A; ESMO: I, A
SRS to the surgical cavity is recommended after complete or incomplete resection of a brain metastasis.
- EANO: I, A; ESMO: I, E
Whole-brain radiotherapy (WBRT) after surgical resection or after SRS should be omitted (not recommended).
- EANO: III, B; ESMO: III, B
WBRT should be considered for the treatment of multiple brain metastases not suitable for SRS, depending on the presence of neurological symptoms, the size, number and location of the metastases, and the choice and availability of CNS-active systemic therapy. In patients with multiple metastases not suitable for SRS and poor performance status, supportive care without WBRT should be considered (EANO: I, B; ESMO: I, B).
- EANO: I, A; ESMO: II, A
A single brain metastasis should be considered for surgical resection. (Surgery should also be considered in case of acute symptoms of raised intracranial pressure, doubt about the neoplastic nature of the lesion, or an unknown primary tumour: EANO: III, C; ESMO: IV, B.)
- EANO: II, B; ESMO: III, B
Patients with non-small-cell lung cancer (NSCLC) with targetable genetic alterations such as EGFR, ALK or ROS1 rearrangement and asymptomatic or oligosymptomatic brain metastases should first be treated with systemic targeted therapy. In NSCLC without a targetable genetic alteration, checkpoint inhibitor immunotherapy alone (PD-L1 ≥50%) or with chemotherapy (PD-L1 <50%) is recommended.
- EANO: II, B; ESMO: II, B
In melanoma, the combination of ipilimumab and nivolumab should be the preferred first-line treatment in asymptomatic patients, both BRAF wild-type and BRAF-mutant. Patients with multiple symptomatic metastases with a BRAF mutation or requiring 4 mg of dexamethasone or more should receive dabrafenib plus trametinib (EANO: IV, B; ESMO: IV, B).
- EANO: III, C; ESMO: III, B
Systemic therapy of asymptomatic or oligosymptomatic brain metastases to defer WBRT should be considered in patients with HER2-positive breast cancer and preserved general condition.
- EANO: IV, n/a; ESMO: IV, B
Corticosteroids should be considered only in symptomatic patients (at the lowest dose and for the shortest possible duration). Primary prophylaxis with an antiepileptic drug should not be given (EANO: I, A; ESMO: I, A).
- EANO: IV, C; ESMO: IV, B
Patients with a history of brain metastases should be followed with brain MRI every 2 to 3 months or whenever neurological progression is suspected.
Study population
Patients with parenchymal brain metastases from solid tumours (such as lung, breast, melanoma). Brain metastases from primary brain tumours, lymphoma or leukaemia are not covered; leptomeningeal metastases are addressed in a separate guideline.
Clinical significance and place in guidelines
This guideline is the main European reference for managing brain metastases, and its key recommendations (SRS for 1 to 4 metastases, SRS as an option for 5 to 10 metastases with a volume below 15 mL, cavity SRS after surgery, and avoiding WBRT after SRS or surgery) are based on trials such as N0574 and the JLGK0901 study. The guideline emphasises decision-making in a multidisciplinary tumour board and choosing systemic therapy based on the tumour's molecular features.
Limitations
According to the authors themselves, because of the low level of evidence, many recommendations rest on expert opinion and consensus. Each recommendation is given two grades (EANO and ESMO) from different systems, which sometimes differ. Newer systemic therapies after 2021 (such as trastuzumab deruxtecan in HER2-positive breast cancer) are not covered.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.