EANO, ESMO Release Joint Guidelines for Brain Metastases Treatment

The European Association of Neuro-Oncology (EANO) and the European Society for Medical Oncology (ESMO) have released joint guidelines and recommendations for the diagnosis, treatment, and follow-up of parenchymal brain metastases (BM).

BMs cause neurological symptoms, such as epileptic seizures, headaches, and motor deficits, within weeks of onset. Many of the signs depend on the location of the BM, and cerebellar BMs typically can cause rapid neurological deterioration.

The screening of individuals is recommended at the time of diagnosis of some cancers, such as lung cancer, metastatic human epidermal growth factor receptor 2, stage IV melanoma, and triple-negative breast cancer.

Magnetic resonance imaging (MRI), with and without contrast agents, should be used for patients with suspected BMs at the recommended 1.5 T field strength. The joint guidelines recommend that a biopsy should be considered only if lesions cannot be distinguished from abscesses, brain tumors, or inflammation with certainty. Cranial computed tomography (CT) scans should only be used for individuals with contraindications for MRI, as CTs are less sensitive than MRIs.

The recommendations for general consideration are that surgery for individuals should be considered when the neoplastic nature of a brain lesion is doubted, the tumor is unknown or when more than one tumor is known, or when the primary tumor rarely generates BM or can affect clinical decision making.

Surgery should also be considered if there is a single BM, multiple resectable BMs for individuals who require steroids and are candidates for immune checkpoint inhibition, or when there are acute symptoms of raised intracranial pressure.

After the surgery, an MRI should be performed within 48 hours.

Stereotactic radiosurgery (SRS) should be used for individuals with a 1 to 4 limit of BMs. It can be considered for individuals with BMs 4 to 10 when the cumulative tumor volume is less than 15 ml. SRS is recommended after complete or incomplete resection of BMs in the resection cavity.

Whole brain radiotherapy (WBRT), a form of external radiation therapy, should be used after SRS is discouraged or after surgery. It should be considered for individuals who are not responsive to SRS or individuals not eligible for SRS.

The peritoneal cancer index is still recommended for individuals with limited and extensive stage small cell lung cancer (SCLC) with response to chemoradiotherapy.

Pharmacotherapy has been recommended based on histological and molecular characteristics of the primary tumor, and previous treatments should be considered for most individuals. The molecular genetic work-up of BMs should be targeted in therapy or immunotherapy instead of primary tumor.

In HER2-positive breast cancer individuals, systemic treatment of asymptomatic or oligosymptomatic BMs should be considered before WBRT. For HER2-negative individuals, standard chemotherapy may be considered for BM after local treatment.

Individuals with non-small cell lung cancer (NSCLC) and asymptomatic or oligosymptomatic BMs should be treated by upfront immune checkpoint inhibition alone or combined with systemic chemotherapy. Likewise, individuals with NSCLC with EGFR or ALK or ROS1 rearrangements and asymptomatic or oligosymptomatic BMs should be treated by upfront systemic targeted therapy.

Individuals with SCLC should be treated by platinum-based chemotherapy, with or without immune checkpoint inhibition, according to the panel.

In BRAD wild-type and BRAD-mutated asymptomatic patients, a combination of ipilimumab and nivolumab is the preferred treatment. Individuals with multiple symptomatic BRAD-mutated BMs or requiring 4 mg of dexamethasone or more should receive dabrafenib plus trametinib.

The recommendations of integrated therapeutic approaches and multimodality treatment of BMs should be individualized and estimated by medical or radiation oncology or surgery. Therapeutic decisions should be discussed at the dedicated BM board or disease-specific tumor board. Randomized trials in individuals with asymptomatic or oligosymptomatic BMs should be to identify the most effective combined modality treatment of systemic therapy.

The panel recommended neurological examinations every 2 to 3 months or earlier when radiological progression is suspected or symptoms develop. MRIs should also be carried out every 2 to 3 months or when neurological progression is suspected. Advanced MRI should be considered for disfiguring treatment-related changes. Neurocognitive functions and ability to consent should also be assessed regularly for a follow-up.

Additional guidelines are that steroids should be considered only for symptomatic patients, and primary anti-convulsant prophylaxis should not be given. Also, decisions about driving should consider epilepsy and cognitive and neurological functions and must adhere to national guidelines and law. Low-molecular-weight heparin should be considered for primary or secondary thromboprophylaxis and treatment of VTW in individuals with BM.

These recommendations are based on expert opinions and consensus, rather than information and results from clinical trials.

Reference

Le Rhun E, Guckenberger M, Smits M, et al. EANO–ESMO clinical practice guidelines for diagnosis, treatment and follow-up of patients with brain metastasis from solid tumours. Ann Oncol.2021;S0923-7534(21)02214-6. doi:10.1016/j.annonc.2021.07.016