New guidelines on the role of emerging therapies in managing adults with metastatic brain tumors

The Congress of Neurological Surgeons (CNS) has updated its guidelines on using emerging therapies to treat metastatic brain tumors, reflecting improvements in pharmaceuticals, radiation therapy software and hardware, and surgical equipment. Jeffrey J. Olson, MD, of the Department of Neurosurgery at Emory University School of Medicine in Atlanta, and colleagues have published the new guidelines in Neurosurgery.

“Advancement of nonsurgical and surgical therapies for metastatic brain tumors is occurring at a rapid rate,” Dr. Olson’s group says. “This has allowed for concrete recommendations to be made on various levels to assist medical and surgical practitioners.” The Joint Guidelines Review Committee of the CNS/AANS has also endorsed the guidelines.

The update is based on a systematic review of 162 English-language primary studies posted in PubMed or Embase between January 1, 2016 and May 3, 2022. Most of the new recommendations focus on the use of targeted therapy:

Non–small-cell lung cancer (NSCLC) parenchymal brain metastases

• Epidermal growth factor receptor (EGFR)-mutant NSCLC:
  • ≥3 untreated metastases: Icotinib and whole-brain radiation therapy (WBRT) are recommended (evidence level I)
  • Any number of metastases: Add EGFR tyrosine kinase inhibitors (TKIs) to WBRT or stereotactic radiosurgery (SRS) (level III)
• Anaplastic lymphoma kinase (ALK) mutation–positive NSCLC and untreated metastases: Alectinib is recommended (level I), as is lorlatinib (level III)
• Newly diagnosed metastases, EGFR and ALK status of NSCLC not assessed:
  • If WBRT is indicated, add gefitinib to the treatment regimen (level I)
  • If gefitinib or the combination of pemetrexed and platinum compounds is indicated, add bevacizumab when not contraindicated by other underlying medical conditions (level III)
• EGFR-negative, ALK-negative NSCLC: Add a TKI (if indicated and not contraindicated by other underlying medical conditions) to the treatment regimen, including radiation therapy (level III)

Melanoma parenchymal brain metastases

• Newly diagnosed metastases secondary to BRAFV600E-positive melanoma: Add dabrafenib plus trametinib to the treatment regimen (level I)
• Metastases are secondary to BRAF-altered melanoma and BRAF inhibitors are indicated: Add immunotherapy to the treatment regimen when not contraindicated by other underlying medical conditions (level III)

Breast adenocarcinoma parenchymal brain metastases

• HER-2–positive breast adenocarcinoma and radiation therapy is indicated: Add trastuzumab to the treatment regimen (level III)
• SRS is indicated: Add lapatinib to that treatment (level III)

Leptomeningeal brain metastases

• NSCLC: Use osimertinib if EGFR-mutant, alectinib if ALK-positive (level III)
• HER-2–positive breast cancer: Use intrathecal trastuzumab (level III)

Laser interstitial thermal therapy is an option for adults who have undergone SRS for brain metastases with subsequent progression apparent on imaging (level III). If progression is due to tumor progression, LITT can be considered equivalent to craniotomy; if due to radiation necrosis, it can be considered equivalent to medical management. In either case, the choice of management should be individualized based on tumor location and the patient’s clinical status.

The guidelines additionally address the use of immune modulators and radiosensitizers. The reviewers found insufficient evidence to make any recommendations for or against interstitial modalities or high-intensity focused ultrasound.