Earlier this summer, the Congress of Neurological Surgeons (CNS) released an update to their 2019 guideline, The Role of Emerging and Investigational Therapies for the Treatment of Adults with Metastatic Brain Tumors. The 2025 update, now titled The Role of Emerging Therapies in the Management of Patients with Metastatic Brain Tumors, updates the evidence-based recommendations with recommendations that are reflective of the latest therapies and research on molecular targeting agents and more. Following a research review of articles published from January 1, 2016 through May 3, 2022, the CNS adjusted their 2019 recommendations as needed.
Following the research review, the CNS noted the most changes occurred regarding targeted therapy and immunotherapy of metastatic brain tumors (MBTs). Additionally, enough information on laser interstitial thermal therapy and radiosensitizers was available to formulate recommendations on both topics. There was a noted insufficiency in data available to create recommendations for interstitial modalities and magnetic resonance imaging-focused ultrasound.
The following overview compares changes between the 2019 and 2025 CNS guidelines regarding emerging therapies for the treatment of adult patients with MBTs.
Guidelines Referenced:
The Role of Emerging Therapies in the Management of Patients with Metastatic Brain Tumors
The Role of Emerging and Investigational Therapies for the Treatment of Adults with Metastatic Brain Tumors
- March 2019
- Full Text
Key Differences Between 2019 Guideline and 2025 Update
| Topic | 2019 Guideline | 2025 Guideline |
|---|---|---|
| Targeted Therapy | The use of afatinib is not recommended in patients with brain metastasis due to breast cancer. There is insufficient evidence to make recommendations regarding: The use of epidermal growth factor receptor inhibitors erlotinib and gefitinib in patients with brain metastasis due to non-small cell lung cancer The use of BRAF inhibitors dabrafenib and vemurafenib in the treatment of patients with brain metastases due to metastatic melanoma The use of HER2 agents trastuzumab and lapatinib to treat patients with brain metastases due to metastatic breast cancer The use of vascular endothelial growth factor agents bevacizumab, sunitinib, and sorafenib in the treatment of patients with solid tumor brain metastases. | The use of afatinib is not recommended in patients with brain metastasis due to breast cancer. In patients with ≥3 untreated brain metastases from epidermal growth factor receptor (EGFR)-mutant non–small cell lung carcinoma (NSCLC), the use of icotinib and WBRT is recommended to improve intracranial PFS. In patients with brain metastases from EGFR-mutant NSCLC, the addition of EGFR tyrosine kinase inhibitors (TKIs) to radiation therapy in the form of WBRT or SRS is suggested to improve OS, PFS, and intracranial PFS. In patients with anaplastic lymphoma kinase (ALK) mutation-positive NSCLC with untreated brain metastases, the use of alectinib is recommended to delay the time to intracranial tumor progression. In patients with untreated brain metastases from ALK mutation–positive NSCLC, lorlatinib is recommended to prolong intracranial tumor control and improve overall PFS. It is recommended that for patients with newly diagnosed brain metastases secondary to NSCLC not assessed for EGFR and ALK mutation status and for whom WBRT is indicated, getinib be added to the treatment regimen to improve local tumor control and OS. For patients with brain metastases secondary to NSCLC not assessed for EGFR and ALK mutation status and for whom targeted therapy in the form of getinib or the combination of pemetrexed and platinum compounds are otherwise indicated, it is suggested that bevacizumab, when not contraindicated by other underlying medical conditions, be added to the treatment regimen to improve CNS control and to a lesser extent PFS and OS. For patients with brain metastases secondary to NSCLC that are EGFR and ALK mutation negative and for whom targeted therapy in the form of TKIs are indicated, it is suggested that TKIs, when not contraindicated by other underlying medical conditions, be added to the treatment regimen, including radiation therapy, to improve CNS control and to a lesser extent PFS and OS. It is recommended that for patients with newly diagnosed brain metastases secondary to melanoma that is BRAFV600E positive, dabrafenib plus trametinib be added to the treatment regimen to obtain improved local tumor control. For patients with brain metastases secondary to BRAF-altered melanoma for whom targeted therapy in the form of BRAF inhibitors are indicated, it is suggested that immunotherapy, when not contraindicated by other underlying medical conditions, be added to the treatment regimen to improve CNS control and to a lesser extent PFS and OS. In adult patients with brain metastases from breast adenocarcinoma that are HER2 positive for whom radiation therapy is indicated, it is suggested that trastuzumab be added to the treatment regimen to improve PFS, median survival, and OS. In adult patients with brain metastases from breast adenocarcinoma for whom SRS is indicated, it is suggested that lapatinib be added to that treatment to improve intracranial response rate and median survival. |
| Leptomeningeal Brain Metastases and Molecular Targeted Agents | Not addressed. | In patients with leptomeningeal disease from NSCLC with EGFR mutations, it is suggested that EGFR TKIs be used to increase median survival, speci cally the third-generation TKI osimertinib for patients with EGFR-mutant NSCLC and the second-generation ALK-TKI alectinib for the treatment of lep- tomeningeal metastases in ALK-positive NSCLC. In patients with leptomeningeal metastases from Her2-positive breast cancer, it is suggested that intrathecal (IT) trastuzumab be used to increase median survival. |
| Parenchymal Brain Metastases and Immune Modulators | Not addressed. | In patients with active, untreated, asymptomatic parenchymal melanoma brain metastases, ipilimumab plus nivolumab is recommended to increase the median OS and be used without radiation to improve the median OS. In patients with parenchymal brain metastases from NSCLC, it is suggested that immune checkpoint inhibitors (ICIs) be used with radiation therapy to increase median survival, decrease incidence of local failure, increase intracranial PFS, and decrease distant intracranial failure. In patients with parenchymal brain metastases from NSCLC that are clinically stable for at least 4 weeks and with programmed death-ligand 1 tumor proportion score >50%, it is suggested that ICIs be used without radiation to improve median OS. In patients with parenchymal brain metastases from breast cancer or colon carcinoma, it is suggested that therapy with ICIs be considered alone or with radiation therapy to increase the median survival and decrease the incidence of local failure. |
| Leptomeningeal Brain Metastases and Immune Modulators | Not addressed. | There is insufficient evidence to make a recommendation regarding the use of immune modulators for the therapy of leptomeningeal brain metastases. |
| Parenchymal Brain Metastases from NSCLC and Radiosensitizers | Not addressed. | When WBRT is used for brain metastases from NSCLC, it is recommended that temozolomide be added to provide a smaller incidence of local failure, longer intracranial PFS, and longer OS. For brain metastases from NSCLC with EGFR mutation-positive status where WBRT or SRS is indicated, it is suggested that EGFR TKIs be added to that therapy to improve intracranial response rate and survival. |
| Parenchymal or Leptomeningeal Brain Metastases and Laser Interstitial Thermal Therapy | Not addressed. | For adults who have undergone SRS for brain metastases with subsequent imaging progression due to tumor progression, it is suggested that LITT be considered as equivalent to craniotomy in terms of PFS and OS and the choice of management should be individualized based on the unique characteristics of the tumor location and the patient’s clinical status. For adults who have undergone SRS for brain metastases with subsequent imaging progression due to radiation necrosis, it is suggested that LITT be considered as equivalent to medical management for radiation necrosis and the choice of management should be individualized based on the unique characteristics of the tumor location and the patient’s clinical status. |
The table reflects the new recommendations added in the 2025 update. To view unchanged recommendations, along with the full guidelines themselves, view the full-text guidelines using the links in the reference section.
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