1. What is the decision or change (e.g., clinical topic, practice guideline, system design, delivery of care) you are facing or struggling with where a summary of the evidence would be helpful?

The purpose of this topic nomination is to evaluate all available evidence, from which, the Congress of Neurological Surgeons (CNS) will update its 2019 Guidelines for the Treatment of Adults with Metastatic Brain Tumors. This update consolidates the 2019 guideline to focus on clinically relevant questions (as evidence on this topic has changed over time). The objective of these guidelines is to establish the best evidence-based management of metastatic brain tumors over all commonly used diagnostic and treatment modalities in regularly encountered clinical situations. We will aim to address the following questions:

The Role of Surgical Resection Surgery for metastatic brain tumors at new diagnosis

1. In adult patients with newly diagnosed metastatic brain tumors (excluding radiosensitive tumor histologies), is surgery, stereotactic radiosurgery (SRS), or whole brain radiation therapy (WBRT) most effective in improving performance status, extending overall survival, extending median survival or improving local control?

Surgery and radiation for metastatic brain tumors

2. In adult patients with newly diagnosed metastatic brain tumors (excluding radiosensitive tumor histologies), is surgical resection followed by WBRT, SRS, or another combination of these modalities most effective in improving favorable performance status, extending overall survival, extending median survival or improving local control?

Surgery for recurrent metastatic brain tumors

3. In adult patients diagnosed with recurrent, non-radiosensitive metastatic brain tumors, does surgical resection most effective in improving favorable performance status, extending overall survival, extending median survival or improving local control?

Surgical technique and recurrence

     4A. In adult patients diagnosed with recurrent, non-radiosensitive metastatic brain tumors, does the surgical technique (en bloc resection or piecemeal resection) affect local control?

     4B. In adult patients diagnosed with recurrent, non-radiosensitive metastatic brain tumors, does the extent of surgical resection (gross total resection or subtotal resection) affect local control?

The Role of Whole Brain Radiation Therapy and Stereotactic Radiosurgery Target population: Adult patients (older than 18 years of age) with newly diagnosed brain metastases.

1. In adult patients with newly diagnosed brain metastases who are treated with whole brain radiation therapy (WBRT), is there an optimal dose/fractionation schedule?
2. In adult patients with newly diagnosed brain metastases does tumor histopathology or molecular status affect the decision to use WBRT, the dose fractionation scheme to be utilized, or its outcomes?
3. In adult patients with newly diagnosed brain metastases, what neurocognitive consequences can result from WBRT (besides)survival outcomes) and what treatments best minimize these neurocognitive consequences?
4. In adult patients with newly diagnosed brain metastases, does the addition of WBRT after surgical resection or radiosurgery improve progression-free or overall survival outcomes when compared with surgical resection or radiosurgery alone?

Target Population: These recommendations apply to adult patients with new or recurrent solitary or multiple brain metastases from solid tumors as detailed in each section.

5. In adult patients with new or recurrent solitary or multiple brain metastases from solid tumors is stereotactic radiosurgery (SRS) more effective than other treatment modalities to reduce tumor volume, local recurrence or to improve overall quality of life?
6. In adult patients with new or recurrent solitary or multiple brain metastases from solid tumors, does the use of SRS after open surgical resection of brain metastasis reduce tumor volume, local recurrence or improve overall quality of life?
7. In adult patients with new or recurrent solitary or multiple brain metastases from solid tumors, does the use of SRS prior to surgical resection of brain metastasis reduce tumor volume, local recurrence or improve overall quality of life?
8. In adult patients with 1 to 4 brain metastases from solid tumors, does the use of SRS alone reduce tumor volume, local recurrence or improve overall quality of life?
9. In adult patients with more than 4 brain metastases from solid tumors, does the use of SRS alone reduce tumor volume, local recurrence and improve overall quality of life?

The Role of Chemotherapy

1. In adult patients with brain metastases does cytotoxic chemotherapy in addition to whole brain radiation therapy (WBRT) for the treatment of their brain metastases reduce progression or recurrence or improve survival? Target population: This recommendation applies to adult patients with newly diagnosed brain metastases amenable to both chemotherapy and radiation treatment.
2. In adult patients with newly diagnosed brain metastases, does cytotxic chemotherapy in addition to stereotactic radiosurgery (SRS) reduce progression or recurrence or improve survival?
3. In adult patients with newly diagnoses brain metastases, does cytotxic chemotherapy alone reduce progression or recurrence or improve survival?

The Role of Systemic Therapy

1. In patients with parenchymal or leptomeningeal brain metastases, does the use of molecular targeted agents provide benefit in terms of local control, overall survival, progression free survival, performance status, or reduction in central nervous system side effects compared to standard management with chemotherapy, immune modulators, stereotactic radiosurgery, whole brain radiotherapy, and surgical resection?
2. In patients with parenchymal or leptomeningeal brain metastases, does the use of immune modulators provide benefit in terms of local control, overall survival, progression free survival, performance status, or reduction in central nervous system side effects compared to standard management with chemotherapy, molecular targeted agents, stereotactic radiosurgery, whole brain radiotherapy, and surgical resection?
3. In patients with parenchymal brain or leptomeningeal metastases, does the use of interstitial modalities provide benefit in terms of local control, overall survival, progression free survival, performance status, or reduction in central nervous system side effects compared to standard management with chemotherapy, immune modulators and molecular targeted agents, stereotactic radiosurgery, whole brain radiotherapy, and surgical resection?
4. In patients with parenchymal or leptomeningeal brain metastases, does the use of intraoperative radiotherapy provide benefit in terms of local control, overall survival, progression free survival, performance status, or reduction in central nervous system side effects compared to standard management with chemotherapy, immune modulators and molecular targeted agents, stereotactic radiosurgery, whole brain radiotherapy, and surgical resection?
5. In patients with parenchymal or leptomeningeal brain metastases, does the use of laser interstitial thermal therapy [LITT] provide benefit in terms of local control, overall survival, progression free survival, performance status, or reduction in central nervous system side effects compared to standard management with chemotherapy, immune modulators and molecular targeted agents, stereotactic radiosurgery, whole brain radiotherapy, and surgical resection?
6. In patients with parenchymal or leptomeningeal brain metastases, does the use of magnetic resonance-guided focused ultrasound provide benefit in terms of local control, overall survival, progression free survival, performance status, or reduction in central nervous system side effects compared to standard management with chemotherapy, immune modulators and molecular targeted agents, stereotactic radiosurgery, whole brain radiotherapy, and surgical resection?

The Role of Steroids and Prophylactic Anticonvulsants

Target population: These recommendations apply to adults diagnosed with brain metastases who have not experienced a seizure.

1. In adults diagnosed with brain metastases who have not experienced a seizure, do steroids improve neurologic symptoms and/or quality of life compared to supportive care only or other treatment options?
2. In adults diagnosed with brain metastases who have not experienced a seizure and have been treated with steroids, what dose best improves neurologic symptoms and/or quality of life?
3. In adults diagnosed with brain metastases who have not experienced a seizure, do prophylactic anti-epileptic drugs (AEDs) decrease the risk of seizures in non-surgical patients who are otherwise seizure free?
4. In adults diagnosed with brain metastases who have not experienced a seizure, do prophylactic AEDs decrease the risk of seizures in the perioperative setting?

2. Why are you struggling with this issue?

The 2019 guidelines were constructed to assess the most current and clinically relevant evidence for management of metastatic brain tumors. They set a benchmark regarding the current evidence base for this management while also highlighting important key areas for future basic and clinical research, particularly on those topics for which no recommendations could be formulated.

A component of that set of guidelines was recognition that updates would eventually be necessary so as to allow the recommendations to be modified to stay abreast of advances in the care and management of metastatic brain tumors.

According to the National Institutes of Health there are 98,000 to 170,000 cases that occur each year. There is a significant amount of new literature available on this topic that will inform a new systematic review.

3. What do you want to see changed? How will you know that your issue is improving or has been addressed?

We believe that new literature outlines improvements in the management of metastatic brain tumors and will inform this systematic review to better address the key questions to identify the most effective known treatments to improve patient outcomes. The CNS guideline that will be developed based on this systematic review will be constructed to assess the most current and clinically relevant evidence for the management of metastatic brain tumors in order to set a benchmark for standard of care will also highlight important key areas for future research.

Only by designing future investigations in a high-quality manner that recognizes and overcomes prior weaknesses noted in these guidelines will advancement toward a remedy of this disease be achieved. The application of published guidelines information based on a comprehensive systematic review of the literature will help inform clinical practice and therefore improve patient outcomes.

4. When do you need the evidence report?

Friday, December 20, 2024

5. What will you do with the evidence report?

The purpose of this topic nomination is to evaluate all available evidence, from which, the Congress of Neurological Surgeons (CNS) will update its 2019 Guidelines for the Treatment of Adults with Metastatic Brain Tumors. This update consolidates the 2019 guideline to focus on clinically relevant questions (as evidence on this topic has changed over time). We plan to include a patient or patient representative in the working group to keep the focus and questions patient centered. We are also in the process of engaging a representative from the American Society of Clinical Oncology (ASCO) and will seek endorsement from ASCO of the published guideline. The CNS maintains in-house infrastructure to lead, promote, and support the creation and methodological processes to produce evidence-based guidelines, which are critical tools to confront a rapidly changing health care environment. Using the CNS’s high quality, rigorous methodological process, a multidisciplinary task force will develop recommendations based on the available evidence provided by the Evidence Based Practice Center. Throughout development, the task force will use evidence-based methodologies and strictly adhere to a priori defined criteria as defined by the National Academy of Medicine’s standards for conducting systematic reviews and clinical evidence-based guidelines.

This topic was initiated by the American Association of Neurological Surgeons/Congress of Neurological Surgeons (AANS/CNS) Joint Section on Tumors. The CNS also recruited from a variety of institutions and subspecialty disciplines to have as broad a representation of opinions and expertise as possible. It is CNS’s goal to follow the National Academy of Medicine’s recommendations to be inclusive and inter-disciplinary when constructing our guidelines and subsequent recommendations. A conscientious effort will also be made to be sure that any conflict of interest is fully disclosed and avoided. Participants who have published extensively in certain areas will be asked to recuse themselves from voting and will be assigned to evaluate evidence in other topics. Every effort will be made to ensure that the guideline is accurate, reliable, and non-biased.

The CNS guidelines attempt to provide essential information for clinicians, globally, helping to improve patient care and outcomes. In addition to developing high quality guidelines, CNS is also committed to dissemination of guidelines in multiple, open access formats, such as publication in peer-reviewed journals (the guideline will be submitted to Neurosurgery), publication on the CNS webpage, webinars, podcasts, conference seminars and courses, as well as other promotional efforts.

Optional Information About You

What is your role or perspective? clinician on behalf of professional Society

If you are you making a suggestion on behalf of an organization, please state the name of the organization - Congress of Neurological Surgeons

May we contact you if we have questions about your nomination? Yes