Amanda Saratzis, MD, FAANS, FCNS – Senior Director, Global Medical Affairs, Oncology, Jazz Pharmaceuticals
Each May, Brain Cancer Awareness Month provides an opportunity to shine a spotlight on one of the most complex and underserved areas of oncology: brain cancer and other central nervous system (CNS) cancers. Although advances have been made in precision medicine and neuro-oncology in recent years, patients with rare brain tumors still face systemic barriers such as delayed diagnosis, limited access to treatment, and limited treatment options, often with devastating outcomes.
Rare brain tumors, such as diffuse midline glioma (DMG), are defined not only by their low incidence but also by their unusual anatomical and biological complexity. Many are caused by distinct molecular changes that cannot be identified by imaging or traditional histopathology alone. As a result, comprehensive biomarker testing is essential for accurate diagnosis, prognosis, and treatment planning for both primary and metastatic CNS tumors. Without timely and thorough molecular profiling, tumors may be misclassified or incorrectly graded, resulting in inappropriate treatment decisions, ineligibility for clinical trials, and loss of access to life-sustaining and life-saving treatments.
Despite their status as standard of care, access to molecular testing remains unstable, especially outside major academic centers. Treatment is ideally started within two weeks after surgery, although it may take two to three weeks for test results to be available. These schedules leave little room for delay.
Brain Tumor Awareness Month is a great time to raise awareness about the need for molecular diagnostic testing for these patients. In the case of DMG, the presence of the critical oncogenic mutation H3 K27M confers a poor prognosis and reduces response to standard treatments, but also guides treatment decisions. Therefore, detection of biomarkers is highly needed to ensure accurate molecular tumor diagnosis and patient eligibility for potential treatments. To achieve this, both patients and clinicians will need early access to molecular testing as well as increased awareness of the important impact of biomarker testing on patient clinical outcomes.
Recent research advances are providing new insights into the biology of these complex tumors, providing hope for patients and their families as they look to the future. Researchers and clinicians are beginning to understand these tumors at an astonishing level of detail. In the case of DMG, recent improvements in surgical techniques that allow safe tissue biopsies for these deep-seated tumors and advances in molecular profiling techniques to analyze these rare specimens have increased the availability of fresh tumor tissue for analysis and dramatically accelerated our knowledge and understanding of this disease. We hope that this knowledge will allow us to better address specific drivers of DMG and identify vulnerabilities that can be attacked with new targeted treatments.
Despite these impressive advances, there is still much work to be done to raise awareness among healthcare professionals and patients about the importance of molecular testing and diagnosis, particularly for H3 K27M and other prevalent targetable mutations, to inform the treatment of glioma patients.
As research advances, molecular testing presents an important opportunity to ensure patients find the right treatment early in their treatment journey. An interesting development is the recent demonstration that cell-free circulating tumor DNA (ctDNA) released into the cerebrospinal fluid (CSF) of brain tumor patients can be detected.
Techniques to sequence and measure critical mutations such as H3 K27M in these “liquid biopsy” specimens offer new opportunities to potentially diagnose and monitor patients over time without necessarily requiring multiple tumor biopsies or brain surgeries. This approach is the next frontier in molecular testing for the diagnosis and management of brain tumors and presents an opportunity to minimize patient risk and improve clinical outcomes through accurate stratification to targeted therapies. Innovative treatment options such as targeted therapies and advanced molecular diagnostic techniques open new doors for patients, and the impact is even greater when molecular testing becomes part of the patient journey.
