Attacking Aggressive Brain Tumors From Every Angle

Neurological Institute – January 2016

 Andrew Sloan, MD

University Hospital’s Neurological Institute is home to the Brain Tumor and Neuro-Oncology Center, a multidisciplinary collaboration focused on discovering novel approaches to treating some of the most aggressive brain tumors. The goal is to pilot and develop more precise and effective approaches that drastically improve outcomes for adult and pediatric patients. 

Engaging the body’s immune system to fight glioblastoma

Andrew Sloan, MD, Peter D. Cristal Chair in Neurosurgery, Professor & Director, University Hospitals Brain Tumor & Neuro-Oncology Center, UH Seidman Cancer Center and the UH Neurological Institute, and Vice Chair Neurological Surgery, UH Cleveland Medical Center & Case Western Reserve University School of Medicine, directs a team of clinical researchers dedicated to harnessing the power of the body’s immune system to target and destroy tumor cells and to bolster itself against the harmful side effects of powerful chemotherapy.

“There is abundant evidence that malignant gliomas are among the most immunosuppressive of all tumors,” Dr. Sloan said. “Our mission is to find a way to ‘cut the brakes’ that these cancer cells put on what should be a significant response from T-lymphocytes, and empower these T-cells to fully attack the invading cancer cells.”

A multicenter trial he co-directs in partnership with the Neuro-Oncology Center at the National Cancer Institute explores the use of several new drugs that counteract the T-cell “checkpoint” proteins CTLA4 and PD-1. These proteins normally function to end an immune response, preventing damage to normal cells.  However, cancer cells, particularly glioblastomas, secrete molecules that trigger these proteins and therefore inhibit T-cell response when cancer cells are present, effectively “cloaking” the tumor so that the immune system does not recognize it. The novel drugs ipilimumab and nivolumab inhibit the tumor cells from hiding and enable the patient’s own immune system to recognize and kill the tumor. This strategy has been proven effective in melanoma and lung cancer and has recently been FDA approved for certain patients with these diseases. 

Glioblastomas are also particularly resistant to even the most potent chemotherapy. Combining standard chemotherapy using temozolamide (TMZ) with another drug called benzyl-guanine (BG) improves tumor response, but also leads to an increase in serious side effects for the patient and decreases survivability.  However, studies by Stanton Gerson, MD, Director of the UH Seidman Cancer Center/Case Comprehensive Cancer Center and Professor, Medicine, Case Western Reserve University School of Medicine,  identified a mutation P140K-MGMT which does not bind to BG and thus allows the bone marrow to better tolerate the combined treatment.   Dr. Sloan’s group is now adapting this strategy for clinical trials in patients with glioblastoma. 

“The hope is that this genetically engineered marrow will strengthen a patient’s ability to tolerate greater exposure to this combination therapy, allowing us to kill the tumor with fewer side effects.” concluded Dr. Sloan.

Enhancing surgical procedures for tumor removal 

For surgical removal of otherwise inoperable tumors, UH Case Medical Center served as one of two hospitals in the country in partnership with Monteris Medical, Inc., to pioneer minimally invasive Laser Interstitial Thermotherapy (LITT). The system uses MRI-guided lasers to ablate tumors without damaging the surrounding healthy tissue. This revolutionary and minimally invasive approach is especially effective in treating glioblastoma, which is often inoperable using traditional open procedures due to the risk of damage to surrounding tissue. At UH Case Medical Center, the system also successfully ablated an inoperable hypothalamic hamartoma lesion which caused uncontrollable seizures in a pediatric patient. Following the procedure, the family reports an improved quality of life for the patient with less medication and fewer seizures. Today, LITT is offered at only a small number of hospitals in the United States, including UH Case Medical Center and the Seidman Cancer Center. 

 

UH Neurological Institute is also leading a clinical trial for a new generation of surgical simulator, the Selman Surgery Rehearsal Platform (SRP), that allows surgeons to plan for and practice complex procedures in a simulation environment that mimics a real surgical procedure, similar to the real-time flight simulators used to train pilots. This particular system is unique in that it combines two-dimensional patient images into a single three-dimensional environment with realistic look and feel. The SRP recently added an operating room version featuring hands free technology that allows the surgeon to seamlessly access and follow the surgical plan, as well as all CT and MRI images, without needing to pause for re-sterilization during a procedure.

 

Warren R. Selman, MD, Director, UH Neurological Institute; Neurosurgeon-in-Chief, University Hospitals; Harvey Huntington Brown Jr. Professor and Chair, Department of Neurological Surgery, Case Western Reserve University School of Medicine, and Dr. Sloan helped develop the system andserve as consultants for Surgical Theater, LLC, a company founded by two former Israeli Air Force officers familiar with the benefits of real-life simulation experience in aeronautics. The SRP will increase surgical efficiency and precision, and reduce procedure time. The team hopes it will also improve patient care by enhancing the surgeon’s preparation for complex procedures, enabling seamless execution of the surgical plan in the operating room.

From novel genetic and immunological approaches to fighting cancer within the body to increasing precision during surgical procedures to remove tumors, the Brain Tumor and Neuro-Oncology Center at UH Neurological Institute continues to identify innovative new ways to combat even the most aggressive brain tumors. The advances made will enhance the high quality of care that UH Case Medical Center is known for in this specialty, and improve treatment options for patients with brain tumors at UH Case Medical Center and around the world.

Visit UHHospitals.org or call 1-877-435-3777 (1-877-435-3777) or 440-771-8537 to refer a patient or learn more.