Neuro-oncology Personalizes Brain Tumor Treatment
and Extends Patient-specific Care Across Houston
The traditional goal of neuro-oncology has been to ensure that patients live as long as possible with enhanced quality of life. Physicians affiliated with the Memorial Hermann Mischer Neuroscience Institute at the Texas Medical Center and UTHealth Medical School have added to that three broader goals: to maximize function through personalized brain tumor treatment, to help patients maintain meaningful life roles insofar as possible at every stage of treatment and recovery, and to provide collaborative care that brings multidisciplinary medical resources to patients at clinic locations across Houston.
“Personalized brain tumor treatment has been made possible by the capability to identify specific cancer genetic signatures, which allows neuro-oncologists to choose one chemotherapeutic drug over another, a dramatic change in the way we treat primary and metastatic brain tumors,” says fellowship-trained neuro-oncologist Sigmund Hsu, M.D., an assistant professor in the Vivian L. Smith Department of Neurosurgery at UTHealth Medical School.
“Before the discovery of these signatures, we made decisions about treatment based on the location of the tumor in the body and how it looked under the microscope during pathological examination. Advancements made through cancer research have allowed us to move away from the shotgun approach to treatment and moved us a step closer to finding the silver bullet.”
Bringing Specialists Together
Dr. Hsu leads the new Mischer Neuroscience Institute Cancer Neurology Clinic for the treatment of patients with neurological issues resulting from chemotherapy, and the Brain Metastases Clinic, whose staff of affiliated neuro-oncologists, neuroradiologists, neuropathologists, oncologists and neurosurgeons works closely with oncologists to provide personalized and innovative care to patients with brain tumors.
“Our goal with both clinics is to provide a much-needed niche service to the general oncologic community,” says Dr. Hsu, who provides consultation at Memorial Hermann-Texas Medical Center, Memorial Hermann Memorial City Medical Center and Memorial Hermann The Woodlands Hospital. “Cancer patients present with a complex mix of health issues. The problem itself may be easy to identify but the cause can be more difficult to determine. Is the problem with a breast cancer patient’s leg related to a herniated disk – completely unrelated to the breast cancer – or is it related to radiation or chemotherapy toxicity or to the malignancy itself? As a neurologist I can look at the big picture from a comprehensive perspective.”
With the addition of genetic counselor Krista Qualmann, M.S., the Mischer Neuroscience Institute now operates a Neurogenetics Clinic offering adult genetic counseling services based on an evaluation of personal and family medical history. Qualmann identifies genetic risk and explains inheritance patterns, provides education on the natural history of disease and discusses the risks, benefits and limitations of available genetic testing options. She also makes recommendations for screening, treatment and management and provides supportive counseling.
The three new clinics extend the range of services for brain tumor patients begun in 2011 with the opening of the Institute’s Pituitary and Vision Change Clinic, which brings together a diverse range of subspecialists to diagnose, evaluate and treat specific disorders. Led by Arthur L. Day, M.D., program director and director of clinical education in neurosurgery at the Mischer Neuroscience Institute and a professor and vice chair in the Vivian L. Smith Department of Neurosurgery at UTHealth Medical School, the clinic uses the same integrative approach that has brought national acclaim to the Institute.
Physicians at the clinic incorporate neurology, endocrinology, neuroophthalmology, stereotactic radiosurgery with Gamma Knife® technology, diagnostic radiology, interventional neuroradiology, radiation oncology and neuropathology for a comprehensive diagnosis and treatment plan.
Covering Many Bases
The team’s combined expertise includes pituitary-region tumors, including non-secretory tumors, TSH-secreting tumors, growth hormone-secreting tumors (acromegaly), corticotrophin-secreting tumors (Cushing’s disease), prolactin-secreting tumors, craniopharyngiomas, Rathke’s cleft cysts and pituitary cysts. Parasellar tumors treated include meningiomas arising from the orbit or skull base near the pituitary gland and optic nerves, craniopharyngiomas, germ cell tumors, epidermoid cysts, gliomas and metastatic tumors.
Physicians affiliated with the Institute are also investigating ways to reduce cytotoxicity in the treatment of brain tumors. The ReACT trial is a significant step forward in using next-generation sequencing (NGS) for the treatment of GBM. “Mutations that lead to epidermal growth factor receptor (EGFR) overexpression or overactivity have been associated with a number of cancers including GBM, in which a specific mutation called EGFRvIII is often observed,” says Dr. Hsu, whose clinical and research interests include the discovery of new and more effective therapies for patients with primary brain tumors, treatment of metastatic cancer to the brain and spinal fluid and the evaluation and treatment of neurological problems in cancer patients. “While we’ve used NGS and genetic-based treatment for brain metastases of melanoma, lung cancer and breast cancer, we’re still in the infancy of using genomics for primary brain tumors such as GBM.”
Last year, the Mischer Neuroscience Institute was chosen as a site for the FoundationOne™ Registry, to which physician researchers report data gathered using proprietary genomic profiling technology to expand patients’ treatment options. FoundationOne’s next-generation sequencing interrogates the entire coding sequence of 236 cancerrelated genes plus 47 introns from 19 genes that are often rearranged or altered in solid tumor cancers. By identifying mutations in these genes, the technology gives physicians more information about which unique tumor types are more likely to respond to certain chemotherapeutic drugs or may be a good match for a clinical trial.
Dr. Hsu was recruited to the Institute by fellowship-trained neurologist and neuro-oncologist Jay-Jiguang Zhu, M.D., Ph.D., who is director of the Clinical Cancer Program and an associate professor in the Vivian L. Smith Department of Neurosurgery at UTHealth Medical School. “Thanks to next-generation sequencing, we understand more about the underlying DNA mutations that drive cancer growth, which has allowed us to adapt treatment to the specific genetics of the tumor,” says Dr. Zhu, who focuses his practice on primary brain tumors and primary central nervous system (CNS) lymphomas as well as brain metastases and leptomeningeal spread of systemic malignancies.
“As we learn more, we’re replacing traditional cytotoxic treatments with less toxic, potentially more effective therapies that target changes in a patient’s unique DNA that promote the survival of cancer cells. These breakthrough approaches to treatment with more clinical trials available at MNI have allowed us to increase our volumes by nearly 50 percent since 2009.”
Dr. Zhu is principal investigator of three clinical trials that give eligible study participants access to new and advanced treatments. The first is a Phase III multicenter, randomized, controlled trial designed to test the efficacy and safety of an experimental, portable, batteryoperated medical device called the NovoTTF-100A for newly diagnosed GBM patients in combination with temozolomide, compared to temozolomide alone. The device, which patients wear on their scalp, provides a constant, safe, lowvoltage electric field that has been shown to reduce tumor cell survival and division capacity.
Dr. Zhu is also principal investigator of a randomized, double-blind, controlled Phase IIB clinical trial testing the efficacy of the vaccine ICT-107 for newly diagnosed GBM patients following resection and chemoradiation. ICT-107 is an autologous vaccine consisting of dendritic cells from the patient’s own immune system, which are isolated from blood by apheresis and pulsed with synthetic peptides from six GBM-specific stem cell-associated antigens – MAGE- 1, HER2, AIM2, TRIP-2, GP100 and interleukin 13 receptor alpha. The sensitized dendritic cells are then returned to the patient by subcutaneous injection as an immunotherapy to attack the tumor.
The third trial, an open-label Phase I/II (Safety Leadin) study of trans sodium crocetinate (TSC) with concomitant radiation therapy and temozolomide in newly diagnosed GBM, examines the safety and efficacy of the radiation sensitizing effect of TSC in combination with fractionated radiation.
Dr. Zhu works with the Institute’s Cancer Research Program as part of a new Brain Tumor Research Program. “Our objective is to gain understanding of the molecular changes in patient tumor specimens,” Dr. Zhu says.
"Understanding those changes will give us prognostic factors that enable us to determine which patients will respond well to a given drug or treatment with multiple drugs. Some genes have already been identified, and we’re looking for others with prognostic value. Knowledge of the molecular changes that take place in cancer cells will help us define treatment targets for specific patients, and aid in choosing chemotherapies or specific molecular-based treatments. Our ultimate goal is to provide personalized cancer care, maximize efficacy and minimize toxicity for each patient.”
Advancements in Pediatric Brain Tumor Treatment
In the pediatric arena, the promising results of translational studies conducted by David Sandberg, M.D., FAANS, FACS, FAAP, director of pediatric neurosurgery at Children’s Memorial Hermann Hospital in the Texas Medical Center, have demonstrated the safety of infusing chemotherapeutic agents directly into the fourth ventricle of the brain. These studies led to a pilot clinical trial, available only at Children’s Memorial Hermann Hospital and The University of Texas MD Anderson Cancer Center, for children with recurrent tumors in this area of the brain. This radically new approach to chemotherapy allows Dr. Sandberg and team members to circumvent the blood-brain barrier and deliver agents directly to the site of disease, minimizing side effects by decreasing systemic drug exposure.
“The collaboration with MD Anderson is good news for children and adolescents with brain tumors,” says Dr. Sandberg, who holds joint appointments as associate professor in the Vivian L. Smith Department of Neurosurgery and the department of Pediatric Neurosurgery at UTHealth Medical School, and is also an associate professor in the department of Neurosurgery at MD Anderson Cancer Center. “Using novel approaches to surgery and chemotherapy, we have the potential to minimize side effects from treatment and achieve better long-term survival rates.”
In addition to the single-center clinical trial for recurrent medulloblastoma, ependymoma and atypical teratoid-rhabdoid tumors using direct infusion of chemotherapy into the fourth ventricle, other novel approaches are being investigated by the combined research team, including administration of natural killer cells into the fourth ventricle to attack tumor cells via cell-directed therapy.
As the Institute continues the expansion of services across the city, neuro-oncology services once available only at Memorial Hermann-Texas Medical Center, Memorial Hermann Memorial City Medical Center and Memorial Hermann The Woodlands Hospital are now provided at Memorial Hermann Southwest Hospital and TIRR Memorial Hermann. “The Mischer Neuroscience Institute’s infrastructure expansion and Memorial Hermann’s presence across Houston have allowed for the extension of neuro-oncology expertise and capabilities outside the Texas Medical Center,” says Dr. Zhu, who also consults on patients with brain tumors at TIRR Memorial Hermann, the top rehabilitation hospital in the southern half of the United States.
Cancer Rehabilitation Programs
In 2013, TIRR Memorial Hermann extended its cancer rehabilitation programs throughout the Greater Houston community and added survivorship wellness programs at key locations. “Many people return to normal life after cancer treatment but a growing number, as a result of their diagnoses, are learning to cope with a decline in function related either to the disease or to the effects of chemotherapy and radiation therapy, which have complications of their own,” says Jacob Joseph, M.D., clinical chief of Specialty Rehabilitation Programs at TIRR Memorial Hermann and an assistant professor of physical medicine and rehabilitation at UTHealth Medical School. “We see a lot of people who are excited to be alive after their cancer treatment, but then they discover they’re living with issues that affect their quality of life. These patients have led us to collaborate with the Mischer Neuroscience Institute and make a concerted effort to address survivorship issues in greater depth.”
Dr. Zhu considers the collaboration with TIRR Memorial Hermann an important part of the comprehensive continuum of care offered by physicians affiliated with the Institute. “Developing biological agents with improved efficacy and reduced toxicity is only half the battle,” he says. “Every patient we treat deserves the opportunity to continue to live life in meaningful ways.”