Why a Precise Diagnosis Is Vital to Treat Brain and Spine Tumors

October 10, 2019, by Brittany Cordeiro, NCI-CONNECT Program Manager

A precise cancer diagnosis is essential to determine the best treatment for an individual. Yet, nearly five to 10 percent of people with a brain or spine tumor receive an inaccurate diagnosis.

Most people first learn they have a tumor from their primary care doctor. They are then referred to neuro-oncologists or doctors who have expertise in their tumor type. Part of this specialized health care team is a neuropathologist, a doctor who examines brain and spine tumor tissue to make a precise diagnosis.

“We come up with the best definition of the tumor possible based on the specific changes we see in the tumor under the microscope,” says Kenneth Aldape, M.D., Ph.D., senior investigator and chief of the NCI Center for Cancer Research's Laboratory of Pathology.

Dr. Aldape studies the genomic and epigenomic alterations in brain and spine tumors—the way genes behave and change in cancer. He characterizes the biology of specific genomic alterations and how they contribute to the development of the disease. He also studies how they impact treatment resistance of aggressive brain tumors. 

The goal of understanding these alterations is to be able to identify and better classify tumor types. “We believe that classifying brain tumors based on their biology will lead to a greater understanding of why specific tumor subtypes may be more or less sensitive to therapies,” Dr. Aldape says.

He is also pushing for precision diagnosis for patients because of the rate of diagnostic discrepancy. “We want to reduce errors because, without a proper diagnosis, a lot of precision medicine may not go as well as planned,” Dr. Aldape says.

Making an Accurate Diagnosis   

Dr. Aldape works on the NCI-CONNECT health care team to help accurately diagnose rare brain and spine tumors. “Some of these rare tumors can be challenging to diagnose because they are so rare,” Dr. Aldape says.

At NIH, all patients who visit the NCI Center for Cancer Research's Neuro-Oncology Branch have their diagnosis reviewed by a neuropathologist. Dr. Aldape receives tumor tissue in the form of a tissue block or unstained slides from the hospital where a patient had his or her surgery. If a patient has not had surgery or a biopsy, he or she can consult with NIH’s neurosurgical oncology team. Dr. Aldape examines the tissue closely under a microscope looking at alterations in the tissue. This is called histopathology.

“We come up with the best morphologic diagnosis, a diagnosis based on the appearance of that tumor under the microscope,” Dr. Aldape says. Then, Dr. Aldape consults with clinical specialists, like the neurosurgeon and neuro-oncologist, to discuss the imaging and clinical features of the tumor. This helps determine what is called the clinical pathologic diagnosis.

Dr. Aldape further extends the diagnostic process to molecular analysis. He uses technologies, such as next generation sequencing and DNA methylation, to understand the molecular alterations of the tumor and obtain a molecular diagnosis. Then, combining the diagnostic information—morphologic, clinical pathologic, and molecular—the team makes an integrated diagnosis.

“This is a unique service we offer routinely to patients as part of our NCI-CONNECT Clinic,” Dr. Aldape says. An integrated diagnosis is often not available at other hospitals because they do not have the technologies to examine the tissue or the pathologist may have never seen a patient with one of these rare brain or spine tumor types before.

“With each patient we see, we are getting more and more experience, and with that we can uncover unexpected and unusual things that may not have been picked up from original pathology,” Dr. Aldape says. Then, the health care team can ensure patients receive the best treatment or participate in the best clinical trial for their tumor type.

Researching New Diagnostic Technologies

Dr. Aldape is passionate about the use of new technologies to improve the diagnostics of cancer and studies these technologies in his lab. Next generation sequencing is an example of a new molecular technique that allows neuropathologists to sequence hundreds—and even thousands—of genes at a time.

“Cancer is a disease of many genes, and we want to know the status of all these genes so we can identify patterns and potential targetable or actionable alterations,” Dr. Aldape says.

Actionable alterations are changes in the tumors that might reveal a vulnerability of these tumors to a specific therapy. “We are looking actively at these genetic alterations in the context of available therapies to help design new clinical trials with our neuro-oncology colleagues,” Dr. Aldape says.

He is also using a new technology called DNA methylation analysis to analyze the genomic alterations in rare brain and spine tumors. “Integrating multiple technologies gives us a better picture of these tumors. Our goal is to help lead the effort to make these molecular technologies the standard of care to better define these tumors to allow us to better treat them,” Dr. Aldape says.

Valuing a Precise Diagnosis

Dr. Aldape encourages patients to talk to their doctor about their diagnosis to ensure they are getting the most precise diagnosis possible. He suggests the patient ask:

• What does my diagnosis mean?
• How often is this diagnosis seen?
• Can we talk to others that may have experience with my diagnosis?

“Beginning this conversation is really the first step for patients to be involved in their care and fully understand their tumor,” Dr. Aldape says. NCI-CONNECT has made precision diagnostics a standard because of the value it adds for patients. Patients should talk to their doctor about their diagnosis whether they are newly diagnosed or were diagnosed years ago.

“Technology is rapidly changing. We can apply new molecular technology to a tumor that was resected 10 years ago,” Dr. Aldape says. “My role is to help patients get the best treatment for their disease.”