Neurofibromatosis type 2 (NF2) is a hereditary disease characterized by benign tumors, called vestibular schwannomas, that occur on the balance (vestibular) nerves leading to the inner ear. A person with NF2 almost always has bilateral vestibular schwannomas—NF2 tumors that affect both ears.
Much rarer than a related disease known as NF1, NF2 occurs in roughly 1 in 25,000 births. Because many NF2 patients are children, Keck Medicine of USC and Children’s Hospital Los Angeles (CHLA) Neurofibromatosis Programs partner to provide patients with specialized pediatric care and expertise in the management of their condition. Once patients reach the age of 18, they are transitioned from CHLA to Keck Medicine of USC, which is also in Los Angeles. Clinicians collaborate between the institutions to ensure that each NF2 patient receives the most current medical and surgical treatments appropriate through all stages of life. The USC Acoustic Neuroma Center works with patients and their families to monitor healing and progress throughout treatment and after surgery. Because the disease is so rare, many patients and their families travel significant distances to receive specialized care for NF2.
Currently, Children’s Hospital Los Angeles (CHLA) is one of 13 sites across the country participating in a clinical trial of NF2 using the chemotherapy drug Avastin (bevacizumab), as a potential therapy for shrinking the NF2 tumors, or stemming their growth. CHLA is working with clinicians from Keck Medicine of USC and other institutions as part of the collaborative trial.
The Hearing Review recently interviewed Rick Friedman, MD, PhD, about NF2 and the current NF2 clinical. A leader in the treatment of acoustic neuromas at Keck Medicine of USC in Los Angeles, and an NIH funded scientist who studies the genetics of common forms of hearing loss, Dr Friedman is the division director of Otology, Neurotology and Skull Base Surgery in the USC Tina and Rick Caruso Department of Otolaryngology–Head and Neck Surgery. He is affiliated with both the USC Acoustic Neuroma Center and Children’s Hospital Los Angeles where the NF2 trial is underway.
Christa S. Nuber, Hearing Review (HR): Dr Friedman, welcome, and please tell us a little about yourself.
Dr Friedman: Thank you. My passion is hearing, and my clinical-scientific interest is maximizing and optimizing the care of patients with vestibular schwannoma, either the sporadic variety or those patients afflicted with NF2. My basic science interest is in the genetics of common forms of hearing loss, such as age-related hearing loss and noise-induced hearing loss.
HR: Can you tell us a little about the NF2 program and the clinical trial at Children’s Hospital of Los Angeles?
Dr Friedman: Certainly. We have a fantastic team that is composed of doctors and scientists at Keck Medicine of USC and at Children’s Hospital Los Angeles. We have a number of participants in our group, including neurologists, neuro-geneticists, neuro-oncologists, medical geneticists, neurosurgeons, and neuro-otologists. In neurotology, our expertise is the hearing and balance nerve, and approaches to the surgical management of these tumors, when indicated. The clinical trial is a national trial that is supported by the US Army and US Department of Defense, and it is an NF Consortium that is funding a multi-center clinical trial for individuals with NF2 using a medication called Avastin (bevacizumab). This is a medication that is really a chemotherapeutic agent used in other diseases with other tumors, but the goal is to try to limit or eliminate the blood supply to these tumors and stop their growth. The data is interesting. There are some cases where it doesn’t appear to help, and there are other cases where it not only stunts tumor growth, it also improves and prolongs hearing preservation in these patients who are really in grave danger for deafness on both sides, because they have tumors on each side.
HR: Is CHLA the coordinating or central site for the NF2 trial, and how many patients are under your care in Los Angeles?
Dr Friedman: The University of Alabama at Birmingham is the coordinating and central site for the Department of Defense NF Consortium Avastin NF2 study. Per their updated reports, 15 of 22 subjects have been enrolled in this study from multiple sites across the country.
CHLA has 3 subjects enrolled in the study, but we are a fairly large NF program. We are a national center for the treatment of these tumors [and we’ve had good outcomes]. I can recall our latest case of a 10-year-old young man, an avid baseball player, for whom we have completed treating both sides. We were able to save his hearing on both sides, and he is now back home in Oklahoma, playing baseball and no longer at risk for losing his hearing.
HR: I understand that the tumors associated with NF2 are benign, meaning that they are not cancerous, but early treatment or tumor removal is crucial because the danger is that they grow large, and put pressure on important nerve centers that govern a person’s hearing and balance. Can you talk about that, and also explain if these tumors can compromise other functions as well?
Dr Friedman: There are different forms of NF2. There is one that–I hate to use the word “benign” because the risk of being deaf is certainly not a benign process–but there is a group of patients who seem to have tumors only on the hearing and balance nerves, and then there is a group of patients who have tumors that occur throughout the brain and [along the] spinal cord. Those are really tough cases because [these patients] can get not only vestibular schwannomas, but schwannomas of other nerves in the head and along the spine that can cause compression. Compression leads to neurological dysfunction, and ultimately leads to death, especially high up in the spinal cord. It is a complicated group of patients to care for.
HR: And, I have heard that the skill of the surgeon and the surgical team is crucial in NF2, because tumor removal itself can potentially damage those delicate nerves that the tumors grow on. Is that correct?
Dr Friedman: Absolutely. These patients need to be [expertly] cared for when it comes to surgery–and not all of them do come to surgery–but when it does come to surgery, it absolutely has to be with a very experienced, qualified team.
I can tell you, in the example I already gave you of our 10-year-old young man, that is a career case. You know, that makes all the hours of training worth it, because we have given a young man a life that will be complete with hearing.
HR: What are the survival rates for NF2 patients who don’t receive timely care and surgical tumor removal compared to patients who do receive that care through your center and others?
Dr Friedman: That’s a great question. Unfortunately, some of these tumors occur in locations that are difficult to get to without compromising quality of life, or even life. The mortality rate from severe cases of NF2 is fairly high, and these patients often don’t live past the third decade of life. Teams like ours can prolong life. I still have to say that in the most severe cases, no matter how hard we try, length of life is less than in patients without NF2. But we can sort of “make a dent” in this disease and prolong life by providing expert care in the form of surgery, chemotherapy, and in some cases, radiation.
HR: That’s interesting that you use chemotherapy and radiation to shrink the tumors even though they are not cancerous.
Dr Friedman: In a disease like NF2 where some of these tumors are in such delicate locations, we have had to explore using chemotherapeutic agents for a technically benign disease, meaning that they are not cancer cells. Our skulls have a limited amount of space for the brain and for the fluid that bathes the brain. So, anything that grows there takes up space, and the brain doesn’t tolerate too much space being taken up without really severe consequences. That’s also true for the spinal cord.
HR: For these patients that you treat with these various interventions, surgery and chemotherapy-oriented interventions, how does the follow-up care with your team play out? For example, how often do the patients return to you at the USC Acoustic Neuroma Center for monitoring or additional tumor removal?
Dr Friedman: There are so many interesting questions that are being pursued by people all across the nation that are studying this disease at the basic level. Among the many patients with NF2 the biology appears to be very different, so we believe that there are other genes that are involved in this disease–that modify the phenotype, or severity, of the disease. There are some people who present with tumors on each of their balance nerves that remain small for life. There are others in whom these tumors grow at a terribly rapid rate. In general, these patients are followed up by our collaborative team, including the Acoustic Neuroma Center, for hearing tests every three months. They get MRIs typically every six months, depending upon whether or not they are on a research protocol, and when we feel that they are symptomatic or their quality of life is deteriorating, then sometimes we do have to intervene surgically multiple times.
HR: You mentioned earlier this medication that some of the participants in the trial are taking to shrink the tumors or slow down their growth. Is the follow up the same for those participants?
Dr Friedman: The follow up for those participants is protocol-specific. They get a fairly rigorous follow up because they are on medication, and medication can have side effects. And, we do need to monitor the efficacy of the medication with more frequent MRIs–probably more like every three months than every six months.
HR: What is the ultimate aim or goal of this current NF2 clinical trial?
Dr Friedman: I think the goal, ultimately, is to try to avoid surgery that carries morbidity. It would be absolutely wonderful to be able to control these tumors chemically rather than surgically. I think we are a little bit away from complete success on that front, but we are making strides and there are a number of drugs that are under investigation to serve as tumor suppressors, or as ways to prolong quality of life.
HR: Thank you, Dr Friedman for your time and your insights today on the NF2 program. Is there anything more you’d like to add about the program?
Dr Friedman: I’d just add that it is terrific, and it is replete with incredibly dedicated doctors, nurses, and caregivers. We are in some ways a unique institution. We have a patient navigator who had a sporadic unilateral tumor, not bilateral tumors like in NF2, and she really helps get patients in, and helps make them feel comfortable…which is so important, because this is such a frightening diagnosis. We are really a patient-centered program, centered around comprehensive, lifelong care–with attention not just to the patient, but also to the patient’s family.
HR: Thank you so much again for sharing your insights today, Dr Friedman, and for your time.
Dr Friedman: Thank you!
To listen to an audio recording of this phone interview, visit the “Hearing Review Conversations” Podcast page.
For more information about the acoustic neuroma and NF2 programs at Keck Medicine of USC, visit the USC website. For more information about the NF2 clinical trial at CHLA, visit the Children’s Hospital Los Angeles website.
Image credits: Keck Medicine of USC