Explore This IssueApril 2015
Panel moderator Michael Seidman, MD, director of otologic and neurotologic surgery and director of the Otolaryngology Research Laboratory at the Henry Ford Health System in Detroit, said history is full of stories of things thought to be impossible that ended up becoming a reality. “It’s critical that we innovate, because there are obviously reasons that we need to,” he said. “There are different ways of doing things.”
Genotype to predict hearing loss. Daniel Choo, MD, director of pediatric otolaryngology–head and neck surgery at Cincinnati Children’s Hospital, said a pediatric patient’s genotype can be used to much greater effect than imaging in predicting hearing loss. “What we saw in our [Pendred syndrome] PDS [gene] mutation patients,” he said, “is that if you have two mutations—so, if you’re homozygous for abnormal pathologic Pendred mutations—first, you start off with worse hearing. But, whatever hearing you have, you have a much greater chance of progressive hearing loss over time.”
This information can be useful in considering cochlear implants. “We’ll have a much lower threshold. As soon as that other ear starts showing a hearing loss … we’ll start that cochlear implant discussion a little earlier,” he said. “It’s probably easier to rehabilitate that child with one ear implant in while there’s still some functional hearing in the other ear, rather than wait until the other ear completely bottoms out.”
Gene mutations and codeine. There is an FDA black box warning for codeine prescriptions for children under the age of nine. Even a typical dose of codeine, which the body converts to morphine, can be overmetabolized, causing a level of morphine in the serum that can suppress the respiratory system.
Physicians can now test for genetic variants that carry a predisposition for this overmetabolizing, Dr. Choo said, so patients, especially young children, can be tested before they are prescribed narcotic pain medications, to minimize risks of overdose and respiratory suppression.
Gentamicin and genetic testing. Mutations in mitochondrial DNA will predispose a person to high sensitivity to the antibiotic gentamicin. Just one dose can cause gentamicin-induced hearing loss, and it’s not a dose-dependent reaction.
A point of care aimed at identifying children at risk for drug-induced hering loss before they are treated with gentamicin, in which genotyping of mitochondrial DNA can be performed in approximately 20 minutes, was developed for the neonatal intensive care unit. But that plan was quashed because, in the NICU, you can introduce candida infections if you switch to the broad spectrum antibiotic cephalosporin. The infection then runs rampant, causing more morbidity than the gentamicin-related hearing loss. “Sound medical practices trump cool molecular diagnostics every time,” Dr. Choo said.
HPV. Human papilloma virus (HPV) can be used as an indicator of prognosis in head and neck cancer in those with HPV-positive disease, but its use is limited, said Christine Gourin, MD, associate professor of otolaryngology–head and neck surgery at Johns Hopkins Medical Center in Baltimore. “HPV is a prognostic biomarker; it is not a therapeutic target,” she said. “We don’t treat people differently in 2015, who are HPV positive, outside of some clinical trials in progress that are designed to see if clinical care can maybe be deintensified.”
EGFR. Epidermal growth factor receptor (EGFR) has been thought to be overexpressed in patients with head and neck squamous cell carcinoma and associated with poorer prognosis, a “hot button marker that people built careers studying,” Dr. Gourin said. But targeting EGFR has been disappointing. “In fact,” she said, “EGFR targeting has not been associated with a response in head and neck cancer in multiple clinical trials, and it seems that resistance to these EGFR-targeted agents is the major problem.”
Findings from the Cancer Genome Atlas—an effort to more fully understand the molecular basis of cancer—show that EGFR is expressed in only a minority of patients with head and neck cancers, in contrast to published data that has indicated it is more common. “We think variability in detection methods can actually lead to overestimation of EGFR positivity,” Dr. Gourin said. She added that there are still ongoing clinical trials targeting the EGFR pathway.
PD-1 and PD-L1: Programmed death ligand-1 (PD-L1) is frequently expressed on tumors and induces immune tolerance to cancer, by reducing the activity of CD4 and CD8 cells expressing its receptor, programmed death-1 [PD-1]. Treatment with the anti-PD-1 antibody nivolumab has produced good results in melanoma patients. “These are sustained responses,” Dr. Gourin said. “They’re really remarkable for melanoma.” The therapy is generating excitement among head and neck cancer clinicians, she said. “This is proving to be a therapeutic target,” Dr. Gourin said, “and shows the most promise that we’ve seen in a long time in our field.”
Tom Collins is a freelance medical writer based in Florida.