Understanding ototoxicity risks for pediatric oncology patients

Understanding ototoxicity risks for pediatric oncology patients
Understanding ototoxicity risks for pediatric oncology patients

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Long-term survival is a likely outcome for children diagnosed with cancer today. As a result of improved cancer treatment and supportive care measures, more than 250,000 patients who had childhood cancer are survivors. The combined 5-year survival rate increased from less than 50% in the 1970s to the current rate of 80%.1 The Children's Oncology Group (COG) estimates that 1 in 570 young adults aged 20 to 34 years is a childhood cancer survivor.1 With these statistics is an increased awareness of the need to reduce the long-term effects of treatment and improve quality of life for these patients.

Hearing loss is one possible adverse effect of childhood cancer treatment. Most cancer treatments for children include agents that put patients at risk for ototoxicity. Partial or complete hearing loss can result in communication difficulties and impaired speech and language development. The time most conducive to learning language is before puberty. Children form a hypothesis about linguistic rules and apply them in their own way based on the language heard.2 An inability to learn language skills in this way because of hearing loss may lead to delays in emotional and social development for the child. Knowledge of the risk factors and appropriate interventions can assist with planning care.


With normal ear function, sound waves entering the external auditory canal hit the tympanic membrane (eardrum) and cause the ossicles (auditory bones) of the middle ear to vibrate (Figure 1). The vibration of the ossicles moves the fluid within the cochlea. Inside the cochlea is the organ of Corti—this holds hair cells. The movement of the fluid in the cochlea stimulates these hair cells, which are nerve receptors for hearing. Specific hair cells react to specific sound frequencies; therefore, the pitch determines which hair cells are stimulated. Signals from the stimulated cochlear hair cells are then transformed into nerve impulses and transmitted to the brain via the auditory nerve. These hair cells cannot regenerate; any damage that occurs to them is permanent.3

The three main types of hearing loss—conductive, sensorineural, and mixed—are described according to the site of damage. Conductive hearing loss is a result of damage to the outer or middle ear that prevents sound waves from progressing into the inner ear. Conductive loss is usually temporary, a result of fluid in the middle ear or otitis media. Sensorineural hearing loss is the result of damage to the inner ear or the auditory nerve. This loss makes accurate perception of speech difficult. A mixed hearing loss is the third type. In this case, both conductive and sensorineural components disrupt the transmission of sound.3


Several factors place a pediatric oncology patient at risk for ototoxicity: presence of CNS tumor, radiation treatment, diminished renal function, IV infusion of ototoxic agents, and age 3 years or younger at the time of ototoxic agent administration.4,5 Agents considered to be ototoxic include platinum-based chemotherapy agents, loop diuretics, and aminoglycoside antibiotics (Table 1). Aminoglycosides and loop diurectics have a synergistic relationship. The risk of damage to the organ of Corti is greater if an aminoglycoside is administered prior to a loop diuretic.3,4,6

Radiation therapy directed at the head is a risk factor for ototoxicity; therefore, hearing loss is a symptom of a brain tumor as well as an adverse effect of its treatment. Radiation therapy-related hearing loss ranges from self-limiting to irreversible, especially if the patient's tumor is a midline, pontine, or brainstem lesion. The loss can be sudden or manifest 3 to 10 years after completion of therapy. Radiation therapy-related hearing loss is conductive through fibrosis or thickening of the tympanic membrane and the ossicles. Otitis media and tinnitus are self-limiting conditions caused by radiation therapy. Atrophy of the organ of Corti and the auditory nerve can cause sensorineural hearing loss. In rare cases, irreversible profound hearing loss manifests up to 8.5 years after radiation therapy to the brain.

The child's age at treatment is a significant factor. The auditory system in children 3 years and younger is still developing and therefore more susceptible to damage. Pharmacokinetics of platinum chemotherapy differ in younger children, resulting in slower clearance and increased exposure to the drug.7 Lastly, many chemotherapeutic agents are nephrotoxic, and diminished renal function is associated with an increased risk of ototoxicity.

Tinnitus and vertigo indicate vestibular injury and impending hearing loss; however, many children are asymptomatic. A parent or caregiver may notice that a young child does not turn toward sound or a teacher may notice inattentiveness at school. High-frequency hearing loss is indicative of future loss in the speech ranges if ototoxic therapy continues, in some cases with as little as one additional course.6


Several audiometric tests are available for monitoring treatment effects on hearing, and the type utilized is based on the child's age, state of health, and ability to cooperate. Table 2 lists audiometric tests with their appropriate ages for administration.3 Baseline measures are obtained before initiating treatment. Typically, newly diagnosed cancer produces great anxiety and stress for the family; therefore, explaining why the hearing test is being performed and what to expect not only reduces anxiety but may instill the child's cooperation.

The Children's Oncology Group guidelines for monitoring audiometric measures throughout treatment recommend that high-risk patients be tested before each course of platinum-based chemotherapy. Patients who are considered high-risk are 3 years or younger, have received radiation to the brain or ear, received a diagnosis of CNS neoplasm, are currently receiving ototoxic or investigative agents, or have received a cumulative dose of more than 360 mg/m2 of cisplatin (Platinol, generics) or a cumulative dose of more than 1,000 mg/m2 of carboplatin (Paraplatin, generics). All other children are considered to have a lower risk and should undergo hearing tests before every other course of platinum-based chemotherapy.

All patients should undergo auditory tests at least 3 weeks after completing a course of platinum-based chemotherapy because hearing deficits may be delayed. In addition, patients should be tested 6 to 8 weeks after their final chemotherapy course. Annual audiometric testing is recommended for children who are off treatment and had received platinum-based chemotherapy and/or radiation to the ear, midline of brain, or brainstem. However, children older than 8 years who are able to self-report symptoms can undergo screening every other year. COG also recommends that children who have been treated with aminoglycoside antibiotics and loop diuretics should undergo periodic audiometric testing, depending on the frequency and duration of treatment with these agents.6


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