Source: journals.lww.com
Author: A. Croutch, Carl AuD

With hearing loss, tinnitus, and imbalance as among the numerous side-effects of cancer treatment,1 audiologists play a critical role in monitoring patients receiving chemotherapy and radiation therapy. Sensorineural hearing loss (SNHL) attributed to chemotherapy and radiation therapy is usually permanent, making audiometric monitoring essential to detect its early occurrence.2

Cisplatin, carboplatin & radiation therapy
Chemotherapy is used to treat cancer, control the growth and spread of cancer cells, and ease cancer symptoms. Cisplatin and carboplatin are two common antineoplastic agents used to treat testicular, ovarian, breast, esophageal, lung, and head and neck cancers among others. Besides hearing loss, these can cause other side effects including kidney, gastrointestinal disorders, allergic reactions, decreased immunity to infections, and hemorrhaging. Cisplatin was first found to have cytotoxic properties in the 1960s, and in 1978 was the first platinum compound approved by the FDA for cancer treatment.3 On the other hand, carboplatin is less potent than cisplatin and does have fewer side effects, especially on kidney problems.3

Both drugs work by interfering with DNA repair mechanisms causing DNA damage and inducing apoptosis in cancer cells. Cancerous cells cannot limit cell division as do normal cells. Normal cells cease dividing when they encounter similar cells whereas cancerous cells do not. The effectiveness of chemotherapy is determined by its ability to damage the RNA or DNA that gives the cell instructions to copy itself. The cells will die if they are unable to divide. The more quickly they are dividing, the more effective is the chemotherapy.4

The incidence of hearing loss in post-chemotherapy patients is highly variable, ranging from 17% to 80% depending on the age, baseline hearing levels, and cisplatin dosage.5 Generally, those receiving a higher dose of cisplatin showed more hearing loss than those receiving a smaller dose.6,7

In addition to chemotherapy, a cancer patient may also be treated with radiation therapy (RT), which is the use of high-energy X-rays or other types of energy such as protons to kill cancer cells. RT also works by destroying the genetic material that regulates cell growth and division. The objective of RT is to kill fewer normal cells since it can damage both cancerous and normal cells. The incidence of SNHL ranges from 0-43% depending on the radiation dosage to the cochlea as well as age and baseline hearing levels.5 Radiation dosage reaching the cochlea may be higher when treating cancer of the nasopharynx, parotid salivary gland, and paranasal sinuses compared to other sites.7

RT can cause both SNHL and conductive hearing loss (CHL). SNHL may occur if the RT is directed near the cochlea, and CHL if it is near the Eustachian tube. Factors that may influence whether a hearing loss occurs include the strength and direction of the beam, location, size of the tumor, patient age, and pre-treatment hearing levels. The frequency of otitis media with effusion in head and neck cancer patients undergoing RT was found to be 39.3% with retracted tympanic membrane and 7.1% with air-fluid levels seen.8 Treatment of head and neck squamous cell carcinoma (HNSCC) patients using radiation can result in mixed (SNHL and CHL) hearing loss, which can be more severe in those with tumors near the ear as well as those treated with cisplatin.7

Stages & grades of cancer
Cancer has four stages: Stage 0 is when the cancer has not spread from its original location (in situ), Stage 1 is when a small cancer has not spread, Stage 2 is when it has grown but not spread, Stage 3 is when it may have spread to near-by tissues possibly the lymph nodes, and Stage 4 is when it has metastasized and spread to at least another body organ. Cancer is also divided into three grades, with the lower grades indicating a slower-growing malignancy and a high grade, a faster-growing one.9

Nasopharyngeal cancer (NPC) is frequently seen in head and neck clinics and offices. Tumors originating in the nasopharynx may be benign or malignant. The majority of nasopharyngeal cancers are nasopharyngeal carcinoma. A carcinoma is a cancer that originates in the epithelial cells, which line the internal and external surfaces of the body. A patient about to undergo chemotherapy and radiation therapy should be seen for a baseline audiogram prior to the initiation of any treatment. An in-depth history of any occupational or recreational noise exposure is essential.

Audiometric test battery
Both chemotherapy and noise exposure can result in high-frequency SNHL. Distinguishing between the two can be difficult, which is why obtaining a baseline audiogram and careful case history is essential. One tip-off may be the high-frequency notch seen between 3000 and 6000 Hz often present in cases of noise trauma.

Speech-in-noise testing should be done since understanding speech in background noise is a common complaint from most adults. Using the Quick Speech-in-Noise (Q-Sin) test may aid in the treatment of these patients.1 Extended high-frequency pure-tone audiometry (EHF-PT) and distortion-product otoacoustic emissions (DP-OAEs) are useful tests in monitoring these patients. Ototoxic effects frequently occur initially at frequencies above 8 kHz. EHF-PT are tested from 8-20 kHz and can often detect hearing loss in these ranges before it affects the speech frequencies. This will enable the oncologist to monitor the treatment and if possible, conserve the patient’s hearing. DP-OAEs are measured from 0.5-8 kHz. They can determine if the outer hair cells are intact since they are usually damaged prior to inner hair cells (IHC) and can result in a more severe hearing loss compared with outer hair cell damage. This may provide useful information to the oncologist. It is also an objective test and can be used regardless of the patient’s age or state of health.2

Criteria for change
In addition to baseline testing, follow-up testing should occur after each treatment, when the course of treatment is completed, and on an annual basis or sooner if indicated. A significant change is considered per the ASHA 1994 guidelines13:

>= 20 dB change at one frequency
>= 10 dB change at two consecutive frequencies
No response at three consecutive frequencies where responses were previously obtained

Ototoxicity can be grouped by using at least 13 different classification systems based on changes from a baseline audiogram to those that focus on the functional impact of the hearing loss. These scales do not consider high-frequency audiometry.13

Despite these grading scales, most clinicians do not use them on a routine basis. How ototoxicity is defined is a significant part of the inconsistencies between pre- and post-clinical data across patient groups.13

Two commonly used ototoxic grading systems in use are the Common Terminology Criteria for Adverse Events version 4 (CTCAEv4) and the American Speech-Language-Hearing Association (ASHA) system. Each of these systems has certain shortcomings.13

To devise a more comprehensive system, Theunissen et al., purposed the TUNE grading system, which details the shortcomings of both the CTCAEv4 and the ASHA systems14 and propose seven different grade levels:

  • Grade 0: No hearing loss
  • Grade 1a: Threshold shift >= 10 dB at 8, 10, and 12.5 kHz OR subjective complaints in the absence of a threshold shift
  • Grade 1b: Threshold shift >= 10 dB at 1, 2, and 4 kHz
  • Grade 2a: Threshold shift >= 20 dB at 8, 10, and 12.5 kHz
  • Grade 2b: Threshold shift >= 20 dB at 1, 2, and 4 kHz
  • Grade 3: Hearing level >= 35 dB at 1, 2, and 4 kHz
  • Grade 4: Hearing level >= 70 dB at 1, 2, and 4 kHz

They feel this system can better assess the effects of hearing loss in daily life and can distinguish between mild, moderate, and severe degrees of ototoxicity compared to the current systems in use.14

Significant changes in DP-OAE findings were a reduction in the signal-to-noise ratio at f2 frequencies below 1 kHz of > 14 dB and a reduction of 7 dB of f2 frequencies above 1 kHz. These criteria were used by Yu, et.al.,2 but no standard criteria are available for defining changes in the DP-OAEs.15

The potential for hearing loss from chemotherapy and radiation therapy is dependent upon the patient’s baseline hearing levels and the strength and frequency of the treatments. Dosage is often determined by the patient’s body surface area indicated by m2. It is calculated by taking the square root of the product of the weight in kilograms times the height in centimeters divided by 3600. The average body surface area for adult men is 1.9 m2 and for women is 1.6 m2.16 Typical doses vary from 25-100 mg/m2. The frequency of treatments is also patient-specific. Chemotherapy is given in cycles—-typically one week of chemotherapy followed by three weeks of rest.

Treatment Options
SNHL may be treated with hearing aids, and CHL by medicine, myringotomy, or PE tube placement. If any hearing loss is found, treatment options should be discussed with the patient. In cases of SNHL that will benefit from amplification, the patient may wish to postpone it until after the cancer treatment has been completed. Some may wish to obtain hearing aids right away to better participate and understand their treatment options. In patients with CHL, a referral to HNS is usually indicated. At Kaiser Permanente, for example, patients with a unilateral CHL without an NPC diagnosis are referred to HNS as that may be an indication of NPC.

Overall, audiologists need to monitor hearing loss in cancer patients undergoing chemotherapy and radiation therapy and provide treatment and counseling when hearing loss has become inevitable.

References:
1. Baguley D, Prayuenyong P. Looking beyond the audiogram in ototoxicity associated with platinum-based chemotherapy. Cancer Chemother Pharmacol. 2020; 82(2): 245-250.

2. Yu K, Choi, C. et.al. Comparison of the effectiveness of monitoring cisplatin-induced ototoxicity with extended high-frequency pure-tone audiometry or distortion-product otoacoustic emission. Korean J of Audiology. 2014;18(2):58-68.

Source:
The Hearing Journal: September 2021 – Volume 74 – Issue 9 – p 44-45

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