Practical Grading System for Evaluating Cisplatin Ototoxicity in Children

K30 Journal Article ReviewDenise Nicholson, Au.D., Ph.D. candidateSenior AudiologistDept of Audiology

Article: Chang, K.W. & Chinosornvatana, N. (2010). Practical Grading System

for Evaluating Cisplatin Ototoxicity in Children. Journal of Clinical Oncology, 28 (10), 1788-1795.

Background Article Clinical applications/future research

Background

Cisplatin is used in the treatment of several childhood malignancies.

Improvement in long-term survival has made the monitoring of long-term side effects more important.

Nephrotoxicity and high frequency hearing loss are the most notable adverse effects of cisplatin in children

Brock et. al (1991)

Audiometry Types of hearing loss◦ Conductive (CHL)- a hearing loss resulting from

something affecting the outer or middle ear.◦ Possible causes include:

Cerumen impaction Serous otitis media Tumor

◦ Sensorineural (SNHL)- A permanent type of hearing loss that may be congenital, due to inner ear or auditory nerve damage, and may be the result of noise exposure, genetics, or ototoxic medications.

May affect certain frequencies more than others May cause distorted sound quality Severity can range from mild to profound May be late onset, stable, or progressive in nature

◦ Mixed – Combination of CHL and SNHL

Implications of HFHL in Children

Unable to hear certain speech sounds

Distortion Speech

understanding in noise

phonics (reading)

Normal Hearing and Degrees of HL

http://helpkidshear.org/resources/starter/degrees.htm

Difficulties Testing Children Age dependent test

procedures Bedside audiograms◦ Background noise◦ Not up to the task

Limited attention span Sedated ABRs & other

objective measures can be utilized

Chang & Chinosornvatana (2010)

Purpose:◦ Present a new ototoxicity grading system,

with clearly defined audiometric criteria.◦ Validation of the grading system Correspondence to audiology treatment

recommendations Compared with currently utilized Common

Terminology Criteria for Adverse Events (CTCAE)

CTCAE Pediatric Grading Scale Based on 1,2,3,4,6, & 8 kHz Grade 1◦ Threshold shift >20dB at 8kHZ in at least 1 ear

Grade 2◦ Threshold shift >20dB at 4kHz and above in at least 1 ear

Grade 3◦ HL sufficient to indicate therapeutic intervention including

hearing aids◦ Threshold shift >20dB at 3kHz and above in at least 1 ear◦ Speech and language svcs indicated

Grade 4◦ Audiologic indication of cochlear implant◦ Speech and language svcs indicated

Brock Pediatric Grading Scale

Bilateral Hearing Loss Grade

< 40 dB at all frequencies 0

≥ 40 dB at 8kHz only 1

≥ 40 dB at 4kHz and above 2

≥ 40 dB at 2kHz and above 3

≥ 40 dB at 1kHz and above 4

Brock et. al (1991)

Patients 134 pediatric patients Received cisplatin or carboplatin◦ Audiologic evaluation performed during 105

(70.5%) of 149 treatment courses◦ 90 had audiograms measured after @ least one

dose of cisplatin or carboplatin◦ 81 received cisplatin, of which, 67 received

cisplatin as their only primary ototoxicchemotherapeutic agent◦ 14 – cisplatin & carboplatin◦ 9 – carboplatin only

Methods

Retrospective chart review◦ Audiologic ◦ Demographic◦ clinical

computerized patient charting database was used to collect:◦ Treatment course data◦ Process measures◦ Audiologist recommendations

Audiologist Recommendations

Hearing Aid◦ Makes certain sounds louder◦ Programming is based on individual’s freq

specific hearing thresholds◦ Limitations Output (especially in the high freqs)

FM system◦ Ideal for children with minimal hearing loss◦ Most often used in classroom setting only

Audiologic Grading

Serial behavioral audiograms (ear specific in all but 7 patients)

Audiograms were graded in a blinded manner (w/out knowledge of tx regimen or clinical hx)

All audiograms assigned CTCAE, Brock, & Chang grades.

Audiologic Grading Continued

CTCAE subjective criteria were not used in order to keep the grading blinded◦ HL at 25-90 dB was averaged at 3 contiguous

frequencies

Chang grading scale – modified version of Brock scale◦ Meant to incorporate functional deficits

caused by HL < 40dB

Chang vs Brock

Chang 2b, Brock 0, CTCAE 3

Data Analysis Linear regression◦ Used to test the relationship between

audiogram-based ototoxicity grades and the following factors: Delivery volume Mannitol usage Dextrose usage Tx length Cumulative and daily cisplatin dosage Patient age patient body-surface area (BSA)

Data Analysis continued

One-tailed, two-sample Mann-Whitney U test was used to assess mannitol usage, comorbidity, radiotherapy coadministration, and metastatic status.

Pearson x squared values were used to test the interaction btwn audiogram-based ototoxicity grades and the final recommendations made by audiologists

Results

No significant difference in mean grade among the different diagnoses (P=.357), using univariate analysis of variance.

Patients with higher Chang grades had higher chance of requiring a HA or FM system

Results: Demographics & Clinical Characteristics

Results continued

Results continued

Results continued

Take home message

Both the Chang and CTCAE grades from audiogram scoring were significantly related to the audiologists’ recommendations (FM or HA use)

Chang scale was more specific than the CTCAE scale

Patients receiving combination radiation therapy, lower BSA, and patients with metastatic disease had higher grades

Limitations of the Study

Retrospective analysis Ear specific data not available on each

patient More treatment options besides FM

systems and hearing aids Audiologist recommendations are based

on various factors Uneven comparison groups

Clinical Considerations/Use

Audiologist can report a grade versus a lengthy descriptive analysis

Promotes interspecialty communication re: ototoxic clinical effects

Modifications to tx protocols when applicable

Helps with counseling families/patients Grading system is practical and easy to

interpret

Future research Prospective analysis Use of a specific audiology test protocol◦ Test high frequencies only, interfrequencies

Establish specific audiology recommendations based on objective data

More balanced groups Mannitol – possible otoprotectant?◦ Randomized controlled study