Download Practical Grading System for Evaluating Cisplatin

Practical Grading System for
Evaluating Cisplatin Ototoxicity in
Children
K30 Journal Article Review
Denise Nicholson, Au.D., Ph.D. candidate
Senior Audiologist
Dept 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



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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 ototoxic
chemotherapeutic 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:

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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 audiogrambased 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



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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