International Journal of Pediatric Otorhinolaryngology 78 (2014) 2301–2304
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Case Report
Hearing loss in a pediatric patient following cisplatin chemotherapy and subsequent exposure to excessive noise Emilia Peleva a,1, Emilie Aloy b,2, Anne-Sophie Carret c,3, Sam J. Daniel a,* a
Department of Otolaryngology-Head and Neck Surgery, McGill University, Montreal, Quebec, Canada Faculte´ de Me´dicine de Montpellier, Universite´ Montpellier 1, Montpellier, France c Division of Hematology-Oncology, Department of Pediatrics, CHU Sainte-Justine/Universite´ de Montre´al, Montreal, Quebec, Canada b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 21 November 2013 Received in revised form 22 August 2014 Accepted 25 August 2014 Available online 1 September 2014
Cisplatin is a commonly-used chemotherapeutic agent that is highly-effective against a variety of pediatric cancers. Unfortunately, it may lead to ototoxicity, with serious consequences on the quality of life of survivors. Patients remain at risk of progression of ototoxicity even after completion of treatment. We report the case of a medulloblastoma survivor with previously documented normal hearing, who developed significant hearing loss and tinnitus following exposure to excessive noise at a nightclub three years after completion of treatment. We highlight the importance of long-term audiological follow up and education about the increased risk of hearing loss in this population. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Cisplatin Ototoxicity Pediatric oncology Late effects Noise-induced hearing loss Progressive hearing loss
1. Introduction Cisplatin is a chemotherapeutic agent commonly-used and highly effective against a variety of pediatric cancers. It is also the single most ototoxic drug in clinical use today, leading to tinnitus and sensorineural hearing loss, which is often permanent, bilateral and progressive [1]. It is estimated that 50–60% of children will develop ototoxicity during platinum-based chemotherapy [1,2]. Some patients will have progression of hearing loss even after completion of chemotherapy [3,4]. The risk of progression is even greater in patients who have received radiotherapy to the head and neck [5]. We report the case of a child who, despite normal hearing following cisplatin chemotherapy and cranial radiotherapy,
* Corresponding author at: The Montreal Children’s Hospital, 2300 Rue Tupper, Rm. B-240, Montreal, QC, Canada, H3H 1P3. Tel.: +1 514 412 4304; fax: +1 514 412 4342. E-mail address: [email protected] (S.J. Daniel). 1 Address: 103 Belgrave Road, Flat 8, London SW1V 2BH, UK. 2 Address: 28 rue de la Cadoule, 34740 Vendargues, France. 3 Address: Pediatric Hematology-Oncology, CHU Sainte-Justine, 3175 Chemin Coˆte Sainte-Catherine, Local A.12.39, Montreal, QC, Canada, H3T 1C5. http://dx.doi.org/10.1016/j.ijporl.2014.08.039 0165-5876/ß 2014 Elsevier Ireland Ltd. All rights reserved.
developed a severe hearing loss over three years later, after exposure to excessive noise.
2. Case report A 13.5 year-old boy underwent craniotomy and macroscopically complete resection of a left cerebellar medulloblastoma. Due to residual tumor on the post-surgical MRI, he underwent a second surgery with complete excision of the residual tumor. The patient then received cranio-spinal radiotherapy of 23.4 Gy in 13 sessions of 1.8 Gy each, followed by a boost to the posterior fossa of 30.6 Gy in 17 sessions of 1.8 Gy each in combination with weekly vincristine as radio-sensitizer. Four weeks after completion of radiotherapy, he began chemotherapy consisting in lomustine, cisplatin, vincristine, and cyclophosphamide. This patient received cisplatin at 75 mg/m2 over 6 h, for a total of six cycles administered over nine months. Furosemide and mannitol were also administered as part of supportive care. Audiological testing included conventional audiometry (0.25–8 kHz), impedance audiometry, Distortion Product Otoacoustic Emission (DPOAE) tests and Transiently-Evoked Otoacoustic
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Table 1 Audiological evaluations.
Conventional (C)
During platinum-based chemotherapy
1
3
2
5
Post-chemotherapy 6
7
8
Freq
9
10
11
12
LE
RE
LE
RE
LE
RE
LE
RE
LE
RE
LE
RE
LE
RE
LE
RE
LE
RE
LE
RE
LE
RE
LE
10 0 10 5 5 5 0 0 – – – – – –
10 0 0 10 10 5 10 5 – – – – – –
5 5 0 0 0 0 0 0 – – –– – – –
10 10 10 10 5 5 5 5 – – – – – –
10 5 0 0 0 0 0 0 – – – – – –
15 5 0 5 0 0 0 0 – – – – – –
10 5 5 0 – 0 – 0 – – – – – –
10 10 5 5 – 0 – 0 – – – – – –
0
0 0
5 5 0
10 5 5 5 0 5 0 0 – 20 – 25 35 >40
5 5 5 0
10 5 5 5 5 0 20 30 – 45 – 65 45 45
0 0 0 0 0 0 0 5 – 30 25 25 35 30
5 0 0 5 0 0 0 5 – 35 40 45 50 45
0 0 5 25 30 25 10 5 – – – – – –
10 5 25 30 35 30 15 – – – – – – –
10 5 0 0 0 0 0 5 35 35 45 65 60 45
10 5 0 5 0 0 10 15 35 40 35 45 45 55
10 0 0 5 0 0 0 5 45 45 45 50 55 40
5 5 0 5 0 0 5 15 35 45 40 40 45 35
ASHA (C/HF) Chang Tymp DPOAE
– 0 Normal –
TEOAE
Normal Normal
–
Normal
4
RE
10 0 10 0 5 10 5 10 5 5 0 5 0 0 0 5 – – – – – – – – – – – – Baseline 0 Normal –
HF
0.25 0.5 1 2 3 4 6 8 9 10 11.2 12.5 14 16
Pre-chemotherapy
Y/– 0 Normal –
N/– 0 LE - H –
–
Normal
Y/– 0 LE - H –
5 5 5
5 5
– – 0 5 – – 5 5 – – 15 10 – – 30 30 35 30 >40 25 N/Baseline 0 Normal – Abnormal
5 5 5 0 10 – 30 – 40 45 >40
5 5 0 15 – 45 – 80 65 40
N/Y 0 Normal –
Y/Y 1a Normal –
N/Y 1a Normal Normal
Y/– 2b Normal 2 +4 bilat
Normal
Normal
Normal
Normal
Y/Y 1a Normal 1 + 2 LE, 1 + 1.4 RE RE
N/Y 1a Normal 1.4 + 2 LE, 1.4 RE
0.25 0.5 1 2 3 4 6 8 9 10 11.2 12.5 14 16 ASHA (C/HF) Chang Tymp DPOAE Abnormal TEOAE
Evaluations were performed: 1) prior to radiotherapy, 2–7) prior to each cisplatin dose, 8) three months after cisplatin chemotherapy, 9) 15 months after cisplatin chemotherapy, 10) 41 months after cisplatin chemotherapy (3 days post-noise exposure), 11) 42 months after cisplatin chemotherapy, 12) 52 months after cisplatin chemotherapy. Freq, frequency; RE, right ear; LE, left ear; Conventional, conventional audiometry; HF, high-frequency audiometry; ASHA, hearing loss based on the American Speech-Language-Hearing Association criteria; Chang, Chang grade assigned; Tymp, tympanogram; DPOAE, Distortion Product Otoacoustic Emission tests, with abnormal frequencies being listed (in kHz, defined as: signal/noise ratio below 6 dB); TEOAE, Transiently-Evoked Otoacoustic Emission test results, as determined by the audiologist. Note 1: The patient has normal hearing (thresholds 20 dB in evaluations #3 and 5 despite hearing loss according to the ASHA criteria). Note 2: Chang grades were assigned based on frequencies up to 12 kHz, whenever possible.
E. Peleva et al. / International Journal of Pediatric Otorhinolaryngology 78 (2014) 2301–2304
Freq
[(Fig._1)TD$IG]
E. Peleva et al. / International Journal of Pediatric Otorhinolaryngology 78 (2014) 2301–2304
2303
Fig. 1. Chang Scale (Modified Brock’s Grading System) and Brock Grading System. Brock Grade: based on results in the better ear with < 40 dB at all lower frequencies. Source: Chang and Chinosornvatana (2010). Practical grading system for evaluating cisplatin ototoxicity in children. J Clin Oncol 28 (10): 1788–1795. Reprinted with permission. ß (2010) American Society of Clinical Oncology. All rights reserved.
Emission (TEOAE) tests. High frequency (HF) audiometry (9–16 kHz) was performed once it became available at our institution. Results from conventional audiometry performed up to 15 months after completion of chemotherapy (Table 1, Evaluations #1–9), demonstrate that the patient had hearing thresholds of 20 dB at all time points, except at 8 kHz in the left ear, where the post-chemotherapy threshold was 30 dB. There was an air-bone gap in the left ear at the pre-chemotherapy hearing test, likely due to radiotherapy. Results from HF audiometry show that there was asymptomatic hearing loss at the post-chemotherapy audiograms (Evaluations #8 and 9). When compared to the first HF audiogram (Evaluation #6), there was hearing loss based on the American SpeechLanguage-Hearing Association (ASHA) criteria [6]. These audiograms were classified as Chang Grades 1a, corresponding to early ototoxicity which is not clinically significant (Fig. 1) [7]. The patient also reports post-chemotherapy tinnitus which is not particularly disruptive. Three years post-chemotherapy, the patient presents with complaints of exacerbation of his tinnitus following excessive noise exposure (going to a nightclub). The audiogram, performed three days after the exposure, shows that the patient has Chang Grade 2b, corresponding to clinically significant hearing loss. Bone conduction audiometry confirms the presence of sensorineural hearing loss at 1 kHz in the left ear and 2–4 kHz bilaterally. HF audiometry is not performed at this time-point. He is seen by an otolaryngologist one week later, and he seems to have recuperated well; the tinnitus has also improved according to the patient. Four weeks after the noise exposure, hearing had returned to normal at conventional frequencies (Evaluation #11). At HF, thresholds in the left ear are similar to pre-noise exposure thresholds, but there is progression of hearing loss in the right ear according to the ASHA criteria. This audiogram still has a Chang Grade of 1a. The patient reported that his tinnitus had returned to post-chemotherapy status. A further evaluation 11 months after noise exposure suggests that the patient’s audiological status is stable (Evaluation #12). 3. Discussion Young patients are more susceptible to developing ototoxicity. This could have devastating consequences in this population as hearing loss has major impacts on communication, development of literacy, academic performance, and on their overall health and quality of life [8,9]. Even mild hearing loss can have serious consequences on academic performance [10]. These consequences may be even greater in patients with neurocognitive disabilities, especially children having received cranial radiation for brain tumors [11]. Cisplatin doses of 400 mg/m2 are associated with an increased risk of developing ototoxicity [4,12]. The patient presented here
received a high cumulative dose of 450 mg/m2. He also received radiotherapy to the head and neck, as well as administration of vincristine, cyclophosphamide, furosemide, and mannitol, which further increase the risk of ototoxicity [5,13,14]. Despite this intensive treatment, this patient did not have clinically significant hearing loss post-chemotherapy. The treatment was deemed successful as this patient went into remission without severe longterm consequences from treatment, until he went to a nightclub to celebrate his 18th birthday, and the exposure to loud music resulted in sudden hearing loss persisting for at least three days after the exposure. The speech hearing thresholds returned to normal by four weeks, but there was permanent progression at the high frequencies (>8 kHz). This is the first published report of a patient with noise-induced hearing loss following treatment with cisplatin. While causality between the exposure to chemotherapy and the delayed ototoxicity post noise exposure cannot be guaranteed, our service has encountered other patients post platinum-based chemotherapy that developed hearing loss following noise exposure. The synergistic effects between ototoxic compounds and noise on hearing loss have also been demonstrated in animal models, and there is evidence of a common pathway (involving oxidative stress) between noise-induced and platinum-induced ototoxicity [15,16]. The hearing loss and tinnitus experienced by this patient and its subsequent recovery could be described as temporary threshold shift (TTS). TTS is known to affect the same frequency range of 3–6 kHz and may occur after a nightclub; however, studies on hearing following exposure to discotheque music usually report threshold shifts of 10 dB and no more than 20–25 dB, which usually recover by 2–4 h following noise exposure [17,18]. The more severe and prolonged threshold shifts in this patient (25– 35 dB and lasting at least three days), and permanent shift at high frequencies, suggests that this loss is more severe and may be related to the previous exposure to ototoxic treatment. Use of HF audiometry allows for earlier and reliable detection of platinum-induced ototoxicity [2,19,20]. HF audiograms in this patient show that there was asymptomatic ototoxic damage at the completion of chemotherapy, which was exacerbated following the exposure to excessive noise. It should be noted that platinuminduced ototoxicity may progress in some patients even after the completion of treatment [3]. Patients who have received radiotherapy to the head and neck are at even greater risk of progression [5] Therefore, the progression at the HF range in this patient could have occurred regardless of noise exposure. 4. Conclusion Ototoxicity is a serious consequence of cisplatin-based chemotherapy. After completion of chemotherapy and radiotherapy to the head and neck, cancer survivors are at higher risk of developing hearing loss from other causes in the future. The
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E. Peleva et al. / International Journal of Pediatric Otorhinolaryngology 78 (2014) 2301–2304
incidence of noise-induced hearing loss in this population may be underreported, but is of serious concern. Noise-induced hearing loss is preventable and patients who have undergone platinum-based chemotherapy and radiotherapy should be counseled to avoid excessive noise and to use hearing protection. As well, long-term follow up for hearing is strongly recommended in this population, in order to document the long-term effects of treatment and, most importantly, to educate patients about the risks and prevention strategies.
References [1] L.P. Rybak, Mechanisms of cisplatin ototoxicity and progress in otoprotection, Curr. Opin. Otolaryngol. Head Neck Surg. 15 (5) (2007) 364–369. [2] K.R. Knight, D.F. Kraemer, C. Winter, E.A. Neuwelt, Early changes in auditory function as a result of platinum chemotherapy: use of extended high-frequency audiometry and evoked distortion product otoacoustic emissions, J. Clin. Oncol. 25 (10) (2007) 1190–1195. [3] T. Al-Khatib, N. Cohen, A.S. Carret, S. Daniel, Cisplatinum ototoxicity in children, long-term follow up, Int. J. Pediatr. Otorhinolaryngol. 74 (8) (2010) 913–919. [4] P. Bertolini, M. Lassalle, G. Mercier, M.A. Raquin, G. Izzi, N. Corradini, et al., Platinum compound-related ototoxicity in children: long-term follow-up reveals continuous worsening of hearing loss, J. Pediatr. Hematol. Oncol. 26 (10) (2004) 649–655. [5] W.K. Low, S.T. Toh, J. Wee, S.M. Fook-Chong, D.Y. Wang, Sensorineural hearing loss after radiotherapy and chemoradiotherapy: a single, blinded, randomized study, J. Clin. Oncol. 24 (12) (2006) 1904–1909. [6] Audiologic Management of Individuals Receiving Cochleotoxic Drug Therapy [Guidelines], 2004. [7] K.W. Chang, N. Chinosornvatana, Practical grading system for evaluating cisplatin ototoxicity in children, J. Clin. Oncol. 28 (10) (2010) 1788–1795.
[8] A.M. Umansky, D.B. Jeffe, J.E. Lieu, The HEAR-QL: quality of life questionnaire for children with hearing loss, J. Am. Acad. Audiol. 22 (10) (2011) 644–653. [9] J.W. Varni, C. Limbers, T.M. Burwinkle, Literature review: health-related quality of life measurement in pediatric oncology: hearing the voices of the children, J. Pediatr. Psychol. 32 (9) (2007) 1151–1163. [10] S. Petrou, D. McCann, C.M. Law, P.M. Watkin, S. Worsfold, C.R. Kennedy, Health status and health-related quality of life preference-based outcomes of children who are aged 7 to 9 years and have bilateral permanent childhood hearing impairment, Pediatrics 120 (5) (2007) 1044–1052. [11] M.A. Askins, B.D. Moore, Preventing neurocognitive late effects in childhood cancer survivors, J. Child Neurol. 23 (10) (2008) 1160–1171. [12] Y. Li, R.B. Womer, J.H. Silber, Predicting cisplatin ototoxicity in children: the influence of age and the cumulative dose, Eur. J. Cancer 40 (16) (2004) 2445–2451. [13] C. Bokemeyer, C.C. Berger, J.T. Hartmann, C. Kollmannsberger, H.J. Schmoll, M.A. Kuczyk, et al., Analysis of risk factors for cisplatin-induced ototoxicity in patients with testicular cancer, Br. J. Cancer 77 (8) (1998) 1355–1362. [14] A. Yancey, M.S. Harris, A. Egbelakin, J. Gilbert, D.B. Pisoni, J. Renbarger, Risk factors for cisplatin-associated ototoxicity in pediatric oncology patients, Pediatr. Blood Cancer 59 (1) (2012) 144–148. [15] D. Henderson, B. Hu, S. McFadden, X. Zheng, Evidence of a common pathway in noise-induced hearing loss and carboplatin ototoxicity, Noise Health 2 (5) (1999) 53–70. [16] P.S. Steyger, Potentiation of chemical ototoxicity by noise, Semin. Hear. 30 (1) (2009) 38–46. [17] E. Emmerich, F. Richter, H. Hagner, F. Giessler, S. Gehrlein, H.G. Dieroff, Effects of discotheque music on audiometric results and central acoustic evoked neuromagnetic responses, Int. Tinnitus J. 8 (1) (2002) 13–19. [18] L.L. Tin, O.P. Lim, A study on the effects of discotheque noise on the hearing of young patrons, Asia. Pac. J. Public Health 12 (1) (2000) 37–40. [19] A.L. Abujamra, J.R. Escosteguy, C. Dall’Igna, D. Manica, L.F. Cigana, P. Coradini, et al., The use of high-frequency audiometry increases the diagnosis of asymptomatic hearing loss in pediatric patients treated with cisplatin-based chemotherapy, Pediatr. Blood Cancer 60 (3) (2013) 474–478. [20] N. Beahan, J. Kei, C. Driscoll, B. Charles, A. Khan, High-frequency pure-tone audiometry in children: a test-retest reliability study relative to ototoxic criteria, Ear Hear. 33 (1) (2012) 104–111.
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Case Report
Hearing loss in a pediatric patient following cisplatin chemotherapy and subsequent exposure to excessive noise Emilia Peleva a,1, Emilie Aloy b,2, Anne-Sophie Carret c,3, Sam J. Daniel a,* a
Department of Otolaryngology-Head and Neck Surgery, McGill University, Montreal, Quebec, Canada Faculte´ de Me´dicine de Montpellier, Universite´ Montpellier 1, Montpellier, France c Division of Hematology-Oncology, Department of Pediatrics, CHU Sainte-Justine/Universite´ de Montre´al, Montreal, Quebec, Canada b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 21 November 2013 Received in revised form 22 August 2014 Accepted 25 August 2014 Available online 1 September 2014
Cisplatin is a commonly-used chemotherapeutic agent that is highly-effective against a variety of pediatric cancers. Unfortunately, it may lead to ototoxicity, with serious consequences on the quality of life of survivors. Patients remain at risk of progression of ototoxicity even after completion of treatment. We report the case of a medulloblastoma survivor with previously documented normal hearing, who developed significant hearing loss and tinnitus following exposure to excessive noise at a nightclub three years after completion of treatment. We highlight the importance of long-term audiological follow up and education about the increased risk of hearing loss in this population. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Cisplatin Ototoxicity Pediatric oncology Late effects Noise-induced hearing loss Progressive hearing loss
1. Introduction Cisplatin is a chemotherapeutic agent commonly-used and highly effective against a variety of pediatric cancers. It is also the single most ototoxic drug in clinical use today, leading to tinnitus and sensorineural hearing loss, which is often permanent, bilateral and progressive [1]. It is estimated that 50–60% of children will develop ototoxicity during platinum-based chemotherapy [1,2]. Some patients will have progression of hearing loss even after completion of chemotherapy [3,4]. The risk of progression is even greater in patients who have received radiotherapy to the head and neck [5]. We report the case of a child who, despite normal hearing following cisplatin chemotherapy and cranial radiotherapy,
* Corresponding author at: The Montreal Children’s Hospital, 2300 Rue Tupper, Rm. B-240, Montreal, QC, Canada, H3H 1P3. Tel.: +1 514 412 4304; fax: +1 514 412 4342. E-mail address: [email protected] (S.J. Daniel). 1 Address: 103 Belgrave Road, Flat 8, London SW1V 2BH, UK. 2 Address: 28 rue de la Cadoule, 34740 Vendargues, France. 3 Address: Pediatric Hematology-Oncology, CHU Sainte-Justine, 3175 Chemin Coˆte Sainte-Catherine, Local A.12.39, Montreal, QC, Canada, H3T 1C5. http://dx.doi.org/10.1016/j.ijporl.2014.08.039 0165-5876/ß 2014 Elsevier Ireland Ltd. All rights reserved.
developed a severe hearing loss over three years later, after exposure to excessive noise.
2. Case report A 13.5 year-old boy underwent craniotomy and macroscopically complete resection of a left cerebellar medulloblastoma. Due to residual tumor on the post-surgical MRI, he underwent a second surgery with complete excision of the residual tumor. The patient then received cranio-spinal radiotherapy of 23.4 Gy in 13 sessions of 1.8 Gy each, followed by a boost to the posterior fossa of 30.6 Gy in 17 sessions of 1.8 Gy each in combination with weekly vincristine as radio-sensitizer. Four weeks after completion of radiotherapy, he began chemotherapy consisting in lomustine, cisplatin, vincristine, and cyclophosphamide. This patient received cisplatin at 75 mg/m2 over 6 h, for a total of six cycles administered over nine months. Furosemide and mannitol were also administered as part of supportive care. Audiological testing included conventional audiometry (0.25–8 kHz), impedance audiometry, Distortion Product Otoacoustic Emission (DPOAE) tests and Transiently-Evoked Otoacoustic
2302
Table 1 Audiological evaluations.
Conventional (C)
During platinum-based chemotherapy
1
3
2
5
Post-chemotherapy 6
7
8
Freq
9
10
11
12
LE
RE
LE
RE
LE
RE
LE
RE
LE
RE
LE
RE
LE
RE
LE
RE
LE
RE
LE
RE
LE
RE
LE
10 0 10 5 5 5 0 0 – – – – – –
10 0 0 10 10 5 10 5 – – – – – –
5 5 0 0 0 0 0 0 – – –– – – –
10 10 10 10 5 5 5 5 – – – – – –
10 5 0 0 0 0 0 0 – – – – – –
15 5 0 5 0 0 0 0 – – – – – –
10 5 5 0 – 0 – 0 – – – – – –
10 10 5 5 – 0 – 0 – – – – – –
0
0 0
5 5 0
10 5 5 5 0 5 0 0 – 20 – 25 35 >40
5 5 5 0
10 5 5 5 5 0 20 30 – 45 – 65 45 45
0 0 0 0 0 0 0 5 – 30 25 25 35 30
5 0 0 5 0 0 0 5 – 35 40 45 50 45
0 0 5 25 30 25 10 5 – – – – – –
10 5 25 30 35 30 15 – – – – – – –
10 5 0 0 0 0 0 5 35 35 45 65 60 45
10 5 0 5 0 0 10 15 35 40 35 45 45 55
10 0 0 5 0 0 0 5 45 45 45 50 55 40
5 5 0 5 0 0 5 15 35 45 40 40 45 35
ASHA (C/HF) Chang Tymp DPOAE
– 0 Normal –
TEOAE
Normal Normal
–
Normal
4
RE
10 0 10 0 5 10 5 10 5 5 0 5 0 0 0 5 – – – – – – – – – – – – Baseline 0 Normal –
HF
0.25 0.5 1 2 3 4 6 8 9 10 11.2 12.5 14 16
Pre-chemotherapy
Y/– 0 Normal –
N/– 0 LE - H –
–
Normal
Y/– 0 LE - H –
5 5 5
5 5
– – 0 5 – – 5 5 – – 15 10 – – 30 30 35 30 >40 25 N/Baseline 0 Normal – Abnormal
5 5 5 0 10 – 30 – 40 45 >40
5 5 0 15 – 45 – 80 65 40
N/Y 0 Normal –
Y/Y 1a Normal –
N/Y 1a Normal Normal
Y/– 2b Normal 2 +4 bilat
Normal
Normal
Normal
Normal
Y/Y 1a Normal 1 + 2 LE, 1 + 1.4 RE RE
N/Y 1a Normal 1.4 + 2 LE, 1.4 RE
0.25 0.5 1 2 3 4 6 8 9 10 11.2 12.5 14 16 ASHA (C/HF) Chang Tymp DPOAE Abnormal TEOAE
Evaluations were performed: 1) prior to radiotherapy, 2–7) prior to each cisplatin dose, 8) three months after cisplatin chemotherapy, 9) 15 months after cisplatin chemotherapy, 10) 41 months after cisplatin chemotherapy (3 days post-noise exposure), 11) 42 months after cisplatin chemotherapy, 12) 52 months after cisplatin chemotherapy. Freq, frequency; RE, right ear; LE, left ear; Conventional, conventional audiometry; HF, high-frequency audiometry; ASHA, hearing loss based on the American Speech-Language-Hearing Association criteria; Chang, Chang grade assigned; Tymp, tympanogram; DPOAE, Distortion Product Otoacoustic Emission tests, with abnormal frequencies being listed (in kHz, defined as: signal/noise ratio below 6 dB); TEOAE, Transiently-Evoked Otoacoustic Emission test results, as determined by the audiologist. Note 1: The patient has normal hearing (thresholds 20 dB in evaluations #3 and 5 despite hearing loss according to the ASHA criteria). Note 2: Chang grades were assigned based on frequencies up to 12 kHz, whenever possible.
E. Peleva et al. / International Journal of Pediatric Otorhinolaryngology 78 (2014) 2301–2304
Freq
[(Fig._1)TD$IG]
E. Peleva et al. / International Journal of Pediatric Otorhinolaryngology 78 (2014) 2301–2304
2303
Fig. 1. Chang Scale (Modified Brock’s Grading System) and Brock Grading System. Brock Grade: based on results in the better ear with < 40 dB at all lower frequencies. Source: Chang and Chinosornvatana (2010). Practical grading system for evaluating cisplatin ototoxicity in children. J Clin Oncol 28 (10): 1788–1795. Reprinted with permission. ß (2010) American Society of Clinical Oncology. All rights reserved.
Emission (TEOAE) tests. High frequency (HF) audiometry (9–16 kHz) was performed once it became available at our institution. Results from conventional audiometry performed up to 15 months after completion of chemotherapy (Table 1, Evaluations #1–9), demonstrate that the patient had hearing thresholds of 20 dB at all time points, except at 8 kHz in the left ear, where the post-chemotherapy threshold was 30 dB. There was an air-bone gap in the left ear at the pre-chemotherapy hearing test, likely due to radiotherapy. Results from HF audiometry show that there was asymptomatic hearing loss at the post-chemotherapy audiograms (Evaluations #8 and 9). When compared to the first HF audiogram (Evaluation #6), there was hearing loss based on the American SpeechLanguage-Hearing Association (ASHA) criteria [6]. These audiograms were classified as Chang Grades 1a, corresponding to early ototoxicity which is not clinically significant (Fig. 1) [7]. The patient also reports post-chemotherapy tinnitus which is not particularly disruptive. Three years post-chemotherapy, the patient presents with complaints of exacerbation of his tinnitus following excessive noise exposure (going to a nightclub). The audiogram, performed three days after the exposure, shows that the patient has Chang Grade 2b, corresponding to clinically significant hearing loss. Bone conduction audiometry confirms the presence of sensorineural hearing loss at 1 kHz in the left ear and 2–4 kHz bilaterally. HF audiometry is not performed at this time-point. He is seen by an otolaryngologist one week later, and he seems to have recuperated well; the tinnitus has also improved according to the patient. Four weeks after the noise exposure, hearing had returned to normal at conventional frequencies (Evaluation #11). At HF, thresholds in the left ear are similar to pre-noise exposure thresholds, but there is progression of hearing loss in the right ear according to the ASHA criteria. This audiogram still has a Chang Grade of 1a. The patient reported that his tinnitus had returned to post-chemotherapy status. A further evaluation 11 months after noise exposure suggests that the patient’s audiological status is stable (Evaluation #12). 3. Discussion Young patients are more susceptible to developing ototoxicity. This could have devastating consequences in this population as hearing loss has major impacts on communication, development of literacy, academic performance, and on their overall health and quality of life [8,9]. Even mild hearing loss can have serious consequences on academic performance [10]. These consequences may be even greater in patients with neurocognitive disabilities, especially children having received cranial radiation for brain tumors [11]. Cisplatin doses of 400 mg/m2 are associated with an increased risk of developing ototoxicity [4,12]. The patient presented here
received a high cumulative dose of 450 mg/m2. He also received radiotherapy to the head and neck, as well as administration of vincristine, cyclophosphamide, furosemide, and mannitol, which further increase the risk of ototoxicity [5,13,14]. Despite this intensive treatment, this patient did not have clinically significant hearing loss post-chemotherapy. The treatment was deemed successful as this patient went into remission without severe longterm consequences from treatment, until he went to a nightclub to celebrate his 18th birthday, and the exposure to loud music resulted in sudden hearing loss persisting for at least three days after the exposure. The speech hearing thresholds returned to normal by four weeks, but there was permanent progression at the high frequencies (>8 kHz). This is the first published report of a patient with noise-induced hearing loss following treatment with cisplatin. While causality between the exposure to chemotherapy and the delayed ototoxicity post noise exposure cannot be guaranteed, our service has encountered other patients post platinum-based chemotherapy that developed hearing loss following noise exposure. The synergistic effects between ototoxic compounds and noise on hearing loss have also been demonstrated in animal models, and there is evidence of a common pathway (involving oxidative stress) between noise-induced and platinum-induced ototoxicity [15,16]. The hearing loss and tinnitus experienced by this patient and its subsequent recovery could be described as temporary threshold shift (TTS). TTS is known to affect the same frequency range of 3–6 kHz and may occur after a nightclub; however, studies on hearing following exposure to discotheque music usually report threshold shifts of 10 dB and no more than 20–25 dB, which usually recover by 2–4 h following noise exposure [17,18]. The more severe and prolonged threshold shifts in this patient (25– 35 dB and lasting at least three days), and permanent shift at high frequencies, suggests that this loss is more severe and may be related to the previous exposure to ototoxic treatment. Use of HF audiometry allows for earlier and reliable detection of platinum-induced ototoxicity [2,19,20]. HF audiograms in this patient show that there was asymptomatic ototoxic damage at the completion of chemotherapy, which was exacerbated following the exposure to excessive noise. It should be noted that platinuminduced ototoxicity may progress in some patients even after the completion of treatment [3]. Patients who have received radiotherapy to the head and neck are at even greater risk of progression [5] Therefore, the progression at the HF range in this patient could have occurred regardless of noise exposure. 4. Conclusion Ototoxicity is a serious consequence of cisplatin-based chemotherapy. After completion of chemotherapy and radiotherapy to the head and neck, cancer survivors are at higher risk of developing hearing loss from other causes in the future. The
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incidence of noise-induced hearing loss in this population may be underreported, but is of serious concern. Noise-induced hearing loss is preventable and patients who have undergone platinum-based chemotherapy and radiotherapy should be counseled to avoid excessive noise and to use hearing protection. As well, long-term follow up for hearing is strongly recommended in this population, in order to document the long-term effects of treatment and, most importantly, to educate patients about the risks and prevention strategies.
References [1] L.P. Rybak, Mechanisms of cisplatin ototoxicity and progress in otoprotection, Curr. Opin. Otolaryngol. Head Neck Surg. 15 (5) (2007) 364–369. [2] K.R. Knight, D.F. Kraemer, C. Winter, E.A. Neuwelt, Early changes in auditory function as a result of platinum chemotherapy: use of extended high-frequency audiometry and evoked distortion product otoacoustic emissions, J. Clin. Oncol. 25 (10) (2007) 1190–1195. [3] T. Al-Khatib, N. Cohen, A.S. Carret, S. Daniel, Cisplatinum ototoxicity in children, long-term follow up, Int. J. Pediatr. Otorhinolaryngol. 74 (8) (2010) 913–919. [4] P. Bertolini, M. Lassalle, G. Mercier, M.A. Raquin, G. Izzi, N. Corradini, et al., Platinum compound-related ototoxicity in children: long-term follow-up reveals continuous worsening of hearing loss, J. Pediatr. Hematol. Oncol. 26 (10) (2004) 649–655. [5] W.K. Low, S.T. Toh, J. Wee, S.M. Fook-Chong, D.Y. Wang, Sensorineural hearing loss after radiotherapy and chemoradiotherapy: a single, blinded, randomized study, J. Clin. Oncol. 24 (12) (2006) 1904–1909. [6] Audiologic Management of Individuals Receiving Cochleotoxic Drug Therapy [Guidelines], 2004. [7] K.W. Chang, N. Chinosornvatana, Practical grading system for evaluating cisplatin ototoxicity in children, J. Clin. Oncol. 28 (10) (2010) 1788–1795.
[8] A.M. Umansky, D.B. Jeffe, J.E. Lieu, The HEAR-QL: quality of life questionnaire for children with hearing loss, J. Am. Acad. Audiol. 22 (10) (2011) 644–653. [9] J.W. Varni, C. Limbers, T.M. Burwinkle, Literature review: health-related quality of life measurement in pediatric oncology: hearing the voices of the children, J. Pediatr. Psychol. 32 (9) (2007) 1151–1163. [10] S. Petrou, D. McCann, C.M. Law, P.M. Watkin, S. Worsfold, C.R. Kennedy, Health status and health-related quality of life preference-based outcomes of children who are aged 7 to 9 years and have bilateral permanent childhood hearing impairment, Pediatrics 120 (5) (2007) 1044–1052. [11] M.A. Askins, B.D. Moore, Preventing neurocognitive late effects in childhood cancer survivors, J. Child Neurol. 23 (10) (2008) 1160–1171. [12] Y. Li, R.B. Womer, J.H. Silber, Predicting cisplatin ototoxicity in children: the influence of age and the cumulative dose, Eur. J. Cancer 40 (16) (2004) 2445–2451. [13] C. Bokemeyer, C.C. Berger, J.T. Hartmann, C. Kollmannsberger, H.J. Schmoll, M.A. Kuczyk, et al., Analysis of risk factors for cisplatin-induced ototoxicity in patients with testicular cancer, Br. J. Cancer 77 (8) (1998) 1355–1362. [14] A. Yancey, M.S. Harris, A. Egbelakin, J. Gilbert, D.B. Pisoni, J. Renbarger, Risk factors for cisplatin-associated ototoxicity in pediatric oncology patients, Pediatr. Blood Cancer 59 (1) (2012) 144–148. [15] D. Henderson, B. Hu, S. McFadden, X. Zheng, Evidence of a common pathway in noise-induced hearing loss and carboplatin ototoxicity, Noise Health 2 (5) (1999) 53–70. [16] P.S. Steyger, Potentiation of chemical ototoxicity by noise, Semin. Hear. 30 (1) (2009) 38–46. [17] E. Emmerich, F. Richter, H. Hagner, F. Giessler, S. Gehrlein, H.G. Dieroff, Effects of discotheque music on audiometric results and central acoustic evoked neuromagnetic responses, Int. Tinnitus J. 8 (1) (2002) 13–19. [18] L.L. Tin, O.P. Lim, A study on the effects of discotheque noise on the hearing of young patrons, Asia. Pac. J. Public Health 12 (1) (2000) 37–40. [19] A.L. Abujamra, J.R. Escosteguy, C. Dall’Igna, D. Manica, L.F. Cigana, P. Coradini, et al., The use of high-frequency audiometry increases the diagnosis of asymptomatic hearing loss in pediatric patients treated with cisplatin-based chemotherapy, Pediatr. Blood Cancer 60 (3) (2013) 474–478. [20] N. Beahan, J. Kei, C. Driscoll, B. Charles, A. Khan, High-frequency pure-tone audiometry in children: a test-retest reliability study relative to ototoxic criteria, Ear Hear. 33 (1) (2012) 104–111.
