Cochleotoxicity and vestibulotoxicity monitoring in patients receiving chemotherapy in South Africa

Abstract

Platinum-based agents can cause ototoxicity, an adverse reaction affecting the inner ear. The ototoxicity is characterised by cochleotoxicity and vestibulotoxicity. Although ototoxic medications play an essential role in modern medicine, they have the capability to cause harm and can have a significant effect on health-related quality of life (HRQoL). Ototoxicity surveillance is vital for possible treatment modifications, early identification and rehabilitation of hearing and vestibular function. Although many ototoxicity monitoring protocols exist and have proved to be effective in identification of ototoxicity, their success of implementation is questionable. One of the major factors affecting current monitoring protocols is the incapacitated state of the cancer patients. Reliable and efficient monitoring protocols that are less labour intensive and time consuming are required. Shortened protocols that target sensitive frequencies for ototoxicity and allow testing outside of traditional settings are required. Technologies need to be validated in order to decentralise services from the traditional models and ensure access for cancer patients at their treatment venue. There is limited knowledge about the current status of ototoxicity monitoring in oncology units in South Africa. This information could guide future practices of ototoxicity monitoring in South Africa.

This project investigated (i) the status of ototoxicity monitoring in South Africa, (ii) the role of innovative technology to support decentralised ototoxicity monitoring, and, lastly, (iii) potential monitoring of vestibulotoxicity in cancer patients.

Study I investigated (i) the national status of ototoxicity monitoring implemented in private and public cancer facilities, (ii) the knowledge and ototoxicity monitoring approaches implemented, and (iii) reported challenges. A descriptive quantitative survey was conducted in public and private oncology units and audiology referral clinics. Provinces included were Gauteng, Free State, Mpumalanga, Limpopo, North West, Western Cape, Northern Cape, Eastern Cape and KwaZulu-Natal. Private (60%) and public (43%) oncology units that provide platinum-based chemotherapy in South Africa and 54% of audiology referral units were (1) surveyed telephonically to determine if ototoxicity monitoring takes place, and (2) a self-administered survey was sent to qualifying oncology units and audiology referral clinics. All public oncology units reported that ototoxicity monitoring only occurred on referral and was not standard practice. All private oncology units indicated that monitoring was on a patient self-referral basis when symptoms occurred. Poor awareness of ototoxicity monitoring best practice guidelines was reported by all oncology units and 14% of audiology referral clinics. Audiology referral clinics reported adequate knowledge of ototoxicity protocols although they were not widely used, with only 43% following best practice guidelines. The most prominent challenges reported by participants were referral system (67% oncology units; 57% audiology referral clinics), environmental noise (83% oncology units; 86% audiology referral clinics) and the compromised status of cancer patients (67% oncology units; 57% audiology referral clinics). There is significant discrepancy in the manner in which ototoxicity monitoring is conducted across South Africa in both the private and public sector. Effective scheduling and test location are key to a successful monitoring programme. Ototoxic monitoring programmes need to become standard for the care of all patients receiving treatment with ototoxic chemotherapy.

Study II investigated mHealth-enabled surveillance in ototoxicity. A longitudinal study of 32 participants receiving chemotherapy was conducted. Baseline and exit audiograms that included conventional and extended high-frequency (EHF) audiometry were recorded at the patient’s treatment venue using a validated mobile health (mHealth) audiometer. Average hearing thresholds at baseline were within the normal range (81.2% left; 93.8% right), reducing at exit testing (71.9% left; 78.1% right). Half (50%) of participants presented with a threshold shift according to ototoxicity monitoring criteria. Frequencies affected most were between 4000 and 16000 Hz, with left ears significantly (p < 0.05) more affected than right ears. During threshold determination, noise levels exceeded the maximum permissible ambient noise levels in up to 43.8% of thresholds determined in low frequencies between 250 and 1000 Hz. Ototoxicity surveillance that included mHealth audiometry and EHF for cancer patients receiving platinum-based chemotherapy proved to be valuable, and testing could take place at the treatment venue. Baseline and exit testing performed could track changes in hearing. Shortened monitoring protocols focusing on high frequencies and EHF may be more efficient, and address the possibility of noise interference in the lower frequencies during testing.

Study III investigated the changes in vestibular and cochlear function in patients receiving platinum-based chemotherapy. A longitudinal study of 32 participants (10-70 years) receiving chemotherapy was conducted. Baseline and exit vestibular and hearing assessments that included video head impulse (VHIT) testing, cervical and ocular vestibular evoked myogenic potentials (VEMP), bedside dynamic visual acuity (DVA) and pure-tone audiometry were performed at the patient’s treatment venue. Half (50%) of the participants showed cochleotoxicity from baseline to exit testing according to ototoxicity criteria, with left ears significantly (p < 0.05) more affected than right ears. There was no consistent relationship between hearing loss and vestibular dysfunction. DVA yielded normal results at baseline and exit testing in all participants. VEMP responses were absent in 28.1% of participants at baseline, reflecting the possible challenges of using VEMP for vestibulotoxicity monitoring. VEMP and VHIT results showed a statistically significant (p<0.05) decline in results from baseline to exit testing; however, participants did not report symptoms related to vestibular dysfunction. As in cocheotoxicity, VHIT also showed left ears significantly (p<0.05) more affected than right ears. VEMP results did not show significant differences between the ears. VHIT can easily be performed at the patient’s treatment venue. However, VEMP at the patient’s treatment venue has proven to be logistically challenging and time-consuming when performed as part of an ototoxicity monitoring programme. Furthermore, considering that VEMP responses are absent in all patients >60 years, VEMP may not be practical as a vestibulotoxicity monitoring tool for older cancer patients. As patients did not report vestibular symptoms that had a functional impact on daily life, patient self-report of symptoms may be sufficient to monitor vestibulotoxicity in the treatment venue for patients who are ill and incapacitated.

The results from the three studies demonstrated that ototoxicity monitoring was not routinely implemented across oncology units in South Africa. Multidisciplinary teamwork and a decentralised approach to ototoxicity monitoring may improve hearing outcomes for cancer patients. mHealth-supported audiometry proved to be a valuable tool for ototoxicity monitoring at the treatment venue. Changes in hearing sensitivity over time could be tracked, improving surveillance in patients with full treatment schedules and compromised health status. VHIT proved to be a useful measure of changes in vestibular function secondary to ototoxicity. Future investigations should determine vestibulotoxicity criteria and optimal protocols for sensitivity and efficiency in monitoring vestibular functioning during chemotherapy treatment at the patient’s treatment venue or hospital ward. This project highlighted that ototoxicity monitoring as standard practice at the patient’s treatment venue would relieve the over-burdened treatment schedule of cancer patients. This would ensure that HRQoL is preserved and an opportunity for early intervention and aural rehabilitation is provided.