Research Career Scientist

Current Research Activities Ototoxicity is a common side effect of platinum-based chemotherapy that leads to significant negative health and psychosocial consequences among adult cancer survivors (Miaskowski et al. 2018; Dillard et al. 2022). Prospectively monitoring patients with cancer for early signs of ototoxicity provides the opportunity to mitigate its

adverse effects when the oncologist is able to modify drug treatment, and/or the audiologist can deliver timely rehabilitation (ASHA 1994; AAA 2009). Unfortunately, significant barriers exist to integrating audiology supportive services into oncologic care. Principal among these are barriers related to care and referral coordination with

oncology, audiology workload, and lack of protocols. Development of interventions is further hampered by uncertain pathophysiology and variable patient susceptibility to ototoxicity, particularly as it relates to the development of tinnitus and difficulties understanding speech in noise. The result is that ototoxicity management

(OtoM) as delivered currently in VA is elective care that occurs sporadically and fails to inform the patient’s ototoxicity risk stratification, oncologic treatment or survivorship plan (Konrad-Martin et al. 2021, 2023). The objectives of Dr. Konrad-Martin’s program of research are to: (i) construct tools to forecast individual patient

susceptibility to ototoxic hearing loss and tinnitus; (ii) test new hypotheses developed in animal models, about the cochlear changes that trigger tinnitus and temporal processing problems in humans; and (iii) characterize ototoxicity and OtoM from the perspectives of the patient and provider. For this research, patients receiving

cisplatin, carboplatin, or oxaliplatin are providing behavioral and physiological measures of auditory function before, during, and after treatment. A subset contribute a blood sample for a genetic association pilot study. i. Forecasting model development. We have developed a prognostic model to mathematically transform the

patient’s personal and treatment features into the expected post-treatment audiogram, which can be expressed on a variety of measurement scales to address the clinical concern for patients, audiologists and oncologists (McMillan et al. in progress). Into this model, we have incorporated population-based data from unexposed

controls on normal test-retest variability in pure tone thresholds. For Dr. Konrad-Martin’s SPiRE, model predictors additionally include the presence and numbers of specific single nucleotide polymorphisms within four genes selected for their potential association with cisplatin ototoxicity, including: ACYP2 (Xu et al., 2015); COMT

(Hagleitner et al., 2014); TPMT (Ross et al., 2009); and TRPV1 (Jiang et al., 2019). ii. Relating ototoxic symptoms to the underlying auditory injury. A combination of wideband acoustic reflex (AR) amplitude growth (Westman et al., 2021), and distortion product otoacoustic emission (DPOAE) levels is being

used to distinguish damage to the cochlear afferent system from outer hair cell dysfunctio n to determine the extent to which tinnitus, speech understanding deficits, and reduced benefit from temporally-based spatial cues can be attributed to cochlear injury, after controlling for cognitive function. Results are examined at one month

and one year after the initial chemotherapy treatment to allow for neuroplasticity within the central auditory pathways (Kaltenbach et al. 1998, 2001; Chambers et al. 2016). (iii) Characterize patient and provider perspectives on ototoxicity and OtoM. Patient and provider perspectives on ototoxicity and OtoM are necessary to determine high value aspects of OtoM and barriers to care. Patient-

centered rating scales and questionnaires are being used to obtain the patient’s perspective on ototoxicity and OtoM. We surveyed 63 VA audiologists and 12 VA oncologists nationally regarding their views on OtoM and barriers to care. These results, together with completed work indicate that although OtoM has been

recommended for patients receiving cisplatin, carboplatin, or chemoradiation to mitigate ototoxicity, OtoM is at best underutilized in VA (Konrad-Martin et al. 2021, 2023).