Patient and Parent Decision-Making in the Setting of Chemotherapy-Induced Sensorineural Hearing Loss.

OBJECTIVES: Children with malignancies may be exposed to ototoxic therapies resulting in sensorineural hearing loss (SNHL). There is no consensus as to when intervention with amplification is necessary due to a variety of factors such as disease status, speech and language development, perceived difficulty with communication, and limitations of technology to fit these challenging losses. The decision to proceed with amplification after cancer can be difficult for patients and families. The purpose of this study is (1) to understand the decision-making (DM) process of childhood cancer survivors (CCSs) with SNHL and their parents and (2) to identify their decisional needs. DESIGN: Semi-structured interviews guided by the Ottawa's decision support framework were recorded and transcribed verbatim. Inclusion criteria were CCSs ages 8 to 30 years old with a Chang grade >1b SNHL and off-therapy; parents of this group were also eligible. Patients with active disease were excluded. Prompts inquired of sources of decisional conflict, role in DM, and DM behaviors. Inductive content analysis of the narrative qualitative data was used. RESULTS: Seven parents of CCSs and 6 CCSs participated. Themes in the CCS group included: (1) making sense of ototoxic SNHL; (2) desiring personalized education and treatment of SNHL; (3) playing an active role in the joint DM process; and (4) accepting hearing aids requires time and effort. The parent group shared the first and last theme with the CCS group and had two unique themes: (1) needing experts to respect the individual's journey to SNHL acceptance and (2) moving past the cancer experience to acceptance. Parents more often framed their DM within the context of already experiencing the trauma of cancer, whereas CCSs did not. One parent said, "You see all the rubble and you've lived through the devastation of the storm, but now you got to figure out what's broken." CCSs expressed bodily concerns regarding amplification, such as discomfort to the ear and difficulty in adjusting to the volume. The following needs were identified: early, re-enforced education regarding late effects risks; open communication among providers, CCSs, and parents; and audiogram result interpretations in patient- and parent-friendly language. CONCLUSIONS: Understanding the DM process from the CCS and parent's perspectives should be considered when providing counseling for hearing amplification in the setting of cancer-related SNHL. Earlier and consistent delivery of late effects education, open communication regarding risk for SNHL, and improved delivery of audiogram results should be targets for meeting unmet needs. These findings should inform the development of decision aids to reduce decisional conflict in this population.

Children with non-central nervous system tumors treated with platinum-based chemotherapy are at risk for hearing loss and cognitive impairments.

Background: Childhood cancer survivors (CCS) with chemotherapy induced sensorineural hearing loss (SNHL) are at risk for neurocognitive impairments. The purpose of this study was to determine the relationship between SNHL and cognitive function among CCS. Procedure: Inclusion: non-CNS solid tumor diagnosis; history of platinum chemotherapy (cisplatin and/or carboplatin); 8-17 years of age; off anti-cancer treatment for ≥6 months; and English speaking. Exclusion: history of intrathecal chemotherapy, cranial radiation, or baseline neurocognitive disorder. Participants completed the NIH Toolbox Cognition Battery at enrollment. T-tests were used to compare participants with normal hearing to those with hearing loss and the total sample with established Toolbox normative data (mean: 50; SD: 10). Results: Fifty-seven individuals enrolled; 52 completed full cognitive testing. Participants were on average 12.2 years of age and 7.0 years since treatment completion. Twenty-one participants (40%) received cisplatin, 27 (52%) carboplatin, and 4 (8%) received both. Fifteen participants (29%) demonstrated SNHL based on the better ear. CCS, regardless of the presence or absence of SNHL, demonstrated significantly lower mean cognitive skills compared to the normative sample in attention, executive function, language- vocabulary and oral reading, processing speed, and fluid, crystallized and total composite scores (all p < 0.01). Participants with SNHL had significantly lower crystallized composite (vocabulary, oral reading) than those with normal hearing (41.9 vs. 47.2, p < 0.05, Cohen's d = 0.62). Conclusions: CCS at risk for platinum induced hearing loss but without cranial radiation or intrathecal chemotherapy exposure demonstrate impaired cognitive skills and those with SNHL demonstrate lower crystallized composite scores.

Assessing quality of life in childhood cancer survivors at risk for hearing loss: a comparison of HEAR-QL and PROMIS measures.

Background: Childhood cancer survivors (CCS) exposed to platinum chemotherapy are at an increased risk of developing hearing loss and reporting decreased quality of life (QOL). This study compared two QOL measures; one developed for children with hearing loss, The Hearing Environments and Refection on Quality of Life (HEAR-QL), and one validated in CCS, the Patient-Reported Outcomes Measurement Information System (PROMIS), to assess their ability to evaluate QOL deficits in this population. Methods: Subject eligibility were restricted to CCS exposed to platinum-based chemotherapy but who were free of known risk factors for cognitive impairment, (non-central nervous system tumor, no cranial radiation, or intrathecal chemotherapy). Participants had to be between 8-17 years, have completed anti-cancer therapy for at least 6 months, and have an audiogram within 1 year, Participants completed the HEAR-QL-26 (7-12 years) or the HEAR-QL-28 (13-18 years) and the PROMIS. Independent samples and/or one sample T-tests were utilized to compare participants with normal hearing and hearing loss, and to compare outcome measures to normative HEAR-QL and PROMIS data. Non-parametric correlations were utilized to evaluate the relationship between QOL and demographic and medical variables, and QOL and severity of hearing loss. Results: Fifty-four CCS were evaluable. The mean age was 12.0 years. Twenty-eight participants (51.9%) received cisplatin, 30 (55.6%) carboplatin, and 4 (7.4%) received both. Twenty participants (37%) demonstrated hearing loss. Participants with hearing loss scored significantly lower on the HEAR-QL than those with normal hearing (mean: 70.3, SD: 21.7, vs mean: 88.0, SD: 9.3, p =.004 for the HEAR-QL-26; mean: 84.7, SD: 10.2 vs mean: 94.8, SD: 3.4, p =.040 for the HEAR-QL-28). Participants with normal hearing scored significantly lower on the HEAR-QL-26 than the normative mean (mean: 88, SD: 9.3, normative mean: 98, SD: 5, p =.000). The PROMIS failed to identify any differences in QOL between participants based on hearing status, or when compared to the normative mean. Conclusion: The HEAR-QL was more sensitive than the PROMIS in identifying QOL deficits in CCS at risk for hearing loss. The HEAR-QL should be considered in studies seeking to improve the QOL of CCS with hearing loss.

Cisplatin Ototoxicity: Examination of the Impact of Dosing, Infusion Times, and Schedules In Pediatric Cancer Patients.

BACKGROUND: Sensorineural hearing loss is a well-known side effect of cisplatin (CDDP). There is limited research on the effect of dosing, infusion times, and schedules of cisplatin administration and their impact on hearing loss. METHODS: A retrospective review of 993 pediatric patients' medical and audiological charts from August 1990 to March 2015 was conducted using stringent inclusion criteria to characterize patients with hearing loss. 248 of these patients received CDDP. Of these, 216 patients had sufficient CDDP infusion data to assess for sensorineural hearing loss attributable to CDDP and its associated risk factors. Chart reviews were performed to extract clinical data including CDDP dosing information. Demographic and clinical characteristics were summarized by descriptive statistics, and univariate and multivariate logistic regressions were performed to examine the relationship between hearing loss and specific parameters of cisplatin administration (amount infused per dose, prescribed infusion time, total number of doses, number of doses per cycle, number of cycles, cumulative cisplatin exposure). Stepwise variable selection procedure was performed in the multivariate model building to extract the best subset of risk factors for the prediction of hearing loss and worsening ototoxicity grade using an established ototoxicity grading scale from the International Society of Pediatric Oncology (SIOP). RESULTS: A total of 153 patients with complete medical and audiologic data were evaluable for analysis. Hearing loss was identified in 72.6% of the patients. Multivariate analysis revealed that age [OR=0.90 (0.84-0.97), p-value=0.0086], radiation to any part of the body, [OR=3.20 (1.29-7.93), p-value=0.012], amount infused per dose (mg/m2) [OR=1.018 (1.002-1.033), p-value=0.029], and cumulative cisplatin exposure (mg/m 2) [OR=1.004 (1-1.008), p-value=0.027] were associated with hearing loss. Similar associations were also found between these risk factors and worsening SIOP grade. CONCLUSION: In one of the largest studies examining the influence of CDDP dosing and schedules on hearing loss, we found the amount of CDDP infused per dose is a significant risk factor. Considerations in designing regimens that reduce the amount of CDDP infused per dose may reduce the risk of hearing loss. Randomized prospective trials are needed.

One or two genetic loci mediate high opiate analgesia in selectively bred mice.

The analgesic responses of humans and laboratory animals are characterized by substantial individual differences. The genetic basis of this variability can be studied experimentally in rodents using a program of selective breeding. One such program selected for high (HA) and low (LA) swim stress-induced analgesia (SSIA) on the hot-plate (56 degrees C) test in Swiss-Webster mice. These lines, which have been selectively bred for more than 25 generations, display markedly divergent opioid-mediated SSIA (3-min swims in 38 degrees C water), morphine analgesia (10 mg/kg, i.p.), and analgesia to the kappa-receptor agonist, U-50,488H (30 mg/kg, i.p.). The present study investigated the mode of inheritance of these opioid analgesias in HA and LA mice, using Mendelian genetic analyses. We report that the differential sensitivity of HA and LA mice to each of these analgesic manipulations appears to be determined oligogenically, by one or at the most two major genetic loci. The loci associated with each type of analgesia do not co-segregate, however, indicating that three distinct oligogenic effects have been identified. These findings suggest that the genetic determination of analgesic mechanisms may have simple components and as such may be amenable to further analysis using molecular genetic techniques.