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Brazilian Journal of Otorhinolaryngology 2022Platinum-based chemotherapeutics play an important role in the treatment of cancer at different levels and are the most cited ototoxic agents when scientific evidence is... (Review)
Review
INTRODUCTION
Platinum-based chemotherapeutics play an important role in the treatment of cancer at different levels and are the most cited ototoxic agents when scientific evidence is analyzed.
OBJECTIVE
To present scientific evidence based on a systematic literature review, PRISMA, in order to systematize information on the ototoxic effects of using antineoplastic drugs.
METHODS
For the selection of studies, the combination based on the Medical Subject Heading Terms (MeSH) was used. The Medline (Pubmed), LILACS, SciELO, SCOPUS, WEB OF SCIENCE and BIREME databases were used, without restriction of language, period, and location. Evaluation of the quality of the articles was carried out, which included articles with a minimum score of 6 in the modified scale of the literature. The designs of the selected studies were descriptive, cohort, and cross-sectional, which were related to the research objective.
RESULTS
Three articles were included in this systematic review. The ototoxicity caused by cisplatin alone varied from 45% to 83.3%, while that caused by the use associated with carboplatin varied from 16.6% to 75%. There was a significant variation in the cumulative doses of these antineoplastic agents, both in isolated and in combination. Auditory changes, especially at high frequencies, were evident after completion of treatment.
CONCLUSION
Auditory changes after the use of platinum-based antineoplastic drugs were found, however, there was an important heterogeneity regarding the frequency of ototoxicity and the cumulative dose of the drugs used.
Topics: Antineoplastic Agents; Cisplatin; Cross-Sectional Studies; Hearing Loss; Humans; Ototoxicity
PubMed: 33757754
DOI: 10.1016/j.bjorl.2021.02.008 -
Advances in Radiation Oncology 2023The aim of this study was to comprehensively review all studies examining clinical outcomes of craniospinal irradiation with proton radiotherapy for medulloblastoma (MB)... (Review)
Review
PURPOSE
The aim of this study was to comprehensively review all studies examining clinical outcomes of craniospinal irradiation with proton radiotherapy for medulloblastoma (MB) to determine whether theoretical dosimetric advantages have translated into superior clinical outcomes (including survival and toxicities) compared with traditional photon-based techniques.
METHODS AND MATERIALS
We performed a systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles reporting on clinical outcomes of pediatric and/or adult patients with MB treated with proton radiotherapy were included. Evidence quality was assessed using a modified Newcastle Ottawa scale and GRADE score.
RESULTS
Thirty-five studies were included, with a total of 2059 patients reported (representing an estimated 630-654 unique patients). None of the studies were randomized, 12 were comparative, 9 were prospective, 3 were mixed, and 22 were retrospective. Average mean/median follow-up was 5.0 years (range, 4 weeks to 12.6 years). The majority of studies (n = 19) reported on treatment with passive scatter proton beams exclusively. Average study quality was 6.0 out of 9 (median, 6; standard deviation, 1.6). Nine studies scored ≥8 out of 9 on the modified Newcastle Ottawa Scale; an overall "moderate" GRADE score was assigned. Well-designed comparative cohort studies with adequate follow-up demonstrate superior neurocognitive outcomes, lower incidence of hypothyroidism (23% vs 69%), sex hormone deficiency (3% vs 19%), greater heights, and reduced acute toxicities in patients treated with protons compared to photons. Overall survival (up to 10 years), progression-free survival (up to 10 years), brain stem injury, and other endocrine outcomes were similar to those reported for photon radiation. There was insufficient evidence to make conclusions on endpoints of quality of life, ototoxicity, secondary malignancy, alopecia, scoliosis, cavernomas, and cerebral vasculopathy.
CONCLUSIONS
Moderate-grade evidence supports proton radiotherapy as a preferred treatment for craniospinal irradiation of MB based on equivalent disease control and comparable-to-improved toxicity versus photon beam radiation therapy.
PubMed: 37008255
DOI: 10.1016/j.adro.2023.101189 -
Revista Da Associacao Medica Brasileira... 2021To present scientific evidence based on a systematic review of the literature (PRISMA), aiming to systematize evidence of the ototoxic effects of hydroxychloroquine...
OBJECTIVE
To present scientific evidence based on a systematic review of the literature (PRISMA), aiming to systematize evidence of the ototoxic effects of hydroxychloroquine (HCQ).
METHODS
The studies were selected using a combination based on the Medical Subject Headings (MeSH). The databases searched were MEDLINE (PubMed), LILACS, SciELO, and BIREME, encompassing articles from January 2010 to May 2020, with no restrictions of language and place of publication.
RESULTS
A total of 148 articles with the potential to be included were retrieved. Of these, two answered the research question, which consisted of seeking evidence of the ototoxic effects of hydroxychloroquine. These studies scored 11 in their quality assessment with the modified protocol by Pithon et al.13.
CONCLUSIONS
The studies reported possible ototoxicity of HCQ. Audiovestibular changes, such as hearing loss, peripheral vestibular syndrome, and tinnitus were evidenced in patients submitted to HCQ. The improvement in the audiological examinations and the regression in the vestibular syndrome after stopping the treatment with HCQ are strong arguments in favor of the ototoxicity caused by this medication. However, there are still divergences about the relationship between ototoxic effects and the use of HCQ.
Topics: Hearing Loss; Humans; Hydroxychloroquine; Ototoxicity
PubMed: 34259762
DOI: 10.1590/1806-9282.67.Suppl1.20200677 -
Therapeutic Drug Monitoring Dec 2023Cisplatin is commonly used to treat solid tumors; however, its use can be complicated by drug-induced hearing loss (ie, ototoxicity). The presence of certain genetic...
BACKGROUND
Cisplatin is commonly used to treat solid tumors; however, its use can be complicated by drug-induced hearing loss (ie, ototoxicity). The presence of certain genetic variants has been associated with the development/occurrence of cisplatin-induced ototoxicity, suggesting that genetic factors may be able to predict patients who are more likely to develop ototoxicity. The authors aimed to review genetic associations with cisplatin-induced ototoxicity and discuss their clinical relevance.
METHODS
An updated systematic review was conducted on behalf of the Canadian Pharmacogenomics Network for Drug Safety, based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 statement. Pharmacogenomic studies that reported associations between genetic variation and cisplatin-induced ototoxicity were included. The evidence on genetic associations was summarized and evaluated, and knowledge gaps that can be used to inform future pharmacogenomic studies identified.
RESULTS
Overall, 40 evaluated reports, considering 47 independent patient populations, captured associations involving 24 genes. Considering GRADE criteria, genetic variants in 2 genes were strongly (ie, odds ratios ≥3) and consistently (ie, replication in ≥3 independent populations) predictive of cisplatin-induced ototoxicity. Specifically, an ACYP2 variant has been associated with ototoxicity in both children and adults, whereas TPMT variants are relevant in children. Encouraging evidence for associations involving several other genes also exists; however, further research is necessary to determine potential clinical relevance.
CONCLUSIONS
Genetic variation in ACYP2 and TPMT may be helpful in predicting patients at the highest risk of developing cisplatin-induced ototoxicity. Further research (including replication studies considering diverse pediatric and adult patient populations) is required to determine whether genetic variation in additional genes may help further identify patients most at risk.
Topics: Adult; Humans; Child; Cisplatin; Antineoplastic Agents; Pharmacogenetics; Ototoxicity; Canada; Acylphosphatase
PubMed: 37726872
DOI: 10.1097/FTD.0000000000001113 -
Otolaryngology--head and Neck Surgery :... Apr 2023To raise awareness of the growing list of non-platinum-based chemo- and immunotherapeutic agents that have been associated with ototoxicity and to introduce the possible...
OBJECTIVE
To raise awareness of the growing list of non-platinum-based chemo- and immunotherapeutic agents that have been associated with ototoxicity and to introduce the possible mechanism of ototoxicity of these agents.
DATA SOURCES
PubMed, Embase, and Web of Science.
REVIEW METHODS
A systematic review was performed following the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-analyses). PubMed, Embase, and Web of Science databases were searched for published reports of ototoxicity from non-platinum-based chemo- and immunotherapeutic agents in adult and pediatric patients. Therapies that utilized any platinum-based agent were excluded.
CONCLUSIONS
Ototoxicity from non-platinum-based chemo- and immunotherapies is an evolving problem. There were 54 reports-39 case reports and 15 cohort studies-documenting ototoxicity from 7 agents/combination therapies. Of these reports, 37 (69%) were published within the last 15 years (after 2005). No recovery of hearing was documented in 21 of 56 cases (38%). Pretreatment audiograms were uncommon (19/54 studies, 35%), despite documented ototoxic associations.
IMPLICATIONS FOR PRACTICE
There is a growing number of novel, ototoxic, non-platinum-based chemo- and immunotherapeutic agents with various potential mechanisms of action. Otolaryngologists will need to prioritize awareness of these agents. This growing list of agents, many of which have reversible effects, suggest a need for standardized ototoxicity monitor protocols so that appropriate and timely management options can be implemented.
Topics: Adult; Child; Humans; Antineoplastic Agents; Cisplatin; Hearing Loss; Ototoxicity; Immunotherapy
PubMed: 35439087
DOI: 10.1177/01945998221094457 -
Journal of Cancer Survivorship :... Feb 2023A cornerstone of treatment for many cancers is the administration of platinum-based chemotherapies and/or ionizing radiation, which can be ototoxic. An accurate... (Review)
Review
PURPOSE
A cornerstone of treatment for many cancers is the administration of platinum-based chemotherapies and/or ionizing radiation, which can be ototoxic. An accurate ototoxicity risk assessment would be useful for counseling, treatment planning, and survivorship follow-up in patients with cancer.
METHODS
This systematic review evaluated the literature on predictive models for estimating a patient's risk for chemotherapy-related auditory injury to accelerate development of computational approaches for the clinical management of ototoxicity in cancer patients. Of the 1195 articles identified in a PubMed search from 2010 forward, 15 studies met inclusion for the review.
CONCLUSIONS
All but 1 study used an abstraction of the audiogram as a modeled outcome; however, specific outcome measures varied. Consistently used predictors were age, baseline hearing, cumulative cisplatin dose, and radiation dose to the cochlea. Just 5 studies were judged to have an overall low risk of bias. Future studies should attempt to minimize bias by following statistical best practices including not selecting multivariate predictors based on univariate analysis, validation in independent cohorts, and clearly reporting the management of missing and censored data. Future modeling efforts should adopt a transdisciplinary approach to define a unified set of clinical, treatment, and/or genetic risk factors. Creating a flexible model that uses a common set of predictors to forecast the full post-treatment audiogram may accelerate work in this area. Such a model could be adapted for use in counseling, treatment planning, and follow-up by audiologists and oncologists and could be incorporated into ototoxicity genetic association studies as well as clinical trials investigating otoprotective agents.
IMPLICATIONS FOR CANCER SURVIVORS
Improvements in the ability to model post-treatment hearing loss can help to improve patient quality of life following cancer care. The improvements advocated for in this review should allow for the acceleration of advancements in modeling the auditory impact of these treatments to support treatment planning and patient counseling during and after care.
Topics: Child; Humans; Adult; Antineoplastic Agents; Prognosis; Ototoxicity; Quality of Life; Cancer Survivors; Neoplasms
PubMed: 36729346
DOI: 10.1007/s11764-022-01315-8 -
The Journal of Antimicrobial... Jul 2024Aminoglycosides (AGs) are important antibiotics in the treatment of Gram-negative sepsis. However, they are associated with the risk of irreversible sensorineural...
BACKGROUND
Aminoglycosides (AGs) are important antibiotics in the treatment of Gram-negative sepsis. However, they are associated with the risk of irreversible sensorineural hearing loss (SNHL). Several genetic variants have been implicated in the development of ototoxicity.
OBJECTIVES
To evaluate the pharmacogenetic determinants of AG-related ototoxicity.
METHODS
This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses and was registered on Prospero (CRD42022337769). In Dec 2022, PubMed, Cochrane Library, Embase and MEDLINE were searched. Included studies were those reporting original data on the effect of the AG-exposed patient's genome on the development of ototoxicity.
RESULTS
Of 10 202 studies, 31 met the inclusion criteria. Twenty-nine studies focused on the mitochondrial genome, while two studied the nuclear genome. One study of neonates found that 30% of those with the m.1555A > G variant failed hearing screening after AG exposure (level 2 evidence). Seventeen additional studies found the m.1555A > G variant was associated with high penetrance (up to 100%) of SNHL after AG exposure (level 3-4 evidence). Nine studies of m.1494C > T found the penetrance of AG-related SNHL to be up to 40%; however, this variant was also identified in those with SNHL without AG exposure (level 3-4 evidence). The variants m.1005T > C and m.1095T > C may be associated with AG-related SNHL; however, further studies are needed.
CONCLUSIONS
This review found that the m.1555A > G and m.1494C > T variants in the MT-RNR1 gene have the strongest evidence in the development of AG-related SNHL, although study quality was limited (level 2-4). These variants were associated with high penetrance of a SNHL phenotype following AG exposure.
Topics: Humans; Aminoglycosides; Ototoxicity; Anti-Bacterial Agents; Pharmacogenetics; Hearing Loss, Sensorineural
PubMed: 38629462
DOI: 10.1093/jac/dkae106 -
The Journal of International Advanced... Mar 2022Nowadays, immunosuppressant drugs are widely used to prevent rejection in organ transplantation and to treat autoimmune diseases. Ototoxicity related to...
BACKGROUND
Nowadays, immunosuppressant drugs are widely used to prevent rejection in organ transplantation and to treat autoimmune diseases. Ototoxicity related to immunosuppressant drugs has been anecdotally reported but scarcely investigated. The aim of this investigation was to systematically review the available data on ototoxicity due to immunosuppressant therapy for transplantation or autoimmune disease.
METHODS
A search of electronic databases (PubMed, Web of Science, and Scopus) was performed in order to identify studies concerning otovestibular toxicity due to immunosuppressant therapy for transplantation or autoimmune disease between January 1980 and November 2020.
RESULTS
Eighteen articles were considered eligible for the review. Totally 131 patients experienced ototoxicity related to immunosuppressive treatment. Hearing loss was the most common clinical manifestation (128 cases) and was mainly bilateral. Tinnitus was reported in 52 cases and vertigo in 2. The immunosuppressant drugs most frequently involved in ototoxic manifestations were calcineurin inhibitors (cyclosporine and tacrolimus), often related to their high serum levels.
CONCLUSION
Immunosuppressant-related ototoxicity is clinically relevant in uncommon but definitely challenging situations. Clinicians should be aware of this and inquire about hearing impairment symptoms during therapy and refer symptomatic patients to an otolaryngologist/audiologist. Further large-scale, prospective investigations are necessary to better characterize the ototoxicity of each class of immunosuppressants.
Topics: Autoimmune Diseases; Hearing Loss; Humans; Immunosuppressive Agents; Ototoxicity; Prospective Studies
PubMed: 35418366
DOI: 10.5152/iao.2022.21416 -
Journal of the Association For Research... Feb 2023Identifying risk factors for tinnitus could facilitate not only the recommendations for prevention measures, but also identifying potential pathways for new... (Meta-Analysis)
Meta-Analysis
AIMS/HYPOTHESIS
Identifying risk factors for tinnitus could facilitate not only the recommendations for prevention measures, but also identifying potential pathways for new interventions. This study reports the first comprehensive systematic review of analytical observational studies able to provide information about causality (i.e., case-control and cohort designs).
METHODS
A literature search of four electronic databases identified epidemiological studies published on tinnitus and different exposures. Independent raters screened all studies, extracted data, and evaluated study quality using the Newcastle-Ottawa Scale. Reported relative risks (RR), hazard ratios (HR), odds ratios (OR), and prevalence ratios (PR) with 95% confidence intervals (CI) were used to compute crude estimates of RR for tinnitus risk factors.
RESULTS
From 2389 records identified, a total of 374 articles were read as full text (24 reviews, 301 cross-sectional studies, 42 cohort studies, and 7 case-control studies). However, from 49 case-control and cohort studies, only 25 adequately reported risk ratios. Using the findings from these studies, positive causal associations were found for various hearing-related factors (i.e., unspecified hearing loss, sensorineural hearing loss, occupational noise exposure, ototoxic platinum therapy, and otitis media). Evidence was also found for a number of non-otological risk factors including temporo-mandibular joint disorder, depression, chronic obstructive pulmonary disease, and hyperlipidemia. Negative associations indicating preventative effects were found for diabetes and high alcohol consumption. No associations were found for low alcohol consumption, body mass index, head injury, heart failure, hypertension, leisure noise exposure, migraine, rheumatoid arthritis, sex, smoking, stroke, and whiplash. However, with the exception of unspecified hearing loss, these findings resulted from pooling no more than 4 studies, illustrating that the vast majority of the associations still remain inconclusive.
CONCLUSIONS
These systematic review and meta-analysis confirm a number of otological and non-otological risk factors for tinnitus. By highlighting major gaps in knowledge, our synthesis can help provide direction for future research that will shed light on the pathophysiology, improve management strategies, and inform more effective preventions.
Topics: Humans; Tinnitus; Cross-Sectional Studies; Hearing Loss; Risk Factors; Hearing Loss, Sensorineural; Observational Studies as Topic
PubMed: 36380120
DOI: 10.1007/s10162-022-00874-y -
Journal of Telemedicine and Telecare Apr 2024Due to the growing burden of disease in South Africa, encompassing conditions such as tuberculosis, human immunodeficiency virus, and cancer, the holistic management of... (Review)
Review
INTRODUCTION
Due to the growing burden of disease in South Africa, encompassing conditions such as tuberculosis, human immunodeficiency virus, and cancer, the holistic management of affected patients incorporating ototoxicity monitoring is a necessity. However, ototoxicity monitoring in developing countries may be limited due to a lack of resources and inadequate healthcare facilities. Subsequently, the use of tele-audiology may be a revolutionary technique with the potential to provide audiology services to under-served populations with limited access.
METHODS
The study aimed to describe the use of tele-audiology services in ototoxicity monitoring through a scoping review of English peer-reviewed articles from June 2009 to June 2020. Seventeen articles were purposively selected from the following databases: PubMed, Science Direct, Taylor and Francis Online, WorldCat, and Google Scholar. Data was extracted as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses diagram and results were analyzed using deductive thematic analysis.
RESULTS AND DISCUSSION
While a minority of the studies indicated that the cost of implementation and network connectivity within a South African context pose as barriers, most researchers reported that tele-audiology provides a reliable, time-efficient, cost-effective, and easily accessible alternative for ototoxicity monitoring. Hardware including the WAHTS, KUDUwave, and OtoID, along with software such as the TabSINT, Otocalc, uHear, and the hearTest, have proven to be useful for ototoxicity monitoring. A need for further investigations regarding the feasibility of tele-audiology implementation in South Africa is evident. Despite this, it provides audiologists with an opportunity to offer contact-less services during COVID-19, thus, confirming its versatility as an augmentative method for ototoxicity monitoring.
Topics: Humans; Audiology; Ototoxicity; COVID-19; PubMed; Software
PubMed: 34989631
DOI: 10.1177/1357633X211068277