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      Incidencia y factores de riesgo en la ototoxicidad por cisplatino Translated title: Incidence and risk factors of cisplatin-induced ototoxicity

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          Abstract

          RESUMEN: Introducción y objetivos: El cisplatino es uno de los fármacos de uso clínico con mayor ototoxicidad. Controlando los umbrales auditivos de los pacientes en tratamiento, podemos realizar una detección precoz de la hipoacusia y adoptar medidas terapéuticas. Con este trabajo pretendemos evaluar la incidencia y severidad de la hipoacusia por cisplatino en nuestro medio, identificando los principales factores de riesgo. Métodos: Monitorización y registro, en un hospital de tercer nivel, de la pérdida auditiva por cisplatino, en los primeros 100 pacientes enviados por oncología que aceptan el seguimiento audiológico, aplicando la audiometría de alta frecuencia y las otoemisiones acústicas. Resultados: Se trata de una población fundamentalmente adulta, con una edad media de 59 años. De los 70 pacientes tratados sólo con cisplatino un 27% manifestó la aparición o el incremento de su hipoacusia. En los 30 restantes, que además de cisplatino recibieron radioterapia, detectamos afectación auditiva en el 53%. Los efectos ototóxicos del cisplatino son dosis dependiente y más intensos con audición normal. En nuestros resultados, ni el género, ni la edad, ni la presencia de hipoacusia previa, fueron factores estadísticamente significativos en la vulnerabilidad. Conclusiones: La susceptibilidad variable al daño ototóxico, el inicio clínicamente insidioso y su irreversibilidad, justifican la conveniencia de monitorizar la ototoxicidad por cisplatino. Los datos clínicos nos permiten calcular el riesgo medio de una población, aunque no sirvan para predecir lo que le ocurrirá a un paciente en concreto.

          Translated abstract

          SUMMARY: Introduction and objectives: Cisplatin is one of the drugs with greater ototoxicity within clinical use. Hearing loss detection and therapeutic measures can be done in early stages by controlling the auditory thresholds of patients on treatment. With this paper we intend to assess the incidence and severity of hearing loss by cisplatin in our environment, identifying major risk factors. Methods: The case study was conducted on a third level hospital by monitoring and recording the hearing loss by cisplatin among the first 100 patients who accepted the audiologic monitoring. Those patients were sent by the oncology department. Then a high frequency audiometry and the otoacoustic emissions was carried out on the patients to evaluate them. Results: Essentially, we refer to a group which us made up of adults with an average age of 59 years old. Out of the 70 patients treated only with cisplatin, 27% experienced hearing loss. Among the remaining 30 patients who received radiotherapy in addition to cisplatin, hearing impairment at 53% was detected. Cisplatin ototoxic effects are dose-dependent and more intense with normal hearing. In our results, gender, age or the presence of previous hearing loss, were not statistically significant factors in vulnerability. Conclusions: the susceptibility variable to ototoxic damage on patients, the clinically insidious onset of hearing loss and its irreversibility, justify the need to monitor the cisplatin ototoxicity. Clinical data allow us to calculate the risk of an average population, although it does not help to predict what will happen to each patient.

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          Most cited references41

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          Ototoxicity in children receiving platinum chemotherapy: underestimating a commonly occurring toxicity that may influence academic and social development.

          To describe the frequency and severity of ototoxicity in a series of pediatric patients treated with platinum-based chemotherapy. Serial audiologic evaluations were conducted for 67 patients aged 8 months to 23 years who received platinum-based chemotherapy. Audiologic data was analyzed to determine time to hearing-loss using American Speech-Language-Hearing Association (ASHA) criteria, and the effects of treatment and patient characteristics on the incidence and severity of ototoxicity. Bilateral decreases in hearing were seen in 61% of patients (median time to hearing loss, 135 days). Children treated for medulloblastoma, osteosarcoma, and neuroblastoma had greater incidence and severity of hearing loss. Agreement between the usually reported National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) and ASHA criteria was inadequate. Traditional reporting of toxicity data (CTCAE) has under-reported ototoxicity and minimized the significance of hearing loss in children. As pediatric patients experience improved survival, the effects and implications of high-frequency hearing loss with regard to academic achievement and speech and language development are important considerations, especially in patients younger than 5 years.
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            Platinum-induced ototoxicity in children: a consensus review on mechanisms, predisposition, and protection, including a new International Society of Pediatric Oncology Boston ototoxicity scale.

            The platinum chemotherapy agents cisplatin and carboplatin are widely used in the treatment of adult and pediatric cancers. Cisplatin causes hearing loss in at least 60% of pediatric patients. Reducing cisplatin and high-dose carboplatin ototoxicity without reducing efficacy is important. This review summarizes recommendations made at the 42nd Congress of the International Society of Pediatric Oncology (SIOP) in Boston, October 21-24, 2010, reflecting input from international basic scientists, pediatric oncologists, otolaryngologists, oncology nurses, audiologists, and neurosurgeons to develop and advance research and clinical trials for otoprotection. Platinum initially impairs hearing in the high frequencies and progresses to lower frequencies with increasing cumulative dose. Genes involved in drug transport, metabolism, and DNA repair regulate platinum toxicities. Otoprotection can be achieved by acting on several these pathways and generally involves antioxidant thiol agents. Otoprotection is a strategy being explored to decrease hearing loss while maintaining dose intensity or allowing dose escalation, but it has the potential to interfere with tumoricidal effects. Route of administration and optimal timing relative to platinum therapy are critical issues. In addition, international standards for grading and comparing ototoxicity are essential to the success of prospective pediatric trials aimed at reducing platinum-induced hearing loss. Collaborative prospective basic and clinical trial research is needed to reduce the incidence of irreversible platinum-induced hearing loss, and optimize cancer control. Wide use of the new internationally agreed-on SIOP Boston ototoxicity scale in current and future otoprotection trials should help facilitate this goal.
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              Understanding platinum-induced ototoxicity.

              Childhood cancer survival rates are now nearly 80% in more developed European countries because of improved therapies and better supportive care. Platinum chemotherapy drugs, such as cisplatin and carboplatin, are the cornerstone of many effective therapeutic protocols for childhood cancer. However, the antitumor efficacy of cisplatin and carboplatin comes at the cost of ototoxicity, which affects at least 60% of pediatric patients. Although ototoxicity is not life threatening, it can have debilitating effects on patients' quality of life. Recently, many initiatives have been launched with the ultimate goal of reducing cisplatin and high-dose carboplatin ototoxicity without compromising antitumor efficacy. This review addresses the incidence of platinum ototoxicity and its clinical presentation, time course, and early diagnostic evaluation. Genetic and non-genetic risk factors for platinum-associated ototoxicity, and their predictive value, are discussed. Recent developments in the prevention of platinum ototoxicity are also summarized. Copyright © 2013 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                orl
                Revista ORL
                Rev. ORL
                Ediciones Universidad de Salamanca (Salamanca, Salamanca, Spain )
                2444-7986
                September 2021
                : 12
                : 3
                : 217-230
                Affiliations
                [3] Valladolid orgnameHospital Clínico Universitario orgdiv1Sección de Bioestadística de la Unidad de Apoyo a la Investigación España
                [2] Valladolid orgnameHospital Clínico Universitario orgdiv1Servicio de Oncología España
                [1] Valladolid orgnameHospital Clínico Universitario orgdiv1Servicio de ORL y Cirugía de Cabeza y Cuello España
                Article
                S2444-79862021000300002 S2444-7986(21)01200300002
                10.14201/orl.24411
                e27d6612-cc91-41ce-be95-ff4ff9f308dc

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 08 November 2020
                : 11 October 2020
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 41, Pages: 14
                Product

                SciELO Spain

                Categories
                Artículo original

                factores de riesgo,radioterapia,hipoacusia,ototoxicidad,cisplatino,radiotherapy,risk factors,cisplatin,ototoxicity,hearing loss

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