Sally Cohen-Cutler1, Kenneth Wong2, Victoria Mena3, Kevin Sianto4, Michael A Wright5, Arthur Olch2, Etan Orgel6. 1. Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Los Angeles, California. 2. Keck School of Medicine, University of Southern California, Los Angeles, California; Radiation Oncology Program, Children's Hospital Los Angeles, Los Angeles, California. 3. Department of Physical Medicine and Rehabilitation, Children's Hospital Los Angeles, Los Angeles, California. 4. Radiation Oncology Program, Children's Hospital Los Angeles, Los Angeles, California. 5. University of South Florida Morsani College of Medicine, Tampa, Florida. 6. Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Los Angeles, California; Keck School of Medicine, University of Southern California, Los Angeles, California. Electronic address: eorgel@chla.usc.edu.
Abstract
PURPOSE: Cranial radiation therapy (RT) and cisplatin-based chemotherapy are essential to treating many pediatric cancers but cause significant ototoxicity. The objective of this study is to determine the relationship between the RT dose and the risk of subsequent hearing loss in pediatric patients treated with cisplatin. METHODS AND MATERIALS: This retrospective study of cisplatin-treated pediatric patients examined ototoxicity from cranial RT. Ototoxicity was graded for each ear according to the International Society of Pediatric Oncology (SIOP) consensus ototoxicity scale. The RT dose to the cochlea was calculated using the mean, median, maximum, and minimum dose received to determine the most predictive parameter for hearing loss. Multivariable logistic regression models then examined risk factors for hearing loss. RESULTS: In 96 children (161 ears) treated with RT + cisplatin, the minimum cochlear RT dose was most predictive of hearing loss. A higher cochlear RT dose was associated with increased hearing loss (odds ratio per 10 Gy dose increase = 1.64; P = .043), with an added risk in those receiving an autologous bone marrow transplantation (hazard ratio = 10.47; P < .001). CONCLUSIONS: This research supports further testing of the minimum cochlear RT dose as a more predictive dose parameter for risk of ototoxicity. The cochlear RT dose was additive to the risk of hearing loss from underlying cisplatin-based chemotherapy. Exposure to autologous bone marrow transplantation was the strongest predictor of developing hearing loss, placing these children at particularly high risk for hearing loss across all cochlear doses. Future prospective studies are crucial to further inform RT dose thresholds and minimize the risk of hearing loss in childhood cancer survivors.
PURPOSE: Cranial radiation therapy (RT) and cisplatin-based chemotherapy are essential to treating many pediatric cancers but cause significant ototoxicity. The objective of this study is to determine the relationship between the RT dose and the risk of subsequent hearing loss in pediatric patients treated with cisplatin. METHODS AND MATERIALS: This retrospective study of cisplatin-treated pediatric patients examined ototoxicity from cranial RT. Ototoxicity was graded for each ear according to the International Society of Pediatric Oncology (SIOP) consensus ototoxicity scale. The RT dose to the cochlea was calculated using the mean, median, maximum, and minimum dose received to determine the most predictive parameter for hearing loss. Multivariable logistic regression models then examined risk factors for hearing loss. RESULTS: In 96 children (161 ears) treated with RT + cisplatin, the minimum cochlear RT dose was most predictive of hearing loss. A higher cochlear RT dose was associated with increased hearing loss (odds ratio per 10 Gy dose increase = 1.64; P = .043), with an added risk in those receiving an autologous bone marrow transplantation (hazard ratio = 10.47; P < .001). CONCLUSIONS: This research supports further testing of the minimum cochlear RT dose as a more predictive dose parameter for risk of ototoxicity. The cochlear RT dose was additive to the risk of hearing loss from underlying cisplatin-based chemotherapy. Exposure to autologous bone marrow transplantation was the strongest predictor of developing hearing loss, placing these children at particularly high risk for hearing loss across all cochlear doses. Future prospective studies are crucial to further inform RT dose thresholds and minimize the risk of hearing loss in childhood cancer survivors.
Authors: Arnold C Paulino; Mark Lobo; Bin S Teh; M Fatih Okcu; Michael South; E Brian Butler; Jack Su; Murali Chintagumpala Journal: Int J Radiat Oncol Biol Phys Date: 2010-03-16 Impact factor: 7.038
Authors: R D Kortmann; J Kühl; B Timmermann; U Mittler; C Urban; V Budach; E Richter; N Willich; M Flentje; F Berthold; I Slavc; J Wolff; C Meisner; O Wiestler; N Sörensen; M Warmuth-Metz; M Bamberg Journal: Int J Radiat Oncol Biol Phys Date: 2000-01-15 Impact factor: 7.038
Authors: Penelope R Brock; Kristin R Knight; David R Freyer; Kathleen C M Campbell; Peter S Steyger; Brian W Blakley; Shahrad R Rassekh; Kay W Chang; Brian J Fligor; Kaukab Rajput; Michael Sullivan; Edward A Neuwelt Journal: J Clin Oncol Date: 2012-04-30 Impact factor: 44.544
Authors: Jeany M Rademaker-Lakhai; Mirjam Crul; Lot Zuur; Paul Baas; Jos H Beijnen; Yvonne J W Simis; Nico van Zandwijk; Jan H M Schellens Journal: J Clin Oncol Date: 2006-02-20 Impact factor: 44.544
Authors: T N Trahair; M R Vowels; K Johnston; R J Cohn; S J Russell; K A Neville; S Carroll; G M Marshall Journal: Bone Marrow Transplant Date: 2007-08-27 Impact factor: 5.483
Authors: Roger J Packer; James G Gurney; Judy A Punyko; Sarah S Donaldson; Peter D Inskip; Marilyn Stovall; Yutaka Yasui; Ann C Mertens; Charles A Sklar; H Stacy Nicholson; Lonnie K Zeltzer; Joseph P Neglia; Leslie L Robison Journal: J Clin Oncol Date: 2003-09-01 Impact factor: 50.717