Low early ototoxicity rates for pediatric medulloblastoma patients treated with proton radiotherapy

Radiation Oncology

Anita Mahajan³  Tribhawan S Vats⁵  Paul W Gidley²  Shiao Y Woo⁴  Mary F McAleer³  David R Grosshans³  Jimmy J Philip³  Murali Chintagumpala¹  Benjamin J Moeller³ 

[1] Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX, USA;Department of Head and Neck Surgery, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA;Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA;Department of Radiation Oncology, University of Louisville, Louisville, KY, USA;Department of Pediatrics, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

关键词: ototoxicity;    medulloblastoma;    pediatric;    radiotherapy;    Proton;   

Others  :  1224371
DOI  :  10.1186/1748-717X-6-58

 received in 2011-04-01, accepted in 2011-06-02,  发布年份 2011

【 摘 要 】

Background

Hearing loss is common following chemoradiotherapy for children with medulloblastoma. Compared to photons, proton radiotherapy reduces radiation dose to the cochlea for these patients. Here we examine whether this dosimetric advantage leads to a clinical benefit in audiometric outcomes.

Methods

From 2006-2009, 23 children treated with proton radiotherapy for medulloblastoma were enrolled on a prospective observational study, through which they underwent pre- and 1 year post-radiotherapy pure-tone audiometric testing. Ears with moderate to severe hearing loss prior to therapy were censored, leaving 35 ears in 19 patients available for analysis.

Results

The predicted mean cochlear radiation dose was 30 ⁶⁰Co-Gy Equivalents (range 19-43), and the mean cumulative cisplatin dose was 303 mg/m² (range 298-330). Hearing sensitivity significantly declined following radiotherapy across all frequencies analyzed (P < 0.05). There was partial sparing of mean post-radiation hearing thresholds at low-to-midrange frequencies and, consequently, the rate of high-grade (grade 3 or 4) ototoxicity at 1 year was favorable (5%). Ototoxicity did not correlate with predicted dose to the auditory apparatus for proton-treated patients, potentially reflecting a lower-limit threshold for radiation effect on the cochlea.

Conclusions

Rates of high-grade early post-radiation ototoxicity following proton radiotherapy for pediatric medulloblastoma are low. Preservation of hearing in the audible speech range, as observed here, may improve both quality of life and cognitive functioning for these patients.

【 授权许可】

   
2011 Moeller et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】

• [1]Knight KR, Kraemer DF, Neuwelt EA: Ototoxicity in children receiving platinum chemotherapy: underestimating a commonly occurring toxicity that may influence academic and social development. J Clin Oncol 2005, 23:8588-8596.
• [2]Kolinsky DC, Hayashi SS, Karzon R, Mao J, Hayashi RJ: Late onset hearing loss: a significant complication of cancer survivors treated with Cisplatin containing chemotherapy regimens. J Pediatr Hematol Oncol 2010, 32:119-123.
• [3]Moeller MP: Current state of knowledge: psychosocial development in children with hearing impairment. Ear Hear 2007, 28:729-739.
• [4]Moeller MP, Tomblin JB, Yoshinaga-Itano C, Connor CM, Jerger S: Current state of knowledge: language and literacy of children with hearing impairment. Ear Hear 2007, 28:740-753.
• [5]Stelmachowicz PG, Pittman AL, Hoover BM, Lewis DE, Moeller MP: The importance of high-frequency audibility in the speech and language development of children with hearing loss. Arch Otolaryngol Head Neck Surg 2004, 130:556-562.
• [6]Walker DA, Pillow J, Waters KD, Keir E: Enhanced cis-platinum ototoxicity in children with brain tumours who have received simultaneous or prior cranial irradiation. Med Pediatr Oncol 1989, 17:48-52.
• [7]Weatherly RA, Owens JJ, Catlin FI, Mahoney DH: Enhanced cis-platinum ototoxicity in children. Laryngoscope 1991, 101:917-924.
• [8]Paulino AC, Lobo M, Teh BS, Okcu MF, South M, Butler EB, Su J, Chintagumpala M: Ototoxicity After Intensity-Modulated Radiation Therapy and Cisplatin-Based Chemotherapy in Children with Medulloblastoma. Int J Radiat Oncol Biol Phys 2010.
• [9]Huang E, Teh BS, Strother DR, Davis QG, Chiu JK, Lu HH, Carpenter LS, Mai WY, Chintagumpala MM, South M, et al.: Intensity-modulated radiation therapy for pediatric medulloblastoma: early report on the reduction of ototoxicity. Int J Radiat Oncol Biol Phys 2002, 52:599-605.
• [10]Polkinghorn WR, Dunkel IJ, Souweidane MM, Khakoo Y, Lyden DC, Gilheeney SW, Becher OJ, Budnick AS, Wolden SL: Disease Control and Ototoxicity Using Intensity-Modulated Radiation Therapy Tumor-Bed Boost for Medulloblastoma. Int J Radiat Oncol Biol Phys 2011.
• [11]Merchant TE, Hua CH, Shukla H, Ying X, Nill S, Oelfke U: Proton versus photon radiotherapy for common pediatric brain tumors: comparison of models of dose characteristics and their relationship to cognitive function. Pediatr Blood Cancer 2008, 51:110-117.
• [12]Lee CT, Bilton SD, Famiglietti RM, Riley BA, Mahajan A, Chang EL, Maor MH, Woo SY, Cox JD, Smith AR: Treatment planning with protons for pediatric retinoblastoma, medulloblastoma, and pelvic sarcoma: how do protons compare with other conformal techniques? Int J Radiat Oncol Biol Phys 2005, 63:362-372.
• [13]St Clair WH, Adams JA, Bues M, Fullerton BC, La Shell S, Kooy HM, Loeffler JS, Tarbell NJ: Advantage of protons compared to conventional X-ray or IMRT in the treatment of a pediatric patient with medulloblastoma. Int J Radiat Oncol Biol Phys 2004, 58:727-734.
• [14]Merchant TE, Gould CJ, Xiong X, Robbins N, Zhu J, Pritchard DL, Khan R, Heideman RL, Krasin MJ, Kun LE: Early neuro-otologic effects of three-dimensional irradiation in children with primary brain tumors. Int J Radiat Oncol Biol Phys 2004, 58:1194-1207.
• [15]Hua C, Bass JK, Khan R, Kun LE, Merchant TE: Hearing loss after radiotherapy for pediatric brain tumors: effect of cochlear dose. Int J Radiat Oncol Biol Phys 2008, 72:892-899.
• [16]Moyers MF, Miller DW: Range, range modulation, and field radius requirements for proton therapy of prostate cancer. Technol Cancer Res Treat 2003, 2:445-447.
• [17]Moyers MF, Miller DW, Bush DA, Slater JD: Methodologies and tools for proton beam design for lung tumors. Int J Radiat Oncol Biol Phys 2001, 49:1429-1438.
• [18]Torres MA, Chang EL, Mahajan A, Lege DG, Riley BA, Zhang X, Lii M, Kornguth DG, Pelloski CE, Woo SY: Optimal treatment planning for skull base chordoma: photons, protons, or a combination of both? Int J Radiat Oncol Biol Phys 2009, 74:1033-1039.
• [19]Brock P, Pritchard J, Bellman S, Pinkerton CR: Ototoxicity of high-dose cis-platinum in children. Med Pediatr Oncol 1988, 16:368-369.
• [20]Neuwelt EA, Brock P: Critical need for international consensus on ototoxicity assessment criteria. J Clin Oncol 2010, 28:1630-1632.
• [21]Yock T, Yeap B, Ebb D, MacDonald S, Pulsifer M, Marcus K, Tarbell N: A phase II trial of proton radiotherapy for medulloblastoma: Preliminary results. J Clin Oncol 2010, 28:18s(abstr CRA9507).
• [22]Pittman AL, Stelmachowicz PG: Hearing loss in children and adults: audiometric configuration, asymmetry, and progression. Ear Hear 2003, 24:198-205.