Pan Charlie C, Eisbruch Avraham, Lee Julia S, Snorrason Rhonda M, Ten Haken Randall K, Kileny Paul R
Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Int J Radiat Oncol Biol Phys. 2005 Apr 1;61(5):1393-402. doi: 10.1016/j.ijrobp.2004.08.019.
To determine the relationship between the radiation dose to the inner ear and long-term hearing loss.
Eligible patients included those receiving curative radiotherapy (RT) for head-and-neck cancer. After enrollment, patients underwent three-dimensional conformal RT planning and delivery (180-200 cGy/fraction) appropriate for their disease site and stage. The inner ear was contoured on axial CT planning images. Dose-volume histograms, as well as the mean and maximal dose for each structure, were calculated. Patients underwent pure tone audiometry at baseline (before treatment) and 1, 6, 12, 24, and 36 months after RT. The threshold level (the greater the value, the more hearing loss) in decibels was recorded for 250, 500, 1000, 2000, 4000, and 8000 Hz. For patients receiving predominantly unilateral RT, the contralateral ear served as the de facto control. The differences in threshold level between the ipsilateral and contralateral ears were calculated, and the temporal pattern and dose-response relation of hearing loss were analyzed using statistical methods that take into account the correlation between two ears in the same subject and repeated, sequential measurements of each subject.
Of the 40 patients enrolled in this study, 35 qualified for analysis. Four patients who received concurrent chemotherapy and RT were analyzed separately. The 31 unilaterally treated patients received a median dose of 47.4 Gy (range, 14.1-68.8 Gy) to the ipsilateral inner ear and 4.2 Gy (range, 0.5-31.3 Gy) to the contralateral inner ear. Hearing loss was associated with the radiation dose received by the inner ear (loss of 210dB was observed in ears receiving >/=45 Gy) and was most appreciable in the higher frequencies (>/=2000 Hz). For a 60-year-old patient with no previous hearing loss in either ear, after receiving 45 Gy, the ipsilateral ear, according to our clinical model, would have a 19.3-dB (95% confidence interval [CI], 15.5-23.0) and 5.4-dB (95% CI, 3.5-7.5) hearing decrement compared with the contralateral ear for 8000 Hz and 1000 Hz, respectively. Age and an initial hearing difference within an ear pair also affected hearing loss. The baseline hearing threshold was inversely related to radiation-induced hearing loss. The degree of hearing loss was dependent on the frequency tested, age, baseline hearing, and baseline difference in hearing between a patient's two ears.
High-frequency (>/=2000 Hz) hearing acuity worsens significantly after RT in a dose-dependent fashion. A larger number of patients needs to be studied to validate these results. This knowledge can be applied to create guidelines regarding future dose limits to the auditory apparatus for patients undergoing head-and-neck RT.
确定内耳辐射剂量与长期听力损失之间的关系。
符合条件的患者包括接受头颈部癌根治性放疗(RT)的患者。入组后,患者接受适合其疾病部位和分期的三维适形RT计划和治疗(180 - 200 cGy/分次)。在内耳的轴向CT计划图像上进行轮廓勾画。计算剂量体积直方图以及每个结构的平均剂量和最大剂量。患者在基线(治疗前)以及RT后1、6、12、24和36个月接受纯音听力测定。记录250、500、1000、2000、4000和8000 Hz处的阈值水平(值越大,听力损失越严重),单位为分贝。对于主要接受单侧RT的患者,对侧耳作为事实上的对照。计算同侧耳和对侧耳之间阈值水平的差异,并使用考虑同一受试者双耳之间相关性以及每个受试者重复、连续测量的统计方法分析听力损失的时间模式和剂量反应关系。
本研究纳入的40例患者中,35例符合分析条件。4例接受同步化疗和RT的患者单独分析。31例接受单侧治疗的患者同侧内耳接受的中位剂量为47.4 Gy(范围,14.1 - 68.8 Gy),对侧内耳接受的剂量为4.2 Gy(范围,0.5 - 31.3 Gy)。听力损失与内耳接受的辐射剂量相关(接受≥45 Gy的耳中观察到210dB的损失),并且在较高频率(≥2000 Hz)最为明显。对于一位双耳既往无听力损失的60岁患者,根据我们的临床模型,接受45 Gy后,同侧耳在8000 Hz和1000 Hz时与对侧耳相比,听力分别下降19.3 dB(95%置信区间[CI],15.5 - 23.0)和5.4 dB(95% CI,3.5 - 7.5)。年龄和一对耳内的初始听力差异也影响听力损失。基线听力阈值与辐射诱导的听力损失呈负相关。听力损失程度取决于测试频率、年龄、基线听力以及患者双耳之间的基线听力差异。
高频(≥2000 Hz)听力敏锐度在RT后以剂量依赖方式显著恶化。需要研究更多患者以验证这些结果。这些知识可用于制定关于未来对头颈部RT患者听觉器官剂量限制的指南。