Trifiletti Daniel M, Lee Cheng-Chia, Schlesinger David, Larner James M, Xu Zhiyuan, Sheehan Jason P
Department of Radiation Oncology, University of Virginia Health System, Charlottesville, Virginia.
Department of Neurosurgery, National Yang-Ming University School of Medicine, Taipei, Taiwan.
Int J Radiat Oncol Biol Phys. 2015 Nov 15;93(4):870-8. doi: 10.1016/j.ijrobp.2015.07.2280. Epub 2015 Jul 29.
Although the use of stereotactic radiosurgery (SRS) in the treatment of multiple brain metastases has increased dramatically during the past decade to avoid the neurocognitive dysfunction induced by whole brain radiation therapy (WBRT), the cumulative neurocognitive effect of numerous SRS sessions remains unknown. Because leukoencephalopathy is a sensitive marker for radiation-induced central nervous system damage, we studied the clinical and dosimetric predictors of SRS-induced leukoencephalopathy.
Patients treated at our institution with at least 2 sessions of SRS for brain metastases from 2007 to 2013 were reviewed. The pre- and post-SRS magnetic resonance imaging sequences were reviewed and graded for white matter changes associated with radiation leukoencephalopathy using a previously validated scale. Patient characteristics and SRS dosimetric parameters were reviewed for factors that contributed to leukoencephalopathy using Cox proportional hazards modeling.
A total of 103 patients meeting the inclusion criteria were identified. The overall incidence of leukoencephalopathy was 29% at year 1, 38% at year 2, and 53% at year 3. Three factors were associated with radiation-induced leukoencephalopathy: (1) the use of WBRT (P=.019); (2) a higher SRS integral dose to the cranium (P=.036); and (3) the total number of intracranial metastases (P=.003).
Our results have established that WBRT plus SRS produces leukoencephalopathy at a much higher rate than SRS alone. In addition, for patients who did not undergo WBRT before SRS, the integral dose was associated with the development of leukoencephalopathy. As the survival of patients with central nervous system metastases increases and as the neurotoxicity of chemotherapeutic and targeted agents becomes established, these 3 potential risk factors will be important to consider.
尽管在过去十年中，立体定向放射外科（SRS）在治疗多发性脑转移瘤方面的应用急剧增加，以避免全脑放射治疗（WBRT）引起的神经认知功能障碍，但多次SRS治疗的累积神经认知效应仍不清楚。由于白质脑病是辐射诱导的中枢神经系统损伤的敏感标志物，我们研究了SRS诱导的白质脑病的临床和剂量学预测因素。
回顾了2007年至2013年在我们机构接受至少2次SRS治疗脑转移瘤的患者。使用先前验证的量表，对SRS前后的磁共振成像序列进行回顾，并对白质变化与放射性白质脑病相关的情况进行分级。使用Cox比例风险模型，回顾患者特征和SRS剂量学参数，以寻找导致白质脑病的因素。
共确定了103名符合纳入标准的患者。白质脑病的总体发生率在第1年为29%，第2年为38%，第3年为53%。三个因素与辐射诱导的白质脑病相关：（1）使用WBRT（P = 0.019）；（2）颅骨的SRS积分剂量较高（P = 0.036）；（3）颅内转移瘤的总数（P = 0.003）。
我们的结果表明，WBRT加SRS产生白质脑病的发生率比单独使用SRS高得多。此外，对于在SRS前未接受WBRT的患者，积分剂量与白质脑病的发生有关。随着中枢神经系统转移瘤患者生存率的提高以及化疗和靶向药物神经毒性的确立，这三个潜在风险因素将是需要考虑的重要因素。
