Foote K D, Friedman W A, Buatti J M, Meeks S L, Bova F J, Kubilis P S
Department of Neurosurgery, University of Florida, Gainesville, USA.
J Neurosurg. 2001 Sep;95(3):440-9. doi: 10.3171/jns.2001.95.3.0440.
The aim of this study was to identify factors associated with delayed cranial neuropathy following radiosurgery for vestibular schwannoma (VS or acoustic neuroma) and to determine how such factors may be manipulated to minimize the incidence of radiosurgical complications while maintaining high rates of tumor control.
From July 1988 to June 1998, 149 cases of VS were treated using linear accelerator radiosurgery at the University of Florida. In each of these cases, the patient's tumor and brainstem were contoured in 1-mm slices on the original radiosurgical targeting images. Resulting tumor and brainstem volumes were coupled with the original radiosurgery plans to generate dose-volume histograms. Various tumor dimensions were also measured to estimate the length of cranial nerve that would be irradiated. Patient follow-up data, including evidence of cranial neuropathy and radiographic tumor control, were obtained from a prospectively maintained, computerized database. The authors performed statistical analyses to compare the incidence of posttreatment cranial neuropathies or tumor growth between patient strata defined by risk factors of interest. One hundred thirty-nine of the 149 patients were included in the analysis of complications. The median duration of clinical follow up for this group was 36 months (range 18-94 months). The tumor control analysis included 133 patients. The median duration of radiological follow up in this group was 34 months (range 6-94 months). The overall 2-year actuarial incidences of facial and trigeminal neuropathies were 11.8% and 9.5%, respectively. In 41 patients treated before 1994, the incidences of facial and trigeminal neuropathies were both 29%, but in the 108 patients treated since January 1994, these rates declined to 5% and 2%, respectively. An evaluation of multiple risk factor models showed that maximum radiation dose to the brainstem, treatment era (pre-1994 compared with 1994 or later), and prior surgical resection were all simultaneously informative predictors of cranial neuropathy risk. The radiation dose prescribed to the tumor margin could be substituted for the maximum dose to the brainstem with a small loss in predictive strength. The pons-petrous tumor diameter was an additional statistically significant simultaneous predictor of trigeminal neuropathy risk, whereas the distance from the brainstem to the end of the tumor in the petrous bone was an additional marginally significant simultaneous predictor of facial neuropathy risk. The overall radiological tumor control rate was 93% (59% tumors regressed, 34% remained stable, and 7.5% enlarged), and the 5-year actuarial tumor control rate was 87% (95% confidence interval [CI] 76-98%). Analysis revealed that a radiation dose cutpoint of 10 Gy compared with more than 10 Gy prescribed to the tumor margin yielded the greatest relative difference in tumor growth risk (relative risk 2.4, 95% CI 0.6-9.3), although this difference was not statistically significant (p = 0.207).
Five points must be noted. 1) Radiosurgery is a safe, effective treatment for small VSs. 2) Reduction in the radiation dose has played the most important role in reducing the complications associated with VS radiosurgery. 3) The dose to the brainstem is a more informative predictor of postradiosurgical cranial neuropathy than the length of the nerve that is irradiated. 4) Prior resection increases the risk of late cranial neuropathies after radiosurgery. 5) A prescription dose of 12.5 Gy to the tumor margin resulted in the best combination of maximum tumor control and minimum complications in this series.
本研究旨在确定与前庭神经鞘瘤(VS或听神经瘤)放射外科手术后迟发性颅神经病变相关的因素,并确定如何操控这些因素以尽量减少放射外科并发症的发生率,同时保持高肿瘤控制率。
1988年7月至1998年6月,佛罗里达大学使用直线加速器放射外科治疗了149例VS患者。在每例患者中,在原始放射外科靶向图像上以1毫米层厚勾勒出患者的肿瘤和脑干轮廓。将所得的肿瘤和脑干体积与原始放射外科计划相结合,生成剂量体积直方图。还测量了各种肿瘤尺寸,以估计将被照射的颅神经长度。患者随访数据,包括颅神经病变证据和影像学肿瘤控制情况,来自一个前瞻性维护的计算机数据库。作者进行了统计分析,以比较由感兴趣的危险因素定义的患者亚组之间治疗后颅神经病变或肿瘤生长的发生率。149例患者中的139例纳入并发症分析。该组临床随访的中位持续时间为36个月(范围18 - 94个月)。肿瘤控制分析包括133例患者。该组放射学随访的中位持续时间为34个月(范围6 - 94个月)。面部和三叉神经病变的总体2年精算发生率分别为11.8%和9.5%。在1994年前治疗的41例患者中,面部和三叉神经病变的发生率均为29%,但在1994年1月以后治疗的108例患者中,这些发生率分别降至5%和2%。对多个危险因素模型的评估表明,脑干的最大辐射剂量、治疗时代(1994年前与1994年或之后相比)以及先前的手术切除都是颅神经病变风险的同时具有信息价值的预测因素。规定给肿瘤边缘的辐射剂量可以替代脑干的最大剂量,预测强度略有损失。脑桥 - 岩骨肿瘤直径是三叉神经病变风险的另一个具有统计学意义的同时预测因素,而从脑干到岩骨中肿瘤末端的距离是面部神经病变风险的另一个边缘显著的同时预测因素。总体放射学肿瘤控制率为93%(59%的肿瘤缩小,34%保持稳定,7.5%增大),5年精算肿瘤控制率为87%(95%置信区间[CI] 76 - 98%)。分析显示,规定给肿瘤边缘10 Gy与超过10 Gy的辐射剂量切点在肿瘤生长风险方面产生了最大的相对差异(相对风险2.4,95% CI 0.6 - 9.3),尽管这种差异无统计学意义(p = 0.207)。
必须注意五点。1)放射外科是治疗小型VS的安全、有效方法。(2)辐射剂量的降低在减少与VS放射外科相关的并发症方面发挥了最重要的作用。(3)与被照射神经的长度相比,脑干的剂量是放射外科后颅神经病变更具信息价值的预测因素。(4)先前的切除增加了放射外科后迟发性颅神经病变的风险。(5)在本系列中,规定给肿瘤边缘12.5 Gy的处方剂量导致了最大肿瘤控制和最小并发症的最佳组合。