Santoni R, Liebsch N, Finkelstein D M, Hug E, Hanssens P, Goitein M, Smith A R, O'Farrell D, Efird J T, Fullerton B, Munzenrider J E
Department of Radiation Oncology, Massachusetts General Hospital, Boston 02114, USA.
Int J Radiat Oncol Biol Phys. 1998 Apr 1;41(1):59-68. doi: 10.1016/s0360-3016(98)00031-5.
To determine the temporal lobe (TL) damage rate in 96 patients treated with high-dose proton and photon irradiation for chordomas and chondrosarcomas of the base of the skull.
The records of 96 consecutive patients treated at Massachusetts General Hospital (MGH) and Harvard Cyclotron Laboratory (HCL) between June 1984 and 1993, for chordomas and chondrosarcomas of the base of the skull were reviewed. All the patients had undergone some degree of resection of the tumor prior to radiation therapy. Seventy-five patients were classified as "primary tumors" and 21 as recurrent or regrowing tumors after one or more surgical procedures. All the patients were randomized to receive 66.6 or 72 cobalt Gray equivalent (CGE) on a prospective dose-searching study by proton and photon irradiation (Radiation Therapy Oncology Group #85-26) with conventional fractionation (1.8 CGE/day, 5 fractions/week). All treatments were planned using the three-dimensional (3D) planning system developed at the Massachusetts General Hospital, and the dose was delivered using opposed lateral fields for the photon component and a noncoplanar isocentric technique for the proton component. Clinical symptoms of TL damage were classified into 4 grades. Computerized tomography (CT) and magnetic resonance imaging (MRI) scans were evaluated for white matter changes. Abnormalities associated with persistent or recurrent tumor were distinguished from radiation-induced changes. TLs were delineated on the original scans of the 10 patients with damage and those of a group of 33 patients with no clinical or MRI evidence of injury. Dose distributions were calculated and dose-volume histograms were obtained for these patients.
Of the patients, 10 developed TL damage, with bilateral injury in 2 and unilateral injury in 8. The cumulative TL damage incidence at 2 and 5 years was 7.6 and 13.2%, respectively. The MRI areas suggestive of TL damage were always separated from the tumor bed. Symptoms were severe to moderate in 8 patients. Several baseline factors, tumor- or host-related, were analyzed to evaluate their predictivity for TL damage: age, gender, tumor site, histology, type of presentation, type and number of surgical procedures, primary tumor volume, prescribed dose, normal tissue involvement, and volume of TL receiving doses ranging between 10 and 50 CGE or more. Only gender, in a univariate analysis (log rank) was a significant predictor of damage (0.0155), with male patients being at significantly higher risk of TL injury. In a stepwise Cox regression that included gender as a variable, no other baseline variable improved the prediction of damage.
The 2- and 5-year cumulative TL damage rates were 7.6 and 13.2%, respectively. Despite the different TL damage rates related to age, tumor volume, number of surgical procedures prior to radiation therapy, and prescribed doses to the tumor, only gender was a significant predictor of damage (p = 0.0155) using a univariate (log rank) test. Chordomas and chondrosarcomas of the base of the skull may represent an interesting model to evaluate the TL damage rates because of their extradural origin, displacing the white matter instead of infiltrating it as gliomas do, because of their longer local recurrence-free survival other than gliomas and other brain tumors and because of the high doses of irradiation delivered to the target volume to obtain local control.
确定96例接受高剂量质子和光子照射治疗颅底脊索瘤和软骨肉瘤患者的颞叶(TL)损伤率。
回顾了1984年6月至1993年间在马萨诸塞州总医院(MGH)和哈佛回旋加速器实验室(HCL)接受治疗的96例连续患者的记录,这些患者患有颅底脊索瘤和软骨肉瘤。所有患者在放疗前均接受了一定程度的肿瘤切除术。75例患者被归类为“原发性肿瘤”,21例为经过一次或多次手术治疗后的复发或再生长肿瘤。所有患者通过质子和光子照射(放射治疗肿瘤学组#85-26)进行前瞻性剂量探索研究,随机接受66.6或72钴格雷当量(CGE),采用常规分割(1. .8 CGE/天,每周5次分割)。所有治疗计划均使用马萨诸塞州总医院开发的三维(3D)计划系统,光子部分使用对侧野照射,质子部分使用非共面等中心技术给予剂量。TL损伤的临床症状分为4级。对计算机断层扫描(CT)和磁共振成像(MRI)扫描评估白质变化。将与持续性或复发性肿瘤相关的异常与辐射诱导的变化区分开来。在10例有损伤的患者以及一组33例无临床或MRI损伤证据的患者的原始扫描上勾勒出TL。计算这些患者的剂量分布并获得剂量体积直方图。
患者中,10例发生TL损伤,2例为双侧损伤,8例为单侧损伤。2年和5年时TL累积损伤发生率分别为7.6%和13.2%。MRI上提示TL损伤的区域总是与肿瘤床分开。8例患者症状为重度至中度。分析了几个与肿瘤或宿主相关的基线因素,以评估它们对TL损伤的预测性:年龄、性别、肿瘤部位、组织学、表现类型、手术类型和数量、原发性肿瘤体积、规定剂量、正常组织受累情况以及接受10至50 CGE或更高剂量的TL体积。在单因素分析(对数秩检验)中,只有性别是损伤的显著预测因素(0.0155),男性患者发生TL损伤的风险显著更高。在将性别作为变量的逐步Cox回归中,没有其他基线变量能改善对损伤的预测。
2年和5年时TL累积损伤率分别为7.6%和13.2%。尽管与年龄、肿瘤体积、放疗前手术次数以及肿瘤规定剂量相关的TL损伤率有所不同,但在单因素(对数秩)检验中,只有性别是损伤的显著预测因素(p = 0.0155)。颅底脊索瘤和软骨肉瘤可能是评估TL损伤率的一个有趣模型,因为它们起源于硬膜外,不像胶质瘤那样浸润白质而是推移白质,因为它们的局部无复发生存期比胶质瘤和其他脑肿瘤更长,还因为为了实现局部控制而向靶体积给予了高剂量照射。