Long-term natural history of hemangioblastomas in patients with von Hippel-Lindau disease: implications for treatment
Long-term natural history of hemangioblastomas in patients with von Hippel-Lindau disease: implications for treatment
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DOI：
10.3171/jns.2006.105.2.248
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发表时间：
2006-08-01
影响因子：
4.1
通讯作者：
Oldfield, Edward H.
中科院分区：
文献类型：
--
作者：
Ammerman, Joshua M.;Lonser, Russell R.;Oldfield, Edward H.
Object.在他们的生活过程中，大多数患有von Hippel-Lindau（VHL）病的患者需要治疗小脑，脑干或脊髓的几种可产生血管母细胞瘤。然而，许多肿瘤从未产生症状，不需要治疗。在早期阶段的病变，后来会产生症状，并最终需要治疗的检测将允许早期切除的脊髓，脑干，或小脑的血管母细胞瘤，并可能确定小脑血管母细胞瘤，可以用放射外科治疗前的一个阶段是禁忌的，因为肿瘤的大小或相关的囊肿的存在。为了确定症状发展的预测特征，可能允许VHL疾病患者中较小的症状前血管母细胞瘤的早期治疗，作者回顾并分析了在美国国立卫生研究院随访超过10年的所有VHL疾病患者的系列临床和影像学结果。通过递归分割和回归分析确定了19名患者（10名男性和9名女性;平均年龄32.6 ± 11.6岁）共143例血管母细胞瘤（平均随访时间12.4 ± 1.4年）。成血管细胞瘤位于小脑（68例成血管细胞瘤，48%的患者）、脑干（17例成血管细胞瘤，12%的患者）和脊髓（58例成血管细胞瘤，40%的患者）。尽管几乎所有的血管母细胞瘤（138个病灶，97%的患者）都有可测量的生长，但只有58个（41%的患者）出现症状。血管母细胞瘤呈断续生长。(mean生长期13 ± 15个月，平均静止期25 ± 19个月）。26例（45%）最终产生症状的血管母细胞瘤在最初的MR成像研究中并不明显。根据部位，血管母细胞瘤的大小和/或肿瘤和囊肿的生长速度预测症状的发展和治疗的需要（p < 0.05）。小脑血管母细胞瘤的生长速度超过112 mm（3）/月或大于69 mm（3），并且相关肿瘤和囊肿的生长速度超过14 mm（3）/月，则出现症状（敏感性100%，特异性72%）。脑干血管母细胞瘤大于245 mm（3）且生长速率大于0.1 mm（3）/月时出现症状（敏感性75%，特异性89%）。大于22 mm的脊髓血管母细胞瘤（3例）出现症状（敏感性79%，特异性94%）。因为血管母细胞瘤表现出一种口吃的生长模式，经常保持无症状，并且不需要长时间的治疗，不合格的放射学进展不是治疗的指征。仅根据放射学进展决定干预个体肿瘤将导致在10年研究期间每位患者约4次额外手术。提供了肿瘤大小和/或肿瘤和囊肿生长速率的阈值，可用于预测症状形成和未来治疗需求。
Object. In the course of their lives most patients with von Hippel-Lindau (VHL) disease require treatment for several symptom-producing hemangioblastomas of the cerebellum, brainstem, or spinal cord. However, many tumors never produce symptoms and do not require treatment. Detection at an early stage of lesions that will later produce symptoms and ultimately require treatment would allow for earlier excision of hemangioblastomas of the spinal cord, brainstem, or cerebellum, and may identify cerebellar hemangioblastomas that can be treated with radiosurgery at a stage before treatment is contraindicated because of tumor size or the presence of an associated cyst.Methods. To identify features predictive of symptom development that might allow for earlier treatment of smaller, presymptomatic hemangioblastomas in patients with VHL disease, the authors reviewed and analyzed the serial clinical and imaging findings in all patients with VHL disease who were followed up at the National Institutes of Health for more than 10 years. Features predictive of symptom formation were determined by recursive partition and regression analyses.Nineteen patients (10 men and nine women; mean age 32.6 +/- 11.6 years) harboring a total of 143 hemangioblastomas were identified (mean follow-up duration 12.4 +/- 1.4 years). Hemangioblastomas were located in the cerebellum (68 hemangioblastomas, 48% of patients), brainstem (17 hemangioblastomas, 12% of patients), and spinal cord (58 hemangioblastomas, 40% of patients). Despite measurable growth in almost all hemangioblastomas (138 lesions, 97% of patients), only 58 (41% of patients) became symptomatic. Hemangioblastomas grew in a stuttering pattern. (mean growth period 13 +/- 15 months, mean quiescent period 25 +/- 19 months). Twenty-six (45%) of the hemangioblastomas that eventually produced symptoms were not among the tumors that were apparent on the initial MR imaging study. Depending on location, the hemangioblastoma size and/or tumor and cyst growth rates predicted symptom development and the need for treatment (p < 0.05). Cerebellar hemangioblastomas growing faster than 112 mm(3)/month or larger than 69 mm(3) with associated tumor and cyst growth rates greater than 14 mm(3)/month became symptomatic (100% sensitivity, 72% specificity). Brainstem hemangioblastomas larger than 245 mm(3) with growth rates greater than 0.1 mm(3)/month became symptomatic (75% sensitivity, 89% specificity). Spinal hemangioblastomas larger than 22 mm(3) became symptomatic (79% sensitivity, 94% specificity).Conclusions. Because hemangioblastomas exhibit a stuttering growth pattern, frequently remain asymptomatic, and do not require treatment for long intervals, unqualified radiographic progression is not an indication for treatment. Basing the decision to intervene in individual tumors solely on radiographic progression would have resulted in approximately four additional procedures per patient during the 10-year study period. Threshold values are presented for tumor size and/or tumor and cyst growth rates that can be used to predict symptom formation and future need for treatment.