Nataf François, Schlienger Michel, Lefkopoulos Dimitri, Merienne Louis, Ghossoub May, Foulquier Jean Noel, Deniaud-Alexandre Elisabeth, Mammar Hamid, Meder Jean-François, Turak Baris, Huart Judith, Touboul Emmanuel, Roux François-Xavier
Department of Neurosurgery, Sainte-Anne Hospital, Paris, France.
Int J Radiat Oncol Biol Phys. 2003 Sep 1;57(1):184-95. doi: 10.1016/s0360-3016(03)00445-0.
To evaluate the efficacy and outcome of Linac radiosurgery (RS) as treatment of cerebral arteriovenous malformations (cAVM) in a series of 57 children.
Between 1984 and 2000, we used Linac radiosurgery to treat 792 patients with cAVM. This series included 57 children (7.2%) under the age of 15 years at the time of RS (range = 7-15 years, median = 12 years). We were able to evaluate 49 of the children (86%) by angiography, 21 boys and 28 girls (sex ratio = 0.75). First symptoms were: hemorrhage, 34 patients (69.4%); seizures, 6 patients (12.5%); headache, 6 patients (12.5%); and progressive neurologic deficit, 1 patient (2.1%). Nidus size ranged from 5 to 50 mm (median = 20 mm). Nidus volume ranged from 0.6 to 16 cc (median = 3.5 cc). Patient distribution according to Spetzler-Martin grade was as follows: Grade 1, n = 5 (11%); Grade 2, n = 18 (35%); Grade 3, n = 21 (40%,); Grade 4, n = 5 (14%); and Grade 5, n = 0%. Twenty-seven patients (55.1%) had other treatment before RS: embolization, n = 14 (31.1%); neurosurgery, n = 9 (20.5%); embolization and neurosurgery, n = 3 (6.1%). RS was performed with the system used for adults. Patients were seated in a Betti armchair. Circular 15 MV X-ray minibeams (6 to 20 mm) were delivered in coronal arcs by a GECGR Saturne 43 Linac. Planification and dosimetry were carried out using the Associated Target Methodology and Dosigray TPS dosimetric systems. The dose at the peripheral isodose (50-70%) ranged from 18 to 28 Gy. Median and mean doses were 25 Gy and 23.8 Gy. Mono-isocentric planification was used in 25 patients (53.2%) and multi-isocentric in 24 patients (2 to 5 isocenters). The overall follow-up ranged from 7 to 172 months (mean 40 months, median 34 months).
The overall rate of obliteration (OR) was 30/49 (61.2%). Mean time to obliteration was 34 months (range = 7 to 172 months). OR varied according to nidus size and volume: OR was 80% for nidus <15 mm, 67% for nidus between 15 and 25 mm, and 42% for nidus >25 mm (p = 0.058). OR was 100% for nidus <1 cc, 73% for nidus between 1 and 4 cc, and 40% for nidus of 4 to 10 cc (p = 0.019). OR according to patient gender was 84.2% for boys and 40% for girls. OR according to minimum dose (Dmin) was 44% for Dmin < 15 Gy (p = 0.01), 89% for D min from 15 to 20 Gy, and 100% for Dmin > 20 Gy (p = 0.01). OR was 62% in nonembolized AVM and 58% in previously embolized AVM (NS). OR according to the number of isocenters was 68.2%, 55.6%, 80%, 50%, and 0% for 1, 2, 3, 4, and 5 isocenters, respectively. After multivariate analysis, only Dmin closely correlated with OR (beta = 0.462; SE = 0.244, p = 0.057). Of the 6 patients with seizures before RS, 5 (80%) were seizure-free without medication after RS. One patient died of pneumonia.
Four patients (8.2%) had bleeding after RS at 39, 45, 51, and 59 months. No new neurologic deficit was found during the follow-up period. Twenty-nine patients underwent magnetic resonance imaging. Thirteen patients (44.8%) showed no parenchymal changes. Thirteen patients (44.8%) had Grade 2 changes, that is, T2 hypersignals. Two patients (6.9%) had Grade 3 changes, and 1 patient (3.4%) had Grade 4 "necrosis-like" changes.
In our experience, Linac RS has proven to be a safe and effective method to treat cerebral AVM in children <15 years, whether used alone or in association with embolization and/or neurosurgery.
评估直线加速器放射外科（RS）治疗57例儿童脑动静脉畸形（cAVM）的疗效和结果。
1984年至2000年间，我们使用直线加速器放射外科治疗792例cAVM患者。该系列包括57例在接受RS治疗时年龄小于15岁的儿童（7.2%）（范围=7 - 15岁，中位数=12岁）。我们能够通过血管造影评估其中49例儿童（86%），21例男孩和28例女孩（性别比=0.75）。首发症状为：出血，34例患者（69.4%）；癫痫发作，6例患者（12.5%）；头痛，6例患者（12.5%）；进行性神经功能缺损，1例患者（2.1%）。病灶大小范围为5至50毫米（中位数=20毫米）。病灶体积范围为0.6至16立方厘米（中位数=3.5立方厘米）。根据Spetzler - Martin分级的患者分布如下：1级，n = 5（11%）；2级，n = 18（35%）；3级，n = 21（40%）；4级，n = 5（14%）；5级，n = 0%。27例患者（55.1%）在接受RS治疗前曾接受其他治疗：栓塞，n = 14（31.1%）；神经外科手术，n = 9（20.5%）；栓塞和神经外科手术，n = 3（6.1%）。RS采用成人使用的系统进行。患者坐在Betti扶手椅上。通过GECGR Saturne 43直线加速器在冠状弧中输送圆形15 MV X射线微束（6至20毫米）。使用相关靶区方法和Dosigray TPS剂量测定系统进行计划和剂量测定。外周等剂量线（50 - 70%）处的剂量范围为18至28 Gy。中位数和平均剂量分别为25 Gy和23.8 Gy。25例患者（53.2%）采用单等中心计划，24例患者（2至5个等中心）采用多等中心计划。总体随访时间范围为7至172个月（平均40个月，中位数34个月）。
总体闭塞率（OR）为30/49（61.2%）。平均闭塞时间为34个月（范围=7至172个月）。OR根据病灶大小和体积而有所不同：病灶<15毫米时OR为80%，病灶在15至25毫米之间时为67%，病灶>25毫米时为42%（p = 0.058）。病灶<1立方厘米时OR为100%，病灶在1至4立方厘米之间时为73%，病灶为4至10立方厘米时为40%（p = 0.019）。根据患者性别OR分别为男孩84.2%，女孩40%。根据最小剂量（Dmin），Dmin < 15 Gy时OR为44%（p = 0.01），Dmin为15至20 Gy时为89%，Dmin > 20 Gy时为100%（p = 0.01）。未栓塞的AVM的OR为62%，先前栓塞过的AVM的OR为58%（无显著差异）。根据等中心数量，1、2、3、4和5个等中心的OR分别为68.2%、55.6%、80%、50%和0%。多因素分析后，只有Dmin与OR密切相关（β = 0.462；标准误=0.244，p = 0.057）。RS治疗前有癫痫发作的6例患者中，5例（80%）RS治疗后无需药物治疗即无癫痫发作。1例患者死于肺炎。
4例患者（8.2%）在RS治疗后39、45、51和59个月时发生出血。随访期间未发现新的神经功能缺损。29例患者接受了磁共振成像检查。13例患者（44.8%）未显示实质改变。13例患者（44.8%）有2级改变，即T2高信号。2例患者（6.9%）有3级改变且1例患者（3.4%）有4级“坏死样”改变。
根据我们的经验，直线加速器RS已被证明是治疗15岁以下儿童脑AVM的一种安全有效的方法，无论单独使用还是与栓塞和/或神经外科手术联合使用。
