Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: Final report of RTOG protocol 90-05
Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: Final report of RTOG protocol 90-05
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DOI：
10.1016/s0360-3016(99)00507-6
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发表时间：
2000-05-01
影响因子：
7
通讯作者：
Farnan, N
中科院分区：
文献类型：
--
作者：
Shaw, E;Scott, C;Farnan, N
目的：为了确定最大耐受剂量的单次放射外科治疗复发的原发性脑肿瘤和脑transferas.Methods和材料：成人大脑或小脑孤立性非脑干肿瘤小于或等于40毫米的最大直径的患者有资格。最大直径≤ 20 mm的肿瘤初始放射外科剂量为18戈伊，2130 mm的肿瘤初始放射外科剂量为15戈伊，31-40 mm的肿瘤初始放射外科剂量为12戈伊。处方剂量为50-90%等剂量线。剂量以3戈伊的增量递增，前提是放射外科手术3个月内不可逆的3级（严重）或任何4级（危及生命）或5级（致命）放射治疗肿瘤组（RTOG）中枢神经系统（CNS）毒性（不可接受的CNS毒性）的发生率< 20%。慢性中枢神经系统毒性也assessed.Results：在1990-1994年，156分析的患者进入，其中36%的人复发原发性脑肿瘤（中位前剂量60戈伊）和64%复发脑转移瘤（中位前剂量30戈伊）。肿瘤最大直径≤ 20 mm、2130 mm和31-40 mm的最大耐受剂量分别为24戈伊、18戈伊和15戈伊。然而，对于< 20 mm的肿瘤，研究人员不愿意将剂量增加到27戈伊，而不是过度毒性，决定了最大耐受剂量。在多变量分析中，最大肿瘤直径是与3级、4级或5级神经毒性风险显著增加相关的一个变量。与< 20 mm的肿瘤相比，21-40 mm的肿瘤发生36级神经毒性的可能性高7.3至16倍。与3-5级神经毒性显著相关的其他变量是肿瘤剂量和Karnofsky体能状态。在放射外科术后6、12、18和24个月，放射性坏死的精确发生率分别为5%、8%、9%和11%。48%的患者在放射外科靶体积内发生肿瘤进展。多变量分析显示两个变量与局部进展风险增加显著相关，即放射外科靶体积进展。原发性脑肿瘤患者（与脑转移瘤患者相比）局部进展的风险高2.85。接受直线加速器治疗的患者（与伽玛刀相比）局部进展的风险高2.84。值得注意的是，61%的伽玛刀治疗的患者复发原发性脑肿瘤相比，30%的患者治疗与直线加速器。结论：单次放射外科治疗的最大耐受剂量为24戈伊，18戈伊，15戈伊的肿瘤小于或等于20 mm，2130 mm，31-40 mm的最大直径为这一人群的患者定义。不可接受的CNS毒性更可能发生在肿瘤较大的患者中，而局部肿瘤控制主要取决于复发肿瘤的类型和治疗单位。(C)2000 Elsevier Science Inc.
Purpose: To determine the maximum tolerated dose of single fraction radiosurgery in patients with recurrent previously irradiated primary brain tumors and brain metastases.Methods and Materials: Adults with cerebral or cerebellar solitary non-brainstem tumors less than or equal to 40 mm in maximum diameter were eligible. Initial radiosurgical doses were 18 Gy for tumors less than or equal to 20 mm, 15 Gy for those 2130 mm, and 12 Gy for those 31-40 mm in maximum diameter. Dose was prescribed to the 50-90% isodose line. Doses were escalated in 3 Gy increments providing the incidence of irreversible grade 3 (severe) or any grade 4 (life threatening) or grade 5 (fatal) Radiation Therapy Oncology Group (RTOG) central nervous system (CNS) toxicity (unacceptable CNS toxicity) was < 20% within 3 months of radiosurgery. Chronic CNS toxicity was also assessed.Results: Between 1990-1994, 156 analyzable patients were entered, 36% of whom had recurrent primary brain tumors (median prior dose 60 Gy) and 64% recurrent brain metastases (median prior dose 30 Gy). The maximum tolerated doses were 24 Gy, 18 Gy, and 15 Gy for tumors less than or equal to 20 mm, 2130 mm, and 31-40 mm in maximum diameter, respectively. However, for tumors < 20 mm, investigators' reluctance to escalate to 27 Gy, rather than excessive toxicity, determined the maximum tolerated dose. In a multivariate analysis, maximum tumor diameter was one variable associated with a significantly increased risk of grade 3, 4, or 5 neurotoxicity. Tumors 21-40 mm were 7.3 to 16 times more likely to develop grade 36 neurotoxicity compared to tumors < 20 mm. Other variables significantly associated with grade 3-5 neurotoxicity were tumor dose and Karnofsky Performance Status. The actuarial incidence of radionecrosis was 5%, 8%, 9%, and 11% at 6, 12, 18, and 24 months following radiosurgery, respectively. Forty-eight percent of patients developed tumor progression within the radiosurgical target volume. A multivariate analysis revealed two variables that were significantly associated with an increased risk of local progression, i.e. progression in the radiosurgical target volume. Patients with primary brain tumors (versus brain metastases) had a 2.85 greater risk of local progression. Those treated on a linear accelerator (versus the Gamma Knife) had a 2.84 greater risk of local progression. Of note, 61 % of Gamma Knife treated patients had recurrent primary brain tumors compared to 30% of patients treated with a linear accelerator.Conclusions: The maximum tolerated doses of single fraction radiosurgery were defined for this population of patients as 24 Gy, 18 Gy, and 15 Gy for tumors less than or equal to 20 mm, 2130 mm, and 31-40 mm in maximum diameter. Unacceptable CNS toxicity was more likely in patients with larger tumors, whereas local tumor control was most dependent on the type of recurrent tumor and the treatment unit. (C) 2000 Elsevier Science Inc.