Boiardi Amerigo, Silvani Antonio, Eoli Marica, Lamperti Elena, Salmaggi Andrea, Gaviani Paola, Fiumani Anna, Botturi Andrea, Falcone Chiara, Solari Alessandra, Filippini Graziella, Di Meco Francesco, Broggi Giovanni
Department of Neuro-oncology, Fondazione IRCSS Istituto Neurologico Carlo Besta, Via Celoria 11, Milan, Italy.
J Neurooncol. 2008 May;88(1):105-13. doi: 10.1007/s11060-008-9540-6. Epub 2008 Feb 19.
In this study, the records of 276 adult patients with recurrent glioblastoma (GBM) treated at recurrence at our institution between 2004 and 2006 were reviewed for progression-free survival (PFS), overall survival (OS), and toxicity. At recurrence, all patients underwent systemic treatment with temozolomide (200 mg/sqm on days 1-5 every 28 days) until tumor progression. Patients, whose tumor was judged resectable without risk of adjunctive neurological deficit, underwent a second surgery with or without positioning of a Rickam/Ommaya reservoir. The reservoir was used for locoregional chemotherapy with mitoxantrone. Two hundred seventy-six rGBL patients (pts) were divided into three subgroups: A 161 pts treated only with temozolomide, B 50 pts re-operated-on +temozolomide, and C 65 pts re-operated on + temozolomide + locoregional CHT. For group A, the 6 month PFS and 6 month survival (ST) were 39.3 and 43%, respectively, with a median survival time (mST) of 5 months (range 4-6) and 25% of pts alive at 9 months. For group B, the 6 month PFS and 6 month survivors were 64 and 74.1%, respectively, with a mST of 8 months (range 6-10) and 25% of pts alive at 12 months. For group C, the 6 month PFS and 6 month survivors were 70.7 and 87.7%, respectively, with a mST of 11 months (range 9-13) and 25% of pts alive at 18 months (A vs. B vs. C, log-rank P < 0.001) (B vs. C, P = 0.041) (A vs. B P = 0.009). Cox proportional hazard model was used to obtain Hazard Ratio (HR) for type of treatment corrected by age and time (in months) between diagnosis and first recurrence: second tumor debulking was statistically effective for survival, reducing by 36% the risk of death (HR = 0.64; 0.46-0.89), but the most significant favorable prognostic factor for survival was the local delivery of mitoxantrone which reduced the risk of death to 50% (HR = 0.50; 0.38-0.68).
在本研究中，我们回顾了2004年至2006年间在我院接受复发性胶质母细胞瘤（GBM）复发治疗的276例成年患者的无进展生存期（PFS）、总生存期（OS）和毒性情况。复发时，所有患者均接受替莫唑胺全身治疗（每28天的第1 - 5天，剂量为200mg/m²），直至肿瘤进展。对于那些经判断肿瘤可切除且无辅助神经功能缺损风险的患者，进行了二次手术，术中或未放置Rickam/Ommaya储液囊。该储液囊用于米托蒽醌的局部化疗。276例复发性GBL患者被分为三个亚组：A组161例仅接受替莫唑胺治疗；B组50例接受二次手术 + 替莫唑胺治疗；C组65例接受二次手术 + 替莫唑胺 + 局部化疗。对于A组，6个月的PFS和6个月生存率（ST）分别为39.3%和43%，中位生存时间（mST）为5个月（范围4 - 6个月），9个月时25%的患者存活。对于B组，6个月的PFS和6个月生存率分别为64%和74.1%，mST为8个月（范围6 - 10个月），12个月时25%的患者存活。对于C组，6个月的PFS和6个月生存率分别为70.7%和87.7%，mST为11个月（范围9 - 13个月），18个月时25%的患者存活（A组与B组与C组比较，对数秩检验P < 0.001）（B组与C组比较，P = 0.041）（A组与B组比较，P = 0.009）。采用Cox比例风险模型，通过年龄和诊断与首次复发之间的时间（以月为单位）校正治疗类型，得出风险比（HR）：二次肿瘤减瘤术对生存具有统计学意义，可使死亡风险降低36%（HR = 0.64；0.46 - 0.89），但对生存最显著的有利预后因素是米托蒽醌的局部给药，可使死亡风险降至50%（HR = 0.50；0.38 - 0.68）。
