六、小结

LGG治疗方案的争议主要在于:①手术的时机,即采取积极的早期手术还是观察和延期手术,特别是位于功能区的肿瘤;②肿瘤分子病理对预后和放、化疗的指导意义;③术后放疗的指证和时机;④替莫唑胺化疗对LGG的确切作用和疗效,是否可以替代放疗;⑤联合放、化疗对高风险患者的意义。遗憾的是,因为LGG的自然病史较长、决定预后的因素众多,相应的Ⅲ期临床随机对照试验难以组织和实施,目前尚缺少确凿的Ⅰ级循证医学证据。相对于各种治疗手段而言,LGG患者的整体预后更取决于患者和肿瘤的自身特点,如患者年龄、神经功能状态、肿瘤大小和组织学类型等;今后还有可能进一步明确各种影像学和分子病理学的预后因素。LGG患者治疗方案的制定需要权衡治疗获益与可能发生并发症之间的得失,特别需要考虑到患者的生活质量,实现“功能性”的肿瘤最大程度切除和术后治疗的个体化原则。

图1-4 LGG建议治疗方案

我们建议LGG的治疗策略如图1-4所示,需要指出的是,对于功能区的LGG,特别是无明显症状和体征或癫痫症状经药物治疗控制良好者,有必要向患者本人和家属详细交代延迟手术和早期手术两种方案的利弊,根据患者和家属的理解程度以及对手术治疗的预期,结合手术者的经验和患者的各种预后因素,制定个体化的治疗方案;而在不具备术前DTI和fMRI检查或术中脑皮质功能描记等定位手段时建议保守治疗,予以观察和间隔3~6个月的MRI检查随访。

(万峰)

参考文献

1.Ruiz J,Lesser GJ.Low-grade gliomas.Curr Treat Options Oncol,2009,10(3-4):231-242

2.Central Brain Tumor Registry of the United States:Statistical Report:Primary Brain Tumors in the United States,2000-2004.Available at http://www.cbtrus.org/reports//2007-2008/2007report.pdf.Accessed February 2010

3.Shaw E,Arusell R,Scheithauer B,et al.Prospective randomized trial of low- versus high-dose radiation therapy in adults with supratentorial low-grade glioma:initial report of a North Central Cancer Treatment Group/Radiation Therapy Oncology Group/Eastern Cooperative Oncology Group study.J Clin Oncol,2002,20(9):2267-2276

4.Duffau H,Capelle L.Preferential brain locations of low-grade gliomas.Cancer,2004,100(12):2622-2626

5.Pignatti F,den Bent M v,Curran D,et al.Prognostic factors for survival in adult patients with cerebral low-grade glioma.J Clin Oncol,2002,20(8):2076-2084

6.Pouratian N,Schiff D.Management of low-grade glioma.Curr Neurol Neurosci Rep,2010,10(3):224-231

7.Whittle IR.What is the place of conservative management for adult supratentorial low-grade glioma.Adv Tech Stand Neurosurg,2010,35:65-79

8.Lwin Z,Gan HK,Mason WP.Low-grade oligodendroglioma:current treatments and future hopes.Expert Rev Anticancer Ther,2009,9(11):1651-1661

9.Chambless LBMD,Thompson RCMD.Low-grade Gliomas:Current Concepts and Controversies.Neurosurgery Quarterly,2010,20(3):173-179

10.Brasil CG,Ciccarelli O,Altmann DR,et al.Low-grade gliomas:six-month tumor growth predicts patient outcome better than admission tumor volume,relative cerebral blood volume,and apparent diffusion coefficient.Radiology,2009,253(2):505-512

11.Hlaihel C,Guilloton L,Guyotat J,et al.Predictive value of multimodality MRI using conventional,perfusion,and spectroscopy MR in anaplastic transformation of low-grade oligodendrogliomas.J Neurooncol,2010,97(1):73-80

12.Scott JN,Brasher PM,Sevick RJ,et al.How often are nonenhancing supratentorial gliomas malignant? A population study.Neurology,2002.59(6):947-949

13.Bauman G,Lote K,Larson D,et al.Pretreatment factors predict overall survival for patients with low-grade glioma:a recursive partitioning analysis.Int J Radiat Oncol Biol Phys,1999,45(4):923-929

14.Claus EB,Black PM.Survival rates and patterns of care for patients diagnosed with supratentorial low-grade gliomas:data from the SEER program,1973-2001.Cancer,2006,106(6):1358-1363

15.Chang EF,Smith JS,Chang SM,et al.Preoperative prognostic classification system for hemispheric low-grade gliomas in adults.J Neurosurg,2008,109(5):817-824

16.Bauman G,Fisher B,Watling C,et al.Adult supratentorial low-grade glioma:long-term experience at a single institution.Int J Radiat Oncol Biol Phys,2009,75(5):1401-1407

17.Schiff D,Brown PD,Giannini C.Outcome in adult low-grade glioma:the impact of prognostic factors and treatment.Neurology,2007,69(13):1366-1373

18.Pouratian N,Mut M,Jagannathan J,et al.Low-grade gliomas in older patients:a retrospective analysis of prognostic factors.J Neurooncol,2008,90(3):341-350

19.Schomas DA,Laack NN,Brown PD.Low-grade gliomas in older patients:long-term follow-up from Mayo Clinic.Cancer,2009,115(17):3969-3978

20.Pallud J,Mandonnet E,Duffau H,et al.Prognostic value of initial magnetic resonance imaging growth rates for World Health Organization grade Ⅱ gliomas.Ann Neurol,2006,60(3):380-383

21.Duffau H,Lopes M,Arthuis F,et al.Contribution of intraoperative electrical stimulations in surgery of low grade gliomas:a comparative study between two series without(1985-1996)and with(1996-2003)functional mapping in the same institution.J Neurol Neurosurg Psychiatry,2005,76(6):845-851

22.Berger MS,Deliganis AV,Dobbins J,et al.The effect of extent of resection on recurrence in patients with low grade cerebral hemisphere gliomas.Cancer,1994,74(6):1784-1791

23.Janny P,Cure H,Mohr M,et al.Low grade supratentorial astrocytomas.Management and prognostic factors.Cancer,1994,73(7):1937-1945

24.Duffau H.Surgery of low-grade gliomas:towards a ‘functional neurooncology’.Curr Opin Oncol,2009,21(6):543-549

25.Sanai N,Polley MY,Berger MS.Insular glioma resection:assessment of patient morbidity,survival,and tumor progression.J Neurosurg,2010,112(1):1-9

26.Robles SG,Gatignol P,Lehericy S,et al.Long-term brain plasticity allowing a multistage surgical approach to World Health Organization Grade II gliomas in eloquent areas.J Neurosurg,2008,109(4):615-624

27.Smith JS,Chang EF,Lamborn KR,et al.Role of extent of resection in the long-term outcome of low-grade hemispheric gliomas.J Clin Oncol,2008,26(8):1338-1345

28.McGirt MJ,Chaichana KL,Attenello FJ,et al.Extent of surgical resection is independently associated with survival in patients with hemispheric infiltrating low-grade gliomas.Neurosurgery,2008,63(4):700-7,author reply 707-708

29.Teixidor P,Gatignol P,Leroy M,et al.Assessment of verbal working memory before and after surgery for lowgrade glioma.J Neurooncol,2007,81(3):305-313

30.Kesari S,Schiff D,Drappatz J,et al.Phase Ⅱ study of protracted daily temozolomide for low-grade gliomas in adults.Clin Cancer Res,2009,15(1):330-337

31.Zhao S,Lin Y,Xu W,et al.Glioma-derived mutations in IDH1 dominantly inhibit IDH1 catalytic activity and induce HIF-1alpha.Science(80- ),2009,324(5924):261-265

32.Ichimura K,Pearson DM,Kocialkowski S,et al.IDH1 mutations are present in the majority of common adult gliomas but rare in primary glioblastomas.Neuro Oncol,2009,11(4):341-347

33.Sanson M,Marie Y,Paris S,et al.Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas.J Clin Oncol,2009,27(25):4150-4154

34.den Bent MJ v,Afra D,de Witte O,et al.Long-term efficacy of early versus delayed radiotherapy for low-grade astrocytoma and oligodendroglioma in adults:the EORTC 22845 randomised trial.Lancet,2005,366(9490):985-990

35.Baumert BG,Stupp R.Low-grade glioma:a challenge in therapeutic options:the role of radiotherapy.Ann Oncol,2008,19 Suppl 7:vii217-22

36.Douw L,Klein M,Fagel SS,et al.Cognitive and radiological effects of radiotherapy in patients with low-grade glioma:long-term follow-up.Lancet Neurol,2009,8(9):810-818

37.Baumert BG,Stupp R.Is there a place for radiotherapy in low-grade gliomas.Adv Tech Stand Neurosurg,2010,35:159-182

38.Kaloshi G,Benouaich-Amiel A,Diakite F,et al.Temozolomide for low-grade gliomas:predictive impact of 1p/19q loss on response and outcome.Neurology,2007,68(21):1831-1836

39.Pouratian N,Gasco J,Sherman JH,et al.Toxicity and efficacy of protracted low dose temozolomide for the treatment of low grade gliomas.J Neurooncol,2007,82(3):281-288

40.Liu R,Solheim K,Polley MY,et al.Quality of life in low-grade glioma patients receiving temozolomide.Neuro Oncol,2009,11(1):59-68

41.Duffau H,Taillandier L,Capelle L.Radical surgery after chemotherapy:a new therapeutic strategy to envision in grade Ⅱ glioma.J Neurooncol,2006,80(2):171-176