Low level of microsatellite instability in paediatric malignant astrocytomas

Aim: Microsatellite instability (MSI) has been proposed as a possible mechanism in the development of cancer. The aim of the current study was to determine whether MSI is involved in the pathogenesis of paediatric malignant astrocytomas. Methods: We screened a cohort of 126 high‐grade astrocytoma samples for MSI using a sensitive and precise method of DNA analysis including a panel of five mononucleotide repeats, in combination with immunohistochemistry for DNA mismatch repair (MMR) proteins. Results: We identified low level of MSI (MSI‐L) in four of 126 (3.2%) paediatric malignant astrocytic tumours. To analyse the molecular profile associated with MSI‐L positive tumours, we performed immunohistochemistry for protein expression of hMSH6 and p53 as well as mutational analysis of the K‐ras gene. In MSI‐L paediatric malignant astrocytic tumours we detected retained nuclear expression of hMSH6 protein and strong nuclear accumulation of p53 protein indicating possible mutations of TP53. There was no correlation between K‐ras mutational status and frequency of MSI in this patient population. Conclusion: Our results suggest that the MSI‐L phenotype is associated with p53 accumulation and/or mutations. However, this represents only a small subgroup of paediatric gliomas with possible distinct biological features, and the deficiencies of DNA MMR genes do not play a main role in the tumourigenesis of the majority of paediatric malignant astrocytomas.     

Molecular biology of adult gliomas: some landmarks for neurosurgeons

BACKGROUND AND PURPOSE: Recent developments in molecular biology have provided the clinician with opportunities to investigate a number of new biomarkers. This has led to an abundant literature reporting the biological role, the relation to survival, and the predictive value of treatment responses in adult glioma patients. Consequently, the clinician must assimilate a large amount of information, raising the question of the genuine role of these biomarkers in the daily care of these patients. METHODS: The authors report the data on biomarkers from the literature relevant to this context. DISCUSSION: Molecular biology today sheds new and valuable light on the natural history of adult glioma, bringing to the forefront a number of therapeutic principles for glioma patients as a group. However, each of these biomarkers does not have sufficient power to amount to a criterion for individual patient therapeutics. CONCLUSIONS: Biomarkers are not pertinent today for decision making, but the authors believe that the principle of including this approach in adult glioma workups must be encouraged as a promising means of study in the years to come.     

Does high‐dose carmustine increase overall survival in supratentorial high‐grade malignant glioma? An EBMT retrospective study

Radiotherapy plus concomitant and adjuvant temozolomide have demonstrated improved survival for glioblastoma. However, prognosis remains poor. High-doses chemotherapy with carmustine is another way to improve response and survival by increasing the dose delivered. Myelotoxicity imposes autologous stem cell rescue. European Group for Blood and Marrow Transplantation experience of this treatment in patients with high-grade glioma was reported here. A retrospective analysis of 217 patients from European Group for Blood and Marrow Transplantation database was realized. Ninety-six patients underwent complete surgical resection while the 121 others had partial resection or only biopsy and were evaluable for an antitumor effect. Patients received 800 mg/m2 of carmustine intravenously at least 1 month after neurosurgery. Forty-eight to 72 hr after chemotherapy, 108 patients received autologous hematopoietic stem cells from bone marrow harvest and 109 patients autologous hematopoietic stem cells from peripheral blood. Radiotherapy was started approximately 40 days after transplantation. Ten deaths were related to the treatment. Of the 121 patients evaluable for tumor response, 64 (53%) presented an objective response. This protocol appear feasible, but with toxicity-related mortality of 4.5%. Median overall survival was 20 months and median time to treatment failure was 7 months. Overall survival and time to treatment were correlated with age, quality of resection and histological subtypes. In glioblastoma multiforme, age and surgery quality appeared to be prognostic factors. Compared with Stupp et al.'s recent study, this study did not favor high-dose carmustine for patients with glioblastoma multiforme with complete surgical resection.     

Characterization and clinical implications of different malignant transformation patterns in diffuse low-grade gliomas

Malignant transformation (MT) of low-grade gliomas (LGGs) to a higher-grade variant seems inevitable, yet it remains unclear which LGG patients will progress to grade 3 or even directly to grade 4 after receiving a long course of treatment. To elucidate this, we conducted a retrospective cohort study based on 229 adults with recurrent LGG. Our study aimed to disclose the characteristics of different MT patterns and to build predictive models for patients with LGG. Patients were allocated into group 2–2 (n = 81, 35.4%), group 2–3 (n = 91, 39.7%), and group 2–4 (n = 57, 24.9%), based on their MT patterns. Patients who underwent MT showed lower Karnofsky performance scale (KPS) scores, larger tumor sizes, smaller extents of resection (EOR), higher Ki-67 indices, lower rates of 1p/19q codeletion, but higher rates of subventricular involvement, radiotherapy, chemotherapy, astrocytoma, and post-progression enhancement (PPE) compared with those in group 2–2 (p < 0.01). On multivariate logistic regression, 1p/19q codeletion, Ki-67 index, radiotherapy, EOR, and KPS score were independently associated with MT (p < 0.05). Survival analyses demonstrated that patients in group 2–2 had the longest survival, followed by group 2–3 and then group 2–4 (p < 0.0001). Based on these independent parameters, we constructed a nomogram model that exhibited superior potential (sensitivity: 0.864, specificity: 0.814, and accuracy: 0.843) compared with PPE in early prediction of MT. Combining the factors of 1p/19q codeletion, Ki-67 index, radiotherapy, EOR, and KPS score that were presented at initial diagnosis could precisely forecast the subsequent MT patterns of patients with LGG.     

A comparative study of short‐ and long‐TE 1H MRS at 3 T for in vivo detection of 2‐hydroxyglutarate in brain tumors

2‐Hydroxyglutarate (2HG) is produced in gliomas with mutations of isocitrate dehydrogenase (IDH) 1 and 2. The ¹H resonances of the J‐coupled spins of 2HG are extensively overlapped with signals from other metabolites. Here, we report a comparative study at 3 T of the utility of the point‐resolved spectroscopy sequence with a standard short TE (35 ms) and a long TE (97 ms), which had been theoretically designed for the detection of the 2HG 2.25‐ppm resonance. The performance of the methods is evaluated using data from phantoms, seven healthy volunteers and 22 subjects with IDH‐mutated gliomas. The results indicate that TE = 97 ms provides higher detectability of 2HG than TE = 35 ms, and that this improved capability is gained when data are analyzed with basis spectra that include the effects of the volume localizing radiofrequency and gradient pulses. Copyright © 2013 John Wiley & Sons, Ltd.     

Validation of a semi‐automatic co‐registration of MRI scans in patients with brain tumors during treatment follow‐up

There is an expanding research interest in high‐grade gliomas because of their significant population burden and poor survival despite the extensive standard multimodal treatment. One of the obstacles is the lack of individualized monitoring of tumor characteristics and treatment response before, during and after treatment. We have developed a two‐stage semi‐automatic method to co‐register MRI scans at different time points before and after surgical and adjuvant treatment of high‐grade gliomas. This two‐stage co‐registration includes a linear co‐registration of the semi‐automatically derived mask of the preoperative contrast‐enhancing area or postoperative resection cavity, brain contour and ventricles between different time points. The resulting transformation matrix was then applied in a non‐linear manner to co‐register conventional contrast‐enhanced T₁‐weighted images. Targeted registration errors were calculated and compared with linear and non‐linear co‐registered images. Targeted registration errors were smaller for the semi‐automatic non‐linear co‐registration compared with both the non‐linear and linear co‐registered images. This was further visualized using a three‐dimensional structural similarity method. The semi‐automatic non‐linear co‐registration allowed for optimal correction of the variable brain shift at different time points as evaluated by the minimal targeted registration error. This proposed method allows for the accurate evaluation of the treatment response, essential for the growing research area of brain tumor imaging and treatment response evaluation in large sets of patients. Copyright © 2016 John Wiley & Sons, Ltd.     

扣带回胶质瘤的临床特点及其锁孔手术治疗

目的分析总结扣带回胶质瘤的临床特点及其锁孔入路治疗的临床效果和意义。方法回顾性分析天坛医院神经外科2001年1月至2003年12月收治的31例扣带回胶质瘤病例,归纳总结其临床特点、肿瘤影像学表现和病理学特点,并对手术效果进行分析。结果患者均以癫痫发作为首发症状,肿瘤局限于扣带回内生长,病理学上均为低级别胶质瘤(WHO分级Ⅱ级)。全部病例均采用经纵裂锁孔手术入路,手术全切除25例,近全切除6例。全部病例术后癫痫症状缓解,术后一过性对侧肢体偏瘫3例,无手术死亡。平均随访26个月,无术后复发。结论扣带回胶质瘤以癫痫发作为常见首发症状,生长方式局限于扣带回,均为低级别胶质瘤。经纵裂锁孔入路手术创伤小,手术效果良好。     

恶性脑胶质瘤单放和放化疗临床疗效5年随诊分析

目的 分析恶性脑胶质瘤术后单纯放射治疗、同步放射治疗加化学治疗的临床疗效。方法 本次研究我们回顾性分析了南开大学附属环湖医院神经外科自2015年10月至2016年9月共99例恶性脑胶质瘤患者资料,单纯放射治疗（单放）组48例,同步放射治疗加化疗（放化）组51例。两组患者均在术后20 d左右开始常规放射治疗,进行2 Gy/天,分30次,共计60 Gy的放疗,持续42天（周六、周日不放疗）。同步放射治疗加化疗（放化）组在持续42 d的放疗中同时加用化疗,方案为口服替莫唑胺胶囊75 mg/m²·d,共计42天;随后同步放射治疗加化疗期结束后4周,接受共计6个周期的替莫唑胺的辅助治疗,每个周期为28天,每个周期的方案为200 mg/m²·d,每日1次,共5 d,然后停药23 d,治疗可一直持续到肿瘤病变出现进展,最长治疗时间为2年。统计所有病例的1、3、5年生存率,分析恶性脑胶质瘤术后单纯放射治疗、同步放射治疗加化学治疗的临床疗效。结果 1、3、5年生存率单放组分别为54.2%、29.2%、10.4%,放化组分别为74.5%、51.0%、31.4%,放化组高于单放组（P<0.05）。放化组恶心、呕吐等急性反应明显加重,骨髓抑制和听力水平下降、记忆力减退等远期损伤两组病例无显著差异性。结论 恶性脑胶质瘤术后采用同步放射治疗加化学治疗可提高疗效。     

轴位弥散和垂直弥散量化分析脑胶质瘤瘤周侵袭性

目的用轴位弥散和垂直弥散量化分析脑胶质瘤瘤周水肿区白质纤维的侵袭性。方法 30例患者进行轴位弥散和垂直弥散磁共振成像,病理证实为脑胶质瘤。30例中16例为低级别脑胶质瘤患者、14例为高级别脑胶质瘤患者,测量、计算和比较患者肿瘤瘤周水肿区和肿瘤对侧正常脑白质的轴位弥散(λ‖)和垂直弥散(λ⊥)。结果低级别脑胶质瘤瘤周水肿的λ‖值(1.31±0.02)、λ⊥值(0.73±0.04)分别与脑胶质瘤对侧正常白质λ‖值(1.29±0.03)、λ⊥值(0.71±0.05)比较,差异均无统计学意义(t分别=1.87、1.73,P均>0.05);高级别脑胶质瘤周水肿的λ‖值(2.21±0.08)、λ⊥值(1.72±0.05)分别与脑胶质瘤对侧正常白质λ‖值(1.29±0.03)、λ⊥值(0.72±0.05)比较,差异均有统计学意义(t分别=56.17、75.12,P均<0.05)。结论低级别脑胶质瘤周边保留大量正常的脑白质,而高级别脑胶质瘤周边大部分脑白质被破坏。脑胶质瘤瘤周水肿区λ‖和λ⊥可作为脑胶质瘤侵袭性的量化指标。     

脑胶质瘤的放射治疗进展

 脑胶质瘤治疗以外科手术为主，由于肿瘤侵蚀性强，与脑组织无明显分界，手术难以彻底切除，易复发，生存期短，死亡率高。因此，术后辅助放射治疗占有重要地位。而脑胶质瘤的预后受患者的年龄、Karnofsky评分、病理类型和侵犯范围等因素的影响，其疗效仍不理想。为探索脑胶质瘤放射治疗的疗效，近年来放射治疗的新设备、新技术不断改善和进步，为脑胶质瘤的放射治疗提供了条件。主要阐述了高分级与低分级脑胶质瘤放射治疗以及放疗联合化疗的现状和进展。