18F-FET PET Imaging in Differentiating Glioma Progression from Treatment-Related Changes: A Single-Center Experience.

18F-FET PET 成像鉴别胶质瘤进展与治疗相关变化: 单中心经验。

  • 影响因子:5.06
  • DOI:10.2967/jnumed.119.234757
  • 作者列表:"Maurer GD","Brucker DP","Stoffels G","Filipski K","Filss CP","Mottaghy FM","Galldiks N","Steinbach JP","Hattingen E","Langen KJ
  • 发表时间:2020-04-01

:In glioma patients, differentiation between tumor progression (TP) and treatment-related changes (TRCs) remains challenging. Difficulties in classifying imaging alterations may result in a delay or an unnecessary discontinuation of treatment. PET using O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) has been shown to be a useful tool for detecting TP and TRCs. Methods: We retrospectively evaluated 127 consecutive patients with World Health Organization grade II-IV glioma who underwent 18F-FET PET imaging to distinguish between TP and TRCs. 18F-FET PET findings were verified by neuropathology (40 patients) or clinicoradiologic follow-up (87 patients). Maximum tumor-to-brain ratios (TBRmax) of 18F-FET uptake and the slope of the time-activity curves (20-50 min after injection) were determined. The diagnostic accuracy of 18F-FET PET parameters was evaluated by receiver-operating-characteristic analysis and χ2 testing. The prognostic value of 18F-FET PET was estimated using the Kaplan-Meier method. Results: TP was diagnosed in 94 patients (74%) and TRCs in 33 (26%). For differentiating TP from TRCs, receiver-operating-characteristic analysis yielded an optimal 18F-FET TBRmax cutoff of 1.95 (sensitivity, 70%; specificity, 71%; accuracy, 70%; area under the curve, 0.75 ± 0.05). The highest accuracy was achieved by a combination of TBRmax and slope (sensitivity, 86%; specificity, 67%; accuracy, 81%). However, accuracy was poorer when tumors harbored isocitrate dehydrogenase (IDH) mutations (91% in IDH-wild-type tumors, 67% in IDH-mutant tumors, P < 0.001). 18F-FET PET results correlated with overall survival (P < 0.001). Conclusion: In our neurooncology department, the diagnostic performance of 18F-FET PET was convincing but slightly inferior to that of previous reports.


: 在胶质瘤患者中,肿瘤进展 (TP) 和治疗相关变化 (TRCs) 之间的分化仍然具有挑战性。影像改变分类困难可能导致治疗延迟或不必要的中止。使用 O-(2-18f-氟乙基)-l-酪氨酸 (18F-FET) 的 PET 已被证明是检测 TP 和 TRCs 的有用工具。方法: 我们回顾性评估了 127 例世界卫生组织 ⅱ-ⅳ 级胶质瘤患者,他们接受了 18F-FET PET 成像来区分 TP 和 TRCs。18F-FET PET 结果通过神经病理学 (40 例患者) 或临床放射学随访 (87 例患者) 验证。测定 18F-FET 摄取的最大肿瘤脑比 (TBRmax) 和时间活动曲线斜率 (注射后 20-50 min)。通过接收器-操作-特性分析和 χ 2 检验评估 18F-FET PET 参数的诊断准确性。使用 Kaplan-Meier 方法估计 18F-FET PET 的预后价值。结果: 诊断 TP 94 例 (74%),TRCs 33 例 (26%)。为了区分 TP 和 TRCs,接受者操作特征分析产生了 1.95 的最佳 18F-FET TBRmax 截止值 (灵敏度,70%; 特异性,71%; 准确性,70%; 曲线下面积,0.75 ± 0.05)。TBRmax 和 slope 的组合达到了最高的准确性 (敏感性,86%; 特异性,67%; 准确性,81%)。然而,当肿瘤含有异柠檬酸脱氢酶 (IDH) 突变时,准确性较差 (IDH-野生型肿瘤为 91%,IDH-突变型肿瘤为 67%,P <0.001)。18F-FET PET 结果与总生存期相关 (P <0.001)。结论: 在我们的神经肿瘤科,18F-FET PET 的诊断性能令人信服,但略逊于以前的报道。



作者列表:["Tiwari V","Mashimo T","An Z","Vemireddy V","Piccirillo S","Askari P","Hulsey KM","Zhang S","de Graaf RA","Patel TR","Pan E","Mickey BE","Maher EA","Bachoo RM","Choi C"]

METHODS:PURPOSE:To generate a preclinical model of isocitrate dehydrogenase (IDH) mutant gliomas from glioma patients and design a MRS method to test the compatibility of 2-hydroxyglutarate (2HG) production between the preclinical model and patients. METHODS:Five patient-derived xenograft (PDX) mice were generated from two glioma patients with IDH1 R132H mutation. A PRESS sequence was tailored at 9.4 T, with computer simulation and phantom analyses, for improving 2HG detection in mice. 2HG and other metabolites in the PDX mice were measured using the optimized MRS at 9.4 T and compared with 3 T MRS measurements of the metabolites in the parental-tumor patients. Spectral fitting was performed with LCModel using in-house basis spectra. Metabolite levels were quantified with reference to water. RESULTS:The PRESS TE was optimized to be 96 ms, at which the 2HG 2.25 ppm signal was narrow and inverted, thereby leading to unequivocal separation of the 2HG resonance from adjacent signals from other metabolites. The optimized MRS provided precise detection of 2HG in mice compared to short-TE MRS at 9.4 T. The 2HG estimates in PDX mice were in excellent agreement with the 2HG measurements in the patients. CONCLUSION:The similarity of 2HG production between PDX models and parental-tumor patients indicates that PDX tumors retain the parental IDH metabolic fingerprint and can serve as a preclinical model for improving our understanding of the IDH-mutation associated metabolic reprogramming.

来源期刊:BMC cancer
作者列表:["Ang SYL","Lee L","See AAQ","Ang TY","Ang BT","King NKK"]

METHODS:BACKGROUND:Gliomas consist of a heterogeneous group of tumors. This study aimed to report the incidences of O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation, 1p19q co-deletion, isocitrate dehydrogenase (IDH) gene mutations, and inactivating mutations of alpha-thalassemia/mental retardation syndrome X-linked (ATRX) in high-grade gliomas in an ethnically diverse population. METHODS:Records of patients who underwent surgery for high-grade gliomas from January 2013 to March 2017 at our institution were obtained. The patients' age, gender, ethnicity, Karnofsky Performance Scale (KPS) score, ability to perform activities of daily living (ADLs), tumor location and biomarkers status were recorded. Data were analyzed using chi-square and Mann-Whitney U tests, Kaplan-Meier estimates and log-rank test. RESULTS:181 patients were selected (56 with grade III gliomas, 125 with grade IV gliomas). In the grade III group, 55% had MGMT promoter methylation, 41% had 1p19q co-deletion, 35% had IDH1 mutation and none had ATRX loss. In the grade IV group, 30% had MGMT promoter methylation, 2% had 1p19q co-deletion, 15% had IDH1 mutation and 8% had ATRX loss. After adjusting for effects of age, surgery and pre-operative ADL statuses, only MGMT promoter methylation was found to be significantly associated with longer overall survival time in grade III (p = 0.024) and IV patients (p = 0.006). CONCLUSIONS:The incidences of MGMT promoter methylation and IDH1 mutation were found to be comparable to globally reported rates, but those of 1p19q co-deletion and ATRX loss seemed to be lower in our cohort. MGMT promoter methylation was associated with increased overall survival in our cohort and might serve as favorable prognostic factor.

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作者列表:["Abbruzzese C","Matteoni S","Persico M","Villani V","Paggi MG"]

METHODS:BACKGROUND:Glioblastoma multiforme is a CNS cancer characterized by diffuse infiltrative growth, aggressive clinical behavior and very poor prognosis. The state-of-art clinical approach to this disease consists of surgical resection followed by radiotherapy plus concurrent and adjuvant chemotherapy with temozolomide. Tumor recurrence occurs in virtually all cases, therefore, despite any treatment, the median survival is very low (14.6 months), which makes the approach to these patients a challenging clinical issue. MAIN BODY:The escalating costs and times required for new medications to reach the bedside make repurposing or repositioning of old drugs, when scientific bases allow their use in other pathologies, an appealing strategy. Here, we analyze a number of literature data concerning the antipsychotic chlorpromazine, the founder of the phenothiazines class of drugs, a medication widely used in the clinics for approximately 60 years. The drug exerts its effects on psychiatric patients by interfering with the dopamine receptor D2, although more recent pharmacodynamics studies ascribe chlorpromazine a series of biological effects on cancer cells, all converging in hindering also glioblastoma survival capabilities. SHORT CONCLUSIONS:On these bases, and assisted by the information on the well-established chlorpromazine toxicity and dosage in humans, we designed a Phase II clinical trial involving the combination of chlorpromazine with the standard treatment, temozolomide, in the adjuvant phase of the therapeutic protocol. Patients displaying hypo-methylation of the MGMT gene, and thus intrinsically resistant to temozolomide, will be enrolled. The endpoints of this study are the analysis of toxicity and clinical activity, as evaluated in terms of Progression-Free Survival, of the association of chlorpromazine with the first-line treatment for this very serious form of cancer.

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