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Aims Amino acid PET and magnetic resonance spectroscopy (MRS) are at the forefront of noninvasive imaging techniques used for detection and subtyping of glioma-suspicious lesions. In this pilot study, we compare l-methyl-11C-methionine PET and MRS for their ability to predict glioma subtypes. Methods Nineteen patients with histologically, confirmed newly diagnosed glioma underwent preoperative l-methyl-11C-methionine PET and MRS in 1 diagnostic session. According to the molecular portfolio and histopathologic diagnosis, patients were subdivided in isocitrate dehydrogenase (IDH) wild-type glioblastoma, IDH wild-type grade II/III glioma, IDH-mutant grade II/III glioma without 1p/19q codeletion, and with 1p/19q codeletion subgroups. Maximum tumor-to-brain ratio (TBRmax), creatine, choline, and N-acetyl aspartate peaks were correlated with postoperative histopathologic tumor diagnoses. Results Maximum tumor-to-brain ratio was highest in glioblastoma patients (4.18) followed by patients with IDH wild-type grade II and III glioma (3.41). The latter TBRmax values were higher compared with those in patients with IDH-mutant grade II/III glioma without 1p/19q codeletion (1.95) and in patients with IDH-mutant 1p/19q codeleted grade II and III glioma (2.79). Magnetic resonance spectroscopy marker distribution showed no clear trend. Receiver operating characteristic analysis revealed TBRmax to be the best performing parameter in identifying IDH status (area under the curve, 0.67) and all spectroscopy markers combined in identifying glioma subgroups (area under the curve, 0.68), respectively. Conclusions l-Methyl-11C-methionine PET and MRS bear limited potential in glioma subgrouping. l-Methyl-11C-methionine PET appears to be superior in differentiating IDH status, whereas MRS is more helpful in glioma subgrouping.

BackgroundLeptomeningeal metastasis (LM) is a predominantly late stage, devastating complication of a variety of malignant solid tumors. Diagnosis relies predominantly on neurological, radiographic, and cerebrospinal fluid (CSF) assessments. Recently, liquid biopsy tests derived from CSF has shown to be a feasible, noninvasive promising approach to tumor molecular profiling for proper brain cancer diagnostic treatment, thereby providing an opportunity for CSF-based personalized medicine. However, LM is typically misleadingly assumed to originate from only one primary tumor type.Case presentationIn this case report, we provide first evidence of the co-occurrence of LM originating from more than one primary tumor types.Discussion and conclusionsBased on this patient case profile, the co-occurrence of LM from two or more primary tumor types should be accounted for when deriving diagnostic conclusions from liquid biopsy tests.

Objective: We aimed to identify and compare glioblastoma (GBM) Phase III trials of the years 2005 to 2018. Methods:A systematic literature search using PubMed and ClinicalTrials.gov was conducted to provide an overview of clinically relevant GBM Phase III trials (years 2005-2018) that also included younger adult patients. A comparative analysis of positive and negative trails as well as a detailed overview of the main findings of the trials with demonstrated significantly improved survival will be shown. Results: Searching PubMed.gov for “glioblastoma OR gbm” and filtering for Phase III clinical trials identified 61 publications. A query on ClinicalTrials.gov for “glioblastoma” filtering for “completed, terminated, interventional, adult, older adult, Phase III” found 29 entries. Among these trials a total of three GBM Phase III trials reporting OS benefit, including the EORTC/NCIC study (PMID: 15758009), EF-14 (NCT00916409) and CeTeG (NCT01149109). A broad overview of the studies identified and a comparison between negative and positive trials will be provided. The latest two identified trials (EF-14 and CeTeG) will be described in more detail. The EF-14 trial randomized 695 patients with newly diagnosed GBM, irrespective of MGMT promoter methylation status, to treatment with temozolomide (TMZ) or tumor treating fields (TTFields) plus TMZ (TTFields/TMZ). ITT analysis showed significantly improved OS (p < 0.001), PFS (p < 0.001) and long-term survival rates by the addition of TTFields to TMZ. Pre-specified subgroup analysis showed, the OS benefit independent of canonical prognostic factors, such as KPS, age, MGMT, and extent of resection. Notably, TTFields/TMZ also improved OS in RPA groups III and IV. In the CeTeG trial, 141 patients with GBM and with MGMT promoter methylation only, were randomized to either lomustine (CCNU) plus temozolomide (CCNU/TMZ) or TMZ alone. Results were provided based on a pre-specified modified ITT analysis stratified for center and RPA class. This trial demonstrated a significant improved median OS (p = 0.049) whereas PFS was not improved in comparison to the control group. The combination of TTFields and TMZ was not associated with a significant increase in systemic adverse events (48% vs 44%, P = 0.58; Grade 3-4, ≥ 5% incidence). 52% of patients experienced mild to moderate skin irritation. The combination of CCNU with TMZ led to a moderate increased rate of patients with AEs grade 3/4 compared to TMZ alone. TTFields/TMZ did not negatively influence Quality of life (QoL) except for itchy skin. CCNU/TMZ did not lead to a reduction of QoL or KPS, neither. Conclusion: This analysis on GBM Phase III trials conducted since 2005 showed that majority of trials did not show a significant improvement in overall survival. CeTeG and EF-14 are, besides trials on elderly patients only, two recent studies with positive survival outcome. Citation Format: Lazaros Lazaridis, Ann-Kathrin Stoppek, Teresa Schmidt, Martin Glas, Sied Kebir. Comparative analysis of randomized glioblastoma Phase III trials since 2005 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT187.

BACKGROUND Tumor Treating Fields (TTFields) are established as modality in glioblastoma (GBM) therapy. GBM is the most aggressive brain tumor in adults, constituting approximately 15 % of all primary brain tumors. At diagnosis, a considerable subgroup of GBM patients is ≥65 years of age. The phase 3 EF-14 trial demonstrated a significant improvement of progression free, overall and longterm survival in newly diagnosed GBM (ndGBM) patients by the addition of TTFields compared temozolomide therapy. No treatment limiting systemic adverse events in the EF-14 trial for ndGBM or in the EF-11 trial for recurrent GBM (rGBM) were observable. Here, we present post-market surveillance data from patients in the EMEA region including elderly patients (≥ 65 years) treated with TTFields. METHODS Based on the MedDRA body system (system organ class) and preferred terms surveillance data of patients in the EMEA region were assessed. Additionally, surveillance data of patients < 65 as well as ≥ 65 years of age in this region were separately analyzed. RESULTS A total of 11,048 patients were treated with TTFields (ndGBM 53.3 %, rGBM 39.5 %, other diagnoses 7.2 %) of whom 2,252 (20.4 %) patients were treated in the EMEA region. 19.6 % of patients treated in this region were ≥65 years of age at the time of TTFields therapy initiation. One or more adverse events were reported by 64 % of EMEA patients < 65 and in 67 % of elderly EMEA patients. The most prevalent adverse event in both age groups was skin reactions, occurring in 30 % of patients < 65 years of age and 33 % elderly patients. Likewise, further adverse events in elderly patients in the EMEA region were comparable to patients younger than 65 years of age, e.g. heat sensation (< 65; ≥ 65: 4 %; 4 %) and general physical health deterioration (14 %; 18 %). CONCLUSION These real-life data demonstrate a good safety profile of TTFields in elderly patients as well as in patients < 65. The most frequent registered adverse event was skin reaction, which is in line with the results of the phase 3 EF-11 trial for rGBM and the EF-14 trial for ndGBM patients. In summary, these results from post-marketing surveillance emphasize the safety of TTFields in GBM treatment, particularly in the elderly population.