NIMG-20. DIFFERENTIATION OF TREATMENT-RELATED CHANGES FROM TUMOR PROGRESSION FOLLOWING BRACHYTHERAPY IN PATIENTS WITH WHO II AND III GLIOMAS USING FET PET

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi132-vi132
Author(s):  
Elena Bauer ◽  
Jan Werner ◽  
Anna Brunn ◽  
Martina Deckert ◽  
Daniel Ruess ◽  
...  

Abstract BACKGROUND Following brachytherapy, the differentiation of radiation-induced changes (e.g., radiation necrosis) from actual tumor progression using MRI is challenging. To overcome this diagnostic uncertainty, we evaluated the diagnostic value of O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET in glioma patients treated with brachytherapy. MATERIAL AND METHODS From 2006-2019, we retrospectively identified WHO grade II or III glioma patients (i) treated with brachytherapy using Iodine-125 seeds, (ii) equivocal or progressive MRI findings inside the radiation field, and (iii) additional FET PET imaging for diagnostic evaluation. Static FET PET parameters such as maximum and mean tumor-to-brain ratios (TBR) and dynamic FET PET parameters (i.e., time-to-peak, slope) were obtained. Diagnostic performances were calculated using receiver operating characteristic curve analyses and Fisher’s exact test. Diagnoses were confirmed histologically or clinicoradiologically. RESULTS Following brachytherapy, suspect MRI findings occurred after a median time of 33 months (range, 5-111 months). In 10 of 21 patients (WHO grade II, n=5; WHO grade III, n=16), treatment-related changes were diagnosed. The best diagnostic performance for identification of treatment-related changes was obtained using maximum TBRs (threshold < 3.20;accuracy, 86%; sensitivity, 100%; specificity, 73%; P=0.007). Mean TBRs reached an accuracy of 76% (threshold < 2.05; sensitivity, 89%; specificity, 64%; P=0.010). Dynamic PET parameters did not reach statistically significant results. CONCLUSION Our data suggest that static FET PET parameters add valuable diagnostic information to diagnose radiation-induced changes in glioma patients treated with brachytherapy.

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii53-ii53
Author(s):  
E K Bauer ◽  
J Werner ◽  
A Brunn ◽  
M Deckert ◽  
D Ruess ◽  
...  

Abstract BACKGROUND Following brachytherapy, the differentiation of radiation-induced changes (e.g., radiation necrosis) from actual tumor progression using MRI is challenging. To overcome this diagnostic uncertainty, we evaluated the diagnostic value of O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET in glioma patients treated with brachytherapy. MATERIAL AND METHODS From 2006–2019, we retrospectively identified WHO grade II or III glioma patients (i) treated with brachytherapy using Iodine-125 seeds, (ii) equivocal or progressive MRI findings inside the radiation field, and (iii) additional FET PET imaging for diagnostic evaluation. Static FET PET parameters such as maximum and mean tumor-to-brain ratios (TBR) and dynamic FET PET parameters (i.e., time-to-peak, slope) were obtained. Diagnostic performances were calculated using receiver operating characteristic curve analyses and Fisher’s exact test. Diagnoses were confirmed histologically or clinicoradiologically. RESULTS Following brachytherapy, suspect MRI findings occurred after a median time of 33 months (range, 5–111 months). In 10 of 21 patients (WHO grade II, n=5; WHO grade III, n=16), treatment-related changes were diagnosed. The best diagnostic performance for identification of treatment-related changes was obtained using maximum TBRs (threshold <3.20; accuracy, 86%; sensitivity, 100%; specificity, 73%; P=0.007). Mean TBRs reached an accuracy of 76% (threshold <2.05; sensitivity, 89%; specificity, 64%; P=0.010). Dynamic PET parameters did not reach statistically significant results. CONCLUSION Our data suggest that static FET PET parameters add valuable diagnostic information to diagnose radiation-induced changes in glioma patients treated with brachytherapy.


2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii81-iii81
Author(s):  
A F Keßler ◽  
J Weiland ◽  
T Linsenmann ◽  
R Ernestus ◽  
C Hagemann ◽  
...  

Abstract BACKGROUND The addition of Tumor Treating Fields (TTFields) to the first-line therapy in glioblastoma (GBM) demonstrated significantly improved progression free survival, overall survival and longterm survival rates in the EF-14 phase 3 trial. However, responder analysis of patients with recurrent GBM (rGBM) treated with TTFields monotherapy (in the EF-11 trial) revealed delayed response monitored by MRI analysis. More recent data suggests that O-(2-18F-fluoroethyl)-L-tyrosine (FET) PET may add valuable information for monitoring therapy response of glioblastoma patients treated with TTFields. Here, we report on FET PET response in a patient with progressive anaplastic astrocytoma WHO grade III (AA) treated with TTFields in combination with temozolomide (TMZ) chemotherapy. METHODS We present a 38-year old patient with an initial diagnosis of a diffuse astrocytoma WHO grade II in 2011, and malignisation to an AA on progression. The treatment regimen included initially radio-chemotherapy (RCT) with TMZ. On further progression of the AA in 2017, TTFields were added to another 6 cycles of TMZ. Several FET PET scans for differentiation of tumor progression from treatment-related changes were performed over time. The definitive diagnosis (tumor progression and grading) was confirmed by histopathology after stereotactic biopsy (SB). RESULTS In 2012, the patient was first diagnosed with a low grade astrocytoma WHO grade II of the right frontal, temporal and parietal lobe including infiltration of thalamus and corpus was confirmed by SB, followed by irradiation. On progression in 2015, a FET PET Scan showed FET avidity in all tumor affected regions of the brain. SB confirmed an AA, while FET PET scans showed only a mild response in the temporoparietal region after 6 cycles of TMZ. In 2017, the next progression without further malignisation was confirmed by SB and treated RCT with 41.4 Gy and TMZ chemotherapy, followed by application of TTFields with an average usage rate of 85.7 % over 6 months. Thus, the TTFields adherence was well above the independent prognostic threshold of 75 %. No additional adverse events due to the combined therapy of TTFields and TMZ were observed. Due to a new contrast enhancing lesion in the right frontal lobe (10x7mm), another FET PET scan was performed 1.5 years later. In this scan, obtained after combined TTFields and RCT therapy a strong response regarding FET avidity was observed. CONCLUSION In summary, FET PET is able to add important additional information for evaluation of treatment response in high grade glioma patients, in particular for TTFields treated patients, while adding TTFields to radiochemotherapy might even enhance treatment response of high grade glioma. Further studies might elucidate the role of FET PET imaging for therapy monitoring in high grade glioma patients treated with TTFields.


2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii6-ii6
Author(s):  
N Galldiks ◽  
G Stoffels ◽  
J Werner ◽  
E K Bauer ◽  
C Baues ◽  
...  

Abstract BACKGROUND In the present study, we characterized the long-term metabolic changes of brain metastases irradiated with stereotactic radiosurgery (SRS) by sequential dynamic PET imaging using the radiolabeled amino acid O-(2-[18F]-fluoroethyl)-L-tyrosine (FET). We hypothesized that this approach is of considerable clinical value to diagnose delayed radiation-induced changes. MATERIAL AND METHODS From 2010–2021, we retrospectively identified patients with brain metastases from solid extracranial primary tumors who (i) were treated with SRS with or without concurrent immunotherapy using checkpoint inhibitors, (ii) had equivocal or progressive MRI findings after SRS, and (iii) subsequently underwent at least two additional dynamic FET PET scans during follow-up for long-term evaluation. Mean tumor-to-brain ratios (TBR) and the dynamic FET PET parameter time-to-peak were obtained. Diagnostic performances were calculated using receiver operating characteristic curve analyses. Diagnoses were confirmed histologically or clinicoradiologically. RESULTS We identified 36 patients with 98 FET PET scans (median number, 3; range, 2–6). Concurrent to SRS, 8 patients (22%) were treated with checkpoint inhibitors. Following SRS, suspicious MRI findings occurred after a median time of 11 months (range, 2–64 months). Subsequently, FET PET scans were acquired over a median period of 13 months (range, 5–60 months). The overall median follow-up time was 26 months (range, 8–101 months). Twenty-one patients (58%) had delayed radiation-induced changes. TBRs calculated from the last available FET PET scan showed the highest accuracy (92%) to identify delayed radiation-induced changes (threshold, 1.95; P<0.001). CONCLUSION FET PET has a high diagnostic accuracy for characterizing the long-term changes of irradiated brain metastases.


2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi128-vi128
Author(s):  
Norbert Galldiks ◽  
Gabriele Stoffels ◽  
Jan Werner ◽  
Elena Bauer ◽  
Christian Baues ◽  
...  

Abstract BACKGROUND In the present study, we characterized the long-term metabolic changes of brain metastases irradiated with stereotactic radiosurgery (SRS) by sequential dynamic PET imaging using the radiolabeled amino acid O-(2-[18F]-fluoroethyl)-L-tyrosine (FET). We hypothesized that this approach is of considerable clinical value to diagnose delayed radiation-induced changes. PATIENTS AND METHODS From 2010-2021, we retrospectively identified patients with brain metastases from solid extracranial primary tumors who (i) were treated with SRS with or without concurrent immunotherapy using checkpoint inhibitors, (ii) had equivocal or progressive MRI findings after SRS, and (iii) subsequently underwent at least two additional dynamic FET PET scans during follow-up for long-term evaluation. Mean tumor-to-brain ratios (TBR) and the dynamic FET PET parameter time-to-peak were obtained. Diagnostic performances were calculated using receiver operating characteristic curve analyses. Diagnoses were confirmed histologically or clinicoradiologically. RESULTS We identified 36 patients with 98 FET PET scans (median number, 3; range, 2-6). Concurrent to SRS, 8 patients (22%) were treated with checkpoint inhibitors. Following SRS, suspicious MRI findings occurred after a median time of 11 months (range, 2-64 months). Subsequently, FET PET scans were acquired over a median period of 13 months (range, 5-60 months). The overall median follow-up time was 26 months (range, 8-101 months). Twenty-one patients (58%) had delayed radiation-induced changes. TBRs calculated from the last available FET PET scan showed the highest accuracy (92%) to identify delayed radiation-induced changes (threshold, 1.95; P< 0.001). CONCLUSIONS FET PET has a high diagnostic accuracy for characterizing the long-term changes of irradiated brain metastases.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii83-ii83
Author(s):  
Nilan Vaghjiani ◽  
Andrew Schwieder ◽  
Sravya Uppalapati ◽  
Zachary Kons ◽  
Elizabeth Kazarian ◽  
...  

Abstract PURPOSE Radiation-induced meningiomas (RIMs) are associated with previous exposure to therapeutic irradiation. RIMs are rare and have not been well characterized relative to spontaneous meningiomas (SMs). METHODS 1003 patients with proven or presumed meningiomas were identified from the VCU brain tumor database. Chart review classified RIM patients and their characteristics. RESULTS Of the 1003 total patients, 76.47% were female with a mean ± SD age of 67.55 ± 15.50 years. 15 RIM patients were identified (66.67% female), with a mean ± SD age of 52.67 ± 15.46 years, 5 were African American and 10 were Caucasian. The incidence of RIMs was 1.49% in our data set. The mean age at diagnosis was 43.27 ± 15.06 years. The mean latency was 356.27 ± 116.96 months. The mean initiating dose was 44.28 ± 14.68 Gy. There was a significant difference between mean latency period and ethnicity, 258.3 months for African American population, and 405.2 months for Caucasian population (p = 0.003). There was a significant difference between the mean number of lesions in females (2.8) versus males (1.2; p = 0.046). Of the RIMs with characterized histology, 6 (55%) were WHO grade II and 5 (45%) were WHO grade I, demonstrating a prevalence of grade II tumors approximately double that found with SMs. RIMs were treated with combinations of observation, surgery, radiation, and medical therapy. Of the 8 patients treated with radiation, 4 demonstrated response. 8 of the 15 patients (53%) demonstrated recurrence/progression despite treatment. CONCLUSION RIMs are important because of the associated higher grade histology, gender, and ethnic incidences, and increased recurrence/progression compared to SMs. Despite the presumed contributory role of prior radiation, RIMs demonstrate a significant rate of responsiveness to radiation treatment.


2021 ◽  
Author(s):  
Kevin Akeret ◽  
Flavio Vasella ◽  
Victor E. Staartjes ◽  
Julia Velz ◽  
Timothy Müller ◽  
...  

AbstractIn contrast to most other tumors, the anatomical extent of brain tumors is not objectified and quantified through staging. Staging systems are built on the understanding of the anatomical sequence of tumor progression and its relation to histopathological dedifferentiation and survival. While major advances in the understanding of primary brain tumors at a histological, cellular and molecular level have been achieved in recent decades, our understanding at a macroscopic anatomical level is limited. The aim of this study was to describe the anatomical phenotype of the most frequent brain tumor entities based on topographic probability and growth behavior analysis. The association of anatomical tumor features with survival probability was assessed and a prototypical staging system for WHO grade II-IV glioma was proposed based on the hypothesized anatomical sequence of tumor progression. The analysis is based on data from a consecutive cohort of 1000 patients with first diagnosis of a primary or secondary brain tumor. On preoperative MRI, the relative tumor density (RTD) of different topographic, phylogenetic and ontogenetic parcellation units was derived through normalization of the relative tumor prevalence to the relative volume of the respective structure. While primary central nervous system lymphoma (PCNSL) showed a high RTD along white matter tracts, the RTD in metastases was highest along terminal arterial flow areas. Neuroepithelial tumors (NT) demonstrated a high and homogeneous RTD along all sectors of the ventriculo-cortical axis, avoiding adjacent units, consistent with a transpallial behavior within phylo-ontogenetic radial units. Additionally, the topographic probability in NT correlated with morphogenetic processes of convergence and divergence of radial units during phylo- and ontogenesis. The anatomical tumor growth behavior was analyzed by comparing pre- and postoperative MRI, showing that a ventriculofugal growth dominates in NT. With progressive histopathological dedifferentiation of NT, a gradual deviation from this neuroepithelial anatomical behavior was found. By comparing survival probability, we identified prognostically critical steps in the anatomical behavior of NT. Based on a hypothesized sequence of anatomical tumor progression, we developed a three-level prototypical staging system for WHO grade II-IV glioma. This staging system proved to be accurate across histological, molecular, radiomorphological and clinical strata based on Kaplan Meier curves and multivariable survival analysis. Similar to staging systems for other tumors, a staging system such as this one may have the potential to inform stage-adapted treatment decisions.


2020 ◽  
pp. 028418512092790
Author(s):  
Jeanette Henkelmann ◽  
Kristina Bremicker ◽  
Timm Denecke ◽  
Karl-Titus Hoffmann ◽  
Ralf Henkelmann ◽  
...  

Background Despite the high sensitivity of magnetic resonance imaging (MRI), early detection of spondylodiscitis (SpD) remains challenging due to its low specificity. Purpose To assess the diagnostic value of diffusion-weighted imaging (DWI) in suspected cases of SpD with ambiguous early MRI findings in the differentiation of degenerative disorders (DD). Material and Methods In this prospective study, 52 patients suspected of having SpD underwent a whole-spine 3-T MRI scan comprising sagittal DWI. Of 58 conspicuous, T2-weighted, signal increased discs, 39 were successfully evaluated using DWI. Apparent diffusion coefficient (ADC) values and ADC maps were blindly analyzed using the region of interest of the conspicuous disc and a normal adjacent reference disc. Intraindividual ratios (conspicuous disc: reference disc) were calculated. Results All conspicuous discs showed increased absolute ADC values, which did not differ significantly between SpD (n = 22) and DD (n = 17). However, ADC ratio was significantly higher in SpD vs. DD ( P < 0.05). In receiver operating characteristic curve analysis, an ADC ratio threshold of 1.6 resulted in 45% sensitivity and 88% specificity (area under the curve = 0.69) for SpD diagnosis. Conclusion The absolute ADC value does not provide a reliable diagnosis of SpD. Increased diffusivity can be an indication of infection but should always be discussed in the context of existing disc degeneration.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii149-ii149
Author(s):  
Lazaros Lazaridis ◽  
Sied Kebir ◽  
Manuel Weber ◽  
Teresa Schmidt ◽  
Kathy Keyvani ◽  
...  

Abstract BACKGROUND Advanced imaging techniques entered the field of neurooncology. In this analysis we compare the diagnostic potential of 18F-fluorethyltyrosine (FET) positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) in their potential to preoperatively predict certain glioma subtypes. AIMS Goal of this analysis ist the evaluation of FET PET and MRS regarding the preoperative prediction of glioma subtypes. METHODS We analyzed 33 patients with histopathologically confirmed newly diagnosed glioma. The patients received FET PET and MRS during one single preoperative diagnostic session. According to the molecular portfolio patients were subdivided in IDH wildtype glioblastoma patients (GBM), IDH wildtype WHO grade II/III glioma patients (Astro_IDHwt), IDH mutant WHO grade II/III glioma patients without 1p/19q codeletion (Astro_IDHmut) and with 1p/19q codeletion (ODG). Mean and maximum tumor-to-brain ratio (TBRmean and TBRmax), N-acetylaspartate, choline and creatine peaks were correlated with postoperative tumor diagnosis. To gain generalizable implications we subdivided the study cohort into a development and validation subcohort. A support vector machine model was fitted to the development subcohort and evaluated on the validation subcohort. Receiver operating characteristic curve served to assess model performance. RESULTS GBM patients had highest TBRmax and TBRmean values (mean: 3.5 and 3.8) and the ODG patients showed the second highest TBRmax and TBRmean values (mean: 2.6 and 3). The distribution of MRS markers exhibited to clear trend. The performance of glioma subtyping was comparatively low for the TBR values (AUC: 0.68) and even lower for the MRS markers (AUC: 0.60). These results are in line with preliminary investigations performed by our institute for the comparison of 11C-methionine PET with MRS in preoperative glioma subtyping. CONCLUSIONS FET PET and MRS bear limited potential in glioma subgrouping. However, FET PET appears to be slightly superior. Investigation in a larger cohort is required to draw definite conclusions.


2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii17-ii17
Author(s):  
Yasuharu Akasaki ◽  
Jun Takei ◽  
Yuko Kamata ◽  
Yohei Yamamoto ◽  
Ryosuke Mori ◽  
...  

Abstract BACKGROUND This trial was designed to evaluate the safety and clinical responses to an immunotherapy with fusions of dendritic and glioma cells in patients with lower grade glioma (LGG; WHO grade II-III glioma). METHOD Autologous cultured glioma cells obtained from surgical specimens were fused with autologous dendritic cells (DC) using polyethylene glycol. The fusion cells (FC) were inoculated intradermally in the cervical region of subjects. Toxicity, progression-free survival (PFS), overall survival (OS), and MRI findings were evaluated. DNA for whole exome and RNA for whole transcriptome extracted from HLA-A*24:02 positive glioma cells were analyzed by next generation sequencer. Variant peptides showing strong binding affinity to HLA-A*24:02 but not the corresponding wild type peptides were selected as candidate of neo-antigens. RESULTS The number of subjects of this trial were 24 (initially diagnosed cases: 20, recurrence cases: 4). WHO grade III cases were 20, and grade II cases were 4. Male were 15, and female were 9. Mean of follow up periods were 53.0 months (the longest follow up period: 1322 months). The number of events on PFS and OS were 8 and 6, respectively. Mean of candidate of neo-antigen peptides in HLA-A*24:02 positive patients (n=8) was 34. Among these candidates, twelve types of common neo-antigen peptide were identified. Neo-antigen peptides specifically expressed in the glioma cells from the effective group were not identified. CONCLUSIONS These results indicate that the efficacy of FC-immunotherapy may not always depend on the number of gene mutations or the expression of the specific neo-antigens. FC-immunotherapy, as a means of producing specific immunity against neo-antigens may safely induce anti-tumor effects in patients with LGG. Analysis of prognostic factor in glioma immunotherapy may be the next area of major interest.


Neurosurgery ◽  
2015 ◽  
Vol 78 (3) ◽  
pp. 401-411 ◽  
Author(s):  
Mohammed Jaber ◽  
Johannes Wölfer ◽  
Christian Ewelt ◽  
Markus Holling ◽  
Martin Hasselblatt ◽  
...  

Abstract BACKGROUND: Approximately 20% of grade II and most grade III gliomas fluoresce after 5-aminolevulinic acid (5-ALA) application. Conversely, approximately 30% of nonenhancing gliomas are actually high grade. OBJECTIVE: The aim of this study was to identify preoperative factors (ie, age, enhancement, 18F-fluoroethyl tyrosine positron emission tomography [18F-FET PET] uptake ratios) for predicting fluorescence in gliomas without typical glioblastomas imaging features and to determine whether fluorescence will allow prediction of tumor grade or molecular characteristics. METHODS: Patients harboring gliomas without typical glioblastoma imaging features were given 5-ALA. Fluorescence was recorded intraoperatively, and biopsy specimens collected from fluorescing tissue. World Health Organization (WHO) grade, Ki-67/MIB-1 index, IDH1 (R132H) mutation status, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status, and 1p/19q co-deletion status were assessed. Predictive factors for fluorescence were derived from preoperative magnetic resonance imaging and 18F-FET PET. Classification and regression tree analysis and receiver-operating-characteristic curves were generated for defining predictors. RESULTS: Of 166 tumors, 82 were diagnosed as WHO grade II, 76 as grade III, and 8 as glioblastomas grade IV. Contrast enhancement, tumor volume, and 18F-FET PET uptake ratio &gt;1.85 predicted fluorescence. Fluorescence correlated with WHO grade (P &lt; .001) and Ki-67/MIB-1 index (P &lt; .001), but not with MGMT promoter methylation status, IDH1 mutation status, or 1p19q co-deletion status. The Ki-67/MIB-1 index in fluorescing grade III gliomas was higher than in nonfluorescing tumors, whereas in fluorescing and nonfluorescing grade II tumors, no differences were noted. CONCLUSION: Age, tumor volume, and 18F-FET PET uptake are factors predicting 5-ALA-induced fluorescence in gliomas without typical glioblastoma imaging features. Fluorescence was associated with an increased Ki-67/MIB-1 index and high-grade pathology. Whether fluorescence in grade II gliomas identifies a subtype with worse prognosis remains to be determined.


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