scholarly journals OTEH-4. Deeper insight into intratumoral heterogeneity by MRI and PET-guided stereotactic biopsies from glioblastoma patients

2021 ◽  
Vol 3 (Supplement_2) ◽  
pp. ii11-ii11
Author(s):  
Atul Anand ◽  
Jeanette Krogh Petersen ◽  
Mark Burton ◽  
Martin Jakob Larsen ◽  
Lars van Brakel Andersen ◽  
...  

Abstract Glioblastoma is one of the most aggressive cancers, but the molecular evolution is still not fully understood. We used PET imaging combined with deep sequencing of glioblastoma biopsies at both the RNA and DNA levels to get a deeper insight into molecular evolution. In the clinical setting, PET imaging provides information about metabolically active tumor areas, but the molecular interpretation is unclear. Our primary objective was to perform an intratumoral spatial comparison of biopsies from potentially aggressive and less aggressive areas in glioblastomas according to PET scans. Additionally, tissue from the tumor periphery was included. We used MRI, 11C-methionine(MET) PET, and 18F-FDG PET was used in combination to obtain a series of neurosurgical stereotactic biopsies from tumor areas with high MET and 18F-FDG uptake (hotspot), low MET and 18F-FDG uptake (coldspot), as well as tumor periphery of six glioblastoma patients that were processed for whole genome, exome, and transcriptome sequencing. Differential gene expression and gene ontology analysis showed that hotspots were enriched in gene sets associated with DNA replication, cell cycle, and ligand receptor interaction. Genome and exome analysis suggested hotspots and coldspots to have similar mutational profiles. However, a limited number of hotspot-specific mutations and fusion transcripts indicated that hotspot tumor cells developed from coldspot cells and point at the potential role of hotspot driver genes in glioblastoma. Our findings reveal that hotspots in glioblastomas represent a more advanced stage of molecular evolution than coldspots.

2020 ◽  
Vol 49 (1) ◽  
pp. 34-38
Author(s):  
David M. Sawyer ◽  
Travis W. Sawyer ◽  
Naghmehossadat Eshghi ◽  
Charles Hsu ◽  
Russell J. Hamilton ◽  
...  

2019 ◽  
Vol 23 (6) ◽  
pp. 2576-2582 ◽  
Author(s):  
Elisa Roccia ◽  
Arthur Mikhno ◽  
R. Todd Ogden ◽  
J. John Mann ◽  
Andrew F. Laine ◽  
...  

Author(s):  
Sumati Sundaraiya ◽  
Abubacker Sulaiman ◽  
Adhithyan Rajendran

AbstractA young gentleman with suspected cardiac sarcoidosis and LV dysfunction whose CMR revealed multifocal subepicardial to mid myocardial linear enhancement in the left ventricular myocardium underwent cardiac 18F-FDG PET imaging. The images revealed patchy regions of increased FDG uptake involving the apical to mid anterolateral, mid to basal anteroseptal/ right ventricular and mildly increased FDG uptake in apical inferior segments of the LV myocardium concordant with CMR findings. Whole body PET CT imaging showed multiple hypermetabolic supra and infra diaphragmatic lymphadenopathy, with no pulmonary lesion identified. Biopsy from the left para aortic lymph node revealed necrotizing granulomatous inflammation consistent with tuberculosis. Based on the histopathological findings of the lymph nodes, diagnosis of cardiac tuberculosis was made, given the similar imaging appearances in both sarcoidosis and TB. This case highlights that cardiac TB although rare, should be included in the differential diagnosis in patients with suspected infiltrative cardiomyopathy, particularly in TB endemic regions.


2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi62-vi62
Author(s):  
Timothy Cloughesy ◽  
Benjamin Ellingson ◽  
Andrei Gafita ◽  
Saewon Chun ◽  
Emese Filka ◽  
...  

Abstract BACKGROUND EGFR activated GBM is highly metabolically active and effective targeting with EGFR TKis in human-tumor models rapidly attenuates glucose metabolism engaging apoptotic machinery. Rapid changes in glucose uptake using 18F-FDG-PET is an effective predictive biomarker of therapeutic response in these models. Clinical 18F-FDG-PET may allow investigators to obtain early readout on EGFR TKi in this patient population. We explore this approach using osimertinib in EGFRamp/p53wt rGBM. METHODS EGFRamp/p53wt rGBM patients were treated with oral osimertinib 240mg for three days followed by 160mg/day until progression. F18-FDG-PET scan was obtained as a double baseline, 24 hours apart, prior to dosing with osimertinib. Third scan was obtained after 3 doses of 240mg. Primary objective defines test-retest variance of tumor FDG uptake before osimertinib and to evaluate if osimertinib significantly decreases glucose utilization after three doses. Study-drug and funding provided by AstraZeneca. RESULTS 12 pts were evaluated, 10 female, median age 57.5 years (44-61). Volumetric mRANO showed no responses, 6 SD, 5 PD, and one NE. Median PFS was 31 days, no patient achieved 6-month-PFS and median OS was 5.5 months. No new adverse event signal appeared. Double baseline PET SUV mean was 0.97 (normalized to whole cerebellum) with upward trend from first to second scan with mean percent change of 2.8 and 95% CI(0.7,5.1). Change in PET from 2nd to 3rd showed mean percent change -3.2 with 95% CI (-11.1,4.8). Preclinical models suggest 15-20% attenuation is needed to predict improved outcomes in patients treated with EGFR-TKi. CONCLUSION F18-FDG-PET has little variance with test-retest showing upward trend with second scan. Post osimertinib F18-FDG-PET shows limited attenuation of tumor FDG uptake. No clinical signal was seen in study. Deeper attenuation of FDG uptake may be needed to show clinical effect from EGFR inhibitors. F18-FDG-PET can be used to evaluate change in tumor glucose utilization.


Author(s):  
Ismaheel O. Lawal ◽  
Kgomotso G. Mokoala ◽  
Gbenga O. Popoola ◽  
Thabo Lengana ◽  
Alfred O. Ankrah ◽  
...  

2004 ◽  
Vol 43 (05) ◽  
pp. 143-149 ◽  
Author(s):  
N. Hamscho ◽  
C. Menzel ◽  
L. Neuss ◽  
A. F. Kovács ◽  
F. Grünwald ◽  
...  

Summary:Aim: For the evaluation of the diagnostic potential of dual time point FDG positron emission tomography (PET) in patients with suspicious focal abdominal up-take, dual time point PET imaging was compared with clinical findings. Patients, methods: In a prospective study, 56 patients exhibiting a solitary suspicious, intense abdominal FDG uptake, underwent dual time point PET imaging for staging or restaging of different malignant tumors, maximal standardized uptake value (SUVmax) measurements included. The first acquisition was started 64.8 ± 19.5, the second 211.3 ± 52.5 min after FDG injection. The final diagnosis based on CT or MRT imaging and a follow-up period of 12.6 ± 2.8 months. Additionally, colonoscopy was done in 6 patients. In another 6 patients histopathology was obtained from CT guided biopsy. Results: Malignant focal abdominal lesions with a SUVmax <2.5 (n = 4) showed an uptake increase of ≥30%. In the remaining malignant cases with an uptake of ≥2.5 (n = 11), up-take increased in 64% and decreased in 36%. Malignant lesions showing FDG uptake decrease (n = 4) had an initial SUVmax value ≥2.5 and remained with a SUVmax ≥2.5 in the second imaging. In benign lesions with an initial SUVmax ≥2.5 (n = 31), the uptake increased in 17 patients (55%) and decreased in 14 patients (45%). All lesions which changed configuration (33%) were confirmed as benign (n = 5). Conclusion: Using dual time point PET abdominal lesions show a very hetergenous uptake pattern regardless of their dignity. Malignancy can only be reliably excluded in lesions which change their configuration and in lesions with an initial SUVmax value <2.5 combined with an SUV decrease in the delayed imaging. Particularly abdominal lesions which show an initial SUVmax ≥2.5 combined with a SUV increase in the delayed imaging are suspicious for malignancy and need further clarification.


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