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PURPOSE: Current therapy strategies still provide only limited success in the treatment of glioblastoma, the most frequent primary brain tumor in adults. In addition to the characterization of the tumor microenvironment, global changes in brain of patients with glioblastoma have been described. However, the impact and molecular signature of neuroinflammation distant of the primary tumor site have not yet been thoroughly elucidated. EXPERIMENTAL DESIGN: We performed translocator protein (TSPO)-PET in patients with newly diagnosed glioblastoma (n=41), astrocytoma WHO grade 2 (n=7) and healthy controls (n=20) and compared TSPO-PET signals of the non-lesion (i.e. contralateral) hemisphere. Back-translation in syngeneic SB28 glioblastoma mice was used to characterize PET alterations on a cellular level. Ultimately, multiplex gene expression analyses served to profile immune cells in remote brain. RESULTS: Our study revealed elevated TSPO-PET signals in contralateral hemispheres of patients with newly diagnosed glioblastoma compared to healthy controls. Contralateral TSPO was associated with persisting epileptic seizures and shorter overall survival independent of the tumor phenotype. Back-translation into syngeneic glioblastoma mice pinpointed myeloid cells as the predominant source of contralateral TSPO-PET signal increases and identified a complex immune signature characterized by myeloid cell activation and immunosuppression in distant brain regions. CONCLUSIONS: Neuroinflammation within the contralateral hemisphere can be detected with TSPO-PET imaging and associates with poor outcome in patients with newly diagnosed glioblastoma. The molecular signature of remote neuroinflammation promotes the evaluation of immunomodulatory strategies in patients with detrimental whole brain inflammation as reflected by high TSPO expression.
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BACKGROUND: The use of positron-emission tomography (PET)/computed tomography (CT) in radiation therapy (RT) has increased. Radiation oncologists (RadOncs) have access to PET/CT with a variety of tracers for different tumor entities and use it for target volume definition. The German Society of Nuclear Medicine (DGN) and the German Society of Radiation Oncology (DEGRO) aimed to identify current patterns of care in order to improve interdisciplinary collaboration. METHODS: We created an online survey on participating RadOncs' use of PET tracers for different tumor entities and how they affect RT indication, dose prescription, and target volume definition. Further topics were reimbursement of PET/CT and organizational information (fixed timeslots and use of PET with an immobilization device [planning/RT-PET]). The survey contained 31 questions in German language (yes/no questions, multiple choice [MC] questions, multiple select [MS] questions, and free-text entry options). The survey was distributed twice via the DEGRO member mailing list. RESULTS: During the survey period (May 22-August 7, 2023) a total of 156 RadOncs (13% of respondents) answered the survey. Among these, 59% reported access to diagnostic PET/CT within their organization/clinic and 24% have fixed timeslots for their patients. 37% of survey participants can perform RT-PET and 29% have the option of providing a dedicated RT technician for planning PET. Besides [18F]-fluorodeoxyglucose (FDG; mainly used in lung cancer: 95%), diagnostic prostate-specific membrane antigen (PSMA)-PET/CT for RT of prostate cancer is routinely used by 44% of participants (by 64% in salvage RT). Use of amino acid PET in brain tumors and somatostatin receptor PET in meningioma is low (19 and 25%, respectively). Scans are reimbursed through private (75%) or compulsory (55%) health insurance or as part of indications approved by the German Joint Federal Committee (Gemeinsamer Bundesausschuss; 59%). 98% of RadOncs agree that PET impacts target volume definition and 62% think that it impacts RT dose prescription. DISCUSSION: This is the first nationwide survey on the role of PET/CT for RT planning among RadOncs in Germany. We find high acceptance of PET results for treatment decisions and target volume definition. Planning PET comes with logistic challenges for different healthcare settings (e.g., private practices vs. university hospitals). The decision to request PET/CT is often based on the possibility of reimbursement. CONCLUSION: PET/CT has become an important tool for RadOncs, with several indications. However, access is still limited at several sites, especially for dedicated RT-PET. This study aims to improve interdisciplinary cooperation and adequate implementation of current guidelines for the treatment of various tumor entities.
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PET is increasingly used for target volume definition in the radiotherapy of glioblastoma, as endorsed by the 2023 ESTRO-EANO guidelines. In view of its growing adoption into clinical practice and upcoming PET-based multi-center trials, this paper aims to assist in overcoming common pitfalls of FET PET-based target delineation in glioblastoma.
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Neoplasias Encefálicas , Glioblastoma , Tomografía de Emisión de Positrones , Planificación de la Radioterapia Asistida por Computador , Glioblastoma/radioterapia , Glioblastoma/diagnóstico por imagen , Humanos , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Fluorodesoxiglucosa F18 , RadiofármacosRESUMEN
PURPOSE: Penile cancer is a rare entity and has a good prognosis in localized stage. Delayed surgical treatment of lymphatic disease is associated with poor overall survival but conventional imaging cannot detect occult lymph node metastasis sufficiently. Imaging cancer related fibroblasts has shown promising results as non-invasive staging tool in various tumor entities but has not yet been evaluated in penile cancer. METHODS: In this single-center pilot study, patients planned for surgical treatment for penile cancer underwent preoperatively [68Ga]Ga-FAPI-46 PET/CT. Post-operative histopathology was compared to [68Ga]Ga-FAPI-46 PET/CT results. RESULTS: From January 2022 to June 2022, a total number 11 patients with histopathologically proven penile cancer underwent surgery and received [68Ga]Ga-FAPI-46 PET/CT prior therapy. 8 primary tumor sites and 4 lymph node regions were analyzed. FAPI uptake was increased on primary tumor site (SUVmax 16.2 (9.1 - 25.8)). Histopathological proven lymph node regions showed highly increased FAPI uptakes (SUVmax 17.9 (16.4 - 23.5) on [68Ga]Ga-FAPI-46 PET/CT. CONCLUSION: In this first pilot cohort, there were no false-positive FAPI uptake which might allow the detection of occult lymph node metastasis by [68Ga]Ga-FAPI-46 PET/CT and might consequently lead to omitting lymph node regions during surgery that had no increased FAPI uptake pre-operatively.
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Cancer immunotherapy with chimeric antigen receptor (CAR) T cells can cause immune effector cell-associated neurotoxicity syndrome (ICANS). However, the molecular mechanisms leading to ICANS are not well understood. Here we examined the role of microglia using mouse models and cohorts of individuals with ICANS. CD19-directed CAR (CAR19) T cell transfer in B cell lymphoma-bearing mice caused microglia activation and neurocognitive deficits. The TGFß-activated kinase-1 (TAK1)-NF-κB-p38 MAPK pathway was activated in microglia after CAR19 T cell transfer. Pharmacological TAK1 inhibition or genetic Tak1 deletion in microglia using Cx3cr1CreER:Tak1fl/fl mice resulted in reduced microglia activation and improved neurocognitive activity. TAK1 inhibition allowed for potent CAR19-induced antilymphoma effects. Individuals with ICANS exhibited microglia activation in vivo when studied by translocator protein positron emission tomography, and imaging mass cytometry revealed a shift from resting to activated microglia. In summary, we prove a role for microglia in ICANS pathophysiology, identify the TAK1-NF-κB-p38 MAPK axis as a pathogenic signaling pathway and provide a rationale to test TAK1 inhibition in a clinical trial for ICANS prevention after CAR19 T cell-based cancer immunotherapy.
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Background: The PRIDE trial (NOA-28; ARO-2024-01; AG-NRO-06; NCT05871021) is designed to determine whether a dose escalation with 75.0 Gy in 30 fractions can enhance the median overall survival (OS) in patients with methylguanine methyltransferase (MGMT) promotor unmethylated glioblastoma compared to historical median OS rates, while being isotoxic to historical cohorts through the addition of concurrent bevacizumab (BEV). To ensure protocol-compliant irradiation planning with all study centers, a dummy run was planned and the plan quality was evaluated. Methods: A suitable patient case was selected and the computed tomography (CT), magnetic resonance imaging (MRI) and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) contours were made available. Participants at the various intended study sites performed radiation planning according to the PRIDE clinical trial protocol. The treatment plans and dose grids were uploaded as Digital Imaging and Communications in Medicine (DICOM) files to a cloud-based platform. Plan quality and protocol adherence were analyzed using a standardized checklist, scorecards and indices such as Dice Score (DSC) and Hausdorff Distance (HD). Results: Median DSC was 0.89, 0.90, 0.88 for PTV60, PTV60ex (planning target volume receiving 60.0 Gy for the standard and the experimental plan, respectively) and PTV75 (PTV receiving 75.0 Gy in the experimental plan), respectively. Median HD values were 17.0 mm, 13.9 mm and 12.1 mm, respectively. These differences were also evident in the volumes: The PTV60 had a volume range of 219.1-391.3 cc (median: 261.9 cc) for the standard plans, while the PTV75 volumes for the experimental plans ranged from 71.5-142.7 cc (median: 92.3 cc). The structures with the largest deviations in Dice score were the pituitary gland (median 0.37, range 0.00-0.69) and the right lacrimal gland (median 0.59, range 0.42-0.78). Conclusions: The deviations revealed the necessity of systematic trainings with appropriate feedback before the start of clinical trials in radiation oncology and the constant monitoring of protocol compliance throw-out the study. Trial registration: NCT05871021.
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INTRODUCTION: [68 Ga]Ga-FAPI-46 PET/CT is a novel hybrid imaging method that previously showed additional diagnostic value in the assessment of distant urothelial carcinoma lesions. We hypothesized that patients with bladder cancer benefit from [68 Ga]Ga-FAPI-46 PET/CT prior to radical cystectomy for locoregional lymph node staging. MATERIALS AND METHODS: Eighteen patients underwent [68 Ga]Ga-FAPI-46 PET/CT for evaluation of lymph node (LN) status in predefined LN regions. Two hundred twenty-nine intraoperatively removed LN served as histopathological reference standard. RESULTS: Urothelial carcinoma (UC) spread was found in ten LN in seven different regions (14.3%). Hereby, [68 Ga]Ga-FAPI-46 PET/CT was positive in four out of seven regions (57.1%) and showed significantly increased FAPI uptake compared to non-pathological regions. In the remaining three out of seven (42.9%) regions, [68 Ga]Ga-FAPI-46 PET/CT was rated negative since no pathological increased FAPI uptake was detected or the proximity of the urinary tract prevented a differentiation from physiological uptake. CT was inconspicuous in these three regions. In total, two FAP-positive LN regions were found without histopathological counterpart. Overall, sensitivity, specificity, positive predictive value, and negative predictive value were 57.1%, 95.2%, 66.7%, and 93.0% for PET imaging. CONCLUSION: In summary, this innovative [68 Ga]Ga-FAPI-46 PET/CT method showed high specificity and negative predictive value in patients with bladder UC with a future potential to optimize therapy planning.
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Cistectomía , Estadificación de Neoplasias , Tomografía Computarizada por Tomografía de Emisión de Positrones , Quinolinas , Neoplasias de la Vejiga Urinaria , Humanos , Masculino , Neoplasias de la Vejiga Urinaria/diagnóstico por imagen , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/cirugía , Femenino , Anciano , Proyectos Piloto , Persona de Mediana Edad , Metástasis Linfática/diagnóstico por imagen , Anciano de 80 o más Años , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Isótopos de GalioRESUMEN
BACKGROUND: To compare Gd-ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and 99mTc-labelled mebrofenin hepatobiliary scintigraphy (HBS) as imaging-based liver function tests after unilateral radioembolisation (RE) in patients with primary or secondary liver malignancies. METHODS: Twenty-three patients with primary or secondary liver malignancies who underwent Gd-EOB-DTPA-enhanced MRI within a prospective study (REVoluTion) were evaluated. REVoluTion was a prospective open-label, non-randomised, therapy-optimising study of patients undergoing right-sided or sequential RE for contralateral liver hypertrophy at a single centre in Germany. MRI and hepatobiliary scintigraphy were performed before RE (baseline) and 6 weeks after (follow-up). This exploratory subanalysis compared liver enhancement on hepatobiliary phase MRI normalised to the spleen (liver-to-spleen ratio (LSR)) and the muscle (liver-to-muscle ratio (LMR)) with mebrofenin uptake on HBS for the total liver (TL) and separately for the right (RLL) and left liver lobe (LLL). RESULTS: Mebrofenin uptake at baseline and follow-up each correlated significantly with LSR and LMR on MRI for TL (≤ 0.013) and RLL (≤ 0.049). Regarding the LLL, mebrofenin uptake correlated significantly with LMR (baseline, p = 0.013; follow-up, p = 0.004), whereas with LSR, a borderline significant correlation was only seen at follow-up (p = 0.051; p = 0.046). CONCLUSION: LSRs and LMR correlate with mebrofenin uptake in HBS. This study indicates that Gd-EOB-DTPA-enhanced MRI and 99mTc-labelled mebrofenin HBS may equally be used to assess an increase in contralateral liver lobe function after right-sided RE. RELEVANCE STATEMENT: MRI may be a convenient and reliable method for assessing the future liver remnant facilitating treatment planning and monitoring of patients after RE-induced hypertrophy induction. KEY POINTS: ⢠Both MRI and HBS can assess liver function after RE. ⢠Liver enhancement on MRI correlates with mebrofenin uptake on HBS. ⢠MRI might be a convenient alternative for estimating future liver remnants after hypertrophy induction.
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Compuestos de Anilina , Gadolinio DTPA , Glicina , Neoplasias Hepáticas , Radiofármacos , Humanos , Estudios Prospectivos , Cintigrafía , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/radioterapia , Imagen por Resonancia Magnética/métodos , Ácido Pentético , HipertrofiaRESUMEN
BACKGROUND: The translocator protein (TSPO) has been proven to have great potential as a target for the positron emission tomography (PET) imaging of glioblastoma. However, there is an ongoing debate about the potential various sources of the TSPO PET signal. This work investigates the impact of the inoculation-driven immune response on the PET signal in experimental orthotopic glioblastoma. METHODS: Serial [18F]GE-180 and O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET) PET scans were performed at day 7/8 and day 14/15 after the inoculation of GL261 mouse glioblastoma cells (n = 24) or saline (sham, n = 6) into the right striatum of immunocompetent C57BL/6 mice. An additional n = 25 sham mice underwent [18F]GE-180 PET and/or autoradiography (ARG) at days 7, 14, 21, 28, 35, 50 and 90 in order to monitor potential reactive processes that were solely related to the inoculation procedure. In vivo imaging results were directly compared to tissue-based analyses including ARG and immunohistochemistry. RESULTS: We found that the inoculation process represents an immunogenic event, which significantly contributes to TSPO radioligand uptake. [18F]GE-180 uptake in GL261-bearing mice surpassed [18F]FET uptake both in the extent and the intensity, e.g., mean target-to-background ratio (TBRmean) in PET at day 7/8: 1.22 for [18F]GE-180 vs. 1.04 for [18F]FET, p < 0.001. Sham mice showed increased [18F]GE-180 uptake at the inoculation channel, which, however, continuously decreased over time (e.g., TBRmean in PET: 1.20 at day 7 vs. 1.09 at day 35, p = 0.04). At the inoculation channel, the percentage of TSPO/IBA1 co-staining decreased, whereas TSPO/GFAP (glial fibrillary acidic protein) co-staining increased over time (p < 0.001). CONCLUSION: We identify the inoculation-driven immune response to be a relevant contributor to the PET signal and add a new aspect to consider for planning PET imaging studies in orthotopic glioblastoma models.
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Background and purpose: The PRIDE trial (NOA-28; ARO-2022-12; NCT05871021) is scheduled to start recruitment in October 2023. Its primary objective is to enhance median overall survival (OS), compared to historical median OS rates, in patients with methylguanine methlyltransferase (MGMT) promotor unmethylated glioblastoma by incorporating isotoxic dose escalation to 75 Gy in 30 fractions. To achieve isotoxicity and counteract the elevated risk of radiation necrosis (RN) associated with dose-escalated regimens, the addition of protective concurrent bevacizumab (BEV) serves as an innovative approach. The current study aims to assess the dosimetric feasibility of the proposed concept. Materials and methods: A total of ten patients diagnosed with glioblastoma were included in this dosimetric analysis. Delineation of target volumes for the reference plans adhered to the ESTRO-EANO 2023 guideline. The experimental plans included an additional volume for the integrated boost. Additionally, the 60 Gy-volume was reduced by using a margin of 1.0 cm instead of 1.5 cm. To assess the risk of symptomatic RN, the Normal Tissue Complication Probability (NTCP) was calculated and compared between the reference and experimental plans. Results: Median NTCP of the reference plan (NTCPref) and of the experimental plan (NTCPex) were 0.24 (range 0.11-0.29) and 0.42 (range 0.18-0.54), respectively. NTCPex was a median of 1.77 (range 1.60-1.99) times as high as the NTXPref. In a logarithmic comparison, the risk of RN is enhanced by a factor of median 2.00 (range 1.66-2.35). The defined constraints for the organs at risk were feasible. Conclusion: When considering the potential protective effect of BEV, which we hypothesized might reduce the risk of RN by approximately two-fold, achieving isotoxicity with the proposed dose-escalated experimental plan for the PRIDE trial seems feasible.
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In renal cell carcinoma (RCC), accurate imaging methods are required for treatment planning and response assessment to therapy. In addition, there is an urgent need for new therapeutic options, especially in metastatic RCC. One way to combine diagnostics and therapy in a so-called theranostic approach is the use of radioligands directed against surface antigens. For instance, radioligands against prostate-specific membrane antigen (PSMA) have already been successfully used for diagnosis and radionuclide therapy of metastatic prostate cancer. Recent studies have demonstrated that PSMA is expressed not only in prostate cancer but also in the neovasculature of several solid tumors, which has raised hopes to use PSMA-guided theranostic approaches in other tumor entities, too. However, data on PSMA expression in different histopathological subtypes of RCC are sparse. Because a better understanding of PSMA expression in RCC is critical to assess which patients would benefit most from theranostic approaches using PSMA-targeted ligands, we investigated the expression pattern of PSMA in different subtypes of RCC on protein level. Immunohistochemical staining for PSMA was performed on formalin-fixed, paraffin-embedded archival material of major different histological subtypes of RCC (clear cell RCC (ccRCC)), papillary RCC (pRCC) and chromophobe RCC (cpRCC). The extent and intensity of PSMA staining were scored semi-quantitatively and correlated with the histological RCC subtypes. Group comparisons were calculated with the Kruskal-Wallis test. In all cases, immunoreactivity was detected only in the tumor-associated vessels and not in tumor cells. Staining intensity was the strongest in ccRCC, followed by cpRCC and pRCC. ccRCC showed the most diffuse staining pattern, followed by cpRCC and pRCC. Our results provide a rationale for PSMA-targeted theranostic approaches in ccRCC and cpRCC.
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Various cellular sources hamper interpretation of positron emission tomography (PET) biomarkers in the tumor microenvironment (TME). We developed an approach of immunomagnetic cell sorting after in vivo radiotracer injection (scRadiotracing) with three-dimensional (3D) histology to dissect the cellular allocation of PET signals in the TME. In mice with implanted glioblastoma, translocator protein (TSPO) radiotracer uptake per tumor cell was higher compared to tumor-associated microglia/macrophages (TAMs), validated by protein levels. Translation of in vitro scRadiotracing to patients with glioma immediately after tumor resection confirmed higher single-cell TSPO tracer uptake of tumor cells compared to immune cells. Across species, cellular radiotracer uptake explained the heterogeneity of individual TSPO-PET signals. In consideration of cellular tracer uptake and cell type abundance, tumor cells were the main contributor to TSPO enrichment in glioblastoma; however, proteomics identified potential PET targets highly specific for TAMs. Combining cellular tracer uptake measures with 3D histology facilitates precise allocation of PET signals and serves to validate emerging novel TAM-specific radioligands.
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Glioblastoma , Glioma , Humanos , Ratones , Animales , Glioblastoma/diagnóstico por imagen , Glioblastoma/metabolismo , Microambiente Tumoral , Glioma/patología , Tomografía de Emisión de Positrones/métodos , Microglía/metabolismo , Proteínas Portadoras/metabolismo , Receptores de GABA/metabolismoRESUMEN
TSPO is a promising novel tracer target for positron-emission tomography (PET) imaging of brain tumors. However, due to the heterogeneity of cell populations that contribute to the TSPO-PET signal, imaging interpretation may be challenging. We therefore evaluated TSPO enrichment/expression in connection with its underlying histopathological and molecular features in gliomas. We analyzed TSPO expression and its regulatory mechanisms in large in silico datasets and by performing direct bisulfite sequencing of the TSPO promotor. In glioblastoma tissue samples of our TSPO-PET imaging study cohort, we dissected the association of TSPO tracer enrichment and protein labeling with the expression of cell lineage markers by immunohistochemistry and fluorescence multiplex stains. Furthermore, we identified relevant TSPO-associated signaling pathways by RNA sequencing.We found that TSPO expression is associated with prognostically unfavorable glioma phenotypes and that TSPO promotor hypermethylation is linked to IDH mutation. Careful histological analysis revealed that TSPO immunohistochemistry correlates with the TSPO-PET signal and that TSPO is expressed by diverse cell populations. While tumor core areas are the major contributor to the overall TSPO signal, TSPO signals in the tumor rim are mainly driven by CD68-positive microglia/macrophages. Molecularly, high TSPO expression marks prognostically unfavorable glioblastoma cell subpopulations characterized by an enrichment of mesenchymal gene sets and higher amounts of tumor-associated macrophages.In conclusion, our study improves the understanding of TSPO as an imaging marker in gliomas by unveiling IDH-dependent differences in TSPO expression/regulation, regional heterogeneity of the TSPO PET signal and functional implications of TSPO in terms of tumor immune cell interactions.
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Glioblastoma , Glioma , Células Madre Mesenquimatosas , Humanos , Glioblastoma/diagnóstico por imagen , Glioblastoma/genética , Macrófagos Asociados a Tumores , Macrófagos , Receptores de GABA/genéticaRESUMEN
ABSTRACT: A 77-year-old man presented with progressive deterioration of physical capacity after successful percutaneous coronary intervention of known chronic coronary syndrome. Transthoracic echocardiography revealed hypertrophy of the left ventricle, and electrocardiogram showed low QRS voltage in all leads. 99m Tc-DPD scintigraphy was conducted to differentiate etiology such as amyloidosis and revealed increased cardiac tracer uptake in the left (grade 3) and right ventricle. Immunofixation showed no signs of paraproteinemia or Bence-Jones proteinuria. Thus, biventricular involvement of ATTR-cardiomyopathy was identified by 99m Tc-DPD scintigraphy. This approach should be considered if hypertrophic phenotype is present in patients with persistent deterioration of physical capacity not attributable to coronary artery disease.
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Amiloidosis , Cardiomiopatías , Humanos , Amiloidosis/diagnóstico por imagen , Cardiomiopatías/diagnóstico por imagen , Ecocardiografía/efectos adversos , Corazón , Cintigrafía , Masculino , AncianoRESUMEN
The 18-kDa translocator protein (TSPO) is gaining recognition as a relevant target in glioblastoma imaging. However, data on the potential prognostic value of TSPO PET imaging in glioblastoma are lacking. Therefore, we investigated the association of TSPO PET imaging results with survival outcome in a homogeneous cohort of glioblastoma patients. Methods: Patients were included who had newly diagnosed, histologically confirmed isocitrate dehydrogenase (IDH)-wild-type glioblastoma with available TSPO PET before either normofractionated radiotherapy combined with temozolomide or hypofractionated radiotherapy. SUVmax on TSPO PET, TSPO binding affinity status, tumor volumes on MRI, and further clinical data, such as O 6-alkylguanine DNA methyltransferase (MGMT) and telomerase reverse transcriptase (TERT) gene promoter mutation status, were correlated with patient survival. Results: Forty-five patients (median age, 63.3 y) were included. Median SUVmax was 2.2 (range, 1.0-4.7). A TSPO PET signal was associated with survival: High uptake intensity (SUVmax > 2.2) was related to significantly shorter overall survival (OS; 8.3 vs. 17.8 mo, P = 0.037). Besides SUVmax, prognostic factors for OS were age (P = 0.046), MGMT promoter methylation status (P = 0.032), and T2-weighted MRI volume (P = 0.031). In the multivariate survival analysis, SUVmax in TSPO PET remained an independent prognostic factor for OS (P = 0.023), with a hazard ratio of 2.212 (95% CI, 1.115-4.386) for death in cases with a high TSPO PET signal (SUVmax > 2.2). Conclusion: A high TSPO PET signal before radiotherapy is associated with significantly shorter survival in patients with newly diagnosed IDH-wild-type glioblastoma. TSPO PET seems to add prognostic insights beyond established clinical parameters and might serve as an informative tool as clinicians make survival predictions for patients with glioblastoma.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Persona de Mediana Edad , Glioblastoma/diagnóstico por imagen , Glioblastoma/genética , Glioblastoma/radioterapia , Pronóstico , Isocitrato Deshidrogenasa/genética , Temozolomida/uso terapéutico , Tomografía de Emisión de Positrones , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/radioterapia , Receptores de GABA/genéticaRESUMEN
PURPOSE: The proPSMA trial at ten Australian centers demonstrated increased sensitivity and specificity for PSMA PET/CT compared to conventional imaging regarding metastatic status in primary high-risk prostate cancer patients. A cost-effectiveness analysis showed benefits of PSMA PET/CT over conventional imaging for the Australian setting. However, comparable data for other countries are lacking. Therefore, we aimed to verify the cost-effectiveness of PSMA PET/CT in several European countries as well as the USA. METHODS: Clinical data on diagnostic accuracy were derived from the proPSMA trial. Costs for PSMA PET/CT and conventional imaging were taken from reimbursements of national health systems and individual billing information of selected centers in Belgium, Germany, Italy, the Netherlands, and the USA. For comparability, scan duration and the decision tree of the analysis were adopted from the Australian cost-effectiveness study. RESULTS: In contrast to the Australian setting, PSMA PET/CT was primarily associated with increased costs in the studied centers in Europe and the USA. Mainly, the scan duration had an impact on the cost-effectiveness. However, costs for an accurate diagnosis using PSMA PET/CT seemed reasonably low compared to the potential consequential costs of an inaccurate diagnosis. CONCLUSION: We assume that the use of PSMA PET/CT is appropriate from a health economic perspective, but this will need to be verified by a prospective evaluation of patients at initial diagnosis.