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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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Current treatment outcome of patients with glioblastoma (GBM) remains poor. Following standard therapy, recurrence is universal with limited survival. Tumors from 173 GBM patients are analysed for somatic mutations to generate a personalized peptide vaccine targeting tumor-specific neoantigens. All patients were treated within the scope of an individual healing attempt. Among all vaccinated patients, including 70 treated prior to progression (primary) and 103 treated after progression (recurrent), the median overall survival from first diagnosis is 31.9 months (95% CI: 25.0-36.5). Adverse events are infrequent and are predominantly grade 1 or 2. A vaccine-induced immune response to at least one of the vaccinated peptides is detected in blood samples of 87 of 97 (90%) monitored patients. Vaccine-specific T-cell responses are durable in most patients. Significantly prolonged survival is observed for patients with multiple vaccine-induced T-cell responses (53 months) compared to those with no/low induced responses (27 months; P = 0.03). Altogether, our results highlight that the application of personalized neoantigen-targeting peptide vaccine is feasible and represents a promising potential treatment option for GBM patients.
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Neoplasias Encefálicas , Vacinas Anticâncer , Glioblastoma , Medicina de Precisão , Vacinas de Subunidades Antigênicas , Humanos , Glioblastoma/imunologia , Glioblastoma/terapia , Feminino , Vacinas de Subunidades Antigênicas/imunologia , Vacinas de Subunidades Antigênicas/uso terapêutico , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/uso terapêutico , Vacinas Anticâncer/administração & dosagem , Masculino , Pessoa de Meia-Idade , Medicina de Precisão/métodos , Idoso , Adulto , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/terapia , Antígenos de Neoplasias/imunologia , Linfócitos T/imunologia , Resultado do Tratamento , Vacinas de Subunidades ProteicasRESUMO
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 , Tomografia por Emissão de Pósitrons , Planejamento da Radioterapia Assistida por Computador , Glioblastoma/radioterapia , Glioblastoma/diagnóstico por imagem , Humanos , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Fluordesoxiglucose F18 , Compostos RadiofarmacêuticosRESUMO
Meningiomas are the most common primary intracranial tumors in adults and are increasing in incidence due to the aging population and the rising availability of neuroimaging. While most exhibit non-malignant behaviour, a subset of meningiomas are biologically aggressive and lead to significant neurological morbidity and mortality. In recent years, meaningful advances in our understanding of the biology of these tumors have led to the incorporation of molecular biomarkers into their grading and prognostication. However, unlike other central nervous system tumors, a unified molecular taxonomy for meningiomas has not yet been established and remains an overarching goal of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy-Not Official WHO (cIMPACT-NOW) working group. There also remains clinical equipoise on how specific meningioma cases and patient populations should be optimally managed. To address these existing gaps, members of the International Consortium on Meningiomas (ICOM) including field-leading experts, have prepared a comprehensive consensus narrative review directed towards clinicians, researchers, and patients. Included in this manuscript are detailed overviews of proposed molecular classifications, novel biomarkers, contemporary treatment strategies, trials on systemic therapies, health-related quality of life studies, and management strategies for unique meningioma patient populations. In each section we discuss the current state of knowledge as well as ongoing clinical and research challenges to road map future directions for further investigation.
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INTRODUCTION: Amyloidosis, including cerebral amyloid angiopathy, and markers of small vessel disease (SVD) vary across dominantly inherited Alzheimer's disease (DIAD) presenilin-1 (PSEN1) mutation carriers. We investigated how mutation position relative to codon 200 (pre-/postcodon 200) influences these pathologic features and dementia at different stages. METHODS: Individuals from families with known PSEN1 mutations (n = 393) underwent neuroimaging and clinical assessments. We cross-sectionally evaluated regional Pittsburgh compound B-positron emission tomography uptake, magnetic resonance imaging markers of SVD (diffusion tensor imaging-based white matter injury, white matter hyperintensity volumes, and microhemorrhages), and cognition. RESULTS: Postcodon 200 carriers had lower amyloid burden in all regions but worse markers of SVD and worse Clinical Dementia Rating® scores compared to precodon 200 carriers as a function of estimated years to symptom onset. Markers of SVD partially mediated the mutation position effects on clinical measures. DISCUSSION: We demonstrated the genotypic variability behind spatiotemporal amyloidosis, SVD, and clinical presentation in DIAD, which may inform patient prognosis and clinical trials. HIGHLIGHTS: Mutation position influences Aß burden, SVD, and dementia. PSEN1 pre-200 group had stronger associations between Aß burden and disease stage. PSEN1 post-200 group had stronger associations between SVD markers and disease stage. PSEN1 post-200 group had worse dementia score than pre-200 in late disease stage. Diffusion tensor imaging-based SVD markers mediated mutation position effects on dementia in the late stage.
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Doença de Alzheimer , Amiloidose , Doenças de Pequenos Vasos Cerebrais , Humanos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/genética , Doenças de Pequenos Vasos Cerebrais/complicações , Imagem de Tensor de Difusão , Imageamento por Ressonância Magnética , Mutação/genética , Presenilina-1/genéticaRESUMO
Background: The tumor-associated disialoganglioside GD2 is a bona fide immunotherapy target in neuroblastoma and other childhood tumors, including Ewing sarcoma and osteosarcoma. GD2-targeting antibodies proved to be effective in neuroblastoma and GD2-targeting chimeric antigen receptors (CAR)- expressing T cells as well as natural killer T cells (NKTs) are emerging. However, assessment of intra- and intertumoral heterogeneity has been complicated by ineffective immunohistochemistry as well as sampling bias in disseminated disease. Therefore, a non-invasive approach for the assessment and visualization of GD2 expression in-vivo is of upmost interest and might enable a more appropriate treatment stratification. Methods: Recently, [64Cu]Cu-NOTA-ch14.18/CHO (64Cu-GD2), a radiolabeled GD2-antibody for imaging with Positron-Emission-Tomography (PET) was developed. We here report our first clinical patients' series (n = 11) in different pediatric tumors assessed with 64Cu-GD2 PET/MRI. GD2-expression in tumors and tissue uptake in organs was evaluated by semiquantitative measurements of standardized uptake values (SUV) with PET/MRI on day 1 p.i. (n = 11) as well as on day 2 p.i. (n = 6). Results: In 8 of 9 patients with suspicious tumor lesions on PET/MRI at least one metastasis showed an increased 64Cu-GD2 uptake and a high tracer uptake (SUVmax > 10) was measured in 4 of those 8 patients. Of note, sufficient image quality with high tumor to background contrast was readily achieved on day 1. In case of 64Cu-GD2-positive lesions, an excellent tumor to background ratio (at least 6:1) was observed in bones, muscles or lungs, while lower tumor to background contrast was seen in the spleen, liver and kidneys. Furthermore, we demonstrated extensive tumor heterogeneity between patients as well as among different metastatic sites in individual patients. Dosimetry assessment revealed a whole-body dose of only 0.03 mGy/MBq (range 0.02-0.04). Conclusion: 64Cu-GD2 PET/MRI enables the non-invasive assessment of individual heterogeneity of GD2 expression, which challenges our current clinical practice of patient selection, stratification and immunotherapy application scheme for treatment with anti-GD2 directed therapies.
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Anticorpos Monoclonais , Neuroblastoma , Criança , Humanos , Anticorpos Monoclonais/uso terapêutico , Neuroblastoma/tratamento farmacológico , Tomografia por Emissão de Pósitrons/métodosRESUMO
PURPOSE: To investigate the impact of [18F]FDG-PET/CT on the management of differentiated thyroid carcinoma (DTC) in routine clinical settings. MATERIAL AND METHODS: In total, 98 patients (55 females, age 56 ± 18 years) with histologically confirmed thyroid cancer, including all types of DTC and poorly differentiated thyroid cancer (PDTC, n = 7), underwent [18F]FDG-PET/CT for staging or recurrence diagnostics performed using a state-of-the art clinical scanner (Biograph mCT, Siemens Healthineers) with a standardized examination protocol. The impact of PET/CT on clinical decision making was prospectively evaluated using standardized questionnaires completed by the referring physicians before and after PET/CT. Patient outcome was analyzed for OS drawn from patient records. RESULTS: Referring physicians were unable to establish a treatment plan for 81% of patients with thyroid cancer in the absence of PET/CT. The use of PET/CT had a notable influence on patient management, leading to the development of a well-defined treatment plan for 92% of patients. Moreover, after PET/CT a change in pre-PET/CT-intended treatments occurred in 32% of cases, and further invasive diagnostic could be waived in 7% of cases. [18F]FDG-PET/CT revealed a tumor detection rate of 68% (local tumor: 19%, lymph node metastases: 40%, distant metastases: 42%). HTg levels, when stimulated via TSH, were considerably higher in patients with metastases detected on PET/CT, compared to those without metastatic findings (p = 0.02). OS was significantly worse in patients with PDTC (p = 0.002) compared to follicular thyroid cancer (FTC) and PTC or even in patients with distant metastases at first diagnosis (p = 0.03). CONCLUSIONS: This prospective registry study confirms that [18F]FDG-PET/CT used in a routine clinical setting has a very important impact on the management of patients with thyroid cancer by initiating treatments and reducing the uses of additional imaging and invasive tests.
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BACKGROUND: Lymph node metastases (LNM) are rare in early-stage endometrial cancer, but a diagnostic systematic lymphadenectomy (LNE) is often performed to achieve reliable N-staging. Therefore, this prospective study aimed to evaluate the benefit of [18F]-Fluorodeoxyglucose (FDG) PET/MRI complementary to SPECT/CT guided sentinel lymphonodectomy (SLNE) for a less invasive N-staging Methods: 79 patients underwent a whole-body FDG-PET/MRI, SLN mapping with 99mTc-Nanocolloid SPECT/CT and indocyanine green (ICG) fluoroscopy followed by LNE which served as ground truth. RESULTS: FDG-PET/MRI was highly specific in N-staging (97.2%) but revealed limited sensitivity (66.7%) due to missed micrometastases. In contrast, bilateral SLN mapping failed more often in patients with macrometastases. The combination of SLN mapping and FDG-PET/MRI increased the sensitivity from 66.7% to 77.8%. Additional SLN labeling with dye (ICG) revealed a complete SLN mapping in 80% (8/10) of patients with failed or incomplete SLN detection in SPECT/CT, reducing the need for diagnostic systematic LNE up to 87%. FDG-PET/MRI detected para-aortic LNM in three out of four cases and a liver metastasis. CONCLUSIONS: The combination of FDG-PET/MRI and SLNE can reduce the need for diagnostic systematic LNE by up to 87%. PET/MRI complements the SLN technique particularly in the detection of para-aortic LNM and occasional distant metastases.
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OBJECTIVES: The purpose of this study was to investigate the imaging characteristics of medication-related osteonecrosis of the jaw (MRONJ) using [18F]fluoride positron emission tomography/computed tomography (PET/CT) and [18F]fluorodeoxyglucose (FDG) PET/magnetic resonance imaging (MRI) for preoperative assessment and to correlate them with microarchitectural and histomorphometric data with respect to clinical findings. METHODS: Twelve patients (five female; mean age 75 ± 7.6 yr) with symptomatic MRONJ underwent both scans on the same day, and imaging findings were used to plan surgical interventions for seven patients. Bone tracer uptake was classified as high, medium, or low, and surgical samples were evaluated using Micro-CT and histomorphometric analysis. RESULTS: CT showed medullary sclerosis in all patients, and MRI revealed gadolinium enhancement in four patients. PET imaging revealed remarkably elevated [18F]fluoride uptake and moderately increased [18F]FDG uptake in MRONJ compared to healthy jawbones, with both differences being statistically significant. [18F]fluoride uptake was associated with necrosis, bacteria, and inflammatory tissue. Micro-CT data did not show significant differences, but histomorphometric analysis revealed higher osteocyte and lacunae densities in the high [18F]fluoride uptake group, and more necrotic bone in the medium [18F]fluoride uptake group. Bacteria were observed in all areas. CONCLUSIONS: In summary, [18F]fluoride PET accurately identified MRONJ extent, revealing functional changes in jawbone remodeling not visible on CT. [18F]FDG PET showed differences in bone and soft tissue, though less pronounced. This method aids in evaluating disease activity and guiding treatment planning, requiring further research for optimal surgical approaches based on tracer uptake.
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BACKGROUND: Breast cancer is a metabolically heterogeneous disease, and although the concept of heterogeneous cancer metabolism is known, its precise role in human breast cancer is yet to be fully elucidated. METHODS: We investigated in an explorative approach a cohort of 42 primary mamma carcinoma patients with positron emission tomography/magnetic resonance imaging (PET/MR) prior to surgery, followed by histopathology and molecular diagnosis. From a subset of patients, which showed high metabolic heterogeneity based on tracer uptake and pathology classification, tumour centre and periphery specimen tissue samples were further investigated by a targeted breast cancer gene expression panel and quantitative metabolomics by nuclear magnetic resonance (NMR) spectroscopy. All data were analysed in a combinatory approach. RESULTS: [18 F]FDG (2-deoxy-2-[fluorine-18]fluoro-d-glucose) tracer uptake confirmed dominance of glucose metabolism in the breast tumour centre, with lower levels in the periphery. Additionally, we observed differences in lipid and proliferation related genes between luminal A and B subtypes in the centre and periphery. Tumour periphery showed elevated acetate levels and enrichment in lipid metabolic pathways genes especially in luminal B. Furthermore, serine was increased in the periphery and higher expression of thymidylate synthase (TYMS) indicated one-carbon metabolism increased in tumour periphery. The overall metabolic activity based on [18 F]FDG uptake of luminal B subtype was higher than that of luminal A and the difference between the periphery and centre increased with tumour grade. CONCLUSION: Our analysis indicates variations in metabolism among different breast cancer subtypes and sampling locations which details the heterogeneity of the breast tumours. Correlation analysis of [18 F]FDG tracer uptake, transcriptome and tumour metabolites like acetate and serine facilitate the search for new candidates for metabolic tracers and permit distinguishing luminal A and B. This knowledge may help to differentiate subtypes preclinically or to provide patients guide for neoadjuvant therapy and optimised surgical protocols based on individual tumour metabolism.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Fluordesoxiglucose F18/metabolismo , Perfilação da Expressão Gênica , Acetatos , Serina , LipídeosRESUMO
AIM/INTRODUCTION: Peptide receptor radionuclide therapy (PRRT) represents a cornerstone of treatment regimens for patients with low proliferative neuroendocrine tumors (NETs). However, in patients experiencing somatostatin receptor-positive NET with higher proliferation rates, a value and potential therapeutic benefit of PRRT as part of multimodal treatment approaches and potentially with addition of radiosensitizing agents has not yet been established. PATIENTS AND METHODS: In this study, 20 patients with histologically confirmed gastroenteropancreatic (GEP) NET with proliferation rates (Ki67) between 15% and 55% were treated either with PRRT only (n = 10) or with a combination therapy (n = 10) comprising PRRT and capecitabine/temozolomide (CAP/TEM) for at least 2 consecutive cycles. RESULTS: Disease control rate in patients treated with PRRT alone was 60% (40% stable disease and 20% partial response). Strikingly, in patients treated with PRRT in combination with radiosensitization (CAP/TEM), the disease control rate was 90% (20% stable disease and 70% partial response). The median progression-free survival in the PRRT only group was 12 months, whereas the median progression-free survival in the PRRT + CAP/TEM group was 26 months and has not been yet reached for all patients in the group during the observation period. The median disease-specific survival for patients with PRRT alone was 51 months, whereas this end point was not yet reached in the PRRT + CAP/TEM group. Moreover, the PRRT + CAP/TEM group showed a significantly higher reduction of SSTR-PET-based metabolic tumor volume and chromogranin A levels compared with the PRRT only group. Importantly, adverse events of all grades did not differ between both groups. CONCLUSIONS: PRRT + CAP/TEM represents a highly promising and well-tolerated therapeutic regimen for patients experiencing somatostatin receptor-positive NET with higher (Ki67 ≥ 15%) proliferation rate. Prospective randomized clinical trials are warranted.
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Neoplasias Intestinais , Tumores Neuroendócrinos , Compostos Organometálicos , Neoplasias Pancreáticas , Neoplasias Gástricas , Humanos , Octreotida/uso terapêutico , Projetos Piloto , Receptores de Somatostatina/metabolismo , Antígeno Ki-67 , Estudos Prospectivos , Neoplasias Pancreáticas/patologia , Tumores Neuroendócrinos/radioterapia , Tumores Neuroendócrinos/metabolismo , Radioisótopos/uso terapêutico , Compostos Organometálicos/uso terapêuticoRESUMO
BACKGROUND: PET imaging after yttrium-90 (Y-90) radioembolization is challenging because of the low positron fraction of Y-90 (32 × 10-6). The resulting low number of events can be compensated by the high sensitivity of long axial field-of-view (LAFOV) PET/CT scanners. Nevertheless, the reduced event statistics require optimization of the imaging protocol to achieve high image quality (IQ) and quantification accuracy sufficient for post-treatment dosimetry. METHODS: Two phantoms (NEMA IEC and AbdoMan phantoms, mimicking human liver) filled with Y-90 and a 4:1 sphere (tumor)-to-background ratio were scanned for 24 h with the Biograph Vision Quadra (Siemens Healthineers). Eight patients were scanned after Y-90 radioembolization (1.3-4.7 GBq) using the optimized protocol (obtained by phantom studies). The IQ, contrast recovery coefficients (CRCs) and noise were evaluated for their limited and full acceptance angles, different rebinned scan durations, numbers of iterations and post-reconstruction filters. The s-value-based absorbed doses were calculated to assess their suitability for dosimetry. RESULTS: The phantom studies demonstrate that two iterations, five subsets and a 4 mm Gaussian filter provide a reasonable compromise between a high CRC and low noise. For a 20 min scan duration, an adequate CRC of 56% (vs. 24 h: 62%, 20 mm sphere) was obtained, and the noise was reduced by a factor of 1.4, from 40% to 29%, using the full acceptance angle. The patient scan results were consistent with those from the phantom studies, and the impacts on the absorbed doses were negligible for all of the studied parameter sets, as the maximum percentage difference was -3.89%. CONCLUSIONS: With 2i5s, a 4 mm filter and a scan duration of 20 min, IQ and quantification accuracy that are suitable for post-treatment dosimetry of Y-90 radioembolization can be achieved.
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BACKGROUND: Histogram indices (HIs) and texture features (TFs) are considered to play an important role in future oncologic PET-imaging and it is unknown how these indices are affected by changes of tracer doses. A randomized undersampling of PET list mode data enables a simulation of tracer dose reduction. We performed a phantom study to compare HIs/TFs of simulated and measured tracer dose reductions and evaluated changes of HIs/TFs in the liver of patients with PETs from simulated reduced tracer doses. Overall, 42 HIs/TFs were evaluated in a NEMA phantom at measured and simulated doses (stepwise reduction of [18 F] from 100% to 25% of the measured dose). [18 F]-FDG-PET datasets of 15 patients were simulated from 3.0 down to 0.5 MBq/kgBW in intervals of 0.25 MBq/kgBW. HIs/TFs were calculated from two VOIs placed in physiological tissue of the right and left liver lobe and linear correlations and coefficients of variation analysis were performed. RESULTS: All 42 TFs did not differ significantly in measured and simulated doses (p > 0.05). Also, 40 TFs showed the same behaviour over dose reduction regarding differences in the same group (measured or simulated), and for 26 TFs a linear behaviour over dose reduction for measured and simulated doses could be validated. Out of these, 13 TFs could be identified, which showed a linear change in TF value in both the NEMA phantom and patient data and therefore should maintain the same informative value when transferred in a dose reduction setting. Out of this Homogeneity 2, Entropy and Zone size non-uniformity are of special interest because they have been described as preferentially considerable for tumour heterogeneity characterization. CONCLUSIONS: We could show that there was no significant difference of measured and simulated HIs/TFs in the phantom study and most TFs reveal a linear behaviour over dose reduction, when tested in homogeneous tissue. This indicates that texture analysis in PET might be robust to dose modulations.
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Fluordesoxiglucose F18 , Neoplasias , Humanos , Redução da Medicação , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Neoplasias/diagnóstico por imagem , Neoplasias/radioterapiaRESUMO
PET/CT scanners with a long axial field-of-view (LAFOV) provide increased sensitivity, enabling the adjustment of imaging parameters by reducing the injected activity or shortening the acquisition time. This study aimed to evaluate the limitations of reduced [18F]FDG activity doses on image quality, lesion detectability, and the quantification of lesion uptake in the Biograph Vision Quadra, as well as to assess the benefits of the recently introduced ultra-high sensitivity mode in a clinical setting. A number of 26 patients who underwent [18F]FDG-PET/CT (3.0 MBq/kg, 5 min scan time) were included in this analysis. The PET raw data was rebinned for shorter frame durations to simulate 5 min scans with lower activities in the high sensitivity (HS) and ultra-high sensitivity (UHS) modes. Image quality, noise, and lesion detectability (n = 82) were assessed using a 5-point Likert scale. The coefficient of variation (CoV), signal-to-noise ratio (SNR), tumor-to-background ratio (TBR), and standardized uptake values (SUV) including SUVmean, SUVmax, and SUVpeak were evaluated. Subjective image ratings were generally superior in UHS compared to the HS mode. At 0.5 MBq/kg, lesion detectability decreased to 95% (HS) and to 98% (UHS). SNR was comparable at 1.0 MBq/kg in HS (5.7 ± 0.6) and 0.5 MBq/kg in UHS (5.5 ± 0.5). With lower doses, there were negligible reductions in SUVmean and SUVpeak, whereas SUVmax increased steadily. Reducing the [18F]FDG activity to 1.0 MBq/kg (HS/UHS) in a LAFOV PET/CT provides diagnostic image quality without statistically significant changes in the uptake parameters. The UHS mode improves image quality, noise, and lesion detectability compared to the HS mode.
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Carriers of mutations responsible for dominantly inherited Alzheimer disease provide a unique opportunity to study potential imaging biomarkers. Biomarkers based on routinely acquired clinical MR images, could supplement the extant invasive or logistically challenging) biomarker studies. We used 1104 longitudinal MR, 324 amyloid beta, and 87 tau positron emission tomography imaging sessions from 525 participants enrolled in the Dominantly Inherited Alzheimer Network Observational Study to extract novel imaging metrics representing the mean (µ) and standard deviation (σ) of standardized image intensities of T1-weighted and Fluid attenuated inversion recovery (FLAIR) MR scans. There was an exponential decrease in FLAIR-µ in mutation carriers and an increase in FLAIR and T1 signal heterogeneity (T1-σ and FLAIR-σ) as participants approached the symptom onset in both supramarginal, the right postcentral and right superior temporal gyri as well as both caudate nuclei, putamina, thalami, and amygdalae. After controlling for the effect of regional atrophy, FLAIR-µ decreased and T1-σ and FLAIR-σ increased with increasing amyloid beta and tau deposition in numerous cortical regions. In symptomatic mutation carriers and independent of the effect of regional atrophy, tau pathology demonstrated a stronger relationship with image intensity metrics, compared with amyloid pathology. We propose novel MR imaging intensity-based metrics using standard clinical T1 and FLAIR images which strongly associates with the progression of pathology in dominantly inherited Alzheimer disease. We suggest that tau pathology may be a key driver of the observed changes in this cohort of patients.
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Doença de Alzheimer , Humanos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Doença de Alzheimer/complicações , Peptídeos beta-Amiloides , Imageamento por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons , Biomarcadores , Atrofia , Proteínas tauRESUMO
223Ra-dichloride (223Ra) and 177Lu-prostate-specific membrane antigen (PSMA) are approved treatments for metastatic castration-resistant prostate cancer (mCRPC). The safety and effectiveness of sequential use of 223Ra and 177Lu-PSMA in patients with mCRPC are not well described. This study aimed to evaluate 177Lu-PSMA safety and efficacy in patients with mCRPC previously treated with 223Ra. Methods: The radiumâlutetium (RALU) study was a multicenter, retrospective, medical chart review. Participants had received at least 1 223Ra dose and, in any subsequent therapy line, at least 1 177Lu-PSMA dose. Primary endpoints included the incidence of adverse events (AEs), serious AEs, grade 3-4 hematologic AEs, and abnormal laboratory values. Secondary endpoints included overall survival, time to next treatment/death, and change from baseline in serum prostate-specific antigen and alkaline phosphatase levels. Results: Data were from 133 patients. Before 177Lu-PSMA therapy, 56% (75/133) of patients received at least 4 life-prolonging therapies; all patients received 223Ra (73% received 5-6 injections). Overall, 27% (36/133) of patients received at least 5 177Lu-PSMA infusions. Any-grade treatment-emergent AEs were reported in 79% (105/133) of patients and serious AEs in 30% (40/133). The most frequent grade 3-4 laboratory abnormalities were anemia (30%, 40/133) and thrombocytopenia (13%, 17/133). Median overall survival was 13.2 mo (95% CI, 10.5-15.6 mo) from the start of 177Lu-PSMA. Conclusion: In this real-world setting, 223Ra followed by 177Lu-PSMA therapy in heavily pretreated patients with mCRPC was clinically feasible, with no indication of impairment of 177Lu-PSMA safety or effectiveness.
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Neoplasias de Próstata Resistentes à Castração , Rádio (Elemento) , Masculino , Humanos , Lutécio/uso terapêutico , Rádio (Elemento)/efeitos adversos , Resultado do Tratamento , Estudos Retrospectivos , Próstata/patologia , Compostos Radiofarmacêuticos/uso terapêutico , Antígeno Prostático Específico , Dipeptídeos/efeitos adversos , Compostos Heterocíclicos com 1 Anel/efeitos adversosRESUMO
BACKGROUND: The European Association of Urology guidelines include the lutetium-177 (177Lu) PSMA-617 prostate-specific membrane antigen (PSMA) ligand as a therapy option for metastatic castration-resistant prostate cancer (mCRPC). A major challenge in clinical practice is to pursue a personalized treatment approach based on robust predictive biomarkers. OBJECTIVE: To assess the performance of 177Lu PSMA in real-world practice and to elaborate clinical biomarkers for evaluating treatment responses. DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective observational study including 233 patients with mCRPC treated with 177Lu PSMA in eight high-volume European centers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Baseline characteristics and clinical parameters during and after 177Lu PSMA treatment were documented. Correlations to treatment response were analyzed using χ2 and log-rank tests, with differences between groups with and without disease progression calculated using a Mann-Whitney U test. Univariate and multivariate-adjusted hazard ratios (HRs) were measured using Cox proportional hazards models. RESULTS AND LIMITATIONS: A prostate-specific antigen (PSA) decrease of ≥30% was observed in 41.7%, 63.5%, and 77.8% of patients after the first, second, and third treatment cycle, respectively. Restaging performed via PSMA positron emission tomography-computed tomography revealed that 33.7% of patients had an imaging-based response, including two patients with a complete response, while 13.4% had stable disease. The median time to progression was 5 mo and the median time until the start of a consecutive antineoplastic therapy was 8.5 mo. Of importance, a PSA decrease ≥30% after the first two cycles of 177Lu PSMA (1 cycle: p = 0.0003; 2 cycles: p = 0.004), absolute PSA after the first three cycles (1 cycle: p = 0.011; 2 cycles: p = 0.0005; 3 cycles: p = 0.002), and a PSA doubling time >6 mo (p = 0.009) were significantly correlated to treatment response. Furthermore, gamma-glutamyl transferase ≤31 U/L at the start of 177Lu PSMA therapy was correlated with 1.5 times higher risk of progression for patients without but not with visceral metastases (p = 0.046). CONCLUSIONS: 177Lu PSMA is an effective treatment option in mCRPC in the real-world setting. A PSA decrease ≥30% after the first two cycles is an early marker of response that can be easily implemented in clinical practice. PATIENT SUMMARY: 177Lu PSMA is a radioactive agent approved for treatment of advanced prostate cancer. We reviewed its use outside of clinical trials for patients treated at eight European centers. We found that 177Lu PSMA is an effective treatment option in real-world practice. A PSA (prostate-specific antigen) decrease of ≥30% after the first two therapy cycles is an early indicator of response to treatment and can be used in personalizing treatments for patients.
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The Dominantly Inherited Alzheimer Network (DIAN) is an international collaboration studying autosomal dominant Alzheimer disease (ADAD). ADAD arises from mutations occurring in three genes. Offspring from ADAD families have a 50% chance of inheriting their familial mutation, so non-carrier siblings can be recruited for comparisons in case-control studies. The age of onset in ADAD is highly predictable within families, allowing researchers to estimate an individual's point in the disease trajectory. These characteristics allow candidate AD biomarker measurements to be reliably mapped during the preclinical phase. Although ADAD represents a small proportion of AD cases, understanding neuroimaging-based changes that occur during the preclinical period may provide insight into early disease stages of 'sporadic' AD also. Additionally, this study provides rich data for research in healthy aging through inclusion of the non-carrier controls. Here we introduce the neuroimaging dataset collected and describe how this resource can be used by a range of researchers.
Assuntos
Doença de Alzheimer , Artrogripose , Humanos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Tomografia por Emissão de Pósitrons , Imageamento por Ressonância Magnética , Neuroimagem , Mutação/genética , Peptídeos beta-Amiloides/genéticaRESUMO
There is a lack of evidence regarding the clinical impact of [18F]fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT, hereinafter referred to as PET/CT), especially regarding management changes and their link to overall survival. We analyzed 52 PET/CTs in 47 stage I-IV breast cancer patients, selected from a prospective oncological PET/CT registry. Indications for PET/CT were primary staging (n = 15), restaging (n = 17), and suspected recurrence (n = 20). PET/CT-induced management changes were categorized as major or minor. PET/CT-induced management changes in 41 of 52 scans (78.8%; 38 of 47 patients (80.9%)), of which major changes were suggested in 18 of 52 scans (34.6%, 17 of 47 patients, 36.2%). PET/CT downstaged 6 of 15 primary staging patients, excluding distant metastases. Major management changes were documented in 3 of 17 restaging exams. PET/CT ruled out clinically suspected recurrence in 6 of 20 cases and confirmed it in 11 of 20. In three cases, locoregional recurrence had already been diagnosed via biopsy. In 30 of 52 exams, additional diagnostic tests were avoided, of which 13 were invasive. PET/CT-based management changes resulted in a 5-year survival rate of 72.3% for the whole study group, 93.3% for the staging group, 53.8% for the restaging group, and 68.4% for the recurrence group. This study shows that PET/CT significantly impacts clinical management decisions in breast cancer patients in different clinical scenarios, potentially determining the patient's tumor stage as the basis for further therapy more reliably and by avoiding unnecessary diagnostic tests.