fluoro-2-deoxy-D-glucose Research Articles

Detection of cancer-associated cachexia in lung cancer patients using whole-body [18F]FDG-PET/CT imaging: A multi-centre study.

Cancer-associated cachexia (CAC) is a metabolic syndrome contributing to therapy resistance and mortality in lung cancer patients (LCP). CAC is typically defined using clinical non-imaging criteria. Given the metabolic underpinnings of CAC and the ability of [18F]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET)/computer tomography (CT) to provide quantitative information on glucose turnover, we evaluate the usefulness of whole-body (WB) PET/CT imaging, as part of the standard diagnostic workup of LCP, to provide additional information on the onset or presence of CAC. This multi-centre study included 345 LCP who underwent WB [18F]FDG-PET/CT imaging for initial clinical staging. A weight loss grading system (WLGS) adjusted to body mass index was used to classify LCP into 'No CAC' (WLGS-0/1 at baseline prior treatment and at first follow-up: N=158, 51F/107M), 'Dev CAC' (WLGS-0/1 at baseline and WLGS-3/4 at follow-up: N=90, 34F/56M), and 'CAC' (WLGS-3/4 at baseline: N=97, 31F/66M). For each CAC category, mean standardized uptake values (SUV) normalized to aorta uptake (<SUVaorta>) and CT-defined volumes were extracted for abdominal and visceral organs, muscles, and adipose-tissue using automated image segmentation of baseline [18F]FDG-PET/CT images. Imaging and non-imaging parameters from laboratory tests were compared statistically. A machine-learning (ML) model was then trained to classify LCP as 'No CAC', 'Dev CAC', and 'CAC' based on their imaging parameters. SHapley Additive exPlanations (SHAP) analysis was employed to identify the key factors contributing to CAC development for each patient. The three CAC categories displayed multi-organ differences in <SUVaorta>. In all target organs, <SUVaorta> was higher in the 'CAC' cohort compared with 'No CAC' (P<0.01), except for liver and kidneys, where <SUVaorta> in 'CAC' was reduced by 5%. The 'Dev CAC' cohort displayed a small but significant increase in <SUVaorta> of pancreas (+4%), skeletal-muscle (+7%), subcutaneous adipose-tissue (+11%), and visceral adipose-tissue (+15%). In 'CAC' patients, a strong negative Spearman correlation (ρ=-0.8) was identified between <SUVaorta> and volumes of adipose-tissue. The machine-learning model identified 'CAC' at baseline with 81% of accuracy, highlighting <SUVaorta> of spleen, pancreas, liver, and adipose-tissue as most relevant features. The model performance was suboptimal (54%) when classifying 'Dev CAC' versus 'No CAC'. WB [18F]FDG-PET/CT imaging reveals groupwise differences in the multi-organ metabolism of LCP with and without CAC, thus highlighting systemic metabolic aberrations symptomatic of cachectic patients. Based on a retrospective cohort, our ML model identified patients with CAC with good accuracy. However, its performance in patients developing CAC was suboptimal. A prospective, multi-centre study has been initiated to address the limitations of the present retrospective analysis.

Improved Diagnostic Accuracy for Polymyalgia Rheumatica using FDG-PET/CT with Clinical Diagnosis or 2012 ACR/EULAR Classification Criteria.

In routine care, clinicians may employ 2-[18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) computed tomography (CT) to validate their initial clinical diagnosis of polymyalgia rheumatica (PMR). Nevertheless, the diagnostic utility of combining FDG-PET/CT findings with clinical presentation has not been explored. Therefore, this study aimed to investigate whether the diagnostic accuracy for PMR could be enhanced by combining FDG-PET/CT findings with the clinical baseline diagnosis or the 2012 ACR/EULAR clinical classification criteria for PMR. An investigation and a validation cohort were included from two countries, encompassing 66/27 and 36/21 PMR/non-PMR patients, respectively. The cohorts comprised treatment-naïve patients suspected of PMR, who initially received a clinical baseline diagnosis and underwent FDG-PET/CT scans. The FDG-PET/CT Leuven-score was applied to classify patients as either PMR or non-PMR and combined with the clinical baseline diagnosis. Final diagnoses were established through clinical follow-up after twelve or six months in the investigation and validation cohorts, respectively. In the investigation cohort, a clinical baseline diagnosis yielded a sensitivity/specificity of 94%/82%, compared with 78%/70% using the ACR/EULAR criteria. Combining the clinical baseline diagnosis with a positive Leuven-score showed a sensitivity/specificity of 80%/93%, compared with 80%/82% for an ACR/EULAR-Leuven-score. In the validation cohort, the baseline diagnosis revealed a sensitivity/specificity of 100%/91%, compared with 92%/76% using the ACR/EULAR criteria. Combining FDG-PET/CT with the baseline diagnosis demonstrated a sensitivity/specificity of 83%/95% compared with 89%/81% for the ACR/EULAR-Leuven-score. Combining FDG-PET/CT findings with the clinical baseline diagnosis or ACR/EULAR clinical classification criteria can improve the diagnostic specificity for PMR.

Sonographic risk stratification of FDG-avid thyroid nodules using the Thyroid Imaging Reporting and Data System.

The increasing usage of positron emission tomography/computed tomography (PET/CT) for detection and monitoring of malignancy has led to an increase in incidental detection of thyroid nodules. Nodules that demonstrate increased avidity for 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) have been shown to carry a high incidence of malignancy and warrant further investigation. At present, there has been limited research on the risk stratification of FDG-avid thyroid incidentalomas. Thus, this study aims to evaluate the efficacy of the ACR TIRADS classification in the risk stratification of such nodules. Data were collected retrospectively for FDG-avid thyroid incidentalomas over a 10-year period. Nodules were characterised using the TIRADS classification and, subsequently, underwent fine-needle aspirate cytology. Cytological findings were classified using the Bethesda reporting system. Non-diagnostic samples (Bethesda class I) were excluded. The remaining samples were divided into two groups: benign (Bethesda class II) or suspicious for malignancy/malignant (Bethesda class III or above). Thirty-six percent of low-risk nodules and 45% of high-risk nodules were malignant, respectively (P = 0.516). The sensitivity and specificity of TIRADS for detection of malignant nodules were 56% and 54%, respectively. There were no malignant TIRADS 1 or 2 nodules. The absence of any suspicious sonographic features had a 1.0 negative predictive value. FDG-avid nodules classified as TIRADS 1 or 2 or have no suspicious ultrasound features have a 0% incidence of malignancy and thus may not require further assessment with fine-needle aspirate cytology (FNA) when detected incidentally. FDG-avid nodules that are TIRADS 3 or above should undergo FNA regardless of size due to the high risk of malignancy and poor sensitivity of the TIRADS classification system.

Low-dose and standard-dose whole-body [18F]FDG-PET/CT imaging: implications for healthy controls and lung cancer patients

Aim: High-sensitivity hybrid positron emission tomography (PET) imaging using advanced whole-body (WB) or total-body PET/computed tomography (CT) systems permits reducing injected tracer activity while preserving diagnostic quality. Such approaches are promising for healthy control studies or exploring inter-organ communication in systemic diseases. This study assessed test/retest variations in the fluoro-2-deoxy-D-glucose (FDG) uptake in key organs from low-dose (LD) and standard-dose (STD) [18F]FDG-PET/CT imaging protocols in healthy controls and lung cancer patients.Methods: A total of 19 healthy controls (19–62 years, 46–104 kg, 10 M/9 F) and 7 lung cancer patients (47–77 years, 50–88 kg, 4 M/3 F) underwent [18F]FDG-PET/CT imaging. All subjects were first injected (“test,” LD) with 28 ± 2 MBq FDG and underwent a dynamic (0–67 min post-injection) WB imaging protocol with LD-CT. Then, 90 min post-LD injection, the subjects were repositioned and injected with 275 ± 16 MBq FDG (“retest,” STD). Second LD-CT and STD-CT scans were acquired for healthy controls and patients, respectively. Static images (55–67 min post-injection) were considered for subsequent analysis. The CT images were used to automatically segment the target volumes of interest. Standardized uptake values normalized to the body weight (SUVBW) were extracted for each volume of interest. The mean SUVBW were compared for both LD/STD conditions with paired t-tests. In patients, FDG-avid lesions were manually delineated on LD and STD static images. Effective dose levels were estimated from both the CT and PET acquisitions.Results: Organ-based mean SUVBW were similar between the LD and STD (mean %difference ≤5%) in both healthy controls and cancer patients, except in the heart. Intra-control test/retest variability was significant in the brain, heart, and skeletal muscle (p &amp;lt; 0.05). While 17 lesions were delineated on the STD images of the patients, only 10/17 lesions were identified on the LD images due to increased image noise. Lesion-based mean SUVBW were similar between LD and STD acquisitions (p = 0.49, %difference = 10%). In patients, the effective doses were (1.9 ± 0.2) mSv (LD-CT), (16.6 ± 5.4) mSv (STD-CT), (0.5 ± 0.1) mSv (LD-PET), and (4.6 ± 0.3) mSv (STD-PET).Conclusion: LD and STD [18F]FDG injections in healthy controls and lung cancer patients yielded comparable mean SUVBW, except in the heart. Dose levels may be reduced for [18F]FDG-PET imaging without a loss in mean SUVBW accuracy, promoting LD-PET/CT protocols for studying multi-organ metabolic patterns. In oncology patients, this approach may be hindered by a lower diagnostic quality in the presence of significant noise.

The effect of prednisolone and a short-term prednisolone discontinuation for the diagnostic accuracy of FDG-PET/CT in polymyalgia rheumatica—a prospective study of 101 patients

Purpose2-[18F]Fluoro-2-deoxy-D-glucose (FDG)–positron emission tomography (PET)/computed tomography (CT) has been suggested as an imaging modality to diagnose polymyalgia rheumatica (PMR). However, the applicability of FDG-PET/CT remains unclear, especially following glucocorticoid administration. This study aimed to investigate the diagnostic accuracy of FDG-PET/CT before and during prednisolone treatment, as well as following short-term prednisolone discontinuation.MethodsTreatment naïve suspected PMR patients were clinically diagnosed at baseline and subsequently had an FDG-PET/CT performed. Patients diagnosed with PMR were administered prednisolone following the first FDG-PET/CT and had a second FDG-PET/CT performed after 8 weeks of treatment. Subsequently, prednisolone was tapered with short-term discontinuation at week 9 followed by a third FDG-PET/CT at week 10. An FDG-PET/CT classification of PMR/non-PMR was applied, utilizing both the validated Leuven score and a dichotomous PMR score. The final diagnosis was based on clinical follow-up after 1 year.ResultsA total of 68 and 27 patients received a final clinical diagnosis of PMR or non-PMR. A baseline FDG-PET/CT classified the patients as having PMR with a sensitivity/specificity of 86%/63% (Leuven score) and 82%/70% (dichotomous score). Comparing the subgroup of non-PMR with inflammatory diseases to the PMR group demonstrated a specificity of 39%/54% (Leuven/dichotomous score). After 8 weeks of prednisolone treatment, the sensitivity of FDG-PET/CT decreased to 36%/41% (Leuven/dichotomous score), while a short-term prednisolone discontinuation increased the sensitivity to 66%/60%.ConclusionFDG-PET/CT has limited diagnostic accuracy for differentiating PMR from other inflammatory diseases. If FDG-PET/CT is intended for diagnostic purposes, prednisolone should be discontinued to enhance diagnostic accuracy.Trial registrationClinicalTrials.gov (NCT04519580). Registered 17th of August 2020.

Modulation of FDG Uptake by Cell Cycle Synchronization Using a T-Type Calcium Channel Inhibitor.

We investigated whether cell cycle synchronization induced by the T-type calcium channel inhibitor mibefradil could increase tumoral 2-[18F] fluoro-2-deoxy-d-glucose (FDG) uptake in vitro and in vivo. Human prostate cancer cells (PC-3) were treated with 10 μM mibefradil for 24, 48, and 72 h to induce G1 arrest. Cell cycle distribution was analyzed at 0, 4, 8, 12, 15, 18, and 24 h after mibefradil withdrawal. Cellular uptake was measured after incubating cells with [3H] Deoxy-d-Glucose (DDG) for 1 h at the same time points used in the cell cycle analysis. The correlation between [3H] DDG uptake and each cell cycle phase was evaluated in the early (0-12 h) and late phases (15-24 h) of synchronization. In vivo FDG PET imaging was performed in PC-3-bearing mice at baseline, 24 h, and 48 h after mibefradil treatment. The G0/G1 fraction of PC-3 cells was significantly increased from 33.1% ± 0.2% to 60.9% ± 0.8% after 24 h mibefradil treatment, whereas the S and G2/M fractions were decreased from 36.3% ± 1.4% to 23.2% ± 1.1% and from 29.7% ± 1.3% to 14.9% ± 0.9%, respectively, which were similar to the results by serum starvation. Mibefradil treatment for 24, 48, and 72 h increased the number of cells in S phase at 18-24 h after withdrawal; however, only the 72 h treatment increased [3H] DDG uptake (145.8 ± 5.8% of control at 24 h after withdrawal). [3H] DDG uptake was positively correlated with the size of the S phase fraction and negatively correlated with the size of the G0/G1 fraction in the late phase of synchronization. DDG uptake was significantly increased by mibefradil-induced cell cycle synchronization and correlated with the sizes of cell cycle fractions. In vivo FDG PET imaging also demonstrated a significant increase in tumor uptake after mibefradil treatment. Quantified tumor FDG uptake (%ID/g) increased from 4.13 ± 2.10 to 4.7 ± 2.16 at 24 h, and 5.95 ± 2.57 at 48 h (p < 0.05). Cell cycle synchronization could be used to increase the diagnostic sensitivity of clinical FDG positron emission tomography.

18F-FDG PET/CT-based radiomics model for predicting the degree of pathological differentiation in non-small cell lung cancer: a multicentre study

To explore the value of 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)/computed tomography (CT)-based radiomics model for predicting the degree of pathological differentiation in non-small-cell lung cancer (NSCLC). Clinical characteristics of 182 NSCLC patients from four centres were collected, and radiomics features were extracted from 18F-FDG PET/CT images. Three logistic regression prediction models were established: clinical model; radiomics model; and nomogram combining radiomics signatures and clinical features. The predictive ability of the models was assessed using receiver operating characteristics curve analysis. Patients from centre 1 were assigned randomly to the training and internal validation cohorts (7:3 ratio); patients from centres 2-4 served as the external validation cohort. The area under the curve (AUC) values for the clinical model in the training, internal validation, and external validation cohort were 0.74 (95% confidence interval [CI]=0.64-0.84), 0.64 (95% CI=0.46-0.81), and 0.74 (95% CI=0.60-0.88), respectively. In the training (AUC: 0.84 [95% CI=0.77-0.92]), internal validation (AUC: 0.81 [95% CI=0.67-0.95]), and external validation cohorts (AUC: 0.74 [95% CI=0.58-0.89]), the radiomics model showed good predictive ability for differentiation. Compared to the clinical and radiomics models, the nomogram has relatively better diagnostic performance, and the AUC values for nomogram in the training, internal validation, and external validation cohort were 0.86 (95% CI=0.78-0.93), 0.83 (95% CI=0.70-0.96), and 0.77 (95% CI=0.62-0.92), respectively. The 18F-FDG PET/CT-based radiomics model showed good ability for predicting the degree of differentiation of NSCLC. The nomogram combining the radiomics signature and clinical features has relatively better diagnostic performance.

From FDG and beyond: the evolving potential of nuclear medicine.

The radiopharmaceutical 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) has been dominantly used in positron emission tomography (PET) scans for over 20years, and due to its vast utility its applications have expanded and are continuing to expand into oncology, neurology, cardiology, and infectious/inflammatory diseases. More recently, the addition of artificial intelligence (AI) has enhanced nuclear medicine diagnosis and imaging with FDG-PET, and new radiopharmaceuticals such as prostate-specific membrane antigen (PSMA) and fibroblast activation protein inhibitor (FAPI) have emerged. Nuclear medicine therapy using agents such as [177Lu]-dotatate surpasses conventional treatments in terms of efficacy and side effects. This article reviews recently established evidence of FDG and non-FDG drugs and anticipates the future trajectory of nuclear medicine.

Prevalence and risk factors for retropharyngeal and retro-styloid lymph node metastasis in hypopharyngeal carcinoma

BackgroundWe evaluated the prevalence and identified the risk factors for retropharyngeal and retro-styloid lymph node metastasis (LNM) in patients with hypopharyngeal carcinoma (HPC). This was achieved using a combination of magnetic resonance (MR) and [18 F]-fluoro-2-deoxy-D-glucose (FDG)–positron emission tomography (PET)/computed tomography (CT) images.MethodsTwo board-certified radiation oncologists retrospectively reviewed pretreatment FDG–PET/CT images and contrast-enhanced thin-slice CT and MR images of 155 patients with HPC who underwent radiotherapy. Fisher’s exact tests and logistic regression analyses were performed to assess the risk factors for LNM.ResultsRetropharyngeal LNM (RPLNM) was confirmed in 20 (13%) patients. Posterior wall (PW) tumors (odds ratio [OR]: 4.128, 95% confidence interval [CI]: 1.339–12.727; p = 0.014) and bilateral or contralateral cervical LNM (OR: 11.577, 95% CI: 2.135–62.789; p = 0.005) were significantly correlated with RPLNM. The RPLNM was found in 9 (32%) of the 28 patients with PW tumors. Of these 9 patients, 2 (7%) had ipsilateral RPLNM, 3 (11%) had contralateral RPLNM, and 4 (14%) had bilateral RPLNM. The PW tumors were significantly associated with contralateral RPLNM (p < 0.001). Retro-styloid LNM (RSLNM) was confirmed in two (1%) patients, both of whom had ipsilateral RSLNM with lymph nodes (LNs) of ≥ 15 mm in the upper limit of ipsilateral level II. A significant association was found between LNs of ≥ 15 mm in the upper limit of ipsilateral level II and ipsilateral RSLNM (p = 0.001).ConclusionsThe RPLNM was identified in 13% of patients with HPC. The PW tumors and bilateral or contralateral cervical LNM were risk factors for RPLNM; particularly, PW tumors were a specific risk factor for contralateral RPLNM. Although the RSLNM was rare, LNs of ≥ 15 mm in the upper limit of ipsilateral level II were a risk factor for ipsilateral RSLNM.

Prognostic Value of 18F-Fluorodeoxyglucose Uptake of Bone Marrow on PET/CT in Patients with Limited Disease Small Cell Lung Cancer

Merve AYIK TURK1, Berna KOMURCUOGLU2, Ahmet YANARTAS3, Ozgur BATUM2, Yunus TURK4, Mehmet Ufuk YILMAZ5 1Izmir Bozyaka Training and Research Hospital, Department of Pulmonology, İzmir 2Dr. Suat Seren Chest Diseases and Surgery Training and Research Hospital, Department of Pulmonology, İzmir 3Dr. Suat Seren Chest Diseases and Surgery Training and Research Hospital, Department of Nuclear Medicine, İzmir 4Dr. Suat Seren Chest Diseases and Surgery Training and Research Hospital, Department of Thoracic Surgery, İzmir 5Medicana Health Groups, Department of Pulmonology, İzmir Keywords: Small cell lung cancer, Prognostic factors, Limited stage, Bone marrow FDG uptake Small cell lung cancer (SCLC) is a malignancy from the neuroendocrine tumor family, which has a poor prognosis and presents with metastases at the time of the diagnosis. The present study investigated the relationship between bone marrow fluorodeoxy-D-glucose (FDG) uptake and survival to evaluate prognosis in limited-stage SCLC. This single-center retrospective study examined a total of 220 patients diagnosed with limited-stage SCLC between January 2010 and June 2019. Bone marrow FDG uptake, serum inflammatory markers, and other factors used to determine the prognosis, as well as overall survival (OS) and progression-free survival (PFS), were recorded and retrospectively analyzed. Within physiological limits, bone marrow standardized uptake value (SUV) mean of &gt; 1.95 was identified as a good prognostic factor for PFS (p= 0.03). The multivariate analysis of OS and PFS revealed that the Eastern Cooperative Oncology Group (ECOG) performance scale (p= 0.001) was a common independent prognostic factor. Stages of the disease, albumin levels and bone marrow-to-liver ratio (BLR) [one of the positron emission tomography/computed tomography (PET/CT) parameters] of &lt; 0.8 were prognostic factors for OS. The bone marrow SUV mean was positively correlated with the primary tumor SUV max and SUV mean. The bone marrow SUV mean is a parameter that can be used to predict PFS in limited-stage SCLC. For OS, in turn, the BLR was identified as an independent factor.

Longitudinal changes in metabolic network activity in early Alzheimer's disease.

The progression of Alzheimer's disease (AD) has been linked to two metabolic networks, the AD-related pattern (ADRP) and the default mode network (DMN). Converting and clinically stable cognitively normal subjects (n=47) and individuals with mild cognitive impairment (n=96) underwent 2-[18 F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) three or more times over 6 years (nscans =705). Expression levels for ADRP and DMN were measured in each subject and time point, and the resulting changes were correlated with cognitive performance. The role of network expression in predicting conversion to dementia was also evaluated. Longitudinal increases in ADRP expression were observed in converters, while age-related DMN loss was seen in converters and nonconverters. Cognitive decline correlated with increases in ADRP and declines in DMN, but conversion to dementia was predicted only by baseline ADRP levels. The results point to the potential utility of ADRP as an imaging biomarker of AD progression.

Chylothorax due to hepatic alveolar echinococcosis with infiltration of diaphragm and left pleura: a case report

BackgroundAlveolar echinococcosis (AE) is an endemic parasitic zoonosis in Germany. In most cases, the liver is the primary organ affected.Case presentationA 59-year old female patient presented with increasing exertional dyspnea and unintentional weight loss. A computed tomography (CT) scan showed a left-sided chylous pleural effusion and multiple intrahepatic masses with infiltration of the diaphragm and the pleura. The findings were initially misinterpreted as hepatocellular carcinoma (HCC) with infiltrating growth. Liver biopsy of one of the masses showed no evidence of malignancy, but an amorphous necrosis of unclear origin. HCC was further ruled out by magnetic resonance imaging (MRI). However, MRI findings were highly suspicious for hepatothoracic dissemination and complications due to AE. Typical histologic findings in a repeated and more specific examination of the liver tissue and a positive serology for echinococcosis confirmed the diagnosis of AE. As the hepatic and pulmonary manifestations were considered inoperable in a curative matter, an anti-parasitic treatment with albendazole was initiated. A video-assisted thoracoscopic surgery (VATS) with removal of the chylous effusion as well as a talc pleurodesis was performed to relieve the patient from dyspnea. Two months later, the patient was asymptomatic and a positron emission tomography (PET)-CT-scan with [18 F] fluoro-2-deoxy-d-glucose (FDG) showed a remarkable diminution of the hepatic manifestation.ConclusionsThis case demonstrates a rare presentation of alveolar echinococcosis with a focus on pulmonary symptoms, emphasizing the importance of evaluation for pulmonary involvement in patients with AE and respiratory symptoms.

FDG PET/CT–based Response Assessment in Malignancies

Response is the logical outcome measure of a treatment in a clinical or research setting. Objective response assessment involves the use of a test to segregate patients who are likely to experience improved survival from those who are not. Early and accurate response assessment is critical for determining therapy effectiveness in clinical settings, for effective trial designs comparing two or more therapies, and for modulating treatment on the basis of response (ie, response-adapted therapy). 2-[fluorine 18]fluoro-2-deoxy-d-glucose (FDG) PET/CT can provide both functional and structural information about a disease process. It has been used at several stages of patient management, including imaging-based tumor response assessment, for various malignancies. FDG PET/CT can be used to differentiate patients with lymphoma who have a residual mass but no residual disease after treatment (ie, complete responders) from those who have a residual mass and residual disease after treatment. Similarly, in solid malignancies, the functional changes in glucose uptake and metabolism precede the structural changes (commonly seen as tumor shrinkage) and necrosis. Response assessment criteria have been developed on the basis of findings on FDG PET/CT images and are continuously being revised to ensure standardization and improve their predictive performance. Published under a CC BY 4.0 license. Quiz questions for this article are available through the Online Learning Center.

Whole-body three-dimensional short tau inversion recovery and T1-weighted in/opposed phase MRI in the detection of neuroblastoma bone marrow metastasis: comparative study with PET/CT utilising bone marrow biopsy as the reference standard

To evaluate the diagnostic accuracy of whole-body (WB) magnetic resonance imaging (MRI) utilising three-dimensional (3D) short tau inversion recovery (STIR) and T1-weighted in/opposed-phase MRI in the detection of neuroblastoma bone marrow metastasis compared to 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)/computed tomography (CT). A prospective study of 20 consecutive histopathologically proven neuroblastoma patients enrolled in this study from January 2021 to August 2022. WB MRI and FDG-PET/CT were performed for all cases. Bone marrow biopsy served as the standard of reference. Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy were calculated. In addition, lesion-by-lesion analysis was performed and the number of bone marrow metastatic lesions in different body segments using both imaging methods was recorded and compared. WB MRI correctly identified true positives and true negatives in all cases with a sensitivity and specificity of 100%. In contrast, FDG-PET/CT showed two false-negative cases that resulted in a sensitivity, specificity, PPV, NPV, and accuracy of 86.7%, 100%, 100%, 71.4%, and 92%, respectively. In the lesion-by-lesion analysis, WB MRI detected more (24.3%) bone marrow metastatic lesions than FDG-PET/CT. Whole-body MRI can reliably identify neuroblastoma bone marrow infiltration, and could be an alternative to PET/CT in that regard.

Correlation of 18F-FDG PET/CT metabolic parameters with the expression of immune biomarkers in the tumour microenvironment in lung adenocarcinoma

To explore the association between metabolic parameters evaluated by integrated 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)/computed tomography (CT) and the expression of immune biomarkers in the tumour microenvironment in lung adenocarcinoma. This study included 134 patients. Metabolic parameters were obtained by PET/CT. Immunohistochemistry analysis was used for FOXP3-TILs (transcription factor forkhead box protein 3 tumour-infiltrating lymphocytes), CD8-TILs, CD4-TILs, CD68-TAMs (tumour-associated macrophages) and galectin-1 (Gal-1) tumour expression. There were significant positive associations between FDG PET metabolic parameters and the median percentage of immune reactive areas (IRA%) covered by FOXP3-TILs and CD68-TAMs. Negative associations with the median IRA% covered by CD4-TILs and CD8-TILs were observed: maximal standardised uptake value (SUVmax), metabolic tumour volume (MTV), total lesion glycolysis (TLG), and IRA% for FOXP3-TILs (rho=0.437, 0.400, 0.414; p<0.0001 for all parameters); SUVmax, MTV, TLG, and IRA% for CD68-TAMs (rho=0.356, 0.355, 0.354; p<0.0001 for all parameters); SUVmax, MTV, TLG, and IRA% for CD4-TILs (rho=-0.164, -0.190, -0.191; p=0.059, 0.028, 0.027, respectively); SUVmax, MTV, TLG, and IRA% for CD8-TILs (rho=-0.305, -0.316, -0.322; p<0.0001 for all parameters). There were significant positive associations between tumour Gal-1 expression and the median IRA% covered by FOXP3-TILs and CD68-TAMs (rho=0.379; p<0.0001; rho=0.370; p<0.0001, respectively), and a significant negative association with the median IRA% covered by CD8-TILs (rho=-0.347; p<0.0001) was observed. Tumour stage (p=0.008), Gal-1 expression (p=0.008), and median IRA% covered by CD8-TILs (p=0.054) were independent risk factors for overall survival. FDG PET may facilitate a comprehensive evaluation of the tumour microenvironment and predict response to immunotherapy.

Usefulness of serum S100A4 and positron-emission tomography on lung cancer accompanied by interstitial pneumonia.

The S100 calcium-binding protein A4 (S100A4) and the accumulation of [18F]-fluoro-2-deoxy-D-glucose (FDG) in noncancerous interstitial pneumonia (IP) area are predictors of postoperative acute exacerbation (AE) of IP after pulmonary resection for lung cancer with IP. However, the significance of combining these markers for predicting short-term outcome and long-term prognosis is not known. Patients diagnosed with IP on preoperative high-resolution computed tomography and who had undergone pulmonary resection for primary lung cancer between April 2010 and March 2019 at Hiroshima University were included in this study. Predictive factors for the cumulative incidence of death from other than lung cancer (CIDOL) were investigated using the Fine and Gray model. CIDOL, perioperative outcome, and cumulative incidence of all death (CIAD) were retrospectively compared based on serum S100A4 and FDG accumulation. A total of 121 patients were included in this study. High S100A4 (hazard ratio [HR], 2.541; p=0.006) and FDG accumulation (HR, 3.199; p=0.038) were significant predictors of CIDOL. AE of IP occurred only in patients with high S100A4/FDG (+). CIDOL of patients with high S100A4/FDG (+) was higher than those with high S100A4/FDG (-) or low S100A4/FDG (+) (p < 0.001), and CIAD of patients with high S100A4/FDG (+) was also higher than those with high S100A4/FDG (-) or low S100A4/FDG (+) patients (p=0.021). Serum S100A4 and FDG accumulation in the noncancerous IP area were significant predictors of CIDOL after lung resection for lung cancer with IP and may help decide the treatment strategy.

PET/CT radiomics for prediction of hyperprogression in metastatic melanoma patients treated with immune checkpoint inhibitors.

This study evaluated pretreatment 2[18F]fluoro-2-deoxy-D-glucose (FDG)-PET/CT-based radiomic signatures for prediction of hyperprogression in metastatic melanoma patients treated with immune checkpoint inhibition (ICI). Fifty-six consecutive metastatic melanoma patients treated with ICI and available imaging were included in the study and 330 metastatic lesions were individually, fully segmented on pre-treatment CT and FDG-PET imaging. Lesion hyperprogression (HPL) was defined as lesion progression according to RECIST 1.1 and doubling of tumor growth rate. Patient hyperprogression (PD-HPD) was defined as progressive disease (PD) according to RECIST 1.1 and presence of at least one HPL. Patient survival was evaluated with Kaplan-Meier curves. Mortality risk of PD-HPD status was assessed by estimation of hazard ratio (HR). Furthermore, we assessed with Fisher test and Mann-Whitney U test if demographic or treatment parameters were different between PD-HPD and the remaining patients. Pre-treatment PET/CT-based radiomic signatures were used to build models predicting HPL at three months after start of treatment. The models were internally validated with nested cross-validation. The performance metric was the area under receiver operating characteristic curve (AUC). PD-HPD patients constituted 57.1% of all PD patients. PD-HPD was negatively related to patient overall survival with HR=8.52 (95%CI 3.47-20.94). Sixty-nine lesions (20.9%) were identified as progressing at 3 months. Twenty-nine of these lesions were classified as hyperprogressive, thereby showing a HPL rate of 8.8%. CT-based, PET-based, and PET/CT-based models predicting HPL at three months after the start of treatment achieved testing AUC of 0.703 +/- 0.054, 0.516 +/- 0.061, and 0.704 +/- 0.070, respectively. The best performing models relied mostly on CT-based histogram features. FDG-PET/CT-based radiomic signatures yield potential for pretreatment prediction of lesion hyperprogression, which may contribute to reducing the risk of delayed treatment adaptation in metastatic melanoma patients treated with ICI.

Retrospective study of the incidence of sarcoidosis-like reaction in patients treated with immunotherapy

To assess the frequency of radiographically evident drug-induced sarcoidosis-like reaction (DISR) in patients treated with anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) therapy, anti-programmed cell death protein 1 (PD-1) therapy, or a combination of both in a single centre. The images and medical records of 457 patients with metastatic melanoma or head and neck cancer treated with either anti-CTLA-4 therapy, anti-PD-1 therapy, or a combination of both at University of California medical centre were reviewed retrospectively and the incidence of radiological manifestations of DISR was assessed among these treatment groups. Radiological manifestations of DISR were found in 19/457 patients (4.1%). The mean interval from the initiation of immunotherapy to development of DISR was 5.5 months (range 2.3-13.5 months). Mean interval from radiological detection of DISR to imaging evidence of resolution was 5.8 months (range 1.6-18.3 months). Three patients out of 81 (3.7%), 11/297 (3.7%), and 5/79 (6.3%) developed sarcoidosis-like reaction after treatment with anti-CTLA-4 antibody, anti-PD-1 antibody, and a combination of both, respectively. Most patients with DISR were asymptomatic and did not require systemic therapy. Most patients did not demonstrate concomitant increased maximum standardised uptake value (SUVmax) in other organs on their integrated 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)/computed tomography (CT). In the present retrospective study of patients treated with immune checkpoint inhibitors (ICIs), DISR occurred in approximately 3.7% of patients treated with either anti-CTLA-4 or anti-PD-1 antibody and 6.3% of patients treated with a combination of both.

The frequency of change in five-point scale score with a Bayesian penalised likelihood PET reconstruction algorithm on interim FDG PET-CT and its potential implications for therapy decisions in Hodgkin's lymphoma

To assess the effect of a Bayesian penalised likelihood (BPL) reconstruction algorithm on the five-point scale (5-PS) score, response categorisation, and potential implications for therapy decisions after interim 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)-computed tomography (CT) (iPET-CT) to guide treatment in classical Hodgkin's lymphoma (HL). The present study included new patients with HL undergoing iPET-CT from 2014-2019 after two cycles of doxorubicin (Adriamycin), bleomycin, vincristine, and dacarbazine (ABVD). Two reporters categorised response using the 5-PS and measured maximum standardised uptake values (SUVmax) of the most avid tumour residuum, mediastinal blood pool, and normal liver with ordered subset expected maximisation (OSEM) and BPL reconstructions. Eighty-one iPET-CT examinations were reviewed. Compared with OSEM, BPL increased the 5-PS score by a single score in 18/81 (22.2%) patients. The frequency of potential treatment intensification by changing a score of 3-4 was 13.6% (11/81) and represented 25% (11/44) of patients with a score of 3 on OSEM. All 11 patients remained in remission without a change in therapy (mean 63 months) except one who required second-line treatment for refractory disease. Median SUVmax of tumour residuum was significantly higher with BPL compared with OSEM (2.7 versus 2.4, p<<0.0001), whilst liver SUVmax was significantly lower for both reporters (up to 6.6%, p<0.0001). BPL PET reconstruction increased the 5-PS score on iPET-CT in 22% of HL patients and can potentially result in unnecessary treatment escalation in over half of these patients.

Preoperative prediction of mediastinal lymph node metastasis in non-small cell lung cancer based on 18F-FDG PET/CT radiomics

To establish and verify a 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)/computed tomography (CT)-based radiomics nomogram to predict mediastinal lymph node metastasis (LNM) in non-small cell lung cancer (NSCLC) patients preoperatively. This retrospective study enrolled 155 NSCLC patients (primary cohort, n=93; validation cohort, n=62). For each patient, 2,704 radiomic features were extracted from the primary lung cancer regions. Four procedures including the Mann-Whitney U-test, Spearman's correlation analysis, minimum redundancy-maximum relevance (mRMR), and least absolute shrinkage and selection operator (LASSO) binary logistic regression were utilised for determining essential features and establishing a radiomics signature. After that, a nomogram was established. The nomogram's potential was assessed based on its discrimination, calibration, and clinical usefulness. The radiomics signature and nomogram predictive performances were evaluated with respect to the area under the receiver operating characteristic curve (AUC), specificity, accuracy, and sensitivity. The radiomics signature composed of eight selected features had good discriminatory performance of LNM versus non-LNM groups an AUC of 0.851 and 0.826 in primary and validation cohorts, respectively. The nomogram also indicated good discrimination with an AUC of 0.869 and 0.847 in the primary and validation cohorts, respectively. Furthermore, good calibration was demonstrated utilising the nomogram. An 18F-FDG PET/CT-based radiomics nomogram that integrates the radiomics signature and age was promoted to predict mediastinal LNM within NSCLC patients, which could potentially facilitate individualised therapy for mediastinal LNM before treatment. The nomogram was beneficial in clinical practice, as illustrated by decision curve analysis.