Multi-modal assessment of a cardiac stem cell therapy reveals distinct modulation of regional scar properties.

BACKGROUND: The initial idea of functional tissue replacement has shifted to the concept that injected cells positively modulate myocardial healing by a non-specific immune response of the transplanted cells within the target tissue. This alleged local modification of the scar requires assessment of regional properties of the left ventricular wall in addition to commonly applied measures of global morphological and functional parameters. Hence, we aimed at investigating the effect of cardiac cell therapy with cardiovascular progenitor cells, so-called cardiac induced cells, on both global and regional properties of the left ventricle by a multimodal imaging approach in a mouse model. METHODS: Myocardial infarction was induced in mice by ligation of the left anterior descending artery, the therapy group received an intramyocardial injection of 1 × 106 cardiac induced cells suspended in matrigel, the control group received matrigel only. [18F]FDG positron emission tomography imaging was performed after 17 days, to assess regional glucose metabolism. Three weeks after myocardial infarction, cardiac magnetic resonance imaging was performed for morphological and functional assessment of the left ventricle. Following these measurements, hearts were excised for histological examinations. RESULTS: Cell therapy had no significant effect on global morphological parameters. Similarly, there was no difference in scar size and capillary density between therapy and control group. However, there was a significant improvement in contractile function of the left ventricle - left ventricular ejection fraction, stroke volume and cardiac output. Regional analysis of the left ventricle identified changes of wall properties in the scar area as the putative mechanism. Cell therapy reduced the thinning of the scar and significantly improved its radial contractility. Furthermore, the metabolic defect, assessed by [18F]FDG, was significantly reduced by the cell therapy. CONCLUSION: Our data support the relevance of extending the assessment of global left ventricular parameters by a structured regional wall analysis for the evaluation of therapies targeting at modulation of healing myocardium. This approach will enable a deeper understanding of mechanisms underlying the effect of experimental regenerative therapies, thus paving the way for a successful translation into clinical application.

Long-term assessment of clinical parameters and positron emission tomography parameters in predicting recurrence in uterine cervical cancer patients receiving definitive chemoradiotherapy.

OBJECTIVE: The objective of this study was to assess the prognostic value of clinical factors and metabolic parameters measured using fluorodeoxyglucose PET (FDG-PET/CT) in predicting disease recurrence, as well as distant metastasis-free survival (DMFS), local recurrence-free survival (LRFS), and overall survival (OS) in patients with uterine cervical cancer who received definitive chemoradiotherapy. METHODS: The clinical data and FDG-PET parameters, including standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of 194 patients with biopsy-confirmed squamous cell carcinoma of cervical cancer were retrospectively analyzed. Univariate and multivariate analyses were used to ascertain prognostic factors associated with DMFS, LRFS, and OS. RESULTS: With a median follow-up of 12.5 years, 96 patients (49.5%) presented with disease recurrence, at a median of 9.9 months after chemoradiotherapy. Patients who experienced recurrence had significantly higher values for all FDG-PET parameters compared to patients who did not. In multivariate regression analysis, lymph node metastasis, MTV, and SUV mean were significantly correlated with distant metastasis, while local recurrence was only predicted by SUV max . Lymph node metastasis, high MTV, SUV mean , and TLG predicted shorter DMFS, while only the primary tumor SUV max predicted LRFS. Age, regional nodal metastasis, and higher MTV independently predicted shorter OS in multivariate analysis. CONCLUSION: We found that metabolic parameters derived from FDG-PET/CT could serve as surrogates for disease recurrence in patients with cervical cancer who were treated with definitive chemoradiotherapy. Patients at high risk of distant metastasis could be defined using SUV mean and MTV, and for local recurrence, by using SUV max .

18F-FDG PET/CT technology for the assessment of brown adipose tissue: an updated review.

INTRODUCTION: This review provides an update of 18 F-fluorodeoxyglucose ([18F] FDG) for Brown adipose tissue (BAT) activity quantification, whose role is not completely understood. AREAS COVERED: We conducted an unstructured search of the literature for any studies employing the [18F] FDG PET in BAT assessment. We explored BAT quantification both in healthy individuals and in different pathologies, after cold exposure and as a metabolic biomarker. The assessment of possible BAT modulators by using [18F] FDG PET is shown. Further PET tracers and novel developments for BAT assessments are also described. EXPERT OPINION: Further PET tracers and imaging modalities are under investigation, but the [18F] FDG PET is currently the method of choice for the evaluation of BAT and further multicentric trials are needed for a better understanding of the BAT physiopathology, also after cold stimuli. The modulation of BAT activity, assessed by [18F] FDG PET imaging, seems a promising tool for the management of conditions such as obesity and type 2 diabetes. Moreover, an interesting possible correlation of BAT activation with prognostic [18F] FDG PET indices in cancer patients should be assessed with further multicentric trials.

Assessment of synaptic loss in mouse models of ß-amyloid and tau pathology using [18F]UCB-H PET imaging.

OBJECTIVE: In preclinical research, the use of [18F]Fluorodesoxyglucose (FDG) as a biomarker for neurodegeneration may induce bias due to enhanced glucose uptake by immune cells. In this study, we sought to investigate synaptic vesicle glycoprotein 2A (SV2A) PET with [18F]UCB-H as an alternative preclinical biomarker for neurodegenerative processes in two mouse models representing the pathological hallmarks of Alzheimer's disease (AD). METHODS: A total of 29 PS2APP, 20 P301S and 12 wild-type mice aged 4.4 to 19.8 months received a dynamic [18F]UCB-H SV2A-PET scan (14.7 ± 1.5 MBq) 0-60 min post injection. Quantification of tracer uptake in cortical, cerebellar and brainstem target regions was implemented by calculating relative volumes of distribution (VT) from an image-derived-input-function (IDIF). [18F]UCB-H binding was compared across all target regions between transgenic and wild-type mice. Additional static scans were performed in a subset of mice to compare [18F]FDG and [18F]GE180 (18 kDa translocator protein tracer as a surrogate for microglial activation) standardized uptake values (SUV) with [18F]UCB-H binding at different ages. Following the final scan, a subset of mouse brains was immunohistochemically stained with synaptic markers for gold standard validation of the PET results. RESULTS: [18F]UCB-H binding in all target regions was significantly reduced in 8-months old P301S transgenic mice when compared to wild-type controls (temporal lobe: p = 0.014; cerebellum: p = 0.0018; brainstem: p = 0.0014). Significantly lower SV2A tracer uptake was also observed in 13-months (temporal lobe: p = 0.0080; cerebellum: p = 0.006) and 19-months old (temporal lobe: p = 0.0042; cerebellum: p = 0.011) PS2APP transgenic versus wild-type mice, whereas the brainstem revealed no significantly altered [18F]UCB-H binding. Immunohistochemical analyses of post-mortem mouse brain tissue confirmed the SV2A PET findings. Correlational analyses of [18F]UCB-H and [18F]FDG using Pearson's correlation coefficient revealed a significant negative association in the PS2APP mouse model (R = -0.26, p = 0.018). Exploratory analyses further stressed microglial activation as a potential reason for this inverse relationship, since [18F]FDG and [18F]GE180 quantification were positively correlated in this cohort (R = 0.36, p = 0.0076). CONCLUSION: [18F]UCB-H reliably depicts progressive synaptic loss in PS2APP and P301S transgenic mice, potentially qualifying as a more reliable alternative to [18F]FDG as a biomarker for assessment of neurodegeneration in preclinical research.

Application of an artificial intelligence-based tool in [18F]FDG PET/CT for the assessment of bone marrow involvement in multiple myeloma.

PURPOSE: [18F]FDG PET/CT is an imaging modality of high performance in multiple myeloma (MM). Nevertheless, the inter-observer reproducibility in PET/CT scan interpretation may be hampered by the different patterns of bone marrow (BM) infiltration in the disease. Although many approaches have been recently developed to address the issue of standardization, none can yet be considered a standard method in the interpretation of PET/CT. We herein aim to validate a novel three-dimensional deep learning-based tool on PET/CT images for automated assessment of the intensity of BM metabolism in MM patients. MATERIALS AND METHODS: Whole-body [18F]FDG PET/CT scans of 35 consecutive, previously untreated MM patients were studied. All patients were investigated in the context of an open-label, multicenter, randomized, active-controlled, phase 3 trial (GMMG-HD7). Qualitative (visual) analysis classified the PET/CT scans into three groups based on the presence and number of focal [18F]FDG-avid lesions as well as the degree of diffuse [18F]FDG uptake in the BM. The proposed automated method for BM metabolism assessment is based on an initial CT-based segmentation of the skeleton, its transfer to the SUV PET images, the subsequent application of different SUV thresholds, and refinement of the resulting regions using postprocessing. In the present analysis, six different SUV thresholds (Approaches 1-6) were applied for the definition of pathological tracer uptake in the skeleton [Approach 1: liver SUVmedian × 1.1 (axial skeleton), gluteal muscles SUVmedian × 4 (extremities). Approach 2: liver SUVmedian × 1.5 (axial skeleton), gluteal muscles SUVmedian × 4 (extremities). Approach 3: liver SUVmedian × 2 (axial skeleton), gluteal muscles SUVmedian × 4 (extremities). Approach 4: ≥ 2.5. Approach 5: ≥ 2.5 (axial skeleton), ≥ 2.0 (extremities). Approach 6: SUVmax liver]. Using the resulting masks, subsequent calculations of the whole-body metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in each patient were performed. A correlation analysis was performed between the automated PET values and the results of the visual PET/CT analysis as well as the histopathological, cytogenetical, and clinical data of the patients. RESULTS: BM segmentation and calculation of MTV and TLG after the application of the deep learning tool were feasible in all patients. A significant positive correlation (p < 0.05) was observed between the results of the visual analysis of the PET/CT scans for the three patient groups and the MTV and TLG values after the employment of all six [18F]FDG uptake thresholds. In addition, there were significant differences between the three patient groups with regard to their MTV and TLG values for all applied thresholds of pathological tracer uptake. Furthermore, we could demonstrate a significant, moderate, positive correlation of BM plasma cell infiltration and plasma levels of ß2-microglobulin with the automated quantitative PET/CT parameters MTV and TLG after utilization of Approaches 1, 2, 4, and 5. CONCLUSIONS: The automated, volumetric, whole-body PET/CT assessment of the BM metabolic activity in MM is feasible with the herein applied method and correlates with clinically relevant parameters in the disease. This methodology offers a potentially reliable tool in the direction of optimization and standardization of PET/CT interpretation in MM. Based on the present promising findings, the deep learning-based approach will be further evaluated in future prospective studies with larger patient cohorts.

Meta-Analysis of the Test-Retest Repeatability of [18F]-Fluorodeoxyglucose Standardized Uptake Values: Implications for Assessment of Tumor Response.

PURPOSE: Currently, guidelines for PET with 18F-fluorodeoxyglucose (FDG-PET) interpretation for assessment of therapy response in oncology primarily involve visual evaluation of FDG-PET/CT scans. However, quantitative measurements of the metabolic activity in tumors may be even more useful in evaluating response to treatment. Guidelines based on such measurements, including the European Organization for Research and Treatment of Cancer Criteria and PET Response Criteria in Solid Tumors, have been proposed. However, more rigorous analysis of response criteria based on FDG-PET measurements is needed to adopt regular use in practice. EXPERIMENTAL DESIGN: Well-defined boundaries of repeatability and reproducibility of quantitative measurements to discriminate noise from true signal changes are a needed initial step. An extension of the meta-analysis from de Langen and colleagues (2012) of the test-retest repeatability of quantitative FDG-PET measurements, including mean, maximum, and peak standardized uptake values (SUVmax, SUVmean, and SUVpeak, respectively), was performed. Data from 11 studies in the literature were used to estimate the relationship between the variance in test-retest measurements with uptake level and various study-level, patient-level, and lesion-level characteristics. RESULTS: Test-retest repeatability of percentage fluctuations for all three types of SUV measurement (max, mean, and peak) improved with higher FDG uptake levels. Repeatability in all three SUV measurements varied for different lesion locations. Worse repeatability in SUVmean was also associated with higher tumor volumes. CONCLUSIONS: On the basis of these results, recommendations regarding SUV measurements for assessing minimal detectable changes based on repeatability and reproducibility are proposed. These should be applied to differentiate between response categories for a future set of FDG-PET-based criteria that assess clinically significant changes in tumor response.

Interim FDG-PET/CT for Response Assessment of Lymphoma.

The clinical use and prognostic value of interim FDG-PET/CT (iPET/CT), which is performed after treatment initiation but prior to its completion, varies by lymphoma subtype. Evidence supporting the prognostic value of iPET/CT is more robust for classical Hodgkin lymphoma (cHL), and in this lymphoma subtype, response-adapted treatment approaches guided by iPET/CT are a widely used standard of care for first-line therapy. The data supporting use of iPET/CT among patients with non-Hodgkin lymphoma (NHL) is less well-established, but failure to achieve complete metabolic response on iPET/CT is generally considered a poor prognostic factor with likely consequences for progression free survival. This review will present the available evidence supporting use of iPET/CT in lymphoma patients, particularly as it relates to prognostication and the ability to inform response-adapted treatment strategies. The latter will be addressed through a discussion on the major iPET-response adapted clinical trials with mention of ongoing trials. Special attention will be given to cHL and a few subtypes of NHL, including diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), and peripheral T cell lymphoma (PTCL).

Prospective assessment using 18F-FDG PET/CT as a novel predictor for early response to PD-1 blockade in non-small-cell lung cancer.

Anti-programmed death-1 (PD-1) blockade is a standard treatment for advanced non-small-cell lung cancer (NSCLC). However, no appropriate modality exists for monitoring its therapeutic response immediately after initiation. Therefore, we aimed to elucidate the clinical relevance of 18F-FDG PET/CT versus CT in predicting the response to PD-1 blockade in the early phase. This prospective study included a total of 54 NSCLC patients. 18F-FDG PET/CT was performed at 4 weeks and 9 weeks after PD-1 blockade monotherapy. Maximum standardized uptake values (SULmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were evaluated. Among all patients, partial metabolic response and progressive metabolic disease after PD-1 blockade were observed in 35.2% and 11.1% on SULmax, 22.2% and 51.8% on MTV, and 27.8% and 46.3% on TLG, respectively, whereas a partial response (PR) and progressive disease (PD), respectively, based on RECIST v1.1 were recognized in 35.2% and 35.2%, respectively. The predictive probability of PR (MTV: 57.9% vs. 21.1%, p = 0.044; TLG: 63.2% vs. 21.1%, p = 0.020) and PD (MTV: 78.9% vs. 47.3%, p = 0.002; TLG: 73.7% vs. 21.1%, p = 0.007) detected based on RECIST at 4 weeks after PD-1 blockade initiation was significantly higher using MTV or TLG on 18F-FDG uptake than on CT. Multivariate analysis revealed that metabolic response by MTV or TLG at 4 weeks was an independent factor for response to PD-1 blockade treatment. Metabolic assessment by MTV or TLG was superior to morphological changes on CT for predicting the therapeutic response and survival at 4 weeks after PD-1 blockade.

PET Imaging of Bromodomain and Extra-Terminal Domain Inhibitors for the Noninvasive Assessment of Metabolic Changes in the Liver and Brain of Early-Stage Alcoholic Liver Disease.

Alcoholic liver disease (ALD) has a significant impact on human health and is one of the leading causes of liver disease mortality. The early and exact diagnosis of ALD is very important since the early stage of disease progression can be reversible. Although ALD can be evaluated by ultrasound, CT, or MRI, there is still no imaging technique sufficient in the diagnosis of early-stage ALD. Of the current studies, epigenetic modulation plays a significant role in the development and progression of ALD. In this work, we evaluate whether BRDs play a vital role in the early-stage ALD using our new PET imaging probe of BET proteins, [11C]CW22. PET/CT imaging of [11C]CW22 and [18F]FDG was used to identify early-stage lesions of livers and brains in the mice model. We found that the average uptake values of livers and brains in early-stage ALD were significantly increased for [11C]CW22 PET/CT imaging but only slightly changed in [18F]FDG PET/CT imaging. Consistently, we also found that BRD 3, 4 protein expression levels were significantly higher in the liver and brain tissues of early-stage ALD. Furthermore, through Pmod software, we found that [11C]CW22 PET/CT uptakes in the brain stem, cerebellum, and midbrain were significantly up-regulated in the early-stage ALD. In conclusion, BRDs were important mediators of damage in early-stage ALD. [11C]CW22 PET/CT imaging can detect the early-phase alcohol-induced damage of livers and brains, which will likely lead to human trials in the future.

First-in-human assessment of the novel LAT1 targeting PET probe 18F-FIMP.

In the first-in-human PET study, we evaluated the biodistribution and tumor accumulation of the novel PET probe, (S)-2-amino-3-[3-(2-18F-fluoroethoxy)-4-iodophenyl]-2-methylpropanoic acid (18F-FIMP), which targets the tumor-related L-type amino acid transporter 1 (LAT1), and compared it with L-[methyl-11C]methionine (11C-MET) and 2-Deoxy-2-18F-fluoro-D-glucose (18F-FDG). 18F-FIMP biodistribution was revealed by whole-body and brain scans in 13 healthy controls. Tumor accumulation of 18F-FIMP was evaluated in 7 patients with a brain tumor, and compared with those of 11C-MET and 18F-FDG. None of the subjects had significant problems due to probe administration, such as adverse effects or abnormal vital signs. 18F-FIMP was rapidly excreted from the kidneys to the urinary bladder. There was no characteristic physiological accumulation in healthy controls. 18F-FIMP PET resulted in extremely clear images in patients with suspected glioblastoma compared with 11C-MET and 18F-FDG. 18F-FIMP could be a useful novel PET probe for LAT1-positive tumor imaging including glioblastoma.

Selectively recommend 18F-FDG PET/CT for patients with de novo nasopharyngeal carcinoma in endemic areas.

INTRODUCTION: To identify the subset of patients with de novo nasopharyngeal carcinoma (NPC) for whom [18F] fluorodeoxyglucose positron emission tomography and computed tomography (18F-FDG PET/CT) should be recommended, and to determine whether PET/CT is a cost-effective decision for precise M staging in endemic areas. MATERIALS AND METHODS: Retrospective analysis of data of 4469 patients diagnosed with de novo NPC between January 2014 and December 2019. The detection rate of distant metastasis was compared between different groups. Univariate and multiple logistic regression analysis was applied to identify the risk factors for distant metastasis. The cost-effectiveness of the diagnostic strategies was assessed. RESULTS: The detection rate of distant metastasis in the whole cohort was 5.46%. In multivariate analysis, male sex, T3-4 stage, N2-3 stage, and high plasma Epstein-Barr virus (EBV) DNA (≥ 14,650 copies/mL) were risk factors for distant metastases. NPC patients with T3-4 stage combined with N2-3 stage, high EBV DNA combined with male sex, or N2-3 stage combined with high EBV DNA were defined as recommended group with relatively higher tendency for metastasis. Distant metastasis incidence in recommended group and unrecommended group were 10.25% and 1.75%, respectively (P < 0.001). In the recommended group, PET/CT significantly improved the detection rate of distant metastasis (13.25% vs 9.02%, P = 0.005). Cost-effectiveness analysis revealed that additional cost for every one percent increase in distant metastasis detection rate was $22,785.58 in the recommended group (< Willingness-to-pay (WTP) threshold of $32,700.00) and $310,912.90 in the unrecommended group. CONCLUSIONS: In patients with de novo NPC, the tendency for metastasis can be predicted based on clinical parameters. 18F-FDG PET/CT should be selectively recommended for the subset of patients with a relatively higher tendency for metastasis.

"The added value of 18f-FDG PET/CT in the assessment of onset and steroid resistant polimyalgia rheumatica".

PMR is a common inflammatory rheumatic disease. Although its clinical characteristics are fully recognized, no specific test for its diagnosis has been established to date. Several studies have described a wide variety of diseases that present with polymyalgic symptoms. A 18FDG-PET/CT scan could help to deal with these differential diagnoses. The goal of our study is to describe the findings of the 18FDG-PET/CT scan in a cohort of PMR patients and to detail how the 18FDG-PET/CT scan improves accuracy when diagnosing other underlying conditions. This cross-sectional study enrolled patients with a diagnosis of PMR who underwent to a 18FDG-PET/CT scan to rule out other diagnosis. The 18FDG-PET/CT scan was performed either following clinical criteria at the onset of clinical symptoms or when the patient became PMR steroid resistant. Patients' demographic, clinical and analytical data at the moment of the 18FDG-PET/CT scan were recorded. The final diagnosis was confirmed according to clinical judgement. A total of 103 patients with PMR were included. In 49.51% of patients, the 18FDG-PET/CT scan was ordered to study resistance to steroid therapy. The final diagnoses of patients were PMR in 70.9% patients, large vessel vasculitis in 15.5%, neoplasms 4.8% and another diagnosis in the rest. The 18FDG-PET/CT scan is a very useful technique for the study of Polymyalgia Rheumatica, not only to help in the diagnostic process, but also due to its role in the identification of a variety of PMR-like patrons.

Physiological skin FDG uptake: A quantitative and regional distribution assessment using PET/MRI.

PURPOSE: To retrospectively assess the repeatability of physiological F-18 labeled fluorodeoxyglucose (FDG) uptake in the skin on positron emission tomography/magnetic resonance imaging (PET/MRI) and explore its regional distribution and relationship with sex and age. METHODS: Out of 562 examinations with normal FDG distribution on whole-body PET/MRI, 74 repeated examinations were evaluated to assess the repeatability and regional distribution of physiological skin uptake. Furthermore, 224 examinations were evaluated to compare differences in the uptake due to sex and age. Skin segmentation on PET was performed as body-surface contouring on an MR-based attenuation correction map using an off-line reconstruction software. Bland-Altman plots were created for the repeatability assessment. Kruskal-Wallis test was performed to compare the maximum standardized uptake value (SUVmax) with regional distribution, age, and sex. RESULTS: The limits of agreement for the difference in SUVmean and SUVmax of the skin were less than 30%. The highest SUVmax was observed in the face (3.09±1.04), followed by the scalp (2.07±0.53). The SUVmax in the face of boys aged 0-9 years and 10-20 years (1.33±0.64 and 2.05±1.00, respectively) and girls aged 0-9 years (0.98±0.38) was significantly lower than that of men aged ≥20 years and girls aged ≥10 years (p<0.001). In women, the SUVmax of the face (2.31±0.71) of ≥70-year-olds was significantly lower than that of 30-39-year-olds (3.83±0.82) (p<0.05). CONCLUSION: PET/MRI enabled the quantitative analysis of skin FDG uptake with repeatability. The degree of physiological FDG uptake in the skin was the highest in the face and varied between sexes. Although attention to differences in body habitus between age groups is needed, skin FDG uptake also depended on age.

Assessment of metastatic lymph nodes in head and neck squamous cell carcinomas using simultaneous 18F-FDG-PET and MRI.

In this study, we investigate the feasibility of using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI), diffusion weighted imaging (DWI), and dynamic positron emission tomography (PET) for detection of metastatic lymph nodes in head and neck squamous cell carcinoma (HNSCC) cases. Twenty HNSCC patients scheduled for lymph node dissection underwent DCE-MRI, dynamic PET, and DWI using a PET-MR scanner within one week prior to their planned surgery. During surgery, resected nodes were labeled to identify their nodal levels and sent for routine clinical pathology evaluation. Quantitative parameters of metastatic and normal nodes were calculated from DCE-MRI (ve, vp, PS, Fp, Ktrans), DWI (ADC) and PET (Ki, K1, k2, k3) to assess if an individual or a combination of parameters can classify normal and metastatic lymph nodes accurately. There were 38 normal and 11 metastatic nodes covered by all three imaging methods and confirmed by pathology. 34% of all normal nodes had volumes greater than or equal to the smallest metastatic node while 4 normal nodes had SUV > 4.5. Among the MRI parameters, the median vp, Fp, PS, and Ktrans values of the metastatic lymph nodes were significantly lower (p = <0.05) than those of normal nodes. ve and ADC did not show any statistical significance. For the dynamic PET parameters, the metastatic nodes had significantly higher k3 (p value = 8.8 × 10-8) and Ki (p value = 5.3 × 10-8) than normal nodes. K1 and k2 did not show any statistically significant difference. Ki had the best separation with accuracy = 0.96 (sensitivity = 1, specificity = 0.95) using a cutoff of Ki = 5.3 × 10-3 mL/cm3/min, while k3 and volume had accuracy of 0.94 (sensitivity = 0.82, specificity = 0.97) and 0.90 (sensitivity = 0.64, specificity = 0.97) respectively. 100% accuracy can be achieved using a multivariate logistic regression model of MRI parameters after thresholding the data with Ki < 5.3 × 10-3 mL/cm3/min. The results of this preliminary study suggest that quantitative MRI may provide additional value in distinguishing metastatic nodes, particularly among small nodes, when used together with FDG-PET.

Prognostic value of 18F-FDG PET and PET/CT for assessment of treatment response to neoadjuvant chemotherapy in breast cancer: a systematic review and meta-analysis.

BACKGROUND: We performed a systematic review and meta-analysis to evaluate the prognostic significance of 18F-FDG PET and PET/CT for evaluation of responses to neoadjuvant chemotherapy (NAC) in breast cancer patients. METHODS: We searched PubMed, Embase, and the Cochrane Library databases until June 2020 to identify studies that assessed the prognostic value of 18F-FDG PET scans during or after NAC with regard to overall (OS) and disease-free survival (DFS). Hazard ratios (HRs) and their 95% confidence intervals (CIs) were pooled meta-analytically using a random-effects model. RESULTS: Twenty-one studies consisting of 1630 patients were included in the qualitative synthesis. Twelve studies investigated the use of PET scans for interim response evaluation (during NAC) and 10 studies assessed post-treatment PET evaluation (after NAC). The most widely evaluated parameter distinguishing metabolic responders from poor responders on interim or post-treatment PET scans was %ΔSUVmax, defined as the percent reduction of SUVmax compared to baseline PET, followed by SUVmax and complete metabolic response (CMR). For the 17 studies included in the meta-analysis, the pooled HR of metabolic responses on DFS was 0.21 (95% confidence interval [CI], 0.14-0.32) for interim PET scans and 0.31 (95% CI, 0.21-0.46) for post-treatment PET scans. Regarding the influence of metabolic responses on OS, the pooled HRs for interim and post-treatment PET scans were 0.20 (95% CI, 0.09-0.44) and 0.26 (95% CI, 0.14-0.51), respectively. CONCLUSIONS: The currently available literature suggests that the use of 18F-FDG PET or PET/CT for evaluation of response to NAC provides significant predictive value for disease recurrence and survival in breast cancer patients and might allow risk stratification and guide rational management.

Semiquantitative assessment of fluorodeoxyglucose uptake in primary tumours on dynamic PET/computed tomography for lymph node metastasis evaluation in patients with lung cancer: a prospective study.

OBJECTIVE: To semiquantitatively estimate fluorine-18-fluorodeoxyglucose (FDG) uptake in primary lung cancer cells using dynamic and dual-time-point (DTP) PET/computed tomography (PET/CT) to obtain a diagnostic index for lymph node metastasis. METHODS: Forty-five patients with lung cancer underwent dynamic and DTP PET/CT examinations. All primary lesions and lymph node metastases were evaluated pathologically. At each time phase, we assessed the maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of the primary tumours. We investigated the relationship between semiquantitative index and the presence of lymph node metastasis for each case and for all cases satisfying indications for segmentectomy. In cases with lymph node metastasis, we assessed the SUVmax of pathologically proven metastatic lymph nodes and nonmetastatic lymph nodes in each dynamic phase for evaluating temporal change. RESULTS: Among 45 patients, 15 had 17 lymph node metastasis. SUVmax, MTV and TLG of primary tumours at each time phase were significantly associated with lymph node metastasis (P < 0.05). In receiver operating characteristic analysis, dynamic second and third phases showed high diagnostic ability for lymph node metastasis. The temporal change in SUVmax in the dynamic phase between primary tumours and metastatic lymph nodes were significantly different (P = 0.065). The temporal change in SUVmax was significantly lower in nonmetastatic lymph nodes than in primary tumours and metastatic lymph nodes (P < 0.0001). CONCLUSIONS: Semiquantitative assessment of FDG uptake in dynamic second and third phases and the assessment of temporal changes in SUVmax on dynamic PET/CT scans were important predictors in diagnosing lymph node metastasis.

Atrial Arrhythmias in Clinically Manifest Cardiac Sarcoidosis: Incidence, Burden, Predictors, and Outcomes.

Background Recent data have suggested a substantial incidence of atrial arrhythmias (AAs) in cardiac sarcoidosis (CS). Our study aims were to first assess how often AAs are the presenting feature of previously undiagnosed CS. Second, we used prospective follow-up data from implanted devices to investigate AA incidence, burden, predictors, and response to immunosuppression. Methods and Results This project is a substudy of the CHASM-CS (Cardiac Sarcoidosis Multicenter Prospective Cohort Study; NCT01477359). Inclusion criteria were presentation with clinically manifest cardiac sarcoidosis, treatment-naive status, and implanted with a device that reported accurate AA burden. Data were collected at each device interrogation visit for all patients and all potential episodes of AA were adjudicated. For each intervisit period, the total AA burden was obtained. A total of 33 patients met the inclusion criteria (aged 56.1±7.7 years, 45.5% women). Only 1 patient had important AAs as a part of the initial CS presentation. During a median follow-up of 49.1 months, 11 of 33 patients (33.3%) had device-detected AAs, and only 2 (6.1%) had a clinically significant AA burden. Both patients had reduced burden after CS was successfully treated and there was no residual fluorodeoxyglucose uptake on positron emission tomography scan. Conclusions First, we found that AAs are a rare presenting feature of clinically manifest cardiac sarcoidosis. Second, AAs occurred in a minority of patients at follow-up; the burden was very low in most patients. Only 2 patients had clinically significant AA burden, and both had a reduction after CS was treated. Registration URL: https://www.clini​caltr​ials.gov; unique identifier NCT01477359.

Imaging in Therapy Response Assessment and Surveillance of Lung Cancer: Evidenced-based Review With Focus on the Utility of 18F-FDG PET/CT.

This review covers the state-of-the-art imaging in therapy assessment and surveillance of lung cancer with focus on the utility of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). We review different qualitative and quantitative response assessment criteria in lung cancer, common pitfalls and atypical patterns of response to immunotherapy, and imaging features of common immune-related adverse events. In addition, the currently recommended imaging workup in surveillance of asymptomatic patients with non-small-cell and small-cell lung cancer and future developments will be discussed.

Posttreatment FDG-Avid Splenic Lesions in DLBCL and HD: Clinical and Radiographic Characteristics for Risk Assessment.

Residual end of treatment (EOT) FDG-avid lesions are often due to infectious or inflammatory process and not due to refractory lymphoma. Nonetheless, such lesions prompt diagnostic and therapeutic interventions. We evaluate clinical and radiological characteristics of patients with EOT FDG-avid splenic lesions. Comparing metabolic volume (MV) ratio between EOT to interim, showed a marked difference between false positive and true positive lesions (0.5 vs 3.6, P = 0.02). EOT SUVmax was also significantly different between the groups (7 vs. 19, P = 0.02). We suggest EOT/interim-MV ratio as a tool to identify patients at low risk of refractory disease allowing non-invasive surveillance.

Sorafenib and everolimus in patients with advanced solid tumors and KRAS-mutated NSCLC: A phase I trial with early pharmacodynamic FDG-PET assessment.

BACKGROUND: Treatment of patients with solid tumors and KRAS mutations remains disappointing. One option is the combined inhibition of pathways involved in RAF-MEK-ERK and PI3K-AKT-mTOR. METHODS: Patients with relapsed solid tumors were treated with escalating doses of everolimus (E) 2.5-10.0 mg/d in a 14-day run-in phase followed by combination therapy with sorafenib (S) 800 mg/d from day 15. KRAS mutational status was assessed retrospectively in the escalation phase. Extension phase included KRAS-mutated non-small-cell lung cancer (NSCLC) only. Pharmacokinetic analyses were accompanied by pharmacodynamics assessment of E by FDG-PET. Efficacy was assessed by CT scans every 6 weeks of combination. RESULTS: Of 31 evaluable patients, 15 had KRAS mutation, 4 patients were negative for KRAS mutation, and the KRAS status remained unknown in 12 patients. Dose-limiting toxicity (DLT) was not reached. The maximum tolerated dose (MTD) was defined as 7.5 mg/d E + 800 mg/d S due to toxicities at previous dose level (10 mg/d E + 800 mg/d S) including leucopenia/thrombopenia III° and pneumonia III° occurring after the DLT interval. The metabolic response rate in FDG-PET was 17% on day 5 and 20% on day 14. No patient reached partial response in CT scan. Median progression free survival (PFS) and overall survival (OS) were 3.25 and 5.85 months, respectively. CONCLUSIONS: Treatment of patients with relapsed solid tumors with 7.5 mg/d E and 800 mg/d S is safe and feasible. Early metabolic response in FDG-PET was not confirmed in CT scan several weeks later. The combination of S and E is obviously not sufficient to induce durable responses in patients with KRAS-mutant solid tumors.