Positron Emission Tomography And Computed Tomography Research Articles

Inter-observer variation in gross tumour volume delineation of oesophageal cancer on MR, CT and PET/CT.

The aim of our study was to assess the inter-observer variability in delineation of the gross tumour volume (GTV) of oesophageal cancer on magnetic resonance (MR) in comparison to computed tomography (CT) and positron emission tomography and CT (PET/CT). Twenty-three consecutive patients with oesophageal cancer treated with chemo-radiotherapy were enrolled. All patients had PET/CT and MR imaging in treatment position. Five observers independently delineated the GTV on CT alone, MR alone, CT with co-registered MR, PET/CT alone and MR with co-registered PET/CT. Volumes of GTV were measured per patient and imaging modality. Inter-observer agreement, expressed in generalized conformity index (CIgen), volumetric conformity index (VCI), planar conformity index (PCI) and inter-delineation distance (IDD) were calculated per patient and imaging modality. Linear mixed models were used for statistical analysis. GTV volume was significantly lower on MR (33.03 cm3) compared to CT (37.1 cm3; p = 0.002) and on PET/CT MR (35.2 cm3; p = 0.018) compared to PET/CT (39.1 cm3). The CIgen was lowest on CT (0.56) and highest on PET/CT MR (0.67). The difference in CIgen between MR (0.61) and CT was borderline significant (p = 0.048). The VCI was significantly higher on MR (0.71; p = 0.007) and on CT MR (0.71; p = 0.004) compared to CT (0.67). The PCI was significantly higher on CT MR (0.67; p = 0.031) compared to CT (0.64). The largest differences were observed in the cranio-caudal direction. The highest inter-observer agreement was found for PET/CT MR and the lowest for CT. MR could reduce the difference in delineation between observers and provide additional information about the local extent of the tumour.

Multifunctional Dendrimer-Peptide Conjugates for MET Receptor-specific Imaging of Cancer Cells

The Mesenchymal Epithelial Transition (MET) receptor tyrosine kinase is frequently upregulated or mutated in various cancers. Targeting MET signaling pathway has been utilized as a treatment for cancer, as since MET overexpression is often associated with poor prognosis. Selective imaging of MET-overexpressing tumor cells would thus provide a high diagnostic value; however, it remains elusive due to a lack of targeted imaging contrast agents. Herein, we have developed a multifunctional diagnostic dendrimer-peptide conjugate (DPC) system with a strong avidity to MET-expressing cancer cells. The system was prepared by conjugating MET-inhibiting peptides (C7) to generation 7 (G7) poly(amidoamine) (PAMAM) dendrimers. Due to the dendrimer-mediated multivalent binding effect, the DPCs exhibited a significantly stronger binding to the human MET protein than free C7, as measured using surface plasmon resonance. Confocal microscopy revealed increased binding of the DPCs to the MET-expressing EBC-1 and UW-Lung-21 cells, whereas a MET knock-out cell line showed negligible interactions with the DPCs. The DPCs were then conjugated with Zirconium-89 for positron emission tomography and computed tomography (PET/CT) scanning, demonstrating their selective accumulation to MET-expressing tumors in vivo. Additionally, the plasma half-life of the DPCs was measured at ~53hours, which was significantly longer than free C7. These results collectively suggest that this DPC system has potential as a targeted imaging platform specific to MET-expressing tumors, which would be applicable to various cancer types.

Metachronous Second Primary in the Form of Nasopharyngeal Carcinoma Following Treatment of Small Cell Neuroendocrine Carcinoma of the Head and Neck: Dual Tracer PET/CT Findings Highlighting SSTR2 Expression and Its Theranostic Implications

AbstractPatients of head and neck squamous cell carcinoma (HNSCC) experience increased risk of developing second primary cancer (SPC) necessitating active surveillance during their disease course. SPCs are associated with poor prognosis and are the leading cause of long-term morbidity and mortality impacting survival of patients with HNSCC. Small cell neuroendocrine carcinoma (SmNEC) is a rare but aggressive neoplasm with poor prognosis and high risk of local recurrence and distant metastasis. We report an exceedingly rare case of nasopharyngeal carcinoma (NPC) presenting as a recurrence in the form of metachronous second primary to primary SmNEC 9 years after chemotherapy. The dual tracer positron emission tomography and computed tomography (PET/CT) imaging approach ([68Ga]Ga-DOTATATE-PET/CT with 18F-FDG-PET/CT) was explored in such metachronous NPCs, and the findings are illustrated with its potential for theranostic applications. NPC is a rare malignancy with significant geographical variations in incidence rates. Somatostatin receptor 2 (SSTR2) expression in NPC is well documented and can serve as a potential theragnostic marker in advanced NPC where the successful outcome is minimal with currently available treatment modalities.

What alters prognosis in patients who were operated for lung cancer with lymph node metastasis?

In this study, we investigated the clinical outcomes of patients who underwent surgery with proven lymph node metastasis. Patients who were operated for lung cancer with pN1 or pN2 were examined in the study. The clinicopathological features and survival of the subjects were evaluated according to pN1-pN2 status, presence of neoadjuvant treatment, Positron emission tomography and computed tomography (PET/CT) avidity on mediastinal lymph nodes and specific lymph node stations. The study examines 100 patients operated from January 2016 to December 2021. Number of cases with pN1 and pN2 disease were 45 (45%) and 55 (55%) respectively. Thirty (30%) patients received neoadjuvant treatment. The 5-year overall survival (OS) and disease-free survival (DFS) of the patients were computed as 42.5% and 42.4% correspondingly. The 5-year cancer-related survival was 55.3%. In pN2 cohort, 5-year DFS was 67.9% in the neoadjuvant group and 15.9% in the non-neoadjuvant group (P = 0.042). In non-neoadjuvant group, 5-year DFS was 19.9% in cases with mediastinal PET/CT avidity and 56.3% in patients without mediastinal PET/CT avidity (P = 0.018). In pN2 disease, the presence of subcarinal or paratracheal lymph node metastasis did not create a significant difference in 5-year OS or DFS, but pulmonary ligament lymph node metastasis was found to be linked with worse survival in both 5-year OS (P = 0.005) and DFS (P = 0.017). The main elements related with poor prognosis were absence of neoadjuvant treatment and pulmonary ligament lymph node metastasis in pN2 disease, detecting PET/CT avid mediastinal lymph nodes in non-neoadjuvant group.

Preclinical characterization of endotoxin-induced uveitis models using OCT, PET/CT and proteomics

Uveitis is a group of inflammatory ocular pathologies. Endotoxin-Induced Uveitis (EIU) model represent a well-known model induced by administration of Lipopolysaccharide (LPS). The aim is to characterize two models of EIU through two routes of administration with novel noninvasive imaging techniques. 29 rats underwent Intraocular Pressure (IOP) measurements, Optical Coherence Tomography (OCT), proteomic analysis, and Positron Emission Tomography and Computed Tomography (PET/CT). Groups included healthy controls (C), BSS administered controls (Ci), systemically induced EIU with LPS (LPSs), and intravitreally induced EIU with LPS (LPSi) for IOP, OCT, and proteomic studies. For 18F-FDG PET/CT study, animals were divided into FDG-C, FDG-LPSs and FDG-LPSi groups and scanned using a preclinical PET/CT system. LPSi animals exhibited higher IOP post-induction compared to C and LPSs groups. LPSi showed increased cellular infiltrate, fibrotic membranes, and iris inflammation. Proinflammatory proteins were more expressed in EIU models, especially LPSi. PET/CT indicated higher eye uptake in induced models compared to FDG-C. FDG-LPSi showed higher eye uptake than FDG-LPSs but systemic uptake was higher in FDG-LPSs due to generalized inflammation. OCT is valuable for anterior segment assessment in experimental models. 18F-FDG PET/CT shows promise as a noninvasive biomarker for ocular inflammatory diseases. Intravitreal induction leads to higher ocular inflammation. These findings offer insights for future inflammatory disease research and drug studies.

Role of Brown Adipose Tissue in Metabolic Health and Efficacy of Drug Treatment for Obesity.

(1) Background: Brown adipose tissue (BAT) is responsible for non-shivering thermogenesis, and its activation has become a new object as both a determinant of metabolic health and a target for therapy. This study aimed to identify the relationships between the presence of BAT, parameters that characterize metabolic health (glucose, lipids, blood pressure (BP)), and the dynamics of body mass index (BMI) during weight-reducing therapy. (2) Methods: The study included 72 patients with obesity. We investigated metabolic parameters, anthropometric parameters, and BP. Dual-energy X-ray absorptiometry (DXA) and positron emission tomography and computed tomography (PET/CT) imaging with 18F-fluorodeoxyglucose (18F-FDG) were performed. (3) Results: Before weight-reducing therapy, BAT was revealed only in 19% patients with obesity. The presence of BAT was associated with a lower risk of metabolic deviations that characterize metabolic syndrome: shorter waist circumference (WC) (p = 0.02) and lower levels of glucose (p = 0.03) and triglycerides (p = 0.03). Thereafter, patients were divided into four groups according to the type of therapy (only lifestyle modification or with Liraglutide or Reduxin or Reduxin Forte). We did not find a relationship between the presence of BAT and response to therapy: percent weight reduction was 10.4% in patients with BAT and 8.5% in patients without BAT (p = 0.78) during six months of therapy. But we noted a significant positive correlation between the volume of BAT and the effectiveness of weight loss at 3 months (r = 0.52, p = 0.016). The dynamic analysis of BAT after 6 months of therapy showed a significant increase in the volume of cold-induced metabolically active BAT, as determined by PET/CT with 18F-FDG in the Liraglutide group (p = 0.04) and an increase in the activity of BAT standardized uptake value (SUV mean and SUV max) in the Reduxin (p = 0.02; p = 0.01, respectively) and Liraglutide groups (p = 0.02 in both settings). (4) Conclusions: The presence of brown adipose tissue is associated with a lower risk of metabolic abnormalities. In general, our study demonstrated that well-established drugs in the treatment of obesity (Liraglutide and Reduxin) have one more mechanism for implementing their effects. These drugs have the ability to increase the activity of BAT. A significant positive relationship between the total volume of BAT and the percentage of weight loss may further determine the priority mechanism of the weight-reducing effect of these medicaments.

Management of chylothorax after retrocrural lymphadectomy in a patient with ovarian cancer: a case report

Introduction and importance: With the widespread use of positron emission tomography and computed tomography (PET/CT), a significantly greater proportion of patients with advanced ovarian cancer (OC) are now diagnosed with superior renal-vein lymph node metastases involving retrocrural and mediastinal nodes. To the authors’ knowledge, retrocrural lymphadenectomy has not yet been reported in patients with OC. The authors performed retrocrural lymph node resection in a patient with ovarian cancer. Case presentation: A 64-year-old woman with ovarian cancer who had not undergone surgery upon initial diagnosis was admitted to the authors’ hospital because tumour markers increased during bevacizumab maintenance therapy. PET/CT imaging revealed adnexal masses and multiple metastases in pelvic, para-aortic, retrocrural, and mediastinal lymph nodes. Reduction surgery was performed, and retrocrural lymph nodes were excised. However, the patient’s postoperative course was complicated by a chylothorax. Because of the failure of conservative treatment, interventional embolization was performed, but failed to obstruct lymphatic vessels. The patient underwent reoperation. A fistula was located where Hem-o-lock clips penetrated the pleura, clearly indicating the injury site, which was then sutured and embedded in the surrounding diaphragmatic tissue and filled with gel sponge. The patient recovered from chylous leakage postoperatively. She later underwent chemotherapy and targeted maintenance therapy. Clinical discussion: The authors may have injured the communicating branch of the thoracic duct posterior to the diaphragm during the first operation and did not ligate it. The accumulated chylous fluid finally penetrated through the weak point on the pleura and led to chylothorax 3 days later. If conservative treatment or interventional embolization are unsuccessful, surgical treatment should be selected in time. Conclusion: The location of the retrocrural lymph node at the anastomosis of the chylous cistern and the thoracic duct may pose a significant risk of chylous leakage as a complication of lymphadenectomy. Full exposure of the surgical field and thorough ligation of the lymphatic vessels may lead to successful superior renal-vein lymphadenectomy.

Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography-Derived Radiomic Models in Prostate Cancer Prognostication.

The clinical integration of prostate membrane specific antigen (PSMA) positron emission tomography and computed tomography (PET/CT) scans represents potential for advanced data analysis techniques in prostate cancer (PC) prognostication. Among these tools is the use of radiomics, a computer-based method of extracting and quantitatively analyzing subvisual features in medical imaging. Within this context, the present review seeks to summarize the current literature on the use of PSMA PET/CT-derived radiomics in PC risk stratification. A stepwise literature search of publications from 2017 to 2023 was performed. Of 23 articles on PSMA PET/CT-derived prostate radiomics, PC diagnosis, prediction of biopsy Gleason score (GS), prediction of adverse pathology, and treatment outcomes were the primary endpoints of 4 (17.4%), 5 (21.7%), 7 (30.4%), and 7 (30.4%) studies, respectively. In predicting PC diagnosis, PSMA PET/CT-derived models performed well, with receiver operator characteristic curve area under the curve (ROC-AUC) values of 0.85-0.925. Similarly, in the prediction of biopsy and surgical pathology results, ROC-AUC values had ranges of 0.719-0.84 and 0.84-0.95, respectively. Finally, prediction of recurrence, progression, or survival following treatment was explored in nine studies, with ROC-AUC ranging 0.698-0.90. Of the 23 studies included in this review, 2 (8.7%) included external validation. While explorations of PSMA PET/CT-derived radiomic models are immature in follow-up and experience, these results represent great potential for future investigation and exploration. Prior to consideration for clinical use, however, rigorous validation in feature reproducibility and biologic validation of radiomic signatures must be prioritized.

Computational Techniques in PET/CT Image Processing for Breast Cancer: A Systematic Mapping Review

The problem arises from the lack of sufficient and comprehensive information about the necessary computer techniques. These techniques are crucial for developing information systems that assist doctors in diagnosing breast cancer, especially those related to positron emission tomography and computed tomography (PET/CT). Despite global efforts in breast cancer prevention and control, the scarcity of literature poses an obstacle to a complete understanding in this area of interest. The methodologies studied were systematic mapping and systematic literature review. For each article, the journal, conference, year of publication, dataset, breast cancer characteristics, PET/CT processing techniques, metrics and diagnostic yield results were identified. Sixty-four articles were analyzed, 44 (68.75%) belong to journals and 20 (31.25%) belong to the conference category. A total of 102 techniques were identified, which were distributed in preprocessing with 7 (6.86%), segmentation with 15 (14.71%), feature extraction with 15 (14.71%), and classification with 65 (63.73%). The techniques with the highest incidence identified in each stage are: Gaussian Filter, SLIC, Local Binary Pattern, and Support Vector Machine with 4, 2, 7, and 35 occurrences, respectively. Support Vector Machine is the predominant technique in the classification stage, due to the fact that Artificial Intelligence is emerging in medical image processing and health care to make expert systems increasingly intelligent and obtain favorable results.

Hybrid PET/MRI of large vessel vasculitis : Radiation dose compared to PET/CT with view on cumulative effective dose.

The diagnosis of large vessel vasculitis (LVV) is often challenging due to the various clinical appearances and the low prevalence. Hybrid imaging by positron emission tomography and computed tomography (PET/CT) is ahighly relevant imaging modality for diagnostics and disease surveillance but may be associated with asignificant amount of radiation dose especially in patients with complications. The aim of this retrospective analysis was to compare the image quality and impact of hybrid imaging methods PET/CT and PET/MRI on the potential for dose reduction. This retrospective single-center study included acohort of 32patients who were referred to PET/MRI for the evaluation of LVV, including graft infections and fever of unknown origin. This cohort was compared to asimilar cohort of 37patients who were examined with PET/CT in the same period. Mean radiation dose as well as image quality to establish adiagnosis were compared between the groups. The mean radiation dose applied in PET/MRI was significantly lower when compared to PET/CT (mean 6.6 mSV vs. 31.7 mSV; p < 0.001). This effect was based on the partially multiphasic CT protocols. At the same time, diagnostic image quality using a4-point scale showed similar results for both imaging modalities in the work-up of LVV. With PET/MRI, the radiation exposure can be significantly reduced with similar image quality and diagnostic impact. Patients with LVV have ahigher risk of receiving aclinically relevant cumulative effective dose (CED) and PET/MRI should be made available to them.

Deep learning radiomics model based on PET/CT predicts PD-L1 expression in non-small cell lung cancer

PurposeProgrammed cell death protein-1 ligand (PD-L1) is an important prognostic predictor for immunotherapy of non-small cell lung cancer (NSCLC). This study aimed to develop a non-invasive deep learning and radiomics model based on positron emission tomography and computed tomography (PET/CT) to predict PD-L1 expression in NSCLC. MethodsA total of 136 patients with NSCLC between January 2021 and September 2022 were enrolled in this study. The patients were randomly divided into the training dataset and the validation dataset in a ratio of 7:3. Radiomics feature and deep learning feature were extracted from their PET/CT images. The Mann-whitney U-test, Least Absolute Shrinkage and Selection Operator algorithm and Spearman correlation analysis were used to select the top significant features. Then we developed a radiomics model, a deep learning model, and a fusion model based on the selected features. The performance of three models were compared by the area under the curve (AUC), sensitivity, specificity, accuracy, positive predictive value, and negative predictive value. ResultsOf the patients, 42 patients were PD-L1 negative and 94 patients were PD-L1 positive. A total of 2446 radiomics features and 4096 deep learning features were extracted per patient. In the training dataset, the fusion model achieved a highest AUC (0.954, 95% confident internal [CI]: 0.890–0.986) compared with the radiomics model (0.829, 95%CI: 0.738–0.898) and the deep learning model (0.935, 95%CI: 0.865–0.975). In the validation dataset, the AUC of the fusion model (0.910, 95% CI: 0.779–0.977) was also higher than that of the radiomics model (0.785, 95% CI: 0.628–0.897) and the deep learning model (0.867, 95% CI: 0.724–0.952). ConclusionThe PET/CT-based deep learning radiomics model can predict the PD-L1 expression accurately in NSCLC patients, and provides a non-invasive tool for clinicians to select positive PD-L1 patients.

Anti-PD-1 Antibody (Tislelizumab) Combined with R-CHOP for the Treatment of Previously Untreated Primary Mediastinal B-Cell Lymphoma: A Prospective Phase II Study

Background: Primary mediastinal B-cell lymphoma (PMBCL) is a rare aggressive B-cell lymphoma of thymic origin. Due to the low incidence rate of PMBCL, there is currently no internationally accepted standard first-line treatment regimen. Dose-adjusted (DA) EPOCH-R which is the more commonly used first-line therapy plan is not so effective because patients usually cannot tolerate it. The R-CHOP regimen is comparable to the R-DA-EPOCH for the first-line treatment of PMBCL in terms of survival and has a better safety profile (Bhatt, V.R. et al, Cancer Treat Rev 2015; Iwanicka el al., Curr Hematol Malig Rep 2014). Meanwhile, patients with PMBCL usually have alterations of 9p24.1, leading to overexpression of PDL-1/2. Previous studies have found that PD-1 monoclonal antibody shows good efficacy in recurrent and refractory PMBCL (Steidl et al., Blood 2011; Zinzani et al., Blood 2017). Tislelizumab, a humanized IgG4 antibody that binds PD-1 with high affinity, minimizes binding to Fcγ receptor 1 (FcγRI) on macrophages by the genetic engineering of Fc segment, abrogating antibody-dependent phagocytosis (ADCP)-induced T-cell clearance. The efficacy and safety of its combination with R-CHOP in previously untreated PMBCL is not yet clear. We speculate that the combination of both may be a new option for the first-line therapy for PMBCL patients with good efficacy and low toxicity. Methods: This is a single-arm, multi-center, phase II clinical study (ChiCTR2100044313). Patients aged 18 years or older with a diagnosis of PMBCL and previously untreated were eligible. Eligible patients received 6 cycles of Tislelizumab (200 mg D1), Rituximab (375 mg/m 2 D1), Cyclophosphamide (750 mg/m 2 D2), Pirarubicin (50 mg/m 2 D2), Vincristine (1.4 mg/m 2, maximum dose 2 mg, D2), Prednisone (100 mg/d D2-6), every 21 days for 1 cycle. Disease response assessments were performed by positron emission tomography and computed tomography (PET-CT) or enhanced CT every two cycles, meanwhile peripheral blood ctDNA was monitored, and treatment-related adverse effects were assessed and recorded. The primary endpoint was objective remission rate (ORR). The secondary endpoints included treatment safety, progression-free survival (PFS) and overall survival (OS), and the exploratory analyses of the correlation between PD-L1 expression in tumor tissues, tumor-associated macrophages (TAM) phenotype in tumor microenvironment and efficacy. Results: From June 2020 to June 2023, 12 patients were enrolled and 9 patients had evaluable efficacy with the median age of 34 years, 3 males and 6 females, all patients had large mediastinal mass at initial diagnosis. 7 patients had PD-L1 expression (VENTANA SP263) above 80% and 2 cases could not be further tested due to insufficient tissue specimens. The ORR was 100%, and the CR rate was 77.8% (7/9) after 6 cycles of treatment. The 5 th and 9 th patient reached PR after 6 cycles of treatment due to irregular hospitalization. And CR was achieved after 2 cycles of regular treatment for the 5 th patient. NGS from formalin-fixed paraffin-embedded (FFPE) and circulating tumor DNA (ctDNA) evaluation from blood were performed across all patients before treatment. 5 patients underwent end of treatment-ctDNA test. Median follow-up 15m (6.8m-26.3m), the third patient was lost to follow-up at 9m. The other patients who achieved CR are still at complete remission. Moreover, we found SOCS1, TNFAIP3 are the most frequently mutated genes in biopsies of PMBCL and only the 5th patient had RHOA mutation which is highly related to PMBCL. The PET-CT and ctDNA assessments were negative in three patients at the end of 6 cycles with 60% concordance, and the 5 th and 9 th patient achieved PR on PET-CT, but the ctDNA assessments were negative. The most common adverse events (AEs) were gastrointestinal reactions, 2 patients experienced grade IV myelosuppression and 1 patient had grade I hyperthyroidism. No treatment-related deaths occurred. Conclusion: Tislelizumab combined with R-CHOP for the treatment of previously untreated PMBCL had good efficacy and sustained response with low toxicity. Longer follow-up is required to access the survival benefit of this regimen. Figure 1: Disease Remission in the Included Patients

Accumulation of endogenous adenosine improves cardiomyocyte metabolism via epigenetic reprogramming in an ischemia-reperfusion model

Adenosine kinase (ADK) plays the major role in cardiac adenosine metabolism, so that inhibition of ADK increases myocardial adenosine levels. While the cardioprotective actions of extracellular adenosine against ischemia/reperfusion (I/R) are well-established, the role of cellular adenosine in protection against I/R remains unknown. Here we investigated the role of cellular adenosine in epigenetic regulation on cardiomyocyte gene expression, glucose metabolism and tolerance to I/R. Evans blue/TTC staining and echocardiography were used to assess the extent of I/R injury in mice. Glucose metabolism was evaluated by positron emission tomography and computed tomography (PET/CT). Methylated DNA immunoprecipitation (MeDIP) and bisulfite sequencing PCR (BSP) were used to evaluate DNA methylation. Lentiviral/adenovirus transduction was used to overexpress DNMT1, and the OSI-906 was administered to inhibit IGF-1. Cardiomyocyte-specific ADK/IGF-1-knockout mice were used for mechanistic experiments.Cardiomyocyte-specific ADK knockout enhanced glucose metabolism and ameliorated myocardial I/R injury in vivo. Mechanistically, ADK deletion caused cellular adenosine accumulation, decreased DNA methyltransferase 1 (DNMT1) expression and caused hypomethylation of multiple metabolic genes, including insulin growth factor 1 (IGF-1). DNMT1 overexpression abrogated these beneficial effects by enhancing apoptosis and decreasing IGF-1 expression. Inhibition of IGF-1 signaling with OSI-906 or genetic knocking down of IGF-1 also abrogated the cardioprotective effects of ADK knockout, revealing the therapeutic potential of increasing IGF-1 expression in attenuating myocardial I/R injury. In conclusion, the present study demonstrated that cardiomyocyte ADK deletion ameliorates myocardial I/R injury via epigenetic upregulation of IGF-1 expression via the cardiomyocyte adenosine/DNMT1/IGF-1 axis.

Comparison of SUVA/V and SUVA-V for Evaluating Atherosclerotic Inflammation in 18F-FDG PET/CT.

This study aimed to compare the clinical significance of two parameters, division of standardized uptake value (SUV) of target arterial activity by background venous blood pool activity (SUVA/V) and subtraction of background venous blood pool activity from SUV of target arterial activity (SUVA-V) of carotid arteries with atherosclerotic plaques using 18F-fluorodeoxyglucose (FDG) positron emission tomography and computed tomography (PET/CT). Patients aged 50 years or more who were diagnosed with carotid artery stenosis of 50% or more with carotid Doppler ultrasonography and had torso 18F-FDG PET/CT were enrolled retrospectively and classified patients who developed cerebrovascular events (CVEs) within 5 years after 18F-FDG PET/CT scan as the active group and patients who did not experience the CVE within 5 years as an inactive group. We calculated SUVA/V and SUVA-V using measurements of SUVmax of carotid arteries and mean SUV of superior vena cava (SVC). SUVA-V, SUVA-V_high, and SUVA-V_low were significantly higher in the active group than in the inactive group, but neither SUVA/V, SUVA/V_high, nor SUVA/V_low showed significant differences between the active and inactive groups. The difference in rank between groups of SUVA/V_high and SUVA/V_low was greater than the difference in rank between groups of SUVA-V_high and SUVA-V_low. The CVE incidence differed between SUVA/V_high and SUVA/V_low of high carotid FDG uptake, but the CVE incidence did not differ between SUVA-V_high and SUVA-V_low of high carotid FDG uptake. SUVA-V may be a more rational solution than SUVA/V for evaluating atherosclerotic plaque inflammation on 18F-FDG PET/CT.

Measurable Residual Disease Testing in Multiple Myeloma Routine Clinical Practice: A Modified Delphi Study.

We used a modified Delphi approach to establish areas of consensus and nonconsensus regarding the utility of determining measurable residual disease (MRD) to assess multiple myeloma (MM) treatment response, which may inform disease management and design of future clinical trials. This modified Delphi study incorporated 2 iterative rounds of surveys to evaluate the opinions of an expert panel of 61 practicing hematological oncologists from across 14 countries in Europe concerning the use of MRD testing in MM management. Survey 1 assessed experts' opinions on MRD testing in different clinical situations and associated challenges. Survey 2 focused on the lack of consensus areas identified in survey 1. Consensus to an individual question was defined a priori as 75% agreement or disagreement by the panel. From the 2 rounds of surveys, the experts reached consensus agreement that MRD testing should be performed in newly diagnosed or relapsed patients who achieved complete response (CR) or better after transplantation. In transplant-ineligible patients, experts recommended MRD testing in those who are ≤70 years old and in CR. If a patient was previously positive on positron-emission tomography and computed tomography (PET/CT), both MRD and PET/CT should be assessed at CR. MRD testing should be performed ≤6 months after transplantation and every 6-12 months in continuously treated patients in CR. There was no consensus on making treatment decisions based on MRD status. MRD testing is an important component of clinical management in MM. Additional data will further clarify the role of MRD in guiding treatment decisions.

The Evolving Treatment Landscape of Merkel Cell Carcinoma.

Merkel cell carcinoma (MCC) has a high risk of recurrence and requires unique treatment relative to other skin cancers. The patient population is generally older, with comorbidities. Multidisciplinary and personalized care is therefore paramount, based on patient preferences regarding risks and benefits. Positron emission tomography and computed tomography (PET-CT) is the most sensitive staging modality and reveals clinically occult disease in ~ 16% of patients. Discovery of occult disease spread markedly alters management. Newly diagnosed, localized disease is often managed with sentinel lymph node biopsy (SLNB), local excision, primary wound closure, and post-operative radiation therapy (PORT). In contrast, metastatic disease is usually treated systemically with an immune checkpoint inhibitor (ICI). However, one or more of these approaches may not be indicated. Criteria for such exceptions and alternative approaches will be discussed. Because MCC recurs in 40% of patients and early detection/treatment of advanced disease is advantageous, close surveillance is recommended. Given that over 90% of initial recurrences arise within 3years, surveillance frequency can be rapidly decreased after this high-risk period. Patient-specific assessment of risk is important because recurrence risk varies widely (15 to > 80%: Merkelcell.org/recur) depending on baseline patient characteristics and time since treatment. Blood-based surveillance tests are now available (Merkel cell polyomavirus (MCPyV) antibodies and circulating tumor DNA (ctDNA)) with excellent sensitivity that can spare patients from contrast dye, radioactivity, and travel to a cancer imaging facility. If recurrent disease is locoregional, management with surgery and/or RT is typically indicated. ICIs are now the first line for systemic/advanced MCC, with objective response rates (ORRs) exceeding 50%. Cytotoxic chemotherapy is sometimes used for debulking disease or in patients who cannot tolerate ICI. ICI-refractory disease is the major problem faced by this field. Fortunately, numerous promising therapies are on the horizon to address this clinical need.

Human brown adipose tissue function: insights from current in vivo techniques.

The identification of brown adipose tissue (BAT) as a thermogenic organ in human adults approximately 20 years ago raised the exciting possibility of activating this tissue as a new treatment for obesity and cardiometabolic disease. 18Fluoro-2-deoxyglucose (18F-FDG) combined positron emission tomography and computed tomography (PET/CT) scanning is the most commonly used imaging modality to detect and quantify human BAT activity in vivo. This technique exploits the substantial glucose uptake by BAT during thermogenesis as a marker for BAT metabolism. 18F-FDG PET has provided substantial insights into human BAT physiology, including its regulatory pathways and the effect of obesity and cardiometabolic disease on BAT function. The use of alternative PET tracers and the development of novel techniques such as magnetic resonance imaging, supraclavicular skin temperature measurements, contrast enhanced ultrasound, near infrared spectroscopy and microdialysis have all added complementary information to improve our understanding of human BAT. However, many questions surrounding BAT physiology remains unanswered, highlighting the need for further research and novel approaches to investigate this tissue. This review critically discusses current techniques to assess human BAT function in vivo, the insights gained from these modalities and their limitations. We also discuss other promising techniques in development that will help dissect the pathways regulating human thermogenesis and determine the therapeutic potential of BAT activation.

Diagnostic value of18F-fluorodeoxyglucose positron emission tomography andcomputed tomography fordifferentiating polymyalgia rheumatica andrheumatoid arthritis: Using classification andregression tree analysis.

Determining which sites were important to differentiate polymyalgia rheumatica (PMR) from rheumatoid arthritis (RA) using 18F-fluorodeoxyglucose (FDG) positron emission tomography and computed tomography (PET-CT) is challenging. Patients with PMR or RA who were undergoing PET-CT were recruited at two mutual-aid hospitals in Japan between 2009 and 2018. Classification and regression tree (CART) analyses were performed to identify FDG uptake patterns that differentiated PMR from RA. We enrolled 35 patients with PMR and 46 patients with RA. Univariate CART analysis showed that FDG uptake in the shoulder joints, spinous processes of the lumbar vertebrae, pubic symphysis, sternoclavicular joints, ischial tuberosities, greater trochanters, and hip joints differentiated PMR from RA. Multivariate CART analysis revealed that FDG uptake by at least one of the ischial tuberosities had the highest diagnostic value for distinguishing PMR from RA (sensitivity, 77.1%; specificity, 82.6%). We performed the same CART analysis to patients who had not undergone treatment (PMR, n = 28; RA, n = 9). Similar results were obtained, and sensitivity and specificity were increased (sensitivity, 89.3%; specificity, 88.8%). In PET-CT, FDG uptake by at least one of the ischial tuberosities best discriminates between PMR and RA.

18F-FMISO PET-guided dose escalation with multifield optimization intensity-modulated proton therapy in nasopharyngeal carcinoma.

The purpose of this study was to evaluate the radiotherapy planning feasibility of dose escalation with intensity-modulated proton therapy (IMPT) to hypoxic tumor regions identified on 18F-Fluoromisonidazole (FMISO) positron emission tomography and computed tomography (PET-CT) in NPC. Nine patients with stages T3-4N0-3M0 NPC underwent 18F-FMISO PET-CT before and during week 3 of radiotherapy. The hypoxic volume (GTVhypo) is automatically generated by applying a subthresholding algorithm within the gross tumor volume (GTV) with a tumor to muscle standardized uptake value (SUV) ratio of 1.3 on the 18F-FMISO PET-CT scan. Two proton plans were generated for each patient, a standard plan to 70Gy and dose escalation plan with upfront boost followed by standard 70GyE plan. The stereotactic boost was planned with single-field uniform dose optimization using two fields to deliver 10 GyE in two fractions to GTVhypo. The standard plan was generated with IMPT with robust optimization to deliver 70GyE, 60GyE in 33 fractions using simultaneous integrated boost technique. A plan sum was generated for assessment. Eight of nine patients showed tumor hypoxia on the baseline 18F-FMISO PET-CT scan. The mean hypoxic tumor volume was 3.9 cm3 (range .9-11.9cm3 ). The average SUVmax of the hypoxic volume was 2.2 (range 1.44-2.98). All the dose-volume parameters met the planning objectives for target coverage. Dose escalation was not feasible in three of eight patients as the D0.03cc of temporal lobe was greater than 75GyE. The utility of boost to the hypoxic volume before standard course of radiotherapy with IMPT is dosimetrically feasible in selected patients. Clinical trials are warranted to determine the clinical outcomes of this approach.

Diffuse Large B-Cell Lymphoma and Related Entities.

Diffuse large B-cell lymphoma (DLBCL) is the most common malignant B-cell neoplasm, with an incidence of 5.6 per 100 000 persons per year and a mean age of onset of approximately 65 years. It is an aggressive type of non-Hodgkin's lymphoma requiring urgent treatment with curative intent. Evidence-based guidelines have not been available to date. For this first international evidence-based DLBCL-specific guideline, various systematic literature searches were performed. 5 systematic reviews, 21 randomized controlled trials (RCTs), and 36 non-randomized studies were used to formulate 42 recommendations. 142 were formulated on the basis of expert consensus. All recommendations were approved in a structured consensus-finding process. For staging, combined positron emission tomography and computed tomography (PET/CT) should be performed (evidence: a prospective registry study). For all patients with a new diagnosis of DLBCL and without contraindications, R-CHOP based immunochemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) should be initiated with curative intent (evidence: RCTs). The individual treatment strategy is tailored to the patient's age and risk constellation. Once immunochemotherapy has been completed, PET/CT should be performed again to check for remission. Patients with PET-positive residual disease that is amenable to radiotherapy should be treated with consolidating irradiation (evidence: retrospective cohort study). This clinical practice guideline on the diagnosis, treatment, and followup of patients with DLBCL and related entities provides a standardized clinical management approach, identifies areas where improvement would be desirable, and can serve as a basis for the development of further studies.