18F-FDG PET-CT Research Articles

Continuing Challenges in the Definitive Diagnosis of Cushing's Disease: A Structured Review Focusing on Molecular Imaging and a Proposal for Diagnostic Work-Up.

The definitive diagnosis of Cushing's disease (CD) in the presence of pituitary microadenoma remains a continuous challenge. Novel available pituitary imaging techniques are emerging. This study aimed to provide a structured analysis of the diagnostic accuracy as well as the clinical use of molecular imaging in patients with ACTH-dependent Cushing's syndrome (CS). We also discuss the role of multidisciplinary counseling in decision making. Additionally, we propose a complementary diagnostic algorithm for both de novo and recurrent or persistent CD. A structured literature search was conducted and two illustrative CD cases discussed at our Pituitary Center are presented. A total of 14 CD (n = 201) and 30 ectopic CS (n = 301) articles were included. MRI was negative or inconclusive in a quarter of CD patients. 11C-Met showed higher pituitary adenoma detection than 18F-FDG PET-CT (87% versus 49%). Up to 100% detection rates were found for 18F-FET, 68Ga-DOTA-TATE, and 68Ga-DOTA-CRH, but were based on single studies. The use of molecular imaging modalities in the detection of pituitary microadenoma in ACTH-dependent CS is of added and complementary value, serving as one of the available tools in the diagnostic work-up. In selected CD cases, it seems justified to even refrain from IPSS.

<sup>18</sup>FDG PET-CT significance for post-treatment monitoring in cervical and uterine cancer patients with suspected recurrence in previously irradiated zones

Early detection of cervical (CC) and endometrial (EC) cancer recurrence in previously irradiated areas remains a difficult task for clinicians and radiologists. 18F-FDG PET-CT scope and limits in this matter are not clear yet.Purpose. To determine 18F-FDG PET-CT significance and diagnostic value in differential diagnosis of locoregional recurrence and post-radiation tissue changes in CC and EC patients with suspected relapse in preirradiated zones.Materials and methods. Follow-up data, including multiparametric MRI (T1-WI, T2-WI, DWI, DCE) and 18FFDG PET-CT full descriptions, were studied in 51pts., in 25(49%) CC and 26 (51%) EC Ia–IIIc FIGO, with suspected loco-regional recurrence in pre-irradiated area, 4–96 months after the end of treatment.Adjuvant combined radiotherapy (conformal pelvic EBRT – 3D-CRT, IMRT, VMAT, endovaginal 192Ir HDR brachytherapy) was performed in 33 (64,7%) pts. after radical surgery, adjuvant chemoradiation with Cisplatin 40 mg/m2 or Carboplatin AUC2 weekly – in 8 (24.2%) of them. 18 (35,3%) pts. were treated with definitive chemoradiation, median EQD2 for HR-CTV D90 81.6 ± 4.4 Gy (CI 95% 72.4 Gy – 93.7 Gy) and 54.6 ± 3.3 Gy (CI 95% 48.8–64.2 Gy) for metastatic pelvic and paraaortic lymph nodes.Indications for 18F-FDG PET-CT (Biograph True64, Siemens, 3.8–4.7 MBq/kg, total 169–356 MBq) in all pts. were suspicious clinical, cytological, complex ultrasound, and multiparametric MRI findings in pre-irradiated zones. Any areas of 18F-FDG pathologically increased uptake were considered hypermetabolic lesions, positive for cancer recurrence.Results. No evidence of loco-regional recurrence in pre-irradiated zones was confirmed in 32 (62.7%) pts. Clinical, morphological and radiological signs of progression were obtained in 16 (31.3%) 18F-FDG PET-CTpositive patients, with SUVmax 2.86–8.8 in this subgroup. 18F-FDG PET-CT false-positive results were obtained in 6 (11.8%) patients, false-negative – in 1 (1.9%) heavy pre-treated CC patient. 18F-FDG PET-CT sensitivity was 94.1%, specificity – 84.2%, positive predictive value – 72.7%, negative predictive value – 96.9%.Conclusions. 18F-FDG-PET-CT has a high diagnostic value in the differential diagnosis of loco-regional relapses and post-radiation tissue changes in CC and EC patients with suspected progression in pre-irradiated zones. But 18F-FDG-PET-CT findings evaluation and interpretation requires a multidisciplinary discussion and consensus for this cohort of patients.

COVID-19 post-vaccination lymphadenopathy: A review of the use of fine needle aspiration cytology.

COVID-19 vaccine-associated clinical lymphadenopathy (C19-LAP) and subclinical lymphadenopathy (SLDI), which are mainly detected by 18F-FDG PET-CT, have been observed after the introduction of RNA-based vaccines during the pandemic. Lymph node (LN) fine needle aspiration cytology (FNAC) has been used to diagnose single cases or small series of SLDI and C19-LAP. In this review, clinical and LN-FNAC features of SLDI and C19-LAP are reported and compared to non-Covid (NC)-LAP. A search for studies on C19-LAP and SLDI histopathology and cytopathology was performed on PubMed and Google Scholar, on 11 January 2023. Reports on LN-FNAC of C19-LAP were retrieved. A total of 14 reports, plus one unpublished case of C19-LAP observed in our institution, diagnosed by LN-FNAC were included in a pooled analysis and compared to the corresponding histopathological reports. In total, 26 cases were included in this review, with a mean age of 50.5 years. Twenty-one lymphadenopathies assessed by LN-FNAC were diagnosed as benign, and three cases as atypical lymphoid hyperplasia; the latter were subsequently confirmed as benign (one by repetition of LN-FNAC, two by histological control). One case of mediastinal lymphadenopathy in a patient suffering from melanoma was reported as reactive granulomatous inflammation, while one unsuspected case was diagnosed as metastasis from melanoma. In all cases, the cytological diagnoses were confirmed by follow-up or excisional biopsy. The high diagnostic value of LN-FNAC in excluding malignant processes was extremely useful in this context and may be particularly valuable when CNB or histological excisions are difficult to perform, as was the case during Covid lockdowns.

Predicting Overall Survival with Deep Learning from 18F-FDG PET-CT Images in Patients with Hepatocellular Carcinoma before Liver Transplantation

Positron emission tomography and computed tomography with 18F-fluorodeoxyglucose (18F-FDG PET-CT) were used to predict outcomes after liver transplantation in patients with hepatocellular carcinoma (HCC). However, few approaches for prediction based on 18F-FDG PET-CT images that leverage automatic liver segmentation and deep learning were proposed. This study evaluated the performance of deep learning from 18F-FDG PET-CT images to predict overall survival in HCC patients before liver transplantation (LT). We retrospectively included 304 patients with HCC who underwent 18F-FDG PET/CT before LT between January 2010 and December 2016. The hepatic areas of 273 of the patients were segmented by software, while the other 31 were delineated manually. We analyzed the predictive value of the deep learning model from both FDG PET/CT images and CT images alone. The results of the developed prognostic model were obtained by combining FDG PET-CT images and combining FDG CT images (0.807 AUC vs. 0.743 AUC). The model based on FDG PET-CT images achieved somewhat better sensitivity than the model based on CT images alone (0.571 SEN vs. 0.432 SEN). Automatic liver segmentation from 18F-FDG PET-CT images is feasible and can be utilized to train deep-learning models. The proposed predictive tool can effectively determine prognosis (i.e., overall survival) and, thereby, select an optimal candidate of LT for patients with HCC.

The Role of Whole-Body Magnetic Resonance Imaging in Assessing Extrapulmonary Metastases in Osteosarcoma Staging and Restaging: A Pilot Study.

The aim of the study is to investigate the role of whole-body magnetic resonance imaging (MRI) in assessing extrapulmonary metastases in primary osteosarcoma staging. We retrospectively reviewed medical data to identify primary osteosarcoma patients with available preoperative whole-body MRI obtained in the staging or restaging. Histopathology was the reference test for assessing the diagnostic performance, if available. Otherwise, oncology board decisions were used as the reference. In addition, the benefits of whole-body MRI to F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) and bone scintigraphy were investigated. In all, 36 patients with osteosarcoma (24 staging, 12 restaging) with a mean age of 16.36 ± 5.63 years (range, 9-29 years) were included in the study. The median follow-up duration was 26.61 months (interquartile range, 33.3 months). Of 36 patients, 8 had skeletal, 1 had a lymph node, and 1 had a subcutaneous metastasis. Whole-body MRI correctly identified all patients with metastatic disease but incorrectly classified a bone infarct in one patient as a skeletal metastasis, equating a scan-level sensitivity, specificity, accuracy, negative predictive value, and positive predictive value of 100%, 96.3%, 97.3%, 100%, and 90.91%. Whole-body MRI contributed to bone scintigraphy by identifying a skeletal metastasis in one patient and positron emission tomography-computed tomography by ruling out a skeletal metastasis in another. Whole-body MRI could accurately identify extrapulmonary metastases in primary osteosarcoma patients for staging or restaging. In addition, it might contribute to the standard whole-body imaging methods.

Are Semiquantitative Methods Superior to Deauville Scoring in the Monitoring Therapy Response for Pediatric Hodgkin Lymphoma?

Tailoring treatment in patients with Hodgkin lymphoma (HL) is paramount to maximize outcomes while avoiding unnecessary toxicity. We aimed to compare the performance of SUVmax reduction (ΔSUVmax%) and the PET ratio (rPET) versus the Deauville score (DS) for assessing the chemotherapy response in pediatric HL patients undergoing 18F-FDG PET-CT. Fifty-two patients with biopsy-proven HL (aged 8-16 years) were enrolled at baseline, interim (after the second or third chemotherapy round) and post-therapy (on completion of first-line chemotherapy). Interim and post-therapy DS, ΔSUVmax% and rPET were compared as response predictors. Patients were classified as responders or non-responders based on a 24-month clinical follow-up. Interim DS showed a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of 100%, 80.4%, 100%, 40% and 82.7%, respectively, in predicting the therapy response. Post-therapy DS showed a sensitivity, specificity, PPV, NPV and accuracy of 66.7%, 97.8%, 95.7%, 80% and 94.2%, repsectively. Interim ΔSUVmax% showed a sensitivity, specificity, PPV, NPV and accuracy of 83.3%, 82.6%, 97.4%, 38.5% and 82.7%, respectively, with a 56.3% cutoff. Post-therapy ΔSUVmax% showed a sensitivity, specificity, PPV, NPV and accuracy of 83.3%, 84.8%, 97.5%, 41.7% and 84.6%, respectively, with a 76.8% cutoff. Compared to ΔSUVmax%, DS showed a significantly higher sensitivity, specificity (p < 0.05) and NPV (p < 0.01). The sensitivity, specificity, PPV, NPV and accuracy of rPET in predicting the therapy response at 24 months were 76.1%, 100%, 100%, 35.3% and 78.8%, respectively, with a cut-off of 1.31. DS and rPET showed comparable predictive performance (p > 0.58). In conclusion, DS is an easier method with better performance than ΔSUVmax% and rPET in predicting the chemotherapy response in pediatric HL patients.

Fast-track pathway for early diagnosis and management of giant cell arteritis: the combined role of vascular ultrasonography and [18F]-fluorodeoxyglucose PET-computed tomography imaging.

Giant cell arteritis (GCA) is a medical emergency, which can lead to irreversible blindness and other ischaemic vascular events if left untreated. Prompt access to specialist assessment, diagnostics in the form of a fast-track pathway (FTP) and access to appropriate treatment are key factors in preventing morbidity associated with this disease. Recent developments in vascular imaging prompted review of our management of GCA patients. Here, we present the newly implemented FTP in GCA at the University College London Hospital, with added vascular imaging in the form of temporal artery ultrasound (TAUS) and [18F]-fluorodeoxyglucose PET-computed tomography ( 18 F-FDG PET-CT) with temporal artery biopsy. The initial pilot data on the FTP showed a significant negative predictive value of the combined TAUS and 18 F-FDG PET-CT, and the vast majority of cases positive on imaging were confirmed by biopsy. Through the new FTP in GCA, the diagnosis was completed within 48-72 h, compared with the conventional pathway time of up to 2-3 weeks awaiting biopsy results. Prompt and accurate diagnosis of GCA enables commencement of corticosteroid (prednisolone) treatment in the appropriate patient population while avoiding unnecessary steroid exposure and toxicity in GCA-negative patients.

Impact of previous glucocorticoid therapy on diagnostic accuracy of [18F] FDG PET-CT in giant cell arteritis

To evaluate the impact of prior glucocorticoid (GC) treatment on the diagnostic accuracy of 18F-FDG PET-CT in giant cell arteritis (GCA). Retrospective study of a consecutive cohort of 85 patients with proven GCA who received high-dose GC before PET-CT. Thirty-nine patients previously treated with methylprednisolone (MP) boluses, of whom 37% were PET-CT (uptakes grade 3 or 2) positive. The positivity rate was 80% with MP doses of 125mg, 33% with 250 or 500mg, and 0% with doses of 1g. If we also classify as positive those cases with a grade 1 uptake (with a circumferencial uptake and smooth linear or long segmental pattern, possibly indicative of "apparently inactive" vasculitis), the positivity rate increases to 62% (100%, 50-60%, and 33% for the different MP doses, respectively). In patients with new-onset GCA treated with high-dose oral GC, PET-CT positivity was 54.5% in patients treated for less than two weeks, 38.5% in those treated for 2 to 4 weeks, and 25% in those treated for 4 to 6 weeks (increasing to 91%, 77%, and 50%, respectively, if we include cases with grade 1 uptake and these characteristics). In patients with relapsing/refractory GCA, or who developed GCA having a prior history of PMR, PET-CT positivity reached 54% despite long-term treatment with low-to-moderate doses of GC (68% including cases with a grade 1 uptake). A late 18F-FDG PET-CT (beyond the first 10 days of treatment) can also be informative in a considerable percentage of cases.

Diagnosis value of 18F-Fluoro-d-glucose positron emission tomography-computed tomography in pulmonary hamartoma: a retrospective study and systematic review

PurposeThe diagnosis of pulmonary hamartoma (PH) based on computed tomography (CT) is a challenge, especially in patients with atypical imaging characteristics. This study was aimed at summarizing the imaging characteristic of 18F-Fluoro-d-glucose positron emission tomography-computed tomography (18F-FDG PET-CT) in PH and exploring the application value of PET-CT in the diagnosis of PH.Data and methodsPatients diagnosed with PH who had undergone PET-CT from literature pertaining were retrospectively analyzed, which were cases of publications from the Cochrane Library, PubMed, Excerpta Medica Database (EMBASE), China National Knowledge Infrastructure (CNKI) and Wanfang databases, from 2008 to June 2022. The other 20 cases of the collection were patients from our hospital from 2008 to June 2022. Patients’ symptoms, imaging characteristics of chest CT, PET-CT characteristics, the reason for PET-CT and the complications were analyzed.ResultsIn this retrospective study, a total of 216 patients were diagnosed with PH and had been examined by PET-CT. 20 of the cases were patients of our hospital from January 2008 to June 2022. The other cases were collected from the literature. The mean diameter of most PH lesions is 1.7 ± 1.0 cm. The mean maximum standardized uptake value (SUVmax) of the PH lesions was 1.2 ± 1.1. Most of their SUVmax were lower than internationally recognized cut-off value (SUVmax = 2.5). PET-CT was superior to CT in the diagnosis of PH but there was a correlation of between CT diagnosis and PET-CT diagnosis for the PH lesions. In order to draw the Receiver operating characteristic (ROC), we selected 29 patients with a clear SUVmax value of their PH lesion, and 29 lung cancer patients with clear SUVmax value in our hospital were collected as a control group. ROC curve analysis showed that the area under curve (AUC) of SUVmax was 0.899, and the optimal diagnostic threshold was SUVmax > 2.65. PET-CT could distinguish PH from malignant lesions with a sensitivity of 89.66% by applying a SUVmax of 2.65 as a cut-off in this study.ConclusionPET-CT might be a useful tool to diagnose PH, which shows a better diagnostic sensitivity than CT. But PET-CT can not be used as a single diagnostic approach, which should be combined with other methods and the patients’ history to make the most correct diagnosis.

Clinical utility of combined assessments of 4D volumetric perfusion CT, diffusion-weighted MRI and 18F-FDG PET-CT for the prediction of outcomes of head and neck squamous cell carcinoma treated with chemoradiotherapy

BackgroundMultiparametric imaging has been seen as a route to improved prediction of chemoradiotherapy treatment outcomes. Four-dimensional volumetric perfusion CT (4D PCT) is useful for whole-organ perfusion measurement, as it reflects the heterogeneity of the tumor and its perfusion parameters. However, there has been no study using multiparametric imaging including 4D PCT for the prognostic prediction of chemoradiotherapy. The purpose of this study was to determine whether combining assessments of 4D PCT with diffusion-weighted MRI (DWI) and 18F-fluorodeoxyglucose PET-CT could enhance prognostic accuracy in head and neck squamous cell carcinoma (HNSCC) patients treated with chemoradiotherapy.MethodsWe examined 53 patients with HNSCC who underwent 4D PCT, DWI and PET-CT before chemoradiotherapy. The imaging and clinical parameters were assessed the relations to locoregional control (LRC) and progression-free survival (PFS) by logistic regression analyses. A receiver operating characteristic (ROC) analysis was performed to assess the accuracy of the significant parameters identified by the multivariate analysis for the prediction of LRC and PFS. We additionally assessed using the scoring system whether these independent parameters could have a complementary role for the prognostic prediction.ResultsThe median follow-up was 30 months. In multivariate analysis, blood flow (BF; p = 0.02) and blood volume (BV; p = 0.04) were significant prognostic factors for LRC, and BF (p = 0.03) and skewness of the ADC histogram (p = 0.02) were significant prognostic factors for PFS. A significant positive correlation was found between BF and BV (ρ = 0.6, p < 0.001) and between BF and skewness (ρ = 0.46, p < 0.01). The ROC analysis showed that prognostic accuracy for LRC of BF, BV, and combination of BF and BV were 77.8%, 70%, and 92.9%, and that for PFS of BF, skewness, and combination of BF and skewness were 55.6%, 63.2%, and 77.5%, respectively. The scoring system demonstrated that the combination of higher BF and higher BV was significantly associated with better LRC (p = 0.04), and the combination of lower BF and lower skewness was significantly associated with worse PFS (p = 0.004).ConclusionA combination of parameters derived from 4DPCT and ADC histograms may enhance prognostic accuracy in HNSCC patients treated with chemoradiotherapy.

Qualitative and Semiquantitative Parameters of 18F-FDG-PET/CT as Predictors of Malignancy in Patients with Solitary Pulmonary Nodule

This study aims to evaluate the reliability of qualitative and semiquantitative parameters of 18F-FDG PET-CT, and eventually a correlation between them, in predicting the risk of malignancy in patients with solitary pulmonary nodules (SPNs) before the diagnosis of lung cancer. A total of 146 patients were retrospectively studied according to their pre-test probability of malignancy (all patients were intermediate risk), based on radiological features and risk factors, and qualitative and semiquantitative parameters, such as SUVmax, SUVmean, TLG, and MTV, which were obtained from the FDG PET-CT scan of such patients before diagnosis. It has been observed that visual analysis correlates well with the risk of malignancy in patients with SPN; indeed, only 20% of SPNs in which FDG uptake was low or absent were found to be malignant at the cytopathological examination, while 45.45% of SPNs in which FDG uptake was moderate and 90.24% in which FDG uptake was intense were found to be malignant. The same trend was observed evaluating semiquantitative parameters, since increasing values of SUVmax, SUVmean, TLG, and MTV were observed in patients whose cytopathological examination of SPN showed the presence of lung cancer. In particular, in patients whose SPN was neoplastic, we observed a median (MAD) SUVmax of 7.89 (±2.24), median (MAD) SUVmean of 3.76 (±2.59), median (MAD) TLG of 16.36 (±15.87), and a median (MAD) MTV of 3.39 (±2.86). In contrast, in patients whose SPN was non-neoplastic, the SUVmax was 2.24 (±1.73), SUVmean 1.67 (±1.15), TLG 1.63 (±2.33), and MTV 1.20 (±1.20). Optimal cut-offs were drawn for semiquantitative parameters considered predictors of malignancy. Nodule size correlated significantly with FDG uptake intensity and with SUVmax. Finally, age and nodule size proved significant predictors of malignancy. In conclusion, considering the pre-test probability of malignancy, qualitative and semiquantitative parameters can be considered reliable tools in patients with SPN, since cut-offs for SUVmax, SUVmean, TLG, and MTV showed good sensitivity and specificity in predicting malignancy.

18F-FDG PET-CT in Cutaneous Metastases in Breast Carcinoma: An unusual presentation.

Cutaneous and subcutaneous metastases are an exceedingly rare presentation in various malignancies. These represent poor prognosis and disease progression. Early detection of such findings helps in changing the management plan. 18F-FDG PET-CT has played a key role in deciding treatment plan for patients with breast cancer, by detecting metastatic sites, with a high sensitivity in detecting cutaneous metastases as seen in the following case.

Global and national trends in the evolution of infective endocarditis

For the recent 20 years, substantial changes have occurred in all aspects of infectious endocarditis (IE), the evolution of risk factors, modernization of diagnostic methods, therapeutic and preventive approaches. The global trends are characterized by increased IE morbidity among people older than 65 who use intravenous psychoactive drugs. The epidemiological trend is represented by reduced roles of chronic rheumatic heart disease and congenital heart defects, increased proportion of IE associated with medical care, valve replacement, installation of intracardiac devices, and increased contribution of Staphylococcus spp. and Enterococcus spp. to the IE etiology. Additional visualization methods (fluorodeoxyglucose positron emission tomography with 18F-fludesoxyglucose (18F-FDG PET-CT), labeled white blood cell single-photon emission computed tomography (SPECT), and modernization of the etiological diagnostic algorithm for determining the true pathogen (immunochemistry, polymerase chain reaction, sequencing) also become increasingly important. The COVID-19 pandemic has also adversely contributed to the IE epidemiology. New prospects of treatment have emerged, such as bacteriophages, lysins, oral antibacterial therapy, minimally invasive surgical strategies (percutaneous mechanical aspiration), endovascular mechanical embolectomy. The physicians' compliance with clinical guidelines (CG) is low, which contributes to the high rate of adverse outcomes of IE, while simple adherence to the CG together with more frequent use of surgical treatment doubles survival. Systematic adherence to CG, timely prevention and implementation of the Endocarditis Team into practice play the decisive role in a favorable prognosis of dynamically changing IE. This article presents the authors' own data that confirm the evolutionary trends of current IE.

The role of MRI and 18F-FDG PET/CT with respect to evaluation of pathological response in the rectal cancer patients after neoadjuvant chemoradiotherapy.

We aimed to evaluate the role of magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) in determining the correct stage and predicting the pathological response. Seventy one patients with pathologic proven rectal adenocarcinoma, clinical stage IIA-IVA, and neoadjuvant chemoradiotherapy (CRT) were evaluated retrospectively. Radiotherapy was delivered 45-50 Gy in 25 fractions with concomitant oral capecitabine. Pelvic MRI, colonoscopy, and 18F-FDG PET-CT were performed before the neoadjuvant treatment (NAT). After NAT, MRI and PET-CT were performed for re-evaluation. The median follow-up time was 25 months (range: 3-57 months). Of the 71 patients who underwent NAT, 57 patients underwent surgery. Downstaging was recorded in 48 (84.2%) of 57 patients who underwent surgery. There was no statistically significant difference between both MRI and PET-CT with pathology results in terms of response evaluation. As a result of the comparison of MRI and PET-CT with pathological results; sensitivity and specificity were 91.6% (44/48) and 22.2% (2/9) for MRI, and 100% (47/47) and 12.5% (1/8) for PET-CT, respectively. PET-CT and MRI are effective in predicting response to NAT and predictive for the pathological response. A more accurate response can be judged when both PET-CT and MRI are executed together in restaging after NAT.

Development and validation of a nonenhanced CT based radiomics model to detect brown adipose tissue.

Purpose: It has been reported that brown adipose tissue (BAT) has a protective effect regarding cardiovascular disease. Positron emission tomography-computed tomography (PET-CT) is the reference method for detecting active BAT; however, it is not feasible to screen for BAT due to the required radionuclides and high-cost. The purpose of this study is to develop and validate a nonenhanced CT based radiomics model to detect BAT and to explore the relationship between CT radiomics derived BAT and cardiovascular calcification. Patients and methods: 146 patients undergoing 18F-FDG PET-CT were retrospectively included from two centers for model development (n = 86) and external validation (n = 60). The data for the model development were randomly divided into a training cohort and an internal validation cohort with a 7:3 ratio, while the external validation data were divided 1:1 into a propensity score matching (PSM) cohort and a randomly sex matched cohort. Radiomics features of BAT and non-BAT depots were extracted from regions of interest (ROI) on nonenhanced CT corresponding to PET studies. Inter-class correlation coefficient (ICC) and Pearson's correlation analysis were performed to select radiomics features with high consistency. Next, least absolute shrinkage and selection operator (LASSO) with linear regression model was used to select radiomics features for model construction. Support vector machine (SVM) was used to develop the model and a radiomics score (RS) was calculated for each depot. The diagnostic performance of the radiomics model was evaluated both on a per-depot and per-patient basis by calculating the area under the receiver operating characteristic curve (AUROC). We further divided patients into BAT-RS group and non-BAT-RS group based on radiomics score and compared their cardiovascular calcification by calculating calcium volume and score. Results: A total of 22 radiomics features were selected for model construction. On a per-depot basis, the AUROCs were 0.87 (95% CI: 0.83-0.9), 0.85 (95% CI: 0.79-0.90), 0.72 (95% CI: 0.67-0.77) and 0.74 (95% CI: 0.69-0.79) for detecting BAT in the training, internal validation, external validation 1 and external validation 2 cohorts, respectively. On a per-patient basis, the radiomics model had high AUROCs of 0.91 (95% CI: 0.84-0.98), 0.77 (95% CI: 0.61-0.92) and 0.85 (95% CI: 0.72-0.98) in the training, external validation 1 and external validation 2 cohorts, respectively. When grouping based on the radiomics model, the BAT-RS group had lower odds of coronary artery calcium (CAC) and thoracic aorta calcium (TAC) compared with the non-BAT-RS group (CAC: 2.8% vs. 20.3%, p = 0.001; TAC: 19.4% vs. 39.2%, p = 0.009). The BAT-RS group had less CAC volume (4.1 ± 4.0 mm3 vs. 147.4 ± 274.3 mm3; p = 0.001), CAC score (2.8 ± 3.0 vs. 169.1 ± 311.5; p = 0.001), TAC volume (301.4 ± 450.2 mm3 vs. 635.3 ± 1100.7 mm3; p = 0.007) and TAC score (496.2 ± 132.6 vs. 749.2 ± 1297.3; p = 0.007) than the non-BAT-RS group. Conclusion: We developed and validated a nonenhanced CT based reliable radiomics model for detecting BAT with PET-CT findings as reference standard. Radiomics signatures from nonenhanced CT can reliably detect BAT and have promising potential to be used in routine clinical settings. Importantly, our study showed that patients with BAT had less cardiovascular calcification.

Comparison of metabolic tumour volume with Standardised Uptake Value (SUV) in F18 FDG pet CT scan in children with Hodgkin lymphoma

Comparison of metabolic tumour volume with Standardised Uptake Value (SUV) in F18 FDG pet CT scan in children with Hodgkin lymphoma

The reduction of 18F-FDG uptake ability of tumor tissue after neoadjuvant chemoradiotherapy in locally advanced rectal cancer can effectively reflect the degree of tumor regression.

To evaluate the predictive value of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) imaging parameters for the response to neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC). From January 2016 to March 2020, 52 LARC patients who underwent 18F-FDG PET-CT scans within 1 week before and 8-9 weeks after nCRT, were enrolled in this study according to a pre-designed screening criteria. After total mesorectal excision (TME) surgery, we assessed tumor response to treatment and analyzed the correlation between imaging parameters obtained from two PET-CT scans and tumor regression status. Tumor response assessment showed that 13 of 52 patients received good response (GR), including 9 cases with pathological complete regression (pCR) and 4 cases with near-pathological complete regression (near-pCR). We also found that the maximum standard uptake value after nCRT (post-SUVmax), the response index (RI), the mean standard uptake values after nCRT (post-SUVmean), and the ratio of tumor SUVmean to liver SUVmean after nCRT (post-Ratio), were correlated with GR and pCR. Among these parameters, post-SUVmax and RI had a near-strong correlation with pCR (rs= -0.58 and 0.59, respectively), and also had a strong correlation with GR (rs = -0.7 and 0.63, respectively). Further ROC analysis showed that post-SUVmax and RI had higher values in predicting whether patients could achieve GR and pCR after nCRT, and the area under the curve (AUC) of both were greater than 0.9. The positive predictive values (PPVs) and negative predictive values (NPVs) of post-SUVmax for GR were 80.01% and 97.3%, and for pCR were 66.68% and 97.5%, respectively. The PPVs and NPVs of the RI values for GR were 84.61% and 94.87%, and for pCR were 69.24% and 100%, respectively. For LARC patients, the analysis of imaging parameters such as post-SUVmax and RI, which can reflect the changes of 18F-FDG uptake capacity of tumor tissues before and after nCRT, is of great value for predicting the response of patients to neoadjuvant therapy and guiding the selection of subsequent treatment strategies.

Abstract A021: Clinical and molecular characterization of naturally-occurring colorectal cancer in rhesus macaques reveals mismatch repair deficiency driven by epigenetic silencing of MLH1

Abstract Naturally occurring colorectal cancers (CRC) in rhesus macaques share many features with their human counterparts and emerge at similar life stages as in human patients, but the carcinogenesis and molecular background remain elusive, limiting the value of the model for human disease and cancer therapy. In order to better understand this naturally occurring model, we established a diagnostic and staging pipeline including imaging (18F-FDG PET, plain and contrast-enhanced CT), histopathology, and clinical assessments. We observed cancer symptoms and co-morbidities in our cohort (n=16, all Indian-origin, 11 females, mean age at arrival 20.2y) such as hypoalbuminemia, fecal occult blood, and microcytic anemia, as frequently described in human CRC patients. Pathologically, all cancers were right-sided, involving the proximal colon and/or ileocecocolic junction, and most were densely fibrotic, restricting the colonic lumen. Most cancers appeared with glandular morphology and some (18.8%) had mucinous components. Immunohistochemistry revealed loss of MLH1 and PMS2 in 100% of investigated CRCs, indicating mismatch repair deficiency which furthermore resulted in microsatellite instability (PCR &amp; fragment analysis). Whole exome sequencing revealed the close genetic relatedness to human CRCs, particularly exemplified by mutations affecting KRAS (37.5%, e.g., p.G12D), APC (31.3%), TP53 (18.8%, e.g. p.R175H), ARID1A (56.3%), and ALK (43.8%), as similarly annotated in the human COSMIC database. Nonetheless, somatic mutations do not explain the loss of MLH1 in the entire CRC cohort. Transcriptomics on the other hand revealed the transcriptional suppression of MLH1 but not MSH2, MSH6, or PMS2 in rhesus CRC in comparison to adjacent healthy colon. Moreover, comparison of differentially expressed gene sets of rhesus CRC with a human annotated database (IPA) confirmed the disease similarities observed clinically, genetically, and histopathologically. Subsequently, we investigated DNA methylation of the promoter region of MLH1 and retranslated markers for the CpG island methylator phenotype (CIMP) as described in human CRC. While only 56.3% of CRCs were considered CIMP positive (≥3/5 markers hypermethylated), 100% of investigated CRCs exhibited MLH1 promoter hypermethylation. As a result, epigenetic silencing is suggested to suppress MLH1 transcription, cause the loss of MLH1 protein, and drive mismatch repair deficiency and genomic instability in naturally occurring CRC in rhesus macaques. We therefore consider spontaneous, uninduced CRC in rhesus macaques, their treatment-naïve nature, and their unaltered immune competence an outstanding model for human disease and in particular for human cancer immunotherapy. Citation Format: Simon Deycmar, Brendan Johnson, Karina Ray, David Caudell Caudell, John Olson, Greg Dugan, W. Shane Sills, Declan Ryan, Christopher Whitlow, Kiran K. Solingapuram Sai, Betsy Ferguson, Benjamin Bimber, Cassandra Cullin, Brandy Dozier, Emily Romero, Francois Villinger, Armando Burgos, Jeff Chou, Bruno Gomes, Michael Hettich, Maurizio Ceppi, Jehad Charo, J. Mark Cline. Clinical and molecular characterization of naturally-occurring colorectal cancer in rhesus macaques reveals mismatch repair deficiency driven by epigenetic silencing of MLH1 [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer; 2022 Oct 1-4; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_1):Abstract nr A021.

The correlation between 18F FDG PET CT metabolic parameters and pathological prognostic factors in early breast cancer patients

The correlation between 18F FDG PET CT metabolic parameters and pathological prognostic factors in early breast cancer patients

Early prediction of residual disease after neoadjuvant chemoradiotherapy and cetuximab for locally advanced esophageal cancer using 18F-FDG PET-CT imaging: a prospective cohort study

Previous studies in locally advanced esophageal cancer (LAEC) suggested that a change in the tumor's metabolic response, i.e., decrease of its interim 18F-FDG uptake compared with baseline, may predict histopathological response. We evaluated the possible predictive correlation between various PET-CT and histopathological parameters following a neoadjuvant biological-containing chemoradiotherapy (CRT) regimen. Patients with resectable LAEC received neoadjuvant cisplatin/5-fluorouracil-based CRT and cetuximab following one cycle of induction chemotherapy and cetuximab. Changes in maximum and mean standardized uptake values (ΔSUV-max and ΔSUV-mean, respectively) and metabolic tumor volume (ΔMTV), measured by PET-CT at baseline and 2 weeks after the onset of treatment, were compared with histopathological findings at surgery. Histopathological response was defined by tumor regression grade (TRG), pathological complete response (pCR) and microscopic or macroscopic residual disease (RD). Of 18 patients, 13 (72%) with adenocarcinoma (AC) and 5 (28%) with squamous cell carcinoma (SCC), were included. None of the changes in the parameters of PET was associated with pCR; only ΔSUV-mean was associated with TRG in the AC cohort. In contrast, both ΔSUV-mean% and ΔSUV-max% were significantly associated with RD, both in the whole cohort and in the AC cohort. Changes in FDG-uptake predicted RD2 at surgery: only patients with less than 13% decrease in SUV-mean% or less than 29% decrease in SUV-max% had RD2, while all patients with RD0 or RD1 had greater reductions [100% specificity and 100% positive predictive value (PPV)]. Changes in ΔSUV-max and ΔSUV-mean after two weeks of onset of cetuximab-based neoadjuvant chemotherapy for LAEC may predict macroscopic RD but not TRG or pCR at surgery.