Imaging of Hypoxia in Liver Tumors With 18F-FMISO PET Before Selective Internal Radiotherapy With 90Y Microspheres.

ABSTRACT: Hypoxia is a known cause of resistance to radiotherapy and chemotherapy. Although there are multiple studies in external radiation therapies based on hypoxia PET, the effect of hypoxia in radioembolization is largely unknown. Here we present 2 cases of hepatocellular carcinoma patients from a prospective study with different lesion characteristics on pretreatment 18F-FMISO PET and varying responses on 18F-FDG PET.

A Rare Case of "Periportal Cuffing" as an Incidental Finding on 18F-FDG PET/CT.

A 7-year-old boy with known diagnosis of hereditary spherocytosis and ulcerative colitis was referred for 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography after detection of a 28 mm lesion suspicious for malignancy in spleen on upper abdomen magnetic resonance imaging (MRI). As an incidental finding, a moderately increased uptake of 18F-FDG was observed in periportal region with no definable mass. MRI revealed compatible findings with "periportal cuffing" as described on ultrasonography.

Pretest PSA and Restaging PSMA PET/CT Predict Survival in Biochemically Recurrent Prostate Cancer.

BACKGROUND: A biochemical recurrence (BCR) risk model was created based on pretest prostate specific antigen (PSA) and groupings by restaging prostate specific membrane antigen (PSMA) PET/CT. METHODS: A cohort of 1216 BCR patients were analyzed for overall survival (OS) according to the PSA threshold and restaging PSMA PET/CT. A Cox regression analysis of OS was carried out to detect significant clinical characteristics. RESULTS: In the cohort, 271 patients had a pretest PSA of <0.5 ng/mL and 945 patients had higher PSA values. The restaging PSMA PET/CT was positive for 834 patients and negative for 369. Of 1203 patients, 133 (11%) died, including 19 of the 369 (5%) patients without positive sites on the restaging PSMA PET/CT, 82 of the 711 (12%) with 1-5 positive sites, and 32 of the 123 (26%) with >5 positive sites. In the Cox regression analysis, four variables significantly predicted OS: treatment center, International Society of Urologic Pathology (ISUP) grade, pretest PSA threshold, and the grouping of positive sites on the restaging PSMA PET/CT. CONCLUSIONS: The pretest PSA and PSMA PET/CT were important for the OS of the BCR patients. The findings argue for the new BCR risk model and serve as framework for ongoing trials.

Comparison of 68Ga-PSMA PET/CT and 18F-PSMA PET/CT of a Patient with Prostate Cancer Recurrence on Urinary Bladder Wall.

Prostate cancer is one of the most prevalent cancers in the world. After radical prostatectomy, prostate-specific antigen (PSA) levels are usually used as a marker of recurrence for prostate cancer. In the case of increased PSA levels, 68Ga-prostate-specific membrane antigen (PSMA) or 18F-PSMA, a new alternative, can be performed for the detection of recurrent disease. We report a case of a 49-year-old male patient with increasing PSA levels who was previously operated 8 years ago. Although no obvious pathological uptake was detected in 68Ga-PSMA positron emission tomography/computed tomography (PET/CT), 18F-PSMA PET/CT revealed a lesion with pathological uptake on the urinary bladder wall.

Correction: von Eyben et al. A Risk Model for Patients with PSA-Only Recurrence (Biochemical Recurrence) Based on PSA and PSMA PET/CT: An Individual Patient Data Meta-Analysis. Cancers 2022, 14, 5461.

In the original publication [...].

The relationship between 18F-FCH uptake intensity and cell content in parathyroid lesions.

PURPOSE: To investigate the relationship between cell content and histopathological features of parathyroid lesions and 18F-FCH uptake intensity on PET/CT images. METHODS: Patients with primary hyperparathyroidism (age > 18) who were referred to 18F-FCH PET/CT were involved. All patients underwent parathyroidectomy. Correlation of SUVmax with following factors were statistically analysed: serum PTH, Ca, P levels and histopathological parameters, total absolute amounts of chief cell, oxyphyllic cell and clear cell components calculated by the multiplication of the volume of the parathyroid lesion and the percentage of each type of cell content (called as Absolutechief, Absoluteoxyphyllic and Absoluteclear reflecting the total amount of each cell group). RESULTS: A total of 34 samples from 34 patients (6M, 28F, mean age: 53.32 ± 15.15, min: 14, max: 84) who had a positive 18F-FCH PET/CT localizing at least one parathyroid lesion were involved. In the whole study group, SUVmax was found to be correlated with the greatest diameter and volume of the lesion and Absolutechief (p = 0.004, p = 0.002 and p = 0.035, respectively). In the subgroup analysis of 28 samples with longest diameter > 1 cm, the correlation between SUVmax and Absolutechief remained significant (p = 0.036) and correlation between SUVmax and volume and longest diameter became stronger (p = 0.011 and p > 0.001, respectively). No correlation was found between SUVmax and Absoluteoxyphyllic or Absoluteclear. CONCLUSIONS: There might be a relationship between 18F-FCH uptake intensity and chief cell content in patients with parathyroid adenoma. Further studies with larger patient groups would be beneficial to support the data.

The Role of 18F-FDOPA PET/CT in Recurrent Medullary Thyroid Cancer Patients with Elevated Serum Calcitonin Levels.

Objectives: To evaluate the diagnostic performance of 18F-dihydroxyphenylalanine (FDOPA) positron emission tomography/computed tomography (PET/CT) in the detection of medullary thyroid carcinoma (MTC) recurrence in patients with elevated calcitonin levels. Methods: The patients who had undergone 18F-FDOPA PET/CT imaging for elevated calcitonin levels after primary surgery of MTC were included in the study. addition, if available 18F-fluorodeoxyglucose (FDG) PET/CT and Gallium-68 (68Ga)- DOTATATE PET/CT images of the patients were evaluated retrospectively. The sensitivity and diagnostic performance of 18F-DOPA PET/CT were investigated. Results: A total of 14 patients (9 F and 5 M; median age: 45) were included in the analysis. Three patients had MEN IIA syndrome and 1 patient had MEN IIB syndrome, 10 patients had a diagnosis of sporadic MTC. Median calcitonin levels of the patients were calculated as 757.5 (min-max: 28.5-7911) pg/mL. Nine patients and 5 patients had undergone ultrasound and contrast-enhanced computed tomography (ceCT) of the neck, respectively, before 18F-FDOPA PET/CT imaging. 18F-FDOPA PET/CT revealed pathological uptake in the thyroid bed, lymph nodes, and distant organs in three, five and two patients, respectively. Median maximum standardized uptake value for the recurrent or metastatic lesions were calculated as 6.4 (min-max: 1.9-18.4). The sensitivity of 18F-FDOPA PET/CT in the detection of recurrent disease was calculated as 64%. Eight patients had 68Ga-DOTATATE PET/CT and 7 of them had 18F-FDG PET/CT within 3 months period before 18F-FDOPA PET/CT. 18F-FDOPA PET/CT revealed recurrent disease in 4 of 5 and 2 of the 5 patients who had negative 18F-FDG PET/CT and negative 68Ga- DOTATATE PET/CT, respectively. Conclusion: 18F-FDOPA PET/CT can detect recurrence in about two- thirds of patients with elevated calcitonin levels after primary surgery for MTC. Due to variable differentiation degree, different receptor status, and clinical behavior of MTC, all three radiopharmaceuticals can be beneficial and are complementary to each other in patient management.

Clinical value of fluorine-18-fluorodeoxyglucose PET/MRI for liver metastasis in colorectal cancer: a prospective study.

PURPOSE: To evaluate the diagnostic performance of liver 18F-FDG PET/MRI in addition to whole-body PET/CT and to compare it with MRI in the detection and clinical management of liver metastasis in patients with colorectal cancer (CRC). MATERIAL AND METHODS: Seventy-eight patients with CRC who underwent whole-body 18F-FDG PET/CT followed by liver PET/MRI were prospectively included. Histopathological confirmation and/or at least 3 months of clinical follow-up after PET/MRI were accepted as gold standard. Lesion and patient-based analyses were performed to evaluate the diagnostics performances of PET/CT, PET/MRI and MRI. In addition, changes of clinical management were evaluated. RESULTS: On lesion-based analysis, for PET/CT, PET/MRI and MRI; sensitivity (Se): 55.6%, 97.2% and 100%; specificity (Sp): 98.5%, 100% and 80.5%; and accuracy (Acc): 70.7%, 98.2% and 93.1% were calculated, respectively. Se and Acc of PET/MRI and MRI were significantly superior than PET/CT (P < 0.001). Se and Acc of PET/MRI and MRI were comparable; however, Sp of PET/MRI was significantly better than MRI (P < 0.001). On patient-based analysis, Se: 75.6%, 100% and 100%; Sp: 97.3%, 100% and 86.5%; and Acc: 85.9%, 100% and 93.5% were calculated, respectively. Se and Acc of PET/MRI were significantly superior than PET/CT (P < 0.001). Also, Se of MRI was significantly superior than PET/CT (P < 0.001). Se of PET/MRI and MRI were comparable, but Sp and Acc of PET/MRI were significantly better than MRI. The additional information obtained from liver PET/MRI changed treatment strategy in 14/78 (18%) patients compared to PET/CT or alone liver MRI. CONCLUSION: Diagnostic performances of PET/MRI and MRI for detection of CRC liver metastasis is superior to PET/CT. PET/MRI especially helps in the accurate detection of liver metastases that are suspicious on MRI and has the potential to change the clinical management of especially oligometastatic patients by identifying uncertain liver lesions.

TACE versus TARE for patients with hepatocellular carcinoma: Overall and individual patient level meta analysis.

BACKGROUND: Transarterial radioembolization (TARE) is increasingly used as an alternative to transarterial chemoembolization (TACE) for the treatment of hepatocellular carcinoma (HCC). We aimed to perform an overall and individual patient data (IPD) meta-analysis of studies comparing TACE and TARE. METHODS: We performed a systematic literature search using pre-specified keywords with the aid of an informationist for articles from inception to 3/2020. The primary endpoint was overall survival (OS), and the secondary endpoint was time to progression (TTP). RESULTS: Seventeen studies met inclusion criteria with 2465 unique patients, with one randomized trial, 4 prospective studies and 12 retrospective studies. Barcelona Clinic Liver Cancer (BCLC) stage B (42.8%) was the most common stage followed by BCLC A (30.3%) and BCLC C (29.0%). There was no difference in OS between the two modalities (-0.55 months, 95% CI -1.95 to 3.05). In three studies with available TTP data, TARE resulted in a longer TTP than TACE (mean TTP 17.5 vs. 9.8 months; mean TTP difference 4.8 months, 95% CI 1.3-8.3 months). IPD-level meta-analysis of 311 patients from three studies showed no difference in overall OS between the two modalities including among subgroups stratified by tumor stage and liver function. Limitations of the current literature include inconsistent length of follow-up, inconsistency in response criteria, and safety reporting. CONCLUSIONS: Current data suggest TARE provides significantly longer TTP than TACE, although the two treatments do not significantly differ in terms of OS. Given limitations of the current data, there is rationale for prospective studies comparing these modalities.

Radiomics analysis of uterine tumors in 18F-fluorodeoxyglucose positron emission tomography for prediction of lymph node metastases in endometrial carcinoma.

BACKGROUND: In this single-center study, we aimed to analyze texture features of primary uterine lesions on 18F-FDG PET/CT to predict lymph node metastases. METHODS: Totally, 157 (mean age: 62 ± 10.2 years) patients were included in the analysis. Histopathological examination results were considered as the standard reference for nodal involvement. On 18F-FDG PET/CT images, only the primary tumor was segmented. SUVmax, SUVmean, SUVpeak, MTV, and TLG of primary uterine lesions were calculated for analyses. For texture analysis first, second, and higher-order texture features were calculated. RESULTS: Mean diameter of primary uterine lesions was calculated as 35± 18.1 mm. Lymph node metastases were detected in 19% of patients in histopathological examination of surgical materials. While 26 patients had pelvic lymph node metastases, 19 patients had additional paraaortic lymph node metastases. On radiomics analysis for 20 features, a significant difference was found between patients with and without lymph node metastasis. With using data mining methods GLZLM ZLNU, EntropyGLCM, Entropyhisto, GLRLM LRHGE, GLZLM HGZE, GLZLM SZHGE, GLRLM HGRE, GLRLM SRHGE were found significant radiomics features to predict lymph node metastasis with a diagnostic accuracy of 0.8. DISCUSSION: The radiomics analysis of intratumoral heterogeneity is a promising method for improving triage of the patients for lymph node dissection in endometrial carcinoma.

A Risk Model for Patients with PSA-Only Recurrence (Biochemical Recurrence) Based on PSA and PSMA PET/CT: An Individual Patient Data Meta-Analysis.

An individual patient meta-analysis followed 1216 patients with PSA-only recurrence (biochemical recurrence, BCR) restaged with [68Ga]Ga-PSMA-11 PET/CT before the salvage treatment for median 3.5 years and analyzed the overall survival (OS). A new risk model included a good risk group with a prescan PSA < 0.5 ng/mL (26%), an intermediate risk group with a prescan PSA > 0.5 ng/mL and a PSMA PET/CT with 1 to 5 positive sites (65%), and a poor risk group with a prescan PSA > 0.5 ng/mL and a PSA PET/CT with > 5 positive sites (9%) (p < 0.0001, log rank test). The poor risk group had a five-year OS > 60%. Adding a BCR risk score by the European Association of Urology did not significantly improve the prediction of OS (p = 0.64). In conclusion, the restaging PSMA PET/CT markedly predicted the 5-year OS. The new risk model for patients with PSA-only relapse requires a restaging PSMA PET/CT for patients with a prescan PSA > 0.5 ng/mL and has a potential use in new trials aiming to improve the outcome for patients with PSA-only recurrence who have polysites prostate cancer detected on PSMA PET/CT.

Prognostic Factors for Effectiveness Outcomes After Transarterial Radioembolization in Metastatic Colorectal Cancer: Results From the Multicentre Observational Study CIRT.

BACKGROUND: Transarterial radioembolisation (TARE) with Yttrium-90 resin microspheres is a treatment option for patients with metastatic colorectal cancer in the liver (mCRC). A better understanding of the prognostic factors and treatment application can improve survival outcomes. METHODS: We analysed the safety and effectiveness of 237 mCRC patients included in the prospective observational study CIRSE Registry for SIR-Spheres Therapy (CIRT) for independent prognostic factors for overall survival (OS), progression-free survival (PFS) and hepatic progression-free survival (hPFS) using the Cox proportional-hazard model. RESULTS: The median OS was 9.8 months, median PFS was 3.4 months and median hPFS was 4.2 months. Independent prognostic factors for an improved overall survival were the absence of extra-hepatic disease (P= .0391), prior locoregional procedures (P= .0037), an Aspartate transaminase to Platelet Ratio Index (APRI) value of ≤0.40 (P< .0001) and International Normalized Ratio (INR) ≤1 (P= .0078). Partition model dosimetry resulted in improved OS outcomes compared to the body surface area model (P = .0120). Independent predictors for PFS were APRI >0.40 (P = .0416) and prior ablation (P = .0323), and for hPFS these were 2 to 5 tumor nodules (P = .0148), Albumin-bilirubin (ALBI) grade 3 (P = .0075) and APRI >0.40 (P = .0207). During the study, 95 of 237 (40.1%) patients experienced 197 adverse events, with 28 of 237 (11.8%) patients having a grade 3 or higher adverse events. CONCLUSION: Including easy-to-acquire laboratory markers INR, APRI, ALBI and using partition model dosimetry can identify mCRC patients that may benefit from TARE.

Elevated Angiogenic Factor Levels After Transarterial Radioembolization for Colorectal Cancer Liver Metastases May Predict a Poor Prognosis.

Objectives: To analyze the change in circulating angiogenic factor levels after transarterial radioembolization (TARE) for colorectal cancer liver metastases (CRCLMs) and its prognostic significance. Methods: Blood samples immediately before TARE and on 1 day, 1 week and 6 weeks after were collected for angiogenic factor analysis in 23 patients. Results: Patients with elevated serum basic fibroblast growth factor and platelet-derived growth factor levels in the 1st week and vascular endothelial growth factor (VEGF) levels in the 6th week after TARE had significantly shorter median overall survival (OS) times. Conclusion: Some early increases in serum angiogenic factor levels and in serum VEGF in the 6th week after TARE for CRCLMs are related to short OS and progression-free survival.

Combined clinical and specific positron emission tomography/computed tomography-based radiomic features and machine-learning model in prediction of thymoma risk groups.

OBJECTIVES: In this single-center study, we aimed to propose a machine-learning model and assess its ability with clinical data to classify low- and high-risk thymoma on fluorine-18 (18F) fluorodeoxyglucose (FDG) (18F-FDG) PET/computed tomography (CT) images. METHODS: Twenty-seven patients (14 male, 13 female; mean age: 49.6 ± 10.2 years) who underwent PET/CT to evaluate the suspected anterior mediastinal mass and histopathologically diagnosed with thymoma were included. On 18F-FDG PET/CT images, the anterior mediastinal tumor was segmented. Standardized uptake value (SUV)max, SUVmean, SUVpeak, MTV and total lesion glycolysis of primary mediastinal lesions were calculated. For texture analysis first, second, and higher-order texture features were calculated. Clinical information includes gender, age, myasthenia gravis status; serum levels of lactate dehydrogenase (LDH), alkaline phosphatase, C-reactive protein, hemoglobin, white blood cell, lymphocyte and platelet counts were included in the analysis. RESULTS: Histopathologic examination was consistent with low risk and high-risk thymoma in 15 cases and 12 cases, respectively. The age and myasthenic syndrome were statistically significant in both groups (P = 0.039 and P = 0.05, respectively). The serum LDH level was also statistically significant in both groups (450.86 ± 487.07 vs. 204.82 ± 59.04; P < 0.001). The highest AUC has been achieved with MLP Classifier (ANN) machine learning method, with a range of 0.830 then the other learning classifiers. Three features were identified to differentiate low- and high-risk thymoma for the machine learning, namely; myasthenia gravis, LDH, SHAPE_Sphericity [only for 3D ROI (nz>1)]. CONCLUSIONS: This small dataset study has proposed a machine-learning model by MLP Classifier (ANN) analysis on 18F-FDG PET/CT images, which can predict low risk and high-risk thymoma. This study also demonstrated that the combination of clinical data and specific PET/CT-based radiomic features with image variables can predict thymoma risk groups. However, these results should be supported by studies with larger dataset.

Can Radiomics Analyses in 18F-FDG PET/CT Images of Primary Breast Carcinoma Predict Hormone Receptor Status?

OBJECTIVES: This study aimed to investigate the role of preoperative 18fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) radiomics features and metabolic parameters of primary breast tumors in predicting hormone receptor (HR) positivity. METHODS: A total of 153 patients with breast carcinoma who underwent preoperative 18F-FDG PET/CT were included. All PET/CT images were retrospectively reevaluated. Radiomics features of primary breast lesions reflecting tumor heterogeneity as well as standardized uptake value (SUV) metrics (SUVmin, SUVmean, SUVmax, and SUVpeak) and volumetric parameters such as metabolic tumor volume and total lesion glycolysis (TLG) were extracted by commercial texture analysis software package (LIFEx; https://www.lifexsoft.org/ index.php). WEKA and SPSS were used for statistical analysis. Binary logistic regression analysis was used to determine texture features predicting HR positivity. Accuracy, F-measure, precision, recall, and precision-recall curve area were used as data-mining performance criteria of texture features to predict HR positivity. RESULTS: None of the radiomics parameters were significant in predicting HR status. Only SUV metrics and TLG were statistically important. Mean ± standard deviations for SUVmean, SUVmax, and SUVpeak for the HR-negative group were significantly higher than those in the HR-positive group (6.73±4.36 vs. 5.20±3.32, p=0.027; 11.55±7.42 vs. 8.63±5.23, p=0.006; and 8.37±6.81 vs. 5.72±4.86; p=0.012). Cut-off values of SUVmean, SUVmax, and SUVpeak for the prediction of HR positivity were 4.93, 8.35, and 6.02, respectively. Among data-mining methods, logistic regression showed the best performance with accuracy of 0.762. CONCLUSION: In addition to the relatively limited number of patients in this study, radiomics parameters cannot predict the HR status of primary breast cancer. SUV levels of the HR-negative group were significantly higher than those of the HR-positive group. To clarify the role of metabolic and radiomics parameters in predicting HR status in breast cancer, further studies involving a larger study population are needed.