The CT and PET/CT findings in primary pulmonary lymphoepithelioma-like carcinoma with pathological correlation: a study of 215 cases.

AIM: To investigate the computed tomography (CT) and integrated positron-emission tomography (PET)/CT findings of primary pulmonary lymphoepithelioma-like carcinoma (PLELC). MATERIALS AND METHODS: The imaging and histopathological data of 215 patients with PLELC confirmed at histopathology were analysed retrospectively. All patients underwent CT, and 70 underwent PET/CT. None of the cohort had nasopharyngeal lymphoepithelioma-like carcinoma. RESULTS: The PLELC was demonstrated as a solitary nodule/mass in 188 cases (188/215, 87%), multiple nodules/masses in 12 cases (12/215, 6%), lobar or segmental consolidation in 15 cases (15/215, 7%). The tumour showed a well-defined margin in 171 cases (171/215, 80%), lobular sign in 177 cases (177/215, 82%), and spicule sign in 91 cases (91/215, 42%). Most of the cases showed homogeneous density in unenhanced CT (128/215, 60%), and vascular shadows inside the tumour in the arterial stage were found in 105 cases (105/158, 66%). Involvement of the bronchus was found in 154 cases (154/215, 72%). Hilar or mediastinal lymph nodes were enlarged in 160 patients (160/215, 74%). Seventy cases demonstrated avid 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) uptake on PET/CT. The range of maximum standardised uptake values (SUVmax) was 2.1-28.5 (14 ± 5.93). Microscopic pathological classification of 124 resected specimens included 87 cases of the Regaud type and 37 cases of the Schmincke type. Epstein-Barr virus (EBV)-encoded small RNAs (EBERs) was positive in all 215 cases. CONCLUSION: PLELC should be suspected when a large, lobulate, well-defined lung tumour with homogeneous density, vascular encasement, and high 18F-FDG uptake is found. Moreover, EBERs are helpful in patients with suspected PLELC.

Novel Fibroblast Activation Protein Inhibitor-Based Targeted Theranostics for Radioiodine-Refractory Differentiated Thyroid Cancer Patients: A Pilot Study.

Background: This exploratory study was meant to assess clinical and safety data with a novel fibroblast activation protein inhibitor-based targeted theranostics as a salvage treatment option in radioiodine-refractory differentiated thyroid cancer (RR-DTC) patients who had progressed on tyrosine kinase inhibitors. Methods: Patients with metastatic RR-DTC who progressed on sorafenib/lenvatinib were prospectively recruited. If [68Ga]Ga-DOTA.SA.FAPi positron emission tomography/computed tomography scan demonstrated moderate-to-excellent uptake in metastases, and patients had given informed consent, they received intravenous [177Lu]Lu-DOTAGA.(SA.FAPi)2 as therapy at eight-weekly intervals. The primary endpoints were thyroglobulin (Tg) response and functional imaging response. The secondary endpoints were visual analog score (VAS) and Eastern Cooperative Oncology Group (ECOG) performance status. The grading of toxicities was performed by using Common Terminology Criteria for Adverse Events (CTCAEV5.0). The sequential images were acquired by a dual-headed gamma camera, and dosimetric calculations were performed by using OLINDA/EXM V2.1. Results: Fifteen patients were recruited [age: 55 ± 9 years (range: 39-67)]. [177Lu]Lu-DOTAGA.(SA.FAPi)2 had median whole-body Teff of 88.06 hours (interquartile range [IQR]: 86.6-99). The colon was identified as a critical organ. The whole-body effective dose was 1.62E-01 ± 1.53E-02 mSv/MBq. A total of 45 cycles were administered, and the median cumulative administered activity was 8.2 ± 2.7 GBq (range 5.5-14 GBq). The median absorbed doses to the tumor lesions were 1.08E+01 (IQR: 4.16E+00 to 8.97E+01) mSv/MBq per cycle. The Serum Tg level significantly decreased after treatment [(median Tg: baseline-10,549 ng/mL (IQR: 3066.5-39,450) versus at the time of assessment: 5649 ng/mL (IQR: 939.5-17,099), p = 0.0005)]. Molecular response assessment revealed no complete response; however, partial response was documented in four, and stable disease in three patients. The VASmax scores [pre-therapy: 9 (IQR: 8-10) versus follow-up: 6 (3-6) (p-0.0001)], and ECOG [3, (IQR: 2-3 vs. 2, (IQR: 2-3) (p-0.0078)] performance scores significantly improved after treatment. None of the patients experienced grade III/IV hematological, renal, or hepatotoxicity. Conclusion: These preliminary data suggest that the novel molecule [177Lu]Lu-DOTAGA.(SA.FAPi)2 is safe, seems effective, and, most importantly, opens up a new avenue for the treatment of aggressive RR-DTC patients who have exhausted all standard line of treatments.

68Ga-Prostate-Specific Membrane Antigen Positron Emission Tomography Maximum Standardized Uptake Value as a Predictor of Gleason Pattern 4 and Pathological Upgrading in Intermediate-Risk Prostate Cancer.

PURPOSE: Accurate risk stratification remains a barrier for the safety of active surveillance in patients with intermediate-risk prostate cancer. [68Ga]Ga-PSMA-11 prostate-specific membrane antigen positron emission tomography/computerized tomography (68Ga-PSMA PET/CT) and the maximum standardized uptake value (SUVmax) may improve risk stratification within this population. MATERIALS AND METHODS: We reviewed men with International Society for Urological Pathology Grade Group (GG) 2-3 disease on transperineal template biopsy undergoing 68Ga-PSMA PET/CT from November 2015 to January 2021. Primary outcome was the presence of high percentage Gleason pattern 4 (GP4) disease per segment at surgery at 3 thresholds: >/<50% GP4, >/<20% GP4, and >/<10% GP4. SUVmax was compared by GP4, and multivariable logistic regression examined the relationship between SUVmax and GP4. Secondary outcome was association between SUVmax and pathological upgrading (GG 1/2 to GG ≥3 from biopsy to surgery). RESULTS: Of 220 men who underwent biopsy, 135 men underwent surgery. SUVmax was higher in high GP4 groups: 5.51 (IQR 4.19-8.49) vs 3.31 (2.64-4.41) >/<50% GP4 (p <0.001); 4.77 (3.31-7.00) vs 3.13 (2.64-4.41) >/<20% GP4 (p <0.001); and 4.54 (6.10-3.13) vs 3.03 (2.45-3.70) >/<10% GP4 (p <0.001). SUVmax remained an independent predictor of >50% (OR=1.39 [95%CI 1.18-1.65], p <0.001) and >20% (OR=1.24 [1.04-1.47], p=0.015) GP4 disease per-segment, and of pathological upgrading (OR=1.22 [1.01-1.48], p=0.036). SUVmax threshold 4.5 predicted >20% GP4 with 58% specificity, 85% sensitivity, positive predictive value 75% and negative predictive value 72%. Threshold 5.4 predicted pathological upgrading with 91% specificity and negative predictive value 94%. CONCLUSIONS: SUVmax on 68Ga-PSMA PET/CT is associated with GP4. SUVmax may improve risk stratification for men with intermediate-risk prostate cancer.

Gastroenteropancreatic grade 3 neuroendocrine tumors: a single entity or a heterogeneous group? A retrospective analysis.

PURPOSE: Grade 3 neuroendocrine tumor (NET G3) is a novel pathologic category within gastro-entero-pancreatic (GEP) neuroendocrine neoplasms (NENs) but its clinical behavior and therapeutic management still remain challenging. Prognostic and predictive factors aiding NET G3 management are needed. PATIENTS AND METHODS: We performed a retrospective analysis from 2015 to 2020 of all patients with > 20% Ki-67, well-differentiated NETs evaluated within our NEN-dedicated multidisciplinary team. We divided the sample according the timing of NET G3 diagnosis, the radiotracers distribution and Ki-67. We analyzed the correlation between these NET G3 features and clinical outcomes. RESULTS: Among 3238 multidisciplinary discussion reports, we selected 55 patients, 48 from GEP and 7 from an occult GEP origin. In 45 patients, NET G3 diagnosis occurred at the beginning of clinical history (upfront-NET G3), whereas in 10, during the NET G1-G2 clinical history (late-NET G3). Patients with ≤ 30% (34/55) vs. > 30% Ki-67 (21/55) had a better overall survival (OS) (p = 0.042); patients with a homogeneous vs. inhomogeneous/negative 68Gallium(68Ga)-DOTA-Peptide Positron Emission Tomography (PET)/computed tomography (CT) showed a trend to a better OS, and a significant better progression-free survival (PFS) (p = 0.033). A better OS was observed for negative/inhomogeneous vs. homogeneous 18-fluorodeoxyglucose (18FDG)-PET/CT (p = 0.027). A trend to a better OS was reported in late- vs. upfront-NET G3, while the latter showed a significantly better response rate (RR) (p = 0.048). CONCLUSION: Our findings suggested that Ki-67 cutoff, functional imaging and the timing to NET G3 diagnosis may help clinicians in more accurate selection of NET G3 management. Prospective studies are needed.

A Comparison among Different Machine Learning Pretest Approaches to Predict Stress-Induced Ischemia at PET/CT Myocardial Perfusion Imaging.

Traditional approach for predicting coronary artery disease (CAD) is based on demographic data, symptoms such as chest pain and dyspnea, and comorbidity related to cardiovascular diseases. Usually, these variables are analyzed by logistic regression to quantifying their relationship with the outcome; nevertheless, their predictive value is limited. In the present study, we aimed to investigate the value of different machine learning (ML) techniques for the evaluation of suspected CAD; having as gold standard, the presence of stress-induced ischemia by 82Rb positron emission tomography/computed tomography (PET/CT) myocardial perfusion imaging (MPI) ML was chosen on their clinical use and on the fact that they are representative of different classes of algorithms, such as deterministic (Support vector machine and Naïve Bayes), adaptive (ADA and AdaBoost), and decision tree (Random Forest, rpart, and XGBoost). The study population included 2503 consecutive patients, who underwent MPI for suspected CAD. To testing ML performances, data were split randomly into two parts: training/test (80%) and validation (20%). For training/test, we applied a 5-fold cross-validation, repeated 2 times. With this subset, we performed the tuning of free parameters for each algorithm. For all metrics, the best performance in training/test was observed for AdaBoost. The Naïve Bayes ML resulted to be more efficient in validation approach. The logistic and rpart algorithms showed similar metric values for the training/test and validation approaches. These results are encouraging and indicate that the ML algorithms can improve the evaluation of pretest probability of stress-induced myocardial ischemia.

Initial Institutional Experience with 18F-Fluciclovine PET-CT in Biochemical Recurrence of Prostate Cancer.

OBJECTIVES: 18F-fluciclovine (fluciclovine) is an amino acid analog approved by the Food and Drug Administration for use as a radiotracer in positron emission tomography (PET) in men with biochemical recurrence of suspected prostate cancer. The purpose of this study was to investigate the initial institutional experience with 18F-fluciclovine in the evaluation of prostate cancer with biochemical recurrence. METHODS: This study was a retrospective review of 135 patients who underwent 18F-fluciclovine PET-computed tomography (PET-CT) at a single institution from August 2018 through January 2020. Prognostic information, including prostate-specific level antigen (PSA) at the time of diagnosis, initial risk, initial Gleason score, and initial stage, was reviewed as well as the PSA level at the time of the scan. The images were reviewed by two radiologists with fellowship training in nuclear medicine and additional training to interpret the fluciclovine studies. A minority of studies were reviewed by a third fellowship-trained radiologist under the guidance of the two nuclear medicine-trained radiologists. In cases with abnormal radiopharmaceutical uptake in lymph nodes, the short-axis dimension of the lymph node or largest lymph node with abnormal uptake was noted. If CT or bone scan was performed within 4 months of the 18F-fluciclovine PET-CT, findings on the alternate imaging were compared with the results of the 18F-fluciclovine PET-CT. RESULTS: Our institutional positivity rate was 75.6%, with 64 (67.4%) patients with metastatic disease and 71 (52.6%) patients with local recurrence detected by fluciclovine. As expected, the rate of positive examinations increased with increasing PSA values measured at the time of imaging (P < 0.001). Of the 54 patients with nodal disease, 35 had nonpathologically enlarged lymph nodes measuring <1 cm in maximum short-axis dimension. In more than half of the patients in this study, with conventional imaging, fluciclovine either discovered otherwise undetectable metastatic disease or suggested the presence of local recurrence. CONCLUSIONS: Our single-institution experience with 18F-fluciclovine PET-CT has the largest number of patients to date in the literature and demonstrates the ability of fluciclovine to help guide clinical management in the detection of early recurrent disease.

18F-FDG PET/CT imaging in the diagnosis of drug-induced lung disease and pulmonary infection in lymphoma.

OBJECTIVE: Lymphoma is a hematological disease with high prevalence. Multi-cycle chemotherapy (CHT) or local radiotherapy is applied usually; however, adverse events have been reported, such as drug-induced lung disease (DILD). Positron emission tomography/computed tomography (PET/CT) is often used to evaluate the lesion, treatment effect, and prognosis of lymphoma. We investigated DILD and pulmonary infection (PI) after multi-cycle CHT in lymphoma patients, to identify DILD and PI, provide guidance for later treatment for them. METHODS: In all, 677 patients diagnosed with lymphoma and who underwent CHT were included. These patients underwent 18fluorodeoxyglucose (18F-FDG) PET/CT before and after CHT at Shandong Cancer Hospital (affiliated with Shandong University) between April 2015 and November 2019. Fifty patients developed DILD, 41 patients had lung infections; lesion characteristics were analyzed based on clinical characteristics, laboratory examinations, and PET/CT imaging. RESULTS: Among the 677 lymphoma patients, there were 50 cases of DILD, with an incidence rate of 7.4%. PET/CT showed an elevated 18fluorodeoxyglucose uptake lung background, septal thickening and reticulation, multiple ground glass-like shadows, and grid-shaped blur shadows, which were more common in the lung periphery and under the pleura. The maximum standardized uptake value in the lung was 2.45 ±â€Š0.52. Pulmonary infections occurred in 41 patients, and the maximum standardized uptake value was 4.05 ±â€Š1.42. Age, sex, CHT cycle, Ann-Arbor stage, and lymphocyte levels were not significantly different between DILD and PI patients. Leukocyte and neutrophils showed significant differences; the PI patients had increased laboratory indexes of leukocyte and neutrophils. The mean number of CHT cycles was 4 cycles for DILD and PI. CONCLUSIONS: PET/CT imaging has high sensitivity and detection rates for primary and metastatic lymphoma lesions. DILD mostly occurs in the middle and late stages of CHT. Laboratory tests and PET/CT can evaluate the lesions and treatment effects, and provide guidance for subsequent treatment plans for patients.

Clinical impact of follow-up imaging on mortality in Korean breast cancer patients: A national cohort study.

BACKGROUND: As the incidence of breast cancer has increased and the survival rate has improved, supporting the optimal follow-up strategy has become an important issue. This study aimed to evaluate follow-up imaging usage after breast cancer surgery and the implications on mortality in Korea. METHODS: This study included 96,575 breast cancer patients diagnosed during 2002-2010 and registered in the Korea Central Cancer Registry, Statistics Korea, and Korean National Health Insurance Service. We evaluated the frequency of breast imaging (mammography and breast MRI) and systemic imaging for evaluating the presence of distant metastasis (chest CT, bone scan, and PET-CT), and performed analyses to determine if they had an effect on mortality. RESULTS: The median follow-up period was 72.9 months (range: 12.0-133.3) and 7.5% of the patients died. Among all patients, 54.7%, 16.2%, 45.6%, and 8.5% received 3 or more mammograms, chest CTs, bone scans, and PET-CTs within 3 years after surgery, respectively. Among patients who developed recurrence after 3 or more years, a comparison of overall mortality and breast-cancer specific mortality according to the frequency of imaging by modality (<3 vs. ≥3) showed that only mammography had significantly reduced mortality (hazard ratio [HR]: 0.72, 95% CI: 0.61-0.84, p < 0.0001; HR: 0.72, 95% CI: 0.61-0.84; p < 0.0001). CONCLUSIONS: This study showed that only frequent mammography reduced mortality and frequent imaging follow-up with other modalities did not when compared to less frequent imaging. This finding provides supportive evidence that clinicians need to adhere to the current guidelines for surveillance after breast cancer surgery.

Modified kernel MLAA using autoencoder for PET-enabled dual-energy CT.

Combined use of PET and dual-energy CT provides complementary information for multi-parametric imaging. PET-enabled dual-energy CT combines a low-energy X-ray CT image with a high-energy γ-ray CT (GCT) image reconstructed from time-of-flight PET emission data to enable dual-energy CT material decomposition on a PET/CT scanner. The maximum-likelihood attenuation and activity (MLAA) algorithm has been used for GCT reconstruction but suffers from noise. Kernel MLAA exploits an X-ray CT image prior through the kernel framework to guide GCT reconstruction and has demonstrated substantial improvements in noise suppression. However, similar to other kernel methods for image reconstruction, the existing kernel MLAA uses image intensity-based features to construct the kernel representation, which is not always robust and may lead to suboptimal reconstruction with artefacts. In this paper, we propose a modified kernel method by using an autoencoder convolutional neural network (CNN) to extract an intrinsic feature set from the X-ray CT image prior. A computer simulation study was conducted to compare the autoencoder CNN-derived feature representation with raw image patches for evaluation of kernel MLAA for GCT image reconstruction and dual-energy multi-material decomposition. The results show that the autoencoder kernel MLAA method can achieve a significant image quality improvement for GCT and material decomposition as compared to the existing kernel MLAA algorithm. A weakness of the proposed method is its potential over-smoothness in a bone region, indicating the importance of further optimization in future work. This article is part of the theme issue 'Synergistic tomographic image reconstruction: part 2'.

18F-FDG PET/CT in ovarian cancer recurrence: Clinical impact, correlation with ceCT and CA-125, and prognostic value.

AIM: To evaluate 18F-FDG-PET/CT for suspected ovarian cancer relapse with negative/inconclusive conventional imaging, or restaging potentially resectable ovarian cancer relapse. MATERIAL AND METHODS: Thirty-six cases and 140 locations were studied. PET/CT, ceCT and serum CA-125 was conducted in all cases. Nineteen cases were requested for restaging, 17 for suspected relapse. We compared ceCT and PET/CT, assessed by histopathology or radiological follow-up, calculating sensitivity (S) and positive predictive value (PPV) by cases and lesions. We evaluated the correlation between size, number, uptake of the lesions and CA-125. We conducted survival analysis, using ROC curves to calculate the optimal cut-off of SUVmax for survival prediction. We checked whether PET/CT modify the therapeutic attitude vs. conventional imaging. RESULTS: PET/CT and ceCT were concordant in 12 cases: 11 positives (30 lesions), all confirmed. There was 1 FN. In the 24 non-concordant, PET/CT was positive in 19 (97 lesions); ceCT in 21 (59 lesions); 54% of the lesions were concordant. Overall, PET/CT detected 127 lesions, with S=97% and PPV=100%. ceCT detected 89 lesions, with S=61% and PPV=90%. No significant correlation was found between CA-125 and the other parameters. PET/CT detected 10 positive cases, with normal CA-125. PET/CT modified therapeutic management in 15 cases. Significant differences were found in survival with SUVmax=11.8 CONCLUSIONS: PET/CT plays an important role in ovarian cancer relapse, with sensitivity and PPV higher than ceCT, modified therapeutic management in up to 42% of cases, and could be a valuable tool for predicting survival.

Surveillance Imaging Following Head and Neck Cancer Treatment and Microvascular Reconstruction.

OBJECTIVES/HYPOTHESIS: To assess the accuracy and utility of positron emission tomography/computed tomography (PET/CT) compared with magnetic resonance imaging (MRI) for detecting head and neck cancer (HNC) recurrence after microvascular reconstructive surgery. STUDY DESIGN: Retrospective cohort study. METHODS: Analysis of HNC patients who underwent microvascular reconstruction at a single, tertiary academic center following ablative surgery from 1998 to 2015. Forty-six patients aged 61.4 ± 15.8 years with both PET/CT and MRI examinations were identified. Two radiologists were blinded and interpreted each imaging study. Recurrence certainty scores were determined via continuous (0-100) and Likert ("Likely" to "Unlikely") scales, with larger values indicating a higher likelihood of recurrence. Pathologic confirmation of recurrence was confirmed in 23 patients (50%). RESULTS: Among those with primary site recurrences, mean recurrence certainty was significantly higher with PET/CT versus MRI on the continuous scale (63.9 vs. 44.4, P = .006). A receiver operating characteristic analysis for predicting primary site recurrence demonstrated a significantly larger area under the curve of 0.79 for PET/CT compared to 0.64 for MRI (P = .044). Categorization of "Likely" primary site recurrence on PET/CT, versus MRI, had higher sensitivity (0.63 vs. 0.40), but lower specificity (0.90 vs. 1.0). MRI demonstrated higher sensitivity (1.0 vs. 0.78) at detecting regional site recurrences. CONCLUSION: PET/CT demonstrates greater sensitivity than MRI as a surveillance tool for primary site recurrence following microvascular reconstruction where clinical evaluation is hindered by anatomical distortion. Therefore, PET/CT should be pursued as first-line imaging, with MRI utilized for confirmation of positive imaging findings at the primary site. LEVEL OF EVIDENCE: 2 Laryngoscope, 131:2713-2718, 2021.

The value of complete remission according to positron emission tomography prior to autologous stem cell transplantation in lymphoma: a population-based study showing improved outcome.

BACKGROUND: Chimeric antigen-receptor T-cell and bispecific antibody therapies will likely necessitate a reconsideration of the role of autologous stem-cell transplantation (ASCT) in lymphoma. Patients who are likely to profit from ASCT need to be better identified. METHODS: Here, we investigated the value of positron emission tomography/computerized tomography (PET/CT) before ASCT. All 521 patients transplanted for lymphoma 1994-2019 at Karolinska (497 conditioned with BEAM) were included. RESULTS: Outcome improved over three calendar periods 1994-2004, 2005-2014, 2015-2019 (2-year overall survival [OS]: 66, 73, 83%; P = 0.018). Non-relapse mortality (NRM) at 100 days over the three periods were 9.8, 3.9, 2.9%, respectively. The OS improvement between 1994 and 2004 and 2005-2014 was due to lower NRM (P = 0.027), but the large OS advance from 2015 was not accompanied by a significant reduction in NRM (P = 0.6). The fraction of PET/CT as pre-ASCT assessment also increased over time: 1994-2004, 2%; 2005-2014, 24%; 2015-2019, 60% (P < 0.00005). Complete responses (PET/CT-CR) were observed in 77% and metabolically active partial responses (PET/CT-PR) in 23%. PET/CT-CR was a predictor for survival in the entire population (P = 0.0003), also in the subpopulations of aggressive B-cell (P = 0.004) and peripheral T-cell (P = 0.024) lymphomas. Two-year OS and progression-free survival (OS/PFS) for patients in PET/CT-CR were in relapsed/refractory aggressive B-cell lymphoma 87%/75% and peripheral T-cell lymphoma 91%/78%. The corresponding figures in PET/CT-PR were 43%/44 and 33%/33%. Patients with solitary PET/CT-positive lesions showed acceptable outcome with ASCT followed by local irradiation (2-year OS/PFS 80%/60%). CT was less discriminative: 2-year OS/PFS: CT-CR, 76%/66%; CT-PR, 62%/51%. Outcome was inferior after BEAC compared with BEAM conditioning. CONCLUSIONS: We conclude that the improved outcome reflects better, PET/CT-informed, identification of patients who should proceed to ASCT. The excellent survival of patients in PET/CT-CR indicates that ASCT should remain part of standard therapy for lymphoma.

Correlations between DW-MRI and 18 F-FDG PET/CT parameters in head and neck squamous cell carcinoma following definitive chemo-radiotherapy.

BACKGROUND: Posttreatment diffusion-weighted magnetic resonance imaging (DW-MRI) and 18F-fluorodeoxygluocose (18 F-FDG) positron emission tomography (PET) with computed tomography (PET/CT) have potential prognostic value following chemo-radiotherapy (CRT) for head and neck squamous cell carcinoma (HNSCC). Correlations between these PET/CT (standardized uptake value or SUV) and DW-MRI (apparent diffusion coefficient or ADC) parameters have only been previously explored in the pretreatment setting. AIM: To evaluate stage III and IV HNSCC at 12-weeks post-CRT for the correlation between SUVmax and ADC values and their interval changes from pretreatment imaging. METHODS: Fifty-six patients (45 male, 11 female, mean age 59.9 + - 7.38) with stage 3 and 4 HNSCC patients underwent 12-week posttreatment DW-MRI and 18 F-FDG PET/CT studies in this prospective study. There were 41/56 patients in the cohort with human papilloma virus-related oropharyngeal cancer (HPV OPC). DW-MRI (ADCmax and ADCmin) and 18 F-FDG PET/CT (SUVmax and SUVmax ratio to liver) parameters were measured at the site of primary tumors (n = 48) and the largest lymph nodes (n = 52). Kendall's tau evaluated the correlation between DW-MRI and 18 F-FDG PET/CT parameters. Mann-Whitney test compared the post-CRT PET/CT and DW-MRI parameters between those participants with and without 2-year disease-free survival (DFS). RESULTS: There was no correlation between DW-MRI and 18 F-FDG PET/CT parameters on 12-week posttreatment imaging (P = .455-.794; tau = -0.075-0.25) or their interval changes from pretreatment to 12-week posttreatment imaging (P = .1-.946; tau = -0.194-0.044). The primary tumor ADCmean (P = .03) and the interval change in nodal ADCmin (P = .05) predicted 2-year DFS but none of the 18 F-FDG PET/CT parameters were associated with 2-year DFS. CONCLUSIONS: There is no correlation between the quantitative DWI-MRI and 18 F-FDG PET/CT parameters derived from 12-week post-CRT studies. These parameters may be independent biomarkers however in this HPV OPC dominant cohort, only selected ADC parameters demonstrated prognostic significance. Study was prospectively registered at http://www.controlled-trials.com/ISRCTN58327080.

Clinical PET/CT utilization during the COVID-19 pandemic: initial experience at Yale University.

OBJECTIVE: To determine temporal changes in PET/CT utilization during the COVID-19 pandemic and examine the impact of epidemiologic, demographic and oncologic factors on PET/CT utilization. METHODS: Clinical PET-CT utilization between 1 January 2020 and 15 June 2020 at a tertiary academic center was assessed using change-point-detection (CPD) analysis. COVID-19 epidemiologic trend was obtained from Connecticut Department of Public Health records. Demographic and oncologic data were gathered from electronic medical records and PET-CT scans by four reviewers in consensus. RESULTS: A total of 1685 cases were reviewed. CPD analysis identified five distinct phases of PET-CT utilization during COVID-19, with a sharp decline and a gradual recovery. There was a 62.5% decline in case volumes at the nadir. These changes correlated with COVID-19 epidemiologic changes in the state of Connecticut, with a negative correlation between COVID-19 cases and PET-CT utilization (τ = -0.54; P value < 0.001). Statistically significant differences in age, race, cancer type and current and prior scan positivity were observed in these five phases. A greater percentage of young patients and minorities were scanned during the pandemic relative to baseline. PET/CT scanning was less impacted for hematologic malignancies than for solid cancers, with less profound decline and better recovery. DISCUSSION: PET-CT cancer imaging was vulnerable to the COVID-19 pandemic at our institution. Epidemiologic, demographic and oncologic factors affected PET-CT utilization.

Improved identification of abdominal aortic aneurysm using the Kernelized Expectation Maximization algorithm.

Abdominal aortic aneurysm (AAA) monitoring and risk of rupture is currently assumed to be correlated with the aneurysm diameter. Aneurysm growth, however, has been demonstrated to be unpredictable. Using PET to measure uptake of [18F]-NaF in calcified lesions of the abdominal aorta has been shown to be useful for identifying AAA and to predict its growth. The PET low spatial resolution, however, can affect the accuracy of the diagnosis. Advanced edge-preserving reconstruction algorithms can overcome this issue. The kernel method has been demonstrated to provide noise suppression while retaining emission and edge information. Nevertheless, these findings were obtained using simulations, phantoms and a limited amount of patient data. In this study, the authors aim to investigate the usefulness of the anatomically guided kernelized expectation maximization (KEM) and the hybrid KEM (HKEM) methods and to judge the statistical significance of the related improvements. Sixty-one datasets of patients with AAA and 11 from control patients were reconstructed with ordered subsets expectation maximization (OSEM), HKEM and KEM and the analysis was carried out using the target-to-blood-pool ratio, and a series of statistical tests. The results show that all algorithms have similar diagnostic power, but HKEM and KEM can significantly recover uptake of lesions and improve the accuracy of the diagnosis by up to 22% compared to OSEM. The same improvements are likely to be obtained in clinical applications based on the quantification of small lesions, like for example cancer. This article is part of the theme issue 'Synergistic tomographic image reconstruction: part 1'.

The Pattern of Use of PET/CT Scans in the Clinical Management of Chronic Lymphocytic Leukemia.

BACKGROUND: The study aimed to evaluate the utilization patterns of positron emission tomography/computed tomography (PET/CT) in chronic lymphocytic leukemia (CLL) patients and to investigate whether the results of these scans influenced treatment decisions. PATIENTS: and Methods: In this observational study, we analyzed patients with CLL or small lymphocytic leukemia (SLL) who underwent at least one PET/CT scan from 2007 to 2018. Patients were divided into two groups: (1) patients who had at least one fluorodeoxyglucose-avid PET/CT scan, and (2) patients who had all negative scans. PET/CT results were retrieved from patients' medical files and were revised by an expert radiologist according to visual score scale, SUVmax/SUVliver mean ratio, and the SUVmax. RESULTS: Of the 524 patients, 160 patients (30.5%) had PET/CT scans, and 120 patients met the inclusion criteria. A total of 219 eligible scans were analyzed; 62 of these scans (28.3%) were reported as positive, and 167 of these scans (76.3%) were performed for staging. There was a significant association between PET/CT results and change of therapy (P < .001); however, 62.9% of the positive PET/CT scans were not followed by a change of treatment. Survival time was not different between the two groups. The SUVmax/SUVliver mean ratio was negatively significantly associated with lymphocytes percent (r = -0.237, P = .042) and positively associated with lactate dehydrogenase levels (r = 0.338, P = .008) among CLL patients. CONCLUSION: Despite the fact that the use of surveillance PET/CT for patients with CLL/SLL is not in the guidelines and that it is not useful for disease management, in practice the test is in frequent use in Israel.

PET/CT helps to determine treatment duration in patients with resected as well as inoperable alveolar echinococcosis.

PURPOSE: The aim of the study was to determine the role of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) at the end of benzimidazole therapy in alveolar echinococcosis. METHODS: A total of 22 patients undergoing PET/CT at the end of benzimidazole therapy were retrospectively registered. Maximum standardized uptake values (SUVmax) were measured in remaining echinococcus manifestations and compared to normal liver tissue. Long-term clinical follow-up was performed, and recorded data included laboratory parameters, clinical information and imaging. RESULTS: All patients had no detectable levels of Em-18 antibodies and all echinococcus manifestations were negative on PET/CT, i.e. without focally increased FDG uptake or uptake higher than normal/non-infected liver tissue. All manifestations displayed significantly less FDG-uptake than normal liver tissue, i.e. SUVmax 1.8 (interquartile range (IQR) 1.5-3.5) vs. 3.0 (IQR 2.6-5.7), (p < 0.001). Patients were clinically followed for a median of 9.5 years (IQR 6.5-32.0 years) after their initial diagnosis and for 4.5 years (IQR 3.0-14.0 years) after discontinuation of benzimidazole therapy. No patient showed signs of recurrent infection at the last clinical visit. The 10-year and 20-year freedom from all-cause mortality was 95.0% (95% confidence interval 69.5% - 99.3%), for both. Two events occurred in 292 patient years of follow-up; i.e. two patients (9%) died, one because of pancreatic cancer, the other one because of unknown reasons with no detectable antibody levels. CONCLUSIONS: Negative FDG-PET/CT results combined with no detectable levels of Em-18 antibodies may allow for the safe discontinuation of benzimidazole therapy in patients with alveolar echinococcosis.

Interim and end-of-treatment PET-CT suffers from high false-positive rates in DLBCL: Biopsy is needed prior to treatment decisions.

The application of positron emission tomography (PET)-computed tomography (CT) in treatment response evaluation has increased in diffuse large B-cell lymphoma (DLBCL), although its predictive value is controversial. We retrospectively analyzed the rate of false-positive PET-CTs performed as interim (n = 94) and end-of-treatment (n = 8) assessments among 102 DLBCL patients treated during 2010-2017 at Oulu University Hospital. In PET-CT Deauville score ≥4 was regarded as positive. A biopsy was performed on 35 patients, and vital lymphoma tissue was detected from nine patients. Positive biopsy findings were associated with poor disease outcomes in this study. This difference was statistically significant: 2-year failure-free survival (FFS) was 44% in patients with a positive biopsy versus 83% for those with a negative biopsy (p = 0.003). The corresponding overall survival (OS) rates were 53% versus 95% (p = 0.010). In the multivariate analyses, a negative biopsy was an independent protective factor in FFS (Hazard Ratio (HR) 0.093 (95% confidence interval [CI] 0.017-0.511); p = 0.006) unrelated to the International Prognostic Index (IPI) (HR 1.139 [95% CI 0.237-5.474] p = 0.871) or stage (HR 1.365 [95% CI 0.138-13.470]; p = 0.790). There was no statistically significant difference in OS according to the PET results, but the FFS rate was significantly higher in patients with a negative PET. The value of PET-CT as an evaluation method suffers from a high false-positive rate, and it is inadequate alone for the justification of treatment decisions. Biopsy results provide more reliable prognostic information for the evaluation of treatment response and outcome and should be used to assess patients with positive PET-CT scans.

FDG-PET/CT in intensive care patients with bloodstream infection.

BACKGROUND: 2-Deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) is an advanced imaging technique that can be used to examine the whole body for an infection focus in a single examination in patients with bloodstream infection (BSI) of unknown origin. However, literature on the use of this technique in intensive care patients is scarce. The purpose of this study was to evaluate the diagnostic yield of FDG-PET/CT in intensive care patients with BSI. METHODS: In this retrospective cohort study, all intensive care patients from our Dutch university medical center who had culture-proven BSI between 2010 and 2020 and underwent FDG-PET/CT to find the focus of infection were included. Diagnostic performance was calculated and logistic regression analysis was performed to evaluate the association between FDG-PET/CT outcome and C-reactive protein level (CRP), leukocyte count, duration of antibiotic treatment, duration of ICU stay, quality of FDG-PET/CT, and dependency on mechanical ventilation. In addition, the impact of FDG-PET/CT on clinical treatment was evaluated. RESULTS: 30 intensive care patients with BSI were included. In 21 patients, an infection focus was found on FDG-PET/CT which led to changes in clinical management in 14 patients. FDG-PET/CT achieved a sensitivity of 90.9% and specificity of 87.5% for identifying the focus of infection. Poor quality of the FDG-PET images significantly decreased the likelihood of finding an infection focus as compared to reasonable or good image quality (OR 0.16, P = 0.034). No other variables were significantly associated with FDG-PET/CT outcome. No adverse events during the FDG-PET/CT procedure were reported. CONCLUSION: FDG-PET/CT has a high diagnostic yield for detecting the infection focus in patients with BSI admitted to intensive care. Poor PET image quality was significantly associated with a decreased likelihood of finding the infection focus in patients with BSI. This could be improved by adequate dietary preparation and cessation of intravenous glucose and glucose-regulating drugs. Recent advances in PET/CT technology enable higher image quality with shorter imaging time and may contribute to routinely performing FDG-PET/CT in intensive care patients with BSI of unknown origin.

Pretreatment maximum standardized uptake value in 18F-fluorodeoxyglucose positron emission tomography-computed tomography as a prognostic factor for ovarian clear cell carcinoma and low-grade serous carcinoma.

OBJECTIVE: The maximum standardized uptake value (SUVmax) derived by positron emission tomography-computed tomography (PET/CT) can be an index of biological tumor aggressiveness, which is assessed using noninvasive tools before the treatment of epithelial ovarian cancer (EOC). This study aimed to evaluate the prognostic value of the pretreatment SUVmax in patients with EOC. MATERIALS AND METHODS: We reviewed the data of patients with EOC who underwent pretreatment 18F-FDG PET/CT between June 2006 and September 2016. The relationships between pretreatment SUVmax and histological subtypes of EOC were determined. Moreover, progression-free survival (PFS) and overall survival (OS) were evaluated according to the pretreatment SUVmax. Risk factors associated with progression or death were also analyzed. RESULTS: Of 148 patients, 66 (44.6%), 11 (7.4%), 34 (23.0%), 19 (12.8%), 15 (10.1%), and three (2.0%) were diagnosed with high-grade serous carcinoma (HGSC), low-grade serous carcinoma (LGSC), clear cell carcinoma (CCC), endometrioid carcinoma, mucinous carcinoma, and others, respectively. The median SUVmax was marginally lower in LGSC (6.80 vs. 10.5; P = 0.059) and significantly lower in CCC (5.92 vs. 10.5; P = 0.001) than in HGSC. A high pretreatment SUVmax (≥9.30) was a prognostic factor for OS in patients with LGSC (P = 0.046). Furthermore, multivariate analysis revealed that a high SUVmax (≥5.85) was an independent prognostic factor for OS (P = 0.046) in patients with CCC. However, a high SUVmax (≥7.77) was a poor predictor of PFS and OS in patients with EOC (P = 0.156 and P = 0.158, respectively). CONCLUSION: Our findings suggest that the pretreatment SUVmax is not only an independent predictor of survival in patients with CCC but also a significant predictor of survival in patients with LGSC.