Tumor Standardized Uptake Value Research Articles

A New Perspective on the Effectiveness of FDG PET/CT in Predicting KRAS Mutation in Colon Cancer Cases.

Aim: The main aim of this study was to evaluate the effectiveness of 18F-fluorodeoxyglucose (18FDG) positron emission tomography/computerized tomography (PET/CT) parameters in predicting the Kristen rat sarcoma viral oncogene(KRAS) mutation status of patients with colon cancer. Materials and Methods: Between April 2013 and December 2020, 79 patients who were diagnosed with colon cancer by colonoscopy underwent staging 18FDG PET/CT with this diagnosis and met all the inclusion criteria were included in this study. Clinical and prognostic features and also imaging (18FDG PET/CT and magnetic resonance imaging) reports of the patients were collected and analyzed retrospectively. Results: KRAS mutation was seen in 32 of patients (40.5%). No significant difference was observed between KRAS mutant and wild-type patients in terms of clinical features (tumor location, findings regarding metastasis, T stage, and tumor differentiation grade in patients who underwent surgery) and overall survival. Progression-free survival was significantly shorter in KRAS mutant patients (p = 0.018). Primary tumor standardized uptake value (SUVmean) was significantly higher in KRAS mutant cases in the whole group (p = 0.024) and in patients in whom KRAS analysis was performed only in the primary lesion (p = 0.036). The cutoff value for predicting KRAS mutation status was 7.01 g/mL (area under the curve [AUC]: 0.650, confidence interval [CI] 95%, 0.56-0.74). Conclusions: When colon and rectal cancer cases were evaluated separately, the primary tumor SUVmean value was significantly higher in KRAS mutant colon cancer cases. However, its effectiveness in predicting KRAS mutation status was low, similar to other parameters in the literature.

The prognostic value of lymph node to primary tumor standardized uptake value ratio in cancer patients: a meta-analysis.

The lymph node to primary tumor standardized uptake value ratio (NTR) is an innovative parameter derived from positron emission tomography/computed tomography (PET/CT) scans that captures the intricate relationship between primary tumors and associated lymph nodes. This meta-analysis aimed to investigate the prognostic value of NTR in cancer patients. A systematic search of PubMed, Cochrane, and Embase databases was conducted to identify studies investigating the association between NTR and survival outcomes in cancer patients. The pooled adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Twelve studies comprising a total of 2037 patients were included in the meta-analysis. Elevated NTR was significantly associated with worse overall survival aHR (2.21, 95% CI 1.63 to 2.99), disease-free survival aHR (3.27, 95% CI 2.12 to 5.05), and distant metastasis-free survival aHR (2.07, 95% CI 1.55 to 2.78) in cancer patients. Subgroup analyses by cancer type showed consistent results across various malignancies, including head and neck squamous cell carcinoma, endometrial carcinoma, lung cancer, breast cancer, and nasopharyngeal carcinoma. This meta-analysis provides evidence for a significant association between elevated NTR and worse survival outcomes in cancer patients. Elevated NTR may serve as a useful prognostic biomarker for cancer patients and could potentially be used to guide treatment decisions and monitor disease progression. Future studies should aim to validate these findings in larger and more diverse patient populations and investigate the underlying mechanisms for the observed association between NTR and survival outcomes.

Comparison of quantitative whole body PET parameters on [68Ga]Ga-PSMA-11 PET/CT using ordered Subset Expectation Maximization (OSEM) vs. bayesian penalized likelihood (BPL) reconstruction algorithms in men with metastatic castration-resistant prostate cancer

BackgroundPSMA PET/CT is a predictive and prognostic biomarker for determining response to [177Lu]Lu-PSMA-617 in patients with metastatic castration resistant prostate cancer (mCRPC). Thresholds defined to date may not be generalizable to newer image reconstruction algorithms. Bayesian penalized likelihood (BPL) reconstruction algorithm is a novel reconstruction algorithm that may improve contrast whilst preventing introduction of image noise. The aim of this study is to compare the quantitative parameters obtained using BPL and the Ordered Subset Expectation Maximization (OSEM) reconstruction algorithms.MethodsFifty consecutive patients with mCRPC who underwent [68Ga]Ga-PSMA-11 PET/CT using OSEM reconstruction to assess suitability for [177Lu]Lu-PSMA-617 therapy were selected. BPL algorithm was then used retrospectively to reconstruct the same PET raw data. Quantitative and volumetric measurements such as tumour standardised uptake value (SUV)max, SUVmean and Molecular Tumour Volume (MTV-PSMA) were calculated on both reconstruction methods. Results were compared (Bland-Altman, Pearson correlation coefficient) including subgroups with low and high-volume disease burdens (MTV-PSMA cut-off 40 mL).ResultsThe SUVmax and SUVmean were higher, and MTV-PSMA was lower in the BPL reconstructed images compared to the OSEM group, with a mean difference of 8.4 (17.5%), 0.7 (8.2%) and − 21.5 mL (-3.4%), respectively. There was a strong correlation between the calculated SUVmax, SUVmean, and MTV-PSMA values in the OSEM and BPL reconstructed images (Pearson r values of 0.98, 0.99, and 1.0, respectively). No patients were reclassified from low to high volume disease or vice versa when switching from OSEM to BPL reconstruction.Conclusions[68Ga]Ga-PSMA-11 PET/CT quantitative and volumetric parameters produced by BPL and OSEM reconstruction methods are strongly correlated. Differences are proportional and small for SUVmean, which is used as a predictive biomarker. Our study suggests that both reconstruction methods are acceptable without clinical impact on quantitative or volumetric findings. For longitudinal comparison, committing to the same reconstruction method would be preferred to ensure consistency.

Customizable Porphyrin Platform Enables Folate Receptor PET Imaging Using Copper-64.

Folate receptors including folate receptor α (FRα) are overexpressed in up to 90% of ovarian cancers. Ovarian cancers overexpressing FRα often exhibit high degrees of drug resistance and poor outcomes. A porphyrin chassis has been developed that is readily customizable according to the desired targeting properties. Thus, compound O5 includes a free base porphyrin, two water-solubilizing groups that project above and below the macrocycle plane, and a folate targeting moiety. Compound O5 was synthesized (>95% purity) and exhibited aqueous solubility of at least 0.48 mM (1 mg/mL). Radiolabeling of O5 with 64Cu in HEPES buffer at 37 °C gave a molar activity of 1000 μCi/μg (88 MBq/nmol). [64Cu]Cu-O5 was stable in human serum for 24 h. Cell uptake studies showed 535 ± 12% bound/mg [64Cu]Cu-O5 in FRα-positive IGROV1 cells when incubated at 0.04 nM. Subcellular fractionation showed that most radioactivity was associated with the cytoplasmic (39.4 ± 2.7%) and chromatin-bound nuclear (53.0 ± 4.2%) fractions. In mice bearing IGROV1 xenografts, PET imaging studies showed clear tumor uptake of [64Cu]Cu-O5 from 1 to 24 h post injection with a low degree of liver uptake. The tumor standardized uptake value at 24 h post injection was 0.34 ± 0.16 versus 0.06 ± 0.07 in the blocking group. In summary, [64Cu]Cu-O5 was synthesized at high molar activity, was stable in serum, exhibited high binding to FRα-overexpressing cells with high nuclear translocation, and gave uptake that was clearly visible in mouse tumor xenografts.

Prediction of 177Lu-DOTATATE Therapy Outcomes in Neuroendocrine Tumor Patients Using Semi-Automatic Tumor Delineation on 68Ga-DOTATATE PET/CT.

Treatment of metastatic neuroendocrine tumors (NET) with 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) results in favorable response only in a subset of patients. We investigated the prognostic value of quantitative pre-treatment semi-automatic 68Ga-DOTATATE PET/CT analysis in NET patients treated with PRRT. The medical records of 94 NET patients who received at least one cycle of PRRT at a single institution were retrospectively reviewed. On each pre-treatment 68Ga-DOTATATE PET/CT, the total tumor volume (TTV), maximum tumor standardized uptake value for the patient (SUVmax), and average uptake in the lesion with the lowest radiotracer uptake (SUVmin) were determined with a semi-automatic tumor delineation method. Progression-free survival (PFS) and overall survival (OS) among the patients were compared based on optimal cutoff values for the imaging parameters. On Kaplan-Meier analysis and univariate Cox regression, significantly shorter PFS was observed in patients with lower SUVmax, lower SUVmin, and higher TTV. On multivariate Cox regression, lower SUVmin and higher TTV remained predictive of shorter PFS. Only higher TTV was found to be predictive of shorter OS on Kaplan-Meier and Cox regression analyses. In a post hoc Kaplan-Meier analysis, patients with at least one high-risk feature (low SUVmin or high TTV) showed shorter PFS and OS, which may be the most convenient parameter to measure in clinical practice. The tumor volume and lowest lesion uptake on 68Ga-DOTATATE PET/CT can predict disease progression following PRRT in NET patients, with the former also predictive of overall survival. NET patients at risk for poor outcomes following PRRT can be identified with semi-automated quantitative analysis of 68Ga-DOTATATE PET/CT.

Correlation between 18-FDG standardized uptake value and tumor grade in patients with resectable non-small cell lung cancer.

Positron-emission tomography (PET) is widely used for staging lung cancer. Although a correlation between the fluorodeoxyglucose standardized uptake value (SUV) and the histologic grade of the tumor has been shown in several studies, little is known about the impact of different clinical variables on this correlation. This study aimed to evaluate the correlation between tumor SUV and tumor grade in a large cohort of patients and to analyse the impact of clinical factors on this correlation. This retrospective cohort study including patients with non-small cell lung cancer age 18-90 years, with clinical stage I-IVA, who underwent curative-intent lung resection. Data from 726 patients was included in this study. There was a strong correlation between SUV and primary tumor grade in the whole cohort (P<0.001), which was significant in both sexes (P<0.001) and in all selected age groups (P<0.001-0.03). There was a significant SUV-grade correlation for the right upper and left lower lobes, as well as for the central location in the right lung (P<0.001, P=0.005 and P=0.04, respectively). Moreover, a significant SUV-grade correlation was found for squamous cell cancer and adenocarcinoma (P<0.001 and P=0.01, respectively), and for T1-T3 factors (P<0.001, P=0.006, P=0.005 respectively). In patients with resectable lung cancer, a significant correlation was observed between the SUV of the primary tumor and its grade. This correlation was maintained for both sexes, age groups, most common histological types and T factors T1-T3.

Prognostic Utility of Neck Lymph Node-to-Primary Tumor Standardized Uptake Value Ratio in Oral Cavity Cancer.

We investigated the prognostic utility of preoperative neck lymph node-to-primary tumor maximum standardized uptake value ratios (NTRs) in oral cavity squamous cell carcinoma (OSCC). We retrospectively reviewed the medical records of 141 consecutive patients who were diagnosed as having OSCC and had received fluorodeoxyglucose-positron emission tomography within 2 weeks prior to radical surgery between 2009 and 2018. To determine the optimal NTR cutoff, receiver operating characteristic analysis for overall survival (OS) was executed. The NTR's prognostic value for disease-free survival (DFS) and OS were determined through Cox proportional hazards analysis and the Kaplan-Meier method. We determined the median (range) follow-up duration to be 35.2 (2.1-122.4) months. The optimal NTR cutoff was 0.273, and patients with a higher NTR (≥0.273) exhibited significantly worse DFS and OS (p = 0.010 and 0.003, respectively). A higher NTR (≥0.273) predicted poorer DFS (hazard ratio: 2.696, p = 0.008) and OS (hazard ratio: 4.865, p = 0.003) in multivariable analysis. We created a nomogram on the basis of the NTR, and it could accurately predict OS (concordance index: 0.774). Preoperative NTRs may be a useful prognostic biomarker for DFS and OS in patients with OSCC who have undergone surgery. NTR-based nomograms may also be helpful prognostic tools in clinical trials.

Prognostic Value of 18F-Fluorodeoxyglucose Uptake of Bone Marrow on PET/CT in Patients with Limited Disease Small Cell Lung Cancer

Merve AYIK TURK1, Berna KOMURCUOGLU2, Ahmet YANARTAS3, Ozgur BATUM2, Yunus TURK4, Mehmet Ufuk YILMAZ5 1Izmir Bozyaka Training and Research Hospital, Department of Pulmonology, İzmir 2Dr. Suat Seren Chest Diseases and Surgery Training and Research Hospital, Department of Pulmonology, İzmir 3Dr. Suat Seren Chest Diseases and Surgery Training and Research Hospital, Department of Nuclear Medicine, İzmir 4Dr. Suat Seren Chest Diseases and Surgery Training and Research Hospital, Department of Thoracic Surgery, İzmir 5Medicana Health Groups, Department of Pulmonology, İzmir Keywords: Small cell lung cancer, Prognostic factors, Limited stage, Bone marrow FDG uptake Small cell lung cancer (SCLC) is a malignancy from the neuroendocrine tumor family, which has a poor prognosis and presents with metastases at the time of the diagnosis. The present study investigated the relationship between bone marrow fluorodeoxy-D-glucose (FDG) uptake and survival to evaluate prognosis in limited-stage SCLC. This single-center retrospective study examined a total of 220 patients diagnosed with limited-stage SCLC between January 2010 and June 2019. Bone marrow FDG uptake, serum inflammatory markers, and other factors used to determine the prognosis, as well as overall survival (OS) and progression-free survival (PFS), were recorded and retrospectively analyzed. Within physiological limits, bone marrow standardized uptake value (SUV) mean of &gt; 1.95 was identified as a good prognostic factor for PFS (p= 0.03). The multivariate analysis of OS and PFS revealed that the Eastern Cooperative Oncology Group (ECOG) performance scale (p= 0.001) was a common independent prognostic factor. Stages of the disease, albumin levels and bone marrow-to-liver ratio (BLR) [one of the positron emission tomography/computed tomography (PET/CT) parameters] of &lt; 0.8 were prognostic factors for OS. The bone marrow SUV mean was positively correlated with the primary tumor SUV max and SUV mean. The bone marrow SUV mean is a parameter that can be used to predict PFS in limited-stage SCLC. For OS, in turn, the BLR was identified as an independent factor.

Influence of Cirrhosis on 68Ga-FAPI PET/CT in Intrahepatic Tumors.

Background Gallium 68 (68Ga)-labeled fibroblast activation protein inhibitor (FAPI) is of great diagnostic value for intrahepatic tumors. However, cirrhosis may lead to increased 68Ga-FAPI uptake in background liver, affecting the diagnostic ability of 68Ga-FAPI. Purpose To assess the effect of cirrhosis on liver parenchyma and intrahepatic tumor uptake of 68Ga-FAPI and to compare the ability of 68Ga-FAPI and fluorine 18 (18F)-labeled fluorodeoxyglucose (FDG) PET/CT to depict intrahepatic tumors in patients with cirrhosis. Materials and Methods In this secondary analysis of a prospective trial, patients who underwent both 68Ga-FAPI and 18F-FDG PET/CT and those who underwent only 68Ga-FAPI PET/CT between August 2020 and May 2022 were considered for inclusion in the cirrhotic or noncirrhotic group, respectively. Patients with cirrhosis were chosen via a comprehensive assessment of imaging and clinical data, and patients without cirrhosis were randomly selected. 68Ga-FAPI and 18F-FDG PET/CT data were measured by two radiologists. Between-groups and within-group data were tested with the Mann-Whitney U test and the Wilcoxon signed-rank test, respectively. Results A total of 39 patients with cirrhosis (median age, 58 years [IQR, 50-68]; 29 male; 24 intrahepatic tumors) and 48 patients without cirrhosis (median age, 59 years [IQR, 51-67]; 30 male; 23 intrahepatic tumors) were evaluated. In patients without intrahepatic tumors, the liver 68Ga-FAPI average standardized uptake value (SUVavg) was higher in the cirrhotic group than in the noncirrhotic group (median SUVavg, 1.42 [IQR, 0.55-2.85] vs 0.45 [IQR, 0.41-0.72]; P = .002). However, no difference was observed in the diagnosis of intrahepatic tumor sensitivity (98% vs 93%, respectively). When compared with 18F-FDG, the sensitivity of 68Ga-FAPI PET/CT in the detection of intrahepatic tumors in patients with cirrhosis (41% vs 98%, respectively) and maximum standardized uptake value of tumors (median SUVmax, 2.60 [IQR, 2.14-4.49] vs 6.68 [IQR, 4.65-10.08]; P < .001) were higher. Conclusion The sensitivity of 68Ga-FAPI in the diagnosis of intrahepatic tumors was not affected by cirrhosis, and diagnostic accuracy of 68Ga-FAPI was higher than that of 18F-FDG in patients with cirrhosis. © RSNA, 2023 Supplemental material is available for this article.

Comparison of [18F]-OC PET/CT and contrast-enhanced CT/MRI in the detection and evaluation of neuroendocrine neoplasms.

Gallium-68 (68Ga)-labeled somatostatin analog (SSA) PET imaging has been widely used in clinical practice of neuroendocrine neoplasms (NENs). Compared with 68Ga, 18F has a great practical and economic advantage. Although a few studies have shown the characteristics of [18F] AlF-NOTA-octreotide ([18F]-OC) in healthy volunteers and small NEN patient groups, its clinical value needs further investigation. Herein, this retrospective study aimed to evaluate the diagnostic accuracy of [18F]-OC PET/CT in detecting NENs, as well as to compare it with contrast-enhanced CT/MRI. We retrospectively reviewed the data of 93 patients who had undergone [18F]-OC PET/CT and CT or MRI scans. Of these patients, there were 45 patients with suspected NENs for diagnostic evaluation, and 48 patients with pathologically confirmed NENs for detecting metastasis or recurrence. [18F]-OC PET/CT images were evaluated visually and semi-quantitatively by measuring maximum standardized uptake value of tumor (SUVmax), tumor-to-background SUVmax ratio (TBR), and SUVmax of hypophysis (SUVhypophysis). A total of 276 suspected NEN lesions were found in these 93 patients. The results of histopathology or radiographic follow-up served as the reference standard for the final diagnosis. Forty-five patients with suspected NENs were confirmed by histopathological examination via resection or biopsy. [18F]-OC PET/CT showed high radiotracer uptake in the lesions of G1-G3 NENs. [18F]-OC PET/CT showed superior performance with 96.3% of sensitivity, 77.8% of specificity, and 88.9% of accuracy in diagnosing NENs compared to CT/MRI. When cutoffs of SUVmax, TBR, and SUVhypophysis were 8.3, 3.1, and 15.4, [18F]-OC PET/CT had the best equilibrium between sensitivity and specificity for differentiating NEN from non-NEN lesions. For a total of 276 suspected NEN lesions, the sensitivity, specificity, and accuracy of [18F]-OC PET/CT for diagnosis of NENs were 90.5%, 82.1%, and 88.8%, respectively, and were higher than those of CT and MRI. G1 and G2 NENs had higher TBR and lower CT enhancement intensity than G3. The SUVmax and TBR had a positive correlation with CT enhancement intensity in G2 rather than in G1 or G3. [18F]-OC PET/CT is a promising imaging modality for initial diagnosis and detecting metastasis or postoperative recurrence in NENs.

Comparison of whole-body DW-MRI with 2-[18F]FDG PET for staging and treatment monitoring of children with Langerhans cell histiocytosis.

To assess and compare the diagnostic accuracy of whole-body (WB) DW-MRI with 2-[18F]FDG PET for staging and treatment monitoring of children with Langerhans cell histiocytosis (LCH). Twenty-three children with LCH underwent 2-[18F]FDG PET and WB DW-MRI at baseline. Two nuclear medicine physicians and two radiologists independently assessed presence/absence of tumors in 8 anatomical areas. Sixteen children also performed 2-[18F]FDG PET and WB DW-MRI at follow-up. One radiologist and one nuclear medicine physician revised follow-up scans and collected changes in tumor apparent diffusion (ADC) and standardized uptake values (SUV) before and after therapy in all detectable lesions. 2-[18F]FDG PET results were considered the standard of reference for tumor detection and evaluation of treatment response according to Lugano criteria. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of WB DW-MRI at baseline were calculated, and the 95% confidence intervals were estimated by using the Clopper-Pearson (exact) method; changes in tumor SUVs and ADC were compared using a Mann-Whitney U test. Agreement between reviewers was assessed with a Cohen's weighted kappa coefficient. Analyses were conducted using SAS software version 9.4. Agreement between reviewers was perfect (kappa coefficient = 1) for all analyzed regions but spine and neck (kappa coefficient = 0.89 and 0.83, respectively) for 2-[18F]FDG PET images, and abdomen and pelvis (kappa coefficient = 0.65 and 0.88, respectively) for WB DW-MRI. Sensitivity and specificity were 95.5% and 100% for WB DW-MRI compared to 2-[18F]FDG PET. Pre to post-treatment changes in SUVratio and ADCmean were inversely correlated for all lesions (r: -0.27, p = 0·06) and significantly different between responders and non-responders to chemotherapy (p = 0.0006 and p = 0·003 for SUVratio and ADCmean, respectively). Our study showed that WB DW-MRI has similar accuracy to 2-[18F]FDG PET for staging and treatment monitoring of LCH in children. While 2-[18F]FDG PET remains an approved radiological examination for assessing metabolically active disease, WB DW-MRI could be considered as an alternative approach without radiation exposure. The combination of both modalities might have advantages over either approach alone.

Prognostic value of preoperative [68Ga]Ga-FAPI-04 PET/CT in patients with resectable pancreatic ductal adenocarcinoma in correlation with immunohistological characteristics.

Our aim was to assess the prognostic value of [68Ga]Ga-FAPI-04 positron emission tomography (PET) uptake in PDAC and to evaluate the correlation between in vivo lesional radioactivity with pathological characteristics of pancreatic ductal adenocarcinoma (PDAC). We retrospectively analyzed treatment-naïve PDAC patients who underwent preoperative [68Ga]Ga-FAPI-04 PET/CT followed by pancreatectomy. The tracer uptake was determined as maximum tumor standardized uptake value (SUVmax), FAPI-avid tumor volume (FTV), total lesion FAP expression (TLF) as well total pancreatic uptake (TSUVmax), total FAPI-avid pancreatic volume (FPV), and total pancreatic FAP expression (TPF). Spearman's correlation analysis was performed to evaluate the association between [68Ga]Ga-FAPI-04 PET/CT imaging and ex vivo immunohistological FAP expression and pathological characteristics of surgical specimens (differentiation, size, vascularity, perineural invasion, and lymph node metastases). Kaplan-Meier and hazard ratio (HR, log-rank) methods were used to evaluate the prognostic value of [68Ga]Ga-FAPI-04 PET/CT and clinicopathological factors. Thirty-seven surgical PDAC patients were included. The ex vivo expression of FAP was significantly associated with the tumor SUVmax and TLF. FAP expression was more abundant in poorly differentiated PDAC than in well- to moderately differentiated neoplasms. Tumor SUVmax or TLF and pancreatic TSUVmax or TPF were significantly correlated with tumor size, differentiation, and perineural invasion, respectively. SUVmax had a significant independent prognostic value for recurrence-free survival (HR = 2.46, P < 0.05), while [68Ga]Ga-FAPI-04 TPF predicted overall survival (HR = 12.82, P < 0.05). The in vivo [68Ga]Ga-FAPI-04 uptake in localized PDAC showed a significant correlation with ex vivo FAP expression and aggressive pathological characteristics. [68Ga]Ga-FAPI-04 PET/CT also presented a potential for postoperative prognostication of PDAC. Elevated fibroblast activity induced by obstructive pancreatitis might be associated with the patient's survival.

Deep learning-based attenuation map generation with simultaneously reconstructed PET activity and attenuation and low-dose application

Objective. In PET/CT imaging, CT is used for positron emission tomography (PET) attenuation correction (AC). CT artifacts or misalignment between PET and CT can cause AC artifacts and quantification errors in PET. Simultaneous reconstruction (MLAA) of PET activity (λ-MLAA) and attenuation (μ-MLAA) maps was proposed to solve those issues using the time-of-flight PET raw data only. However, λ-MLAA still suffers from quantification error as compared to reconstruction using the gold-standard CT-based attenuation map (μ-CT). Recently, a deep learning (DL)-based framework was proposed to improve MLAA by predicting μ-DL from λ-MLAA and μ-MLAA using an image domain loss function (IM-loss). However, IM-loss does not directly measure the AC errors according to the PET attenuation physics. Our preliminary studies showed that an additional physics-based loss function can lead to more accurate PET AC. The main objective of this study is to optimize the attenuation map generation framework for clinical full-dose 18F-FDG studies. We also investigate the effectiveness of the optimized network on predicting attenuation maps for synthetic low-dose oncological PET studies. Approach. We optimized the proposed DL framework by applying different preprocessing steps and hyperparameter optimization, including patch size, weights of the loss terms and number of angles in the projection-domain loss term. The optimization was performed based on 100 skull-to-toe 18F-FDG PET/CT scans with minimal misalignment. The optimized framework was further evaluated on 85 clinical full-dose neck-to-thigh 18F-FDG cancer datasets as well as synthetic low-dose studies with only 10% of the full-dose raw data. Main results. Clinical evaluation of tumor quantification as well as physics-based figure-of-merit metric evaluation validated the promising performance of our proposed method. For both full-dose and low-dose studies, the proposed framework achieved <1% error in tumor standardized uptake value measures. Significance. It is of great clinical interest to achieve CT-less PET reconstruction, especially for low-dose PET studies.

Prognostic factors of toxicity of immune checkpoint inhibitors in nonsmall cell lung cancer and small cell lung cancer patients: The ToxImmune study.

Immunotherapy alone or in combination has clearly improved the survival of patients with lung cancer. However, it may also be responsible for adverse events impacting these patients' quality of life. The ToxImmune study aims to identify prognostic factors that can help to predict immune-related adverse events. We included all patients aged 18 years and older who had received at least one dose of immune checkpoint inhibitors, with or without other therapy, between June 2015 and December 2020 and were diagnosed with nonsmall cell lung cancer or small-cell lung cancer. Patients' baseline demographic characteristics, biological blood markers, and imaging by PET-scanner were collected from electronic medical records. All adverse events (AEs) and immune-related AEs (irAEs) were recorded (Common Terminology Criteria For Adverse Events V.5.0). Sixty-four patients were included, of whom 60 (94%) presented at least one irAE. The incidence of Common Terminology Criteria for Adverse Events (CTCAE) grade 2 and grade 3-4 was 34% and 8% respectively. Female sex, Primitive Tumor Standardized Uptake Value Max (SUVmax) <5, number of metastases ≥3 and immunotherapy received after the first line were found to be significant risk factors for immune-related adverse events. Based on the number of risk factors, the ToxImmune score predicts the risk of having a grade ≥2 adverse event (primitive tumor SUV ≥ 5=0 vs. primitive tumor SUV <5=1, number of metastases <3=0 vs. number of metastases ≥3=1 and L1=0 vs. L1 ≥ 1). The incidence of grade ≥2 adverse events was 20%, 55% and 90% with ToxImmune scores 0, 1 and=2 respectively (p=.003). Median progression-free survival (PFS) times were 19.2months, 6.64 months and 2.63 months for ToxImmune scores 0, 1 and=2 respectively, p=.13. Median overall survival times were 22.6months, 16.4months and 9.8months for ToxImmune scores 0, 1 and ≥2 respectively, p=.24. The disease control rate (DRR) was 78% in ToxIummune score 0 group, and 50% in ToxImmune score 1 and ≥2 groups (p=.363). The ToxImmune score, which is grounded on objective clinical parameters, indicates that cases with a high score had an advanced threat of severe adverse events. The ToxImmune score could therefore be used in clinical practice to identify patients treated for lung cancer with immunotherapy and at risk of severe AE.

Glucose Infusion Induced Change in Intracellular pH and Its Relationship with Tumor Glycolysis in a C6 Rat Model of Glioblastoma.

The reliance on glycolytic metabolism is a hallmark of tumor metabolism. Excess acid and protons are produced, leading to an acidic tumor environment. Therefore, we explored the relationship between the tumor glycolytic metabolism and tissue pH by comparing 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and hyperpolarized [1-13C]pyruvate MR spectroscopy imaging (MRSI) to chemical exchange saturation transfer (CEST) MRI measurements of tumor pH. 106 C6 glioma cells were implanted in the brains of male Wistar rats (N = 11) using stereotactic surgery. A 60-min PET acquisition after a bolus of FDG was performed at 11-13days post implantation, and standardized uptake value (SUV) was calculated. CEST measurements were acquired the following day before and during constant infusion of glucose solution. Tumor intracellular pH (pHi) was evaluated using amine and amide concentration-independent detection (AACID) CEST MRI. The change of pHi (∆pHi) was calculated as the difference between pHi pre- and during glucose infusion. Rats were imaged immediately with hyperpolarized [1-13C]pyruvate MRSI. Regional maps of the ratio of Lac:Pyr were acquired. The correlations between SUV, Lac:Pyr ratio, and ∆pHi were evaluated using Pearson's correlation. A decrease of 0.14 in pHi was found after glucose infusion in tumor region. Significant correlations between tumor glycolysis measurements of Lac:Pyr and ∆pHi within the tumor (ρ = 0.83, P = 0.01) and peritumoral region (ρ = 0.76, P = 0.028) were observed. No significant correlations were found between tumor SUV and ∆pHi within the tumor (ρ = - 0.45, P = 0.17) and peritumor regions (ρ = - 0.6, P = 0.051). AACID detected the changes in pHi induced by glucose infusion. Significant correlations between tumor glycolytic measurement of Lac:Pyr and tumoral and peritumoral pHi and ∆pHi suggest the intrinsic relationship between tumor glycolytic metabolism and the tumor pH environment as well as the peritumor pH environment.

MRI- and PET-Based Assessment of Radiological and Clinical Factors Associated With Cervical Cancer Response to External Beam Radiation Therapy.

Introduction In the era of MRI-guided external beam radiation therapy (EBRT), complete radiological response (CR) is often seen in cervical cancer (CC) with 4-6 weeks of chemotherapy and EBRT. The clinical and radiological factors associated with this observation were investigated in this study. Materials and methods One hundred and twenty-four CC patients treated with concurrent chemotherapy, EBRT, and brachytherapy (BT) from January 2008 to July 2015 were retrospectively screened. Initial primary gross tumor volume (GTVINITIAL) was estimated after contouring on a planning CT scan registered with pre-EBRT PET and MRI. The maximum standardized uptake value (SUV) of GTVINITIAL from each PET scan report was collected. Spearman's rank correlation coefficient (rho) values were calculated to assess the relationships among age, tumor size, and SUV. Tumor radiological response during EBRT prior to BT was calculated by contouring the final primary gross tumor volume (GTVFINAL) using MRI obtained prior to BT. CRrates during EBRT were estimated from GTVINITIAL and GTVFINAL and compared by the level of various factors using Fisher's exact test (two-sided). Results Forty-eight patients met the inclusion criteria of the study with a median age of 50 years. The median GTVINITIAL was 82 cc. The median SUV was 14.9. A significant correlation was seen between SUV and GTVINITIAL with a larger tumor size associated with a higher SUV. CR rates were numerically higher for patients who were aged <50 years, or with >37.5 Gy radiation dose at or before the second MRI, or with GTVINITIAL <100 cc, or with no nodes involved or with stages IB or IIA. Conclusions Our study identified higher CC primary tumor CR rates during EBRT in younger patients (<50) with smaller tumors (100 cc) without nodal involvements as well as a positive correlation between PET FDG (18F-fluorodeoxyglucose)-SUV and CC primary tumor size.

191P Correlation of early change in standardized uptake value (SUV) on positron emission tomography (PET/CT) with recurrence-free survival (RFS) and overall survival (OS) in patients with primary operable HER2-positive breast cancer (TBCRC026)

Predictive biomarkers of response to HER2-directed therapy are essential to inform treatment decisions. The TBCRC026 trial reported that early changes in tumor standardized uptake values corrected for lean body mass (SULmax) on FDG-PET/CT predicted pathologic complete response (pCR) to neoadjuvant trastuzumab and pertuzumab (HP) in HER2-positive breast cancer (PMID:33999652). We hypothesized that early changes on FDG-PET/CT will predict RFS/OS.

The Relationship between Preoperative FDG PET/CT Uptake and Survival in Patients with Lung Cancer

IntroductionDespite all advances in diagnosis and treatment, lung cancer is the leading cause of cancer death in both sexes worldwide. Because of the different survival rates in lung cancer, additional factors are needed to determine prognosis. In this study, we aimed to investigate the relationship between survival and clinical data of primary tumor SUV (Standardized Uptake Value) to evaluate the role of FDG-PET ([18F]-fluoro-2-deoxy-D-glucose Positron Emission Tomography) as a prognostic factor in lung cancer.Material and methodsThe data of patients who underwent anatomic resection and preoperative positron emission tomography/computed tomography (PET/CT) were performed retrospectively between February 2006 and October 2019 in the Department of Thoracic Surgery, Faculty of Medicine, Gaziantep University.ResultsAll cases were 666 patients, 64 of whom (9.6%) were females and 602 of them (90.4%) were males. The mean age of the patients was 61.91±9.6 years. Histologically, there were 369 (55.4%) epidermoid carcinomas, 233 (34.9%) adenocarcinomas. The overall mean survival was 68.2 months and the median survival was 63.6 months. The mean mass SUV values of the patients were 13.73 ± 6.65. The effect of histological type, TNM stage, metastasis and recurrence on survival was statistically significant (p &lt; 0.05). According to the univariate analysis (Cox regression analysis), it was found that 1 unit increase in SUV value contributed to a statistically significant increase in mortality risk (p = 0.002, HR: 1.024, 95% CI: 1.009-1.040).ConclusionsIn our study on 666 patients, unlike literature, no statistically significant relationship was found between SUV value and survival.

Evaluation of the 18F-FDG-PET/CT uptake association with pathological and immunohistochemistry features in esophagogastric adenocarcinoma.

The present study aimed to analyze the association between 18F-fluorodeoxyglucose (FDG) uptake and histologic panel in esophagogastric adenocarcinoma. We retrospectively enrolled 26 patients with histologically confirmed esophageal, gastroesophageal junction and gastric adenocarcinoma that have been submitted to pretreatment FDG-PET/CT. We collected the cancer tissue sample of each patient and performed immunohistochemical analyses of the glucose transport protein 1 (GLUT-1), Ki-67, cysteine aspartate-specific proteinases (Caspase)-3 and hexokinase-1, and evaluated the association of these parameters with FDG uptake. The FDG uptake was measured by tumor standardized uptake value (SUV), metabolic tumor volume (MTV), and Total Lesion Glycolysis (TLG). Besides, we analyzed the association of FDG uptake and tumor location, Lauren's histologic subtype, grade of cellular differentiation and intratumoral inflammatory infiltrate. We found a positive association between GLUT-1 with SUV and TLG, Caspase-3 and SUV and inflammation grade with SUV. Tumor inflammation infiltrate, GLUT-1 and Caspase-3 correlated with 18F-FDG uptake in PET/CT in esophagogastric adenocarcinoma. These findings may help understand the pathologic PET/CT significance in cancer. Understanding the meaning of the 18F-FDG uptake in the field of tumor histologic and immunohistochemistry features is essential to allow the evolution of PET/CT application in esophageal and gastric carcinomas.

Prognostic Significance of Adipose Tissue Distribution and Metabolic Activity in PET/CT in Patients with Metastatic Colorectal Cancer.

In this study, we aimed to evaluate the prognostic significance of adipose tissue distribution and metabolic activity in PET/CT to predict survival in patients with metastatic colorectal cancer (mCRC). The volume, density (HU), and FDG uptake (standardized uptake value (SUV)) of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) and maximum FDG uptake of the tumor tissue were measured. Subcutaneous adipose tissue of volume-to-density ratio (SAT ratio) was calculated. The median OS for the patients with SAT ratio value < -1.1 and ≥ -1.1 were 38.5 (95% CI 31.54-45.58) and 24.5 (95% CI 14.13-34.93) months, respectively (p = 0.05). During follow-up, 69 patients experienced disease progression. The median progression-free survival (PFS) was 11.03months (95% CI: 9.11-12.95). Median PFS for patients with tumor SUV max value < 11.5 and ≥ 11.5 were 9.2 (95% CI 7.25-11.27) and 12.6 (95% CI 10.02-15.27) months, respectively (p = 0.14). Forty-eight patients received bevacizumab therapy. VAT SUV mean (HR: 0.09; 95% CI 0.01-0.52, p = 0.008) was significantly associated with PFS in patients receiving bevacizumab. SAT ratio was the significant parameter for the OS (HR: 0.58; 95% CI 0.33-1.01, p = 0.05) and PFS (HR: 1.99; 95% CI 1.02-3.91, p = 0.043). SAT ratio was an independent prognostic factor for survival in patients with mCRC. Higher SAT volume is correlated with longer survival in mCRC patients.