Positron Emission Tomography Metrics Research Articles

Association Between Pretreatment 11C-Methionine Positron Emission Tomography Metrics, Histology, and Prognosis in 125 Newly Diagnosed Patients with Adult-Type Diffuse Glioma Based on the World Health Organization 2021Classification

To clarify the relationships between 11C-methionine (MET) positron emission tomography (PET) metrics and the histology, genetics, and prognosis of adult-type diffuse glioma (ADG) based on the World Health Organization (WHO) 2021 classification. A total of 125 newly diagnosed ADG patients were enrolled. We compared the maximum standardized uptake value (SUVmax), tumor-to-normal ratio (TNR), metabolic tumor volume (MTV), and total lesion methionine uptake (TLMU) to the histology and genetics of the ADG patients. We also evaluated the prognoses of the 93 surgically treated patients. The isocitrate dehydrogenase (IDH) wild (w) ADG patients showed significantly higher MET-PET metrics (p<0.05 for all parameters), significantly shorter overall survival (OS) and progression-free survival (PFS) (p<0.0001 for both) than those of the IDH mutant (m) ADG patients. In the IDHm ADG group, the SUVmax, MTV, and TLMU values were significantly higher in IDHm grade (G) 4 astrocytoma patients than IDHm G2/3 astrocytoma patients (p<0.05 for all), but not than G2-3 oligodendroglioma patients. The PFS was significantly shorter in the G4 astrocytoma patients versus the G2/3 astrocytoma and G3 oligodendroglioma patients (p<0.05 for both). The SUVmax and TNR values were significantly higher in recurrent patients than non-recurrent patients (p<0.01 for both), but no significant differences were found in MTV or TLMU values. MET-PET metrics well reflect the histological subtype, WHO grade and prognosis of ADG based on the 2021 WHO classification, with the exception of oligodendroglial tumors. Volumetric parameters were not significantly associated with recurrence, unlike the SUVmax and TNR.

A longitudinal MRI and TSPO PET-based investigation of brain region-specific neuroprotection by diazepam versus midazolam following organophosphate-induced seizures

Acute poisoning with organophosphorus cholinesterase inhibitors (OPs), such as OP nerve agents and pesticides, can cause life threatening cholinergic crisis and status epilepticus (SE). Survivors often experience significant morbidity, including brain injury, acquired epilepsy, and cognitive deficits. Current medical countermeasures for acute OP poisoning include a benzodiazepine to mitigate seizures. Diazepam was long the benzodiazepine included in autoinjectors used to treat OP-induced seizures, but it is now being replaced in many guidelines by midazolam, which terminates seizures more quickly, particularly when administered intramuscularly. While a direct correlation between seizure duration and the extent of brain injury has been widely reported, there are limited data comparing the neuroprotective efficacy of diazepam versus midazolam following acute OP intoxication. To address this data gap, we used non-invasive imaging techniques to longitudinally quantify neuropathology in a rat model of acute intoxication with the OP diisopropylfluorophosphate (DFP) with and without post-exposure intervention with diazepam or midazolam. Magnetic resonance imaging (MRI) was used to monitor neuropathology and brain atrophy, while positron emission tomography (PET) with a radiotracer targeting translocator protein (TSPO) was utilized to assess neuroinflammation. Animals were scanned at 3, 7, 28, 65, 91, and 168 days post-DFP and imaging metrics were quantitated for the hippocampus, amygdala, piriform cortex, thalamus, cerebral cortex and lateral ventricles. In the DFP-intoxicated rat, neuroinflammation persisted for the duration of the study coincident with progressive atrophy and ongoing tissue remodeling. Benzodiazepines attenuated neuropathology in a region-dependent manner, but neither benzodiazepine was effective in attenuating long-term neuroinflammation as detected by TSPO PET. Diffusion MRI and TSPO PET metrics were highly correlated with seizure severity, and early MRI and PET metrics were positively correlated with long-term brain atrophy. Collectively, these results suggest that anti-seizure therapy alone is insufficient to prevent long-lasting neuroinflammation and tissue remodeling.

Full kinetic modeling analysis of [18F]fluorocholine Positron Emission Tomography (PET) at initial diagnosis of high-grade glioma

PurposeThe main objective was to characterize the tracer uptake kinetics of [18F]fluoromethylcholine ([18F]F-CHO) in high-grade gliomas (HGG) through a full PET kinetic modeling approach. Secondarily, we aimed to explore the relationship between the PET uptake measures and the HGG molecular features. Materials and methodsTwenty-four patients with a suspected diagnosis of HGG were prospectively included. They underwent a dynamic brain [18F]F-CHO-PET/CT, from which a tumoral time-activity curve was extracted. The plasma input function was obtained through arterial blood sampling with metabolite correction. These data were fitted to 1- and 2-tissue-compartment models, the best of which was selected through the Akaike information criterion. We assessed the correlation between the kinetic parameters and the conventional static PET metrics (SUVmax, SUVmean and tumor-to-background ratio TBR). We explored the association between the [18F]F-CHO-PET quantitative parameters and relevant molecular biomarkers in HGG. ResultsTumoral time-activity curves in all patients showed a rapid rise of [18F]F-CHO uptake followed by a plateau-like shape. Best fits were obtained with near-irreversible 2-tissue-compartment models. The perfusion-transport constant K1 and the net influx rate Ki showed strong correlation with SUVmax (r = 0.808–0.861), SUVmean (r = 0.794–0.851) and TBR (r = 0.643–0.784), p < 0.002. HGG was confirmed in 21 patients, of which those with methylation of the O-6-methylguanine-DNA methyltransferase (MGMT) gene promoter showed higher mean Ki (p = 0.020), K1 (p = 0.025) and TBR (p = 0.001) than the unmethylated ones. Conclusion[18F]F-CHO uptake kinetics in HGG is best explained by a 2-tissue-compartment model. The conventional static [18F]F-CHO-PET measures have been validated against the perfusion-transport constant (K1) and the net influx rate (Ki) derived from kinetic modeling. A relationship between [18F]F-CHO uptake rate and MGMT methylation is suggested but needs further confirmation.

Investigating PET Responses to Treatment in Nodular Lymphocyte-Predominant Hodgkin Lymphoma.

There is no standard treatment for nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). Although response by positron emission tomography (PET) for classic Hodgkin lymphoma (cHL) has allowed for response-adapted treatment, similar approaches for NLPHL have not been developed. This is in part due to the lack of data for PET response to treatment. Therefore, we sought to investigate PET responses to management for NLPHL. We retrospectively identified 47 patients who were diagnosed with or treated for NLPHL between 2001-2018 at a single institution and underwent a staging PET. We recorded clinical data and PET metrics for patients who received various forms of management, including chemotherapy (CT), radiation therapy (RT), combined modality therapy (CMT = CT+RT, with rituximab in a subset), rituximab monotherapy, and observation after excision. Metabolic response was scored according to the Deauville 5-point scale criteria, with complete metabolic response defined as a score 1-3. We identified 47 patients with median age of 26 (IQR = 17-50). They predominantly were male (74.5%) and had early stage (23.4% I, 36.2% II) versus advanced stage (29.8% III, 10.5% IV) NLPHL. The majority of patients had their immunoarchitectural pattern scored (n = 36, 76.6%), with typical pattern (A/B) being the most frequent type (58.3%). The median follow-up was 5.7 years (IQR = 2.3-9.3). Overall survival was 100% at 5 years and 92.3% at 10 years. Primary management included CMT (n = 10, 21.3%; with rituximab in a subset n = 1, 10.0%), CT alone (n = 22, 46.8%; with rituximab in a subset n = 5, 22.7%), RT alone (n = 8, 17.0%), rituximab alone (n = 3, 6.4%), and observation after excision (n = 4, 8.5%). On baseline PET, median SUVmax was 10.7 (range = 1.7-35.4). Of the 10 patients who received CMT, the complete metabolic response rates were 42.9% at interim-chemotherapy PET and 75% at post-chemotherapy PET, which improved to 100% after consolidative radiotherapy. There was no difference in complete metabolic response rate to chemotherapy for typical versus variant pattern (P = 0.60). Of the 22 patients who received CT alone, 66.7% had a complete metabolic response at the interim PET and 72.7% at the end of chemotherapy. For RT, rituximab alone, and observation, the complete metabolic response rates at median 3 months (range 1-5 months) after treatment were 87.5%, 66.7%, 75.0%, respectively. Based on our cohort, we found that patients with NLPHL had a lower complete metabolic response to CT (∼75%) compared to cHL (∼85-90%) and PET-response was improved following RT for those receiving CMT. There was no significant difference in PET-response for those with variant versus typical immunoarchitectural patterns. Our findings will allow for the development of PET response-adapted therapy for NLPHL.

Relevance of 18F-DOPA visual and semi-quantitative PET metrics for the diagnostic of Parkinson disease in clinical practice: a machine learning-based inference study

PurposeTo decipher the relevance of visual and semi-quantitative 6-fluoro-(18F)-L-DOPA (18F-DOPA) interpretation methods for the diagnostic of idiopathic Parkinson disease (IPD) in hybrid positron emission tomography (PET) and magnetic resonance imaging.Material and methodsA total of 110 consecutive patients (48 IPD and 62 controls) with 11 months of median clinical follow-up (reference standard) were included. A composite visual assessment from five independent nuclear imaging readers, together with striatal standard uptake value (SUV) to occipital SUV ratio, striatal gradients and putamen asymmetry-based semi-quantitative PET metrics automatically extracted used to train machine learning models to classify IPD versus controls. Using a ratio of 70/30 for training and testing sets, respectively, five classification models—k-NN, LogRegression, support vector machine, random forest and gradient boosting—were trained by using 100 times repeated nested cross-validation procedures. From the best model on average, the contribution of PET parameters was deciphered using the Shapley additive explanations method (SHAP). Cross-validated receiver operating characteristic curves (cv-ROC) of the most contributive PET parameters were finally estimated and compared.ResultsThe best machine learning model (k-NN) provided final cv-ROC of 0.81. According to SHAP analyses, visual PET metric was the most important contributor to the model overall performance, followed by the minimum between left and right striatal to occipital SUV ratio. The 10-time cv-ROC curves of visual, min SUVr or both showed quite similar performance (mean area under the ROC of 0.81, 0.81 and 0.79, respectively, for visual, min SUVr or both).ConclusionVisual expert analysis remains the most relevant parameter to predict IPD diagnosis at 11 months of median clinical follow-up in 18F-FDOPA. The min SUV ratio appears interesting in the perspective of simple semi-automated diagnostic workflows.

Bayesian penalized likelihood PET reconstruction impact on quantitative metrics in diffuse large B-cell lymphoma.

Evaluate the quantitative, subjective (Deauville score [DS]) and reader agreement differences between standard ordered subset expectation maximization (OSEM) and Bayesian penalized likelihood (BPL) positron emission tomography (PET) reconstruction methods. A retrospective review of 104 F-18 fluorodeoxyglucose PET/computed tomography (CT) exams among 52 patients with diffuse large B-cell lymphoma. An unblinded radiologist moderator reviewed both BPL and OSEM PET/CT exams. Four blinded radiologists then reviewed the annotated cases to provide a visual DS for each annotated lesion. Significant (P < .001) differences in BPL and OSEM PET methods were identified with greater standard uptake value (SUV) maximum and SUV mean for BPL. The DS was altered in 25% of cases when BPL and OSEM were reviewed by the same radiologist. Interobserver DS agreement was higher for OSEM (>1 cm lesion = 0.89 and ≤1 cm lesion = 0.84) compared to BPL (>1 cm lesion = 0.85 and ≤1 cm lesion = 0.81). Among the 4 readers, average intraobserver visual DS agreement between OSEM and BPL was 0.67 for lesions >1cm and 0.4 for lesions ≤1 cm. F-18 Fluorodeoxyglucose PET/CT of diffuse large B-cell lymphoma reconstructed with BPL has higher SUV values, altered DSs and reader agreement when compared to OSEM. This report finds volumetric PET measurements such as metabolic tumor volume to be similar between BPL and OSEM PET reconstructions. Efforts such as adoption of European Association Research Ltd accreditation should be made to harmonize PET data with an aim at balancing the need for harmonization and sensitivity for lesion detection.

Investigating Metabolic Response after CAR-T Therapy and Bridging Radiotherapy for Relapsed/Refractory B-Cell Lymphoma

Introduction: For patients with aggressive relapsed/refractory B-cell lymphoma (R/R BCL) undergoing CAR-T therapy, metabolic treatment response assessed at the 1-month interval following CAR-T infusion is associated with likelihood of disease progression (Kuhnl A, et al. Blood Adv 2022). In particular, SUV max on 1-month 18F-FDG positron emission tomography (PET) imaging is predictive of disease progression (Zaki A, et al. Blood Adv 2022). However, for patients who undergo bridging radiotherapy (RT) prior to CAR-T infusion, it remains unclear how to interpret metabolic activity for irradiated sites on surveillance PET imaging following CAR-T. We sought to characterize metabolic activity after CAR-T and bridging RT in a cohort of patients with R/R BCL. Methods: This IRB-approved retrospective cohort study included patients with R/R BCL who underwent bridging RT prior to CAR-T infusion at a single institution from January 1, 2019 to April 30, 2022. We measured baseline patient characteristics, treatment factors, and PET metrics prior to bridging RT. We then assessed tumor metabolic activity on surveillance PET imaging following CAR-T infusion until the time of disease progression (defined as Deauville 5 disease) or last follow up. Results: We identified 10 patients who completed bridging RT prior to CAR-T infusion with at least one post-CAR-T disease assessment with PET imaging. Median follow up was 152 days from CAR-T infusion (range: 31-1095). Most patients (90%) had bulky disease (≥7.5 cm) and all had elevated LDH at baseline. Bridging RT dosing ranged from 20-38.5 Gy (median: 20 Gy) over 5-14 fractions (median: 5 fractions). Bridging RT fields were directed at bulky disease sites for 8 of 9 patients with bulky disease. The median metabolic tumor volume (MTV) irradiated with bridging RT was 149 mL (range: 26-803) and the median proportion of total MTV irradiated was 97% (range: 8.7-100). The median time between pre-bridging RT PET imaging and CAR-T infusion was 49 days (range: 37-124) and the median time between the end of bridging RT and CAR-T infusion was 12 days (range: 5-106). On pre-bridging RT PET, the median SUV max in the irradiated field was 23.3 (range: 9.1-36.1) (Figure 1). On 1-month post-CAR-T PET, the median SUV max in the irradiated field decreased to 3.2 (range: 0-6.1) and median delta SUV max was -87% (range: -68% to -100%). At the 1-month post-CAR-T interval, 40% of patients had a complete metabolic response (Deauville 3 or below), 40% had Deauville 4 disease, and 20% had Deauville 5 disease. Among the 4 patients with Deauville 4 disease at 1-month post-CAR-T, 3 patients developed complete metabolic responses and 1 patient had persistent Deauville 4 disease on subsequent PET imaging. No patients in the cohort developed disease progression within the irradiated fields. At last follow up, 3 patients had developed Deauville 5 disease, and for 2 of the 3 patients, areas of disease progression included unirradiated sites of disease that were present on pre-bridging RT PET imaging. Conclusions: In this small retrospective cohort of patients undergoing bridging RT prior to CAR-T therapy for R/R BCL, patients with concern for refractory disease on initial imaging assessment demonstrated complete response or stable disease on subsequent follow up imaging. Caution may be warranted in interpreting metabolic activity levels on initial post-CAR-T surveillance PET imaging, and validation in larger cohorts is needed to better understand metabolic activity dynamics in disease sites treated with bridging RT prior to CAR-T therapy. Figure 1. SUV Max in Disease Sites Treated with Bridging RT* *Each line corresponds to one patient treated with bridging RT prior to CAR-T therapy. SUV max plotted on the vertical axis reflects metabolic activity within the irradiated fields. Time intervals indicated in months on the horizontal axis reflect the approximate time from CAR-T infusion with the exact range in days indicated in parentheses. The magnification box demonstrates metabolic activity at the 1-month post-CAR-T interval with corresponding Deauville score indicated by color. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Prospective Evaluation of Interim FDG-PET Imaging during Chemoradiation for Anal SCC

<h3>Purpose/Objective(s)</h3> De-escalation of therapy for anal squamous cell carcinoma is under investigation in multiple prospective randomized trials. Imaging metrics from (F-18) fluorodeoxyglucose positron emission tomography (PET) before and during chemoradiation may serve as a biomarker to tailor treatment and aid in appropriate patient and dose selection. <h3>Materials/Methods</h3> From June 2012 to July 2021, 56 patients with anal canal cancer were enrolled in two prospective studies (30 and 26 patients, respectively) of PET prior to and during CRT after receiving ∼30 Gy. PET metrics of the primary site were calculated for the pre-treatment and interim images, including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) based on 40% SUVmax (MTV40, TLG40) or SUV 2.5 (MTV2.5, TLG2.5) thresholds. Associations between absolute pre-treatment and interim PET metrics and freedom from local/regional recurrence (FFLR) were investigated using the Cox proportional hazards method. Local/regional recurrence was defined as primary or nodal (in-field) recurrence. No adjustment was made for multiple comparisons. <h3>Results</h3> Forty-four patients were eligible for analysis. Patients with non-squamous cell histology (adenocarcinoma, melanoma) (3 patients), recurrent anal cancer (1 patient), metastatic disease (1 patient), and incomplete studies due to treatment toxicity or patient choice (7 patients) were excluded. Median follow-up was 2.4 years. Clinical stage was T3 or T4 in 43% of patients, and 52% were node positive. Seven patients have expired and disease recurrence patterns following treatment included local/regional (5 patients) and distant disease (7 patients). On univariate analysis, age, T and N stage, duration of treatment, and HIV status did not significantly correlate with FFLR. TLG2.5 (1.05 [0.99-1.11]) was marginally associated with FFLR. No pretreatment metrics or other interim metrics were significantly associated with FFLR. Multivariate analysis was not conducted given the small number of events (N=5). <h3>Conclusion</h3> In this expanded pilot study, characteristics of PET acquired during treatment of anal canal cancer were not significantly associated with FFLR. Given the limited number of FFLR events, definitive conclusions about the utility of interim PET cannot be drawn. The correlation of various PET metrics with FFLR warrants further investigation to determine if interim PET as an imaging biomarker can be used to personalize treatment, potentially in the setting of dose de-escalation.

Clinical use of cardiac 18F-FDG viability PET: a retrospective study of 44 patients undergoing post-test revascularization.

The coupling between coronary artery disease and the development of ischemic heart failure is well-established. For these patients, assessment of potentially viable but dysfunctional myocardial tissue (hibernation) is considered critical to guide optimal surgical treatment. Assessment with positron emission tomography (PET) theoretically provides measurements of hibernating tissue and maximal myocardial glucose uptake (MGU) in all cardiac territories. However, the clinical benefits of these measures are not thoroughly studied. We therefore aimed to investigate whether cardiac viability testing with combined Rubidium-82 (82Rb) and 18F-fluorodeoxyglucose (18F-FDG) predicts post-intervention improvement in left ventricle ejection fraction (LVEF) and survival. This retrospective study consisted of 131 patients with ischemic heart failure referred for dynamic 82Rb/18F-FDG PET viability testing prior to revascularization. The FDG viability scan was done during a hyperinsulinemic-euglycemic clamp and included PET measures static FDG hibernation and absolute MGU as well as myocardial blood flow and coronary flow reserve. In total, 44/131 patients undergoing viability testing were subsequently revascularized. Following revascularization, 26 patients had LVEF improvement of at least 5% while 18 patients had no improvement. A poor correlation between areas of intervention and areas of hibernation was observed. Receiver operating characteristics for all PET metrics did not predict improvement in LVEF. Furthermore, hibernation failed to predict survival regardless of whether patients underwent subsequent revascularization. Dynamic viability PET metrics (hibernation and MGU) do not predict post-intervention improvement in LVEF or overall survival in ischemic heart failure patients undergoing revascularization. In a clinical setting, the value of these measurements may therefore be limited. Kindly check and confirm the Given names and Family names for all the authors.All names are correct!

Generation and validation of a PET radiomics model that predicts survival in diffuse large B cell lymphoma treated with R-CHOP14: A SAKK 38/07 trial post-hoc analysis.

Functional parameters from positron emission tomography (PET) seem promising biomarkers in various lymphoma subtypes. This study investigated the prognostic value of PET radiomics in diffuse large B-cell lymphoma (DLBCL) patients treated with R-CHOP given either every 14 (testing set) or 21 days (validation set). Using the PyRadiomics Python package, 107 radiomics features were extracted from baseline PET scans of 133 patients enrolled in the Swiss Group for Clinical Cancer Research 38/07 prospective clinical trial (SAKK 38/07) [ClinicalTrial.gov identifier: NCT00544219]. The international prognostic indices, the main clinical parameters and standard PET metrics, together with 52 radiomics uncorrelated features (selected using the Spearman correlation test) were included in a least absolute shrinkage and selection operator (LASSO) Cox regression to assess their impact on progression-free (PFS), cause-specific (CSS), and overall survival (OS). A linear combination of the resulting parameters generated a prognostic radiomics score (RS) whose area under the curve (AUC) was calculated by receiver operating characteristic analysis. The RS efficacy was validated in an independent cohort of 107 DLBCL patients. LASSO Cox regression identified four radiomics features predicting PFS in SAKK 38/07. The derived RS showed a significant capability to foresee PFS in both testing (AUC, 0.709; p<0.001) and validation (AUC, 0.706; p<0.001) sets. RS was significantly associated also with CSS and OS in testing (CSS: AUC, 0.721; p<0.001; OS: AUC, 0.740; p<0.001) and validation (CSS: AUC, 0.763; p<0.0001; OS: AUC, 0.703; p=0.004) sets. The RS allowed risk classification of patients with significantly different PFS, CSS, and OS in both cohorts showing better predictive accuracy respect to clinical international indices. PET-derived radiomics may improve the prediction of outcome in DLBCL patients.

Assessing tumor metabolic heterogeneity of non-small cell lung cancer with total body PET-CT imaging on the uExplorer: Analysis of dynamic changes of 18F-FDG uptake.

e20549 Background: Total body positron emission tomography (PET) of uExplorer enables imaging of highly quantitative parameters beyond the standardized uptake value (SUV). The aim of this prospective study is to assess the dynamic changes of 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) uptake in characterizing tumor heterogeneity of non-small cell lung cancer (NSCLC). Methods: Sixteen NSCLC patients were prospectively enrolled in a prospective study (NCT04654234, GASTO-1067) between September 2020 and December 2020. All patients underwent a dynamic total-body 18F-FDG PET/CT scan before any treatment. The primary lung tumor, metastatic regional lymph node and inflammatory lymph node were manually delineated by a nuclear medicine physician and a radiation oncologist. Total Body PET was acquired between 0 – 60 mins after the injection of FDG from the subject’s feet. We compared lesion heterogeneity and different image-derived PET metrics including the SUV-mean, Patlak-derived influx rate constant (Ki) and distribution volume (DV). Results: The SUV-mean and Ki-mean of primary lung tumor and metastatic lymph node were significantly higher than inflammatory lymph node (p &lt; 0.001), while there was no significantly different of DV(p &gt; 0.05). By the scatter plot of SUV-mean and Ki-mean of primary lung tumor, 9 patients had been separated into high dynamic FDG metabolic (H-DFM) group and 7 in low DFM(L-DFM) group. The SUV-mean(p = 0.0002) and Ki-mean(p = 0.0002) of primary lung tumor were significantly higher in H-DFM group, whereas there is no difference in metastatic lymph node of both group. Interestingly, the SUV-mean and Ki-mean of primary lung tumor were higher than that of metastatic lymph node(p = 0.0002) in H-DFM group. On the contrast, the SUV-mean and Ki-mean of primary lung tumor were lower than that of metastatic lymph node(p = 0.05) in L-DFM group. There is no significant difference of DV-mean among primary lung tumor, metastatic lymph node and inflammatory lymph node in both arms. Conclusions: The results demonstrated that dynamic parameters from total body PET scan has the potential of providing complementary information of tumor heterogeneity in NSCLC than conventional static SUV imaging. The characteristics of H-DFM and L-DFM group could be taken into account for evaluation of further treatment response.

Plausibility and redundancy analysis to select FDG-PET textural features in non-small cell lung cancer.

BackgroundRadiomics refers to the extraction of a large number of image biomarker describing the tumor phenotype displayed in a medical image. Extracted from positron emission tomography (PET) images, radiomics showed diagnostic and prognostic value for several cancer types. However, a large number of radiomic features are nonreproducible or highly correlated with conventional PET metrics. Moreover, radiomic features used in the clinic should yield relevant information about tumor texture. In this study, we propose a framework to identify technical and clinical meaningful features and exemplify our results using a PET non‐small cell lung cancer (NSCLC) dataset.Materials and methodsThe proposed selection procedure consists of several steps. A priori, we only include features that were found to be reproducible in a multicenter setting. Next, we apply a voxel randomization step to identify features that reflect actual textural information, that is, that yield in 90% of the patient scans a value significantly different from random texture. Finally, the remaining features were correlated with standard PET metrics to further remove redundancy with common PET metrics. The selection procedure was performed for different volume ranges, that is, excluding lesions with smaller volumes in order to assess the effect of tumor size on the results. To exemplify our procedure, the selected features were used to predict 1‐yr survival in a dataset of 150 NSCLC patients. A predictive model was built using volume as predictive factor for smaller, and one of the selected features as predictive factor for bigger lesions. The prediction accuracy of the both models were compared with the prediction accuracy of volume.ResultsThe number of selected features depended on the lesion size included in the analysis. When including the whole dataset, from 19 features reflecting actual texture only two were found to be not strongly correlated with conventional PET metrics. When excluding lesions smaller than 11.49 and 33.10 mL (25 and 50 percentile of the dataset), four out of 27 features and 13 out of 29 features remained after eliminating features highly correlated with standard PET metrics. When excluding lesions smaller than 103.9 mL (75 percentile), 33 out of 53 features remained. For larger lesions, some of these features outperformed volume in terms of classification accuracy (increase of 4–10%). The combination of using volume as predictor for smaller and one of the selected features for larger lesions also improved the accuracy when compared with volume only (increase from 72% to 76%).ConclusionWhen performing radiomic analysis for smaller lesions, it should be first carefully investigated if a textural feature reflects actual heterogeneity information. Next, verification of the absence of correlation with all conventional PET metrics is essential in order to assess the additional value of radiomic features. Radiomic analysis with lesions larger than 11.4 mL might give additional information to conventional metrics while at the same time reflecting actual tumor texture. Using a combination of volume and one of the selected features for prediction yields promise to increase accuracy and reliability of a radiomic model.

Baseline SUVmax is related to tumor cell proliferation and patient outcome in follicular lymphoma.

Follicular lymphoma (FL) is the most common indolent lymphoma. Despite the clear benefit of CD20-based therapy, a subset of FL patients still progress to aggressive lymphoma. Thus, identifying early biomarkers that incorporate positron emission tomography metrics could be helpful to identify patients with a high risk of treatment failure with rituximab. We retrospectively included a total of 132 untreated FL patients separated into training and validation cohorts. Optimal threshold of baseline whole-body maximum standardized uptake (SUVmax) was first determined in the training cohort (n=48) to predict progression-free survival (PFS). The PET results were investigated along with the tumor and immune microenvironment, which were determined by immunochemistry and transcriptome studies involving gene set enrichment analyses and immune cell deconvolution, together with the tumor mutation profile. We report that baseline SUVmax>14.5 was associated with poorer PFS than baseline SUVmax≤14.5 (hazard ratio =0.28; P=0.00046). Neither immune T-cell infiltration nor immune checkpoint expression were associated with baseline PET metrics. By contrast, FL samples with Ki-67 staining ≥10% showed enrichment of cell cycle/DNA genes (P=0.013) and significantly higher SUVmax values (P=0.007). Despite similar oncogenic pathway alterations in both SUVmax groups of FL samples, four out of five cases harboring the infrequent FOXO1 transcription factor mutation were seen in FL patients with SUVmax>14.5. Thus, high baseline SUVmax reflects FL tumor proliferation and, together with Ki-67 proliferative index, can be used to identify patients at risk of early relapse with rituximab chemotherapy.

Risk stratification in diffuse large B-cell lymphoma using lesion dissemination and metabolic tumor burden calculated from baseline PET/CT†

We analyzed the prognostic value of a new baseline positron emission tomography (PET) parameter reflecting the spread of the disease, the largest distance between two lesions (Dmax). We tested its complementarity to metabolic tumor volume (MTV) in a large cohort of diffuse large B-cell lymphoma (DLBCL) patients from the REMARC trial (NCT01122472). MTVs were defined using the 41% maximum standardized uptake value threshold. From the three-dimensional coordinates, the centroid of each lesion was automatically obtained and considered as the lesion location. The distances between all pairs were calculated. Dmax was obtained for each patient and normalized with the body surface area [standardized Dmax (SDmax)]. From the REMARC trial, 290 patients aged 60-80 years were included: 91% had an advanced stage and 71% International Prognostic Index (IPI) ≥3. High versus low SDmax significantly impacted progression-free survival (PFS) (P < 0.0001) and overall survival (OS) (P= 0.0027). Patients with SDmax > 0.32 m-1 (n= 82) had a 4-year PFS and OS of 46% and 71%, respectively, against 77% and 87%, respectively, for patients with low SDmax. High SDmax and high MTV were independent prognostic factors of PFS (P= 0.0001 and P= 0.0010, respectively) and OS (P= 0.0028 and P= 0.0004, respectively). Combining MTV and SDmax yielded three risk groups with no (n= 109), one (n= 122) or two (n= 59) factors (P < 0.0001 for both PFS and OS). The 4-year PFS were 90%, 63%, 41%, respectively, and the 4-year OS were 95%, 79%, 66%, respectively. In addition, patients with at least two of the three factors including high SDmax, high MTV, Eastern Cooperative Oncology Group (ECOG) ≥2 had a higher number of central nervous system relapse (P= 0.017). SDmax is a simple feature that captures lymphoma dissemination, independent from MTV. These two PET metrics, SDmax and MTV, are complementary to characterize the disease, reflecting the tumor burden and its spread. This score appeared promising for DLBCL baseline risk stratification.

Relationship between semiquantitative 18F-fluorodeoxyglucose positron emission tomography metrics and necrosis in classical Hodgkin lymphoma

Semiquantitative 18F-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) parameters have been proposed as prognostic markers in classical Hodgkin lymphoma (cHL). In non-Hodgkin lymphoma necrosis as assessed by 18F-FDG PET or computed tomography (CT) (necrosisvisual) correlates with an adverse prognosis. We investigated whether semiquantitative 18F-FDG PET metrics correlate with necrosisvisual, determined the incidence of necrosisvisual and explored the prognostic impact of these factors in cHL. From 87 cHL cases treated with ABVD, (escalated) BEACOPP or CHOP chemotherapy between 2010 and 2017, 71 had both a NEDPAS/EARL accredited 18F-FDG PET and a contrast enhanced CT scan. Semiquantitative 18F-FDG PET parameters were determined using Hermes Hybrid 3D software. Necrosisvisual, defined by photopenic tumor areas on 18F-FDG PET and attenuation values between 10 and 30 Hounsfield units (HUs) on CT, was assessed blinded to outcome. Univariate Cox regression survival analyses of progression free survival (PFS) were performed. Necrosisvisual was observed in 18.3% of cHL patients. Bulky disease (tumor mass >10 cm in any direction) (P = 0.002) and TLG (P = 0.041) but no other semiquantitative parameters were significantly associated with necrosisvisual. In exploratory univariate survival analysis for PFS the covariates IPS, bulky disease, MTV and TLG were prognostic, while necrosisvisual was not.

Impact of Anatomic Location of Bone Metastases on Prognosis in Metastatic Castration-Resistant Prostate Cancer.

Whole-body assessments of 18F-NaF positron emission tomography (PET)/computed tomography (CT) provide promising quantitative imaging biomarkers of metastatic castration-resistant prostate cancer (mCRPC). This study investigated whether the distribution of metastases across anatomic regions is prognostic of progression-free survival. Fifty-four mCRPC patients with osseous metastases received baseline NaF PET/CT. Patients received chemotherapy (n= 16) or androgen receptor pathway inhibitors (n= 38). Semiautomated analysis using Quantitative Total Bone Imaging software extracted imaging metrics for the whole, axial, and appendicular skeleton as well as 11 skeletal regions. Five PET metrics were extracted for each region: number of lesions (NL), standardized maximum uptake value (SUVmax), average uptake (SUVmean), sum of uptake (SUVtotal), and diseased fraction of the skeleton (volume fraction). Progression included that discovered by clinical, biochemical, or radiographic means. Univariate and multivariate Cox proportional hazard regression analyses were performed between imaging metrics and progression-free survival, and were assessed according to their hazard ratios (HR) and concordance (C)-indices. The strongest univariate models of progression-free survival were pelvic NL and SUVmax with HR= 1.80 (NL: false discovery rate adjusted P= .001, SUVmax: adjusted P= .001). Three other region-specific metrics (axial NL: HR= 1.59, adjusted P= .02, axial SUVmax: HR= 1.61, adjusted P= .02, and skull SUVmax: HR= 1.58, adjusted P= .04) were found to be stronger prognosticators relative to their whole-body counterparts. Multivariate model including region-specific metrics (C-index= 0.727) outperformed that of whole-body metrics (C-index= 0.705). The best performance was obtained when region-specific and whole-body metrics were included (C-index= 0.742). Quantitative characterization of metastatic spread by anatomic location on NaF PET/CT enhances potential prognostication. Further study is warranted to optimize the prognostic and predictive value of NaF PET/CT in mCRPC patients.

Lower Grade Gliomas: Relationships Between Metabolic and Structural Imaging with Grading and Molecular Factors

Positron emission tomography (PET) is a valuable tool for the characterization of brain tumors invivo. However, few studies have investigated the correlation between carbon-11-methionine (11C-METH) PET metrics and the clinical, radiological, histological, and molecular features of patients affected by lower grade gliomas (LGGs). The present observational study evaluated the relationships between 11C-METH PET metrics and structural magnetic resonance imaging (MRI) findings with the histomolecular biomarkers in patients with LGGs who were candidates for surgery. We enrolled 96 patients with pathologically proven LGG (51 men, 45 women; age 44.1 ± 13.7 years; 45 with grade II, 51 with grade III), who had been referred from March 2012 to January 2015 for tumor resection and had undergone preoperative 11C-METH PET. The semiquantitative metrics for 11C-METH PET included maximum standardized uptake value (SUVmax), SUV ratio to normal brain, and metabolic tumor burden (MTB). The PET semiquantitative metrics were analyzed and compared with the MRI features, histological diagnosis, isocitrate dehydrogenase-1/2 status, and 1p/19q codeletion. Histological grade was associated with SUVmax (P= 0.002), SUV ratio (P= 0.011), and MTB (P= 0.001), with grade III lesions showing higher values. Among the nonenhancing lesions on MRI, SUVmax (P= 0.001), SUV ratio (P= 0.003) and MTB (P < 0.001) were significantly different statistically for grade II versus grade III. The MRI lesion volume correlated poorly with MTB (r2= 0.13). The SUVmax and SUV ratio were greater (P < 0.05) in isocitrate dehydrogenase-1/2 wild-type lesions, and the SUV ratio was associated with the presence of the 1p19q codeletion. The 11C-METH PET metrics correlated significantly with histological grade and the molecular profile. Semiquantitative PET metrics can improve the preoperative evaluation of LGGs and thus support clinical decision-making.

Risk-adapted therapy for advanced-stage Hodgkin lymphoma.

More than 80% of patients with advanced-stage Hodgkin lymphoma are now cured with contemporary treatment approaches. The ongoing challenge is how to further improve outcomes by identifying both high-risk patients who may benefit from more intensive frontline therapy to reduce the risk of relapse as well as lower-risk patients who may do just as well with less intensive therapy. Numerous trials have used an interim positron emission tomography (PET) response-adapted approach to evaluate early escalation or deescalation of therapy for patients with a positive or negative interim PET scan, respectively. Recent trials have incorporated novel agents, including brentuximab vedotin (BV) and the immune checkpoint inhibitors, in the frontline setting. Based on results of the ECHELON-1 trial, the Food and Drug Administration approved BV in combination with adriamycin, vinblastine, and dacarbazine chemotherapy for stage III to IV Hodgkin lymphoma. Improved methods to assess higher risk at diagnosis using quantitative PET metrics, such as metabolic tumor volume and total lesion glycolysis, and incorporation of emerging biomarkers may further refine patient selection for more intensive upfront therapy. The ultimate goal is to achieve the highest level of efficacy for an individual patient while minimizing the short- and long-term toxicities.

Baseline PET-Derived Metabolic Tumor Volume Metrics Did Not Predict Outcomes in Follicular Lymphoma Patients Treated with First-Line Immunochemotherapy and Antibody Maintenance in the Phase III GALLIUM Study

Baseline PET-Derived Metabolic Tumor Volume Metrics Did Not Predict Outcomes in Follicular Lymphoma Patients Treated with First-Line Immunochemotherapy and Antibody Maintenance in the Phase III GALLIUM Study

What is the prognostic impact of FDG PET in locally advanced head and neck squamous cell carcinoma treated with concomitant chemo-radiotherapy? A systematic review and meta-analysis

PurposeEvidence is conflicting on the prognostic value of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in head and neck squamous cell carcinoma. The aim of our study was to determine the impact of semiquantitative and qualitative metabolic parameters on the outcome in patients managed with standard treatment for locally advanced disease.MethodsA systematic review of the literature was conducted. A meta-analysis was performed of studies providing estimates of relative risk (RR) for the association between semiquantitative metabolic parameters and efficacy outcome measures.ResultsThe analysis included 25 studies, for a total of 2,223 subjects. The most frequent primary tumour site was the oropharynx (1,150/2,223 patients, 51.7%). According to the available data, the majority of patients had stage III/IV disease (1,709/1,799, 94.9%; no information available in four studies) and were treated with standard concurrent chemoradiotherapy (1,562/2,009 patients, 77.7%; only one study without available information). A total of 11, 8 and 4 independent studies provided RR estimates for the association between baseline FDG PET metrics and overall survival (OS), progression-free survival (PFS) and locoregional control (LRC), respectively. High pretreatment metabolic tumour volume (MTV) was significantly associated with a worse OS (summary RR 1.86, 95% CI 1.08–3.21), PFS (summary RR 1.81, 95% CI 1.14–2.89) and LRC (summary RR 3.49, 95% CI 1.65–7.35). Given the large heterogeneity (I2 > 50%) affecting the summary measures, no cumulative threshold for an unfavourable prognosis could be defined. No statistically significant association was found between SUVmax and any of the outcome measures.ConclusionFDG PET has prognostic relevance in the context of locally advanced head and neck squamous cell carcinoma. Pretreatment MTV is the only metabolic variable with a significant impact on patient outcome. Because of the heterogeneity and the lack of standardized methodology, no definitive conclusions on optimal cut-off values can be drawn.