Metabolic Tumor Volume Research Articles

Indicators describing the tumor lesion aggregation and dissemination and their impact on the prognosis of patients with diffuse large B cell lymphoma receiving chimeric antigen receptor T cell therapy.

Chimeric antigen receptor (CAR) T cell therapy has markedly improved the prognosis of patients with diffuse large B-cell lymphoma (DLBCL). The relative positioning of tumor lesions in lymphoma varies among patients, manifesting as either aggregation (clumped together) or dissemination (spread throughout the body). Prognostic significance of factors indicating the relative positioning of tumor lesions in CAR T cell therapy remains underexplored. For aggregation, prior research proposed the tumor volume surface ratio (TVSR), linking it to prognosis in chemotherapy. Regarding dissemination, indicators such as disease stage or extranodal involvement, commonly used in clinical practice, have not demonstrated prognostic significance in CAR T cell therapy. This study aims to analyze current indicators of tumor aggregation or dissemination and introduce a novel indicator to assess the prognostic value of tumor lesions' relative positioning in DLBCL patients undergoing CAR T cell therapy. This retrospective study included 42 patients receiving CAR T cell therapy. Lesion image information was obtained from the last PET/CT scan prior to CAR T cell infusion, including total metabolic tumor volume, total tumor surface, diameter of lymphoma masses, and the sites of tumor lesions. We evaluated TVSR and bulky disease as descriptors of tumor aggregation. We refined existing indicators, stage III&IV and >1 site extranodal involvement, to distill a new indicator, termed 'extra stage', to better represent tumor dissemination. The study examined the prognostic significance of tumor aggregation and dissemination. Our findings indicate that TVSR, while prognostically valuable in chemotherapy, lacks practical prognostic value in CAR T cell therapy. Conversely, bulky disease emerged as an optimal prognostic indicator of tumor aggregation. Both bulky disease and extra stage were associated with poor prognosis and exhibiting synergistic prognostic impact in CAR T cell therapy. Overall, the relative positioning of tumor lesions significantly influences the prognosis of patients with DLBCL receiving CAR T cell therapy. The ideal scenario involves tumors with minimal dissemination and no aggregation.

Abstract B019: Assessing Circulating TumOur DNA as a prognostic biomarker in endometrial cancer (The CODEC Study)

Abstract Introduction/Background: Endometrial cancer (EC) is the most common gynecological cancer in the developing world. While significant progress has been made through molecular sub-classification, the treatment of EC for many women remains contentious and better biomarkers are required to guide therapy selection. Circulating tumor DNA (ctDNA) a ‘liquid biopsy’, involves collection of tumor specific DNA via a blood test and can quantify cancer burden and detect tumor specific genomic information. The CODEC study is a prospective pilot study to assess the utility of ctDNA as a prognostic biomarker in EC with the hope that it may help predict relapse and guide selection of adjuvant therapy. Methodology: Women with Type 2 EC planned for surgery and consenting to the collection of biospecimens were enrolled prior to surgery and followed prospectively. Blood was collected perioperatively and then every three months for up to two years and at relapse. Broad sequencing of participants’ tumors was performed, the results of which guided the design of personalized droplet digital PCR (ddPCR) assays for ctDNA analysis. ctDNA was extracted from 5ml of plasma and tested in quadruplicate. PET defined metabolic tumor volume was compared to ctDNA and analysis of ctDNA and relapse free survival (RFS) performed using a Cox proportional hazards regression model. Results: Somatic mutations to guide ddPCR analysis were detected in 45 enrolled women stages 1- 4 including pathogenic variants in POLE. ctDNA results are currently available for 30 participants (remaining results awaited). 12/30 participants had detectable ctDNA preoperatively and 5/25 at Time Point 3 (2-6 weeks post-surgery). ctDNA levels varied significantly across the cohort but results to date indicate that perioperative ctDNA positivity is associated with relapse. Interestingly in those that had detectable ctDNA preoperatively, the majority had a rise in ctDNA intraoperatively. Conclusion: This proof-of-concept analysis showed that ctDNA can successfully be detected in the perioperative setting and is the first study in EC to compare ctDNA with PET findings. Although testing is still underway, the early results indicate that ctDNA maybe a useful biomarker to predict relapse and guide the selection of adjuvant therapy. Citation Format: Rachel Delahunty, Rainier Arnolda, Thuan Tzen Koh, Michael Hofman, Hayley Johnston, Patricia Wojtowicz, Caitlyn Nguyen, Nicole Brooks, Kym Reid, Julie Lamont, Thomas Jobling, Deborah Neesham, Vanessa Obers, Clair Shadbolt, Brooke Sawyer, Paul Smith, Jennifer Ellis, Geradline Goss, Mila Volcheck, Madawa Jayawardana, Sandun Silva, Chelsee Hewitt, Kate Jones, Andrew Fellowes, Orla McNally, Stephen Wong, Elizabeth Christie, Costas Yannakou. Assessing Circulating TumOur DNA as a prognostic biomarker in endometrial cancer (The CODEC Study) [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B019.

Clinical evaluation of AI-generated total metabolic tumor volume on 18F-FDG PET/CT for patients with metastatic lung cancer treated with immunotherapy

Clinical evaluation of AI-generated total metabolic tumor volume on 18F-FDG PET/CT for patients with metastatic lung cancer treated with immunotherapy

Overall survival and short-term efficacy analysis of cervical squamous cell carcinoma with skeletal muscle and 18F-FDG PET/CT parameters

2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) can provide tumor biological metabolism and skeletal muscle composition information. The aim of this study was to evaluate overall survival (OS) and short-term efficacy of cervical squamous cell carcinoma combining tumor biological metabolism and skeletal muscle composition parameters. Eighty two patients with cervical squamous cell carcinoma were included in the study, who received 18F-FDG PET/CT scans before treatment. Clinical characteristics, tumor biological metabolism parameters [standardized uptake value, metabolic tumor volume (MTV), total lesion glycolysis, heterogeneity of tumors, etc.] and body composition parameters were recorded. The survival analysis of cervical squamous cell carcinoma patients was performed by univariate and multivariate analysis. A combined model included clinical indicators, tumor metabolism parameters and sarcopenia was constructed to evaluate OS of patients. According to the Response Evaluation Criteria in Solid Tumours version 1.1, the relationship between sarcopenia with tumor metabolism parameters and short-term efficacy was investigated in subgroup. The results indicate that sarcopenia and high value of the sum of MTV of lesions and metastases (MTVtotal) were poor prognostic factors in patients with cervical squamous cell carcinoma. The combination of sarcopenia, MTVtotal and clinical factors provided an improved prediction of OS especially in the long term after treatment. Nutritional status of the patients and tumor metabolism may not affect the short-term efficacy of chemoradiotherapy in cervical squamous cell carcinoma patients.

Predicting programmed death-ligand 1 (PD-L1) expression with fluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) metabolic parameters in resectable non-small cell lung cancer

BackgroundProgrammed death-ligand 1 (PD-L1) expression is a predictive biomarker for immunotherapy in non-small cell lung cancer (NSCLC). PD-L1 and glucose transporter 1 expression are closely associated, and studies demonstrate correlation of PD-L1 with glucose metabolism.AimThe aim of this study was to investigate the association of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) metabolic parameters with PD-L1 expression in primary lung tumour and lymph node metastases in resected NSCLC.MethodsWe conducted a retrospective analysis of 210 patients with node-positive resectable stage IIB–IIIB NSCLC. PD-L1 tumour proportion score (TPS) was determined using the DAKO 22C3 immunohistochemical assay. Semi-automated techniques were used to analyse pre-operative [18F]FDG-PET/CT images to determine primary and nodal metabolic parameter scores (including max, mean, peak and peak adjusted for lean body mass standardised uptake values (SUV), metabolic tumour volume (MTV), total lesional glycolysis (TLG) and SUV heterogeneity index (HISUV)).ResultsPatients were predominantly male (57%), median age 70 years with non-squamous NSCLC (68%). A majority had negative primary tumour PD-L1 (TPS < 1%; 53%). Mean SUVmax, SUVmean, SUVpeak and SULpeak values were significantly higher (p < 0.05) in those with TPS ≥ 1% in primary tumour (n = 210) or lymph nodes (n = 91). However, ROC analysis demonstrated only moderate separability at the 1% PD-L1 TPS threshold (AUCs 0.58–0.73). There was no association of MTV, TLG and HISUV with PD-L1 TPS.ConclusionThis study demonstrated the association of SUV-based [18F]FDG-PET/CT metabolic parameters with PD-L1 expression in primary tumour or lymph node metastasis in resectable NSCLC, but with poor sensitivity and specificity for predicting PD-L1 positivity ≥ 1%.Clinical relevance statementWhilst SUV-based fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography metabolic parameters may not predict programmed death-ligand 1 positivity ≥ 1% in the primary tumour and lymph nodes of resectable non-small cell lung cancer independently, there is a clear association which warrants further investigation in prospective studies.Trial registrationNon-applicableKey Points• Programmed death-ligand 1 immunohistochemistry has a predictive role in non-small cell lung cancer immunotherapy; however, it is both heterogenous and dynamic.• SUV-based fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) metabolic parameters were significantly higher in primary tumour or lymph node metastases with positive programmed death-ligand 1 expression.• These SUV-based parameters could potentially play an additive role along with other multi-modal biomarkers in selecting patients within a predictive nomogram.

Prognostic role of quantitative [18F]FDG PET/CT parameters in adrenocortical carcinoma

PurposeWe aimed to evaluate the prognostic potential of baseline [18F]FDG PET/CT for overall survival (OS) in patients with adrenocortical carcinoma (ACC).MethodsWe performed a retrospective analysis of 67 treatment-naïve ACC patients with available [18F]FDG PET/CT at time of initial diagnosis. Pretherapeutic PETs of primary tumors were manually segmented and quantitative parameters (maximum/mean/peak standardized uptake value (SUVmax/mean/peak), metabolic tumor volume (MTV) and tumor lesion glycolysis (TLG, defined as TV*SUVmean) were derived. Based on a visual read, absence (M0) or presence of metastatic disease (M1) were evaluated. Kaplan–Meier and Cox regression analyses were used to determine the prognostic value of the above mentioned markers on overall survival adjusted for established prognostic markers.Results24/67 patients (36%) presented with M0 based on PET/CT, while the remaining 43/67 (64%) had M1-status. 32/67 patients died during follow-up and median OS was 48 months. In 12% of patients FDG-PET detected additional metastatic lesion not clearly visible by CT only. In univariable analysis, all quantitatively derived PET parameters failed to reach significance (P ≥ 0.1), and only PET/CT-based M1-status and Ki-67 were associated with increased mortality (M1: HR 13.89, 95% CI 4.15–86.32, P < 0.001; Ki-67 HR 1.29, 95% CI 1.16–1.42; P < 0.0001). Using multivariable Cox regression analyses, M1-status (HR 9.69, 95% CI 2.82–60.99) and Ki-67 index (HR 1.29, 95% CI 1.13–1.04; P < 0.05) remained significant associated with OS.ConclusionIn treatment-naïve ACC patients, the quantitative PET parameter failed to predict OS, but presence of metastases detected by [18F]FDG PET/CT and Ki-67 index were independently associated with shorter OS. Therefore, a simple visual PET-based read-out is of prognostic value at initial diagnosis, while time-consuming PET-based quantification can be omitted.

2-[18]F FDG PET/CT dissemination features in adult burkitt lymphoma Are predictive of outcome.

This retrospective study investigated the prognostic role of disease dissemination features (Dmax and Dmaxbsa) measured by 2-[18F]FDG PET/CT in newly diagnosed Burkitt Lymphoma (BL) patients, comparing their performance with other metabolic parameters. We included 78 patients diagnosed with BL between 2010 and 2022 with an available baseline PET, interim PET/CT (iPET) and end of treatment PET/CT (eotPET) and with a minimum of two 2-[18F]FDG avid lesions present at the baseline scan. Dmax was calculated from the three-dimensional coordinates of the baseline metabolic tumor volume (MTV) by using LIFEx software; Dmaxbsa was calculated as Dmax normalized for body surface area according to the Du Bois method. We evaluated their effect on metabolic treatment response evaluated by PET, on progression free survival (PFS) and on overall survival (OS). Dmaxbsa was significantly associated with tumor stage, bulky and extranodal disease, MTV and TLG. At a median follow-up of 49 months, the median PFS and OS were 45 and 48 months. Dmax and Dmaxbsa were significantly higher in not complete metabolic response than complete metabolic response group at iPET and eotPET.As far as PFS, parameters including iPET/CT, eotPET/CT outcomes, MTV and TLG showed to be independent prognostic factors while Dmax and Dmaxbsa were not significantly associated with the outcome. Dissemination features, together with eotPET/CT results, MTV and TLG, demonstrated to be significantly correlated with OS. In conclusion, in this study we demonstrated that dissemination features derived by 2[18F]-FDG PET/CT were significantly correlated with response to treatment and long-term outcome, independently from other PET features.

Machine Learning and Texture Analysis of [18F]FDG PET/CT Images for the Prediction of Distant Metastases in Non-Small-Cell Lung Cancer Patients.

The aim of our study was to predict the occurrence of distant metastases in non-small-cell lung cancer (NSCLC) patients using machine learning methods and texture analysis of 18F-labeled 2-deoxy-d-glucose Positron Emission Tomography/Computed Tomography {[18F]FDG PET/CT} images. In this retrospective and single-center study, we evaluated 79 patients with advanced NSCLC who had undergone [18F]FDG PET/CT scan at diagnosis before any therapy. Patients were divided into two independent training (n = 44) and final testing (n = 35) cohorts. Texture features of primary tumors and lymph node metastases were extracted from [18F]FDG PET/CT images using the LIFEx program. Six machine learning methods were applied to the training dataset using the entire panel of features. Dedicated selection methods were used to generate different combinations of five features. The performance of selected machine learning methods applied to the different combinations of features was determined using accuracy, the confusion matrix, receiver operating characteristic (ROC) curves, and area under the curve (AUC). A total of 104 and 78 lesions were analyzed in the training and final testing cohorts, respectively. The support vector machine (SVM) and decision tree methods showed the highest accuracy in the training cohort. Seven combinations of five features were obtained and introduced in the models and subsequently applied to the training and final testing cohorts using the SVM and decision tree. The accuracy and the AUC of the decision tree method were higher than those obtained with the SVM in the final testing cohort. The best combination of features included shape sphericity, gray level run length matrix_run length non-uniformity (GLRLM_RLNU), Total Lesion Glycolysis (TLG), Metabolic Tumor Volume (MTV), and shape compacity. The combination of these features with the decision tree method could predict the occurrence of distant metastases with an accuracy of 74.4% and an AUC of 0.63 in NSCLC patients.

Evaluation of therapeutic effect and prognostic value of 18F-FDG PET/CT in different treatment nodes of DLBCL patients.

In the present study, we aimed to investigate the role of baseline (B), interim (I) and end-of-treatment (Eot) 18F-FDG PET/CT in assessing the prognosis of diffuse large B cell lymphoma (DLBCL), so as to identify patients who need intensive treatment at an early stage. A total of 127 DLBCL patients (62 men; 65 women; median age 62years) were retrospectively analyzed in this study. Baseline (n = 127), interim (n = 127, after 3-4 cycles) and end-of-treatment (n = 53, after 6-8 cycles) PET/CT images were re-evaluated; semi-quantitative parameters such as maximum standardized uptake value of lesion-to-liver ratio (SUVmax(LLR)) and lesion-to-mediastinum ratio (SUVmax(LMR)), total metabolic tumor volume (TMTV) and total metabolic tumor volume (TLG) were recorded. ΔTLG1 was the change of interim relative to baseline TLG (I to B), ΔTLG2 (Eot to B). ΔSUVmax and ΔTMTV were the same algorithm. The visual Deauville 5-point scale (D-5PS) has been adopted as the major criterion for PET evaluation. Visual analysis (VA) and semi-quantitative parameters were assessed for the ability to predict progression-free survival (PFS) and overall survival (OS) by using Kaplan-Meier method, cox regression and logistic regression analysis. When visual and semi-quantitative analysis are combined, the result is only positive if both are positive. At a median follow-up of 34months, the median PFS and OS were 20 and 32months. The survival curve analysis showed that advanced stage and IPI score with poor prognosis, ΔSUVmax(LLR)1 < 89.2%, ΔTMTV1 < 91.8% and ΔTLG1 < 98.8%, ΔSUVmax(LLR)2 < 86.4% were significantly related to the shortening of PFS in patient (p < 0.05). ΔSUVmax(LLR)1 < 83.2% and ΔTLG1 < 97.6% were significantly correlated with the shortening of OS in patients (p < 0.05). Visual analysis showed that incomplete metabolic remission at I-PET and Eot-PET increased the risk of progress and death. In terms of predicting recurrence by I-PET, the combination of visual and semi-quantitative parameters showed higher positive predictive value (PPV) and specificity than a single index. Three to four cycles of R-CHOP treatment may be a time point for early prediction of early recurrence/refractory (R/R) patients and active preemptive treatment. Combined visual analysis with semi-quantitative parameters of 18F-FDG PET/CT at interim can improve prognostic accuracy and may allow for more precise screening of patients requiring early intensive therapy.

Value of [18F]FDG PET/CT parameters of the primary tumor in assessing overall survival in NSCLC patients with cN1-cN3 lymph nodes involvement.

The aim of this retrospective study was to assess the value of 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ([18F]FDG PET/CT parameters in cN1-cN3 non-small cell lung cancer (NSCLC) patients. 59 consecutive patients (35 M, 24 F) with NSCLC who underwent pretreatment [18F]FDG PET/CT were enrolled to this study. Several primary tumor PET parameters, including the maximum and mean standardized uptake value (SUVmax and SUVmean), the metabolic active tumor volume (MTV) and the total lesion glycolysis (TLG = MTVxSUVmean), were extracted and analysed. Overall survival was defined as time from primary diagnosis to death or the last info. In the whole analysed group 44 patients underwent curative treatment, while 15, because of the severity of the disease, were classified for palliative treatment. Univariate Cox analysis of clinical and metric PET parameters revealed that MTV was a significant prognostic factor for OS (p = 0.024), while TLG and curative treatment showed a trend for significance (p < 0.1). In multivariate Cox regression (MTV and curative treatment) MTV remained a significant factor (p = 0.047). Metabolic tumor volume of the primary tumor was the only independent prognostic factor for cN1-cN3 NSCLC patients.

Need for Objective Task-Based Evaluation of Image Segmentation Algorithms for Quantitative PET: A Study with ACRIN 6668/RTOG 0235 Multicenter Clinical Trial Data.

Reliable performance of PET segmentation algorithms on clinically relevant tasks is required for their clinical translation. However, these algorithms are typically evaluated using figures of merit (FoMs) that are not explicitly designed to correlate with clinical task performance. Such FoMs include the Dice similarity coefficient (DSC), the Jaccard similarity coefficient (JSC), and the Hausdorff distance (HD). The objective of this study was to investigate whether evaluating PET segmentation algorithms using these task-agnostic FoMs yields interpretations consistent with evaluation on clinically relevant quantitative tasks. Methods: We conducted a retrospective study to assess the concordance in the evaluation of segmentation algorithms using the DSC, JSC, and HD and on the tasks of estimating the metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of primary tumors from PET images of patients with non-small cell lung cancer. The PET images were collected from the American College of Radiology Imaging Network 6668/Radiation Therapy Oncology Group 0235 multicenter clinical trial data. The study was conducted in 2 contexts: (1) evaluating conventional segmentation algorithms, namely those based on thresholding (SUVmax40% and SUVmax50%), boundary detection (Snakes), and stochastic modeling (Markov random field-Gaussian mixture model); (2) evaluating the impact of network depth and loss function on the performance of a state-of-the-art U-net-based segmentation algorithm. Results: Evaluation of conventional segmentation algorithms based on the DSC, JSC, and HD showed that SUVmax40% significantly outperformed SUVmax50%. However, SUVmax40% yielded lower accuracy on the tasks of estimating MTV and TLG, with a 51% and 54% increase, respectively, in the ensemble normalized bias. Similarly, the Markov random field-Gaussian mixture model significantly outperformed Snakes on the basis of the task-agnostic FoMs but yielded a 24% increased bias in estimated MTV. For the U-net-based algorithm, our evaluation showed that although the network depth did not significantly alter the DSC, JSC, and HD values, a deeper network yielded substantially higher accuracy in the estimated MTV and TLG, with a decreased bias of 91% and 87%, respectively. Additionally, whereas there was no significant difference in the DSC, JSC, and HD values for different loss functions, up to a 73% and 58% difference in the bias of the estimated MTV and TLG, respectively, existed. Conclusion: Evaluation of PET segmentation algorithms using task-agnostic FoMs could yield findings discordant with evaluation on clinically relevant quantitative tasks. This study emphasizes the need for objective task-based evaluation of image segmentation algorithms for quantitative PET.

Prognostic value of baseline and interim [18F]FDG PET metabolic parameters in pediatric Hodgkin's lymphoma.

Hodgkin lymphoma (HL) in pediatric populations has a high survival rate but poses risks for long-term morbidities. Although [18F]fluoro‑2‑deoxy‑2‑d‑glucose positron emission tomography ([18F]FDG PET) scans offer potential for improved risk stratification, the definitive prognostic value of quantitative [18F]FDG PET parameters remains unclear for pediatric HL. A single-center, retrospective study included pediatric patients diagnosed with HL between 2016 and 2023 treated according to EuroNet-PHL-C1 and DAL/GPOH-HD protocols. Patients underwent baseline and interim PET/CT scans after two chemotherapy cycles. Event-free survival (EFS) was the primary endpoint, Deauville score was the secondary endpoint. Quantitative [18F]FDG PET parameters included SUVmax, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) that were evaluated using two segmentation methods (SUV 2.5, 41% SUVmax). Survival outcomes were assessed using Cox regression analysis. A total of 115 patients (50 males, median age 14.2years) were studied, with a median follow-up period of 35months. During this period, 16 cases (13.9%) of relapse or progression were noted. Baseline and interim MTV 2.5, MTV 41%, TLG 2.5, and TLG 41%, along with interim SUVmax, were significantly associated with worse EFS and correlated with post-treatment Deauville scores. In multivariable analysis, interim MTV 2.5 > 0ml (adj. hazard ratio, HR: 3.89, p = 0.009) and interim TLG 41% ≥ 30g (adj. HR: 7.98, p = 0.006) were independent risk factors for EFS. Baseline and interim [18F]FDG PET parameters can serve as significant prognostic indicators for EFS and treatment response in pediatric HL. These quantitative measures could enhance individualized, risk-adapted treatment strategies for children and adolescents with HL.

Predictive Value of Corrected 18 F-FDG PET/CT Baseline Parameters for Primary DLBCL Prognosis: A Single-center Study.

Objective The purpose of this study was to evaluate the prognostic significance of corrected baseline metabolic parameters in fluorodeoxyglucose positron emission tomography imaging ( 18 F-FDG PET/CT) for 3-year progression-free survival (PFS) in patients with primary diffuse large B cell lymphoma (DLBCL). Patients and Methods Retrospective clinical and pathological data were collected for 199 patients of DLBCL diagnosed between January 2018 and January 2021. All patients underwent 18 F-FDG PET/CT scans without any form of treatment. The corrected maximum standardized uptake value (corSUVmax), corrected mean standardized uptake value (corSUVmean), corrected whole-body tumor metabolic volume sum (corMTVsum), and corrected total lesion glycolysis of whole body (corTLGtotal) were corrected using the SUVmean in a 1-cm diameter mediastinal blood pool (MBP) from the descending thoracic aorta of patients. Kaplan-Meier survival curves and Cox regression were used to examine the predictive significance of corrected baseline metabolic parameters on 3-year PFS of patients. The incremental values of corrected baseline metabolic parameters were evaluated by using Harrell's C-indices, receiver operating characteristic, and Decision Curve Analysis. Results The multivariate analysis revealed that only the National Comprehensive Cancer Network (NCCN)-International Prognostic Index (IPI) and corMTVsum had an effect on 3-year PFS of patients ( p < 0.05, respectively). The Kaplan-Meier survival analysis demonstrated significant differences in PFS between the risk groups classified by corSUVsum, corMTVsum, and corTLGtotal (log-rank test, p < 0.05). The predictive model composed of corMTVsum and corTLGtotal surpasses the predictive performance of the model incorporating MTVsum and TLGtotal. The optimal performance was observed when corMTVsum was combined with NCCN-IPI, resulting in a Harrell's C index of 0.785 and area under the curve values of 0.863, 0.891, and 0.947 for the 1-, 2-, and 3-year PFS rates, respectively. Conclusion The corMTVsum offers significant prognostic value for patients with DLBCL. Furthermore, the combination of corMTVsum with the NCCN-IPI can provide an accurate prediction of the prognosis.

Association of circulating tumor HPV16DNA levels and quantitative PET parameters in patients with HPV-positive head and neck squamous cell carcinoma

Circulating tumor DNA (ctDNA), which circulates in the blood after being shed from cancer cells in the body, has recently gained attention as an excellent tumor marker. The purpose of this study was to evaluate whether ct human papillomavirus (HPV) 16 DNA (ctHPV16DNA) levels were associated with quantitative PET parameters in patients with HPV-positive head and neck (HN) squamous cell carcinoma (SCC). Fifty patients with oropharyngeal SCC (OPSCC) and 5 with SCC of unknown primary (SCCUP) before treatment were included. They all underwent blood sampling to test ctHPV16DNA levels and FDG PET-CT examinations. Quantitative PET parameters included SUVmax, metabolic tumor volume (MTV), MTV of whole-body lesions (wbMTV), and 56 texture features. ctHPV16DNA levels were compared to texture features of primary tumors in OPSCC patients (Group A) or the largest primary or metastatic lymph node lesions in OPSCC and SCCUP patients (Group B) and to other PET parameters. Spearman rank correlation test and multiple regression analysis were used to confirm the associations between ctHPV16DNA levels and PET parameters. ctHPV16DNA levels moderately correlated with wbMTV, but not with SUVmax or MTV in Groups A and B. ctHPV16DNA levels exhibited a weak negative correlation with low gray-level zone emphasis in Groups A and B. Multiple regression analysis revealed that wbMTV and high gray-level zone emphasis were the significant factors for ctHPV16DNA levels in Group B. These results were not observed in Group A. This study demonstrated that ctHPV16DNA levels correlated with the whole-body tumor burden and tumor heterogeneity visualized on FDG PET-CT in patients with HPV-positive HNSCC.

TMTV-Net: fully automated total metabolic tumor volume segmentation in lymphoma PET/CT images - a multi-center generalizability analysis.

Total metabolic tumor volume (TMTV) segmentation has significant value enabling quantitative imaging biomarkers for lymphoma management. In this work, we tackle the challenging task of automated tumor delineation in lymphoma from PET/CT scans using a cascaded approach. Our study included 1418 2-[18F]FDG PET/CT scans from four different centers. The dataset was dividedinto 900 scans for development/validation/testing phasesand 518 for multi-center external testing. The former consisted of 450 lymphoma, lung cancer, and melanoma scans, along with 450 negative scans, while the latter consisted of lymphoma patients from different centers with diffuse large B cell, primary mediastinal large B cell, and classic Hodgkin lymphoma cases. Our approach involves resampling PET/CT images into different voxel sizes in the first step, followed by training multi-resolution 3D U-Nets on each resampled dataset using a fivefold cross-validation scheme. The models trained on different data splits were ensemble. After applying soft voting to the predicted masks, in the second step, we input the probability-averaged predictions, along with the input imaging data, into another 3D U-Net. Models were trained with semi-supervised loss. We additionally considered the effectiveness of using test time augmentation (TTA) to improve the segmentation performance after training. In addition to quantitative analysis including Dice score (DSC) and TMTV comparisons, the qualitative evaluation was also conducted by nuclear medicine physicians. Our cascaded soft-voting guided approach resulted in performance with an average DSC of 0.68 ± 0.12 for the internal test data from developmental dataset, and an average DSC of 0.66 ± 0.18 on the multi-site external data (n = 518), significantly outperforming (p < 0.001) state-of-the-art (SOTA) approaches including nnU-Net and SWIN UNETR. While TTA yielded enhanced performance gains for some of the comparator methods, its impact on our cascaded approach was found to be negligible (DSC: 0.66 ± 0.16). Our approach reliably quantified TMTV, with a correlation of 0.89 with the ground truth (p < 0.001). Furthermore, in terms of visual assessment, concordance between quantitative evaluations and clinician feedback was observed in the majority of cases. The average relative error (ARE) and the absolute error (AE) in TMTV prediction on external multi-centric dataset were ARE = 0.43 ± 0.54 and AE = 157.32 ± 378.12 (mL) for all the external test data (n = 518), and ARE = 0.30 ± 0.22 and AE = 82.05 ± 99.78 (mL) when the 10% outliers (n = 53) were excluded. TMTV-Net demonstrates strong performance and generalizability in TMTV segmentation across multi-site external datasets, encompassing various lymphoma subtypes. A negligible reduction of 2% in overall performance during testing on external data highlights robust model generalizability across different centers and cancer types, likely attributable to its training with resampled inputs. Our model is publicly available, allowing easy multi-site evaluation and generalizability analysis on datasets from different institutions.

The role of preoperative [11C]methionine PET in defining tumor-related epilepsy and predicting short-term postoperative seizure control in temporal lobe low-grade gliomas.

Surgery is the mainstay of treatment for low-grade glioma (LGG)-related epilepsy. However, the goal of achieving both oncological radical resection and seizure freedom can be challenging. PET with [11C]methionine (MET) has been recently introduced in clinical practice for the management of patients with LGGs, not only to monitor the response to treatments, but also as a preoperative tool to define the metabolic tumor extent and to predict tumor grading, type, and prognosis. Still, its role in defining tumor-related epilepsy and postoperative seizure outcomes is limited. The aim of this preliminary study was to investigate the role of MET PET in defining preoperative seizure characteristics and short-term postoperative seizure control in a cohort of patients with newly diagnosed temporal lobe low-grade gliomas (tLGGs). Patients with newly diagnosed and histologically proven temporal lobe grade 2/3 gliomas (2021 WHO CNS tumor classification) who underwent resection at the authors' institution between July 2011 and March 2021 were included in this retrospective study. MET PET images were acquired, fused with MRI scans, and qualitatively and semiquantitatively analyzed. Any eventual PET/MRI involvement of the temporomesial area, seizure characteristics, and 1-year seizure outcomes were reported. A total of 52 patients with tLGGs met the inclusion criteria. MET PET was positive in 41 (79%) patients, with a median metabolic tumor volume of 14.56 cm3 (interquartile range [IQR] 6.5-28.2 cm3). The median maximum and mean tumor-to-background ratio (TBRmax, TBRmean) were 2.24 (IQR 1.58-2.86) and 1.53 (IQR 1.37-1.70), respectively. The metabolic tumor volume was found to be related to the presence of seizures at disease onset, but only in noncodeleted tumors (p = 0.014). Regarding patients with uncontrolled seizures at surgery, only the temporomesial area PET involvement showed a statistical correlation both in the univariate (p = 0.058) and in the multivariate analysis (p = 0.030). At 1-year follow-up, seizure control was correlated with MET PET-derived semiquantitative data. Particularly, higher TBRmax (p = 0.0192) and TBRmean (p = 0.0128) values were statistically related to uncontrolled seizures 1 year after surgery. This preliminary study suggests that MET PET may be used as a preoperative tool to define seizure characteristics and outcomes in patients with tLGGs. These findings need to be further validated in larger series with longer epileptological follow-ups.

Tumor and metastatic lymph nodes metabolic activity on 18F-FDG-PET/CT to predict progression-free survival in locally advanced cervical cancer.

The present study investigated the predictive diseases progression value of preoperative fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with local advanced cervical cancer (LACC). In total, 267 patients [median age 58 (range: 27-85) years old] with LACC underwent 18F-FDG PET/CT prior to any treatment. The maximum standardized uptake values (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary lesion and metastatic lymph nodes were measured on PET/CT and correlated with clinicopathological features and progression-free survival (PFS). The median follow-up was 36.52 (range: 3.09-61.29) months. During the observation period, 80 (30.0%) patients exhibited disease progression. Univariate analysis showed that FIGO stage, concurrent chemoradiotherapy (CRT), serum level of carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC-Ag), primary tumor MTV (pMTV) and TLG (pTLG), lymph nodes SUVmax (nSUVmax) and TLG (nTLG), and total metabolic activity (sMTV, sTLG) were associated with PFS. nSUVmax ≥ 5.29, CEA ≥ 7.11ng/ml and deficiency of concurrent CRT were independent risk factor for PFS (p = 0.006, p = 0.008, p = 0.014). The 3-year PFS for patients with high nSUVmax were 42.2% compared to 56.3% for low nSUVmax values. Pretreatment cervical and lymph nodes metabolic parameters were associated with PFS in patients with LACC.

Predictive value of metabolism and its heterogeneity parameters measured by preoperative 18 F-FDG PET/CT for mediastinal occult lymph node metastasis in cN0 lung invasive adenocarcinoma.

To explore the potential of intratumoral metabolism and its heterogeneous parameters, as measured by preoperative fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) imaging, to predict mediastinal occult lymph node metastasis in cN0 lung invasive adenocarcinoma. Seventy five patients were consecutively enrolled from January 2018 to December 2022. All patients underwent 18F-FDG PET/CT scans within two weeks before surgery, and had mediastinal lymph node metastasis confirmed by pathologic diagnosis after surgery. Metabolic parameters including the maximum standardized uptake value (SUVmax), mean SUV (SUVmean), maximum average SUV (SUVpeak), tumor metabolic volume (MTV), and metabolic heterogeneity (HF) were measured. The relationship between primary focal metabolism, its heterogeneity parameters, and occult mediastinal lymph node metastasis was analyzed using an independent-sample t-test, analysis of covariance, and Mann-Whitney U test. A multivariate logistic regression model was used to analyze independent risk factors for mediastinal lymph node metastasis, while the receiver operating characteristic (ROC) curve assessed the predictive value of metabolic heterogeneity parameters for mediastinal occult lymph node metastasis. A total of 20 out of 75 patients (26.7%) were pathologically confirmed to have mediastinal lymph node metastasis. Analysis of covariance showed that the SUVmax, SUVmean, SUVpeak and MTV were significantly higher in patients with metastasis than in those without (all P<0.05). The metabolic heterogeneity parameters HF2 and HF3 were significantly higher in patients with mediastinal lymph node metastasis than in those without (P=0.013, 0.001), but not HF1. Multivariate Logistic regression analysis identified that tumor size, SUVmax, SUVpeak, lymph node SUVmax, and HF2 of the primary tumor as independent risk factors for mediastinal lymph node metastasis. Metabolic heterogeneity 3 demonstrated high predictive value for mediastinal occult lymph node metastasis (AUC=0.720, P=0.004). Metabolism and heterogeneity, as measured by preoperative 18F-FDG PET/CT in lung invasive adenocarcinoma, potentially have clinical value for predicting mediastinal occult lymph node metastasis.

Diagnostic value of FDG PET-CT in differentiating lung adenocarcinoma from squamous cell carcinoma

BackgroundLung cancer is the leading cause of cancer-related deaths worldwide. The combination of fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) and computed tomography (CT) has a major impact on the diagnosis, staging, treatment planning and follow-up of lung cancer patients. The maximum standardized uptake value (SUVmax) is an easily performed and most widely used semi-quantitative index for the analysis of FDG PET images and estimation of metabolic activity. This study aimed to investigate the role of PET/CT in differentiating adenocarcinoma (ADC), the most common lung cancer, from squamous cell carcinoma (SCC) by comparing FDG uptake measured as SUVmax.ResultsBetween 2019 and 2022, 76 patients diagnosed with non-small cell lung cancer (NSCLC) at the Department of Pathology, Atatürk University Faculty of Medicine, with histopathologic evidence of adenocarcinoma or squamous cell carcinoma, underwent retrospective analysis using PET/CT scanning to measure PET parameters of the lesions and compare them with histopathology. Among 76 NSCLC patients included in the study, 43 (57%) were histopathologically diagnosed as ADC and 33 (43%) as SCC. SUVmax, SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) values of lesions in patients with SCC were statistically significantly higher than those in patients with ADC (p values 0.007, 0.009, 0.003 and 0.04, respectively).ConclusionsLung SCC has higher metabolic uptake values than ADC, and PET/CT can be used to differentiate them.

Predictive Role of Preoperative Whole-Body 18F-FDG PET/CT for Risk Stratification of Early-Stage (FIGO I-IIA) Cervical Cancer Patients Treated by Surgery.

The aim of the present study was to investigate the predictive value of maximum standardized uptake value (SUVmax) measured on preoperative 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in International Federation of Gynecology and Obstetrics (FIGO 2009) stage I-IIA cervical cancer patients who were treated with radical hysterectomy. A total of 47 patients with FIGO stage I-IIA cervical cancer who were evaluated preoperatively with biopsy and 18F-FDG PET/CT followed by radical hysterectomy were included in the study. Correlation between SUVmax and pathological risk factors or survival was studied. The mean SUVmax was significantly higher in patients with large tumor size (≥4 cm), advanced stage (IIA>IB>IA) and depth of invasion >50%. No significant difference was noted in SUVmaxbetween patients with and without pelvic lymph node involvement (P=0.639). SUVmax of the primary tumor with and without lymph-vascular invasion were 12.95 and 10.35, respectively (P=0.5). No significant difference was noted between patients with high SUVmax and low SUVmax with regards to overall survival (OS) and disease-free survival (DFS), using an optimal cut-off value of 7.65 for OS and DFS obtained from receiver operating characteristic (ROC) curve analysis. Patient with tumor size >4cm had 5.9 times more probability of mortality compared to tumor size <4cm (P=0.09). The present study observations showed that although SUVmaxis associated with pathological variables, it does not independently predict oncological outcomes in FIGO stage IA-IIA cervical cancer patients who were treated with radical hysterectomy. These findings suggest that SUVmax of primary tumor may be used for risk stratification, but not for prognostication insurgically treated early-stage cervical cancer patients. Not using other parameters of 18F-FDG PET/CT like metabolic tumor volume (MTV), tumor lysis glycolysis (TLG), small sample size,variation in calculation of SUVmax, histopathologic heterogeneity, inclusion of stage IA patients in the study were constraints of present study. Furtherstudies with large sample size using multi metabolic parameters of 18F-FDG PET/CT, including the SUVmax,SUVmean,SUVpeak, MTV and TLG are needed.