Total Lesion Glycolysis Values Research Articles

Abstract PO3-27-01: Prediction of pathological complete response to neoadjuvant treatment in loco-regional advancedbreast cancer by using advanced PET/CT metabolic parameters

Abstract Prediction of pathological complete response to neoadjuvant treatment in loco-regional advanced breast cancer by using advanced PET/CT metabolic parameters. Abstract: Background: The standard treatment for locally advanced breast cancer (LABC) is neoadjuvant systemic therapy followed by surgery. The usefulness of FDG PET/CT for evaluating the treatment efficacy in breast cancer is well established; however, the role of quantitative functional PET/CT parameters, such as the metabolic tumor volume (MTV) and total lesion glycolysis (TLG), remains inconclusive. The aim of this study was to determine the correlation between quantitative functional parameters derived from PET/CT in LABC patients at staging and the response to neoadjuvant therapy. Methods: Seventy-eight consecutive patients (aged 25-82 y) with confirmed LABC (stages II-III) who underwent PET/CT as a part of their staging assessment and received neoadjuvant therapy followed by surgery were retrospectively included in this study. All patients underwent an FDG PET/CT at staging; and values of SUV max, SUV mean, MTV, and TLG were determined from the PET/CT studies. The patients were divided into two groups, based on the completeness of histopathologic response to neoadjuvant therapy, both in the primary tumor and axillary lymph nodes. Clinical, imaging and demographic data were collected from patient’s medical record. Results: A complete pathologic response (pCR) was achieved in 33/78 (42%) patients. Among patients with ER/PR positive, Her2-neu negative tumors, in 23/27 (85%) patients only partial pathologic response was reached; 91% of patients with ER/PR negative, Her2-neu positive and 43% of Triple-negative patients had complete pathological? response. For the primary breast tumor response, a higher SUV max, 10.7±5.34 for pCR vs. 7.24±4.62 for non-pCR group was measured, p-value=0.003; threshold value of 6.625. A higher SUV mean in the primary tumor resulted in a significantly higher rate of pCR, 5.95±2.36 vs 4,4±2.16, p=0.004, with a threshold value of 5.795. Neither MTV, not TLG were predictive parameters of the primary tumor response. For lymph nodes response, SUV max and SUV mean had no role in the prediction of pCR. Statistically significant difference however, was found between pCR and non-pCR in MTV values in the involved lymph nodes, with a median =2.13 cm³ [0-7.85] in pCR group vs 5.43 cm³ [3.11-15.3] in non-pCR, p=0.01 (threshold value 2.375) as well as in TLG measurements, with a median of 4.64 [0-19.8] vs. 12.7 [3.21-23.1], p=0.047, (25-75 IQR). Conclusion: Primary breast tumor SUV max/mean values have a significant correlation with the treatment response and threshold values were found. Low MTV and TLG measurements in lymph nodes may predict pCR. Neither MTV nor TLG had were found to have a significant role in the prediction of the primary tumor response. Citation Format: Maisun Shamya, Olga Kagna, Zohar Keidar, Tala Palchan-Hazan, Salem Billan, Roxolyana Abdah-Bortnyak. Prediction of pathological complete response to neoadjuvant treatment in loco-regional advancedbreast cancer by using advanced PET/CT metabolic parameters [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-27-01.

Total lesion glycolysis by 18 F-fluorodeoxyglucose positron emission tomography predicts tumor aggressiveness in patients with extrahepatic bile duct carcinoma.

18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG-PET/CT) parameters are prognostic factors in multiple malignancies. However, the prognostic value in bile duct carcinoma is unclear. We evaluated the impact of metabolic parameters of 18 F-FDG-PET/CT in resectable extrahepatic bile duct carcinoma. We retrospectively reviewed the records of 100 patients with extrahepatic bile duct carcinoma who had undergone 18 F-FDG-PET/CT and subsequent surgical resection between January 2017 and January 2023. We calculated maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) and investigated their prognostic significance. The optimal cutoff values of SUVmax, MTV, and TLG for predicting overall survival (OS) after surgery were 3.88, 3.55 and 7.55, respectively. In multivariate analysis, each metabolic parameter influenced both OS and recurrence-free survival (RFS). TLG showed the lowest Akaike information criteria statistic value, indicating that it had the best ability to predict OS and RFS. High TLG was significantly associated with the number of lymph node metastases and poorly differentiated type. Patients with high TLG showed poorer RFS and OS, which were significantly worse than in those with low TLG. Tumor TLG predicted tumor malignancy potential and could be a useful prognostic predictor for extrahepatic bile duct carcinoma.

Volume-based 18F-FDG PET/CT predicts prognosis and outcome of active surveillance for intra-abdominal desmoid tumor.

Desmoid tumor (DT) is a rare monoclonal, fibroblastic proliferation characterized by a variable and often unpredictable clinical course. Initial active surveillance is recommended by current guideline, and surgery is one of the main therapies for DT. Predicting the prognosis and outcome of active surveillance for intra-abdominal DT is pressing issue. The study included eighteen patients with intra-abdominal DT. Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) were measured. We analyzed their relationship with the outcome of active surveillance, as well as clinical, prognostic, and pathological data. The MTV and TLG of recurrent DT were significantly higher than those of non-recurrent DT (P < 0.001 and P = 0.00, respectively). The ROC curve suggested that the appropriate cutoff values for distinguishing recurrent DT from non-recurrent DT were 760.8 for MTV (sensitivity = 1, specificity = 0.857 and AUC = 0.929), and 1318.4 for TLG (sensitivity = 1, specificity = 0.786, and AUC = 0.911). The cutoff values of MTV and TLG significantly correlated with PFS using the Kaplan-Meier method (P = 0.002 and P = 0.007, respectively). MTV and TLG could distinguish DTs with subsequent progression from stable ones (P = 0.004 and P = 0.004, respectively). The ROC curve suggested that the appropriate cutoff values for distinguishing DTs with subsequent progression from stable ones were 197.1 for MTV (sensitivity = 0.9, specificity = 1, and AUC = 0.900), and 445.45 for TLG (sensitivity = 0.9, specificity = 1, and AUC = 0.900). Volume-based 18F-FDG-PET can predict prognosis of intra-abdominal DT. MTV and TLG can predict the outcome of active surveillance for intra-abdominal DT. MTV and TLG can potentially be predictors of surgical risk and difficulty.

Evaluating therapeutic efficacy of extended shelf-life 90 Y glass microspheres in transarterial radioembolization for colorectal cancer: a quantitative FDG PET/CT analysis.

There is a lack of sufficient evidence regarding the use of extended shelf-life (ExSL) Yttrium-90 ( 90 Y) glass radiomicrospheres in metastatic colorectal cancer (mCRC) patients. We aimed to investigate the efficacy of ExSL 90 Y glass radiomicrospheres with a personalized treatment approach by analyzing 18 F-FDG PET/CT quantitative parameters [metabolic tumor volume (MTV) and total lesion glycolysis (TLG)] separately before and after the treatment. A total of 93 radioembolization sessions involving 77 patients were included. Simplicit 90 Y software was utilized to perform multicompartmental voxel-based dosimetry. Adverse events were recorded using the CTCAE v5.0 criteria. The survival data were recorded in detail. The overall disease control rate was 84.9%, with a median overall survival (OS) of 12.7 months and median progression-free survival (PFS) of 8.3 months. A statistically significant increase in treatment response rate was observed when there was an increase in absorbed tumor dose for pre-treatment unit MTV ( P = 0.005) and TLG ( P = 0.004) values. We didn't observe any additional side effects/vital risks that could be considered clinically significant. Our study has provided evidence on the therapeutic effectiveness and safety in terms of dose-toxicity profile of ExSL 90 Y glass microspheres in a large cohort of mCRC patients. With a personalized treatment approach, the increase in radiation dose absorbed by the tumor has shown a significant contribution to treatment response rate, as indicated by quantitative measurements obtained through 18 F-FDG PET/CT.

Predictive model for epileptogenic tubers from all tubers in patients with tuberous sclerosis complex based on 18F-FDG PET: an 8-year single-centre study

BackgroundMore than half of patients with tuberous sclerosis complex (TSC) suffer from drug-resistant epilepsy (DRE), and resection surgery is the most effective way to control intractable epilepsy. Precise preoperative localization of epileptogenic tubers among all cortical tubers determines the surgical outcomes and patient prognosis. Models for preoperatively predicting epileptogenic tubers using 18F-FDG PET images are still lacking, however. We developed noninvasive predictive models for clinicians to predict the epileptogenic tubers and the outcome (seizure freedom or no seizure freedom) of cortical tubers based on 18F-FDG PET images.MethodsForty-three consecutive TSC patients with DRE were enrolled, and 235 cortical tubers were selected as the training set. Quantitative indices of cortical tubers on 18F-FDG PET were extracted, and logistic regression analysis was performed to select those with the most important predictive capacity. Machine learning models, including logistic regression (LR), linear discriminant analysis (LDA), and artificial neural network (ANN) models, were established based on the selected predictive indices to identify epileptogenic tubers from multiple cortical tubers. A discriminating nomogram was constructed and found to be clinically practical according to decision curve analysis (DCA) and clinical impact curve (CIC). Furthermore, testing sets were created based on new PET images of 32 tubers from 7 patients, and follow-up outcome data from the cortical tubers were collected 1, 3, and 5 years after the operation to verify the reliability of the predictive model. The predictive performance was determined by using receiver operating characteristic (ROC) analysis.ResultsPET quantitative indices including SUVmean, SUVmax, volume, total lesion glycolysis (TLG), third quartile, upper adjacent and standard added metabolism activity (SAM) were associated with the epileptogenic tubers. The SUVmean, SUVmax, volume and TLG values were different between epileptogenic and non-epileptogenic tubers and were associated with the clinical characteristics of epileptogenic tubers. The LR model achieved the better performance in predicting epileptogenic tubers (AUC = 0.7706; 95% CI 0.70–0.83) than the LDA (AUC = 0.7506; 95% CI 0.68–0.82) and ANN models (AUC = 0.7425; 95% CI 0.67–0.82) and also demonstrated good calibration (Hosmer‒Lemeshow goodness-of-fit p value = 0.7). In addition, DCA and CIC confirmed the clinical utility of the nomogram constructed to predict epileptogenic tubers based on quantitative indices. Intriguingly, the LR model exhibited good performance in predicting epileptogenic tubers in the testing set (AUC = 0.8502; 95% CI 0.71–0.99) and the long-term outcomes of cortical tubers (1-year outcomes: AUC = 0.7805, 95% CI 0.71–0.85; 3-year outcomes: AUC = 0.8066, 95% CI 0.74–0.87; 5-year outcomes: AUC = 0.8172, 95% CI 0.75–0.87).ConclusionsThe 18F-FDG PET image-based LR model can be used to noninvasively identify epileptogenic tubers and predict the long-term outcomes of cortical tubers in TSC patients.

Analysis of PET-CT Derived Radiomic Biomarkers with Efficacy, Safety, and Expansion of Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed or Refractory Large B-Cell Lymphoma (LBCL)

Introduction In LBCL, the presence of bulky disease is known to be an adverse prognostic factor, indicating poorer outcomes. The ZUMA-1 clinical trial (Neelapu, NEJM 2017) showed that high tumor burden, as measured by the sum of the product of diameters (SPD), was associated with lower durable response after Chimeric Antigen Receptor T-Cell Therapy (CAR T ). Radiomic biomarkers such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG) have been recently studied to assess three-dimensional measurement of tumor activity and metabolic volume in LBCL. There is a paucity of understanding on the impact of radiomic biomarkers on outcomes and CAR T expansion kinetics in LBCL CAR T recipients. We studied the association of these radiomic biomarkers with efficacy, toxicity, and CAR T expansion in this single institution retrospective study of patients with LBCL who received axi-cel. Methods 189 patients with relapsed or refractory LBCL who were treated with axi-cel from 12/2017 to 5/2022 were studied. The closest PET-CT scan to CAR T leukapheresis date was identified for each patient. After excluding cases with unavailable pre-apheresis PET-CT scans, 172 patients were included in the statistical analysis. Two reviewers independently used a semi-automated contouring software (MIM, v. 7.1.2) to measure maximum standardized uptake value (SUV Max), mean SUV, total MTV and TLG values of malignant lesions. CD19 CAR T expansion was measured by real-time flow cytometry with anti-idiotype-FMC63 conjugated to Dylight 65013. Areas under the curve (AUCs) were calculated for CAR T expansion in the 28 days following infusion using the linear trapezoidal method on raw values, and the results were transformed using a base-10 logarithm. Patients were categorized into high and low biomarker groups based on whether their values exceeded or were below the respective median. For univariate analyses, continuous variables were compared using a Mann-Whitney U-test, categorical using a Chi-square test, and time-to-event using a log-rank test. Within a multivariable framework, regressions (linear, logistic, Cox) were fit to control for potential confounders. Results Median duration of follow up was 33 months (IQR: 17.9, 44.7). MTV was highly correlated with TLG (r=0.87). High MTV was associated with bulky disease defined as &amp;gt;10cm (p&amp;lt;0.01), high IPI at apheresis (p&amp;lt;0.04), bridging treatment (p&amp;lt;0.01), pre-lymphodepletion lactate dehydrogenase (p&amp;lt;0.01), and autologous stem cell transplant (p=0.02). Complete response (CR) rate was greater for those in the low MTV group (79.3%) compared to high MTV group (52.3%), (p&amp;lt;0.01), as well as those with high TLG (77.9%) compared to low TLG group (46%), (p&amp;lt;0.01). Low MTV was significantly associated with better progression free survival (PFS) in a univariate analysis (p=0.03); median PFS was 33.5 months (IQR 3.06, 39.55) for low MTV versus 6.1 months (IQR 6.38, NA) for high MTV. Low MTV was also significantly associated with better overall survival (OS) in a univariate analysis (p&amp;lt;0.01); median OS was not reached for the low MTV group but was 31.8 months for the high MTV group (IQR 16.5, NA) (Figure 1). After multivariable regression analysis, PFS was no longer different by MTV biomarker level ( p= 0.07), but OS was still significantly different ( p= 0.01). Neither PFS nor OS were significantly associated with the binary TLG variable. The proportion of cytokine release syndrome (CRS) or immune cell associated neurologic toxicity syndrome (ICANS) of any grade or severe grade ICANS were significantly higher for the high MTV and TLG groups as compared to their respective low groups. Length of stay was significantly longer for those in the high MTV and TLG groups (Table 1). A higher day 14 CAR T cell expansion was seen in the high TLG as compared to the low group (0.89 vs 0.63 cells/μL, p=0.002). However, there was no statistically significant difference in CAR T expansion as measured by AUC between the high and low MTV or TLG cohort. Conclusion Our study demonstrates poor outcomes for efficacy, safety, and healthcare utilization endpoints in patients with high tumor bulk as measured by volumetric tumor assessment on PET-CT. Furthermore, we show a differential peripheral day 14 CAR T expansion with higher expansion seen in patients with higher tumor bulk. Strategies like tumor debulking prior to CAR T therapy and earlier referral in patients with high tumor bulk may improve clinical outcomes.

The relationship between 18F-FDG PET/CT parameters and histopathological-immunohistochemical properties in breast cancer

In this study, it is aimed to determine the correlation between histopathologic-immunohistochemical factors, tumor subtypes and fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) parameters such standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG) in breast cancer (BC). Initial PET/CT examination of 110 histopathologically proven BC patients (age ranging 27-92, mean age 56.18 ± 14.59) were included in this retrospective study. The relationship between histopathological-immunohistochemical factors, tumor subtypes and PET/CT parameters were analyzed by regression analysis. The mean SUV max value of 110 breast tumors was 7.73 ± 5.62 (range 1.4 - 34.15). Histological subtypes were; invasive ductal carcinoma (n:94, 85.5%), invasive lobular carcinoma (n=6, 5.5%) and other types (n=10, 9.1%). The distribution of BC subtypes was as follows; Luminal A (Lum A) (n=38; 34.5%), Luminal B (Lum B) (n=56; 50.9%), HER2-positive (n=3; 2.7%) and Triple Negative (TN) (n=13; 11.8%). Univariate regression analysis revealed significantly higher SUV max values in ductal carcinomas than lobular carcinomas (p=0.03). SUVmax values of the Lum B, HER2 positive and TN groups were higher than Lum A group (p=0.03, p&lt;0.001, p&lt;0.001 respectively). Univariate regression analyses also showed that the MTV and TLG values of TN group were significantly higher than Lum A group (p=0.011, p=0.007, respectively). In multivariate regression analyses, no significant difference was observed in above mentioned groups. MTV, TLG and SUVmax values significantly correlated with histopathological-immunohistochemical factors and tumor subtypes in BC. So that, these parameters can be used to predict the tumors’ behavior.

Application of an artificial intelligence-based tool in [18F]FDG PET/CT for the assessment of bone marrow involvement in multiple myeloma

Purpose[18F]FDG PET/CT is an imaging modality of high performance in multiple myeloma (MM). Nevertheless, the inter-observer reproducibility in PET/CT scan interpretation may be hampered by the different patterns of bone marrow (BM) infiltration in the disease. Although many approaches have been recently developed to address the issue of standardization, none can yet be considered a standard method in the interpretation of PET/CT. We herein aim to validate a novel three-dimensional deep learning-based tool on PET/CT images for automated assessment of the intensity of BM metabolism in MM patients.Materials and methodsWhole-body [18F]FDG PET/CT scans of 35 consecutive, previously untreated MM patients were studied. All patients were investigated in the context of an open-label, multicenter, randomized, active-controlled, phase 3 trial (GMMG-HD7). Qualitative (visual) analysis classified the PET/CT scans into three groups based on the presence and number of focal [18F]FDG-avid lesions as well as the degree of diffuse [18F]FDG uptake in the BM. The proposed automated method for BM metabolism assessment is based on an initial CT-based segmentation of the skeleton, its transfer to the SUV PET images, the subsequent application of different SUV thresholds, and refinement of the resulting regions using postprocessing. In the present analysis, six different SUV thresholds (Approaches 1–6) were applied for the definition of pathological tracer uptake in the skeleton [Approach 1: liver SUVmedian × 1.1 (axial skeleton), gluteal muscles SUVmedian × 4 (extremities). Approach 2: liver SUVmedian × 1.5 (axial skeleton), gluteal muscles SUVmedian × 4 (extremities). Approach 3: liver SUVmedian × 2 (axial skeleton), gluteal muscles SUVmedian × 4 (extremities). Approach 4: ≥ 2.5. Approach 5: ≥ 2.5 (axial skeleton), ≥ 2.0 (extremities). Approach 6: SUVmax liver]. Using the resulting masks, subsequent calculations of the whole-body metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in each patient were performed. A correlation analysis was performed between the automated PET values and the results of the visual PET/CT analysis as well as the histopathological, cytogenetical, and clinical data of the patients.ResultsBM segmentation and calculation of MTV and TLG after the application of the deep learning tool were feasible in all patients. A significant positive correlation (p < 0.05) was observed between the results of the visual analysis of the PET/CT scans for the three patient groups and the MTV and TLG values after the employment of all six [18F]FDG uptake thresholds. In addition, there were significant differences between the three patient groups with regard to their MTV and TLG values for all applied thresholds of pathological tracer uptake. Furthermore, we could demonstrate a significant, moderate, positive correlation of BM plasma cell infiltration and plasma levels of β2-microglobulin with the automated quantitative PET/CT parameters MTV and TLG after utilization of Approaches 1, 2, 4, and 5.ConclusionsThe automated, volumetric, whole-body PET/CT assessment of the BM metabolic activity in MM is feasible with the herein applied method and correlates with clinically relevant parameters in the disease. This methodology offers a potentially reliable tool in the direction of optimization and standardization of PET/CT interpretation in MM. Based on the present promising findings, the deep learning-based approach will be further evaluated in future prospective studies with larger patient cohorts.

High values of baseline volumetric PET biomarkers in classical Hodgkin's lymphoma as predictors of unfavourable prognosis

Purpose: To analyse the prognostic value of the initial volumetric PET biomarkers – the total metabolic tumor volume (MTV) and the total lesion glycolysis (TLG) – in classic Hodgkin's lymphoma (cHL) and determine their optimal threshold values for prognosis.Material and methods. This retrospective study included 62 cHL patients with different stages who underwent staging with 18F-FGD PET/CT. The follow-up period was from 6 to 61 months after the baseline PET/CT, 41 patients remained in remission, 10 patients had refractory course, 11 relapsed. The examinations were processed with automatic (multi-foci segmentation – MFS) method to obtain MTV and TLG using two fixed absolute thresholds (SUVmax ≥ 2.5 and SUVmax ≥ 4.0) and one relative threshold (41% of SUVmax).Results. In subgroups with disease remission (n = 41) and refractory course or relapse (n = 21), statistically significant differences between MTV and TLG with the two thresholds were found – SUVmax ≥ 2.5 and 41% of SUVmax (p &lt; 0.05). When using threshold of SUVmax ≥ 4.0 statistically differences between the mean of MTV and TLG were no detected.Univariate analysis revealed correlation between progression-free survival and volumetric PET biomarkers (MTV and TLG) with three thresholds (SUVmax ≥ 2.5, SUVmax ≥ 4.0, and 41% of SUVmax).Conclusion. In cHL high values of initial volumetric PET biomarkers – MTV and TLG – calculated with three thresholds (SUVmax ≥ 2.5, SUVmax ≥ 4.0, and 41% of SUVmax) are associated with unfavourable prognosis – a high probability of refractory disease course or relapse.The optimal prognostic thresholds values of MTV and TLG in the analysed group were determined respectively: SUVmax ≥ 2.5 – 204 cm3 and 961, at 41% of SUVmax – 105 cm3 and 620.

Impact of tumour region of interest delineation method for mid-treatment FDG-PET response prediction in head and neck squamous cell carcinoma undergoing radiotherapy.

The aim of this study was to evaluate the impact of tumour region of interest (ROI) delineation method on mid-treatment 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) response prediction in mucosal head and neck squamous cell carcinoma during radiotherapy. A total of 52 patients undergoing definitive radiotherapy with or without systemic therapy from two prospective imaging biomarker studies were analysed. FDG-PET was performed at baseline and during radiotherapy (week 3). Primary tumour was delineated using a fixed SUV 2.5 threshold (MTV2.5), relative threshold (MTV40%) and a gradient based segmentation method (PET Edge). PET parameters SUVmax, SUVmean, metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were calculated using different ROI methods. Absolute and relative change (∆) in PET parameters were correlated to 2-year locoregional recurrence. Strength of correlation was tested using receiver operator characteristic analysis using area under the curve (AUC). Response was categorized using optimal cut-off (OC) values. Correlation and agreement between different ROI methods was determined using Bland-Altman analysis. A significant difference in SUVmean, MTV and TLG values were noted between ROI delineation methods. When measuring relative change at week 3, a greater agreement was seen between PET Edge and MTV2.5 methods with average difference in ∆SUVmax, ∆SUVmean, ∆MTV and ∆TLG of 0.0%, 3.6%, 10.3% and 13.6% respectively. A total of 12 patients (22.2%) experienced locoregional recurrence. ∆MTV using PET Edge was the best predictor of locoregional recurrence (AUC =0.761, 95% CI: 0.573-0.948, P=0.001; OC ∆>50%). The corresponding 2-year locoregional recurrence rate was 7% vs. 35%, P=0.001. Our findings suggest that it is preferable to use gradient based method to assess volumetric tumour response during radiotherapy and offers advantage in predicting treatment outcomes compared with threshold-based methods. This finding requires further validation and can assist in future response-adaptive clinical trials.

Retrospective Analysis of the Predictive Value of 18F-FDG PET/CT Metabolic Parameters for PD-L1 Expression in Cervical Cancer

Immunotherapy targeting PD-1/PD-L1 has been proven to be effective for cervical cancer treatment. To explore non-invasive examinations for assessing the PD-L1 status in cervical cancer, we performed a retrospective study to investigate the predictive value of 18F-FDG PET/CT. The correlations between PD-L1 expression, clinicopathological characteristics and 18F-FDG PET/CT metabolic parameters were evaluated in 74 cervical cancer patients. The clinicopathological characteristics included age, histologic type, tumor differentiation, FIGO stage and tumor size. The metabolic parameters included maximum standard uptake (SUVmax), mean standard uptake (SUVmean), total lesion glycolysis (TLG) and tumor metabolic volume (MTV). In univariate analysis, SUVmax, SUVmean, TLG, tumor size and tumor differentiation were obviously associated with PD-L1 status. SUVmax (rs = 0.42) and SUVmean (rs = 0.40) were moderately positively correlated with the combined positive score (CPS) for PD-L1 in Spearman correlation analysis. The results of multivariable analysis showed that the higher SUVmax (odds ratio = 2.849) and the lower degree of differentiation (Odds Ratio = 0.168), the greater probability of being PD-L1 positive. The ROC curve analysis demonstrated that when the cut-off values of SUVmax, SUVmean and TLG were 10.45, 6.75 and 143.4, respectively, the highest accuracy for predicting PD-L1 expression was 77.0%, 71.6% and 62.2%, respectively. The comprehensive predictive ability of PD-L1 expression, assessed by combining SUVmax with tumor differentiation, showed that the PD-L1-negative rate was 100% in the low probability group, whereas the PD-L1-positive rate was 84.6% in the high probability group. In addition, we also found that the H-score of HIF-1α was moderately positively correlated with PD-L1 CPS (rs = 0.51). The SUVmax and differentiation of the primary lesion were the optimum predictors for PD-L1 expression in cervical cancer. There was a great potential for 18F-FDG PET/CT in predicting PD-L1 status and selecting cervical cancer candidates for PD1/PD-L1 immune checkpoint therapy.

Evaluación de la supervivencia de los pacientes con cáncer de recto metastásico mediante parámetros radiómicos y volumétricos de la PET/TC con [18F]FDG de estadificación

ObjectiveThe aim of this study was to predict the prognosis in patients with metastatic rectal cancer (mRC) by obtaining a model with machine learning (ML) algorithms through volumetric and radiomic data obtained from baseline 18-Fluorine Fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) images. MethodsSixty-two patients with mRC who underwent [18F]FDG PET/CT imaging for staging between January 2015 and January 2021 were evaluated using LIFEx software. The volume of interest (VOI) of the primary tumor was generated and volumetric and textural features were obtained from this VOI. In addition, the total metabolic tumor volume (tMTV) and total lesion glycolysis (TLG) values of tumor foci in the whole body were evaluated. Clinical and radiomic data were evaluated with ML algorithms to create a model that predicts survival. Significant associations between these features and 1- and 2-year survival were investigated. ResultsThe random forest algorithm was the most successful in predicting 2-year survival (AUC: 0.843, precision-recall curve: 0.822 and Matthew's correlation coefficient: 0.583). The model obtained with this algorithm was able to predict 49 patients with 79.03% accuracy. While tMTV and TLG values were successful in predicting 1-year survival (p: 0.002 and 0.007, respectively), texture characteristics of the primary tumor did not show a significant relationship with 1-year survival. ConclusionsIn addition to the important role of [18F]FDG PET/CT in staging patients with mRC, this study shows that it is possible to predict survival with ML methods, with parameters obtained using texture analysis of the primary tumor and whole body volumetric parameters.

18FDG PET/CT Parameters for the Prediction of CAR T-Cell Therapy Response among Patients with Large B-Cell Lymphoma

<h3>Purpose/Objective(s)</h3> To define the prognostic value of quantitative positron emission tomography/computed tomography (PET/CT) parameters in diffuse large B-cell lymphoma (DLBCL) patients undergoing CAR T-cell therapy. <h3>Materials/Methods</h3> Sixty-three patients who had PET-CT scans done pre-CAR T infusion were retrospectively identified and analyzed in a single institution database of DLBCL patients treated with commercially available CD19-targeted CAR T-cell therapy (axi-cel, tisa-cel). The predictive and prognostic value of low vs. high metabolic tumor volume (MTV), total lesion glycolysis (TLG), and SUV were analyzed with cutoff values determined by the sample mean for MTV and TLG and mode for SUV. The response evaluation was conducted based on the post-CAR T best overall response, which was defined as the lowest disease burden measured on the PET scan at any time after CAR T-cell therapy. Univariate analysis was conducted using logistic regression, while the multivariate analysis was performed using logistic regression and Cox proportional hazards models, controlling for age ≥60, gender, CAR T product, and receiving bridging therapy. <h3>Results</h3> The median follow-up was 10.7 months (range, 0.6 - 46.5 months). The best objective overall response (complete response-CR and partial response) and CR rates post-CAR T were 78% (n=49) and 54% (n=34), respectively. On univariate analysis, low pre-CAR T TLG and MTV were predictive of CR post-CAR T (OR=4.7, p=0.01, OR=8.03, p=0.001, respectively). Patients with high pre-CAR T TLG or MTV had an increased risk of mortality (OR=3.6, p=0.03, OR=4.04, p=0.02), and a high pre-CAR T TLG was associated with a non-significant trend of increased grade 3-4 neurological events (OR=2.8, p=0.2). There was also a trend to shorter OS among patients with high SUVmax pre-CAR T (8.3 months vs. 24.4 months, p=0.3). On multivariate analysis, bulky disease (≥5 cm) (HR=6.08, 95% CI: 2.6-14.2, p=< 0.001), high MTV (HR=2.4, 95% CI: 1.13-4.9, p=0.022), and high TLG (HR=2.35, 95% CI: 1.1-5.0, p=0.026) were significantly associated with inferior OS. <h3>Conclusion</h3> High pre-CAR T MTV and TLG values are significantly associated with inferior CR and OS rates and a trend toward higher risk of severe neurotoxicity among patients with LBCL treated with CAR T-cell therapy. Bulky disease (≥ 5 cm) is associated with significantly inferior OS. These data suggest that there may be a role for pre- CAR T radiation therapy targeting bulky site(s) with high FDG avidity, regardless of symptoms, thereby reducing disease burden prior to CAR-T cell therapy, which may lead to improved efficacy and reduced CAR T-related adverse events.

The prognostic relationship of 18F-FDG PET/CT metabolic and volumetric parameters in metastatic ALK + NSCLC.

The aim of this study is to determine the role of metabolic and volumetric parameters obtained from 18Fluorine-Fluorodeoxyglucose PET/computed tomography (18F-FDG PET/CT) imaging on progression-free survival (PFS) and overall survival (OS) in patients with advanced nonsquamous cell lung carcinoma (NSCLC) with anaplastic lymphoma kinase (ALK) rearrangement. Pre and post-treatment PET/CT images of the ALK + NSCLC patients between January 2015 and July 2020 were evaluated. The highest standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) values were obtained from pre-tyrosine kinase inhibitor (TKI) basal PET/CT (PETpre) and post-TKI PET/CT (PETpost) images. Total MTV (tMTV) and total TLG (tTLG) values were calculated by summing MTV and TLG values in all tumor foci. The change (Δ) in pSUVmax, pMTV, pTLG, tMTV and tTLG before and after treatment was calculated.The relationship of these parameters with OS and PFS was analyzed. tTLGpre, tMTVpre, pTLGpre, pMTVpre, ∆SUVmax, ∆tMTV and ∆tTLG values were found to be associated with OS; ∆tMTV, ∆tTLG, tTLGpre, tMTVpre, pTLGpre and pMTVpre were associated with PFS. The cutoff values in both predicting OS and PFS were calculated as -31.6 and 391.1 for ∆tMTV and tTLGpre, respectively. In Cox regression analysis, ∆tMTV and stage for OS and ∆tMTV and tTLGpre for PFS were obtained as prognostic factors. Metabolic and volumetric parameters, especially TLG values in the whole body before treatment and change in whole body MTV value, obtained from PET/CT may be useful in predicting prognosis and determining treatment strategies for patients with advanced ALK + NSCLC.

Volumetric Evaluation of Staging 18F-FDG PET/CT Images in Patients with Esophageal Cancer.

Objectives:The aim of this study was to evaluate the metastatic potential of primary tumor and survival in esophageal cancer (EC) patients by using metabolic tumor volume (MTV) and total lesion glycolysis (TLG) from the staging 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) images. Another aim is to determine a tumor volume-based cut-off value to predict long-term survival.Methods:Medical records of EC patients were retrospectively evaluated. Sixty-two patients with staging 18F-FDG PET/CT and at least five years of follow-up were included in the study. The region of interest to the primary tumor and all metastatic sites was created and MTV and TLG values of the primary tumor (MTVp, TLGp) and total tumor volume (MTVt and TLGt) values were obtained. The relationship between the obtained MTV and TLG values and short-time (one-year) and long time (five-year) survival was investigated.Results:Significant factors on survival were determined as lymph node or distant metastasis (p=0.024, 0.008, respectively) at the staging PET/CT. A significant relationship between volumetric parameters of the primary tumor and total tumor burden (MTVp, TLGp, MTVwb and TLGwb) between survivors and non-survivors for one-year and five-year was detected. In receiver operating characteristics analysis, the most significant volumetric parameter was MTVwb, with area under curve 0.771 in estimated five-year survival. The best cut-off value was detected as 36.1 mL with 78% sensitivity and 75% specificity for MTVwb in determining long-term survivors.Conclusion:Tumor burden in 18F-FDG PET/CT images at the time of staging of patients with EC will contribute to the prediction of long-term survivors.

Application of diffusion kurtosis imaging and 18F-FDG PET in evaluating the subtype, stage and proliferation status of non-small cell lung cancer.

BackgroundLung cancer has become one of the deadliest tumors in the world. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for approximately 80%-85% of all lung cancer cases. This study aimed to investigate the value of diffusion kurtosis imaging (DKI), diffusion-weighted imaging (DWI) and 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) in differentiating squamous cell carcinoma (SCC) and adenocarcinoma (AC) and to evaluate the correlation of each parameter with stage and proliferative status Ki-67.MethodsSeventy-seven patients with lung lesions were prospectively scanned by hybrid 3.0-T chest 18F-FDG PET/MR. Mean kurtosis (MK), mean diffusivity (MD), apparent diffusion coefficient (ADC), maximum standard uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured. The independent samples t test or Mann–Whitney U test was used to compare and analyze the differences in each parameter of SCC and AC. The diagnostic efficacy was evaluated by receiver operating characteristic (ROC) curve analysis and compared with the DeLong test. A logistic regression analysis was used for the evaluation of independent predictors. Bootstrapping (1000 samples) was performed to establish a control model, and calibration curves and ROC curves were used to validate its performance. Pearson’s correlation coefficient and Spearman’s correlation coefficient were calculated for correlation analysis.ResultsThe MK and ADC values of the AC group were significantly higher than those of the SCC group (all P< 0.05), and the SUVmax, MTV, and TLG values of the SCC group were significantly higher than those of the AC group (all P<0.05). There was no significant difference in the MD value between the two groups. Moreover, MK, SUVmax, TLG and MTV were independent predictors of the NSCLC subtype, and the combination of these parameters had an optimal diagnostic efficacy (AUC, 0.876; sensitivity, 86.27%; specificity, 80.77%), which was significantly better than that of MK (AUC = 0.758, z = 2.554, P = 0.011), ADC (AUC = 0.679, z = 2.322, P = 0.020), SUVmax (AUC = 0.740, z = 2.584, P = 0.010), MTV (AUC = 0.715, z = 2.530, P = 0.011) or TLG (AUC = 0.716, z = 2.799, P = 0.005). The ROC curve showed that the validation model had high accuracy in identifying AC and SCC (AUC, 0.844; 95% CI, 0.785-0.885);. The SUVmax value was weakly positively correlated with the Ki-67 index (r = 0.340, P< 0.05), the ADC and MD values were weakly negatively correlated with the Ki-67 index (r = -0.256, -0.282, P< 0.05), and the MTV and TLG values were weakly positively correlated with NSCLC stage (r = 0.342, 0.337, P< 0.05).ConclusionDKI, DWI and 18F-FDG PET are all effective methods for assessing the NSCLC subtype, and some parameters are correlated with stage and proliferation status.

Prognostic value of MTV and TLG of 18 F-FDG PET in patients with head and neck squamous cell carcinoma: A meta-analysis.

Background:The current systematic review and meta-analysis explored the value of metabolic tumor volume (MTV) as well as total lesion glycolysis (TLG) in predicting the prognosis of head and neck squamous cell carcinoma (HNSCC) using 18 F-FDG PET parameters.Methods:This work identified relevant studies in the English language by searching several electronic databases, like Cochrane Library, EMBASE, and PubMed. In addition, pooled hazard ratios (HRs) were also calculated to analyze whether MTV and TLG were significant in predicting prognosis.Results:The present study included 15 primary studies involving HNSCC cases. As for the elevated TLG, it attained the pooled HR of 1.85 (95% confidence interval [CI], 1.16–2.94; P = .000; I2 = 78.3%) in predicting overall survival (OS), whereas that for elevated MTV was1.22 (95%CI, 1.09–1.36; P = .000; I2 = 82.4%). Besides, for elevated MTV, it attained the pooled HR of 1.34 (95%CI, 1.15–1.56, P = .000; I2 = 86.0%) in predicting disease-free survival (DFS); while the elevated TLG was related to DFS. Sensitivity analysis confirmed that our results are reliable. As for MTV, the ROC-stratified subgroups for DFS and multivariate analyses-stratified subgroups for OS showed statistically significant differences, with no obvious heterogeneities across different studies. For TLG, other methods-stratified subgroups for OS showed statistically significant differences, with no obvious heterogeneity across different studies.Conclusion:This work indicated that PET/CT is of predictive significance across HNSCC cases. Although the included articles used different methods and recruited HNSCC cases with high clinical heterogeneity; however, our findings confirmed that an elevated MTV can predict the increased risk of side reactions or even death among HNSCC cases and that an elevated TLG can predict a higher death risk.

F18]FDG PET/CT-Derived Metabolic and Volumetric Biomarkers Can Predict Response to Treatment in Locally Advanced Cervical Cancer Patients.

Simple SummaryCarcinoma of the uterine cervix is one of the most common and severe malignancies in women. Up to 40% of locally advanced cervical cancer patients treated with definitive chemoradiation therapy will not respond or will develop disease recurrence. The aim of this retrospective study was to evaluate the relationship between quantitative metabolic and volumetric parameters extracted from FDG PET/CT imaging data and the response rate to definitive chemoradiation therapy in this group of patients. FDG PET/CT studies of 90 cervical cancer patients were analyzed, and it was found that quantitative metabolic and volumetric parameters such as SUVmax, SUVmean, MTV, and TLG are higher in locally advanced cervical cancer patients who will not respond to definitive chemoradiation therapy. Specifically, in patients who are not metastatic at staging, MTV and TLG values can serve as a predictor for treatment response and thus may alter treatment strategy.(1) Purpose: Current study aimed at evaluating the relationship between quantitative metabolic and volumetric FDG PET/CT parameters and the response to definitive chemoradiation therapy in locally advanced cervical cancer patients; (2) Methods: Ninety newly diagnosed locally advanced cervical cancer patients (FIGO IB2-IVA) were investigated. All patients underwent PET/CT at staging and after treatment. Metabolic and volumetric parameters, including SUVmax, SUVmean, Total Lesion Glycolysis (TLG), and Metabolic Tumor Volume (MTV) of the primary tumor and metastatic lymph nodes were measured and compared between patients with and without complete metabolic response (CMR). A similar analysis was performed in a subgroup of FIGO IB2-IIB patients; (3) Results: SUVmax and SUVmean of the primary tumor as well as those of metastatic lymph nodes, MTV, and TLG were found to be significantly different between CMR and non-CMR patients. In a subgroup of patients with FIGO IB2-IIB disease, MTV and TLG identified women who will achieve CMR with a threshold of 31.1 cm3 for MTV and 217.8 for TLG; (4) Conclusions: PET/CT-derived quantitative metabolic and volumetric parameters are higher in locally advanced cervical cancer patients who will not respond to definitive chemoradiation therapy. Specifically, in patients who are not metastatic at staging, MTV and TLG values can serve as a predictor for treatment response and thus may alter treatment strategy.

Baseline 18 F-FDG PET/CT May Portend the Prognosis of Patients With Waldenström Macroglobulinemia/Lymphoplasmacytic Lymphoma After First-Line Treatment.

The outcome of patients with Waldenström macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) is variable. We aim to study if baseline 18 F-FDG PET/CT has some prognostic significance in WM/LPL. Thirty-three patients with newly diagnosed WM/LPL who underwent baseline 18 F-FDG PET/CT and received active treatment thereafter were recruited in this retrospective study. Semiquantitative indices of baseline 18 F-FDG PET/CT were measured as total lesion glycolysis (TLG), metabolic tumor volume (MTV), and SUV max . The patients were followed up for at least 3 years or until reaching the endpoint, which were defined as progression-free survival (PFS) and the time to next treatment (TTNT). The overall response rate of the first-line treatment in the recruited patients was 84.8% (28/33). The 3-year PFS and overall survival rates were 56.3% and 89.3%, respectively. Patients with PFS <36 months and TTNT <36 months showed TLG and MTV significantly higher than those with PFS ≥36 months and TTNT ≥36 months ( P < 0.05). SUV max in patients with PFS <36 months was significantly higher than those with PFS ≥36 months ( P = 0.033). Receiver operating characteristic analysis demonstrated that cutoff values of TLG >291.28 SUVbw * mL, MTV >108.78 mL, and SUV max >3.16 were optimal for predicting PFS <36 months. Kaplan-Meier analysis showed that TLG >291.28 SUVbw * mL and MTV >108.78 mL were predictive for shorter PFS ( P = 0.003) and TTNT ( P = 0.002). In multivariate analysis, TLG >291.28 SUVbw * mL and MTV >108.78 mL were independent predictors for shorter PFS (hazard ratio, 3.06; 95% confidence interval, 1.09-8.57; P = 0.033) and TTNT (hazard ratio, 10.01; 95% confidence interval, 2.56-39.22; P = 0.001). The metabolic indices of TLG and MTV in baseline 18 F-FDG PET/CT were independent prognostic factors to predict PFS and TTNT in patients with WM/LPL.

Improving the imaging diagnostic strategy for pulmonary artery masses based on 18F-FDG PET/CT integrated with CTPA.

To evaluate the diagnostic accuracy of computed tomography pulmonary angiography (CTPA) and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for pulmonary artery (PA) masses. Of 2889 patients with PA filling defects of PA on CTPA, 79 consecutive patients suspicious for PA malignancy who subsequently underwent 18F-FDG PET/CT were enrolled. All masses were diagnosed on the basis of pathological findings or clinical imaging follow-up. For each mass, morphological CT signs, standardized uptake value (SUVmax and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on 18F-FDG PET/CT were used as diagnostic markers. Expansive growth, irregular margin, invasion, CT contrast uptake, and wall eclipse sign were strongly associated with the malignant nature of masses. The coexistence of at least 5 CT signs perfectly identified malignant masses, whereas the detection of no more than 4 CT signs did not accurately discriminate between the natures of masses. Mean SUVmax, SUVmean, MTV, and TLG values were significantly higher in malignant masses compared to those in benign masses. The diagnostic accuracy of 18F-FDG PET/CT parameters (SUV, MTV, and TLG) was excellent in detecting malignant masses. Among patients with 3 or 4 pathological CT signs, SUVmax > 3.4 significantly increased the identification of malignancies. CTPA is a useful imaging modality for diagnosing PA masses, especially when at least 5 abnormal CT signs are identified. Similarly, 18F-FDG PET/CT accurately identified malignant masses and provided additional valuable information on diagnostic uncertainties after CTPA.