Total Glycolytic Activity Research Articles

18F-FDG-PET/CT Uptake by Noncancerous Lung as a Predictor of Interstitial Lung Disease Induced by Immune Checkpoint Inhibitors

Rationale and objectiveImmune checkpoint inhibitors (ICIs) have improved lung cancer prognosis; however, ICI-related interstitial lung disease (ILD) is fatal and difficult to predict. Herein, we hypothesized that pre-existing lung inflammation on radiological imaging can be a potential risk factor for ILD onset. Therefore, we investigated the association between high uptake in noncancerous lungs (NCL) on 18F- FDG-PET/CT and ICI-ILD in lung cancer. MethodsPatients with primary lung cancer who underwent FDG-PET/CT within three months prior to ICI therapy were retrospectively included. Artificial intelligence was utilized for extracting the NCL regions (background lung) from the lung contralateral to the primary tumor. FDG uptake by the NCL was assessed via the SUVmax (NCL-SUVmax), SUVmean (NCL-SUVmean), and total glycolytic activity (NCL-TGA=NCL-SUVmean × NCL volume [ml]). NCL-SUVmean and NCL-TGA were calculated using the following four SUV thresholds: 0.5, 1.0, 1.5, and 2.0. ResultsOf the 165 patients, 28 (17%) developed ILD. Univariate analysis showed that high values of NCL-SUVmax, NCL-SUVmean2.0 (SUV threshold=2.0), and NCL-TGA1.0 (SUV threshold=1.0) were significantly associated with ILD onset (all p=0.003). Multivariate analysis adjusted for age, tumor FDG uptake, and pre-existing interstitial lung abnormalities revealed that a high NCL-TGA1.0 (≥149.45) was independently associated with ILD onset (odds ratio, 6.588; p=0.002). Two-year cumulative incidence of ILD was significantly higher in the high NCL-TGA1.0 group than in the low group (58.4% vs. 14.4%; p<0.001). ConclusionsHigh uptake of NCL on FDG-PET/CT is correlated with ICI-ILD development, which could serve as a risk stratification tool before ICI therapy in primary lung cancer.

Role of serial fluorodeoxyglucose positron emission tomography-computed tomography (18FDG-PET-CT) in assessing treatment response in treatment naïve chronic pulmonary aspergillosis subjects.

The role of 2-deoxy-2-18(F) fluoro-D-glucose (FDG) positron emission tomography (PET)-computed tomography (CT) in assessing treatment response in chronic pulmonary aspergillosis (CPA) remains to be determined. To compare changes in FDG-PET/CT parameters in CPA subjects with treatment success or failure. We treated consecutive treatment-naïve CPA subjects with six months of oral itraconazole. We performed PET-CT at baseline and six months. A multi-disciplinary team categorized response as treatment success or failure. We recorded the maximum standardised uptake value (SUVmax), SUVpeak, and total glycolytic activity (TLG). After treatment, FDG uptake similar to the background uptake or ≥13 units decline in Z-score was considered a complete metabolic response (CMR). A >25%, >30%, and > 45% decline in SUVmax, SUVpeak, and TLG was labelled as a partial metabolic response (PMR). A >30%, >30%, or >75% increase in the SUVmax, SUVpeak, and TLG represented progressive metabolic disease. We included 94 CPA subjects (63 males) with a mean age of 46.2 years. A follow-up PET-CT was performed on 77 subjects. We recorded treatment success and failure in 43 and 34 subjects. The median SUVmax at baseline was 6.7, which significantly reduced with treatment. CMR was seen in 18.6% of those with treatment success and none with treatment failure. A higher proportion of subjects with treatment success achieved PMR. 19% of the subjects with treatment success had progressive metabolic disease. FGD-PET/CT demonstrated metabolic activity in all CPA subjects. Most PET-CT parameters improved with treatment; however, one-fifth of the subjects were misclassified on PET-CT.

Effect of Immunosuppressive Therapy and Biopsy Status in Monitoring Therapy Response in Suspected Cardiac Sarcoidosis

BackgroundPatients with suspected cardiac sarcoidosis frequently undergo fluorodeoxyglucose (FDG)–positron emission tomography (PET)/computed tomography (CT) imaging to assess disease activity at baseline and after treatment initiation. ObjectivesThis study investigated the effect of immunosuppressive therapy and biopsy status to achieve complete treatment response (CTR), partial treatment response (PTR), or no response (NR) on myocardial FDG-PET/CT. MethodsThis study analyzed 83 patients with suspected cardiac sarcoidosis (aged 53 ± 1.8 years, 71% were male, 69% were White, 61% had a history of biopsy-confirmed sarcoidosis) who were treatment naive, had evidence of myocardial FDG at baseline, and underwent repeat PET imaging after treatment initiation. CTR was graded visually, and PTR/NR were measured both visually and quantitatively using the total glycolytic activity. Patients were also evaluated for the occurrence of death, sustained ventricular arrhythmias, and heart failure admissions. ResultsOverall, 59 patients (71%) achieved CTR/PTR (30%/41%) at follow-up scan (P = 0.04). Total glycolytic activity and visual estimate of PTR/NR had excellent agreement (κ = 0.86 [95% CI: 0.72-0.99]; P < 0.0001). In patients receiving prednisone only, the highest rates of CTR/PTR were observed in patients initiated on moderate or high dose (P < 0.01). In a regression model, moderate prednisone start dose (P = 0.03) was more strongly associated with achieving CTR/PTR than was high prednisone start dose. However, the latter patients were tapered faster between start dose and follow-up scan (P < 0.01). After a median follow-up of 4.7 (IQR: 3.1-7.8) years, patients who were biopsy-proven (vs non-biopsy-proven; P = 0.029) and with preserved left ventricular function (P = 002) were less likely to experience major adverse cardiac events. Outcomes based on treatment response status (CTR vs PTR vs NR; P = 0.23) were not significantly different. ConclusionsAmong patients with suspected sarcoidosis and evidence of myocardial inflammation, treatment response by serial FDG-PET was variable, but a favorable response was more common when using moderate-to-high intensity prednisone dose. Biopsy-proven individuals and those with preserved systolic function were less likely to experience adverse outcomes during follow-up.

The Significance of FDG PET/CT-Derived Parameters in Determining Prognosis of Cases with Pancreatic Adenocarcinoma: A Prospective Study.

Background and objectives: Pancreatic adenocarcinoma represents one of the common malignancies with a relatively poor prognosis. However, early detection of this type of cancer may prove to be curable. Recent advancements in the radiological techniques might represent a hope for the early diagnosis and prediction of prognosis of pancreatic adenocarcinoma. This study aimed to assess the prognostic value of the primary tumor volumetric parameters obtained from FDG PET/CT first stage for the overall survival (OS) and progression-free survival (PFS) of patients with pancreatic adenocarcinoma and to explore the possible correlation between serum matrix metalloproteinase-2 (MMP-2) and the patients’ characteristics. Methods: Fifty patients with pancreatic adenocarcinoma were subjected to FDG PET/CT scan. The SUVpeak, SUVmax, and the metabolic tumor volume (MTV) were determined, as well as the SUVmean of the liver. Moreover, serum levels of MMP-2 were assessed. Follow-up of the patients was carried out for sixty months with determination of PFS and OS. Results: Peak SUV ≥ 3.9 was significantly correlated with the primary pancreatic lesions’ mean total glycolytic activity of >92 g, and MTV and was directly correlated with mortality. There was a positive correlation between peak SUV ≥ 3.9 and 50% SUVmax threshold > 82. Moreover, there was significant correlation between the total glycolytic activity and the studied clinicopathologic factors, except the age and sex of the patients and ECOG performance status. In addition, FDG uptake and the tumor glycolytic activity were substantially linked with a shorter PFS. Similarly, a strong correlation was found between MTV and PFS. Serum MMP-2 levels showed a significant relationship with the performance status, tumor stage, SUVmax threshold, and the glycolytic activity. Conclusions: Peak SUV, main lesion SUVmax, serum MMP-2, and the tumor glycolytic activity are good predictors of PFS of patients with pancreatic adenocarcinoma.

Quantitative 18F-FDG PET-CT scan characteristics correlate with tuberculosis treatment response

BackgroundThere is a growing interest in the use of F-18 FDG PET-CT to monitor tuberculosis (TB) treatment response. Tuberculosis lung lesions are often complex and diffuse, with dynamic changes during treatment and persisting metabolic activity after apparent clinical cure. This poses a challenge in quantifying scan-based markers of burden of disease and disease activity. We used semi-automated, whole lung quantification of lung lesions to analyse serial FDG PET-CT scans from the Catalysis TB Treatment Response Cohort to identify characteristics that best correlated with clinical and microbiological outcomes.ResultsQuantified scan metrics were already associated with clinical outcomes at diagnosis and 1 month after treatment, with further improved accuracy to differentiate clinical outcomes after standard treatment duration (month 6). A high cavity volume showed the strongest association with a risk of treatment failure (AUC 0.81 to predict failure at diagnosis), while a suboptimal reduction of the total glycolytic activity in lung lesions during treatment had the strongest association with recurrent disease (AUC 0.8 to predict pooled unfavourable outcomes). During the first year after TB treatment lesion burden reduced; but for many patients, there were continued dynamic changes of individual lesions.ConclusionsQuantification of FDG PET-CT images better characterised TB treatment outcomes than qualitative scan patterns and robustly measured the burden of disease. In future, validated metrics may be used to stratify patients and help evaluate the effectiveness of TB treatment modalities.

Lung Injury on Antiretroviral Therapy in Adults With Human Immunodeficiency Virus/Tuberculosis.

Immune restoration on antiretroviral therapy (ART) can drive inflammation in people living with human immunodeficiency virus (HIV) who have pulmonary tuberculosis (TB), but its effects on the lungs have not been assessed. We evaluated associations between pulmonary inflammation, recovery of pathogen-specific CD4 T-cell function, and lung injury prior to and after ART initiation in adults with HIV and pulmonary TB. This was a prospective cohort study in South Africa, following adults with HIV and pulmonary TB prior to and up to 48 weeks after ART initiation. Pulmonary-specific inflammation was defined as total glycolytic activity (TGA) on [18]F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) at baseline and 4 weeks after ART initiation. Spirometry, respiratory symptom tests, and flow cytometry were performed at the same times to assess lung involvement and the frequency of mycobacteria-specific CD4 T-cells. In addition, we evaluated lung function longitudinally up to 48 weeks after ART initiation. Greater lung TGA on FDG PET-CT was associated with worse lung function and respiratory symptoms prior to ART initiation, and nearly half of subjects experienced worsening lung inflammation and lung function at Week 4 of ART. Worsening Week 4 lung inflammation and pulmonary function were both associated with greater increases in pathogen-specific functional CD4 T-cell responses on ART, and early decreases in lung function were independently associated with persistently lower lung function months after TB treatment completion. Increases in pulmonary inflammation and decreases in lung function are common on ART, relate to greater ART-mediated CD4 T-cell restoration, and are associated with the persistent impairment of lung function in individuals with HIV/TB.

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

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

Increased Metabolic Activity on 18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography in Human Immunodeficiency Virus-Associated Immune Reconstitution Inflammatory Syndrome.

Immune reconstitution inflammatory syndrome (IRIS) represents an unexpected inflammatory response shortly after initiation of antiretroviral therapy (ART) in some human immunodeficiency virus (HIV)-infected patients with underlying neoplasia or opportunistic infections, including tuberculosis. We hypothesized that IRIS is associated with increased glycolysis and that 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) could help identify high-risk subjects. In this prospective cohort study, 30 HIV-infected patients (CD4+ count <100 cells/µL) underwent FDG-PET/CT scans at baseline and 4-8 weeks after ART initiation. Ten patients developed IRIS (6 mycobacterial). At baseline, total glycolytic activity, total lesion volume, and maximum standardized uptake values (SUVs) of pathologic FDG uptake (reflective of opportunistic disease burden) were significantly higher in IRIS vs non-IRIS (P = .010, .017, and .029, respectively) and significantly correlated with soluble inflammatory biomarkers (interferon-γ, myeloperoxidase, tumor necrosis factor, interleukin 6, soluble CD14). Baseline bone marrow (BM) and spleen FDG uptake was higher in mycobacterial IRIS specifically. After ART initiation, BM and spleen mean SUV decreased in non-IRIS (P = .004, .013) but not IRIS subjects. Our results were supported by significantly higher glucose transporter 1 (Glut-1) expression of CD4+ cells and monocytes after ART initiation in IRIS/mycobacterial IRIS compared with non-IRIS patients. We conclude that increased pathologic metabolic activity on FDG-PET/CT prior to ART initiation is associated with IRIS development and correlates with inflammatory biomarkers. Abnormally elevated BM and spleen metabolism is associated with mycobacterial IRIS, HIV viremia, and Glut-1 expression on CD4+ cells and monocytes. NCT02147405.

Abstract CT005: FLT3 ligand (CDX-301) and stereotactic radiotherapy for advanced non-small cell lung cancer

Abstract Background We previously demonstrated, in a murine model, that localized radiotherapy and fms-like tyrosine kinase 3 (FLT3) ligand can act synergistically to control non-small cell lung cancer (NSCLC). Here we present preliminary results from an ongoing prospective clinical trial testing this combination in patients with advanced NSCLC. Methods Patients with advanced NSCLC that has previously been treated with at least one line of systemic therapy, at least two sites of active disease based on pre-treatment FDG-PET, and ECOG performance status 0-2 are eligible for this trial. Study subjects receive 5 daily subcutaneous injections of CDX-301 (75 µg/kg) concurrent with stereotactic body radiotherapy (SBRT) directed at a single intrathoracic site of disease. SBRT doses may range from 30 to 54 Gy, delivered over one week in 1, 3, or 5 fractions, depending on the target size and location. The primary study endpoint is survival without disease progression four months after treatment (PFS4). We hypothesize that the PFS4 rate will exceed 40%. Secondary endpoints include dose-limiting toxicities (grade ≥3 adverse events observed within 30 days of treatment and attributed to study therapy) and responses on PET based on total glycolytic activity (TGA), which is a volumetric measure of disease burden. Lesions targeted with SBRT are not included in radiographic response assessments. Based on PET Response Criteria in Solid Tumors (PERCIST) guidelines, a reduction in TGA of 45% or greater is classified as a partial response (PR). Results Nine subjects received study therapy between October 2016 and October 2017. Subjects were previously treated with a median of 2.5 courses of systemic therapy (range: 1-3). Seven subjects were previously treated with immune checkpoint inhibitors targeting the PD-1/PD-L1 axis. No dose-limiting toxicities were observed. On PET performed two months after treatment, PR of lesions not targeted with SBRT (“abscopal effect”) was observed in 5/9 subjects. Responses were observed in unirradiated pulmonary, nodal, and osseous lesions. With a median follow-up duration of 5 months (range: 4 to 13 months), five subjects have developed disease progression, and two subjects have died. PFS4 was achieved in 5/9 subjects overall and in 5/5 subjects who demonstrated PR on PET. PR and PFS4 were achieved in 5/7 subjects who were previously treated with immunotherapy and in 0/2 subjects who were not previously treated with immunotherapy. Conclusion The combination of CDX-301 and stereotactic radiotherapy for advanced NSCLC has yielded promising early results, with frequent abscopal effects and a high PFS4 rate. This regimen may be particularly effective for patients who have previously been treated with immune checkpoint inhibitors targeting the PD-1/PD-L1 axis. Enrollment is ongoing to further characterize treatment efficacy and to explore the immunological effects of combining CDX-301 and SBRT. Citation Format: Nitin Ohri, Balazs Halmos, Haiying Cheng, Tony Abraham, Tahir Yahya, Madhur Garg, William Bodner, Rafi Kabarriti, Shalom Kalnicki, Michael J. Yellin, Tibor Keler, Chandan Guha. FLT3 ligand (CDX-301) and stereotactic radiotherapy for advanced non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT005.

A semi-automatic technique to quantify complex tuberculous lung lesions on 18F-fluorodeoxyglucose positron emission tomography/computerised tomography images

BackgroundThere is a growing interest in the use of 18F-FDG PET-CT to monitor tuberculosis (TB) treatment response. However, TB causes complex and widespread pathology, which is challenging to segment and quantify in a reproducible manner.To address this, we developed a technique to standardise uptake (Z-score), segment and quantify tuberculous lung lesions on PET and CT concurrently, in order to track changes over time. We used open source tools and created a MATLAB script. The technique was optimised on a training set of five pulmonary tuberculosis (PTB) cases after standard TB therapy and 15 control patients with lesion-free lungs.ResultsWe compared the proposed method to a fixed threshold (SUV > 1) and manual segmentation by two readers and piloted the technique successfully on scans of five control patients and five PTB cases (four cured and one failed treatment case), at diagnosis and after 1 and 6 months of treatment. There was a better correlation between the Z-score-based segmentation and manual segmentation than SUV > 1 and manual segmentation in terms of overall spatial overlap (measured in Dice similarity coefficient) and specificity (1 minus false positive volume fraction). However, SUV > 1 segmentation appeared more sensitive. Both the Z-score and SUV > 1 showed very low variability when measuring change over time. In addition, total glycolytic activity, calculated using segmentation by Z-score and lesion-to-background ratio, correlated well with traditional total glycolytic activity calculations. The technique quantified various PET and CT parameters, including the total glycolytic activity index, metabolic lesion volume, lesion volumes at different CT densities and combined PET and CT parameters. The quantified metrics showed a marked decrease in the cured cases, with changes already apparent at month one, but remained largely unchanged in the failed treatment case.ConclusionsOur technique is promising to segment and quantify the lung scans of pulmonary tuberculosis patients in a semi-automatic manner, appropriate for measuring treatment response. Further validation is required in larger cohorts.

Upregulation of α-enolase protects cardiomyocytes from phenylephrine-induced hypertrophy.

Cardiac hypertrophy often refers to the abnormal growth of heart muscle through a variety of factors. The mechanisms of cardiomyocyte hypertrophy have been extensively investigated using neonatal rat cardiomyocytes treated with phenylephrine. α-Enolase is a glycolytic enzyme with "multifunctional jobs" beyond its catalytic activity. Its possible contribution to cardiac dysfunction remains to be determined. The present study aimed to investigate the change of α-enolase during cardiac hypertrophy and explore its role in this pathological process. We revealed that mRNA and protein levels of α-enolase were significantly upregulated in hypertrophic rat heart induced by abdominal aortic constriction and in phenylephrine-treated neonatal rat cardiomyocytes. Furthermore, knockdown of α-enolase by RNA interference in cardiomyocytes mimicked the hypertrophic responses and aggravated phenylephrine-induced hypertrophy without reducing the total glycolytic activity of enolase. In addition, knockdown of α-enolase led to an increase of GATA4 expression in the normal and phenylephrine-treated cardiomyocytes. Our results suggest that the elevation of α-enolase during cardiac hypertrophy is compensatory. It exerts a catalytic independent role in protecting cardiomyocytes against pathological hypertrophy.

Standardized Added Metabolic Activity Predicts Survival After Intra-arterial Resin-Based 90Y Radioembolization Therapy in Unresectable Chemorefractory Metastatic Colorectal Cancer to the Liver.

Standardized added metabolic (SAM) activity is a functional objective measurement of the total tumoral metabolic activity that avoids partial volume effect and thresholding, which limit conventional PET parameters. The purpose of this study is to investigate the role of SAM in predicting survival in unresectable, chemorefractory colorectal hepatic metastatic disease treated with resin-based Y radioembolization. This is a prospective correlative study of patients with unresectable, chemorefractory colorectal liver metastasis who underwent F-FDG PET/CT and CT/MRI before and after Y. Target RECIST, PERCIST, change in total glycolytic activity (ΔTGA), and ΔSAM treatment response were assessed. Percentage changes in diameter, SUVpeak, TGA, and SAM were calculated pre- and post-Y therapy and objective response was defined as >30% change (responders). Survival analysis by Kaplan-Meier, log-rank, and Cox proportional hazard models were performed and significance was set at <0.05. Sixteen patients (mean age of 61.6) were enrolled and performed a total of 20 Y therapies. After Y, target ΔSAM showed an objective response rate of 40% vs. 35%, 30%, and 22.2% based on target ΔTGA, PERCIST, and RECIST criteria, respectively. Median overall survival (OS) of the cohort after Y was 9.2 months (CI 95% 2.2-16.2). Patients demonstrating objective response based on ΔSAM had a median OS of 22.7 months (CI 95% 12.4-33.0) vs. 6.7 (CI 95% 4.2-9.2) in non-responders (P = 0.007). On multivariate analysis, hazard ratios for the objective response group based on target ΔSAM were 0.01 (P = 0.03) vs. 0.05 (P = 0.08), 0.20 (P = 0.29), and 0.91 (P = 0.98) based on target ΔTGA, PERCIST, and RECIST criteria, respectively. In unresectable colorectal liver metastatic disease refractory to standard chemotherapy, ΔSAM predicted OS for assessment of response following Y radioembolization therapy, whereas RECIST, PERCIST, and ΔTGA did not.

Pretreatment FDG-PET metrics in stage III non-small cell lung cancer: ACRIN 6668/RTOG 0235.

ACRIN 6668/RTOG 0235 evaluated the prognostic value of positron emission tomography with (18)F-fluorodeoxyglucose (FDG-PET) uptake before and after definitive, concurrent, platinum-based chemoradiotherapy for locally advanced non-small cell lung cancer (NSCLC). In this secondary analysis, we evaluate volumetric pretreatment PET measures as predictors of clinical outcomes. Patients with stage III NSCLC underwent FDG-PET prior to treatment. A commercially available gradient-based segmentation tool was used to contour all visible hypermetabolic lesions on each scan. For each patient, the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total glycolytic activity (TGA) for all contoured lesions were recorded. Cox proportional hazards regression models were used to evaluate clinical variables and PET metrics as predictors of overall survival (OS) and locoregional control (LRC). Time-dependent covariables were added to the models when necessary to address nonproportional hazards. All statistical tests were two-sided. Complete data were available for 214 patients in the OS analysis and 189 subjects in the LRC analysis. In multivariable analysis incorporating clinical and imaging data available prior to treatment, MTV was an independent predictor of OS (HR = 1.04 per 10 cm(3) increase, 95% CI = 1.03 to 1.06, P < .001). High MTV was also associated with increased risk of locoregional failure at baseline (HR = 1.16 per 10 cm(3) increase, 95% CI = 1.08 to 1.23, P < .001) and at six months (HR = 1.05 per 10 cm(3) increase, 95% CI = 1.02 to 1.07, P < .001) but not at 12 months or later time points. Pretreatment MTV is a predictor of clinical outcomes for NSCLC patients treated with chemoradiotherapy. Quantitative PET measures may serve as stratification factors in clinical trials for this patient population and may help guide novel trial designs.

18F-FDG PET/CT as a semiquantitative imaging marker in HPV-p16-positive oropharyngeal squamous cell cancers.

There is evidence that the status of human papilloma virus subtype 16 (HPV-p16) alters the prognosis of patients with oropharyngeal squamous cell cancer (OSCC). We sought to establish whether there is a relationship between HPV-p16 status and 18F-FDG uptake in the prognosis of OSCC. Patients with newly diagnosed OSCC at our institution between June 2011 and June 2012 were retrospectively evaluated. All patients underwent a baseline 18F-FDG PET/computed tomographic scan and HPV-p16 testing. Tumour maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean) and total glycolytic activity (TGA) [defined as metabolic tumour volume (MTV) multiplied by SUVmean] were measured. All PET/computed tomographic scans were reviewed on a Siemens Syngo.via (version VA11B_HF03) workstation. A designated operator defined the region of the primary tumour with the MTV segmented by 40% of the SUVmax fixed threshold method. Seventy-nine patients aged 27-84 years met the criteria for inclusion in the study. The types of primary tumour were tonsillar squamous cell carcinoma in 48% and base of tongue squamous cell carcinoma in 29%. The mean SUVmax was 17.5 and 17.7 in HPV-p16-positive and HPV-p16-negative groups, respectively (P=0.90). The mean MTV was 8.36 and 7.07 ml in HPV-p16-positive and HPV-p16-negative patients, respectively (P=0.42). The mean TGA values were 96.3 and 82.5 g among the HPV-p16-positive and HPV-p16-negative patients (P=0.54). There was no significant difference between HPV-p16 status and tumour grading for any of the imaging markers. There were no statistically significant differences between HPV-p16-positive and HPV-p16-negative OSCC for any of the metabolic imaging markers (SUVmax, SUVmean, MTV and TGA) measured in this study.

SU‐D‐9A‐02: Relative Effects of Threshold Choice and Spatial Resolution Modeling On SUV and Volume Quantification in F18‐FDG PET Imaging of Anal Cancer Patients

Purpose:PET imaging with F18‐FDG is utilized for treatment planning, treatment assessment, and prognosis. A region of interest (ROI) encompassing the tumor may be determined on the PET image, often by a threshold T on the PET standard uptake values (SUVs). Several studies have shown prognostic value for relevant ROI properties including maximum SUV value (SUVmax), metabolic tumor volume (MTV), and total glycolytic activity (TGA). The choice of threshold T may affect mean SUV value (SUVmean), MTV, and TGA. Recently spatial resolution modeling (SRM) has been introduced on many PET systems. SRM may also affect these ROI properties. The purpose of this work is to investigate the relative influence of SRM and threshold choice T on SUVmean, MTV, TGA, and SUVmax.Methods:For 9 anal cancer patients, 18F‐FDG PET scans were performed prior to treatment. PET images were reconstructed by 2 iterations of Ordered Subsets Expectation Maximization (OSEM), with and without SRM. ROI contours were generated by 5 different SUV threshold values T: 2.5, 3.0, 30%, 40%, and 50% of SUVmax. Paired‐samples t tests were used to compare SUVmean, MTV, and TGA (a) for SRM on versus off and (b) between each pair of threshold values T. SUVmax was also compared for SRM on versus off.Results:For almost all (57/60) comparisons of 2 different threshold values, SUVmean, MTV, and TGA showed statistically significant variation. For comparison of SRM on versus off, there were no statistically significant changes in SUVmax and TGA, but there were statistically significant changes in MTV for T=2.5 and T=3.0 and in SUVmean for all T.Conclusion:The near‐universal statistical significance of threshold choice T suggests that, regarding harmonization across sites, threshold choice may be a greater concern than choice of SRM. However, broader study is warranted, e.g. other iterations of OSEM should be considered.

PET/CT planning during chemoradiotherapy for esophageal cancer.

PurposeTo evaluate the usefulness of positron emission tomography/computed tomography (PET/CT) for field modification during radiotherapy in esophageal cancer.Materials and MethodsWe conducted a retrospective study on 33 patients that underwent chemoradiotherapy (CRT). Pathologic findings were squamous cell carcinoma in 32 patients and adenocarcinoma in 1 patient. All patients underwent PET/CT scans before and during CRT (after receiving 40 Gy and before a 20 Gy boost dose). Response evaluation was determined by PET/CT using metabolic tumor volume (MTV), total glycolytic activity (TGA), MTV ratio (rMTV) and TGA ratio (rTGA), or determined by CT. rMTV and rTGA were reduction ratio of MTV and TGA between before and during CRT, respectively.ResultsSignificant decreases in MTV (MTV2.5: mean 70.09%, p < 0.001) and TGA (TGA2.5: mean 79.08%, p<0.001) were found between before and during CRT. Median rMTV2.5 was 0.299 (range, 0 to 0.98) and median rTGA2.5 was 0.209 (range, 0 to 0.92). During CRT, PET/CT detected newly developed distant metastasis in 1 patient, and this resulted in a treatment strategy change. At a median 4 months (range, 0 to 12 months) after completion of CRT, 8 patients (24.2%) achieved clinically complete response, 11 (33.3%) partial response, 5 (15.2%) stable disease, and 9 (27.3%) disease progression. SUVmax (p = 0.029), rMTV50% (p = 0.016), rMTV75% (p = 0.023) on intra-treatment PET were found to correlate with complete clinical response.ConclusionPET/CT during CRT can provide additional information useful for radiotherapy planning and offer the potential for tumor response evaluation during CRT. rMTV50% during CRT was found to be a useful predictor of clinical response.

PET-Based Primary Tumor Volumetric Parameters and Survival of Patients With Non—Small Cell Lung Carcinoma

The purpose of the study was to assess metabolic tumor volume and total glycolytic activity of the primary tumor as prognostic parameters for outcome in patients with non-small cell lung carcinoma (NSCLC). Thirty-nine patients who had undergone a baseline staging PET/CT examination at our institution for the diagnosis of NSCLC were retrospectively identified. The maximum standardized uptake value (SUV(max)), metabolic tumor volume, and total glycolytic activity were segmented from PET using the gradient method; 12-month survival and overall survival at the end of follow-up were used as outcome measures. Multivariate logistic regression, receiver operating characteristic curve analysis, and Kaplan-Meier curves for survival analysis were generated and compared using the Mantel-Cox log-rank test. The mean gradient-based metabolic tumor volume and gradient-based total glycolytic activity were significantly greater in the patients who died (93.3 mL and 597.5 g) than in those who survived (19.3 mL and 193.9 g, respectively) (p < 0.003 and p < 0.031). There was no statistically significant difference in the mean SUV(max) between the patients who survived (12.7) at 12 months and those who had died (13.1) (p = 0.85). On multivariate analysis, gradient-based metabolic tumor volume was the only variable associated with 12-month mortality when adjusted for all other factors.(.) The area under the curve (AUC) for gradient-based metabolic tumor volume was 0.77 (p < 0.006). A significant difference in the time to survival was observed between high and low gradient-based metabolic tumor volume (log-rank p < 0.05) cohorts using the median gradient-based metabolic tumor volume (9.7 mL) as the cut point. PET-based volumetric imaging parameters are potential prognostic markers of outcome in patients with NSCLC.

Intra-reader reliability of FDG PET volumetric tumor parameters: effects of primary tumor size and segmentation methods

To establish the effects of size and segmentation methods on intra-reader reliability of primary tumor metabolic tumor volume (MTV) and total glycolytic activity (TGA) in human solid tumors. This is a retrospective study of 121 patients who had a baseline FDG PET/CT scan for oncologic staging. Volumetric parameter readings were performed in random order on two separate occasions, 12 weeks apart, by the same reader. The MTV and TGA were segmented using gradient and fixed maximum standardized uptake value (SUVmax) threshold methods. Intra-reader reliability was established by the intraclass correlation coefficient (ICC) and Bland-Altman analysis. The biases for MTV were 2.95, 14.76 and 11.13% for gradient segmentation, 38 and 50% SUVmax fixed threshold segmentations, respectively (p < 0.0001). For TGA, the corresponding biases were 0.76, 10.36 and 7.46% (p < 0.0001). There were no statistically significant differences in the biases between the first and second reads for MTV segmented for small and large volume tumors by the gradient method (p < 0.34) or 50% SUVmax threshold segmentation (p < 0.08). However, there were statistically significant differences in the corresponding biases for the 38% SUVmax threshold segmentation (p < 0.04). There were no statistically significant differences in the biases between the first and second reads for TGA segmented for small and large volume tumors (p < 0.98). Intra-reader reliability for primary tumor FDG MTV and TGA is affected by the tumor size and segmentation methods. The segmentation bias was smaller for gradient method than percentage fixed threshold method for MTV. The segmentation biases were smaller for TGA than MTV.

18F-FDG Metabolic Tumor Volume and Total Glycolytic Activity of Oral Cavity and Oropharyngeal Squamous Cell Cancer: Adding Value to Clinical Staging

(18)F-FDG metabolic tumor volume (MTV) and total glycolytic activity (TGA) have been proposed as potential prognostic imaging markers for patient outcome in human solid tumors. The purpose of this study was to establish whether MTV and TGA add prognostic information to clinical staging in patients with oral and oropharyngeal squamous cell carcinomas (SCCs). The Institutional Review Board approved this Health Insurance Portability and Accountability Act-compliant single-institution retrospective study. Forty-five patients with histologically proven oral or oropharyngeal SCC underwent PET/CT for initial cancer staging and were included in the study. MTV was measured using a gradient-based method (PET Edge) and fixed-threshold methods at 38%, 50%, and 60% of maximum standardized uptake value (SUV). The TGA is defined as MTV × mean SUV. Bland-Altman analysis was used to establish the reliability of the methods of segmentation. Outcome endpoints were overall survival (OS) and progression-free survival. Cox proportional hazards univariate and multivariate regression analyses were performed. In Cox regression models, MTV and TGA were the only factors significantly associated with survival outcome after adjusting for all other covariates including American Joint Committee on Cancer (AJCC) stage, with hazards ratio of 1.06 (95% confidence interval, 1.01-1.10; P = 0.006) and 1.00 (95% confidence interval, 1.00-1.01; P = 0.02). The model fit was significantly better when MTV was added to AJCC stage in model I (χ(2) value change, 1.16-6.71; P = 0.01) and when TGA was added to AJCC stage in model II (χ(2) value change, 1.16-4.37; P = 0.04). The median cutoff point of 7.7 mL for primary tumor MTV was predictive of time to OS (log rank P = 0.04). The median cutoff point of 55 g for PET Edge primary tumor TGA was predictive of time to OS (log rank P = 0.08), though the result was not statistically significant. Gradient-based segmentations of primary tumor MTV and TGA are potential (18)F-FDG markers for time to survival in patients with oral and oropharyngeal SCC and may provide prognostic information in addition to AJCC stage. These exploratory imaging markers need validation in larger cohort studies.

Postchemoradiotherapy Positron Emission Tomography Predicts Pathologic Response and Survival in Patients With Esophageal Cancer

To correlate the prechemoradiotherapy (CRT) and post-CRT metabolic tumor volume (MTV) on positron emission tomography (PET) scanning with the pathologic response and survival in patients receiving preoperative CRT for esophageal cancer. The medical records of 37 patients with histologically confirmed Stage I-IVA esophageal cancer treated with CRT with or without surgical resection were reviewed. Of the 37 patients, 21 received preoperative CRT (57%) and 16 received definitive CRT (43%). All patients had a pre-CRT and 32 had a post-CRT PET scan. The MTV was measured on the pre-CRT PET and post-CRT PET scan, respectively, using a minimum standardized uptake value (SUV) threshold x, where x = 2, 2.5, 3, or the SUV maximum × 50%. The total glycolytic activity (TGA(x)) was defined as the mean SUV × MTV(x). The MTV ratio was defined as the pre-CRT PET MTV/post-CRT MTV. The SUV ratio was defined similarly. A single pathologist scored the pathologic response using a tumor regression grade (TRG) scale. The median follow-up was 1.5 years (range, 0.4-4.9). No significant correlation was found between any parameters on the pre-CRT PET scan and the TRG or overall survival (OS). Multiple post-CRT MTV values and post-TGA values correlated with the TRG and OS; however, the MTV(2.5(Post)) and TGA(2.5(Post)) had the greatest correlation. The MTV(2) ratio correlated with OS. The maximum SUV on either the pre-CRT and post-CRT PET scans or the maximum SUV ratio did not correlate with the TRG or OS. Patients treated preoperatively had survival similar compared with those treated definitively with a good PET response (p = 0.97) and significantly better than that of patients treated definitively with a poor PET response (p < 0.0001). The maximum SUV was not a predictive or prognostic parameter. The MTV(2.5) and TGA(2.5) were useful markers for predicting the response and survival on the post-CRT PET scan. The MTV(2) ratio also correlated with survival. Post-CRT PET can potentially guide therapy after CRT.