Total Glycolytic Volume Research Articles

A reduced physiological 18F-fluorodeoxyglucose uptake in the brain and liver caused by malignant lymphoma being deprived of the tracer.

Purpose : To investigate whether or not the physiological brain and liver FDG uptake are decreased in patients with highly accelerated glycolysis lesions. Methods : We retrospectively analyzed 51 patients with malignant lymphoma. We compared the FDG uptake in the brain and liver of the patients with that in a control group. In 24 patients with a complete response (CR) or partial response (PR) to treatment, we compared the brain and liver uptake before and after treatment. Results : The maximum standardized uptake value (SUVmax) and total glycolytic volume (TGV) of the brain as well as the SUVmax and mean standardized uptake value (SUVmean) of the liver in malignant lymphoma patients were 13.1 ± 2.3, 7386.3 ± 1918.4, 3.2 ± 0.5, and 2.3 ± 0.4, respectively ; in the control group, these values were 14.9 ± 2.4, 8566.2 ± 1659.5, 3.4 ± 0.4, and 2.5 ± 0.3, respectively. The SUVmax and TGV of the brain and the SUVmean of the liver in malignant lymphoma patients were significantly lower than the control group. The SUVmax and TGV of the brain after treatment were significantly higher than before treatment. Both the SUVmax and SUVmean of liver after treatment were higher than before treatment, but not significant. Conclusion : A decreased physiological brain and liver FDG uptake is caused by highly accelerated lesion glycolysis. J. Med. Invest. 68 : 181-185, February, 2021.

P2.02-047 Association of FDG PET, Complete Pathological Response and Overall Survival in Patients with Pancoast Tumors Treated with Trimodality Therapy

Induction chermoradiotherapy (CRT) and surgical resection is considered standard care for treatment of node negative Pancoast tumors. However, not all patients benefit from this approach and there are no well-defined preoperative parameters to identify patients for whom addition of surgery may be unnecessary due to local control with CRT alone. We investigated whether baseline FDG positron emission tomography (PET) scan parameters or changes post induction may predict complete pathological response (pCR) to CRT and hence obviate the need for subsequent resection. We conducted a retrospective review of our prospectively maintained single institution database with supplemental chart review to evaluate: PET, histopathological, and clinical outcome parameters in consecutive patients undergoing curative intent trimodality treatment of Pancoast tumors from 2001 to 2015. Metabolic parameters based on the standardized uptake values (SUV) were calculated including SUVmax (maximum SUV value), SUVPTL (peak tumor-to-liver ratio), and TGV (total glycolytic volume, mean SUV x tumor volume). Two pathologists independently reviewed specimens to assess percentage viable tumor in resected tumors. Nineteen patients (10 females), median age 61 (42-75) yrs completed trimodality treatment with Cisplatin, Etoposide and 45Gy in the majority of cases. Histopathological was data available for all patients. Of the 19 patients baseline PET was available in 15 and post induction PET in 13. Baseline SUVmax < 9.4 was associated with pCR in 4/4 vs. 4/11 patients (p=0.03). A trend towards improved locoregional control with cPR did not reach significance. No PET measured parameter was associated with locoregional control. Baseline TGV > 441 was associated with reduced disease free survival (DFS) 5.7(0.7-10.5) vs. NR months (p=0.002), and overall survival (OS) 15.9 (3.1-28.8) vs. NR months (p=0.04). No change in PET parameter measured post induction was associated with cPR, local recurrence, DFS or OS. In our series, low baseline SUVmax was associated with complete pathological response. If confirmed in a larger cohort, including multivariate analysis of other prognostic and predictive factors, this may allow patients at high perioperative risk to be better stratified to either definitive CRT or trimodality therapy. A larger series may be able to identify an association between metabolic response on FDG-PET and CPR, DFS or overall survival.

SU‐E‐J‐275: Review ‐ Computerized PET/CT Image Analysis in the Evaluation of Tumor Response to Therapy

Purpose:To review the literature in using computerized PET/CT image analysis for the evaluation of tumor response to therapy.Methods:We reviewed and summarized more than 100 papers that used computerized image analysis techniques for the evaluation of tumor response with PET/CT. This review mainly covered four aspects: image registration, tumor segmentation, image feature extraction, and response evaluation.Results:Although rigid image registration is straightforward, it has been shown to achieve good alignment between baseline and evaluation scans. Deformable image registration has been shown to improve the alignment when complex deformable distortions occur due to tumor shrinkage, weight loss or gain, and motion. Many semi‐automatic tumor segmentation methods have been developed on PET. A comparative study revealed benefits of high levels of user interaction with simultaneous visualization of CT images and PET gradients. On CT, semi‐automatic methods have been developed for only tumors that show marked difference in CT attenuation between the tumor and the surrounding normal tissues. Quite a few multi‐modality segmentation methods have been shown to improve accuracy compared to single‐modality algorithms. Advanced PET image features considering spatial information, such as tumor volume, tumor shape, total glycolytic volume, histogram distance, and texture features have been found more informative than the traditional SUVmax for the prediction of tumor response. Advanced CT features, including volumetric, attenuation, morphologic, structure, and texture descriptors, have also been found advantage over the traditional RECIST and WHO criteria in certain tumor types. Predictive models based on machine learning technique have been constructed for correlating selected image features to response. These models showed improved performance compared to current methods using cutoff value of a single measurement for tumor response.Conclusion:This review showed that computerized PET/CT image analysis holds great potential to improve the accuracy in evaluation of tumor response.This work was supported in part by the National Cancer Institute Grant R01CA172638.

SU‐E‐QI‐20: A Review of Advanced PET and CT Image Features for the Evaluation of Tumor Response

Purpose:To review the literature in using quantitative PET and CT image features for the evaluation of tumor response.Methods:We reviewed and summarized more than fifty papers that use advanced, quantitative PET/CT image features for the evaluation of tumor response. We also discussed future works on extracting disease‐specific features, combining multiple and complementary features in response modeling, delineating tumor in multimodality images, and exploring biological explanations of these advanced features.Results:Advanced PET image features considering spatial information, such as tumor volume, tumor shape, total glycolytic volume, histogram distance, and texture features (characterizing spatial distribution of FDG uptake) have been found more informative than the traditional SUVmax for the prediction of tumor response. Advanced CT features, including volumetric, attenuation, morphologic, structure, and texture descriptors, have also been found advantage over the traditional RECIST and WHO criteria in certain tumor types.Conclusions:Advanced, quantitative FDG PET/CT image features have been shown promising for the evaluation of tumor response. With the emerging multi‐modality imaging performed at multiple time points for each patient, it becomes more important to analyze the serial images quantitatively, select and combine both complementary and contradictory information from various sources, for accurate and personalized evaluation of tumor response to therapy.

Metabolic Response to Preoperative Chemotherapy Predicts Prognosis for Patients Undergoing Surgical Resection of Colorectal Cancer Metastatic to the Liver

Biological characteristics of colorectal cancer liver metastases (CRCLM) are increasingly recognized as major determinants of patient outcome. The purpose of this study was to evaluate the prognostic value of metabolic response to preoperative chemotherapy as quantified by (18)F-FDG positron emission tomography (PET) for patients undergoing liver resection of CRCLM. All patients (n = 80) who had staging PET before liver resection for CRCLM at Austin Health in Melbourne between 2004 and 2011 were included. Thirty-seven patients had PET and CT imaging before and after preoperative chemotherapy. Semiquantitative PET parameters-maximum standardized uptake variable (SUVmax), metabolic tumour volume (MTV), and total glycolytic volume (TGV)-were derived. Metabolic response was determined by the proportional change in PET parameters (∆SUVmax, ∆MTV, ∆TGV). Prognostic scores, CT RECIST response, and tumour regression grading (TRG) were also assessed. Correlation to recurrence-free (RFS) and overall survival (OS) was assessed using Kaplan-Meier survival and multivariate analysis. Semiquantitative parameters on staging PET before chemotherapy were not predictive of prognosis, whereas all parameters after chemotherapy were prognostic for RFS and OS. Only ∆SUVmax was predictive of RFS and OS on multivariate analysis. Patients with metabolically responsive tumours had an OS of 86 % at 3 years vs. 38 % with nonresponsive or progressive tumours (p = 0.003). RECIST and TRG did not predict outcome. Tumour metabolic response to preoperative chemotherapy as quantified by PET is predictive of prognosis in patients undergoing resection of CRCLM. Assessing metabolic response uniquely characterizes tumour biology, which may allow future optimization of patient and treatment selection.

18Fluorine-fluorodeoxyglucose positron emission tomography/computed tomography total glycolytic volume in thymic epithelial neoplasms evaluation: a reproducible image biomarker

(18)Fluorine-fluorodeoxyglucose positron emission tomography/computed tomography is not yet accepted as a standard pretreatment evaluation of thymic epithelial neoplasm (TEN). Statistical correlation between standardized uptake value of tumor/mediastinum ratio and patients' WHO risk class has been reported. PET metabolic tumor volume (MTV) and total glycolytic volume (TGV) have been reported as additional prognostic imaging biomarkers in several human tumors. Purpose of study was to establish whether MTV and TGV add prognostic information in TEN. A retrospective dynamic cohort study of prospectively collected data (2006-2012) on 23 consecutive patients with pathologically proven TEN (no thymic carcinoma) was conducted. All patients underwent chest CT, and PET for staging. SUV T/M ratio, semi-quantitative and volumetric analyses of TEN were calculated. Patients were categorized according to WHO classification (low-risk and high-risk thymomas). Statistical analysis was performed with bootstrap method. Multi-collinearity was established using Pearson correlation coefficient. Cut-off point for TGV was compared using Mantel Cox log rank test. SUV T/M ratio, MTV, and TGV correlate with low- and high-risk TEN. However, the statistical correlation between TGV and WHO classification (ρ=0.897) was higher than SUV T/M ratio (ρ=0.873). Since sample distributions were not uniformly smooth, only one cut-off value was identified: a TGV of 383 served as a cut-off value between low-risk and high-risk TEN. TGV is a PET reproducible imaging marker in patients with TEN, provides prognostic information, and could be useful in pretreatment stratification of patients. Nevertheless, it needs validation in larger cohort studies.

A Phase II Study of Intermittent Sunitinib Malate as Second-Line Therapy in Progressive Malignant Pleural Mesothelioma

There is no accepted second-line therapy for patients with advanced malignant pleural mesothelioma (MPM), whose disease has progressed after first-line chemotherapy. The multitargeted tyrosine kinase inhibitor sunitinib malate targets several pathways overexpressed in mesothelioma. This phase II study assessed objective response to sunitinib and correlative biomarkers in patients with progressive pretreated MPM. Eligible patients had confirmed MPM, radiological progression after chemotherapy, Eastern Cooperative Oncology Group performance status 0 to 1, and measurable disease. Patients received oral sunitinib 50 mg daily for 28 of every 42 days. The primary endpoint was objective radiological response. Patients without prior pleurodesis had fluorodeoxyglucose positron emission tomographic response assessed by total glycolytic volume criteria. Correlative biomarkers included serum mesothelin, vascular endothelial growth factor (VEGF)-A, VEGF-C, interleukin-8, sVEGFR-2, sVEGFR-3, and s-kit. Fifty-three patients received sunitinib between July 2006 and December 2009; 51 were assessable for response. Patients received a median of two cycles (range, 1-12); 40% required dose reduction. Fatigue was the most prominent toxicity. Six patients (12%) had a confirmed radiological partial response, 34 (65%) had stable disease, and 11 (22%) had progressive disease as best response. Six of 20 patients had a decrease in fluorodeoxyglucose positron emission tomographic total glycolytic volume of 15% or more. Median overall survival was 6.1 months, and median time to progression was 3.5 months. Correlative biomarkers did not predict treatment response. Sunitinib has activity in a subset of patients with pretreated MPM. Consideration should be given to different treatment schedules and examination of other biomarkers for further study of sunitinib in MPM.

SU-D-BRB-04: FDG-PET Histogram Distances: Novel Predictors of Tumor Response to Chemoradiotherapy.

To examine the accuracy of FGD-PET histogram distances as predictors of pathologic tumor response to chemo-radiotherapy (CRT) in esophageal cancer. Twenty patients were included. A rigid registration was used to align the post-CRT PET/CT with the pre-CRT PET/CT images. The primary tumor was delineated using a region-growing algorithm with a threshold of SUV = 2.5 on the pre-CRT PET. Two histograms of SUVs within the tumor were constructed on the pre-CRT PET and registered post-CRT PET, respectively. The differences between the two histograms reflected changes in the SUV distribution and were therefore potential predictors of tumor response. The differences were quantitatively measured by histogram distances using 12 bin-to-bin and 8 cross-bin algorithms. The accuracy of histogram distances in predicting pathologic tumor response to CRT was measured using the area under ROC curve (AUC), prediction accuracy, and the Mann-Whitney tests, in comparison with traditional PET response measures and texture features. Cross-bin histogram distances were shown to be significant (p<0.05) predictors of pathologic tumor response. They were more accurate than bin- to-bin histogram distances (not significant). The most accurate cross-bin histogram distances were: Quadratic-Chi distance (AUC=0.89, accuracy=80%, p=0.003), Earth Mover distance (AUC=0.83,accuracy=80%, p=0.014), diffusion distance (AUC = 0.82, accuracy=85%, p=0.02) and Match distance (AUC = 0.79, accuracy=80%, p=0.03). This family of novel predictors were more accurate than traditional PET response measures using SUVmax (AUC=0.76, accuracy=75%, p=0.05), SUVpeak (AUC=0.74, accuracy=70%, p=0.08), Total Glycolytic Volume (AUC=0.76, accuracy=70%, p=0.05), as well as texture features based on the cooccurrence matrix (Inertia: AUC=0.85, accuracy=80%, p=0.01). The cross-bin histogram distances characterized changes in the SUV distribution within a tumor and showed high accuracy for the prediction of pathologic response to CRT in esophageal cancer. This workwas supported in part by the National Cancer Institute Grant R21 CA131979.

Multimodal Imaging with 18F-FDG PET and Cerenkov Luminescence Imaging After MLN4924 Treatment in a Human Lymphoma Xenograft Model

Cerenkov luminescence imaging (CLI) is an emerging imaging technique that combines aspects of both optical and nuclear imaging fields. The ability to fully evaluate the correlation and sensitivity of CLI to PET is critical to progress this technique further for use in high-throughput screening of pharmaceutical compounds. To achieve this milestone, it must first be established that CLI data correlate to PET data in an in vivo preclinical antitumor study. We used MLN4924, a phase 2 oncology therapeutic, which targets and inhibits the NEDD8-activating enzyme pathway involved in the ubiquitin-proteasome system. We compared the efficacious effects of MLN4924 using PET and Cerenkov luminescence image values in the same animals. Imaging of (18)F-FDG uptake was performed at 5 time points after drug treatment in the subcutaneously implanted diffuse large B-cell lymphoma tumor line OCI-Ly10. Data were acquired with both modalities on the same day, with a 15-min delay between CLI and PET. PET data analysis was performed using percentage injected dose per cubic centimeter of tissue (%ID/cm(3)), average standardized uptake values, and total glycolytic volume. CLI measurements were radiance, radiance per injected dose (radiance/ID), and total radiant volume. A strong correlation was found between PET total glycolytic volume and CLI total radiant volume (r(2) = 0.99) and various PET and CLI analysis methods, with strong correlations found between PET %ID/cm(3) and CLI radiance (r(2) = 0.83) and CLI radiance/ID (r(2) = 0.82). MLN4924 demonstrated a significant reduction in tumor volume after treatment (volume ratio of treated vs. control, 0.114 at day 29). The PET and CLI data presented confirm the correlation and dynamic sensitivity of this new imaging modality. CLI provides a preclinical alternative to expensive PET instrumentation. Future high-throughput studies should provide for quicker turnaround and higher cost-to-return benefits in the drug discovery process.

Establishing locoregional control of malignant pleural mesothelioma using high-dose radiotherapy and 18F-FDG PET/CT scan correlation

The management of malignant pleural mesothelioma represents one of the most challenging issues in oncology, as there is no proven long-term benefit from surgery, radiotherapy or chemotherapy alone or in combination. Locoregional progression remains the major cause of death, but radical surgical resection may produce major postoperative morbidity. While radical or postoperative radiotherapy using conventional techniques has resulted in severe toxicity with no impact on survival, recent advances in radiotherapy delivery may be more effective. We treated patients with locally advanced mesothelioma whose tumours had been sub optimally resected with high-dose three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT) to large volumes of one hemithorax, using CT and positron emission tomography (PET) scan-based treatment planning. Clinical outcomes were assessed by determining patterns of failure and metabolic changes in total glycolytic volume (TGV) between pre- and post-irradiation( 18) F-FDG PET/CT scans and by recording acute and late toxicity grades. Fourteen patients were analysed with 40 PET scans performed before and up to 4.5years after radiotherapy. Eleven patients had pleurectomy/decortications, one had an extrapleural pneumonectomy and two had no surgery. Four patients who received chemotherapy had all progressed prior to radiotherapy. After radiotherapy, the in-field local control rate was 71%. No progression occurred in two patients, one was salvaged with further radiotherapy to a new site, four recurred inside the irradiated volume all with concurrent distant metastases and the other seven had distant metastases only. The TGVs were reduced by an average of 67% (range 12-100%) after doses of 45 to 60Gy to part or all of one hemithorax. There were no serious treatment-related toxicities. Median survival was 25months from diagnosis and 17months after starting radiotherapy. We have established that mesothelioma can be locally controlled with high radiation doses using 3DCRT or IMRT, and that strict normal tissue dose constraints have limited radiation toxicities. Radiotherapy should be considered to prevent or delay the local manifestations of progressive disease in suitable patients after surgery including extrapleural pneumonectomy and pleurectomy/decortication. Higher radiation doses may allow more effective palliation.

SU‐D‐BRC‐03: Spatial‐Temporal PET‐CT Features for Predicting Pathological Response of Esophagus Cancer to Chemo‐Radiation Therapies

Purpose: The purpose of this study is to develop new PET‐CT features for predicting the pathology response of esophagus tumor to chemo‐radiation therapies, and to compare their discriminant power with SUV‐max and SUV‐peak. Methods: Fifteen patients with locally advanced esophagus cancer and treated with tri‐modality therapies were studied. All patients underwent a Pre‐treatment and a Post‐treatment PET/CT. The Pre‐ and Post‐ CT images were first aligned with a rigid registration constrained in the chest region. All images were then projected into the Pre‐PET coordinate. Two different tumor regions of interest (ROI‐SUV2.5 and ROI‐SUVPeak) were produced. Various features capturing tumor shape, texture and intensity information were extracted, resulting in a total of 432 features for each patient. Receiver operating characteristic analyses were performed to investigate and compare the discriminant power of each feature. The ground truth was set to be the pathological response in the surgical specimen. Finally, trend analysis was conducted to examine whether a tumor is more likely a responder as the value of a feature increases or decreases. Results: Five among all 432 features have higher discriminant power than that of SUV‐max and SUV‐peak. These include two shape features, one intensity feature, one texture feature and one shape plus intensity feature. Among them, the Decline of Total Glycolytic Volume feature is extracted from the Diff‐SUV image. All five features were based on the larger tumor region ROI‐SUV2.5. Conclusions: Results demonstrated that shape, texture and intensity information are all important for predicting esophagus tumor pathological response to chemo‐radiation therapies. Integrating both spatial and temporal information is also important. Features based on a larger tumor region seem to be better than those based on a single point or a smaller tumor region.This work is supported in part by NIH 1R21CA131979.

Serum Soluble Mesothelin Concentrations in Malignant Pleural Mesothelioma: Relationship to Tumor Volume, Clinical Stage and Changes in Tumor Burden

To examine the clinical utility of soluble mesothelin in patients with malignant pleural mesothelioma. A total of 97 patients (female: 11; male: 86) were prospectively enrolled, longitudinal serum samples collected, and mesothelin concentrations determined. Baseline mesothelin levels were analyzed relative to tumor stage, presence of metastatic disease, the positron emission tomography (PET) parameters maximum standardized uptake value, tumor volume, total glycolytic volume, and survival. Changes in mesothelin level were correlated to objective response to chemotherapy, as assessed radiologically and by PET imaging, and with patient survival. Baseline mesothelin levels greater than 5 nmol/L were a significant negative prognostic indicator (HR = 2.25; 95% CI, 1.20-4.21) and correlated with tumor stage and volume. In 55 patients who received chemotherapy, change in mesothelin correlated with radiological response (χ(2) = 11.32; P = 0.023) and change in metabolically active tumor volume (r = 0.58; P < 0.01). Median survival for patients with a reduction in mesothelin following chemotherapy (19 months) was significantly longer than for patients with increased mesothelin (5 months; P < 0.001). These findings show the potential value of changes in mesothelin levels for prognostication and monitoring of treatment response in mesothelioma.

Does positron emission tomography offer prognostic information in malignant pleural mesothelioma?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether positron emission tomography is useful in the diagnosis and prognosis of malignant pleural mesothelioma (MPM). Altogether 136 papers were found using the reported search, of which 15 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We conclude that fluorodeoxyglucose-positron emission tomography (FDG-PET) accurately differentiates benign from malignant pleural disease, helps detect recurrence and provides prognostic information in terms of staging, survival and mortality. Eleven studies evaluated the role of FDG-PET in the diagnosis and prognosis of MPM. Malignant disease had a higher standardised uptake value (SUV) (6.5 ± 3.4 vs. 0.8 ± 0.6; P < 0.001) than benign pleural disease. Shorter median survival (9.7 vs. 21 months; P = 0.02) was associated with high SUV (>10) than low SUV (<10). PET accurately upstaged 13% and downstaged 27% of cases initially staged with computed tomography (CT). In patients undergoing chemotherapy, higher total glycolytic volume led to a lower median survival (4.9 vs. 11.5 months; P = 0.09), while a decline in FDG uptake was associated with a longer time to tumour progression (14 vs. 7 months; P = 0.02). Four studies observed the role of FDG-PET-CT in the diagnosis and prognosis of MPM. SUV was found to be higher in MPM compared to benign pleural disease (6.5 vs. 0.8; P < 0.001). A higher SUV(max) was observed in primary pleural lesions of metastatic (7.1 vs. 4.7; P = 0.003) compared to non-metastatic disease. Patients who underwent surgery had equivalent survival to those excluded based on scan results (20 vs. 12 months; P = 0.3813). One study compared the utility of PET and PET-CT in the diagnosis and prognosis of mesothelioma. PET-CT was found to be more accurate than PET in terms of staging (P < 0.05) disease. Overall, PET accurately diagnoses MPM, predicts survival and disease recurrence. It can guide further management by predicting the response to chemotherapy and excluding surgery in patients with extrathoracic disease. Combined PET-CT has additional benefits in accurately staging disease.

S37 Comparison of dynamic contrast enhanced MRI (DCE-MRI) parameters with integrated PET-CT and serum mesothelin in the baseline assessment of malignant pleural mesothelioma

Integrated PET-CT scans and serum mesothelin measurement have shown early promise in predicting prognosis and evaluating treatment response in malignant pleural mesothelioma (MPM) but may be less reliable with sarcomatoid...

Decreased brain FDG uptake in patients with extensive non-Hodgkin’s lymphoma lesions

Faint brain [(18)F]fluoro-2-deoxyglucose (FDG) uptake has sporadically been reported in patients with FDG-avid large or diffusely extended tumors. The purpose of this study was to investigate whether there is a correlation between massive tumor uptake and decreased brain uptake on FDG positron emission tomography/computed tomography (PET/CT). Sixty-five patients with histologically confirmed non-Hodgkin's lymphoma who underwent FDG-PET/CT were enrolled. Thirty control subjects were also included to evaluate normal brain FDG uptake. PET/CT examinations were retrospectively reviewed. The volumetric regions of interest were placed over lesions by referring to CT and PET/CT fusion images to measure mean standardized uptake value (SUVavg). The products of SUVavg and tumor volume were calculated as total glycolytic volume (TGV). The maximum SUV (SUVmax) and SUVavg were measured in the cerebrum and cerebellum. The values of TGV and brain FDG uptake were plotted and analyzed with a linear regression method. In the lymphoma patients, there were statistically significant negative correlations between TGV and brain SUVs. Demonstrating a significant negative correlation between TGV and brain uptake validated the phenomenon of decreased brain FDG uptake. Diversion of FDG from the brain to the lymphoma tissue may occur during the FDG accumulation process. Recognition of this phenomenon prevents unnecessary further neurological examinations in such cases.

Reproducibility of 18F-FDG and 3′-Deoxy-3′-18F-Fluorothymidine PET Tumor Volume Measurements

The objective of this study was to establish the repeatability and reproducibility limits of several volume-related PET image-derived indices-namely tumor volume (TV), mean standardized uptake value, total glycolytic volume (TGV), and total proliferative volume (TPV)-relative to those of maximum standardized uptake value (SUV(max)), commonly used in clinical practice. Fixed and adaptive thresholding, fuzzy C-means, and fuzzy locally adaptive Bayesian methodology were considered for TV delineation. Double-baseline (18)F-FDG (17 lesions, 14 esophageal cancer patients) and 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) (12 lesions, 9 breast cancer patients) PET scans, acquired at a mean interval of 4 d and before any treatment, were used for reproducibility evaluation. The repeatability of each method was evaluated for the same datasets and compared with manual delineation. A negligible variability of less than 5% was measured for all segmentation approaches in comparison to manual delineation (5%-35%). SUV(max) reproducibility levels were similar to others previously reported, with a mean percentage difference of 1.8% +/- 16.7% and -0.9% +/- 14.9% for the (18)F-FDG and (18)F-FLT lesions, respectively. The best TV, TGV, and TPV reproducibility limits ranged from -21% to 31% and -30% to 37% for (18)F-FDG and (18)F-FLT images, respectively, whereas the worst reproducibility limits ranged from -90% to 73% and -68% to 52%, respectively. The reproducibility of estimating TV, mean standardized uptake value, and derived TGV and TPV was found to vary among segmentation algorithms. Some differences between (18)F-FDG and (18)F-FLT scans were observed, mainly because of differences in overall image quality. The smaller reproducibility limits for volume-derived image indices were similar to those for SUV(max), suggesting that the use of appropriate delineation tools should allow the determination of tumor functional volumes in PET images in a repeatable and reproducible fashion.

Prediction of Response to Neoadjuvant Radiotherapy in Patients With Locally Advanced Rectal Cancer by Means of Sequential 18FDG-PET

Morphologic imaging techniques perform poorly in assessing the response to preoperative radiotherapy (RT), mainly because of desmoplastic reactions. The aim of this study was to investigate the potential of sequential 18-fluoro-2-deoxy-d-glucose (18FDG-PET) in assessing the response of rectal cancer to neoadjuvant RT and to determine which parameters can be used as surrogate markers for histopathologic response. 18FDG-PET scans were acquired before and during the 5th week after the end of RT. Tracer uptake was assessed semiquantitatively using standardized uptake values (SUV). The percentage differences (%Δ) between pre- and post-RT scans in SUV(max), SUV(mean), metabolic volume (MV), and total glycolytic volume (tGV) were calculated. Forty-five consecutive patients with histologically confirmed rectal adenocarcinoma were enrolled. After neoadjuvant RT, 20 of the 45 patients were classified as histopathologic responders and 25 as non-responders. Intense 18F-FDG uptake was seen in all tumors before neoadjuvant RT (average SUV(max) 12.9 ± 6.0). When patients were classified as histologic responders and nonresponders, significant differences in %ΔSUV(max) (55.8% vs. 37.4%, p = 0.023) and %ΔSUV(mean) (40.1% vs. 21.0%, p = 0.001) were observed between the two groups. For %ΔMV and %ΔtGV, decreases were more prominent in responders but were not significantly different from those in nonresponders. As demonstrated by receiver operating characteristic analysis, %ΔSUV(mean) was a more powerful discriminator than was %ΔSUV(max). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for optimal threshold of %ΔSUV(mean) (24.5%) were 80%, 72%, 76%, 70%, and 82% respectively. Sequential 18FDG-PET allows assessment of the response to preoperative RT. Both %ΔSUV(mean) and %ΔSUV(max) correlate with histopathologic response and can be used to evaluate and compare the effectiveness of different neoadjuvant treatment strategies. The maximum accuracy figures and the positive predictive value figures for both Δ%SUV(mean) and Δ%SUV(max) are, however, too low to justify modification of the standard treatment protocol of an individual patient.

A Novel Prognostic Model for Malignant Mesothelioma Incorporating Quantitative FDG-PET Imaging with Clinical Parameters

Existing prognostic systems for malignant pleural mesothelioma do not incorporate imaging information. We aimed to identify the contribution of quantitative fluorodeoxyglucose positron emission tomography (FDG-PET) analysis to other prognostic variables in this disease. Patients with malignant pleural mesothelioma underwent helical thoracoabdominal computed tomography and FDG-PET scans at baseline. Patients were treated as clinically indicated and followed for survival. FDG-PET variables derived included total glycolytic volume, a composite of tumor volume and glycolytic activity. Ninety-three patients were accrued from 2003 to 2006. Of 89 eligible assessable patients, 28 had undergone pleurodesis before enrolment. Seventeen patients remained alive at analysis; median survival is 15.4 months. On univariate analysis, significant prognostic factors were: total glycolytic volume on FDG-PET (P = 0.003), sarcomatoid histology (P < 0.0005), weight loss (P = 0.031), computed tomography stage (P = 0.015), and European Organization for Research and Treatment of Cancer good prognostic score (P = 0.049). In patients with epithelioid or biphasic histology, baseline total glycolytic volume remained predictive of survival in patients with (P = 0.01) or without (P = 0.018) previous pleurodesis. In multivariate analysis, no variable other than histology contributed to the model in patients with sarcomatoid histology; total glycolytic volume and weight loss contributed to the models in patients with nonsarcomatoid histology. computed tomography-assessed tumor-node-metastasis stage did not contribute to the model. A nomogram, which incorporates quantitative PET parameters and pleurodesis into prognostic information, is presented. Sarcomatoid histology remains the strongest prognostic factor. In patients with non sarcomatoid disease, volumetric FDG-PET parameters are more predictive of survival than tumor-node-metastasis staging, suggesting that tumor volume and glycolytic activity may be more important determinants of prognosis in malignant pleural mesothelioma than anatomic extent of disease.

Assessment of tumour response with 18F-fluorodeoxyglucose positron emission tomography using three-dimensional measures compared to SUVmax—a phantom study

SUVmax is currently the most common semi-quantitative method of response assessment on FDG PET. By defining the tumour volume of interest (VOI), a measure of total glycolytic volume (TGV) may be obtained. We aimed to comprehensively examine, in a phantom setting, the accuracy of TGV in reflecting actual lesion activity and to compare TGV with SUVmax for response assessment. The algorithms for VOI generation from which TGV was derived included fixed threshold techniques at 50% of maximum (MAX50), 70% of maximum (MAX70), an adaptive threshold of 50% of (maximum + background)/2 (BM50) and a semi-automated iterative region-growing algorithm, GRAB. Comparison with both actual lesion activity and response scenarios was performed. SUVmax correlated poorly with actual lesion activity (r = 0.651) and change in lesion activity (r = 0.605). In a response matrix scenario SUVmax performed poorly when all scenarios were considered, but performed well when only clinically likely scenarios were included. The TGV derived using MAX50 and MAX70 algorithms performed poorly in evaluation of lesion change. The TGV derived from BM50 and GRAB algorithms however performed extremely well in correlation with actual lesion activity (r = 0.993 and r = 0.982, respectively), change in lesion activity (r = 0.972 and r = 0.963, respectively) and in the response scenario matrix. TGVGRAB demonstrated narrow confidence bands when modelled with actual lesion activity. Measures of TGV generated by iterative algorithms such as GRAB show potential for increased sensitivity of metabolic response monitoring compared to SUVmax, which may have important implications for improved patient care.

Early Prediction of Response to Chemotherapy and Survival in Malignant Pleural Mesothelioma Using a Novel Semiautomated 3-Dimensional Volume-Based Analysis of Serial 18F-FDG PET Scans

The aim of chemotherapy for mesothelioma is to palliate symptoms and improve survival. Measuring response using CT is challenging because of the circumferential tumor growth pattern. This study aims to evaluate the role of serial (18)F-FDG PET in the assessment of response to chemotherapy in patients with mesothelioma. Patients were prospectively recruited and underwent both (18)F-FDG PET and conventional radiological response assessment before and after 1 cycle of chemotherapy. Quantitative volume-based (18)F-FDG PET analysis was performed to obtain the total glycolytic volume (TGV) of the tumor. Survival outcomes were measured. Twenty-three patients were suitable for both radiological and (18)F-FDG PET analysis, of whom 20 had CT measurable disease. After 1 cycle of chemotherapy, 7 patients attained a partial response and 13 had stable disease on CT assessment by modified RECIST (Response Evaluation Criteria in Solid Tumors) criteria. In the 7 patients with radiological partial response, the median TGV on quantitative PET analysis fell to 30% of baseline (range, 11%-71%). After 1 cycle of chemotherapy, Cox regression analysis demonstrated a statistically significant relationship between a fall in TGV and improved patient survival (P = 0.015). Neither a reduction in the maximum standardized uptake value (P = 0.097) nor CT (P = 0.131) demonstrated a statistically significant association with patient survival. Semiquantitative (18)F-FDG PET using the volume-based parameter of TGV is feasible in mesothelioma and may predict response to chemotherapy and patient survival after 1 cycle of treatment. Therefore, metabolic imaging has the potential to improve the care of patients receiving chemotherapy for mesothelioma by the early identification of responding patients. This technology may also be useful in the assessment of new systemic treatments for mesothelioma.