Whole-body Metabolic Burden Research Articles

Prognostic value of texture analysis of the primary tumour in high-risk neuroblastoma: An 18 F-DOPA PET study.

To evaluate the prognostic value of texture analysis of the primary tumour with 18 fluorine-dihydroxyphenylalanine positron emission tomography/X-ray computed tomography (18 F-DOPA PET/CT) in patients affected by high-risk neuroblastoma (HR-NBL). We retrospectively analysed 18 patients with HR-NBL, which had been prospectively enrolled in the course of a previous trial investigating the diagnostic role of 18 F-DOPA PET/CT at the time of the first onset. Texture analysis of the primary tumour was carried out on the PET images using LifeX. Conventional indices, histogram parameters, grey level co-occurrence (GLCM), run-length (GLRLM), neighbouring difference (NGLDM) and zone-length (GLZLM) matrices parameter were extracted; their values were compared with the overall metastatic load, expressed by means of whole-body metabolic burden (WBMB) score and the progression-free/overall survival (PFS and OS). There was a direct correlation between WBMB and radiomics parameter describing uptake intensity (SUVmean : p=.004) and voxel heterogeneity (entropy: p=.026; GLCM_Contrast: p=.001). Conversely, texture indices of homogeneity showed an inverse correlation with WBMB (energy: p=.026; GLCM_Homogeneity: p=.006). On the multivariate model, WBMB (p<.01) and the first standardised uptake value (SUV) quartile (p<.001) predicted PFS; OS was predicted by WBMB and the N-myc proto-oncogene protein (MYCN) amplification (p<.05) for both. Textural parameters describing heterogeneity and metabolic intensity of the primary HR-NBL are closely associated with its overall metastatic burden. In turn, the whole-body tumour load appears to be one of the most relevant predictors of progression-free and overall survival.

Prognostic Value of Interim 18F-DOPA and 18F-FDG PET/CT Findings in Stage 3-4 Pediatric Neuroblastoma.

This retrospective study aimed to determine the prognostic value of imaging parameters derived from midtherapy 18F-fluorodihydroxyphenylalanine (18F-DOPA) and 18F-FDG PET in pediatric patients with stage 3-4 neuroblastoma. We enrolled 32 stage 3-4 pediatric neuroblastoma patients who underwent 18F-DOPA and 18F-FDG PET/CT scans before and after 3 chemotherapy cycles. We measured metabolic and volumetric parameters and applied a metabolic burden scoring system to evaluate the primary tumor extent and soft tissue metastases and that of bone/bone marrow involvement. The associations between these parameters and clinical outcomes were investigated. Over a median follow-up period of 47 months (range, 3-137 months), 16 patients experienced disease progression, and 13 died. After adjustment for clinical factors, multivariate Cox proportional hazard models showed that interim tumor FDG/FDOPA SUVmax (hazard ratio [HR], 5.94; 95% confidence interval [CI], 1.10-34.98) and interim FDOPA whole-body metabolic burden scores (WBMB) (HR, 7.30; 95% CI, 1.50-35.50) were significant prognostic factors for overall survival (OS). Only interim FDOPA WBMB scores (HR, 7.05; 95% CI, 1.02-48.7) were predictive of progression-free survival. Based on median cutoff values, prognosis (OS and progression-free survival) was significantly associated with an interim FDOPA WBMB score ≥21.92 (all P < 0.05) and interim tumor FDG/FDOPA (SUVmax) score ≥0.57 with poor OS (P < 0.05). Our results indicate that midtreatment FDG and FDOPA PET/CT could serve as prognostic markers in stage 3-4 neuroblastoma patients.

Prognostic value of 18F-DOPA PET/CT at the time of recurrence in patients affected by neuroblastoma

The aim of this study was to investigate the relationship between (123)I-metaiodobenzylguanidine (MIBG) scan semi-quantification and a new (18)F-DOPA positron emission tomography (PET)/CT score in patients with suspected or documented neuroblastoma (NB) relapse and to assess the association between these two parameters and progression-free survival (PFS)/overall survival (OS). We analysed 24 NB patients who had undergone (123)I-MIBG and (18)F-DOPA PET/CT scans at the time of suspected relapse, after applying a proper scoring system for each scan. In time-to-event analyses, the score distributions were regarded as continuous and were categorized in tertiles and medians. We used Kaplan-Meier curves and Cox proportional hazard models for PFS and OS in order to estimate the independent prognostic impact of (123)I-MIBG and (18)F-DOPA PET/CT scans. The (123)I-MIBG and (18)F-DOPA scores were highly and positively correlated (Spearman's rho = 0.8, p < 0.001). Over a median follow-up of 14 months (range 6-82), 12 cases of disease progression and 6 deaths occurred. Multivariate Cox models showed a higher risk of disease progression [hazard ratio (HR) 17.0, 95% confidence interval (CI) 2.7-109] in NB patients with (123)I-MIBG score > 3 (3rd tertile) and an even higher risk (HR:37.2, 95% CI 2.4-574) in those with (18)F-DOPA whole-body metabolic burden (WBMB) >7.5 (median), after adjustment for all main clinical/pathological factors considered. Kaplan-Meier analyses showed a significant association with OS (log-rank p = 0.01 and p = 0.03 for (123)I-MIBG and (18)F-DOPA WBMB, respectively). Our results confirm the good agreement between (18)F-DOPA PET/CT and (123)I-MIBG scan in patients affected by NB relapse. In time-to-event analyses, (123)I-MIBG scan and (18)F-DOPA PET/CT scores were independently and significantly associated with disease progression.

Current Evidence Base of FDG-PET/CT Imaging in the Clinical Management of Malignant Pleural Mesothelioma: Emerging Significance of Image Segmentation and Global Disease Assessment

Increasingly, integrated positron emission tomography-computed tomography (PET/CT) imaging is playing a crucial role in the assessment of patients with known or suspected malignant pleural mesothelioma (MPM). Based on the data reported in the literature, this combined modality is likely to become the instrument of choice for examining patients of MPM. The research on this subject has focused on the following five domains: (1) differentiation of MPM from other benign pleural diseases, (2) preoperative staging for the selection of appropriate candidates for surgery, (3) evaluation for therapy response and post-treatment surveillance for recurrence, (4) prognostication based upon the intensity of 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) uptake, and (5) planning of radiotherapy. These represent the bases for critical decision making in the management of mesothelioma, and FDG-PET/CT offers potential advantages over conventional CT imaging and thus can play a pivotal role in this regard. Optimal characterization of this potentially fatal disease with a high negative predictive value for MPM, superior capability for cancer staging initially and at the later course of disease, and ability for measuring therapeutic response and the precise determination of the target volume for radiotherapy planning represent distinct advantages of this promising molecular imaging tool. In this communication, we have explored the promising role of integrated FDG-PET/CT in the overall management of this serious malignancy. From the available data, the major role of PET-CT at present appears to be in the preoperative disease staging, response to treatment assessment, and post-treatment disease surveillance of MPM. In all these three areas, PET-CT convincingly shows better results than conventional anatomical imaging alone and thereby can aid in exploring novel therapeutic approaches. Disease prognosis and radiotherapy planning are evolving areas where this modality has demonstrated significant promise, but this has to be investigated further. The differentiating of MPM from benign pleural disease is a challenging issue; though in limited studies, it has shown promising results, single standardized uptake value (SUV) cutoff technique cannot be the optimal way for this purpose. Dual time point and delayed imaging helps further in this setting; however, more data require to be accrued in this area. We, in this review, have also discussed the feasibility of a new method of image segmentation based on an iterative thresholding algorithm, which permits definition of the boundaries of lesions based on PET images alone to provide lesional metabolically active tumor volumes, lesional partial volume corrected SUV (PVC-SUV) measurements, lesional PVC metabolic burden (PVC-MB) (calculated as the product of lesional MVP and lesional PVC-SUV), and whole body metabolic burden (WBMB) (calculated as the sum of lesional PVC-MB of all lesions). This global disease assessment, we believe, will be the way forward for assessing this malignancy with a non-invasive imaging modality.

6-[F-18]Fluoro-l-Dihydroxyphenylalanine Positron Emission Tomography Is Superior to Conventional Imaging with 123I-Metaiodobenzylguanidine Scintigraphy, Computer Tomography, and Magnetic Resonance Imaging in Localizing Tumors Causing Catecholamine Excess

Catecholamine excess is rare, but symptoms may be life threatening. The objective of the study was to investigate the sensitivity of 6-[F-18]fluoro-l-dihydroxyphenylalanine positron emission tomography ((18)F-DOPA PET), compared with (123)I-metaiodobenzylguanidine ((123)I-MIBG) scintigraphy and computer tomography (CT)/magnetic resonance imaging (MRI) for tumor localization in patients with catecholamine excess. All consecutive patients with catecholamine excess visiting the University Medical Center Groningen, Groningen, The Netherlands, between March 2003 and January 2008 were eligible. Forty-eight patients were included. The final diagnosis was pheochromocytoma in 40, adrenal hyperplasia in two, paraganglioma in two, ganglioneuroma in one, and unknown in three. Sensitivities and discordancy between (18)F-DOPA PET, (123)I-MIBG, and CT or MRI were analyzed for individual patients and lesions. Metanephrines and 3-methoxytyramine in plasma and urine and uptake of (18)F-DOPA with PET were measured to determine the whole-body metabolic burden and correlated with biochemical tumor activity. The gold standard was a composite reference standard. (18)F-DOPA PET showed lesions in 43 patients, (123)I-MIBG in 31, and CT/MRI in 32. Patient-based sensitivity for (18)F-DOPA PET, (123)I-MIBG, and CT/MRI was 90, 65, and 67% (P < 0.01 for (18)F-DOPA PET vs. both (123)I-MIBG and CT/MRI, P = 1.0 (123)I-MIBG vs. CT/MRI). Lesion-based sensitivities were 73, 48, and 44% (P < 0.001 for (18)F-DOPA PET vs. both (123)I-MIBG and CT/MRI, P = 0.51 (123)I-MIBG vs. CT/MRI). The combination of (18)F-DOPA PET with CT/MRI was superior to (123)I-MIBG with CT/MRI (93 vs. 76%, P < 0.001). Whole-body metabolic burden measured with (18)F-DOPA PET correlated with plasma normetanephrine (r = 0.82), urinary normetanephrine (r = 0.84), and metanephrine (r = 0.57). To localize tumors causing catecholamine excess, (18)F-DOPA PET is superior to (123)I-MIBG scintigraphy and CT/MRI.

Determination of whole-body metabolic burden as a quantitative measure of disease activity in lymphoma: a novel approach with fluorodeoxyglucose-PET

Currently, there is no definite consensus regarding the best index to assess disease activity with fluorodeoxyglucose-PET imaging. Maximum standardized uptake value (SUVmax) is most frequently used in day-to-day practice for this purpose. This approach very often reflects the metabolic activity of only a small sample of the total ongoing process in the entire body. Here we introduce a new concept called metabolic burden (MB) to measure disease activity in cancer patients. MB was calculated by measuring the volume (VCT) around a lesion that appeared on computed tomography (CT), the mean SUV that appeared on PET of the CT volume (SUVmean CT), and the recovery coefficient (RC) using the following formula: (Equation is included in full-text article.) If CT was unavailable, a region of interest (ROI) around the lesion was defined by a 40% SUVmax threshold and the volume and SUVmean were determined for that ROI. The whole-body metabolic burden (WBMB) was calculated as the sum of the individual MBs of all the lesions identified. We retrospectively reviewed 19 patients with non-Hodgkin's lymphoma who were treated with commercially available anti-CD20 radioimmunotherapy agents or conventional chemotherapy. All had a pretreatment and posttreatment fluorodeoxyglucose-PET and CT scan within 1-3 months of receiving systemic therapy. Either abnormal areas appearing on PET alone or corresponding lesions on CT were used to calculate the tumor volume (TV). Nodes of less than 2 cm occurring in clusters were grouped together into a single ROI. Thirty-eight regional collections in 14 patients were found in combined pretreatment and posttreatment studies and were assessed. The TVs varied in pretreatment size from 5.8 to 857 cm and posttreatment from 0 to 81 cm. Pretreatment WBMB varied from 27 to 10 218 cm and posttreatment from 0 to 279 cm. We then compared the standard indices of SUVmean and SUVmax with those of WBMB to determine which of the indices would have the best sensitivity as a predictor of therapeutic response. Five of the 19 patients had a complete response. In 14 patients with partial response, the average change in WBMB was 80%, the TV decreased by 76%, the SUVmax decreased by 42%, and the SUVmean decreased by 38.5%. The results of this analysis demonstrate that measurement of WBMB may prove to be superior to the existing methods in assessing and managing patients with non-Hodgkin's lymphoma. This index may be the best way to monitor the changes in WBMB as a patient is undergoing treatment.