Preoperative FDG-PET Research Articles

Abstract P2-02-12: Gain-of-function of mutant P53 elevates glucose uptake via membrane translocation of GLUT1 in breast cancer

Abstract Background High rate of glycolysis exhibited by cancer cells plays a crucial role in carcinogenesis and tumor progression. Previous study showed that gain-of-function (GOF) by mutant P53 drives the Warburg effect via GLUT1 membrane translocation in malignancies. Also, in the patients with a preoperative 18F-fluorodeoxy glucose positron emission tomography (FDG-PET), which enables to estimate glucose uptake by tumor as standardize uptake value (SUV), we identified high SUV as a poor prognostic marker. In this study, we wondered whether P53 mutation promotes GLUT1 membrane translocation and increases glucose uptake in MCF10A cells and patients with breast cancer. Methods Transcriptomic profiling was carried out using gene expression data from 66 breast cancer patients who underwent preoperative FDG-PET to identify a molecular signature associated with SUV. Gene network analyses revealed dysregulation of P53 pathway. We generated both MCF10A cell lines with P53-knock down and P53-mutant which include sequence variants (R175H, R273H, and R248W). Glucose uptake assay and confocal imaging studies with 2NDBG were performed. Confocal imaging system was used to detect GLUT1 membrane expression. In case-matched patients according to P53 mutation (n=114), we compared SUV. Mutational analysis of exons 5-9 of the P53 gene was carried out using Sanger sequencing. Results Glucose uptake assay showed that the level of glucose uptake was increased in P53 mutant MCF10A cell lines with a 1.5-1.8 fold change compare with wild-type MCF10A. The increase of glucose uptake by mutant-P53 was reproducible with the experiments with 2NBGD. By contrast, stable knock down of P53 did not induce an elevation of glucose uptake in MCF10A cells. The confocal imaging studies captured translocation to membrane of GLUT1 in mutant P53-MCF10A. However, in wild-type MCF10A, GLUT1 was diffusely expressed in cytoplasm. . In tumors from patients, membraneous expression of GLUT1 was significantly higher in tumors with p53 mutation than in tumors with intact p53 (P=0.022). Further, the mean SUV of p53-mutational group was significantly higher than that of wild-type p53-group (7.49 vs. 5.44, P=0.013). In multivariate analysis for recurrence-free survival, p53 mutational status carried prognostic significance (hazard ratio 3.73, 95% CI 1.15-12.07) independent of tumor size, nodal status, and estrogen receptor status. Conclusion We showed that GOF by P53 mutation promotes GLUT1 translocation to membrane, which consequently induces glucose influx in MCF10A cells, elucidating that P53 mutation contributes to the increase of SUV in patients with breast cancer. Citation Format: Ahn SG, Bae SJ, Yoon CI, Cha C, Park SE, Jeong J. Gain-of-function of mutant P53 elevates glucose uptake via membrane translocation of GLUT1 in breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-02-12.

Clinical Significance of 18F-Fluorodeoxyglucose-Positron Emission Tomography-Positive Lymph Nodes to Outcomes of Trimodal Therapy for Esophageal Squamous Cell Carcinoma.

The clinical significance of lymph node (LN) status determined by preoperative 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) has not been investigated in patients with locally advanced esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemoradiotherapy (NCRT) followed by surgery (trimodal therapy). This study reviewed 132 consecutive patients with ESCC who had been preoperatively evaluated using FDG-PET before and after NCRT to analyze associations among LN status according to PET findings, pathologic LN metastasis, and prognosis of ESCC after trimodal therapy. Lymph nodes that were PET-positive both before and after NCRT comprised significant predictive markers of pathologic LN metastasis in station-by-station analyses (sensitivity, specificity, and accuracy respectively 41.7%, 95.0%, and 92.7% before, and 12.0%, 99.4%, and 95.6% after NCRT; both p < 0.0001). The numbers of LNs evaluated using PET before and after NCRT were significantly associated with those of pathologic metastatic LNs. Uni- and multivariable analyses selected LN status determined by PET before NCRT as a significant independent predictor of both recurrence-free [LN-negative vs LN-positive: hazard ratio (HR) 1.90; 95% confidence interval (CI) 1.02-3.23; p = 0.045] and overall survival (HR 2.62; 95% CI 1.29-5.30; p = 0.01). The status of LN determined by preoperative FDG-PET is significantly associated with pathologic LN status and the prognosis of ESCC with trimodal therapy. Thus, FDG-PET is a useful diagnostic tool for preoperative prediction of pathologic LN metastasis and survival among patients with ESCC.

Usefulness of Preoperative &lt;sup&gt;18&lt;/sup&gt;F-FDG PET/CT for Patients with Thymic Epithelial Tumors

The purpose of this study was to investigate the relationship between preoperative FDG-PET parameters and the World Health Organization (WHO) classification or Masaoka staging system of thymic epithelial tumors. We retrospectively reviewed 32 patients with histologically proven thymic epithelial tumors who underwent FDG-PET/CT before surgical resection. FDG-PET parameters, including the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolytic activity (TLG), were measured. These PET parameters were compared in the Masaoka staging system and WHO classification. A receiver operating characteristics (ROC) analysis was performed to identify the cut-off values of PET parameters for the accurate differentiation of early and advanced stages in the Masaoka staging system. There were 17 low-risk thymomas (1 type A, 9 type AB, and 7 type B1), 8 high-risk thymomas (4 type B2 and 4 type B3), and 7 thymic carcinomas (7 squamous cell carcinoma). Their Masaoka stages were as follows: 24 in the early stage (stages I and II) and 8 in the advanced stage (stage III). Regarding the WHO classification, only SUVmax showed a significant difference (P < 0.05). In the Masaoka stage, all PET parameters were significantly higher in the advanced stage than in the early stage (P < 0.05). In the ROC analysis to predict the early and advanced stages in thymic epithelial tumors, the area under the curve was the highest for TLG among the PET parameters examined and the cut-off value of TLG for discriminating the early from advanced stage with maximal sensitivity and specificity was 30.735. Although volumetric PET parameters, such as MTV and TLG, did not correlate with the WHO classification, a significant correlation was observed between SUVmax and the WHO classification. In the Masaoka staging system, volumetric PET parameters may achieve more precise staging than SUVmax.

Interregional metabolic connectivity of 2-deoxy-2[18 F]fluoro-D-glucose positron emission tomography in vagus nerve stimulation for pediatric patients with epilepsy: A retrospective cross-sectional study.

With the recognition of epilepsy as a network disease that disrupts the organizing ability of resting-state brain networks, vagus nerve stimulation (VNS) may control epileptic seizures through modulation of functional connectivity. We evaluated preoperative 2-deoxy-2[18 F]fluoro-D-glucose (FDG) positron emission tomography (PET) in VNS-implanted pediatric patients with refractory epilepsy to analyze the metabolic connectivity of patients and its prognostic role in seizure control. Preoperative PET data of 66 VNS pediatric patients who were followed up for a minimum of 1year after the procedure were collected for the study. Retrospective review of the patients' charts was performed, and five patients with inappropriate PET data or major health issues were excluded. We conducted an independent component analysis of FDG-PET to extract spatial metabolic components and their activities, which were used to perform cross-sectional metabolic network analysis. We divided the patients into VNS-effective and VNS-ineffective groups (VNS-effective group, ≥50% seizure reduction; VNS-ineffective group, <50% reduction) and compared metabolic connectivity differences between groups using a permutation test. Thirty-four (55.7%) patients showed >50% seizure reduction from baseline frequency 1year after VNS. A significant difference in metabolic connectivity evaluated by preoperative FDG-PET was noted between groups. Relative changes in glucose metabolism were strongly connected among the areas of brainstem, cingulate gyrus, cerebellum, bilateral insula, and putamen in patients with <50% seizure control after VNS. This study shows that seizure outcome of VNS may be influenced by metabolic connectivity, which can be obtained from preoperative PET imaging. This study of metabolic connectivity analysis may contribute in further understanding of the mechanism of VNS in intractable seizures.

Presurgical Identification of Uterine Smooth Muscle Malignancies through the Characteristic FDG Uptake Pattern on PET Scans.

The unidentified presence of uterine smooth muscle malignancies poses a tremendous risk in women planning surgery for presumed benign leiomyomas. We sought to investigate whether preoperative FDG PET may be useful to identify leiomyosarcomas (LMS) and smooth muscle tumors of uncertain malignant potential (STUMP). Methods. We investigated patients with rapidly growing uterine masses which were suspected of being malignant on ultrasound or MRI. Among the 21 patients who underwent FDG PET, we identified 7 LMS, 1 STUMP, and 13 leiomyomas. PET-derived parameters and FDG uptake patterns were analyzed retrospectively. Results. The SUVmax values of LMS/STUMP (range: 3.7–11.8) were significantly higher than those observed in leiomyomas (range: 2.0–9.4; P=0.003) despite a significant overlap. The metabolic tumor/necrosis ratio was significantly higher in LMS/STUMP than in leiomyomas (P < 0.001), with no significant intergroup overlaps. All LMS/STUMP revealed a characteristic pattern of FDG uptake, identifying a specific “hollow ball” sign (corresponding to areas of coagulative tumor necrosis). In contrast, this sign was invariably absent in patients with leiomyomas. Conclusion. The characteristic FDG uptake pattern instead of SUV on PET images allows identifying LMS/STUMP in patients with rapidly growing uterine masses, avoiding the deleterious consequences of regular surgery for presumed benign leiomyomas.

Objective 3D surface evaluation of intracranial electrophysiologic correlates of cerebral glucose metabolic abnormalities in children with focal epilepsy.

To determine the spatial relationship between 2-deoxy-2[18 F]fluoro-D-glucose (FDG) metabolic and intracranial electrophysiological abnormalities in children undergoing two-stage epilepsy surgery, statistical parametric mapping (SPM) was used to correlate hypo- and hypermetabolic cortical regions with ictal and interictal electrocorticography (ECoG) changes mapped onto the brain surface. Preoperative FDG-PET scans of 37 children with intractable epilepsy (31 with non-localizing MRI) were compared with age-matched pseudo-normal pediatric control PET data. Hypo-/hypermetabolic maps were transformed to 3D-MRI brain surface to compare the locations of metabolic changes with electrode coordinates of the ECoG-defined seizure onset zone (SOZ) and interictal spiking. While hypometabolic clusters showed a good agreement with the SOZ on the lobar level (sensitivity/specificity = 0.74/0.64), detailed surface-distance analysis demonstrated that large portions of ECoG-defined SOZ and interictal spiking area were located at least 3 cm beyond hypometabolic regions with the same statistical threshold (sensitivity/specificity = 0.18-0.25/0.94-0.90 for overlap 3-cm distance); for a lower threshold, sensitivity for SOZ at 3 cm increased to 0.39 with a modest compromise of specificity. Performance of FDG-PET SPM was slightly better in children with smaller as compared with widespread SOZ. The results demonstrate that SPM utilizing age-matched pseudocontrols can reliably detect the lobe of seizure onset. However, the spatial mismatch between metabolic and EEG epileptiform abnormalities indicates that a more complete SOZ detection could be achieved by extending intracranial electrode coverage at least 3 cm beyond the metabolic abnormality. Considering that the extent of feasible electrode coverage is limited, localization information from other modalities is particularly important to optimize grid coverage in cases of large hypometabolic cortex. Hum Brain Mapp 38:3098-3112, 2017. © 2017 Wiley Periodicals, Inc.

Significance of preoperative fluorodeoxyglucose-positron emission tomography in prediction of tumor recurrence after liver transplantation for hepatocellular carcinoma patients: a Japanese multicenter study.

In the present study, we conducted a multicenter nationwide survey to investigate the effects of preoperative fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) on the prediction of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). From 16 Japanese LT centers, data were collected on 182 recipients with HCC who underwent living donor liver transplantation (LDLT) between February 2005 and November 2013. PET-positive status was defined as increased uptake of FDG in the tumor compared to the surrounding non-tumor liver tissue. The median follow-up after LDLT was 54.5months (range 1-125months). Postoperative HCC recurrence occurred in 23 patients. Multivariate analysis revealed that exceeding the Milan criteria (MC), alpha-fetoprotein (AFP) level≥115ng/ml, and PET-positive status were significant and independent risk factors for recurrence. In the over-MC group, a subgroup of patients with AFP level<115ng/ml and PET-negative status (n=22) had a significantly lower 5-year recurrence rate than the other patients (n=27, 19% vs. 53%, P=0.019). These results suggest that preoperative FDG-PET status offers additional information on HCC recurrence risk after LT. Over-MC patients with PET-negative status and lower AFP level may achieve successful outcome comparable to that of within-MC patients.

Clinical Significance of 18F-FDG-PET in Invasive Lobular Carcinoma.

The diagnostic utility of 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) for breast cancer is controversial. The histological type or tumor size of breast cancer has been reported to be associated with a greater likelihood of positive FDG uptake. Compared to invasive ductal carcinomas (IDCs), invasive lobular carcinomas (ILCs) have a lower level of FDG uptake and are detected at a significantly lower sensitivity. The role of preoperative FDG-PET for ILCs may, thus, be limited. Few data evaluating the significance of FDG-PET in ILCs are available. Here, we evaluated the clinical significance of FDG-PET for ILC patients. We retrospectively investigated the cases of 196 consecutive patients with primary breast cancer who were diagnosed as having ILC (n=15) or IDC (n=181) and underwent FDG-PET preoperatively. Fifteen (7.7%) of patients were histopathologically diagnosed as ILC. A univariate analysis revealed that tumor size, extent of tumor, estrogen receptor (ER) expression and progesterone receptor (PgR) expression were significantly different between the ILC and IDC groups. The maximum standardized uptake value (SUVmax) values of the primary tumors were not significantly different between the two groups but, regardless of the larger size of tumor or ductal spread, the SUVmax was relatively lower in the ILC group compared to the IDC group. The tumors in two ILC cases showed no FDG uptake. Among the ILC cases, there were linear associations between SUVmax and tumor size and between SUVmax and the nuclear grade by Pearson correlation (r=0.447, p=0.048 and r=0.519, p=0.024, respectively). Our findings imply that the preoperative FDG uptake in ILC may be reflective of the tumor size and the nuclear grade of the tumor. FDG uptake may be useful and predictive of aggressive features or prognosis in ILC patients.

The predictive value of FDG-PET with 3D-SSP for surgical outcomes in patients with temporal lobe epilepsy

PurposeWe retrospectively evaluated the diagnostic value of 18F-2-fluorodeoxy-d-glucose positron emission tomography (FDG-PET) with statistical analysis for the foci detection and predictive utility for postsurgical seizure outcome of patients with mesial temporal lobe epilepsy (mTLE). MethodWe evaluated 40 patients who were diagnosed mTLE and underwent selective amygdalohippocampectomy (SAH) or anterior temporal lobectomy (ATL) in our institute. Preoperative interictal FDG-PET with statistical analysis using three-dimensional stereotactic surface projection (3D-SSP) was detected with several clinical data including seizure semiology, MRI, scalp electroencephalography, surgical procedure with SAH or ATL and postsurgical outcome. The region of interest (ROI) was defined on ⿿Hippocampus & Amygdala⿿, ⿿Parahippocampal gyrus & Uncus⿿, ⿿T1 & T2⿿, and ⿿T3 & Fusiform gyrus⿿. We obtained the ratio of hypometabolism difference (RHD) by 3D-SSP, and evaluated the relation among hypometabolic extent, surgical outcome and surgical procedure. ResultThe RHD in each ROIs ipsilateral to operative side was significantly higher than that of contralateral side in good outcome group. Hypometabolism of ⿿Hippocampus & Amygdala⿿ was most reliable prognostic factor. Patients of discordant with presurgical examinations hardly showed obvious lateralized hypometabolism. Nevertheless, when they have significantly high RHD in mesial temporal lobe, good surgical outcome was expected. There was not significant difference of RHD distribution between SAH and ATL in good outcome group. ConclusionSignificant hypometabolism in mesial temporal lobe on FDG-PET with 3D-SSP is useful to predict good surgical outcome for patients with mTLE, particularly in discordant patients with hypometabolism in mesial temporal structure. However, FDG-PET is not indicative of surgical procedure.

Reproducibility and uptake time dependency of volume-based parameters on FDG-PET for lung cancer.

BackgroundVolume-based parameters, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), on F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) are useful for predicting treatment response in nonsmall cell lung cancer (NSCLC). We aimed to examine intra- and inter-operator reproducibility to measure the MTV and TLG, and to estimate their dependency on the uptake time.MethodsFifty NSCLC patients underwent preoperative FDG-PET. After an injection of FDG, the whole body was scanned twice: at the early phase (61.4 ± 2.8 min) and delayed phase (117.7 ± 1.6 min). Two operators independently defined the tumor boundary using three different delineation methods: (1) the absolute SUV threshold method (MTVp and TLGp; p = 2.0, 2.5, 3.0, 3.5), (2) the fixed% SUVmax threshold method (MTVq% and TLGq%; q = 35, 40, 45), and (3) the adaptive region-growing method (MTVARG and TLGARG). Parameters were compared between operators and between phases.ResultsBoth the intra- and inter-operator reproducibility were high for all parameters using any method (intra-class correlation > 0.99 each). MTV3.0 and MTV3.5 resulted in a significant increase from the early to delayed phase (P < 0.05 for both), whereas MTV2.0 and MTV2.5 neither increased nor decreased (P = n.s.). All of the MTVq% values significantly decreased over time (P < 0.01), whereas MTVARG and TLG with any delineation method increased significantly (P < 0.05).ConclusionsHigh reproducibility of MTV and TLG was obtained by all of the methods used. MTV2.0 and MTV2.5 were the least sensitive to uptake time, and may be good alternatives when we compare images acquired with different uptake times, although applying constant uptake time is important for volume measurement.

Implication of 18F-fluorodeoxyglucose uptake by affected lymph nodes in cases with differentiated thyroid cancer.

In this study, we evaluated the usefulness of positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) to detect metastatic lymph nodes in differentiated thyroid cancer. We also investigated whether certain factors, including the size of the metastasis to the lymph nodes, are associated with FDG avidity. A total of 22 consecutive patients with differentiated thyroid cancer who underwent FDG-PET preoperatively were enrolled in this study. Lymph node metastasis was diagnosed in the final pathology in 10 of the 22 patients (45.5%). The mean maximum standardized uptake value of the metastatic lymph nodes was 4.53 (range, 0-23.5). The 22 cases with differentiated thyroid cancer were divided into two groups based on lymph node metastasis. Clinicopathological variables other than FDG uptake of metastatic lymph nodes were not predictors of lymph node metastasis of thyroid cancer. The sensitivity, specificity, overall accuracy and false-negative rates of preoperative FDG-PET in the prediction of lymph node status were 40.0, 100, 72.7 and 60.0%, respectively. The false-positive rate of FDG-PET evaluation was 0%. The mean largest dimension of metastasis was 23.0 mm for FDG-positive cases and 10.9 mm for FDG-negative cases. There was a marked difference in the size of metastases between FDG-positive and -negative cases; however, even in patients with node metastasis >10 mm, the false-negative rate was 50.0%. Therefore, FDG-PET imaging was not found to be sufficient for the evaluation of lymph node status, particularly in cases with small metastases. Our findings indicate that preoperative FDG-PET evaluation of the lymph nodes cannot be considered predictive of the final pathology.

Increased 18F-FDG uptake in the trapezius muscle in patients with spinal accessory neuropathy

To investigate 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) signal changes of denervated muscles in patients with electrophysiologically confirmed neuropathy. MethodsThis is a case series of three cancer patients who were referred to the electromyography laboratory in 2013 due to shoulder discomfort after surgery including neck dissection. Spinal accessory neuropathy was diagnosed based on electrophysiological studies. Patients' medical history, electrophysiological data, and FDG-PET images were reviewed retrospectively. Mean standard uptake values (SUV) of trapezius muscles were measured. ResultsThe patients (3 men, aged 61–78years) showed spinal accessory neuropathy with different degrees of severity. In all patients, preoperative or postoperative FDG-PET showed increased FDG uptake in the ipsilateral trapezius muscle. These results were compatible with previously reported glucose hypermetabolism in denervated skeletal muscles. ConclusionThis is the first clinical report of increased FDG uptake by denervated muscles in electrophysiologically confirmed neuropathy.

Solitary Fibrous Tumors of the Pleura of the Thorax: CT and FDG PET Characteristics in a Tertiary Referral Center.

This study was conducted to describe the characteristics of a solitary fibrous tumor of the pleura (SFTP) on chest CT, and FDG PET. Furthermore, we analyze the prognosis of SFTP using large data confirmed in a tertiary referral hospital.From January 1997 to March 2012, 41 patients (21 males and 20 females; median age: 59 yr; age range: 27–85 yr) who were pathologically diagnosed with SFTP were consecutively examined. The CT findings, including the size, shape, homogeneity, and anatomic location (chest wall, intrapulmonary/fissure space, diaphragm, and mediastinum) of the SFTP, the 18F-fluorodeoxyglucose positron emission tomography (FDG PET) findings, and the histopathology findings were evaluated.Most of the patients had a mass-type (70.7%), oval/elliptical (80.5%), and homogeneous (70.7%) SFTP with a median diameter of 6.0 cm (range: 1–17). The most common anatomic location was the chest wall (43.9%), followed by the intrapulmonary/fissure space (22.0%), diaphragm (22.0%), and mediastinum (12.3%). For all the 9 patients, the mean maxSUV was 2.9 (SD = 1.16; range: 1.2–4.9) on FDG PET. The malignant SFTP (median: 3.6, range: 2.5–4.9) showed more hypermetabolic than benign SFTP (median: 2.0, range: 1.2–3.1) (P = 0.049).Through familiarity with the various features of the SFTP with regard to its size and location on the preoperative CT and FDG PET, we can add this rare pleural neoplasm to the differential diagnosis of other more common conditions. Moreover, an appropriate treatment choice can be made.

Large cell neuroendocrine carcinoma of the lung: CT and FDG PET findings

PurposeTo evaluate the CT and 18fluorine FDG PET findings of large cell neuroendocrine carcinomas (LCNECs) of the lung and to evaluate whether CT and FDG PET findings can help predict the clinical outcome. Material and methodsThirty-one patients (Male:Female=29:2; mean age, 69 years) who underwent surgical resection of an LCNEC of the lung were included in this retrospective study. The tumours were assessed with respect to morphologic characteristics and the maximum standardised uptake value (SUVmax) on pre-operative CT and FDG PET. For patients undergoing curative resection (n=26), disease-free survival was evaluated using the Kaplan–Meier test. The prognostic significance was assessed using a multivariate Cox proportional hazards regression analysis. ResultsThe mean tumour diameter was 3.8±2.1cm. Eight tumours (25.8%) were located centrally in the lung, and 23 (74.2%) were located peripherally. The margins were lobulated in 29 patients (93.5%) and well defined in 20 (64.5%). The mean SUVmax was 9.0±3.8. The five-year disease-free survival rate was 46.3%. The shorter disease-free survival was related to the TNM stage greater than stage I, no lobulated margin of a tumour, a SUVmax >12.9 of a tumour, a long diameter >5.6cm of a tumour, or female gender (P=0.115, P=0.134, P=0.056, P=0.168, P=0.113, respectively). The multivariate analysis indicated that a long diameter >5.6cm (hazard ratio, 9.265; 90% confidence interval (CI), 1.996–42.992; P=0.017), female gender (hazard ratio, 5.579; 90% CI, 1.398–22.264; P=0.041), no lobulated margin (hazard ratio, 9.955; 90% CI, 1.433–69.136; P=0.051), and SUVmax >12.9 (hazard ratio, 4.062; 90% CI, 1.235–13.368; P=0.053) were independent predictors of shorter disease-free survival. ConclusionsLCNECs of the lung more commonly occurred peripherally and exhibited well-defined and lobulated margins on CT. The mean SUVmax was consistent with malignant tumours. Female gender, a larger tumour diameter, no lobulated margin, and higher SUVmax were poor prognostic factors.

18F-FDG uptake on PET correlates with biological potential in early oral squamous cell carcinoma

Conclusion: The maximum standardized uptake value (SUVmax) of early oral squamous cell carcinoma (OSCC) may have a role as an imaging biomarker for assessment of malignant potential, including cell metabolism and angiogenesis. Objective: The usefulness of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) has been proven in various cancers, including OSCC. Moreover, in several carcinomas, the SUVmax of the tumor has been shown to correlate with the histological type, tumor stage, differentiation, and prognosis. Here, we investigated whether the SUVmax of early OSCC was associated with the biological features. Methods: Twenty-seven patients with newly diagnosed early OSCC who underwent preoperative FDG-PET and curative surgical resection were included in this study. Tumor sections were stained by immunohistochemistry for glucose transporter 1 (GLUT1), L-type amino acid transporter 1 (LAT1), CD98, microvessels (CD34), cell proliferation marker (Ki-67), and cell cycle regulator (p53). The correlation between SUVmax and clinicopathological findings or the expression level of these molecules was analyzed. Results: SUVmax of primary OSCC was significantly higher in patients with T2 stage. Moreover, patients whose tumors showed vascular invasion had a tendency to show higher SUVmax. A significant correlation was observed between SUVmax and the expression of LAT1 or microvessel density.

24. Statistical parametric mapping of regional glucose metabolism in mesial temporal lobe epilepsy associated with hippocampal sclerosis

Objective This study was designed to use statistical parametric mapping (SPM) of preoperative interictal FDG-PET to compare the brain metabolisms of patients with mesial temporal lobe epilepsy/hippocampal sclerosis (MTLE/HS) who underwent resective surgery and controls. Another aim of this study was to analyze potential differences in SPM-PET within the group of MTLE/HS patients in terms of gender, side of HS, histopathological findings, and postoperative outcomes. Methods We analyzed FDG-PET scans from 49 patients with MTLE/HS and 24 control subjects. Using SPM, we analyzed the differences in regional glucose metabolism between the patient and the control groups and within the patient group using multiple variables. Results We revealed widespread hypometabolism in the patient group in comparison to the control group in temporal and extratemporal areas on the epileptogenic side (ES). On the nonepileptogenic side (NES), we observed most the hypometabolism in the thalamus and the anterior and middle cingulate gyri (GCA and GCM). In the group of patients with more severe HS (Wyler III/IV), we observed statistically significant hypometabolism in the insula on the ES in comparison to the patients with Wyler I/II HS. In patients with poor postoperative outcomes (ILAE III-V), we found statistically significant hypometabolism in the insula on the ES and the TP on the NES compared to the ILAE I and II group. Patients with encephalitis/meningoencephalitis and/or febrile seizures in their history showed significant hypermetabolism in the TP either on the ES or the NES and in the middle temporal gyrus on the NES compared to the patients without any insult in their history. Significance Our study showed that there are widespread significant changes in metabolism in MTLE/HS patients in comparison to controls, either inside or outside the temporal lobe and mostly ipsilateral to the side of HS. There are significant differences among these patients in terms of postoperative outcomes, degree of HS, and insults in their history.

Limitations of 18F-2-Deoxy-d-Glucose Positron Emission Tomography in N1 Detection in Patients With Pathologic Stage II-N1 and Implications for Management

The definitive use of 18F-2-deoxy-d-glucose positron emission tomography (FDG-PET) to detect nodal metastasis in patients with early-stage non-small cell lung cancer (NSCLC) being evaluated for local nonsurgical management, such as stereotactic body radiation therapy and minimally invasive percutaneous ablative therapies, underscores the importance of diagnosing N1 disease by FDG-PET. The purpose of this study was to evaluate FDG-PET in the detection of N1 disease and to determine if FDG-PET-positive N1 disease predicts poor survival in patients with pathologic stage II-N1 NSCLC. We reviewed all patients who underwent surgical resection for lung cancer at MD Anderson Cancer Center from 2000 to 2011 who had pathologic stage T1 to T2 and N1 disease and a preoperative FDG-PET. We compared the clinicopathologic characteristics and survival of patients who had PET-positive N1 and PET-negative N1 disease. A total of 104 patients met the inclusion criteria. The pathologic stage in 87 patients was IIA (T1a N1, T1b N1 or T2a N1) and in 17 patients was IIB (T2b N1). Only 25 of 104 patients (24%) had PET-positive N1 disease. There was no clinical or pathologic difference between the patients who had PET-positive N1 and PET-negative N1 disease. No significant difference was found in the survival rates between patients from the PET-positive N1 and the PET-negative N1 groups (p = 0.9). FDG-PET has poor sensitivity in detecting N1 disease, and N1-positive disease on FDG-PET does not have an effect on survival. FDG-PET should not be used alone to determine management in patients with early-stage non-small cell lung cancer being evaluated for local nonsurgical management.

Standardized uptake value of ¹⁸F-fluorodeoxyglucose positron emission tomography for prediction of tumor recurrence in breast cancer beyond tumor burden.

Introduction18F-fluorodeoxyglucose positron emission tomography (FDG-PET) can reveal the metabolic activity of malignant tumors. Recent advances gained from molecular studies suggest that tumor biology can be a good predictor of prognosis in breast cancer. We compared the ability of maximum standardized uptake values (SUVmax) derived by FDG-PET with tumor burden in predicting tumor recurrence for patients with breast cancer.Methods496 patients with breast cancer who underwent preoperative FDG-PET between April 2004 and May 2009 were retrospectively identified. SUVmax was obtained by FDG-PET, and the cutoff point was defined using a time-dependent receiver operating characteristic curve for recurrence-free survival (RFS). The primary endpoint was RFS.ResultsIn multivariate analysis for RFS, SUVmax carried independent prognostic significance (hazard ratio, 2.39; 95% confidence interval, 1.20 to 4.76; P = 0.012). When the patients were classified into four groups according to the combined factors of tumor size (≤2 cm versus >2 cm) and SUVmax (<4 versus ≥4), RFS differed significantly (P < 0.001). Similarly, SUVmax had prognostic value in combination with nodal status (negative versus positive) or stage (I versus II and III) (P < 0.001 and P = 0.001, respectively). In hormone receptor–positive disease, SUVmax remained a significant prognostic factor for RFS based on multivariate analysis.ConclusionsOur results highlight the prognostic value of FDG-PET in prediction of tumor relapse for patients with breast cancer. Particularly in patients with hormone receptor–positive disease, the tumor metabolic information provided by FDG-PET is more significantly correlated with prognosis than tumor burden.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-014-0502-y) contains supplementary material, which is available to authorized users.

Preoperative FDG-PET Predicts Early Recurrence and a Poor Prognosis After Resection of Pancreatic Adenocarcinoma

The aim of this study was to evaluate the clinical utility of preoperative 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) as a prognostic predictor of resectable pancreatic adenocarcinoma. A total of 128 patients with resected pancreatic adenocarcinoma who preoperatively underwent FDG-PET examinations were studied. The maximum standard uptake value (SUVmax) was calculated for each primary lesion. A receiver operating characteristics (ROC) curve was constructed to estimate the optimal cutoff value of the SUVmax. In order to determine which outcomes of interest were appropriately demonstrated, ROC curve analyses were conducted for six outcomes: 6-, 12-, and 24-month disease-free survival (DFS), and 6-, 12-, and 24-month overall survival (OS). A multivariate analysis was conducted to identify prognostic factors. The ROC curves revealed that the SUVmax predicted the 6-month DFS most optimally (area under the curve 0.757), with a cutoff value of 6.0. Of the 69 patients with an SUVmax≥6.0, 34 (49%) developed recurrence within 6months. In contrast, only 3 of 59 (5%) patients with an SUVmax<6.0 exhibited early recurrence (p<0.001). The median OS time was 37months in patients with an SUVmax<6.0 and 18months in patients with an SUVmax≥6.0 (p<0.001). The multivariate analysis revealed lymph node metastasis (hazard ratio [HR] 2.31; p=0.001) and an SUVmax≥6.0 (HR 2.05; p=0.002) to be significantly correlated with a poor survival. An SUVmax≥6.0 was a significant predictor of early postoperative recurrence and subsequent poor survival following resection of pancreatic adenocarcinoma.

In vivo imaging of cellular proliferation in renal cell carcinoma using 18F-fluorothymidine PET.

The ability to measure cellular proliferation non-invasively in renal cell carcinoma may allow prediction of tumour aggressiveness and response to therapy. The aim of this study was to evaluate the uptake of 18F-fluorothymidine (FLT) PET in renal cell carcinoma (RCC), and to compare this to 18F-fluorodeoxyglucose (FDG), and to an immunohistochemical measure of cellular proliferation (Ki-67). Twenty seven patients (16 male, 11 females; age 42-77) with newly diagnosed renal cell carcinoma suitable for resection were prospectively enrolled. All patients had preoperative FLT and FDG PET scans. Visual identification of tumour using FLT PET compared to normal kidney was facilitated by the use of a pre-operative contrast enhanced CT scan. After surgery tumour was taken for histologic analysis and immunohistochemical staining by Ki-67. The SUVmax (maximum standardized uptake value) mean±SD for FLT in tumour was 2.59±1.27, compared to normal kidney (2.47±0.34). The mean SUVmax for FDG in tumour was similar to FLT (2.60±1.08). There was a significant correlation between FLT uptake and the immunohistochemical marker Ki-67 (r=0.72, P<0.0001) in RCC. Ki-67 proliferative index was mean ± SD of 13.3%±9.2 (range 2.2% - 36.3%). There is detectable uptake of FLT in primary renal cell carcinoma, which correlates with cellular proliferation as assessed by Ki-67 labelling index. This finding has relevance to the use of FLT PET in molecular imaging studies of renal cell carcinoma biology.