Tumor FDG Uptake Research Articles

OA141] Preparing data for multiparametric PET/MRI: Influence of PET point spread function modelling and EPI distortion correction on the spatial correlation of 18F-FDG-PET uptake and diffusion weighted MRI in head/neck cancer

Purpose Multiparametric imaging may improve disease characterization. The combination of 18F-flourodeoxyglucose (FDG) Positron Emission Tomography (PET) and Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) has been suggested to improve the assessment of tumour heterogeneity [1] . However, PET image resolution is limited compared to MRI while DW-MRI is prone to image distortions, potentially compromising the spatial correspondence of the modalities. The aim of this study was to assess relative differences and improvements of the quality of PET and DW-MRI by employing Point Spread Function (PSF) modelling and distortion correction, respectively. Methods Data was collected from 11 patients with head/neck cancers, each scanned on a fully-integrated PET/MRI (Siemens Biograph mMR) twice on separate days [2] . PET [60 min post injection of 18F-FDG (4MBq/kg)] was reconstructed [3D OP-OSEM, 3 iterations, 21 subsets] with and without PSF modelling. DW-MRI [repetition time/echo time 3000/84 ms, parallel imaging factor 4, effective echo spacing 0.145 ms] was corrected for distortions using B0-mapping and compared to an anatomical reference [T2-weighted turbo spin echo]. Voxelwise correlations of FDG uptake and the apparent diffusion coefficient (ADC) derived from DW-MRI were measured in tumours. Results The inclusion of PSF modelling in PET image reconstruction increased overall FDG uptake in tumours [max: 5 %, mean: 12%] and enhanced image quality. Distortion correction improved DW-MRI fidelity compared to the reference. The impact of PSF modelling on voxelwise correlation coefficients of FDG uptake and the ADC was not significant [p = 0.17]. DW-MRI distortion correction had a large and significant influence on correlation coefficients [p = 0.001]. Conclusions This study investigated the consequences of improving quality of PET and DW-MRI for the spatial correlation of the modalities in patients with head/neck cancers. Voxelwise correlation of FDG uptake and ADC was affected by DW-MRI distortion correction, but not by using PSF modelling during PET image reconstruction. Accordingly, optimized data acquisition and processing can help increase the value of PET/MRI data for voxelwise multiparametric analysis.

Differences on metabolic behavior between intra and extrahepatic cholangiocarcinomas at 18F-FDG-PET/CT: prognostic implication of metabolic parameters and tumor markers.

Cholangiocarcinoma is an infrequent neoplasm barely studied with 18F-FDG-PET/CT. We evaluated the metabolic behavior of cholangiocarcinoma in PET/CT according to its location (intra or extrahepatic) and analyzed the relationship between metabolic parameters of the primary tumor and tumor markers (CA19-9 and CEA), determining their prognostic significance. Retrospective study of PET/CT of 60 patients with untreated cholangiocarcinoma, divided into two groups according to tumor location. FDG uptake was evaluated visually and semiquantitatively [SUVmax and tumor-to-liver ratio (TLR)], and differences between intra and extrahepatic cholangiocarcinomas were tested, both for FDG uptake in the primary tumor and for the presence of regional or distant disease (per-patient), as well as regarding tumor marker levels. A correlation between metabolic parameters and tumor markers was performed, and prognostic value of these factors was determined (univariate and multivariate analyses). Intrahepatic cholangiocarcinomas were significantly more FDG-avid than extrahepatic ones (p = 0.006 for SUVmax; p = 0.002 for TLR). There were differences neither between both groups considering the capacity of PET/CT to detect regional (p = 0.261) and distant involvement (p = 0.876), nor regarding the levels of tumor markers (p = 0.160 for CA19-9; p = 0.708 for CEA). Metabolic parameters and tumor markers showed a weak positive correlation (R2 0.22-0.27). At the multivariate analysis, advanced stage (p = 0.024), increased CEA (p = 0.022), and higher TLR (p = 0.003) were significantly related with shorter overall survival. Intra and extrahepatic cholangiocarcinomas behave differently on PET/CT, though no differences between both groups exist in its capacity to detect regional or distant disease. Metabolic parameters and levels of tumor markers seem to relate with tumor burden, impacting in prognosis.

18 F-Fluorodeoxyglucose positron emission tomography can be used to determine the indication for endoscopic resection of superficial esophageal cancer.

18F‐Fluorodeoxyglucose positron emission tomography (FDG‐PET) is a useful imaging modality that reflects the tumor activity. However, FDG‐PET is mainly used for advanced cancer, not superficial cancer. In this study, we investigated the relationship between the superficial tumor depth of esophageal cancer and the FDG uptake to determine the indications for endoscopic resection (ER). From 2009 to 2017, 444 patients with esophageal cancer underwent esophagectomy or endoscopic submucosal dissection (ESD), and 195 patients were pathologically diagnosed with superficial cancer. Among them, 146 patients were examined by FDG‐PET before esophagectomy or ESD. In these 146 patients, the relationship between the pathological tumor depth and FDG uptake was analyzed. The mean maximum standardized uptake value in pT1a‐EP/LPM tumors was 1.362 ± 0.890, that in pT1a‐MM/pT1b‐SM1 tumors was 2.453 ± 1.872, and that in pT1b‐SM2/SM3 tumors was 4.265 ± 3.233 (P < .0001). Among 51 pT1a‐EP/LPM tumors, 10 (19.6%) showed positive detection of FDG. For pT1a‐MM/pT1b‐SM1 and pT1b‐SM2/SM3 tumors, the detection rate was 52.9% (18/34) and 82.0% (50/61), respectively. The detection rate of pT1a‐EP/LPM was significantly lower than in the other two groups (P < .0001). Among 10 FDG‐PET‐positive lesions, only 1 had no apparent reason for PET positivity; however, 9 of 10 had a suitable reason for detectability by PET and inadequacy for ER. Negative detection of superficial esophageal squamous cell carcinoma by FDG‐PET is useful to determine the indication for ER when the tumor depth cannot be diagnosed even after performing magnifying endoscopy with narrow band imaging and endoscopic ultrasonography. When FDG uptake is recognized, a therapeutic modality other than ER should be considered.

Itraconazole treatment of primary malignant melanoma of the vagina evaluated using positron emission tomography and tissue cDNA microarray: a case report

BackgroundPrimary malignant melanoma of the vagina is extremely rare, with a poorer prognosis than cutaneous malignant melanoma. Previous studies have explored the repurposing of itraconazole, a common oral anti-fungal agent, for the treatment of various cancers. Here, we describe a patient with metastatic, unresectable vaginal malignant melanoma treated with 200 mg oral itraconazole twice a day in a clinical window-of-opportunity trial.Case presentationA 64-year-old Japanese woman with vaginal and inguinal tumours was referred to our institution. On the basis of an initial diagnosis of vaginal cancer metastatic to the inguinal lymph nodes, we treated her with itraconazole in a clinical trial until the biopsy and imaging study results were obtained. During this period, biopsies were performed three times, and 18F-fluoro-deoxyglucose positron emission tomography (FDG/PET)–computed tomography (CT) was performed twice. Biopsy results confirmed the diagnosis of primary malignant melanoma of the vagina. Imaging studies revealed metastases to multiple sites, including the brain, for which she underwent gamma-knife radiosurgery. During the window period before nivolumab initiation, the patient received itraconazole for 30 days. Within a week of itraconazole initiation, pain in the inguinal nodes was ameliorated. PET–CT on days 6 and 30 showed a reduction in tumour size and FDG uptake, respectively. The biopsied specimens obtained on days 1, 13, and 30 were subjected to cDNA microarray analysis, which revealed a 100-fold downregulation in the transcription of four genes: STATH, EEF1A2, TTR, and CDH2. After 12 weeks of nivolumab administration, she developed progressive disease and grade 3 immune-related hepatitis. Discontinuation of nivolumab resulted in the occurrence of left pelvic and inguinal pain. Following re-challenge with itraconazole, the patient has not reported any pain for 4 months.ConclusionThe findings of this case suggest that itraconazole is a potential effective treatment option for primary malignant melanoma of the vagina. Moreover, we identified potential itraconazole target genes, which could help elucidate the mechanism underlying this disease and potentially aid in the development of new therapeutic agents.

Value of Preoperative PET-CT in the Prediction of Pathological Stage of Gastric Cancer.

Preoperative precise staging is essential for the treatment of gastric cancer (GC); however, the diagnostic accuracy of conventional modalities needs to be increased. The present study investigated the clinical value of positron emission tomography-computed tomography (PET-CT) for the staging of GC. This was a retrospective study of 117 patients with a clinical diagnosis of advanced GC who underwent PET-CT followed by gastrectomy. The incidence of FDG uptake in the primary tumor or lymph nodes and its relationship with clinicopathological factors, particularly pathological stage (pStage) III/IV, were examined. FDG uptake in the primary tumor was noted in 83 patients (70.9%). FDG uptake in the lymph nodes was detected in 21 patients (17.9%), and its sensitivity and specificity for lymph node metastasis were 22.7 and 90.5%, respectively. Multiple logistic regression analyses showed that FDG uptake in the primary tumor (odds ratio (OR) 2.764; 95% confidence interval (CI) 1.104-7.459, p = 0.029) and that in the lymph nodes (OR 4.660; 95% CI 1.675-13.84, p = 0.003) were factors independently associated with pStage III/IV. FDG uptake in the primary tumor detected pStage III/IV with higher sensitivity (80.4%) and that in lymph nodes found pStage III/IV with higher specificity (88.7%) than those of upper endoscopy plus CT (60.9 and 67.6%, respectively). PET-CT appears to be a useful complementary modality in the assessment of pStage III/IV because of the high sensitivity of FDG uptake in the primary tumor and the high specificity of FDG uptake in the lymph nodes.

Monoclonal human auto-antibodies: Novel tools for the understanding of neuropsychiatric symptoms

We investigated whether 18F-fluorodeoxyglucse (FDG) uptake of bone marrow (BM) on positron emission tomography/computed tomography (PET/CT) has implications for predicting clinical outcomes in patients with small cell lung cancer (SCLC).We retrospectively enrolled 70 SCLC patients who underwent FDG PET/CT prior to treatment. On PET/CT, maximum FDG uptake of all tumor lesions (Tmax), coefficient of variation (COV) of FDG uptake of primary tumor, and mean FDG uptake of BM (BM SUV) were measured. The relationships of BM SUV with PET/CT parameters of SCLC and serum markers were evaluated. Univariate and multivariate analyses were performed to assess the significance of BM SUV for predicting progression-free survival (PFS) and overall survival (OS).BM SUV had significant positive correlations with Tmax, COV of primary tumor, white blood cell count, and serum C-reactive protein level (p < .05). On univariate analysis, BM SUV showed significant association with only PFS (p = .006). On multivariate analysis, Veterans Administration Lung Cancer Study Group (VALSG) stage, N stage, M stage, Tmax, and BM SUV were independent prognostic factors for PFS (p < .05) and, for OS, VALSG stage and M stage were independent prognostic factors (p < .05). Among patients with limited disease, patients with high FDG uptake of BM had significantly worse PFS than did those with low FDG uptake of BM (p < .05), but, there was no significant difference in PFS between patients with extensive disease and patients with limited disease and high FDG uptake of BM (p > .05).FDG uptake of BM was an independent predictor of disease progression in SCLC patients. Patients with limited disease and high FDG uptake of BM had similar PFS to those with extensive disease.

Prognostic significance of 18F-fluorodeoxyglucose uptake of bone marrow measured on positron emission tomography in patients with small cell lung cancer

ObjectivesWe investigated whether 18F-fluorodeoxyglucse (FDG) uptake of bone marrow (BM) on positron emission tomography/computed tomography (PET/CT) has implications for predicting clinical outcomes in patients with small cell lung cancer (SCLC). MethodsWe retrospectively enrolled 70 SCLC patients who underwent FDG PET/CT prior to treatment. On PET/CT, maximum FDG uptake of all tumor lesions (Tmax), coefficient of variation (COV) of FDG uptake of primary tumor, and mean FDG uptake of BM (BM SUV) were measured. The relationships of BM SUV with PET/CT parameters of SCLC and serum markers were evaluated. Univariate and multivariate analyses were performed to assess the significance of BM SUV for predicting progression-free survival (PFS) and overall survival (OS). ResultsBM SUV had significant positive correlations with Tmax, COV of primary tumor, white blood cell count, and serum C-reactive protein level (p < .05). On univariate analysis, BM SUV showed significant association with only PFS (p = .006). On multivariate analysis, Veterans Administration Lung Cancer Study Group (VALSG) stage, N stage, M stage, Tmax, and BM SUV were independent prognostic factors for PFS (p < .05) and, for OS, VALSG stage and M stage were independent prognostic factors (p < .05). Among patients with limited disease, patients with high FDG uptake of BM had significantly worse PFS than did those with low FDG uptake of BM (p < .05), but, there was no significant difference in PFS between patients with extensive disease and patients with limited disease and high FDG uptake of BM (p > .05). ConclusionFDG uptake of BM was an independent predictor of disease progression in SCLC patients. Patients with limited disease and high FDG uptake of BM had similar PFS to those with extensive disease.

A novel genomic signature predicting FDG uptake in diverse metastatic tumors

BackgroundBuilding a universal genomic signature predicting the intensity of FDG uptake in diverse metastatic tumors may allow us to understand better the biological processes underlying this phenomenon and their requirements of glucose uptake.MethodsA balanced training set (n = 71) of metastatic tumors including some of the most frequent histologies, with matched PET/CT quantification measurements and whole human genome gene expression microarrays, was used to build the signature. Selection of microarray features was carried out exclusively on the basis of their strong association with FDG uptake (as measured by SUVmean35) by means of univariate linear regression. A thorough bioinformatics study of these genes was performed, and multivariable models were built by fitting several state of the art regression techniques to the training set for comparison.ResultsThe 909 probes with the strongest association with the SUVmean35 (comprising 742 identifiable genes and 62 probes not matched to a symbol) were used to build the signature. Partial least squares using three components (PLS-3) was the best performing model in the training dataset cross-validation (root mean square error, RMSE = 0.443) and was validated further in an independent validation dataset (n = 13) obtaining a performance within the 95% CI of that obtained in the training dataset (RMSE = 0.645). Significantly overrepresented biological processes correlating with the SUVmean35 were identified beyond glycolysis, such as ribosome biogenesis and DNA replication (correlating with a higher SUVmean35) and cytoskeleton reorganization and autophagy (correlating with a lower SUVmean35).ConclusionsPLS-3 is a signature predicting accurately the intensity of FDG uptake in diverse metastatic tumors. FDG-PET might help in the design of specific targeted therapies directed to counteract the identified malignant biological processes more likely activated in a tumor as inferred from the SUVmean35 and also from its variations in response to antineoplastic treatments.

Predictors of unexpected nodal upstaging in patients with cT1-3N0 non-small cell lung cancer (NSCLC) submitted to thoracoscopic lobectomy.

In the last decades, the use of video-assisted thoracoscopic surgery (VATS) lobectomy for the treatment of early stage non-small cell lung cancer is continuously growing. This is mainly due to the development of more advanced surgical devices, to the rising incidence of peripheral lung tumors and is also favored by the increased reliability of preoperative staging techniques. Despite this progress, postoperative unexpected nodal upstaging is still a relevant issue. Aim of this study is to identify possible predictors of unexpected nodal upstaging in patients affected by cT1-3N0 NSCLC submitted to VATS lobectomy. A total of 231 cases of cT1-3N0 patients submitted to thoracoscopic lobectomy at our centre between June 2012 and October 2016 were retrospectively reviewed. All data regarding clinical staging by means of computed tomography (CT) and positron-emission tomography (PET)/CT were collected and reviewed. The subsequent pathological staging has been analyzed, with special regards to the possible type of nodal involvement, and the number of pathological nodal stations. Most of the patients included in this study were in a clinical stage cT1aN0, cT1bN0 (stage IA) and cT2aN0 (stage IB), 86 (37.2%) patients, 73 (31.6%) patients and 62 (26.8%) patients, respectively. Postoperative histopathological analysis showed that the most frequent tumor histotype was adenocarcinoma (192 patients, 83.1%). Thirty-eight (16.5%) patients had a nodal upstaging; among these, 17 (7.4%) patients had N2 disease (8 patients with isolated mediastinal nodal involvement, 9 patients with N1 + N2 disease) and 21 (9.1%) patients had an isolated hilar nodal involvement (N1). At bivariate analysis, the clinical T (cT)-parameter (P=0.023), the histotype (P=0.029) and the pathological T (pT)-parameter (P=0.003) were identified as statistically significant predictors of nodal upstaging. Concerning the type of nodal upstaging, the pT was found to be statistically significant (P=0.042). At bivariate analysis for the number of involved nodal stations, a statistical significance was highlighted for the parameters cT (P=0.030) and pT (P=0.027). With linear logistic regression, histology as well as pT reached statistical significance (P=0.0275 and P=0.0382, respectively). No correlation was found between nodal upstaging and the intensity of FDG uptake in the primary lung tumor or with the timing between PET and surgery. There is a strong correlation between the clinical staging of the parameter T evaluated with CT and the possible unexpected nodal upstaging. The same correlation with nodal upstaging is found for pT. At equal clinical stage, in patients affected by adenocarcinoma of the lung the relative risk of having a postoperative unexpected nodal upstaging is almost 7 times higher than in patients with squamous cell carcinoma.

Usefulness of metabolic activity of adipose tissue in FDG PET/CT of colorectal cancer.

To determine the relationship between metabolic activity of adipose tissue on FDG PET/CT and prognosis in colorectal cancer. A total of 176 colorectal cancer patients with curative surgical resection were retrospectively enrolled. Volume and metabolic activity of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) on FDG PET/CT images were measured. The maximum standardized uptake value (SUV) of primary tumor (SUVtumor) was also obtained. Univariate analysis with log-rank test and multivariate Cox regression analyses were used to evaluate prognostic values of volume and metabolic activity of SAT and VAT as well as SUVtumor and clinicopathologic factors. Of 176 patients, 26 experienced recurrence during follow-up. SUVtumor showed significant correlation with serum C-reactive protein level (r=0.242, p=0.001), SUV of VAT (r=0.167, p=0.026), and size of primary tumor (r=0.341, p<0.001). In univariate analysis with log-rank test, SUV of VAT (p=0.009) and SAT (p=0.006), volume of VAT (p=0.015), N stage (p<0.001), M stage (p<0.001), tumor involvement of resection margin (p=0.001), and lymphatic invasion (p=0.024) were significantly associated with recurrence-free survival (RFS). However, SUVtumor showed no significant association with RFS. In multivariate Cox regression analysis, SUV of VAT (p=0.016), presence of lymph node metastasis (p<0.001), and tumor involvement of resection margin (p=0.011) were independent prognostic factors for RFS. The SUV of VAT in patients with colorectal cancer is significantly associated with FDG uptake of primary tumor. It is an independent predictor for RFS.

Prognostic and Predictive Value of FDG-PET as an Aid in Oesophageal Cancer Management

18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is widely used for cancer staging before treatment and detection of recurrence during post-treatment surveillance. It is increasingly being recognised that tumour FDG uptake values may not only be prognostic, but could have predictive value to assess for treatment response during and after neoadjuvant therapy in oesophageal cancer (OC). This review focusses on the available evidence concerning the prognostic or predictive role of FDG-PET and evaluates the potential value of FDG-PET in guiding treatment decisions in OC. The correlation between pretreatment maximum standardised uptake value (SUVmax) and prognosis has been demonstrated by multiple studies, although the results are inconsistent and sometimes conflicting. With regard to the predictive value for FDG-PET, post-SUVmax after neoadjuvant chemotherapy appears to hold better promise compared to chemoradiotherapy due to the confounding effect of radiation oesophagitis. Since a number of studies have demonstrated that FDG-PET can discriminate responders from non-responders to induction chemotherapy, the predictive value of FDG-PET imaging was evaluated prospectively and the initial results of CALGB 80803 suggested that changing chemotherapy regimen based on FDG-PET response to induction chemotherapy may improve pathologic complete response rate in PET non-responders when an alternative chemotherapy is used. Furthermore, additional research has suggested that FDG-PET response after induction chemotherapy or neoadjuvant chemotherapy may enrich a patient subset who may potentially avoid subsequent surgery after chemoradiotherapy. However, the majority of reports published on FDG-PET in OC are limited to small, retrospective, and single-institutional studies. Therefore, much of the current evidence-to-date is still hypothesis-generating and would require vigorous validation before FDG-PET could become part of routine clinical practice to direct treatment decisions.

Clinicopathological Features of Ductal Carcinoma In Situ from 18F-FDG-PET Findings.

The presence of ductal carcinoma in situ (DCIS) can increase the risk of developing an invasive ductal carcinoma (IDC), but it is difficult to predict what will occur if a DCIS is left untreated. We reported the usefulness of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) for DCIS, and that the presence of FDG uptake in the tumor could be considered a predictor of invasive potential in patients with DCIS. In this study, we retrospectively evaluated the clinicopathological features of DCIS by using FDG-PET findings, and we evaluated the possibility of using FDG-PET in DCIS cases as a biomarker of which lesions will go on to become invasive. We investigated the cases of 185 consecutive patients with primary breast cancer who were diagnosed as having DCIS or IDC and underwent FDG-PET preoperatively. We divided the cases into two groups on the basis of histology; DCIS vs. IDC (n=171). The DCIS cases were divided into two groups on the basis of FDG uptake in the primary tumor. Fourteen of the 185 patients (7.4%) were revealed to have a DCIS. The analysis revealed that the SUVmax and the number of cases not detected by FDG-PET were significantly different between the DICS and IDC groups. The extent of the primary tumor was not significantly different between the two groups. In six cases (42.9%) of the 14 DCIS cases, no FDG uptake was detected by FDG-PET. The extent of tumor did not significantly differ between the two groups. In addition, all six cases without FDG uptake were of the diffuse-spread type, without mass formation. All eight cases with mass formation had FDG uptake. Our present findings suggest that the FDG-PET uptake reflects tumor burden or tumor density, which should be considered to be associated with the presence of invasion.

Abstract SY02-03: Imaging cancer metabolism in patients: FDG PET and beyond

Abstract The identification of altered energy metabolism as a hallmark of cancer (1) leads to opportunities to exploit cancer metabolism as a target for diagnosis. This has been most widely exploited using the elevated rate of glycolysis observed in most tumors as a target for imaging (2)–in particular, positron emission tomography (PET) imaging of the glucose analog 18F-fluorodeoxyglucose (FDG). FDG PET, now combined with anatomic imaging in the form of PET/CT, has become an important tool for cancer detection, staging, and response assessment, widely used in oncologic clinical practices around the world (3,4). Clinical use of FDG PET has increased our appreciation of aberrant glycolysis as a feature of more aggressive, less differentiated tumors (5,6). At the same time, the variability of tumor FDG uptake seen in clinical imaging has highlighted some of the limitations of imaging tumor glycolysis and has spurred the development of new imaging probes and novel imaging modalities designed to image other facets of cancer energy metabolism. In addition, the use of therapeutics that are targeted to and/or influenced by cancer metabolic phenotype (7) drives applications of cancer metabolic imaging to clinical challenges beyond detection to predicting and and monitoring response to targeted therapy (8). This talk highlights current uses of FDG PET/CT for cancer staging and response evaluation, as well as alternative PET probes targeted to other metabolic substrates such as amino acids, lipids, and TCA intermediates (9). It also highlights other methods for imaging cancer metabolism in patients, including magnetic resonance spectroscopy, optical imaging, chemical exchange saturation transfer (CEST), MR metabolomics, and MR imaging of hyperpolarized 13C-labeled metabolic substrates such as pyruvate (10-14). Unique features and advantages of each modality are highlighted, as are approaches to image analysis common across modalities, including quantitative imaging and kinetic analysis. Finally, the talk emphasizes the benefit of multimodality imaging as an approach to fully characterize cancer metabolism, using glutaminolysis imaging as an example of active investigation. Supported in part by Komen SAC130060, DOE DE-SE0012476, NIH P30-CA016520, and NIH R01-CA211337.

Strong association of epidermal growth factor receptor status with breast cancer FDG uptake.

Imaging tumor FDG uptake could complement breast cancer biomarkers of risk and treatment response. Although breast cancer FDG uptake is reputedly influenced by major biomarker states, the role of epidermal growth factor receptor (EGFR) expression remains largely unexplored. This is a retrospective study that included 499 patients with primary breast cancer at initial presentation. Tumor FDG uptake was measured on pretreatment PET/CT as maximum standardized uptake value (SUVmax), and biomarkers were assessed by immunohistochemistry of tumor tissue. Regression analysis was performed for predictors of high tumor FDG uptake (SUVmax ≥8.6). SUVmax was higher in ER- (36.5%; 11.2±6.0 vs. 8.3±5.3), PR- (42.3%; 10.9±6.0 vs. 8.2±5.2), and triple-negative tumors (19.8%; 12.0±6.9 vs. 8.7±5.2; all p<0.0001). EGFR expression (28.5%) was more frequent in ER-, PR-, triple-negative, cytokeratin 5/6 (CK5/6)+and mutant P53 (mP53)+tumors (all p<0.0001). EGFR+ was associated with higher SUVmax among all tumors (11.9±6.0 vs. 8.3±5.3), ER- tumors (p<0.0001), PR- and + tumors (p<0.0001 and 0.027), hormone receptor- and + tumors (p<0.0001 and 0.004), human epidermal growth factor receptor 2 (HER2)- and + tumors (p<0.0001 and 0.006), non-triple negative tumors (p<0.0001), CK5/6- and + tumors (p=0.021 and <0.0001), and mP53- and + tumors (p<0.0001 and 0.008). Tumors had high FDG uptake in 73.2% of EGFR+ and 40.6% of EGFR- tumors. On regression analysis, significant multivariate predictors of high tumor FDG uptake were large size, EGFR+ and CK5/6+ for the entire subjects, and EGFR+ and CK5/6+ for ER- and hormone receptor negative subgroups. High FDG uptake was able to sub-stratify EGFR+ tumors that were more likely to be ER- and CK5/6+, and EGFR- tumors more likely to be mP53+. Primary breast tumor FDG uptake is strongly influenced by EGFR status beyond that by other major biomarkers including hormone receptor and HER2 status, and EGFR expression is a strong independent predictor of high breast tumor FDG uptake.

EP-1288: Correlation between PET/CT primary tumor FDG uptake and lymph node metastases in cervical cancer

EP-1288: Correlation between PET/CT primary tumor FDG uptake and lymph node metastases in cervical cancer

Characterization of an Orthotopic Colorectal Cancer Mouse Model and Its Feasibility for Accurate Quantification in Positron Emission Tomography.

Quantification in positron emission tomography (PET) imaging of an orthotopic mouse model of colorectal cancer (CRC) is challenging due to difficult tumor delineation. We aimed to establish a reproducible delineation approach, evaluate its feasibility for reliable PET quantification and compare its added translational value with its subcutaneous counterpart. A subcutaneous Colo205-luc2 tumor fragment harvested from a donor mouse was transplanted onto the caecum of nude mice, with (n=10) or without (n=10) the addition of an X-ray detectable thread. Animals underwent 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET imaging, complemented with X-ray computed tomography (CT) and magnetic resonance imaging (MRI, 7T). Animals without a thread underwent additional contrast enhanced (Exitron) CT imaging. Tumors were delineated on the MRI, μPET image or contrast enhanced μCT images and correlations between in vivo and ex vivo [18F]FDG tumor uptake as well as between image-derived and caliper-measured tumor volume were evaluated. Finally, cancer hallmarks were assessed immunohistochemically for the characterization of both models. Our results showed the strongest correlation between both in vivo and ex vivo uptake (r=0.84, p<0.0001) and image-derived and caliper-measured tumor volume (r=0.96, p<0.0001) when the tumor was delineated on the MR image. Orthotopic tumors displayed an abundance of stroma, higher levels of proliferation (p=0.0007), apoptosis (p=0.02), and necrosis (p<0.0001), a higher number of blood vessels (p<0.0001); yet lower tumor hypoxia (p<0.0001) as compared with subcutaneous tumors. This orthotopic mouse model proved to be a promising tool for the investigation of CRC through preclinical imaging studies provided the availability of anatomical MR images for accurate tumor delineation. Furthermore, the tumor microenvironment of the orthotopic tumor resembled more that of human CRC, increasing its likelihood to advance translational nuclear imaging studies of CRC.

Relation between tumor FDG uptake and hematologic prognostic indicators in stage I lung cancer patients following curative resection.

Hematologic parameters of systemic inflammation are receiving attention as promising prognostic indicators in cancer patients. Here, we investigated the relation and compared the prognostic values of circulating blood cell-based parameters and tumor 18F-fluoro-2-deoxyglucose (FDG) uptake in patients with stage I nonsmall cell lung cancers (NSCLC).Subjects were 1034 patients with newly diagnosed stage I NSCLC who underwent FDG positron emission tomography/computed tomography (PET/CT) followed by curative resection. Total white blood cell (WBC) count, absolute neutrophil, lymphocyte and platelet counts, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were obtained. Tumor FDG uptake was measured as SUVmax.WBC, neutrophil and lymphocyte counts, and NLR demonstrated weak but significant correlation to tumor SUVmax. Using the upper quartile as cutoff, patients with high tumor SUVmax had significantly higher WBC, neutrophil and lymphocyte counts, and greater NLR. There were 144 recurrences (13.9%) over a median follow-up of 29.5 months. On Cox proportional hazards regression analysis, WBC count, tumor SUVmax, age, gender, smoking, cell type, and tumor stage were significant univariate prognostic factors. On multivariate analysis, high tumor SUVmax (HR = 2.22; 95% CI, 1.52–3.25; P < 0.001), tumor stage 1B (HR = 2.11; 95% CI, 1.47–3.01; P < 0.001), and old age (HR = 1.03; 95% CI, 1.01–1.05; P = 0.002) were significant independent predictors of poor survival. Finally, high tumor SUVmax remained a significant predictor of prognosis in both low and WBC count groups.Circulating blood counts showed significant correlation to tumor FDG uptake in early stage NSCLC. WBC count was a significant univariate variable, but tumor FDG uptake was a superior and independent predictor of outcome. Hence, tumor FDG uptake effectively stratified prognosis in patients with low as well as high WBC count.

FDG-PET reproducibility in tumor-bearing mice: comparing a traditional SUV approach with a tumor-to-brain tissue ratio approach

Background: Current [F-18]-fluorodeoxyglucose positron emission tomography (FDG-PET) procedures in tumor-bearing mice typically includes fasting, anesthesia, and standardized uptake value (SUV)-based quantification. Such procedures may be inappropriate for prolonged multiscan experiments. We hypothesize that normalization of tumor FDG retention relative to a suitable reference tissue may improve accuracy as this method may be less susceptible to uncontrollable day-to-day changes in blood glucose levels, physical activity, or unnoticed imperfect tail vein injections.Material and methods: Fed non-anesthetized tumor-bearing mice were administered FDG intravenously (i.v.) or intraperitoneally (i.p.) and PET scanned on consecutive days using a Mediso nanoScan PET/magnetic resonance imaging (MRI). Reproducibility of various PET-deduced measures of tumor FDG retention, including normalization to FDG signal in reference organs and a conventional SUV approach, was evaluated.Results: Day-to-day variability in i.v. injected mice was lower when tumor FDG retention was normalized to brain signal (T/B), compared to normalization to other tissues or when using SUV-based normalization. Assessment of tissue radioactivity in dissected tissues confirmed the validity of PET-derived T/B ratios. Mean T/B and SUV values were similar in i.v. and i.p. administered animals, but SUV normalization was more robust in the i.p. group than in the i.v. group.Conclusions: Multimodality scanners allow tissue delineation and normalization of tumor FDG uptake relative to reference tissues. Normalization to brain, but not liver or kidney, improved scan reproducibility considerably and was superior to traditional SUV quantification in i.v. tracer-injected animals. Day-to-day variability in SUV’s was lower in i.p. than in i.v. injected animals, and i.p. injections may therefore be a valuable alternative in prolonged rodent studies, where repeated vein injections are undesirable.

P1.05-049 Neoadjuvant Erlotinib Treatment in Patients with Resectable Non-Small Cell Lung Carcinoma

The value of neo-adjuvant therapy in patients with resectable non-small cell lung carcinoma (NSCLC) is limited. Recent advances in targeted therapy have provided novel treatment options for NSCLC with promising results. The Epidermal Growth Factor Receptor (EGFR) is over expressed or may harbor activating mutations in adenocarcinoma in particular. Inhibition of EGFR with tyrosine-kinase inhibitor (TKI) therapy has a favorable outcome in advanced stage patients with activating mutations. The purpose of this study was to prospectively evaluate 18F-FDG-PET metabolic response to neoadjuvant erlotinib, in patients with resectable NSCLC. This study was designed as a multicenter open-label phase II trial, performed in the Netherlands. Patients received preoperative erlotinib 150 mg once daily for 3 weeks. Metabolic response evaluation was performed using FDG-PET/CT scan. Tumor FDG uptake and changes were measured by standardized uptake values (SUV). Metabolic response was classified using EORTC criteria. Metabolic response was compared to the histopathological response and survival. From December 2006 until November 2010, 60 patients were enrolled in this study. In 43 patients (18 male, 25 female), FDG-PET/CT scans and histopathologic response monitoring were available. 14 patients (33%) showed a metabolic response. Histopathologic examination showed a response in 13 patients (30%). In predicting histopathologic response FDG-uptake showed an area under the curve of 72%. Metabolic responders show an improved overall and progression free survival in comparison to patients without metabolic response. FDG-PET/CT may be used as a predictive tool to identify patients with advantage of neoadjuvant EGFR-TKI treatment in resectable NSCLC.

P1.03-074 Combined Use of PET/CT and Clinical Features Yields a Higher Diagnostic Rate of Mediastinal Lymph Node Metastasis in Lung Adenocarcinoma

The aims of this study were to investigate the correlation between 8F-fluorodeoxyglucose (FDG) uptake of the primary tumor and mediastinal lymph node metastasis (MLNM) in lung adenocarcinoma, and to improve the diagnostic capability of tumor FDG uptake and other risk factors in predicting occult MLNM preoperatively. We reviewed 360 consecutive pulmonary adenocarcinoma patients who underwent preoperative PET/CT scan and subsequent surgery. Resected tumors were classified according to the 2011 IASLC/ATS/ERS classification. Univariate and multivariate analysis were conducted to evaluate the associations between clinicopathological variables and MLNM. The receiver operating characteristic (ROC) curve analysis was performed to quantify the predictive value of these factors. Of all the 360 patients, 54 were pathological N2 diseases. On univariate analysis, CEA level, nodule type, nodal SUVmax, tumor SUVmax, size, location and histologic subtype were associated with MLNM. On multivariate analysis, CEA≥5.0 ng/ml (p < 0.001), solid nodule (p = 0.012), tumor SUVmax ≥ 3.7 (p < 0.027), nodal SUVmax ≥ 2.0 (p < 0.001) and centrally located tumors (p = 0.035) were independent risk factors that associated with MLNM. The area under the ROC curve (AUC) for tumor SUVmax in predicting MLNM was 0.764 and AUC of nodal SUVmax was 0.730. The combined use of five factors yielded a higher AUC of 0.885 for N2 disease. The tumor SUVmax among histologic subtypes differed significantly (p < 0.001). Primary tumor SUVmax of PET/CT was shown a good predictor for MLNM in patients with lung adenocarcinoma, and the underlying mechanism may attribute to the close association between tumor FDG uptake and IASLC/ATS/ERS adenocarcinoma subtypes. The combined use of tumor SUVmax with factors like nodal SUVmax, solid nodule, centrally located tumor and increased CEA level improved the diagnostic capacity for predicting N2 disease preoperatively.