Median Standardized Uptake Value Research Articles

SUVmax and Tumor Size Predict Surgical Outcome of Synchronous Multiple Primary Lung Cancers.

To assess surgical outcomes in synchronous multiple primary lung cancer (SMPLC) and correlations with clinicopathological features and prognostic/predictive factors.We retrospectively reviewed patients diagnosed with early-stage nonsmall cell lung cancer (NSCLC) between January 2006 and June 2012. In total, 564 patients with resectable NSCLC underwent a preoperative positron emission tomography-computed tomography scan followed by anatomic resection. We reviewed the clinical features of 35 SMPLC patients. Surgical outcomes, prognosis, and tumor imaging features were evaluated (median follow-up = 44 months).In total, 35 eligible SMPLC patients (6.21%) were identified (11 men [31%], 24 women [69%], mean age = 65 years]). The tumors were bilateral in 17 patients (49%) and in different lobes of the ipsilateral lung in 18 patients (51%). Most patients (26/35, 74%) had 2 primary tumors, and 26% (9/35) had more than 2 tumors (6 with 3 tumors; 3 with 4 tumors). The median size of the most advanced tumor was 3.0 cm (range 0.9–54). The median standard uptake value (SUV) of the largest tumor was 3.1 (range 1.0–13.3). The patients were treated as follows: 30 lobectomies, 2 sublobar resections, 2 sequential bilateral lobectomies, and 1 bi-lobectomy. Twenty-four patients (69%) received adjuvant therapy. The overall cumulative 5-year survival was 91.5% (median overall survival = 45.5 months). Patients with a reference tumor ≤ 3 cm and SUV ≤ 3.1 had an expected 5-year survival of 100%. Patients with a reference tumor > 3 cm and SUV > 3.1 had an expected 5-year survival rate of 53.3%.SMPLC patients can benefit from aggressive surgery. The size and SUVmax of the reference tumor may predict postoperative outcomes.

Rapid development of image analysis research tools: Bridging the gap between researcher and clinician with pyOsiriX

We present pyOsiriX, a plugin built for the already popular dicom viewer OsiriX that provides users the ability to extend the functionality of OsiriX through simple Python scripts. This approach allows users to integrate the many cutting-edge scientific/image-processing libraries created for Python into a powerful DICOM visualisation package that is intuitive to use and already familiar to many clinical researchers. Using pyOsiriX we hope to bridge the apparent gap between basic imaging scientists and clinical practice in a research setting and thus accelerate the development of advanced clinical image processing. We provide arguments for the use of Python as a robust scripting language for incorporation into larger software solutions, outline the structure of pyOsiriX and how it may be used to extend the functionality of OsiriX, and we provide three case studies that exemplify its utility.For our first case study we use pyOsiriX to provide a tool for smooth histogram display of voxel values within a user-defined region of interest (ROI) in OsiriX. We used a kernel density estimation (KDE) method available in Python using the scikit-learn library, where the total number of lines of Python code required to generate this tool was 22. Our second example presents a scheme for segmentation of the skeleton from CT datasets. We have demonstrated that good segmentation can be achieved for two example CT studies by using a combination of Python libraries including scikit-learn, scikit-image, SimpleITK and matplotlib. Furthermore, this segmentation method was incorporated into an automatic analysis of quantitative PET-CT in a patient with bone metastases from primary prostate cancer. This enabled repeatable statistical evaluation of PET uptake values for each lesion, before and after treatment, providing estaimes maximum and median standardised uptake values (SUVmax and SUVmed respectively). Following treatment we observed a reduction in lesion volume, SUVmax and SUVmed for all lesions, in agreement with a reduction in concurrent measures of serum prostate-specific antigen (PSA).

Prognostic Value of 18-Fluorodeoxyglucose-Positron Emission Tomography After Transarterial Chemoembolization in Patients With Hepatocellular Carcinoma Undergoing Orthotopic Liver Transplantation

IntroductionThe aim of this study was to analyze the correlation between 18-FDG positron emission tomography (PET)/computed tomography (CT), histological necrosis, and prognosis after transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) patients undergoing orthotopic liver transplantation (OLT). PatientsFrom January 2007 through December 2013, 81 patients with HCC and liver cirrhosis were included in our liver transplantation program. For this study we selected patients who underwent 18-FDG PET/CT pre-TACE and post-TACE. All patients underwent liver transplantation within 8 weeks after PET/CT. ResultsTwenty patients with a median age of 58 years (range, 46–69 years) underwent an 18-FDG PET/CT before and after TACE. The median Standardized Uptake Value (SUV) before TACE was 3.8 (range, 2.6–8.7), with a median post-TACE SUV of 0% (range, 0–4). Among patients whose post-TACE SUV decreased to <3, >70% necrosis was observed upon study of a hepatectomy sample, with a survival rate of 100% and 80% at 1 and 3 years, respectively. ConclusionIn conclusion, performance of an 18-FDG PET/CT before and after TACE with comparison of SUV values among patients with HCC awaiting OLT provided valuable information regarding the effectiveness of TACE.

Response to chemotherapy estimates by FDG PET is an important prognostic factor in patients with Ewing sarcoma.

Response to chemotherapy is a prognostic factor in patients with Ewing sarcoma (ES); the role of FDG PET to predict response in these patients has not been thoroughly investigated. We evaluated the diagnostic accuracy and the potential of FDG PET to predict response to chemotherapy (CHT). We analyzed data of 50 patients with ES (median age 12.6 years). All patients were treated with neoadjuvant CHT, and underwent surgery for local control. All patients had (18)F-FDG PET/CT at diagnosis and after induction CHT, prior to local control. We compared response assessed by histopathology with FDG PET using standard uptake values (SUVs). Median SUV at diagnosis (SUV I) was 5 (range 1.2-17), and median SUV after neoadjuvant chemotherapy (SUV II) was 1.8 (range 0-8.4). Median SUV II/I ratio was 0.3 (range 0-1). SUV at diagnosis was significantly lower in patients with good histological response than in patients with poor histological response (median 3.8 vs. 7.2, p 0.02). We found a significant correlation between SUV II and outcome; the positive predictive value of an SUV II ≤ 2.5 for favorable response was 84.21 %, and the median SUV II was significantly higher in patients with disease progression (2.3 vs. 1.6, p = 0.04). In multivariate analysis, necrosis and SUV II were significant predictors of outcome. (18)F-FDG PET demonstrates high diagnostic accuracy for response to initial chemotherapy in patients with ES and it correlates with outcome. The role of FDG PET in predicting response and outcome should be further investigated.

A prospective study of the impact of fluorodeoxyglucose positron emission tomography with concurrent non‐contrast CT scanning on the management of operable pancreatic and peri‐ampullary cancers

BackgroundThe role of fluorodeoxyglucose (FDG) positron emission tomography (PET/CT) scanning in operable pancreas cancer is unclear. We, therefore, wanted to investigate the impact of PET/CT on management, by incorporating it into routine work‐up. MethodsThis was a single‐institution prospective study. Patients with suspected and potentially operable pancreas, distal bile duct or ampullary carcinomas underwent PET/CT in addition to routine work‐up. The frequency that PET/CT changed the treatment plan or prompted other investigations was determined. The distribution of standard uptake values (SUV) among primary tumours, and adjacent to biliary stents was characterised. ResultsFifty‐six patients were recruited. The surgical plan was abandoned in 9 (16%; 95% CI: 6–26) patients as a result of PET/CT identified metastases. In four patients, metastases were missed and seven were inoperable at surgery, not predicted by PET/CT. Unexpected FDG uptake resulted in seven additional investigations, of which two were useful. Among primary pancreatic cancers, a median SUV was 4.9 (range 2–12.1). SUV was highest around the biliary stent in 17 out of 28 cases. PET/CT detected metastases in five patients whose primary pancreatic tumours demonstrated mild to moderate avidity (SUV < 5). ConclusionsPET/CT in potentially operable pancreas cancer has limitations. However, as a result of its ability to detect metastases, PET/CT scanning is a useful tool in the selection of such patients for surgery.

Incidence of Internal Mammary Lymph Nodes with Silicone Breast Implants at MR Imaging after Oncoplastic Surgery.

To assess the incidence of benign and malignant internal mammary lymph nodes (IMLNs) at magnetic resonance (MR) imaging among women with a history of treated breast cancer and silicone implant reconstruction. The institutional review board approved this HIPAA-compliant retrospective study and waived informed consent. Women were identified who (a) had breast cancer, (b) underwent silicone implant oncoplastic surgery, and (c) underwent postoperative implant-protocol MR imaging with or without positron emission tomography (PET)/computed tomography (CT) between 2000 and 2013. The largest IMLNs were measured. A benign IMLN was pathologically proven or defined as showing 1 year of imaging stability and/or no clinical evidence of disease. Malignant IMLNs were pathologically proven. Incidence of IMLN and positive predictive value (PPV) were calculated on a per-patient level by using proportions and exact 95% confidence intervals (CIs). The Wilcoxon rank sum test was used to assess the difference in axis size. In total, 923 women with breast cancer and silicone implants were included (median age, 46 years; range, 22-89 years). The median time between reconstructive surgery and first MR imaging examination was 49 months (range, 5-513 months). Of the 923 women, 347 (37.6%) had IMLNs at MR imaging. Median short- and long-axis measurements were 0.40 cm (range, 0.20-1.70 cm) and 0.70 cm (range, 0.30-1.90 cm), respectively. Two hundred seven of 923 patients (22.4%) had adequate follow-up; only one of the 207 IMLNs was malignant, with a PPV of 0.005 (95% CI: 0.000, 0.027). Fifty-eight of 923 patients (6.3%) had undergone PET/CT; of these, 39 (67.2%) had IMLN at MR imaging. Twelve of the 58 patients (20.7%) with adequate follow-up had fluorine 18 fluorodeoxyglucose-avid IMLN, with a median standardized uptake value of 2.30 (range, 1.20-6.10). Only one of the 12 of the fluorodeoxyglucose-avid IMLNs was malignant, with a PPV of 0.083 (95% CI: 0.002, 0.385). IMLNs identified at implant-protocol breast MR imaging after oncoplastic surgery for breast cancer are overwhelmingly more likely to be benign than malignant. Imaging follow-up instead of immediate metastatic work-up may be warranted.

Positron Emission Tomography/Computed Tomography for the Pleural Staging of Malignant Pleural Mesothelioma: How Accurate Is It?

Background: Careful clinical staging in patients with malignant pleural mesothelioma (MPM) is fundamental in management planning. Positron emission tomography/computed tomography (PET/CT) is increasingly recognized as an important staging modality. Objectives: The purpose of this study was to assess whether the metabolic activity of the pleural tumor detected with PET/CT correlates with specific endoscopic features and pleural distribution of the lesions as assessed by medical thoracoscopy. Methods: Consecutive patients with MPM and available PET/CT performed before thoracoscopy were separated into 2 groups, according to their standardized uptake value (SUV). Kaplan-Meier-analysis for survival was performed on groups with low and high SUV. Agreement between PET/CT and thoracoscopy evaluation was analyzed using Cohen's kappa coefficient. The Wilcoxon test was used to compare the median SUV, and the χ² test was used to evaluate differences in endoscopic findings. Results: A total of 32 patients were included. The median maximum SUV (SUV max) was 6.1 and patients were separated into 2 groups based on this cutoff. Patients with SUV max <6.1 had a better survival than those with SUV max ≥6.1 (p = 0.005). The comparison between PET/CT and thoracoscopy showed a fair agreement for visceral and diaphragmatic pleural involvement and moderate agreement for the presence of nodular lesions. There was a statistically significant association between median SUV max and visceral pleural involvement; nodular lesions and visceral pleural involvement were more common in the high-SUV group than in the low-SUV group (p = 0.0012 and p = 0.03, respectively). Conclusions: PET/CT data may be predictive of thoracoscopic features of MPM associated with prognosis and staging, but the correlation is moderate at best. A degree of disagreement exists between these two modalities, which supports thoracoscopy as the gold standard for assessment of local invasion in MPM.

Results of 68Gallium-DOTATATE PET/CT Scanning in Patients with Multiple Endocrine Neoplasia Type 1

Screening for neuroendocrine tumors (NETs) in patients with multiple endocrine neoplasia type 1 (MEN1) is recommended to detect primary and metastatic tumors, which can result in significant morbidity and mortality. The utility of somatostatin receptor imaging (68)Gallium-DOTATATE PET/CT in patients with MEN1 is not known. The aim of this study was to prospectively determine the accuracy of (68)Gallium-DOTATATE PET/CT vs (111)In- pentetreotide single-photon emission CT (SPECT)/CT and anatomic imaging in patients with MEN1. We performed a prospective study comparing (68)Gallium-DOTATATE PET/CT, (111)In-pentetreotide SPECT/CT, and triphasic CT scan to clinical, biochemical, and pathologic data in 26 patients with MEN1. (68)Gallium-DOTATATE PET/CT detected 107 lesions; (111)In-pentetreotide SPECT/CT detected 33 lesions; and CT scan detected 48 lesions. Lesions detected on (68)Gallium-DOTATATE PET/CT had high standard uptake value (SUV)(max) (median SUV(max) = 72.8 [range 19 to 191]). In 7 of the 26 patients (27%), (68)Gallium-DOTATATE PET/CT was positive, with a negative (111)In-pentetreotide SPECT/CT, and in 10 patients (38.5%), additional metastases were detected (range 0.3 cm to 1.5 cm). In 8 of the 26 patients (31%), there was a change in management recommendations as a result of the findings on (68)Gallium-DOTATATE PET/CT that were not seen on (111)In-pentetreotide SPECT/CT and CT scan. (68)Gallium-DOTATATE PET/CT is more sensitive for detecting NETs than (111)In-pentetreotide SPECT/CT and CT scan in patients with MEN1. This imaging technique should be integrated into radiologic screening and surveillance of patients with MEN1 because it can significantly alter management recommendations.

18F-fluorodeoxyglucose Positron Emission Tomography in Kaposi Sarcoma Herpesvirus-Associated Multicentric Castleman Disease: Correlation With Activity, Severity, Inflammatory and Virologic Parameters.

Kaposi sarcoma herpesvirus (KSHV)-associated multicentric Castleman disease (MCD) is a lymphoproliferative inflammatory disorder commonly associated with human immunodeficiency virus (HIV). Its presentation may be difficult to distinguish from HIV and its complications, including lymphoma. Novel imaging strategies could address these problems. We prospectively characterized (18)F-fluorodeoxyglucose positron emission tomography (PET) findings in 27 patients with KSHV-MCD. Patients were imaged with disease activity and at remission with scans evaluated blind to clinical status. Symptoms, C-reactive protein level, and HIV and KSHV loads were assessed in relation to imaging findings. KSHV-MCD activity was associated with hypermetabolic symmetric lymphadenopathy (median maximal standardized uptake value [SUVmax], 6.0; range, 2.0-8.0) and splenomegaly (3.4; 1.2-11.0), with increased metabolism also noted in the marrow (2.1; range, 1.0-3.5) and salivary glands (3.0; range, 2.0-6.0). The (18)F-fluorodeoxyglucose PET abnormalities improved at remission, with significant SUVmax decreases in the lymph nodes (P = .004), spleen (P = .008), marrow (P = .004), and salivary glands (P = .004). Nodal SUVmax correlated with symptom severity (P = .005), C-reactive protein level (R = 0.62; P = .004), and KSHV load (R = 0.54; P = .02) but not HIV load (P = .52). KSHV-MCD activity is associated with (18)F-FDG PET abnormalities of the lymph nodes, spleen, marrow, and salivary glands. These findings have clinical implications for the diagnosis and monitoring of KSHV-MCD and shed light on its pathobiologic mechanism.

Noninvasive Differential Diagnosis of Pulmonary Nodules Using the Standardized Uptake Value Index.

We previously showed that the standardized uptake value (SUV) index, which was defined as the ratio of the maximum SUV of the tumor to mean SUV of the liver, was a surrogate marker of lung cancer aggressiveness. In this study of patients with pulmonary nodules (PNs), we explored whether the SUV index could be used to differentiate small malignant from small benign PNs. A total of 284 patients with solitary PNs ≤2 cm in size underwent positron emission tomography/computed tomography and surgery. The associations between pathological findings and clinical factors were evaluated. The median SUV indices of lung cancer, metastatic PNs and benign nodules were 1.2, 1.5, and 0.6, respectively (P <0.01). A SUV index cut-off value of 1.2 was used to differentiate benign from malignant nodules. When patients were grouped according to SUV index cut-off values of <1.2 or ≥1.2, the following cases were false-negative: lung adenocarcinoma (P <0.01), kidney as primary site (P <0.01), and metastatic PNs with long disease-free survival (P = 0.02). As a noninvasive diagnostic marker, the SUV index was found to be useful for differentiating benign from malignant small PNs.

The Presence of FDG PET/CT Focal, Not Osteolytic, Lesion(s) Identifies a Sub-Group of Patients with Smoldering Multiple Myeloma with High-Risk of Progression into Symptomatic Disease

Smoldering multiple myeloma (SMM) is an asymptomatic plasma cell disorder whose risk of progression to symptomatic MM (MM) is highly variable. Therefore, the identification of predictors of progression into MM is a relevant end point. Several markers (serum M protein, percentage of bone marrow plasma cells, free light chain, FLC, ratio, immunophenotyping of aberrant plasma cells and focal lesions, FLs at MRI) have already been established to identify sub-groups of SMM patients (pts) with a highest risk of progression into MM. Among imaging methods, FDG-PET/CT is a reliable technique for assessing early skeletal involvement and for predicting outcomes at the onset of MM. However, no data are available regarding the impact of PET/CT FLs in SMM on time to progression (TTP) into symptomatic disease.To address this issue, we prospectively studied pts with a suspected diagnosis of SMM with FDG-PET/CT. A cohort of 73 pts, with a median age of 61 years old (range 27-83) and a confirmed diagnosis of SMM, followed for a median of 2.2 years, is herein reported. By study design, all the pts were studied with PET/CT at baseline. Bone marrow involvement was described as negative, diffuse or focal. The number of FLs, as well as size and associated standardized uptake values (SUV) were recorded. For each FL, the presence of eventual underlying osteolytic lesion was investigated by the CT part of the scan; pts with osteolytic lesions were excluded from the present study, as they were considered as having symptomatic MM. Follow-up took place every 3-4 months and included clinical history, serum and urine markers and PET/CT plus axial MRI for occurrence of symptoms or an increase in M component. Progression to MM was defined by the presence of CRAB features. Skeletal progression was defined by the appearance of one or more sites of osteolytic bone destruction, pathological fractures and/or soft masses at PET/CT or MRI. The start of systemic therapy was defined as the date of event for the analysis of TTP.Baseline patient characteristics were as follows: 83% had IgG isotype, 8% IgA and 9% BJ, with a median M component of 2.5 g/dL; 70% had ISS stage I, 23% stage II and 7% stage III. Median plasma cell involvement on bone marrow (BMPC) was 30% (range 5-100%), with 16% of the pts having more than 60% BMPC. The median serum involved/uninvolved FLC ratio was 14.39 (range 1.28-2255), with 11% of the pts presenting with a ratio ≥ 100. PET/CT was negative in 64/73 pts (88%) and positive in 9/73 (12%) of them; 5 pts had 1 FLs, 1 pt 2 FLs, 2 pts more than 3 FLs and 1 pt a diffuse bone marrow involvement. Median SUV max value was 4.45 (range 2.5-5.2). No significant differences between patients with positive or negative PET/CT were found regarding the other baseline characteristics.At the time of the present analysis, 63% of the pts remained in the asymptomatic phase while 37% of them progressed to MM, in a median time of 4 years, including 21% with skeleton involvement, with/without the appearance of other CRAB symptoms, and 16% with exclusive serological signs of progression. Sixty six per cent of the pts with positive PET/CT progressed to MM in comparison to 33% of the pts with negative PET/CT (P = 0.034). The relative risk of progression of the pts with a positive PET/CT was 2.3 (95% CI 09.-5.9, P= 0.06). Moreover, the relative risk of skeletal progression was 4.0 (95% CI 1.3-12, P= 0.013), with a median TTP of 2.2 years for pts with positive PET/CT versus 7 years for those with negative PET/CT (figure 1). The probability of progression within 2 and 3 years for pts with positive PET/CT was 48% and 65%, respectively, in comparison to 32% and 42% for negative pts.In conclusion, approximately 10% of the pts with SMM have a positive PET/CT, mainly with few FLs, without underlying osteolytic lesion, with a low FDG uptake. PET/CT positivity significantly increased the risk of progression of SMM into active MM. PET/CT could become a new risk factor to define high risk SMM. A larger cohort of pts will be presented at the meeting. Further studies are warranted to find and optimal cut off point of FLs to capture the higher risk of progression at 2 year and to merge with other prognostic factors. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Hypoxia, blood flow and metabolism in squamous-cell carcinoma of the head and neck: correlations between multiple immunohistochemical parameters and PET.

BackgroundThe relationship between the uptake of [18F]fluoroerythronitroimidazole ([18F]FETNIM), blood flow ([15O]H2O) and 2-[18F]fluoro-2-deoxyglucose ([18F]FDG) and immunohistochemically determined biomarkers was evaluated in squamous-cell carcinomas of the head and neck (HNSCC).Methods[18F]FETNIM and [18F]FDG PET were performed on separate days on 15 untreated patients with HNSCC. Hypoxia imaging with [18F]FETNIM was coupled with measurement of tumor blood flow using [15O]H2O. Uptake of [18F]FETNIM was measured as tumor-to-plasma ratio (T/P) and fractional hypoxic volume (FHV), and that of [18F]FDG as standardized uptake value (SUV) and the metabolically active tumor volume (TV). Tumor biopsies were cut and stained for GLUT-1, Ki-67, p53, CD68, HIF-1α, VEGFsc-152, CD31 and apoptosis. The expression of biomarkers was correlated to PET findings and patient outcome.ResultsNone of the PET parameters depicting hypoxia and metabolism correlated with the expression of the biomarkers on a continuous scale. When PET parameters were divided into two groups according to median values, a significant association was detected between [18F]FDG SUV and p53 expression (p =0.029) using median SUV as the cut-off. There was a significant association between tumor volume and the amount of apoptotic cells (p =0.029). The intensity of VEGF stained cells was associated with [18F]FDG SUV (p =0.036). Patient outcome was associated with tumor macrophage content (p =0.050), but not with the other biomarkers. HIF-1α correlated with GLUT-1 (rs =0.553, p =0.040) and Ki-67 with HIF-1α (rs =506, p =0.065). p53 correlated inversely with GLUT-1 (rs = −618, p =0.019) and apoptosis with Ki-67 (rs = −638, p =0.014).ConclusionsA high uptake of [18F]FDG expressed as SUV is linked to an aggressive HNSCC phenotype: the rate of apoptosis is low and the expressions of p53 and VEGF are high. None of the studied biomarkers correlated with perfusion and hypoxia as evaluated with [15O]H2O-PET and [18F]FETNIM-PET. Increased tumor metabolism evaluated with PET may thus signify an aggressive phenotype, which should be taken into account in the management of HNSCC.

False-positive fluorodeoxyglucose positron emission tomography results after chemotherapy in patients with metastatic seminoma

IntroductionThe treatment of residual masses after chemotherapy in seminomas remains a controversial topic. Postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) in all patients would lead to severe overtreatment with a high rate of complications and additional procedures. For this reason, fluorodeoxyglucose positron emission tomography (FDG-PET) was introduced. FDG-PET has an accuracy of 88%. In 15% of cases, FDG-PET findings are false positive (FP) with unclear consequences. Therefore, we retrospectively investigated the rate of unnecessary procedures due to FP results on FDG-PET. Materials and methodsBetween July 2003 and September 2013 we performed 305 PC-RPLNDs in 277 patients, 22 because of metastatic seminoma. Of them, 11 patients had a preoperative FDG-PET at least 6 weeks after chemotherapy. Indication for surgery was a marker-negative progression of the lesion in 7 patients who did not undergo FDG-PET, a marker-negative progression with a negative result on FDG-PET in 2 patients, and a positive result on FDG-PET with normal markers in 9 patients. Furthermore, PC-RPLND was indicated in 3 patients because of ureteral compression/infiltration with ureteral stents or nephrostomies. In 1 patient, there was uncertainty whether the initial retroperitoneal tumor contained choriocarcinoma elements. Standardized uptake values (SUVs) were recorded for all patients undergoing FDG-PET. ResultsThe FDG-PET findings were FP in 7 of 11 (64%) patients. The median age of the patients was 45.4 years (39–49). The median SUV in the patients was 6.6 (3.1–11.6), and the median diameter of the residual mass was 6.8cm (2.9–11). In 4 of 7 patients, intraoperative or postoperative complications occurred (polar artery ligation with functional loss, bilateral non–nerve-sparing technique with retrograde ejaculation, ureteral replacement with an ileal segment, and pulmonary embolism). ConclusionIn patients with metastatic seminoma who received chemotherapy, FDG-PET is a valuable tool to evaluate whether the residual mass contains viable tumor tissue or only necrosis. Nevertheless, because of FP results, a subgroup is overtreated with consecutive mortality or morbidity. We suggest an alternative therapy algorithm. In case of a positive result on FDG-PET studies, at least 8 weeks after the end of the chemotherapy, only a minority require surgery (e.g., patients with ureteral compression, patients with high risk of recurrence, or patients with unclear initial histology). In all other cases, we suggest a repeat FDG-PET study at least 6 weeks after the initial PET scan. Only in cases of increased SUVs or progressive disease histology should be obtained, all others can be on active surveillance.

PET Scans as a Predictive Marker of Survival in Advanced Colorectal Cancer

BackgroundThe clinical utility of fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan in predicting the outcome of patients with metastatic colorectal cancer (mCRC) has not been well studied. We hypothesized that standardized uptake value (SUV) in FDG-PET scans after treatment predicts outcomes among patients with mCRC. Patients and MethodsWe retrospectively reviewed mCRC patients who had FDG-PET scans before their treatment and measured their SUV on follow-up imaging at the Karmanos Cancer Institute. Primary end points of time to progression (TTP) and overall survival (OS) were compared in 2 groups: follow-up (posttreatment) SUV of 0 versus > 0. ResultsThe study population consisted of 44 patients (median age of 58.1 years). Forty (91%) of the patients were treated first-line, 34 (77%) received an oxaliplatin-based regimen, and 7 (16%) received an irinotecan-based regimen. Thirty-four (77%) patients received concurrent bevacizumab. Median pretreatment SUV was 9.2 (range, 1.7-46.3), and median posttreatment SUV (in n = 41) was 4.0 (range, 0-14). The median percent change in SUV was −68.5% (range, −9.2% to −100%). The median time interval between scans was 2.6 months. There was no statistically significant difference noted between metabolic responders and nonresponders with regard to TTP and OS. However, patients with a posttreatment SUV of 0 had significantly longer OS than those with posttreatment SUV of > 0 (median, 42 vs. 25.2 months, respectively), and slightly longer TTP (median, 8.2 vs. 6.9 months, respectively). ConclusionSystemic therapy significantly decreased SUV on follow-up PET scans in advanced colorectal cancer patients. Absence of FDG uptake on follow-up PET scans was associated with markedly longer OS and slightly longer TTP.

Effect of furosemide administration before F-18 fluorodeoxyglucose positron emission tomography/computed tomography on urine radioactivity and detection of uterine cervical cancer

In evaluating uterine cervical cancer with ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), there may be overlap between the FDG activity at tumor sites and nonspecific radioactivity in the urine. We evaluated the efficacy of furosemide premedication with routine hydration to obtain better contrast and less overlap between cervical cancer and the urinary bladder. We retrospectively evaluated 166 patients who had primary or relapsed cervical cancer and underwent FDG PET/CT scanning with (133 patients) or without (33 patients) furosemide premedication (10 mg intravenous, slowly injected 30 min before the scan). We calculated bladder and tumor maximum and median standardized uptake value (SUVmax and SUVmed), and overlap between tumor and urinary activity was detected visually. Overlap between urinary and tumor radioactivity was observed in 8 of 133 scans (6%) in patients who receive furosemide and in 3 of 33 scans (9%) in patients who did not receive furosemide. The SUVmax and SUVmed for the bladder were significantly lower in patients who were pretreated with furosemide (SUVmax, 6.3; SUVmed, 4.6) than patients who were not pretreated with furosemide (SUVmax, 8.8 [P ≤ 0.008]; SUVmed, 6.5 [P ≤ 0.002]). The tumor SUVmax and SUVmed were similar between the patient groups. Furosemide premedication before FDG PET/CT scanning may enable improved evaluation of activity and extension of cervical cancer.

Thyroid incidentalomas discovered on positron emission tomography CT scanning – Malignancy rate and significance of standardised uptake values

AimsIncreasing use of 18F-Fluorodeoxy glucose (FDG) Positron Emission Tomography Computed Tomography (PET CT) has resulted in an increased frequency of incidentally discovered areas of focally increased FDG uptake within the thyroid gland – thyroid incidentalomas. We aimed to compare radiological characteristics of thyroid incidentalomas with cytology, histology and ultrasound findings. Materials and methodsWe examined all FDG PET CT scan reports for all patients undergoing this investigation over a 6 year period in a single tertiary cancer centre. All PET CT scans followed an agreed proforma allowing reports mentioning “thyroid” to be identified. Reports commenting on a positive finding within the thyroid gland were investigated further manually. Incidental mentions of thyroid with no underlying abnormality were discounted from analysis. ResultsIn the study period, 7221 patients underwent FDG PET CT scanning in our unit. Within this group 75 (1%) showed diffuse FDG uptake and 81 (1.1%) showed focal uptake (thyroid incidentalomas). Only 30 patients (37%) with incidentalomas had further investigation and malignancy rate was 23% (7/30). Median Standardised Uptake Values (SUV) in malignant lesions was 9.9 (range 3.5–17.8) whilst in benign lesions and diffuse lesions it was 5.4 (2.8–32) and 4.2 (2.1–25.6) respectively (p = 0.0013, Kruskal Wallis). ConclusionThere remains a need to develop a standardised approach to the investigation and management of thyroid incidentalomas discovered on FDG PET CT scanning. Up to 1 in 4 of these patients will harbour thyroid malignancy.

Absence of a Relationship between Tumor 18F-fluorodeoxyglucose Standardized Uptake Value and Survival in Patients Treated with Definitive Radiotherapy for Non–Small-Cell Lung Cancer

Introduction:A recent meta-analysis suggested that patients with non–small-cell lung cancer (NSCLC) whose primary tumors have a higher standardized uptake value (SUV) derived from 18F-fluorodeoxyglucose positron emission tomography (PET) have a worse prognosis in comparison with those with tumors with lower values. However, previous analyses have had methodological weaknesses. Furthermore, the prognostic significance over the full range of SUV values in patients treated nonsurgically remains unclear. The aim of this retrospective study was to investigate the relationship between survival and maximum SUV (SUVmax) analyzed as a continuous variable, in patients with NSCLC, staged using PET/computed tomography (CT) and treated with radiotherapy with or without chemotherapy.Methods:Eligible patients had a histological diagnosis of NSCLC, were treated with radical radiotherapy with or without chemotherapy as their primary treatment, and had pretreatment PET/CT scans. SUVmax, defined as the maximum pixel SUV value retrieved from the primary tumor, was analyzed primarily as a continuous variable for overall survival.Results:Eighty-eight patients met eligibility criteria: stage I, 19; stage II, 10; and stage III, 59. Median SUVmax was 15.0 (range, 2.5–56). Higher stage was associated with higher SUVmax values (p = 0.048). In univariate analysis, there was no evidence of a prognostic effect of SUVmax (hazard ratio per doubling = 0.83; 95% confidence interval, 0.62–1.11; p = 0.22). Analyzing SUVmax as a dichotomous variable (median cut point = 15.0), the hazard ratio (high: low) for risk of death was 0.71, with p = 0.18 (95% confidence interval, 0.44–1.15).Conclusions:In this cohort of patients, increasing SUVmax derived from 18F-fluorodeoxyglucose–PET/CT was associated with increasing tumor, node, metastasis (TNM) stage. We found no evidence of an association of increasing SUVmax with a shorter survival. Previous reports of an association between prognosis and SUVmax may partly be the result of methodological differences between this study and previous reports and an association between stage and SUVmax.

Visibility Of Bone Lesions In Relapsed Multiple Myeloma Can Be Improved By FDG-PET Scanning

Osseous involvement is one the predominant features of patients with multiple myeloma (MM). Whole body X-ray (WBX) is the standard method for detecting skeleton abnormalities but has limited value in relapsing disease since it cannot make a distinction between old and new active skeleton lesions. Therefore changes in metabolic activity might be a more useful method to detect new skeleton lesions in MM. This can be assessed by [F-18] fluorodeoxyglucose positron emission tomography (FDG-PET) imaging. Consequently WBX and FDG-PET was studied in relapsing MM prior to treatment. In addition immunohistochemical staining on bone marrow biopsies was performed for glucose transport protein (GLUT) 3 expression, micro vessel density (MVD), and vascular endothelial growth factor (VEGF) to demonstrate whether these parameters might be predictive for the in vivo scanning results. This study included 44 patients (median age 62 yr (range 48-78)) with a median of 3.5 (range 2-12) relapses. Thus far 86% of the patients were treated with autologous stem cell transplantation in combination with bortezomib (78%) or lenalidomide (65%). New lesions on FDG-PET were more frequently demonstrated than new lesions on WBX (p=0.00001). In 78% of the patients FDG-PET demonstrated a median of 4 lesions (range 0-22) per patient with a median standard uptake value (SUV) max of 5.7 (range 0-24). In 42% of the patients new X-ray lesions (median 0 (range 0-7)) were demonstrated and these were concordant with the results of FDG-PET. In 5 % of the patients new X-ray lesions were observed without FDG-PET lesions. For the relapsing patients treatment consisted of dexamethasone in combination with bortezomib (65%) or lenalidomide (50%). CR was obtained in 27% of the patients, PR in 39% and progressive disease in 22%. Average time to next treatment (TTNT) was 11.7 months (2-43). However FDG-PET positivity was not predictive for PFS (p =0.55) and OS (p=0.40) neither if PET positivity was defined as more than 3 lesions nor if the cut off value of SUV max > 4.2 was applied. Immunohistochemical staining on bone marrow biopsies (n=20) with CD34 demonstrated a significant increased MVD of 39 ± 54 (mean ± SD, normal bone marrow MVD 3.5 ± 2.9), in particular when clusters of plasma cells were present. These enhanced MVD was associated with a significant increased expression of VEGF and GLUT-3. However MVD (p = 0.16), VEGF (p = 0.70) or GLUT-3 (p =0.70) expression were not predictive for having a positive or negative FDG-PET. In summary, our results demonstrate that FDG-PET is more informative than WBX for detecting skeleton lesions in relapsing MM patients. However, and in contrast to what was previously shown in patients with newly diagnosed MM, FDG-PET it is not predictive for treatment outcome. This might be due to heterogeneity in studied patients and treatments. Disclosures:No relevant conflicts of interest to declare.

Focal Arterial Inflammation Precedes Subsequent Calcification in the Same Location

Background— Arterial calcium (Ca) deposition has been identified as an active inflammatory process. We sought to test the hypothesis that local vascular inflammation predisposes to subsequent arterial calcium deposition in humans. Methods and Results— From a hospital database, we identified 137 patients (age, 61±13 years; 48.1% men) who underwent serial positron-emission tomography/computed tomography (1–5 years apart). Focal arterial inflammation was prospectively determined by measuring 18F-flourodeoxyglucose uptake (using baseline positron-emission tomography) within predetermined locations of the thoracic aortic wall and was reported as a standardized uptake value. A separate, blinded investigator evaluated calcium deposition (on the baseline and follow-up computed tomographic scans) along the same standardized sections of the aorta. New calcification was prospectively defined using square root–transformed difference of calcium volume score, with a cutoff value of 2.5. Accordingly, vascular segment was classified as either with or without subsequent calcification. Overall, 67 (9%) of aortic segments demonstrated subsequent calcification. Baseline median (interquartile range) standardized uptake value was higher in segments with versus without subsequent calcification (2.09 [1.84–2.44] versus 1.92 [1.72–2.20], P =0.002). This was also true in the subset of segments with Ca present at baseline (2.08 [1.81–2.40] versus 1.86 [1.66–2.09], P =0.02), as well as those without (2.17 [1.87–2.51] versus 1.93 [1.73–2.20], P =0.04). Furthermore, across all patients, subsequent Ca deposition was associated with the underlying 18F-flourodeoxyglucose uptake (inflammatory signal), measured as standardized uptake value (odds ratio [95% confidence interval]=2.94 [1.27–6.89], P =0.01) or target-to-background ratio (2.59 [1.18–5.70], P =0.02), after adjusting for traditional cardiovascular risk factors. Conclusions— Here, we provide first-in-man evidence that arterial inflammation precedes subsequent Ca deposition, a marker of plaque progression, within the underlying location in the artery wall.

Feasibility and Predictability of Perioperative PET and Estrogen Receptor Ligand in Patients with Invasive Breast Cancer

The presence of estrogen receptor (ER) in breast cancer is a prognostic indicator for both disease-free and overall survival. 16α-(18)F-fluoro-17β-estradiol ((18)F-FES) with PET is a noninvasive test for evaluation of ER expression and has been used for predicting response to endocrine therapy in patients with ER-positive metastatic breast cancer. The purpose of this study was to correlate (18)F-FES PET and ER expression in patients with primary, operable breast cancer. Forty-eight patients were prospectively enrolled in an institutional review board-approved protocol and signed an informed consent form. All patients had undergone (18)F-FES PET preoperatively. Clinical characteristics, tumor characteristics, and treatment outcomes were recorded. Immunohistochemical analysis for ER and progesterone receptor (PgR) percentage expression (46 surgical, 2 core biopsy specimens) was performed. (18)F-FES PET standardized uptake value (SUV) of the breast lesion was correlated with percentage immunohistochemistry ER and PgR expression. (18)F-FES PET SUV was quantified, with a value of 1.5 or more considered positive, and ER and PgR was quantified, with 1% or more considered positive. Formalin-fixed paraffin-embedded tissue was available for 44 patients (42 surgical, 2 core biopsy specimens). We used a microarray platform, and estrogen-related gene expression data (ESR1, ESR2, and PGR) were compared with (18)F-FES PET SUV (Spearman rank correlation). Tumor size, ductal histology, grade, HER2-neu overexpression, PgR expression, estradiol level, body mass index (BMI), and lean BMI were compared with (18)F-FES PET uptake using univariate and multivariate analysis. Forty-eight patients completed our protocol, and 2 patients did not undergo surgery because bone metastases were identified preoperatively on (18)F-FES PET. Eighty-three percent of our patients were stage I or II, with a median tumor size of 1.9 cm. Forty-one patients underwent a sentinel node biopsy. Twenty-one patients had nodal involvement. (18)F-FES PET identified 5 patients with axillary nodal uptake (median SUV, 3.0; range, 1.7-6.9). These 5 patients had ER-positive breast cancer, and all had more than 4 positive nodes at the time of axillary node dissection. (18)F-FES PET SUV was associated with immunohistochemistry ER expression. The sensitivity and specificity of the (18)F-FES PET for the breast lesion were 0.85 and 0.75, respectively. Estrogen and progesterone gene expression (ESR1, ESR2, and PGR) was not associated with (18)F-FES PET SUV (Spearman rank correlation). We found a significant correlation between (18)F-FES PET SUV and tumor size (P = 0.0015) but not with ductal histology, grade, HER2-neu overexpression, PgR, estradiol, BMI, or lean BMI (logistic regression). ER expression (P < 0.001) and tumor size (P < 0.0001) were significant on multivariate regression analysis. (18)F-FES PET SUV correlated with ER immunohistochemistry expression but not gene expression in our patients with early breast cancer. We found that size of primary tumor was significantly associated with (18)F-FES PET SUV. (18)F-FES PET is highly predictive for metastatic disease and helped in the identification of patients with metastatic disease in a preoperative setting.