Glucose metabolism of human prostate cancer mouse xenografts

We hypothesized that the glucose metabolism of prostate cancer is modulated by androgen. We performed in vivo biodistribution and imaging studies of [F-18] fluorodeoxyglucose (FDG) accumulation in androgen-sensitive (CWR-22) and androgen-independent (PC-3) human prostate cancer xenografts implanted in castrated and noncastrated male athymic mice. The growth pattern of the CWR-22 tumor was best approximated by an exponential function (tumor size in mm3 = 14.913 e(0.1086 x days), R2 = .96, n = 5). The growth pattern of the PC-3 tumor was best approximated by a quadratic function (tumor size in mm3 = 0.3511 x days2 + 49.418 x day - 753.33, R2 = .96, n = 3). The FDG accumulation in the CWR-22 tumor implanted in the castrated mice was significantly lower, by an average of 55%, in comparison to that implanted in the noncastrated host (1.27 vs. 2.83, respectively, p < .05). The 3-week maximal standardized uptake value (SUVmax) was 0.99 +/- 0.43 (mean +/- SD) for CWR-22 and 1.21 +/- 0.32 for PC-3, respectively. The 5-week SUVmax was 1.22 +/- 0.08 for CWR-22 and 1.35 +/- 0.17 for PC-3, respectively. The background muscle SUVmax was 0.53 +/- 0.11. Glucose metabolism was higher in the PC-3 tumor than in the CWR-22 tumor at both the 3-week (by 18%) and the 5-week (by 9.6%) micro-PET imaging sessions. Our results support the notions that FDG PET may be useful in the imaging evaluation of response to androgen ablation therapy and in the early prediction of hormone refractoriness in men with metastatic prostate cancer.     

The distribution of periodontal disease and loss of attachment in jaw sextants in different age groups--cross-sectional study

The distribution of periodontal disease stages is not the same in both human jaws, parts of the same jaw or in different ages of life. In the sample of 2,730 sextants, 455 persons 15+ years of age, analysis of distribution of both periodontal disease and loss of attachment in jaw sextants in different age groups was made, using the Community Periodontal Index (CPI) and Loss of Attachment (LA). Statistical significance testing was checked using the Pearson Chi-Square-test with probability of 95%. Healthy periodontium is mostly found in upper anterior sextant (36%, p < 0.001), and bleeding on probing in lower right sextant (25.45%, p < 0.001). There is most calculus in lower anterior sextant (48.19%, p < 0.001), followed by upper posterior (15-17%). Deep pockets are more often in lower anterior sextant (31.87%, p < 0.001), and upper and lower posterior sextants are without teeth in 18-20.5% of cases, but lower anterior sextant in only 7.73% (p < 0.001). Cumulative minimal loss of attachment (0-3 mm) significantly is more often present in upper anterior sextant (21.2%, p < 0.001), while values 5-11 mm are more often in lower anterior sextant (25-43%, p < 0.001). Loss of attachment > or = 12 mm appears in only 1.4% present sextants and it is rear on left jaw side. Significant differences in distribution of both periodontal disease and loss of attachment appear in age 30+.     

Incidentalomes parotidiens en TEP-18F-FDG : prévalence,diagnostic et impact thérapeutique

Objective

Parotid gland incidentalomas are unexpected hypermetabolic foci in the parotid region that can be found when scanning the whole-body by PET/CT. The role of SUVmax is controversial to differentiate benign or malignant tumours in this indication. The aim of this study was to determine PET/CT features of malignant parotid incidentaloma, in order to improve medical care.

Assessment of 18FDG PET for diagnosis of pancreatic tumors

The paper examines the informational value of positron emission tomography (PET) using 18FDG in the diagnosis of malignant of neoplasms of the pancreas and in the estimation of the extent of a metastatic involvement. Forty-four patients (26 males and 18 females whose age ranged from 28 to 60 years) with histologically verified cancer of the pancreas were examined. The study was conducted in the whole body mode on an Ecat Exact 47 positron emission tomograph following 70-90 minutes of administration of 18FDG, 370-420 MBk. To assess the findings, the differential accumulation ratio (DAR) of formation/liver was calculated. The mean DAR in patients with benign and malignant pancreatic tumors was 1.17 +/- 0.064 and 4.90 +/- 0.3 (p < 0.05). There was a false positive case in a patient with an exacerbation of chronic pancreatitis in the study. A relationship was observed between the level of tumor tissue 18FDG capture and the degree of malignancy. PET scanning in the whole body mode estimates the extent of a tumorous process. The authors' data show that the liver was most commonly involved in a metastatic process (96.6%). Hence, 18FDG PET is a highly informative technique in the diagnosis of malignant pancreatic tumors and in the estimation of the extent of a metastatic process and permits a differential diagnosis between benign and malignant tumors.     

La fluorocholine(18F) a une utilité clinique dans le cancer de la prostate et le carcinome hépatocellulaire… parfois chez le même malade

Case reportIn order to stage hepatocellular carcinoma (HCC), a patient was referred to PET/CT using fluorodeoxyglucose(18F) (FDG) and, if necessary, fluorocholine(18F) (FCH). HCC was proven by biopsy of a hepatic mass discovered on CT performed for a biological recurrence of prostate cancer.ResultFDG PET/CT did not show any anomaly. FCH PET/CT was thus performed and showed various foci: the hepatic mass, a large abdominal adenopathy and an unexpected subcentimetre lung nodule. The diagnostic uncertainty mostly concerned this lung nodule which was biopsied and consisted of a metastasis of the prostate cancer. Due to the presence of two metastatic cancers, the patient's management was altered, with chemotherapy for the HCC and hormone therapy for the prostate cancer.ConclusionSeveral types of cancer take-up fluorocholine(18F), which is a powerful tool to detect metastases, in particular in case of rising levels of marker with a negative FDG PET/CT. Even when FDG PET/CT is positive, FCH may reveal unexpected foci with other metabolic characteristics, although it is not specific of a given primary cancer, as well as FDG. For staging of HCC, we thus recommend to perform PET/CT with both tracers.     

Récidive biologique de cancer de la prostate : intérêt de la TEP/TDM à la fluorocholine (18F) du corps entier

Case reportA patient was referred to fluorocholine (18F) PET/CT to restage a biological recurrence of his prostate cancer. There was a doubt on local and lymph node recurrence on MRI.ResultPET/CT showed several pelvic foci evocative of local and lymph node recurrence, more extensive than the MRI anomaly without bone lesion; this recurrence was treated by hormone therapy. But FCH PET/CT also revealed a left cerebral focus. Cerebral MRI was therefore performed which confirmed an anomaly evocative of a grade II brain lesion.ConclusionThis observation illustrates the fact that, in case of prostate cancer, a whole-body imaging, including the skull, is useful, even when foci are detected in the pelvis. Several types of cancer take-up fluorocholine (18F): in case of a visceral distant focus in a patient with prostate cancer, the hypothesis of a second primary cancer should be considered.     

Implications of False Negative and False Positive Diagnosis in Lymph Node Staging of NSCLC by Means of 18F-FDG PET/CT

Background

Integrated ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) is widely performed in hilar and mediastinal lymph node (HMLN) staging of non-small cell lung cancer (NSCLC). However, the diagnostic efficiency of PET/CT remains controversial. This retrospective study is to evaluate the accuracy of PET/CT and the characteristics of false negatives and false positives to improve specificity and sensitivity.

Methods

219 NSCLC patients with systematic lymph node dissection or sampling underwent preoperative PET/CT scan. Nodal uptake with a maximum standardized uptake value (SUVmax) >2.5 was interpreted as PET/CT positive. The results of PET/CT were compared with the histopathological findings. The receiver operating characteristic (ROC) curve was generated to determine the diagnostic efficiency of PET/CT. Univariate and multivariate analysis were conducted to detect risk factors of false negatives and false positives.

Results

The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET/ CT in detecting HMLN metastases were 74.2% (49/66), 73.2% (112/153), 54.4% (49/90), 86.8% (112/129), and 73.5% (161/219). The ROC curve had an area under curve (AUC) of 0.791 (95% CI 0.723-0.860). The incidence of false negative HMLN metastases was 13.2% (17 of 129 patients). Factors that are significantly associated with false negatives are: concurrent lung disease or diabetes (p<0.001), non-adenocarcinoma (p<0.001), and SUVmax of primary tumor >4.0 (p=0.009). Postoperatively, 45.5% (41/90) patients were confirmed as false positive cases. The univariate analysis indicated age > 65 years old (p=0.009), well differentiation (p=0.002), and SUVmax of primary tumor ≦4.0 (p=0.007) as risk factors for false positive uptake.

Conclusion

The SUVmax of HMLN is a predictor of malignancy. Lymph node staging using PET/CT is far from equal to pathological staging account of some risk factors. This study may provide some aids to pre-therapy evaluation and decision-making.     

Problème diagnostique posé par une lésion hépatique hypermétabolique en TEP à la fluorocholine (18F) : à propos d’un cas

IntroductionWe report a case of atypical fluorocholine (18F) PET/CT hypermetabolic hepatic lesion discovered during the staging of a prostate carcinoma.Case reportBecause of elevated PSA serum level, the patient had prostate biopsies which elicited an adenocarcinoma with a Gleason score of 8 (4 + 4). Pelvic MRI did not display any extracapsular disease extension. The PET/CT scan demonstrated a prostatic focal uptake and a liver increased uptake area matching with a segment VII hepatic nodule measuring 25 mm within a fatty liver, which was hypometabolic on the PET scan and hypodense on the CT scan. The liver ultrasound study reported the lesion as a focal spared area of healthy liver tissue within steatosis, whereas MRI diagnostic conclusion was inflammatory hepatocellular adenoma. When asking the patient, it appeared that the hepatic nodule had been known for 7 years, its size was unchanged, and, from previous radiologic imaging, it had been considered as an adenoma. However, there was no histological proof.DiscussionIn the interpretation of the PET/CT scan findings, we excluded a hepatocellular carcinoma and a prostate metastasis due to the long period of time during which the nodule had been followed up without significant change. We thought that focal nodular hyperplasia, which is fluorocholine avid, was the most likely diagnosis, knowing that hepatocellular adenomas, including the inflammatory type, have not been reported to display increased fluorocholine uptake. We noticed that the patient's fatty liver uptake was low, which could have accounted for a falsely increased uptake by the nodule. But, similarly to other authors, we could not find any relationship between CT density and fluorocholine uptake.ConclusionThis case shows a discrepancy between the radiologic and nuclear medicine findings. However, this hepatic nodule is likely to be benign because of the lesion characteristics and the patient medical history.     

Comparison of the Prognostic Value of F-18 Pet Metabolic Parameters of Primary Tumors and Regional Lymph Nodes in Patients with Locally Advanced Cervical Cancer Who Are Treated with Concurrent Chemoradiotherapy

Objective

This study investigated the metabolic parameters of primary tumors and regional lymph nodes, as measured by pre-treatment F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) to compare the prognostic value for the prediction of tumor recurrence. This study also identified the most powerful parameter in patients with locally advanced cervical cancer treated with concurrent chemoradiotherapy.

Methods

Fifty-six patients who were diagnosed with cervical cancer with pelvic and/or paraaortic lymph node metastasis were enrolled in this study. Metabolic parameters including the maximum standardized uptake value (SUVmax), the metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumors and lymph nodes were measured by pre-treatment F-18 FDG PET/CT. Univariate and multivariate analyses for disease-free survival (DFS) were performed using the clinical and metabolic parameters.

Results

The metabolic parameters of the primary tumors were not associated with DFS. However, DFS was significantly longer in patients with low values of nodal metabolic parameters than in those with high values of nodal metabolic parameters. A univariate analysis revealed that nodal metabolic parameters (SUVmax, MTV and TLG), paraaortic lymph node metastasis, and post-treatment response correlated significantly with DFS. Among these parameters, nodal SUVmax (hazard ratio [HR], 4.158; 95% confidence interval [CI], 1.1–22.7; p = 0.041) and post-treatment response (HR, 7.162; 95% CI, 1.5–11.3; p = 0.007) were found to be determinants of DFS according to a multivariate analysis. Only nodal SUVmax was an independent pre-treatment prognostic factor for DFS, and the optimal cutoff for nodal SUVmax to predict progression was 4.7.

Conclusion

Nodal SUVmax according to pre-treatment F-18 FDG PET/CT may be a prognostic biomarker for the prediction of disease recurrence in patients with locally advanced cervical cancer.     

Clinicopathologic Features and Molecular Characteristics of Glucose Metabolism Contributing to 1?F-fluorodeoxyglucose Uptake in Gastrointestinal Stromal Tumors

Fluorine-18 fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography–computed tomography (PET/CT) is useful in the preoperative diagnosis of gastrointestinal stromal tumors (GISTs); however, the molecular characteristics of glucose metabolism of GIST are unknown. We evaluated ¹⁸F-FDG uptake on preoperative PET/CT of 40 patients and analyzed the expression of glycolytic enzymes in resected GIST tissues by qRT-PCR, western blotting, and immunohistochemistry. Results of receiver operating characteristic curve analysis showed that the maximum standardized uptake value (SUVmax) cut-off value of 4.99 had a sensitivity of 89.5%, specificity was 76.2%, and accuracy of 82.5% for identifying tumors with a high risk of malignancy. We found that ¹⁸F-FDG uptake correlated positively with tumor size, risk grade, and expression levels of glucose transporter 1 (GLUT1), hexokinase 1 (HK1), and lactate dehydrogenase A (LDHA). Elevated HK and LDH activity was found in high-risk tumors. Among the isoforms of GLUT and HK, GLUT1 and HK1 expression increased with higher tumor risk grade. In addition, overexpression of glycolytic enzymes M2 isoform of pyruvate kinase (PKM2) and LDHA was observed in GISTs, especially in high-risk tumors. These results suggest that upregulation of GLUT1, HK1, PKM2, and LDHA may play an important role in GIST tumorigenesis and may be useful in the preoperative prediction of malignant potential.     

Gastroenteropancreatic neuroendocrine tumors: standardizing therapy monitoring with 68Ga-DOTATOC PET/CT using the example of somatostatin receptor radionuclide therapy

The purpose of this study was to standardize therapy monitoring of hepatic metastases from gastroenteropancreatic neuroendocrine tumors (GEP-NETs) during the course of somatostatin receptor radionuclide therapy (SRRT). In 21 consecutive patients with nonresectable hepatic metastases of GEP-NETs, chromogranin A (CgA) and 68Ga-DOTATOC PET/CT were compared before and after the last SRRT. On 68Ga-DOTATOC PET/CT, the maximum standard uptake values (SUVmax) of normal liver and hepatic metastases were calculated. In addition, the volumes of hepatic metastases (volume of interest [VOI]) were measured using four cut-offs to separate normal liver tissue from metastases (SUVmax of the normal liver plus 10% [VOIliver+10%], 20% [VOIliver+20%], 30% [VOIliver+30%] and SUV = 10 [VOI10SUV]). The SUVmax of the normal liver was below 10 (7.2 ± 1.3) in all patients and without significant changes. Overall therapy changes (Δ) per patient (mean [95% CI]) were statistically significant with p < .01 for ΔCgA = -43 (-69 to -17), ΔSUVmax = -22 (-29 to-14), and ΔVOI10SUV = -53 (-68 to -38)% and significant with p < .05 for ΔVOIliver+10% = -29 (-55 to -3)%, ΔVOIliver+20% = -32 (-62 to -2) and ΔVOIliver+30% = -37 (-66 to -8). Correlations were found only between ΔCgA and ΔVOI10SUV (r = .595; p < .01), ΔSUVmax and ΔVOI10SUV (0.629, p < .01), and SUVmax and ΔSUVmax (r = -.446; p < .05). 68Ga-DOTATOC PET/CT allows volumetric therapy monitoring via an SUV-based cut-off separating hepatic metastases from normal liver tissue (10 SUV recommended).     

Dynamic FDG-PET Imaging to Differentiate Malignancies from Inflammation in Subcutaneous and In Situ Mouse Model for Non-Small Cell Lung Carcinoma (NSCLC)

Background

[¹⁸F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) has been widely used in oncologic procedures such as tumor diagnosis and staging. However, false-positive rates have been high, unacceptable and mainly caused by inflammatory lesions. Misinterpretations take place especially when non-subcutaneous inflammations appear at the tumor site, for instance in the lung. The aim of the current study is to evaluate the use of dynamic PET imaging procedure to differentiate in situ and subcutaneous non-small cell lung carcinoma (NSCLC) from inflammation, and estimate the kinetics of inflammations in various locations.

Methods

Dynamic FDG-PET was performed on 33 female mice inoculated with tumor and/or inflammation subcutaneously or inside the lung. Standardized Uptake Values (SUVs) from static imaging (SUVmax) as well as values of influx rate constant (Ki) of compartmental modeling from dynamic imaging were obtained. Static and kinetic data from different lesions (tumor and inflammations) or different locations (subcutaneous, in situ and spontaneous group) were compared.

Results

Values of SUVmax showed significant difference in subcutaneous tumor and inflammation (p<0.01), and in inflammations from different locations (p<0.005). However, SUVmax showed no statistical difference between in situ tumor and inflammation (p = 1.0) and among tumors from different locations (subcutaneous and in situ, p = 0.91). Values of Ki calculated from compartmental modeling showed significant difference between tumor and inflammation both subcutaneously (p<0.005) and orthotopically (p<0.01). Ki showed also location specific values for inflammations (subcutaneous, in situ and spontaneous, p<0.015). However, Ki of tumors from different locations (subcutaneous and in situ) showed no significant difference (p = 0.46).

Conclusion

In contrast to static PET based SUVmax, both subcutaneous and in situ inflammations and malignancies can be differentiated via dynamic FDG-PET based Ki. Moreover, Values of influx rate constant Ki from compartmental modeling can offer an assessment for inflammations at different locations of the body, which also implies further validation is necessary before the replacement of in situ inflammation with its subcutaneous counterpart in animal experiments.     

Analysis of PSA velocity in 1666 healthy subjects undergoing total PSA determination at two consecutive screening rounds

The study purpose was to assess PSA velocity (PSAV) in healthy subjects in order to establish a reliable cutoff for the differential diagnosis of prostate cancer in a screening setting. We studied a series of 1666 healthy men aged 55 to 74 years undergoing two total PSA determinations at a four-year interval within a population-based randomized screening trial at the Centro per lo Studio e la Prevenzione Oncologica of Florence. First and second screening round PSA assays (PSA1 and PSA2) were carried out with the same method and by the same laboratory. PSAV (PSA1-PSA2/year) was determined in non-cancer subjects in the overall series or in specific age and PSA subgroups, and in subjects with cancer detected at the second screening round. Average PSAV in 1648 non-cancer subjects was 0.07 ng/mL/year (range -2.18+5.99, 95% CI 0.05-0.09); at least one third of subjects showed a decrease in PSA (negative PSAV), mostly of limited magnitude and in the low PSA range. Average PSAV in the 18 cancer patients was 1.16 ng/mL/year (range 0.10-5.6, 95% CI 0.56-1.77), which is significantly higher (p<0.01) than in non-cancer subjects. None of the cancer patients showed a PSA decrease over time. Whatever cutoff was taken for PSAV, its power to discriminate cancer was limited: in particular the previously used PSAV cutoff of 0.75 ng/mL/year would have included only 42 of the 1648 non-cancer subjects (specificity 97.5%) but excluded eight of the 18 cancer patients (sensitivity 55.5%). At best, with the adopted screening protocol PSAV (cutoff 0.10 ng/mL/year) could have spared 27.9% of non-cancer subjects with PSA > or =2.5 ng/mL further diagnostic assessment and 22.7% of non-cancer subjects with PSA > or =4 ng/mL random sextant biopsy, while missing no cancers. This study provides a reliable estimate of PSAV based on a large unbiased population sample. PSAV is widely variable over time, particularly at low PSA values. PSAV might be of value as an indicator for diagnostic assessment and random sextant biopsy in a screening setting.     

Evaluation of 18F-PSMA-1007 PET/CT in prostate cancer patients with biochemical recurrence after radical prostatectomy

PurposeProstate-specific membrane antigen (PSMA) ligands targeting has shown promising results in staging of prostate cancer (PCa). The aim of present study was to evaluate the value of ¹⁸F-PSMA-1007 PET/CT in PCa patients with biochemical recurrence.Methods71 patients with PCa after radical prostatectomy (RP) were included in the present study. Median prostate-specific antigen (PSA) level was 1.27 ng/mL (range 0.01–67.40 ng/mL, n = 69). All patients underwent whole-body PET/CT imaging after injection of 333±38 MBq ¹⁸F-PSMA-1007. The distribution of PSMA-positive lesions was assessed. The influence of PSA level, androgen deprivation therapy and primary Gleason score on PSMA-positive finding and uptake of ¹⁸F-PSMA-1007 were evaluated.Results56 (79%) patients showed at least one pathological finding on ¹⁸F-PSMA-1007 PET/CT. The rates of positive scans were 50%, 80%, 100%, 100% among patients with PSA levels ≤0.5, 0.51–1.0, 1.1–2.0 and >2.0 ng/mL, respectively. The median Gleason score was 8 (range 7–10), and higher Gleason score (≤7 vs. ≥8) leads to higher detection rates (58.3% (14/24) vs. 88.9% (32/36), P = 0.006). The median SUVmax of positive findings in patients with PSA levels ≤0.5, 0.51–1.0, 1.1–2.0 and >2.0 ng/mL were 4.51, 4.27, 11.50 and 14.08, respectively. The median SUVmax in patients with PSA level >2.0 ng/mL was significantly higher than that in patients with PSA ≤2.0 ng/mL (14.08 vs. 6.13, P<0.001).Conclusion¹⁸F-PSMA-1007 PET/CT demonstrated a high detection rate for patients with a raised PSA level after radical prostatectomy even in patients with extremely low PSA level (eg. PSA level ≤0.5 ng/mL), which was essential for further clinical management for PCa patients.     

Integrated 18F-fluorodeoxyglucose-positron emission tomography/dynamic contrast-enhanced computed tomography to phenotype non-small cell lung carcinoma

AbstractWe applied modern molecular and functional imaging to the pretreatment assessment of lung cancer using combined dynamic contrast-enhanced computed tomography (DCE-CT) and 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) to phenotype tumors. Seventy-four lung cancer patients were prospectively recruited for 18F-FDG-PET/DCE-CT using PET/64-detector CT. After technical failures, there were 64 patients (35 males, 29 females; mean age [± SD] 67.5 ± 7.9 years). DCE-CT yielded tumor peak enhancement (PE) and standardized perfusion value (SPV). The uptake of 18F-FDG quantified on PET as the standardized uptake value (SUVmax) assessed tumor metabolism. The median values for SUVmax and SPV were used to define four vascular-metabolic phenotypes. There were associations (Spearman rank correlation [rs]) between tumor size and vascular-metabolic parameters: SUVmax versus size (rs = .40, p = .001) and SUV/PE versus size (r = .43, p < .001). Patients with earlier-stage (I-IIA, n = 30) disease had mean (± SD) SUV/PE 0.36 ± 0.28 versus 0.56 ± 0.32 in later-stage (stage IIB-IV, n = 34) disease (p = .007). The low metabolism with high vascularity phenotype was significantly more common among adenocarcinomas (p = .018), whereas the high metabolism with high vascularity phenotype was more common among squamous cell carcinomas (p = .024). Other non-small cell lung carcinoma tumor types demonstrated a high prevalence of the high metabolism with low vascularity phenotype (p = .028). We show that tumor subtypes have different vascular-metabolic associations, which can be helpful clinically in managing lung cancer patients to hone targeted therapy.     

Prognostic Value of SUVmax Measured by Pretreatment Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Patients with Ewing Sarcoma

AimThe aim of this retrospective study was to determine whether glucose metabolism assessed by using Fluorine-18 (F-18) fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) provides prognostic information independent of established prognostic factors in patients with Ewing sarcoma.MethodsWe retrospectively reviewed the medical records of 34 patients (men, 19; women, 15; mean age, 14.5 ± 9.7 years) with pathologically proven Ewing sarcoma. They had undergone F-18 FDG PET/CT as part of a pretreatment workup between September 2006 and April 2012. In this analysis, patients were classified by age, sex, initial location, size, and maximum standardized uptake value (SUVmax). The relationship between FDG uptake and survival was analyzed using the Kaplan-Meier method with the log-rank test and Cox’s proportional hazards regression model.ResultsThe median survival time for all 34 subjects was 999 days and the median SUV by using PET/CT was 5.8 (range, 2–18.1). Patients with a SUVmax ≤ 5.8 survived significantly longer than those with a SUVmax > 5.8 (median survival time, 1265 vs. 656 days; p = 0.002). Survival was also found to be significantly related to age (p = 0.024), size (p = 0.03), and initial tumor location (p = 0.036). Multivariate analysis revealed that a higher SUVmax (p = 0.003; confidence interval [CI], 3.63–508.26; hazard ratio [HR], 42.98), older age (p = 0.023; CI, 1.34–54.80; HR, 8.59), and higher stage (p = 0.03; CI, 1.21–43.95; HR, 7.3) were associated with worse overall survival.ConclusionsSUVmax measured by pretreatment F-18-FDG PET/CT can predict overall survival in patients with Ewing sarcoma.     

Algorithm for a DNA-cytophotometric diagnosis and grading of malignancy

An algorithm for processing data on nuclear DNA content obtained cytophotometrically was developed (1) to obtain an objective discrimination between benign and malignant lesions in conventional cytologic smears secondarily stained according to Feulgen and (2) to obtain an objective degree of tumor malignancy on a continuous scale of malignancy grades. Investigations in 258 malignant tumors (95 malignant lymphomas, 52 uterine cervix carcinomas, 28 prostate carcinomas, 18 breast carcinomas, 45 malignant bone tumors and 19 larynx carcinomas) and in 74 benign lesions in these organs yielded a diagnostic accuracy of no false-positive, no false-negative and 21% suspicious diagnoses. The probability that "suspicious" cases were malignant was 81%. The overall diagnostic accuracy for non-negative cases thus amounted to 100%. Results in 95 patients with different malignant lymphomas and in 16 patients with squamous-cell carcinoma of the larynx demonstrated the prognostic validity of the DNA-grading system.     

Diagnostic utility of CYFRA 21-1 and CEA assays in pericardial fluid for the recognition of neoplastic pericarditis

A positive cytology result in pericardial fluid is the gold standard for recognition of malignant pericardial effusion. Unfortunately, in 30-50% of patients with malignant pericardial effusion cytological examination of the pericardial fluid is negative. Tumor marker assessment in pericardial fluid may help to recognize malignant pericardial effusion. The aim of our study was to estimate the value of CYFRA 21-1 and CEA measurement in pericardial fluid for the recognition of malignant pericardial effusion. To our knowledge this is the first study on CYFRA 21-1 assessment in pericardial effusion. The examined group consisted of 50 patients with malignant pericardial effusion and 34 patients with non-malignant pericardial effusion. Median CEA concentrations in malignant pericardial effusion and non-malignant pericardial effusion were 80 ng/mL (0-317) and 0.5 ng/mL (0-18.4), respectively (p<0.001). Median CYFRA 21-1 concentrations in malignant pericardial effusion and non-malignant pericardial effusion were 260 ng/mL (5.3-10080) and 22.4 ng/mL (1.87-317.6), respectively (p<0.001). The optimal cutoff value for CYFRA 21-1 in pericardial effusion was 100 ng/mL. CYFRA 21-1 >100 ng/mL or CEA >5 ng/mL were found in 14/15 patients with malignant pericardial effusion and negative pericardial fluid cytology. We therefore strongly recommend the use of CYFRA 21-1 and/or CEA in addition to pericardial fluid cytology for the recognition of malignant pericardial effusion.     

Adding Maximum Standard Uptake Value of Primary Lesion and Lymph Nodes in 18F-Fluorodeoxyglucose PET Helps Predict Distant Metastasis in Patients with Nasopharyngeal Carcinoma

Objective

To find out the most valuable parameter of ¹⁸F-Fluorodeoxyglucose positron emission tomography for predicting distant metastasis in nasopharyngeal carcinoma.

Methods

From June 2007 through December 2010, 43 non-metastatic NPC patients who underwent ¹⁸F-Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) before radical Intensity-Modulated Radiation Therapy were enrolled and reviewed retrospectively. PET parameters including maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glucose (TLG) of both primary tumor and cervical lymph nodes were calculated. Total SUVmax were recorded as the sum of SUVmax of primary tumor and cervical lymph nodes. Total SUVmean, Total MTV and Total TLG were calculated in the same way as Total SUVmax.

Results

The median follow-up was 32 months (range, 23–68 months). Distant metastasis was the main pattern of treatment failure. Univariate analysis showed higher SUVmax, SUVmean, MTV, and TLG of primary tumor, Total SUVmax, Total MTV, Total TLG, and stage T3-4 were factors predicting for significantly poorer distant metastasis-free survival (p = 0.042, p = 0.008, p = 0.023, p = 0.023, p = 0.024, p = 0.033, p = 0.016, p = 0.015). In multivariate analysis, Total SUVmax was the independent predictive factor for distant metastasis (p = 0.046). Spearman Rank correlation analysis showed mediate to strong correlationship between Total SUVmax and SUVmax-T, and between Total SUVmax and SUVmax-N(Spearman coefficient:0.568 and 0.834;p = 0.000 and p = 0.000).

Conclusions

Preliminary results indicated that Total SUVmax was an independently predictive factor for distant metastasis in patients of nasopharyngeal carcinoma treated with Intensity-Modulated Radiation Therapy.