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).

Detection of relevant colonic neoplasms with PET/CT: promising accuracy with minimal CT dose and a standardised PET cut-off.

OBJECTIVE: To determine the performance of FDG-PET/CT in the detection of relevant colorectal neoplasms (adenomas > or =10 mm, with high-grade dysplasia, cancer) in relation to CT dose and contrast administration and to find a PET cut-off. METHODS: 84 patients, who underwent PET/CT and colonoscopy (n = 79)/sigmoidoscopy (n = 5) for (79 x 6 + 5 x 2) = 484 colonic segments, were included in a retrospective study. The accuracy of low-dose PET/CT in detecting mass-positive segments was evaluated by ROC analysis by two blinded independent reviewers relative to contrast-enhanced PET/CT. On a per-lesion basis characteristic PET values were tested as cut-offs. RESULTS: Low-dose PET/CT and contrast-enhanced PET/CT provide similar accuracies (area under the curve for the average ROC ratings 0.925 vs. 0.929, respectively). PET demonstrated all carcinomas (n = 23) and 83% (30/36) of relevant adenomas. In all carcinomas and adenomas with high-grade dysplasia (n = 10) the SUV(max) was > or =5. This cut-off resulted in a better per-segment sensitivity and negative predictive value (NPV) than the average PET/CT reviews (sensitivity: 89% vs. 82%; NPV: 99% vs. 98%). All other tested cut-offs were inferior to the SUV(max). CONCLUSION: FDG-PET/CT provides promising accuracy for colorectal mass detection. Low dose and lack of iodine contrast in the CT component do not impact the accuracy. The PET cut-off SUV(max) > or = 5 improves the accuracy.

Prostate carcinoma: diffusion-weighted imaging as potential alternative to conventional MR and 11C-choline PET/CT for detection of bone metastases.

In a technical development study approved by the institutional ethics committee, the feasibility of fast diffusion-weighted imaging as a replacement for conventional magnetic resonance (MR) imaging sequences (short inversion time inversion recovery [STIR] and T1-weighted spin echo [SE]) and positron emission tomography (PET)/computed tomography (CT) in the detection of skeletal metastases from prostate cancer was evaluated. MR imaging and carbon 11 ((11)C) choline PET/CT data from 11 consecutive prostate cancer patients with bone metastases were analyzed. Diffusion-weighted imaging appears to be equal, if not superior, to STIR and T1-weighted SE sequences and equally as effective as (11)C-choline PET/CT in detection of bone metastases in these patients. Diffusion-weighted imaging should be considered for further evaluation and comparisons with PET/CT for comprehensive whole-body staging and restaging in prostate and other cancers.

Focal colorectal uptake in (18)FDG-PET/CT: maximum standard uptake value as a trigger in a semi-automated screening setting.

BACKGROUND: Focal colorectal uptake in (18)FDG-PET/CT may be associated with a malignancy and can be quantified. This provides the basis for an automatic trigger threshold above which cases are flagged for colonoscopic evaluation and below which for individual assessment. PURPOSE: To determine the lowest maximum standard uptake (SUVmax) in colorectal cancer that could be used as a threshold to trigger endoscopic evaluation and to evaluate whether the SUVmax needs to be further normalised to a priori known extrinsic factors. METHODS: The SUVmax was measured in 54 colorectal carcinomas and correlated with gender, age, blood glucose level, injected activity, body mass index and time to scan using t test or correlation coefficients (Pearson or Spearman, according to distribution). RESULTS: There was no correlation between SUVmax and any of the extrinsic factors mentioned above. The lowest SUVmax value was 5 [mean ± SD (range): 11.1 ± 4.8 (5.0-24.6)]. CONCLUSION: In contrast to most other screening techniques, semi-automation in colorectal screening seems possible with PET/CT. This opens the door for further study into the feasibility of automated screening. Independent from extrinsic factors, an SUVmax ≥5.0 in a focal colorectal uptake in (18)FDG-PET/CT should automatically trigger for endoscopic evaluation, if not contraindicated. Cases with SUVmax <5 should be assessed individually before referral for endoscopy. Thus, more interpretation time could be spent on those cases with a lower uptake and more ambiguous diagnosis.

Visualization of somatostatin receptors in prostate cancer and its bone metastases with Ga-68-DOTATOC PET/CT.

PURPOSE: To assess DOTATOC-affine somatostatin receptor expression in advanced prostate cancer and its bone metastases with regard to DOTATOC-mediated receptor therapies, using a Ga-68-DOTATOC PET/CT. PROCEDURES: Twenty consecutive patients with advanced prostate cancer underwent bone scintigraphy, followed by Ga-68-DOTATOC PET/CT within 3 weeks. Through side-by-side comparison with bone scintigraphy, the number of visible bone metastases on PET was determined. In addition, in cases of visible metastases, the maximum standard uptake value (SUV(max)) of Ga-68-DOTATOC was measured in the metastases and in normal bone. In patients who did not undergo a prostatectomy (n = 12), the SUV(max) was additionally measured in the prostate and in adjacent tissue. For focal lesions, the difference in SUV(max) (Delta SUV(max)) between the metastases and normal bone was calculated. For patients still having their prostate, a Delta SUV(max) between the prostate and its adjacent tissue was calculated. RESULTS: Sixty four of 216 metastases (30%) were visible in 13 patients with focal metastases. Of six patients with diffuse metastases (superscan), one showed diffuse metastases, three showed a total of ten focal metastases, and two showed no correlate on PET. One patient with a neuroendocrine prostate cancer showed no correlate on PET. The maximum Delta SUV(max) between metastases and normal bone was 4.9 (mean = 1.6 +/- 0.9) and between the prostate and adjacent tissue 5.9 (mean = 2.8 +/- 1.6). CONCLUSIONS: In prostate cancer and its bone metastases, DOTATOC-affine somatostatin receptors (subtype 2 and 5) can be visualized with Ga-68-DOTATOC PET/CT. But their expression is so weak that other conjugates should be tested for receptor-mediated therapies which are better at addressing the prostate cancer-specific somatostatin receptor subtypes 1 and 4-or even other receptors.

Discordance analysis characteristics as a new method to compare the diagnostic accuracy of tests: example of complexed versus total prostate-specific antigen.

BACKGROUND: ROC curve analysis is used to compare the overall diagnostic accuracy of tests, but its application to subgroups selected by a concentration range of only one marker may show severe biases. We developed a new approach, which we have named discordance analysis characteristics (DAC). METHODS: The DAC method is based on a generalization of the McNemar test so that for a given pair of cutoff values only those patients are analyzed who are categorized differently by the two tests compared. The analyses are performed for all cutoff pairs that deliver identical sensitivities for both tests. We used data for total (tPSA) and complexed prostate-specific antigen (cPSA) from a recently published multicenter study to demonstrate the DAC method. RESULTS: The example shows that ROC analyses of subgroups can give contradictory results about the diagnostic accuracy of two markers, depending on the marker used for the selection of subgroups. The DAC method avoids artifacts attributable to questionable selection of subgroups and facilitates overall and local comparisons of the diagnostic accuracy of tests. The DAC results of the analyzed data set suggest that cPSA has higher diagnostic accuracy than does tPSA. CONCLUSIONS: The DAC method is a suitable tool for comparing the clinical usefulness of laboratory markers. The DAC method could be considered as an additional tool to ROC analysis and could replace comparative ROC analyses of diagnostic tests, especially within subgroups defined by only one of the markers.

Bicycle riding has no important impact on total and free prostate-specific antigen serum levels in older men.

OBJECTIVES: To investigate whether bicycle riding significantly alters total prostate-specific antigen (tPSA), free PSA (fPSA), and percent free PSA (%fPSA) serum concentrations in potential candidates for prostate cancer screening. METHODS: Thirty-three men, ranging in age from 50 to 74 years (mean 61 +/- 8), rode a 13-mile bicycle course. Blood samples for PSA analysis were drawn immediately before and 1 hour after cycling for 90 minutes. The precycling and postcycling tPSA, fPSA, and %fPSA values were compared using the Wilcoxon matched-pairs test, with P = 0.01 set as the significance level. RESULTS: Changes between precycling and postcycling values for tPSA (P = 0.517), fPSA (P = 0.048), and %fPSA (P = 0.166) were not statistically significant. CONCLUSIONS: Physical activity combined with perineal pressure as induced by a 13-mile bicycle tour has no diagnostic impact on PSA values.

A multicenter clinical trial on the use of complexed prostate specific antigen in low prostate specific antigen concentrations.

PURPOSE: The determination of complexed prostate specific antigen (cPSA) has been suggested to be promising for prostate cancer (PCa) diagnosis. In a multicenter trial we evaluate the diagnostic use of PSA forms in the low total PSA (tPSA) range. MATERIALS AND METHODS: A total of 283 white men with and 417 without PCa and tPSA concentrations between 0 and 6 ng/ml were retrospectively analyzed. All 700 untreated subjects underwent a multisector needle biopsy of the prostate. The Elecsys analyser 1010 (Roche Diagnostics, Mannheim, Germany) was used for determination of tPSA and free PSA. Determination of cPSA and tPSA was performed using immunoassays of the Bayer Immuno 1 system (Bayer Diagnostics, Tarrytown, New York). RESULTS: Receiver operating characteristics analyses for discrimination between cases with and without PCa were performed. The areas under the curves (AUC) for cPSA, tPSA and free-to-total PSA (f/tPSA) showed no significant differences in the tPSA ranges of 0 to 6 (700 cases), 0 to 4 (510) and 0.5 to 2.5 ng/ml (253). Within the tPSA range of 2.5 to 4 ng/ml (230 cases) the AUC for cPSA (0.61) was significantly larger than that for tPSA (Roche 0.51, Bayer 0.54) but did not differ from the AUC of f/tPSA (Roche). On the basis of the cutoffs for 95% specificity or sensitivity, no significant increase in corresponding sensitivity or specificity was found between tPSA with cPSA. CONCLUSIONS: In the tPSA range of less than 4 ng/ml no improvement in diagnostic accuracy was shown between cPSA with tPSA or the ratio of f/tPSA. The search for a useful marker in the low PSA range must continue.