PET Interpretation Research Articles

Efficacy of conventional whole-body 18F-FDG PET/CT in the incidental findings of parotid masses

The objective of this study was to evaluate the incidence of incidental parotid masses with conventional whole-body ¹⁸F-deoxyglucose (FDG) PET/CT and assess the ability of PET/CT to characterize these unexpected parotid lesions. Fifty eight incidental findings of parotid masses with routine FDG PET/CT whole-body scan were reviewed in this retrospective analysis, which were selected from the patients without any known or suspected parotid disease in our PET center, from June 2005 to May 2009. 51 cases were operated or underwent a biopsy after a short-term PET/CT study; the remaining 7 cases had a follow-up. Parotid mass that showed both noncontrast CT (irregular shape and blurry border) and PET malignant features (high FDG uptake, SUV(max) > 3.0) was considered as positive for malignancy. Correlation of FDG PET/CT with histology or follow-up outcome was performed. Fifty eight unexpected findings of parotid masses accounted for 0.3% of the total cases in 4 years, including 11 (19.0%) malignant tumors and 47 (81.0%) benign lesions. 13 lesions manifested single nodule with malignant CT features and intense FDG activity, of which 6 were proved to be malignant; thus, sensitivity and positive predictive values were 54.5% (6 of 11) and 46.2% (6 of 13), respectively. 45 lesions showed either single nodule with benign CT features, or a low FDG uptake (SUV(max) ≤ 3.0), of which 40 were true negatives; therefore, specificity and negative predictive values were 85.1% (40 of 47) and 88.9% (40 of 45), respectively. All parotid masses except 9 benign and 1 malignant showed a high FDG uptake. Compared with SUV only, combined interpretation of PET and CT results displayed a lower sensitivity (90.9-54.5%), but a higher specificity (19.1-85.1%) and a higher overall accuracy. Whole-body FDG-PET/CT at the time of surveying the entire body condition is helpful for detecting the asymptomatic parotid masses. Combined noncontrast CT is an essential evidence for improving the diagnostic accuracy of FDG-PET/CT for parotid masses.

Interim 18-FDG-Positron Emission Tomography/Computed Tomography (PET) Failed to Predict Different Outcome in Diffuse Large B-Cell Lymphoma (DLBCL) Patients Treated with Rituximab-CHOP.

Abstract 99Introduction. The PET scan has a definite role to assess the response at the end of treatment of DLBCL. The evaluation of response by PET after few courses of chemotherapy might be useful to predict chemosensitivity and possibly the outcome in this subset of patients. So far, the predictive value of interim PET in DLBCL pts is still contradictory. The visual analysis of PET results by dichotomous evaluation as positive or negative is often difficult to apply and standardized criteria of interpretation of interim PET have not been established yet. Moreover, published data are often based on retrospective studies, including miscellanea of subtypes and therapies. Our study was aimed to determine the predictive value of interim and final PET on PSF in DLBCL patients. Patients and Methods. From April 2004 to December 2008, 82 newly diagnosed DLBCL patients treated in 5 Hematology Department were included. Clinical features were as follows: median age 56 years (range 19-81); 42 males and 40 females, 29 patients stage I-II and 53 stage III-IV; according to IPI score 47 at low/low-intermediate risk and 35 at intermediate/intermediate-high. All patients were treated according to planned therapy, not modified by PET-2 results, with 6-8 R-CHOP. All patients had PET scan performed at the diagnosis, during treatment (PET-2) and at the end of therapy (PET-3). All PET results were defined as positive or negative by visual dichotomous consensus response criteria. Results. All patients were evaluable for response. PET-2 was performed after 2 R-CHOP in 46 pts, after 3 in 13 and after 4 in 23. At the end of therapy 73 pts (89%) achieved a CR and 9 (11%) were non responders. Fifty-five patients (67%) were negative and 27 (33%) positive at the PET-2 and 69 pts (84%) were negative and 13 (16%) positive at the PET-3. The concordance between clinical CR and PET-3 negativity was 99%: one CR pt was false PET-3 positive due to parothid carcinoma . Correlation between PET results and outcome was evaluated. There was correlation between PET-2 results and CR rate: CR 96% in PET-2 negative pts vs 74% in PET-2 positive (p .004). With a median FU of 18 months, PFS was 78%. PET-2 did not correlate with PFS (p .198): 46/55 (84%) PET-2 negative patients were in CCR and 20/27 (74%) PET-2 positive patients did not progres (Figure 1A). Conversely PET-3 strongly predicted PFS (p .015): 58/69 (84%) were in CCR and 8/13 (61%) did not progressed. (Figure 1B). A further analysis for progression event was performed to adjust the effect of PET-2 analysis for other known risk factors (age up to/over 60, stage, Performance status, LDH, number of extranodal sites, IPI, bulky, Bone Marrow involvement): only LDH (p .005)and IPI 0-2 vs 3-5 (p .001 ) were confirmed as independent predictors of progression event. Conclusions. Our results indicate that in this omogeneous group of DLBCL patients treated with R-CHOP interim PET failed to predict outcome. However, a longer follow up is necessary to validate our data. Conversely PET results at the end of treatment strongly correlate with PFS. Prospective larger studies will be needed to establish the real role of interim PET to predict the outcome in this subset of patients. [Display omitted] Disclosures:Ladetto:CELGENE: Honoraria; JANSSEN-CILAG: Research Funding. Vitolo:Roche: lecture fees.

Comparative Assessment of Different Criteria for Interim-PET Interpretation in a Cohort of Hodgkin Lymphoma Patients Treated in a Single Center.

Abstract 3657Poster Board III-593 IntroductionInterim-PET scan performed early during treatment is the most important prognostic factor in Hodgkin lymphoma (HL). However, simple reproducible criteria for scan interpretation are lacking and still await standardization. Aim of the studyTo evaluate in a cohort of ABVD-treated HL patients in a single centre the overall accuracy of different criteria of interim PET interpretation in which interim scan was not decisional for treatment change. Patients and methodsFrom December 2003 till June 2008, 75 HL patients were consecutively admitted to hematology department of Santa Croce Hospital in Cuneo. Baseline and interim-PET (PET-2) scans were performed with a PET/CT equipment. Limited-stage patients (I-IIA) were treated with ABVD x 3-4 plus Involved-field radiotherapy; advanced-stage (IIB-IVB) patients with ABVD x 6 plus consolidation radiotherapy on bulky disease. The injected dose was 370 MBq/70 kg. 2D images were acquired a mean of 71 (47-122) minutes after Fluorodeoxyglucose (FDG) injection. Images were reconstructed with OSEM (3 iteration, 26 subsets). PET-2 was performed after a median of 11(8-13) days from 2nd ABVD end, and no treatment change was allowed based on PET-2 results. Two expert nuclear medicine physicians independently interpreted the PET-2 scans and jointly reviewed the discordant cases. Six interpretation criteria on the basis of literature reports were used: three qualitative, two quantitative, based on Standardized Uptake Value (SUV) assessment, and one with a qualitative/dimensional approach, with a dimensional cutoff value for FDG correction of 15 mm.: Juweid 2007 (Ju), Gallamini 2007 (Ga), Barrington 2008 (Ba) for qualitative, SUVmax determination, SUVmax variation (deltaSUV) for quantitative, and Barrington + dimensional (Ba/d) for a qualitative/dimensional approach. ResultsClinical characteristics of the patients were: mean age 33 (14 - 73), male sex 39/75, limited vs. advanced stage 37/38, International Prognostic Score (IPS), (in 69/75 patients) was 0 in 17,1 in 19, 2 in 19, 3 in 8, 4 in 5, 5-7 in 1 patients. After a mean follow-up of 937 days 67 patients are in CR, and 8 experienced treatment failure, three of them have died. In case of residual FDG uptake the mean diameter of the persisting lesion was 19.9 mm. Overall, 2/8 patients with treatment failure (True PET-2+) and all the 9 patients with false+ or false- PET-2 (whatever criteria) showed a persistent FDG uptake in a single lesion, with a median diameter of 14 millimetres. Sensitivity and specificity, were:100%,70%, for Ju; 63%, 87% for Ga; 63%, 91% for Ba; 75%, 93% for SUVmax; 50%, 94% for deltaSUV; 89%, 89% for Ba/d. Among the qualitative assays Ba and Ba/d showed the best results. The latter were equivalent to both quantitative assay. Using the Ba /d score 8 patients showed false-positive scans: 6/8 with stage IIA and 7/8 with bulky disease, and the 3-year failure-free survival for the entire cohort and for advanced-stage patients were 98%, 53% and 96% and 25% for PET-2 negative and positive patients, respectively. ConclusionsThis study suggest that (1) the criteria of the Harmonization Study for end-treatment evaluation of response should not be used for PET-2 interpretation (2) the lower performance of qualitative in respect to the quantitative criteria is offset by the adjunction of dimensional parameters; (3) due to the small size of the residual lesion with a persistent FDG avidity in PET-2, the contribute of the dimensional criteria could sensibly improve the performance of qualitative criteria, such as Ba, that are currently used for multicenter clinical trials. Disclosures:No relevant conflicts of interest to declare.

The 18F-FDG SUVmax Reduction After Two Cycles of R-CHOP Regimen Predicts Progression Free Survival of Patients with Diffuse Large B-Cell Lymphoma.

Abstract 2931Poster Board II-907 Introduction:PET assessment of early response allows to predict outcome of patients with DLBCL, but the more accurate criteria for early PET interpretation remain to be define. So we evaluated the prognostic value of PET after two cycles of immuno-chemotherapy and compared a semiquantitative approach using FDG uptake reduction, with two methods of visual analysis. Patients and methods:Forty five consecutive patients with newly diagnosed DLBCL treated in a single institution with rituximab and CHOP or CHOP-like regimen underwent 18F-FDG PET at baseline (PET0) and after 2 cycles of induction treatment (PET2). Images were interpreted visually according to two separate methods: - Juweid criteria (JCO 2007; 25: 571) (visual analysis-1) – A visual comparison of the FDG uptake between the residual mass and the normal hepatic tissue, a PET being considered as positive when the uptake of at least one residual mass was found greater than the liver (visual analysis-2). The quantitative approach was based on the lymphoma FDG uptake estimated by the maximal standardized uptake value (SUVmax) corrected to body weight. The SUV reduction between PET0 and PET2 (ΔSUVmax) was calculated for each patient. The ΔSUVmax cut-off was estimated to 65% by ROC analysis. Results:Patient median age was 50 years (range, 24 – 79) and 37 patients (73%) were younger than 61 years. The age-adjusted IPI score was, 2 or 3, 1 and 0 in 26 (49%), 16 (36%) and 7 (16%) patients respectively. With a median follow-up of 25 months, 6 (13%) out of 45 patients progressed or relapsed after treatment and 4 died from progressive disease. According to the visual analysis-1, PET2 was interpreted as negative in 16 (36%) patients and positive in the 29 remaining patients. Using the visual analysis-2, PET2 was negative in 25 cases (56%) and positive in 20 cases. The quantitative analysis showed a ΔSUVmax < 65% in 9 patients and a ΔSUVmax >= 65% in 36 patients (80%). The estimated efficiency of the three methods to predict patient outcome is detailed below:Visual analysis-1Visual analysis-2ΔSUVmaxpSensitivity83%83%67%NSSpecificity38%*62% ¤87%* ¤* 0.0001 ¤0.05Negative predictive value94%96%94%NSPositive predictive value17%25%44%NSAccuracy44%*64% ¤84% * ¤* 0.0002 ¤0.05The probability of 2-years progression-free survival (PFS) for patients with a negative PET2 according to the visual analysis was slightly higher than those with a positive PET2 when using as well the Juweid criteria (93% vs 83%; p = 0.3), as the visual analysis-2 (95% vs 75%: p = 0.04).However, the quantitative aproach allows to better identify and split up the population of patients with a good outcome from those with a poor outcome, since the 2-years PFS was 56% in patients with a ΔSUVmax reduction less than 65% compared to a 94% 2-years PFS probability in patients with a ΔSUVmax higher than 65% (p=0.0009). A multivariate analysis was performed including the IPI score and the ΔSUVmax reduction as explanatory variables for PFS, showing that the PET2 result assessed by the ΔSUVmax reduction remains the only independant prognosis factor for PFS (p = 0.008; RR = 10). Conclusion:SUV-based assessment of PET after two courses of immuno-chemotherapy is more reliable to patient outcome than visual analysis. The SUVmax reduction is an early prognostic factor for DLBCL patients that may help to reduce false positive interpretations, and provides a useful tool to guide risk-adapted treatment. Disclosures:No relevant conflicts of interest to declare.

FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0

The aim of this guideline is to provide a minimum standard for the acquisition and interpretation of PET and PET/CT scans with [18F]-fluorodeoxyglucose (FDG). This guideline will therefore address general information about [18F]-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) and is provided to help the physician and physicist to assist to carrying out, interpret, and document quantitative FDG PET/CT examinations, but will concentrate on the optimisation of diagnostic quality and quantitative information.

Prediction of the Need for Surgical Intervention in Obstructive Crohn's Disease by 18F-FDG PET/CT

We preoperatively determined the accuracy of (18)F-FDG PET/CT for differentiating fixed muscle hypertrophy and fibrotic stenoses from acute transmural inflammatory stenoses in patients with Crohn's disease (CD) scheduled to undergo surgical resection for obstructive symptoms. Seventeen patients with known CD prospectively underwent (18)F-FDG PET/CT before already-planned surgery for obstructive symptoms. Image interpretation was by consensus of 2 readers with knowledge of patient participation in the study but not of other clinical history. Lesions were qualitatively graded on a 5-point scale for the presence of increased (18)F-FDG uptake consistent with active inflammation. Maximum lean standardized uptake value (SUL(max)) was determined for lesions scored 1 or more. Imaging results were compared with the pathologic grading of inflammation and predominant histopathologic subtype for each patient's surgical specimen, whether mainly inflammation, fibrosis, or muscle hypertrophy. Thirteen of the 17 patients underwent surgery (median, 28 d after PET/CT; range, 2-148 d), and 12 of these 13 had histopathologic correlation. Despite the predominant histopathologic subtype (inflammation, 5; fibrosis, 4; and muscle hypertrophy, 3), acute and chronic inflammation, fibrosis (median, 50%; range, 40%-90%), and muscle hypertrophy (median, 20-fold thickening; range, 9- to 40-fold thickening) were found in all patients. SUL(max) was significantly higher in severe than in mild-to-moderate chronic inflammation (8.2 +/- 2.8 vs. 4.7 +/- 2.5, P = 0.04). No patient with predominantly fibrosis or muscle hypertrophy (n = 7) had an SUL(max) greater than 8. Visually, 10 of 12 patients on PET/CT were considered to have active inflammation of the bowel. Patients with CD who undergo surgery for obstructive symptoms have histopathologically mixed findings of inflammation, fibrosis, and muscle hypertrophy. Qualitative PET interpretations were quite sensitive, but additional semiquantitative analyses using SUL(max) helped identify patients with active inflammation. This information may be beneficial for referring gastroenterologists considering medical therapy versus surgery for patients with CD who present with obstructive symptoms.

Pseudomyxoma Peritonei: Role of 18F-FDG PET in preoperative evaluation of pathological grade and potential for complete cytoreduction

Introduction For pseudomyxoma peritonei (PMP), survival depends on pathological grade and completeness of cytoreductive surgery. The aim of the study was to assess the ability of preoperative 18F-FDG PET to determine these 2 prognosis indicators. Material and methods In this prospective single centre study, all patients presenting with PMP were included. They underwent a preoperative 18F-FDG PET with a double radiological evaluation and an explorative laparotomy with the objective of optimal cytoreduction followed by a hyperthermic intra-operative intraperitoneal chemotherapy (HIPEC). Patients with non resectable disease underwent debulking surgery without HIPEC. The Completeness of Cytoreduction was assessed by CC score. Results Thirty-four patients were included. PET scanning was positive for 19 patients with grade II (hybrid form) or III (Peritoneal Mucinous Carcinomatosis) and for 2 patients with grade I (disseminated peritoneal adenomucinosis), and negative for 3 patients with grade II - III and for 10 patients with grade I. PET scanning was positive for 6 patients with CC score 2 - 3 and for 16 patients with CC score 0, and negative for 2 patients with CC score 2 - 3 and for 10 patients with CC score 0. The 18F-FDG PET interpretation distinguished 2 patients groups (grade I and grade II - III) with a sensitivity of 90% and a specificity of 77%. Moreover, probability of complete cytoreduction when PET was negative was over 80%. Conclusion Preoperative 18F-FDG PET may predict pathological grade and completeness of cytoreduction which are the two main prognostic factors in patients with PMP.

Expert Opinions on Positron Emission Tomography and Computed Tomography Imaging in Lymphoma

Revised guidelines for the staging and response criteria of Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL) were recently published to include the expanding role of positron emission tomography/computed tomography (PET/CT) using (18)F-fluoro-2-deoxyglucose. Here, we discuss the new guidelines and the need for standardized PET acquisition and interpretation in HL and NHL. We also discuss how the role for CT is evolving in the process of making treatment decisions and provide insight on how best to standardize the use of PET/CT for making therapeutic choices.

Prognostic Value of Interim 18F-FDG PET in Patients with Diffuse Large B-Cell Lymphoma: SUV-Based Assessment at 4 Cycles of Chemotherapy

Interim (18)F-FDG PET (after 1-4 cycles of chemotherapy) may be useful for tailoring a risk-adapted therapeutic strategy in lymphoma. The purpose of this study was to investigate whether semiquantification of standardized uptake values (SUVs) may help to improve the prognostic value of (18)F-FDG PET, compared with visual analysis, after 4 cycles of chemotherapy. In a previous report, we showed that a 65.7% reduction in maximal SUV (SUVmax) between baseline (PET0) and 2 cycles of chemotherapy (PET2) better predicted event-free survival in 92 prospective patients with diffuse large B-cell lymphoma, by reducing false-positive interpretation of visual analysis. Eighty patients also underwent (18)F-FDG PET after induction had been completed, at 4 cycles of chemotherapy (PET4). Images were interpreted visually (as negative or positive) and by computing the optimal percentage of SUVmax reduction between PET0 and PET4. Survival curves were estimated using Kaplan-Meier analysis and compared using the log-rank test. Median follow-up was 41 mo. With visual analysis, the 2-y estimate for event-free survival was 82% in the PET4-negative group, compared with 25% in the PET4-positive group (P < 0.0001, accuracy of predicting event-free survival, 81.3%). An optimal cutoff of 72.9% SUVmax reduction from PET0 to PET4 yielded a 2-y estimate for event-free survival of 79% in patients with reduction of more than 72.9%, versus 32% in those with reduction of 72.9% or less (P < 0.0001; accuracy of predicting event-free survival, 77.5%). Although SUV semiquantification helps reduce false-positive interim (18)F-FDG PET interpretations at 2 cycles, its performance is equivalent to visual analysis at 4 cycles, when most of the therapeutic effect has occurred upstream. This approach may be useful for objectively tailoring consolidation strategies.

Validation of the International Harmonization Project (IHP) Guidelines in Early Stage Hodgkin Lymphoma (HL) Treated with Adriamycin, Vinblastine and Gemcitabine (AVG) (CALGB 50203): Early Results.

Clinical trials are underway using FDG PET imaging as a response surrogate for risk-adapted treatments to achieve favorable long term outcome while reducing therapy-related toxicities in patients with HL. The IHP provided “guidelines” to standardize FDG PET-based response evaluation. Before implementation in clinical practice, further validation of these guidelines is necessary. Our objective was to validate IHP criteria for response evaluation after 2 cycles of therapy with prospectively collected data in CALGB 50203, a trial of AVG for the initial treatment of stages I and II non-bulky HL. IHP-based PET interpretation was also compared with CT-based lesion size changes.Methods: Treatment consisted of doxorubicin 25 mg/m2, vinblastine 6 mg/m2 and gemcitabine 800mg/m2 every 2 weeks for 12 treatments (6 cycles). Responses were assessed according to the International Workshop criteria (JCO 1999: 17: 1244–53). FDG-PET imaging (PET/CT: 60 pts, PET alone: 15 pts) and a separate dedicated diagnostic CT scan of involved sites was performed at baseline and after two cycles of AVG (PET-2). No treatment change was allowed on the basis of the PET-2 results. Of 99 assessable patients, 75 had PET-alone (14) or PET/CT (61) after 2 cycles; median age:34 yrs (18–80), 32% were ≥45 yrs, stages: 78% IA-IIA, 22% IIB. The primary interpretation of PET-2 studies was based on IHP criteria (JCO 2007; 25:571). The % change in the sum of the products of the diameter (%SPD) of all measurable lesions were compared between baseline and at cycle-2 CT. PET-2 and cycle-2 CT data were correlated with progression free survival (PFS).Results: Fifty-six patients (75%) achieved a CR/CRu, 21% a partial response (PR), 4% had stable disease (SD). After a median follow up of 2.1 yrs (1.2–3.4 years), 19 of 75 patients relapsed/progressed, with an estimated 2-year PFS of 0.87 (95% CI [0.74,0.94]Only 10 of 56 patients (18%) with CR/CRu were PET positive at PET-2 compared to 13/19 (68%) of those with SD or PR (p<0.0001). Twelve of 23 (52%) PET-2 positive patients relapsed compared to 7 of 52 (13.5%) who were PET-2 negative. The 2-yr probability of PFS was 0.87, [95% CI (0.74,0.94)] among PET-2 negative patients vs. 0.47 [95% CI (0.26,0.66)] in those who were PET-2 positive, p=0.0001. In an exclusive analysis of PET/CT scans, the 2-yr probability of PFS was 0.90, [95% CI (0.75,0.96)] among PET-2 negative patients vs. 0.35 [95% CI (0.13,0.59)] in those who were PET-2 positive, p<0.0001. The best PFS cut-point for %SPD change at cycle-2 was 70%. After cycle-2, PET-negative patients had a higher %SPD change compared to PET-positive patients (74.5% vs. 64.5%, p=0.003). Adjusted for baseline SPD, patients with <70% change were at 5.3 times higher risk of relapse. The 2-yr probability of PFS was 0.89, [95% CI (0.73,0.95)] among patients with > 70% change vs. 0.55 [95% CI (0.36,0.71)] in those with < 70% change, p=0.003.Conclusion: IHP-based interpretation of FDG PET after 2 cycles of chemotherapy yields a high correlation with 2-year PFS, in particular for combined PET/CT, thus, it could be used as a response surrogate for risk-adapted treatments. The prediction of PFS using FDG-PET is superior to %SPD change after 2 cycles of therapy. Ongoing studies will prospectively define the role of interim FDG PET in tailoring treatment to optimize benefits and minimize risks.

Avid Flourine-18 FDG uptake in a tonsillolith: Additional benefits of incorporating CT appearances in the interpretation of PET/CT

This case describes an incidental finding of unilateral avid Flourine-18-fluorodeoxyglucose (FDG) uptake in the right lingual tonsil associated with a tonsillolith in a patient with head and neck cancer. The lesion was detected incidentally during PET–CT study in a post-operated 68-year-old gentleman with previous history of infiltrating basal cell carcinoma in the left posterior auricular region and left facial palsy. Follow up computed tomography (CT) scan revealed no evidence of middle ear disease. This case illustrates the additional benefits of incorporating CT appearances into the interpretation of PET–CT studies apart from using it only for anatomical localization. Had it not been for the CT correlation on PET–CT study, there would have been a greater likelihood of considering the tonsillar FDG uptake as malignant leading to further unwarranted invasive procedures.

Does Reducing CT Artifacts from Dental Implants Influence the PET Interpretation in PET/CT Studies of Oral Cancer and Head and Neck Cancer?

In patients with oral head and neck cancer, the presence of metallic dental implants produces streak artifacts in the CT images. These artifacts negate the utility of CT for the spatial localization of PET findings and may propagate through the CT-based attenuation correction into the PET images. In this study, we evaluated the efficacy of an algorithm that reduces metallic artifacts in CT images and the impact of this approach on the quantification of PET images. Fifty-one patients with and 9 without dental implants underwent a PET/CT study. CT images through the patient's dental implants were reconstructed using both standard CT reconstruction and an algorithm that reduces metallic artifacts. Attenuation correction factors were calculated from both sets of CT images and applied to the PET data. The CT images were evaluated for any reduction of the artifacts. The PET images were assessed for any quantitative change introduced by metallic artifact reduction. For each reconstruction, 2 regions of interest were defined in areas where the standard CT reconstruction overestimated the Hounsfield units (HU), 2 were defined in underestimated areas, and 1 was defined in a region unaffected by the artifacts. The 5 regions of interest were transferred to the other 3 reconstructions. Mean HU or mean Bq/cm(3) were obtained for all regions. In the CT reconstructions, metallic artifact reduction decreased the overestimated HUs by approximately 60% and increased the underestimated HUs by approximately 90%. There was no change in quantification in the PET images between the 2 algorithms (Spearman coefficient of rank correlation, 0.99). Although the distribution of attenuation (HU) changed considerably in the CT images, the distribution of activity did not change in the PET images. Our study demonstrated that the algorithm can enhance the structural and spatial content of CT images in the presence of metallic artifacts. The CT artifacts do not propagate through the CT-based attenuation correction into the PET images, confirming the robustness of CT-based attenuation correction in the presence of metallic artifacts. The study also demonstrated that considerable changes in CT images do not change the PET images.

Influence of Cell Proportions and Proliferation Rates on FDG Uptake in Squamous-Cell Esophageal Carcinoma: A PET Study

We investigated the influence of cell proportions and proliferation activities on tumor maximum standard uptake value (SUV(max)) in patients with squamous-cell esophageal cancer (SCEC). Sixteen (16) patients with untreated SCEC were examined with (18)F-flourodeoxyglucose positron emission tomography (FDG-PET). The tumor SUV(max) were calculated. Tumors were resected by transthoracic esophagectomy. Tissues were stained with hematoxylin and eosin for the measurement of cell proportions and MIB-1 for measurement of proliferation indices (PIs). Tumor SUV and histologic data were related by using multiple linear regression analysis. The mean proportion of tumor cells in the tumor site was 58.1% (+/-12.1%); the proportion of inflammatory cells was 34.2% (+/-14.2%); the PI of tumor cells was 70.5% (+/-11.8%); and the PI of inflammatory cells was 22.2% (+/-7.6%). The tumor PI was the only variable that was significantly associated with the FDG uptake in the tumor site (p = 0.04). The correlation was low (Pearson-coefficient Gamma = 0.51). The Pearson-correlation-coefficient between tumor SUV and the fraction of inflammatory cells was Gamma = 0.37 and between tumor SUV and PI of inflammatory cells Gamma = 0.13. In untreated SCEC-patients, the tumor maximum FDG uptake is weakly associated with the proliferation rate of tumor cells. In contrast, neither the proportion nor the PI of inflammatory cells in the tumor site significantly correlates with the maximum SUV and should not profoundly affect PET interpretations.

FDG-PET in Hodgkin lymphoma

The high negative predictive value of FDG-PET in therapy control of Hodgkin lymphoma is proven by the data acquired up to now. Thus, the analysis of the HD15 trial has shown that consolidation radiotherapy might be omitted in PET negative patients after effective chemotherapy. Further response adapted therapy guided by PET seems to be a promising approach in reducing the toxicity for patients undergoing chemotherapy. The criteria used for the PET interpretation have been standardized by the German study groups for Hodgkin lymphoma patients and will be reevaluated in the current studies.

F-18 FDG PET and PET/CT Evaluation of Response to Chemotherapy in Bone and Soft Tissue Sarcomas

F-18 FDG PET has been used to grade sarcomas and assess response to therapy in advanced disease. Certain chemotherapy agents are thought to induce an inflammatory response in the tumor bed that can make interpretation of post-therapy FDG PET scans difficult. A review of our experience with PET in assessing therapy response in osseous and soft tissue sarcomas (OSTS) is presented. This is a retrospective study (January 1999 to December 2004) of 14 patients with histologic diagnosis of OSTS, who had 2 consecutive PET examinations for evaluation of chemotherapy response. The group included 8 men and 6 women, with age range of 18 to 56 years (average, 36 +/- 14). Semiquantitative assessment of FDG uptake was performed by calculating maximum standard uptake value (SUVmax) before and after treatment. The response to therapy was assessed independently by tumor necrosis at post-therapy surgery and according to European Organization for Research and Treatment of Cancer (EORTC) criteria for PET. The follow-up PET examinations were performed at an interval of 28 to 166 days (average, 90 +/- 45). All patients ended the ifosfamide regimen at 7 to 36 (average, 16 +/- 9) days before the follow-up PET scans. Five of them received methotrexate, adriamycin, and/or cisplatin as well. Based on the EORTC criteria alone, 3 patients (21.4%) had progression of disease (increase in SUVmax of 29%-69%; mean, 48% +/- 20%), 5 patients (35.7%) had stable disease, and 6 patients (42.8%) had partial response (decrease in SUVmax of 27%-84%; mean, 62% +/- 23%). Across all patients, the tumor necrosis postchemotherapy ranged from 5% to 100% (mean, 64% +/- 34%). In 8 patients (57.1%) the tumor necrosis correlated with the SUVmax changes. However, for 3 patients, the SUVmax changes indicated partial response despite necrosis of fewer than 90% of the surgical specimens, whereas 3 patients with >90% tumor necrosis had SUVmax changes indicative of stable disease. The pathologically determined degree of necrosis postneoadjuvant chemotherapy was concordant with PET-assessed EORTC classification of response in 57.1% of the cases. However, a significant number of patients had discrepancies, which may be in part explained by chemotherapy-induced inflammation. The latter should be considered during post-therapy PET interpretation in OSTS.

PET Versus PET-CT in Patient With Suspicion of Non-Hodgkin Lymphoma Recurrence

We present the case of a 62-year-old patient with a history of non-Hodgkin lymphoma (stage III) in complete remission after 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone with rituximab (CHOP-R) in 2006. The patient was referred for a PET-CT scan because of suspicion of recurrence. On PET there were multiple lung lesions, a submandibular lesion (right side) and an impressive retroperitoneal mass with a hypermetabolic wall, and central necrosis invading all retroperitoneal structures (aorta). There was also an additional lesion in the anterior abdominal wall below the liver. It was concluded that it was recurrent non-Hodgkin lymphoma (stage IV). Contrast enhanced CT demonstrated a large, rupturing abdominal aortic aneurysm (AAA) with saccular ectasia of the posterior wall compatible with a mycotic aneurysm. The other sites of hypermetabolism corresponded to metastatic infectious lesions. Histopathology confirmed the mycotic infection. The patient underwent urgent surgery including bilateral axillofemoral stenting and removing a clot from the AAA twice. Intravenous antibiotics were started. This case clearly denotes the importance of contrast enhanced hybrid PET-CT systems in which the CT information is relevant for PET interpretation and not only for anatomic repair. With PET alone, the diagnosis would have been completely different.

FDG PET in lymphoma: The need for standardization of interpretation. An observer variation study

To measure and describe patterns of interobserver variation in visual interpretation of 18-FDG PET in malignant lymphoma. Eleven nuclear medicine physicians with different levels of PET experience independently reviewed 37 18F-FDG PET scans of lymphoma patients (10 obtained at presentation, 27 during or after therapy). They were requested to identify and localize suspicious lymphoma sites and to assign a stage to the baseline scans, and to interpret the remaining scans for the presence of viable lymphoma. Individual (extra-)nodal regions were assessed for the likelihood of malignancy as positive, negative or equivocal. These results were compared to expert readings after dichotomization in conservative and sensitive reading classifications. Sixty-one percent and 56% (using sensitive and conservative reading, respectively) of the baseline scans were scored in accordance with the experts. Fourteen of the 27 scans obtained for therapy evaluation with viable tumour sites were scored in accordance with the experts in 82% and 94% of the patients, using conservative and sensitive reading, respectively. The 13 negative scans were scored in agreement with the experts in only 45% of the cases. False positivity pertained especially to the neck, periclavicular, axilla, mediastinum, lung and bone marrow. More experienced observers tended to have fewer false negative scores. There are substantial disparities among nuclear medicine physicians' interpretations of FDG PET scans of lymphoma patients, which may affect patient care and results of multi-institutional clinical trials. A well-defined set of criteria is urgently needed to improve consistency.

Comparison of 68Ga-DOTATOC PET and 111In-DTPAOC (Octreoscan) SPECT in patients with neuroendocrine tumours

Neuroendocrine tumours (NETs) can be imaged with scintigraphy using radiolabelled somatostatin analogues. The aim of our study was to compare the value of (68)Ga-DOTATOC PET and (111)In-DTPAOC SPECT (Octreoscan) in the detection of NET manifestations. Twenty-seven NET patients were prospectively examined. (68)Ga-DOTATOC PET and (111)In-DTPAOC SPECT were performed using standard techniques. Treatment was not applied in between. Mean and maximum standardised uptake values (SUVs) were calculated for PET findings. Tumour/non-tumour ratios were calculated for SPECT findings. Findings were compared by a region-by-region analysis and verified with histopathology, CT and MRI within 21 days. SUVs of positive lesions on (68)Ga-DOTATOC PET ranged from 0.7 to 29.3 (mean SUV) and from 0.9 to 34.4 (maximum SUV). Tumour/non-tumour ratios on (111)In-DTPAOC SPECT ranged from 1.8 to 7.3. In imaging lung and skeletal manifestations, (68)Ga-DOTATOC PET was more efficient than (111)In-DTPAOC SPECT. All discrepant lung findings and 77.8% of discrepant osseous findings were verified as true positive PET interpretations. In regional comparison of liver and brain, (68)Ga-DOTATOC PET and (111)In-DTPAOC SPECT were identical. In lymph nodes, the pancreas and the gastro-intestinal system, different values of the two techniques were not indicated in regional analyses. In a single patient, surgical interventions were changed on the basis of (68)Ga-DOTATOC PET findings. (68)Ga-DOTATOC PET is superior to (111)In-DTPAOC SPECT in the detection of NET manifestations in the lung and skeleton and similar for the detection of NET manifestations in the liver and brain. (68)Ga-DOTATOC PET is advantageous in guiding the clinical management.

Characterization of the Solitary Pulmonary Nodule: 18F-FDG PET Versus Nodule-Enhancement CT

The purpose of this study was to directly compare nodule-enhancement CT and 18F-FDG PET in the characterization of indeterminate solitary pulmonary nodules (SPNs) greater than 7 mm in size. Examinations from patients undergoing both nodule-enhancement CT and 18F-FDG PET to characterize the same indeterminate SPN were reviewed. For nodule-enhancement CT, an SPN was considered malignant when it showed an unenhanced to peak contrast-enhanced increase in attenuation greater than 15 H. Fluorine-18-FDG PET studies were blindly reinterpreted by two qualified nuclear radiologists. SPNs qualitatively showing hypermetabolic activity greater than the mediastinal blood pool were interpreted as malignant. These interpretations were compared with the original prospective clinical readings and to semiquantitative standardized uptake value (SUV) analysis. Results were compared with pathologic and clinical follow-up. Forty-two pulmonary nodules were examined. Twenty-five (60%) were malignant, and 17 (40%) were benign. Nodule-enhancement CT was positive in all 25 malignant nodules and in 12 benign nodules, with sensitivity and specificity of 100% and 29%, respectively, and with a positive predictive value (PPV) and negative predictive value (NPV) of 68% and 100%, respectively. Qualitative 18F-FDG PET interpretations were positive in 24 of the 25 malignant nodules and in four benign nodules. Fluorine-18-FDG PET was considered negative in one malignant nodule and in 13 of the 17 benign nodules. This correlates with a sensitivity and specificity of 96% and 76%, respectively, and with a PPV and NPV of 86% and 93%, respectively. Original prospective 18F-FDG PET and semiquantitative SUV analysis showed sensitivity, specificity, PPV, and NPV of 88%, 76%, 85%, and 81% and 84%, 82%, 88%, and 78%, respectively. Due to its much higher specificity and only slightly reduced sensitivity, 18F-FDG PET is preferable to nodule-enhancement CT in evaluating indeterminate pulmonary nodules. However, nodule-enhancement CT remains useful due to its high NPV, convenience, and lower cost. Qualitative 18F-FDG PET interpretation provided the best balance of sensitivity and specificity when compared with original prospective interpretation or SUV analysis.

Abstracts from the Seventh Congress of the European Association for Neuro-Oncology

BACKGROUND: Conventional interpretation of methionine PET (Met-PET) scans in suspected brain tumors uses the ratio of the tracer uptake within the lesion to the corresponding contralateral area. The precise location at which the region of interest used to calculate the reference value is placed is vital, because local variations in methionine uptake may significantly alter the calculated ratio. Identifying a precise mirror region is complicated by the distorting effect of the tumor and the need for manual realignment of the image. METHOD: Patients with low-grade primary brain tumors or benignlesions were identified on the basis of a tissue diagnosis or surveillance neuroimaging that excluded a high-grade tumor. These conditions were selected because they primarily involve a single hemisphere, with methionine uptake in the unaffected hemisphere being essentially normal. A total of 180 Met-PET scans performed during 2003 – 2005 were identified from the database at the Max Planck Institute for Neurological Research, coded, and anonymized for analysis. Scans demonstrating midline lesions, significant mass effect, or evidence of substantial previous surgery were then excluded. A methionine template was prepared using data from patients who had undergone both FDG and Met-PET scans within eight weeks, with normalization to a previously developed FDG template. Methionine scans were coregistered to the template, after masking of any tumor, and the diseased hemispheres stripped. Mean uptake maps for each hemisphere were calculated on a voxel-by-voxel basis and merged to create the normal methionine uptake map. Scans unsuitable for inclusion into the normal map were reanalyzed using the contralateral hemisphere and the normal uptake map for reference values, allowing the methods to be compared. RESULTS: Good correlation was found between uptake ratios using reference values calculated by both methods. Reference values could be reliably calculated in tumors that were previously problematic to analyze, such as those that cross the midline. Coregistration of the normal map was impaired in some cases by loss of the normal architecture, but valid reference values were obtained despite this. CONCLUSION: Use of a normal uptake may facilitate calculation of PET uptake ratios in brain tumors. Further research is required to evaluate the correlation with histological findings and the accuracy of image coregistration in the presence of distorting tumors.