Increased lesion detectability in patients with locally advanced breast cancer-A pilot study using dynamic whole-body [18F]FDG PET/CT.

BACKGROUND: Accurate diagnosis of axillary lymph node (ALN) metastases is essential for prognosis and treatment planning in breast cancer. Evaluation of ALN is done by ultrasound, which is limited by inter-operator variability, and by sentinel lymph node biopsy and/or ALN dissection, none of which are without risks and/or long-term complications. It is known that conventional 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) has limited sensitivity for ALN metastases. However, a recently developed dynamic whole-body (D-WB) [18F]FDG PET/CT scanning protocol, allowing for imaging of tissue [18F]FDG metabolic rate (MRFDG), has been shown to have the potential to increase lesion detectability. The study purpose was to examine detectability of malignant lesions in D-WB [18F]FDG PET/CT compared to conventional [18F]FDG PET/CT. RESULTS: This study prospectively included ten women with locally advanced breast cancer who were referred for an [18F]FDG PET/CT as part of their diagnostic work-up. They all underwent D-WB [18F]FDG PET/CT, consisting of a 6 min single bed dynamic scan over the chest region started at the time of tracer injection, a 64 min dynamic WB PET scan consisting of 16 continuous bed motion passes, and finally a contrast-enhanced CT scan, with generation of MRFDG parametric images. Lesion visibility was assessed by tumor-to-background and contrast-to-noise ratios using volumes of interest isocontouring tumors with a set limit of 50% of SUVmax and background volumes placed in the vicinity of tumors. Lesion visibility was best in the MRFDG images, with target-to-background values 2.28 (95% CI: 2.04-2.54) times higher than target-to-background values in SUV images, and contrast-to-noise values 1.23 (95% CI: 1.12-1.35) times higher than contrast-to-noise values in SUV images. Furthermore, five imaging experts visually assessed the images and three additional suspicious lesions were found in the MRFDG images compared to SUV images; one suspicious ALN, one suspicious parasternal lymph node, and one suspicious lesion located in the pelvic bone. CONCLUSIONS: D-WB [18F]FDG PET/CT with MRFDG images show potential for improved lesion detectability compared to conventional SUV images in locally advanced breast cancer. Further validation in larger cohorts is needed. CLINICAL TRIAL REGISTRATION: The trial is registered in clinicaltrials.gov, NCT05110443, https://www. CLINICALTRIALS: gov/study/NCT05110443?term=NCT05110443&rank=1 .

[18F]FDOPA PET/CT is superior to [68Ga]DOTATOC PET/CT in diagnostic imaging of pheochromocytoma.

BACKGROUND: Both [18F]FDOPA (FDOPA) and [68Ga]DOTATOC PET/CT (DOTATOC) are widely used for detection of pheochromocytomas/paraganglioma (PPGL). However, direct comparisons of the performance of the two tracers are only available in small series. We conducted a retrospective comparative analysis of FDOPA and DOTATOC to assess their sensitivity and accuracy in detecting PPGL when administered based on suspicion of PPGL. We consecutively included patients referred on suspicion of PPGL or PPGL recurrence who were scanned with both FDOPA and DOTATOC. Both scans were reviewed retrospectively by two experienced observers, who were blinded to the final diagnosis. The assessment was made both visually and quantitatively. The final diagnosis was primarily based on pathology. RESULTS: In total, 113 patients were included (97 suspected of primary PPGL and 16 suspected of recurrence). Of the 97 patients, 51 had pheochromocytomas (PCC) (in total 55 lesions) and 6 had paragangliomas (PGL) (in total 7 lesions). FDOPA detected and correctly localized all 55 PCC, while DOTATOC only detected 25 (sensitivity 100% vs. 49%, p < 0.0001; specificity 95% vs. 98%, p = 1.00). The negative predictive value (100% vs. 63%, p < 0.001) and diagnostic accuracy (98% vs. 70%, p < 0.01) were higher for FDOPA compared to DOTATOC. FDOPA identified 6 of 6 patients with hormone producing PGL, of which one was negative on DOTATOC. Diagnostic performances of FDOPA and DOTATOC were similar in the 16 patients with previous PPGL suspected of recurrence. CONCLUSIONS: FDOPA is superior to DOTATOC for localization of PCC. In contrast to DOTATOC, FDOPA also identified all PGL but with a limited number of patient cases.

Early acquisition of [18F]FDOPA PET/CT imaging in patients with recurrent or residual medullary thyroid cancer is safe-and slightly better!

PURPOSE: The aim of this study was to compare early (15 min) and late (60 min) [18F]FDOPA PET/CT acquisition times in the detection of recurrence/residual disease in medullary thyroid cancer (MTC) patients. MATERIALS AND METHODS: Thirty-two dual-phase [18F]FDOPA PET scans were retrospectively reviewed. Scan indications were (1) suspected recurrence of MTC, (2) treatment monitoring, or (3) restaging. In four scans, no final verification could be obtained, and one scan was excluded due to non-consistency with the acquisition protocol. Images were analyzed visually and semiquantitatively (using SUVmax). On both per-scan and per-lesion basis, early (median time 15 min) and late (median time 60 min) acquisition were compared by number and SUVmax of detected MTC lesions, and a washout rate between the two acquisitions was calculated. Sensitivity and specificity of early and late acquisition were also compared. RESULTS: Out of the 27 eligible PET scans, twenty were classified as PET positive and 7 as PET negative. By subsequent histology and/or combination of imaging and clinical data during follow-up, the MTC diagnosis was verified, showing a scan-based sensitivity and specificity of 100% and 87.5%, respectively, for the early acquisition, and for the late acquisition both were 100%. However, there were no statistically significant difference in detection rate between the two acquisitions. Lesions on the early acquisition were significantly more intense compared to lesions on the late acquisition (median washout rate of - 33% (- 57 to + 50%)). CONCLUSION: Our study confirms that it is safe to omit the late [18F]FDOPA PET/CT acquisition in the detection of recurrent/residual MTC.

Assessment of Correlation between Dual-Energy Ct (De-Ct)-Derived Iodine Concentration and Local Flourodeoxyglucose (Fdg) Uptake in Patients with Primary Non-Small-Cell Lung Cancer.

(1) The current literature contains several studies investigating the correlation between dual-energy-derived iodine concentration (IC) and positron emission tomography (PET)-derived Flourodeoxyglucose (18F-FDG) uptake in patients with non-small-cell lung cancer (NSCLC). In previously published studies, either the entire tumor volume or a region of interest containing the maximum IC or 18F-FDG was assessed. However, the results have been inconsistent. The objective of this study was to correlate IC with FDG both within the entire volume and regional sub-volumes of primary tumors in patients with NSCLC. (2) In this retrospective study, a total of 22 patients with NSCLC who underwent both dual-energy CT (DE-CT) and 18F-FDG PET/CT were included. A region of interest (ROI) encircling the entire primary tumor was delineated, and a rigid registration of the DE-CT, iodine maps and FDG images was performed for the ROI. The correlation between tumor measurements and area-specific measurements of ICpeak and the peak standardized uptake value (SUVpeak) was found. Finally, a correlation between tumor volume and the distance between SUVpeak and ICpeak centroids was found. (3) For the entire tumor, moderate-to-strong correlations were found between SUVmax and ICmax (R = 0.62, p = 0.002), and metabolic tumor volume vs. total iodine content (R = 0.91, p < 0.001), respectively. For local tumor sub-volumes, a negative correlation was found between ICpeak and SUVpeak (R = −0.58, p = 0.0046). Furthermore, a strong correlation was found between the tumor volume and the distance in millimeters between SUVpeak and ICpeak centroids (R = 0.81, p < 0.0001). (4) In patients with NSCLC, high FDG uptakes and high DE-CT-derived iodine concentrations correlated on a whole-tumor level, but the peak areas were positioned at different locations within the tumor. 18F-FDG PET/CT and DE-CT provide complementary information and might represent different underlying patho-physiologies.

Clinical feasibility and impact of data-driven respiratory motion compensation studied in 200 whole-body 18F-FDG PET/CT scans.

BACKGROUND: This study examines the clinical feasibility and impact of implementing a fully automated whole-body PET protocol with data-driven respiratory gating in patients with a broad range of oncological and non-oncological pathologies 592 FDG PET/CT patients were prospectively included. 200 patients with lesions in the torso were selected for further analysis, and ungated (UG), belt gated (BG) and data-driven gating (DDG) images were reconstructed. All images were reconstructed using the same data and without prolonged acquisition time for gated images. Images were quantitatively analysed for lesion uptake and metabolic volume, complemented by a qualitative analysis of visual lesion detection. In addition, the impact of gating on treatment response evaluation was evaluated in 23 patients with malignant lymphoma. RESULTS: Placement of the belt needed for BG was associated with problems in 27% of the BG scans, whereas no issues were reported using DDG imaging. For lesion quantification, DDG and BG images had significantly greater SUV values and smaller volumes than UG. The physicians reported notable image blurring in 44% of the UG images that was problematic for clinical evaluation in 4.5% of cases. CONCLUSION: Respiratory motion compensation using DDG is readily integrated into clinical routine and produce images with more accurate and significantly greater SUV values and smaller metabolic volumes. In our broad cohort of patients, the physicians overwhelmingly preferred gated over ungated images, with a slight preference for DDG images. However, even in patients with malignant disease in the torso, no additional diagnostic information was obtained by the gated images that could not be derived from the ungated images.

A comparative study of standardized quantitative and visual assessment for predicting tumor volume and outcome in newly diagnosed diffuse large B-cell lymphoma staged with 18F-FDG PET/CT.

BACKGROUND: Semi-automated quantitative measurement of metabolic tumor volume (MTV) for prognosis in diffuse large B-Cell lymphoma (DLBCL) has gained considerable interest lately. However, simple tumor volume measures may be inadequate for assessment of prognosis in DLBCL as other characteristics such as growth pattern and metabolic heterogeneity may be just as important. In addition, MTV measurements require delineation of tumor lesions by semi-automated software, which can be time-consuming. We hypothesized that a simple visual assessment of tumor volume performs as well as standardized MTV measurements in DLBCL prognostication. MATERIALS AND METHODS: Quantitative and visual analyses of pre-therapy 18F-FDG PET/CT scans in 118 patients with newly diagnosed DLBCL were conducted. Quantitative analyses were performed using Hermes TumourFinder® to obtain MTV2.5 (SUV 2.5 cut-off) and MTV41 (41% SUVmax isocontour cut-off). Visual assessments included a binary prediction (good/poor prognosis) as well as tumor burden based on a visual analog scale (MTVVAS) and an estimated volume (eMTV). Three experienced nuclear medicine physicians who were blinded to clinical outcome performed visual evaluations. Progression-free survival was evaluated by Kaplan-Meier curves and log-rank test. Inter-observer variability was evaluated by Fleiss' kappa for multiple observers. RESULTS: In the quantitative analysis, a ROC-determined MTV2.5 cut-off (log-rank p = 0.11) seemed to outperform MTV41 (log-rank p = 0.76) for PFS prediction. TLG2.5 (log-rank p = 0.14) and TLG41 (log-rank p = 0.34) were not associated with outcomes. By visual analysis, all three reviewers were able to stratify patients into good/poor prognosis (reviewer A log-rank p = 0.002, reviewer B log-rank p = 0.016, and reviewer C log-rank p = 0.012) with fair inter-observer agreement (Fleiss' kappa 0.47). MTVVAS and eMTV were not consistently correlated with the outcome. CONCLUSION: Predictions of outcome after first-line treatment for DLBCL were surprisingly good when left to the unsupervised, subjective judgment of experienced readers of lymphoma 18F-FDG-PET/CT. The study highlights the importance of non-standardized clinical judgments and shows potential loss of valuable prognostic information when relying solely on semi-automated MTV measurements.

Simple dichotomous assessment of cranial artery inflammation by conventional 18F-FDG PET/CT shows high accuracy for the diagnosis of giant cell arteritis: a case-control study.

PURPOSE: To estimate the diagnostic accuracy of conventional 18F-FDG PET/CT of cranial arteries in the diagnosis of giant cell arteritis (GCA). METHODS: The study was a retrospective case-control study. The reference diagnosis was fulfillment of the 1990 ACR criteria for GCA. All patients had new-onset GCA. Conventional 18F-FDG PET/CT was performed before glucocorticoid treatment. Controls were age- and sex-matched patients with a previous history of malignant melanoma (MM) undergoing surveillance PET/CT >6 months after MM resection. PET images were evenly cropped to include only head and neck and were assessed in random order by four nuclear medicine physicians blinded to reference diagnosis. Temporal (TA), maxillary (MA) and vertebral (VA) arteries were visually rated for 18F-FDG uptake. Interreader agreement was evaluated by Fleiss kappa. RESULTS: A total of 44 patients and 44 controls were identified. In both groups, the mean age was 69 years (p = 0.45) and 25/44 were women. 35/41 GCA patients were temporal artery biopsy positive (TAB). Considering only FDG uptake in TA and/or MA, diagnostic sensitivity and specificity was 64 and 100%. Including VA, sensitivity increased to 82% and specificity remained 100%. Interreader agreement was 91% and Fleiss kappa 0.82 for the PET diagnosis based on the cranial arteries. CONCLUSION: Conventional 18F-FDG PET/CT is an accurate and reliable tool to diagnose cranial arteritis in glucocorticoid-naïve GCA patients. The high diagnostic specificity suggests that TAB can be omitted in patients with 18F-FDG uptake in cranial arteries. 18F-FDG PET/CT performed in patients with suspected vasculitis should always include the head and neck.

Assessment of very early response evaluation with 18F-FDG-PET/CT predicts survival in erlotinib treated NSCLC patients-A comparison of methods.

We evaluated whether changes in 18F-Fluoro-D-Glucose (18F-FDG)-uptake evaluated early during erlotinib treatment predict survival in non-small cell lung cancer (NSCLC) patients. Positron emission tomography (PET)/CT scans from 56 NSCLC patients before and after 7-10 days of erlotinib treatment were analyzed with four different methods: Visual evaluation and percentage change in lean body mass corrected standardized uptake values (SULs): SULpeak, SULmax and total lesion glycolysis (TLG). The semi-quantitative parameters abilities to predict progression free survival (PFS) and overall survival (OS) were compared and we found that percentage change in SULpeak, SULmax and TLG all correlated with PFS and OS with the strongest correlation found for TLG (R=0.51, P < 0.001). The highest area under the curve (AUC) for predicting OS was for TLG (0.70 (0.56-0.85)) with a sensitivity of 0.68 and a specificity of 079. All methods except visual evaluation, SULpeak at 15% and 30%, and TLG at 40% cut-off separates the survival curves for the response categories for PFS. For OS, visual evaluation and SULmax did not, whereas TLG at 4 different cut-off levels and SULpeak at the three lowest cut-off levels did. IN CONCLUSION: Early change in 18F-FDG-uptake during erlotinib correlated to both PFS and OS. TLG, as suggested by PERCIST 1.0, shows the strongest correlation to survival, whereas visual evaluation seems to be less sensitive at this very early time-point, but lower cut-off levels for discriminating between response categories seem to be relevant as we find that 20-25% change for both response and progression is optimal.

Correlation between circulating mutant DNA and metabolic tumour burden in advanced non-small cell lung cancer patients.

BACKGROUND: Mutated circulating cell-free DNA (cfDNA) has been suggested as a surrogate marker of tumour burden and aggressiveness of disease. We examined the association between the level of plasma mutant cfDNA and metabolic tumour burden (MTB) measured by 18F-fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT). Furthermore, the presence of mutant cfDNA was correlated with patient survival. METHODS: Forty-six advanced non-small cell lung cancer (NSCLC) patients were included. At the time of inclusion, blood sampling and a PET/CT scan were performed. cfDNA was isolated and next-generation sequencing (NGS) was performed (Ion AmpliSeq Colon and Lung Cancer panel v2). MTB was defined by a volumetric PET parameter. RESULTS: NGS succeeded in 41 patients. Mutations were detected in the blood of 24 patients. A significant correlation between the allele frequency of the most frequent mutation and MTB was found (P=0.001). Patients with detectable mutated cfDNA had a significantly shorter median overall survival compared with patients without (3.7 versus 10.6 months, P=0.019). This impact on survival was independent of the MTB. CONCLUSIONS: Level of mutated cfDNA tends to correlate with MTB in advanced-stage NSCLC patients. Patients with detectable mutant DNA in plasma had an inferior survival, indicating that this could be an important predictor of survival.

18F-FDG PET/CT for Very Early Response Evaluation Predicts CT Response in Erlotinib-Treated Non-Small Cell Lung Cancer Patients: A Comparison of Assessment Methods.

The purpose of this study was to determine which method for early response evaluation with 18F-FDG PET/CT performed most optimally for the prediction of response on a later CT scan in erlotinib-treated non-small cell lung cancer patients. Methods:18F-FDG PET/CT scans were obtained before and after 7-10 d of erlotinib treatment in 50 non-small cell lung cancer patients. The scans were evaluated using a qualitative approach and various semiquantitative methods including percentage change in SUVs, lean body mass-corrected (SUL) SULpeak, SULmax, and total lesion glycolysis (TLG). The PET parameters and their corresponding response categories were compared with the percentage change in the sum of the longest diameter in target lesions and the resulting response categories from a CT scan obtained after 9-11 wk of erlotinib treatment using receiver-operating-characteristic analysis, linear regression, and quadratic-weighted κ. Results: TLG delineation according to the PERCIST showed the strongest correlation to sum of the longest diameter (R = 0.564, P < 0.001), compared with SULmax (R = 0.298, P = 0.039) and SULpeak (R = 0.402, P = 0.005). For predicting progression on CT, receiver-operating-characteristic analysis showed area under the curves between 0.79 and 0.92, with the highest area under the curve of 0.92 (95% confidence interval [CI], 0.84-1.00) found for TLG (PERCIST). Furthermore, the use of a cutoff of 25% change in TLG (PERCIST) for both partial metabolic response and progressive metabolic disease, which is the best predictor of the CT response categories, showed a κ-value of 0.53 (95% CI, 0.31-0.75). This method identifies 41% of the later progressive diseases on CT, with no false-positives. Visual evaluation correctly categorized 50%, with a κ-value of 0.47 (95% CI, 0.24-0.70). Conclusion: TLG (PERCIST) was the optimal predictor of response on later CT scans, outperforming both SULpeak and SULmax The use of TLG (PERCIST) with a 25% cutoff after 1-2 wk of treatment allows us to safely identify 41% of the patients who will not benefit from erlotinib and stop the treatment at this time.

Inter-observer agreement improves with PERCIST 1.0 as opposed to qualitative evaluation in non-small cell lung cancer patients evaluated with F-18-FDG PET/CT early in the course of chemo-radiotherapy.

BACKGROUND: The purpose of this study is to determine whether a qualitative approach or a semi-quantitative approach provides the most robust method for early response evaluation with 2'-deoxy-2'-[(18)F]fluoro-D-glucose (F-18-FDG) positron emission tomography combined with whole body computed tomography (PET/CT) in non-small cell lung cancer (NSCLC). In this study eight Nuclear Medicine consultants analyzed F-18-FDG PET/CT scans from 35 patients with locally advanced NSCLC. Scans were performed at baseline and after 2 cycles of chemotherapy. Each observer used two different methods for evaluation: (1) PET response criteria in solid tumors (PERCIST) 1.0 and (2) a qualitative approach. Both methods allocate patients into one of four response categories (complete and partial metabolic response (CMR and PMR) and stable and progressive metabolic disease (SMD and PMD)). The inter-observer agreement was evaluated using Fleiss' kappa for multiple raters, Cohens kappa for comparison of the two methods, and intraclass correlation coefficients (ICC) for comparison of lean body mass corrected standardized uptake value (SUL) peak measurements. RESULTS: The agreement between observers when determining the percentage change in SULpeak was "almost perfect", with ICC = 0.959. There was a strong agreement among observers allocating patients to the different response categories with a Fleiss kappa of 0.76 (0.71-0.81). In 22 of the 35 patients, complete agreement was observed with PERCIST 1.0. The agreement was lower when using the qualitative method, moderate, having a Fleiss kappa of 0.60 (0.55-0.64). Complete agreement was achieved in only 10 of the 35 patients. The difference between the two methods was statistically significant (p < 0.005) (chi-squared). Comparing the two methods for each individual observer showed Cohen's kappa values ranging from 0.64 to 0.79, translating into a strong agreement between the two methods. CONCLUSIONS: PERCIST 1.0 provides a higher overall agreement between observers than the qualitative approach in categorizing early treatment response in NSCLC patients. The inter-observer agreement is in fact strong when using PERCIST 1.0 even when the level of instruction is purposely kept to a minimum in order to mimic the everyday situation. The variability is largely owing to the subjective elements of the method.

PET-CT for staging and early response: results from the Response-Adapted Therapy in Advanced Hodgkin Lymphoma study.

International guidelines recommend that positron emission tomography-computed tomography (PET-CT) should replace CT in Hodgkin lymphoma (HL). The aims of this study were to compare PET-CT with CT for staging and measure agreement between expert and local readers, using a 5-point scale (Deauville criteria), to adapt treatment in a clinical trial: Response-Adapted Therapy in Advanced Hodgkin Lymphoma (RATHL). Patients were staged using clinical assessment, CT, and bone marrow biopsy (RATHL stage). PET-CT was performed at baseline (PET0) and after 2 chemotherapy cycles (PET2) in a response-adapted design. PET-CT was reported centrally by experts at 5 national core laboratories. Local readers optionally scored PET2 scans. The RATHL and PET-CT stages were compared. Agreement among experts and between expert and local readers was measured. RATHL and PET0 stage were concordant in 938 (80%) patients. PET-CT upstaged 159 (14%) and downstaged 74 (6%) patients. Upstaging by extranodal disease in bone marrow (92), lung (11), or multiple sites (12) on PET-CT accounted for most discrepancies. Follow-up of discrepant findings confirmed the PET characterization of lesions in the vast majority. Five patients were upstaged by marrow biopsy and 7 by contrast-enhanced CT in the bowel and/or liver or spleen. PET2 agreement among experts (140 scans) with a κ (95% confidence interval) of 0.84 (0.76-0.91) was very good and between experts and local readers (300 scans) at 0.77 (0.68-0.86) was good. These results confirm PET-CT as the modern standard for staging HL and that response assessment using Deauville criteria is robust, enabling translation of RATHL results into clinical practice.

Using positron emission tomography (PET) response criteria in solid tumours (PERCIST) 1.0 for evaluation of 2'-deoxy-2'-[18F] fluoro-D-glucose-PET/CT scans to predict survival early during treatment of locally advanced non-small cell lung cancer (NSCLC).

INTRODUCTION: The demand for early-response evaluation with 2'-deoxy-2'-[18F] fluoro-D-glucose (F-18-FDG) positron emission tomography combined with whole body CT (PET/CT) is rapidly growing. This study was initiated to evaluate the applicability of the PET response criteria in solid tumours (PERCIST 1.0) for response evaluation. METHODS: We performed a retrospective study of 21 patients with locally advanced non-small cell lung cancer (NSCLC), who had undergone both a baseline and a follow-up F-18-FDG-PET/CT scan during their treatments. The scans were performed at our institution in the period September 2009 and March 2011 and were analysed visually and according to PERCIST 1.0 by one board-certified nuclear medicine physician. The response was compared with overall survival (OS) and progression-free survival (PFS). The variation in key parameters affecting the F-18-FDG uptake was assessed. RESULTS: A kappa of 0.94 corresponding to an almost perfect agreement was found for the comparison of the visual evaluation with PERCIST. Patients with partial metabolic response and stable metabolic disease (as evaluated by PERCIST 1.0) had statistically significant longer median time to progression: 8.4 months (confidence interval (CI) 5.1-11.8 months) as compared with 2.7 months (CI 0-5.6 months) in patients classified with progression. The variation in uptake time between baseline and follow-up scans was more than the recommended 15 min in 48% of patients. CONCLUSIONS: PERCIST 1.0 is readily implementable and highly comparable with visual evaluation of response using early F-18-FDG-PET/CT scanning for locally advanced NSCLC patients. In spite of variations in parameters affecting F-18-FDG uptake, evaluation of F-18-FDG-PET/CT during treatment with PERCIST 1.0 is shown to separate non-responders from responders, each with statistically significant differences in both OS and PFS.

Accuracy of 18F-FDG PET-CT in triaging lung cancer patients with suspected brain metastases for MRI.

OBJECTIVE: Brain metastases are common in lung cancer. Whole-body 2-deoxy-2-[fluorine-18]fluoro-D-glucose ([F]FDG) PET/computed tomography (CT) is used for general staging, but MRI is the best modality for characterizing brain abnormalities. We aimed to determine whether PET/CT is suitable for selecting patients for MRI on the suspicion of brain metastases. MATERIALS AND METHODS: F-FDG PET/CT (from the vertex to mid-thigh) was performed in 1108 consecutive patients suspected of lung cancer. The final diagnoses were extracted from medical records as lung cancer, with or without brain metastases, other kinds of cancers, or no cancer. The sensitivity, specificity, and positive predictive value for detecting brain metastases were calculated. Interobserver variation was tested in a subset of 88 PET/CT scans. RESULTS: Of the 1108 referred patients, 596 had lung cancer. Sixty-six had brain metastases. One PET/CT was false positive. Thirty-one scans were true positive among the 43 patients who were diagnosed with brain metastases 1 month before to 3 months after PET/CT (metastasis prevalence, 7.3%). Twelve PET/CT scans were false negative. Sensitivity, specificity, and positive predictive values were 72, 100, and 97%, respectively. Interobserver agreement between two experienced observers was high (κ=0.83), whereas agreement between the experienced and the inexperienced observer was poor. CONCLUSION: The sensitivity of brain PET/CT for detecting brain metastases in lung cancer was above 70%, and the specificity was very high. Thus, PET/CT may be suitable for selecting patients for MRI in diagnostic centers that do not perform routine MRI in the pretherapeutic staging workup. The agreement among experienced readers was very high.

(18)F-fluorodeoxyglucose-positron emission tomography/computed tomography after one cycle of chemotherapy in patients with diffuse large B-cell lymphoma: results of a Nordic/US intergroup study.

We evaluated the predictive value of interim positon emission tomography (I-PET) after one course of chemoimmunotherapy in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). One hundred and twelve patients with DLBCL were enrolled. All patients had PET/computed tomography (CT) scans performed after one course of chemotherapy (PET-1). I-PET scans were categorized according to International Harmonization Project criteria (IHP), Deauville 5-point scale (D 5PS) with scores 1-3 considered negative (D 5PS > 3) and D 5PS with scores 1-4 considered negative (D 5PS = 5). Ratios of tumor maximum standardized uptake value (SUVmax) to liver SUVmax were also analyzed. We found no difference in progression-free survival (PFS) between PET-negative and PET-positive patients according to IHP and D 5PS > 3. The 2-year PFS using D 5PS = 5 was 50.9% in the PET-positive group and 84.8% in the PET-negative group (p = 0.002). A tumor/liver SUVmax cut-off of 3.1 to distinguish D 5PS scores of 4 and 5 provided the best prognostic value. PET after one course of chemotherapy was not able to safely discriminate PET-positive and PET-negative patients in different prognostic groups.

Mediastinal staging in Non-Small-Cell Lung Carcinoma: computed tomography versus F-18-fluorodeoxyglucose positron-emission tomography and computed tomography.

BACKGROUND: After the diagnosis Non-Small-Cell Lung Carcinoma (NSCLC) has been established, consideration must turn toward the stage of disease, because this will impact directly on management and prognosis. Staging is used to predict survival and to guide the patient toward the most appropriate treatment regimen or clinical trial. Distinguishing malignant involvement of the mediastinal lymph nodes (N2 or N3) from the hilar lymph nodes, or no lymph nodes (N0 or N1) is critical, because malignant involvement of N2 or N3 lymph nodes usually indicates non-surgically resectable disease. The purpose of this study was to examine and compare CT versus integrated F18-FDG PET/low dose CT (FDG PET/CT) for mediastinal staging in NSCLC, and the desire was to safely distinguish between malignant and benign lesions without the need for invasive procedures. All results were controlled for reproducibility. METHODS: 114 participants with NSCLC were included in a prospective cohort study. Blinded CT and FDG PET/CT images were reviewed. The participants' mediastinums were staged based on lymph node sizes (CT), or on FDG uptake (FDG PET/CT). Reference standard was tissue sampling. RESULTS: We found that there was no measureable difference between CT and FDG PET/CT mediastinal staging results; overall two-thirds of the participants in the study were correctly staged, and almost one-third of the participants were falsely staged. CONCLUSION: Neither CT nor FDG PET/CT could obviate the need for further invasive staging prior to thoracotomy in patients with NSCLC; for that purpose, the results of both modalities were too meagre. Therefore, these patients still depend on invasive staging methods. In our study, invasive staging was accomplished by mediastinoscopy. However, today this is increasingly replaced by EBUS or EUS.

Routine bone marrow biopsy has little or no therapeutic consequence for positron emission tomography/computed tomography-staged treatment-naive patients with Hodgkin lymphoma.

PURPOSE: To investigate whether bone marrow biopsy (BMB) adds useful information to [(18)F]fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) staging in patients with Hodgkin lymphoma (HL). PATIENTS AND METHODS: Newly diagnosed patients with HL undergoing a pretherapeutic staging that encompasses both PET/CT and BMB were included in this retrospective study. The pattern of skeletal FDG uptake was categorized as uni-, bi-, or multifocal (≥ three lesions). Clinical stage, risk assessment, and treatment plan were determined with and without the contribution of BMB results according to the Ann Arbor classification and the guidelines from the German Hodgkin Study Group. RESULTS: A total of 454 patients with HL were included of whom 82 (18%) had focal skeletal PET/CT lesions and 27 (6%) had positive BMB. No patients with positive BMB were assessed as having stage I to II disease by PET/CT staging. BMB upstaged five patients, assessed as being stage III before BMB; none of the 454 patients would have been allocated to another treatment on the basis of BMB results. Focal skeletal PET/CT lesions identified positive and negative BMBs with a sensitivity and specificity of 85% and 86%, respectively. The positive and negative predictive values of focal skeletal PET/CT lesions for BMB results were 28% and 99%, respectively. CONCLUSION: A consistent finding of this study was the absence of positive BMBs in PET/CT-assessed stage I to II disease. The omission of staging BMB would not have changed the risk assessment or treatment strategy in this cohort of 454 newly diagnosed patients with HL.

Characterization of pulmonary lesions in patients with suspected lung cancer: computed tomography versus [¹8F] fluorodeoxyglucose-positron emission tomography/computed tomography.

Pulmonary nodules are of high clinical importance, given they may prove to be an early manifestation of lung cancer. Pulmonary nodules are small, focal, radiographic opacities that may be solitary or multiple. A solitary pulmonary nodule is a single, small (<-30 mm in diameter) opacity. Larger opacities are called masses and are often malignant. As imaging techniques improve and more nodules are detected, the optimal management of pulmonary nodules remains unclear. However, the question of malignancy of any given nodule remains the same. A standard contrast-enhanced computed tomography (CT) scan is often the first examination, followed by a number of other examinations. The purpose of this study was to examine the clinical feasibility of CT versus integrated [18F]fluorodeoxyglucose-positron emission tomography (PET)/low-dose CT scan in patients with suspected lung cancer and pulmonary lesions on CT. All results were controlled for reproducibility. We found that when used early in the work-up of the lesions, CT raised the prevalence of lung cancer in the population to the point where further diagnostic imaging examination could be considered futile. We also found that the overall diagnostic accuracy, as well as the classification probabilities and predictive values of the two modalities were not significantly different; the reproducibility of these results was substantial.