Accuracy of positron emission tomography in identifying hilar (N1) lymph node involvement in non-small cell lung cancer: Implications for stereotactic body radiation therapy.

PURPOSE: To assess the efficacy of preoperative positron emission tomography (PET) to stage the ipsilateral hilum in resected non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: All patients who underwent surgery for NSCLC between 1995 and 2008 were evaluated. Patients who underwent preoperative PET imaging at our institution and had hilar nodal sampling were included. Those whose primary tumors extended to the hilum or who received preoperative chemotherapy or radiation therapy were excluded. All PET studies were interpreted by an attending nuclear medicine radiologist and were scored as positive or negative in the hilum or peribronchial area based on visual analysis alone. A 2-sided Fisher exact test compared patient subgroups. RESULTS: During the time interval, 1558 patients underwent surgery for NSCLC, of whom 484 were eligible for this analysis. The ipsilateral hilum was positive on preoperative PET in 107 patients. The median number of N1 lymph nodes sampled was 4 (range, 1-31). Positive ipsilateral N1 lymph nodes were identified pathologically in 91 patients (19%). Among the 91 patients with involved N1 lymph nodes, 40 were PET positive resulting in a sensitivity of 44%. Among 393 patients without pathologic involvement of hilar lymph nodes, 326 were PET negative resulting in a specificity of 83%. The positive predictive and negative predictive values were 37% and 86%, respectively. CONCLUSIONS: Positron emission tomography appears to have limitations in staging the ipsilateral hilar lymph nodes. Invasive sampling is appropriate if treatment would differ based on the nodal status.

Impact of (18)F-Fluoride PET on Intended Management of Patients with Cancers Other Than Prostate Cancer: Results from the National Oncologic PET Registry.

UNLABELLED: The National Oncologic PET Registry prospectively assessed the impact of PET with (18)F-sodium fluoride (NaF PET) on intended management of Medicare patients with suspected or known osseous metastasis. We report our findings for cancers other than prostate and make selected comparisons to our previously reported prostate cancer cohort. METHODS: Data were collected from both referring and interpreting physicians before and after NaF PET in patients (age ≥ 65 y) stratified for initial staging (IS; n = 570), for suspected first osseous metastasis (FOM; n = 1,814; breast, 781 [43%]; lung, 380 [21%]; and all other cancers, 653 [36%]), and for suspected progression of osseous metastasis (POM; n = 435). RESULTS: The dominant indication was bone pain. If NaF PET were unavailable, conventional bone scintigraphy would have been ordered in 85% of patients. In IS, 28% of patients had suspected or confirmed nonosseous metastasis. If neither conventional bone scintigraphy nor NaF PET were available, referring physicians would have ordered other advanced imaging more than 70% of the time rather than initiate treatment for suspected FOM (11%-16%) or POM (18%-22%). When intended management was classified as either treatment or nontreatment, the intended management change for each cancer type was highest in POM, lower in IS, and lowest in FOM. For suspected FOM, intended management change was lower in breast (24%), lung (36%), or other cancers (31%), compared with prostate cancer (44%) (P < 0.0001), but the NaF PET finding (normal/benign/equivocal, probable, or definite metastases) frequencies were similar across cancer types. After normal/benign/equivocal PET results, 15% of breast, 30% lung, and 38% prostate cancer patients had treatment, likely reflecting differences in management of nonosseous disease. For patients with definite metastasis on NaF PET, nonprostate, compared with prostate, cancer patients had post-PET plans for more frequent biopsy, alternative imaging, chemotherapy, and radiotherapy. In the smaller IS and POM cohorts, differences among cancer types were not significant. CONCLUSION: Overall, NaF PET led to change in intended management in a substantial fraction of nonprostate cancer patients. In the setting of suspected FOM, NaF PET had a lower immediate impact on the treat/nontreat decision in nonprostate versus prostate cancer patients, which is consistent with current practice guidelines.

Impact of 18F-fluoride PET in patients with known prostate cancer: initial results from the National Oncologic PET Registry.

UNLABELLED: Under Medicare's Coverage with Evidence Development policy, PET using (18)F-sodium fluoride (NaF PET) to identify osseous metastasis became a covered service if prospective registry data were collected. The National Oncologic PET Registry (NOPR) developed a NaF PET registry built on the foundation of its prior registry for PET with (18)F-FDG. Men with prostate cancer represented 72% of the cases. METHODS: Prospective data before and after NaF PET were collected from referring and interpreting physicians. The analysis set consisted of consenting men age 65 y or older with prostate cancer undergoing NaF PET for initial staging (IS, n = 1,024), suspected first osseous metastasis (FOM, n = 1,997), or suspected progression of osseous metastasis (POM, n = 510). RESULTS: Referring physicians indicated that if NaF PET were not available, other advanced imaging (body CT, MR imaging, or (18)F-FDG PET) would be their plan in about half of the cases. After NaF PET, the postimaging plan was revised to treatment in 77%, 52%, and 71% for IS, FOM, and POM, respectively. When intended management was classified as either treatment or nontreatment, the overall change in intended management ranged from 44% to 52% and from 12% to 16% if no effect was assumed for those cases with pre-PET plans for other imaging (imaging-adjusted impact). Interpreting physicians recorded definite findings of bone metastasis in 14%, 29%, and 76% for IS, FOM, and POM, respectively. The intended care patterns varied widely across indication and scan abnormality category combinations. CONCLUSION: NaF PET has high overall impact, principally related to its effect on replacing intended use of other advanced imaging. Its imaging-adjusted impact was similar to that observed with (18)F-FDG PET for restaging or suspected recurrence in other cancer types.

Neuropathologic heterogeneity does not impair florbetapir-positron emission tomography postmortem correlates.

Neuropathologic heterogeneity is often present among Alzheimer disease (AD) patients. We sought to determine whether amyloid imaging measures of AD are affected by concurrent pathologies. Thirty-eight clinically and pathologically defined AD and 17 nondemented patients with quantitative florbetapir F-18 (F-AV-45) positron emission tomography (PET) imaging during life and postmortem histological ß-amyloid quantification and neuropathologic examination were assessed. AD patients were divided on the basis of concurrent pathologies, including those with Lewy bodies (LBs) (n = 21), white matter rarefaction (n = 27), severe cerebral amyloid angiopathy (n = 11), argyrophilic grains (n = 5), and TAR DNA binding protein-43 inclusions (n = 18). Many patients exhibited more than 1 type of concurrent pathology. The ratio of cortical to cerebellar amyloid imaging signal (SUVr) and immunohistochemical ß-amyloid load were analyzed in 6 cortical regions of interest. All AD subgroups had strong and significant correlations between SUVr and histological ß-amyloid measures (p µ 0.001). All AD subgroups had significantly greater amyloid measures versus nondemented patients, and mean amyloid measures did not significantly differ between AD subgroups. When comparing AD cases with and without each pathology, AD cases with LBs had significantly lower SUVr measures versus AD cases without LBs (p = 0.002); there were no other paired comparison differences. These findings indicate that florbetapir-PET imaging is not confounded by neuropathological heterogeneity within AD.

Are discordant positron emission tomography and pathological assessments of the mediastinum in non-small cell lung cancer significant?

OBJECTIVE: Many patients with non-small cell lung cancer have positive mediastinal lymph nodes on preoperative positron emission tomography (PET) but do not have mediastinal involvement after surgery. The prognostic significance of this discordance was assessed. METHODS: This Institutional Review Board-approved study evaluated patients treated with upfront surgery at Duke Cancer Institute (Durham, NC) for non-small cell lung cancer from 1995 to 2008. Those staged with PET with pN0-1 disease after negative invasive mediastinal assessment were included. Mediastinal lymph nodes were scored as positive or negative based on visual analysis of the preoperative PET. Clinical outcomes of the PET-positive and PET-negative cohorts were estimated using the Kaplan-Meier method and compared using a log-rank test. Prognostic factors were assessed using a multivariate analysis. RESULTS: A total of 547 patients were assessed, of whom 105 (19%) were PET positive in the mediastinum. The median number of mediastinal lymph node stations sampled was 4 (range, 1-9). The 5-year risk of local recurrence was 26% in PET-positive versus 21% in PET-negative patients (P = .50). Patterns of local failure were similar between the 2 groups. Distant recurrence (35% vs 29%; P = .63) and overall survival (44% vs 54%; P = .52) were comparable for PET-positive and PET-negative patients. On multivariate analysis, a positive PET was not significant for local recurrence (hazard ratio [HR], 1; P = 1), distant recurrence (HR, 0.82; P = .42), or overall survival (HR, 1.08; P = .62). CONCLUSIONS: Patients with positive mediastinal lymph nodes on preoperative PET, but negative on histologic analysis, are not at increased risk of disease recurrence. Pathologic staging remains the standard.

Does the preparation and utilization of 99mTc-sulfur colloid affect the outcomes of breast lymphoscintigraphy?

UNLABELLED: The purpose of this study was to determine whether certain factors in the preparation and use of (99m)Tc-sulfur colloid affected the number of sentinel lymph nodes (SLNs) detected during SLN mapping and during intraoperative SLN identification. The factors that were investigated included the use of a dry heat block versus a hot water bath to heat the (99m)Tc-sulfur colloid bulk vial, amount of (99m)TcOH4(-) added to form the sulfur colloid particles, time between the unit dose calibration and the injection of the dose, and breast quadrant in which the injection occurred. METHODS: Data were collected retrospectively and quantitatively analyzed from images and reports of 488 patients with breast cancer who had undergone SLN mapping and intraoperative SLN identification from January 1, 2008, to June 30, 2011, inclusive. The dependent variables assessed were the number of SLNs visualized during lymphoscintigraphy, number of radioactive SLNs removed during surgery, and total number of lymph nodes removed intraoperatively. RESULTS: There was no significant difference in outcomes when comparing the amount of (99m)TcOH4(-) added during the preparation process to form the sulfur colloid particles, time between the unit dose calibration time and the time that the unit doses were injected, or location in the breast tissue in which the unit dose was administered. Initially, there were observed significant differences in outcomes when the heating methods used to prepare the (99m)Tc-sulfur colloid were compared. When the increased number of patients who were administered a calibrated unit dose activity of 74 MBq in the group using a dry heat block preparation method was taken into account, however, the findings were not significant. CONCLUSION: The use of a dry heat block versus a hot water bath to heat the (99m)Tc-sulfur colloid bulk vial, amount of (99m)TcOH4(-) added to form sulfur colloid particles, time between the unit dose calibration and the injection of the dose, and breast quadrant in which the injection occurred do not affect the number of SLNs detected during SLN mapping and during intraoperative SLN identification.

First-in-man evaluation of 2 high-affinity PSMA-avid small molecules for imaging prostate cancer.

UNLABELLED: This phase 1 study was performed to determine the pharmacokinetics and ability to visualize prostate cancer in bone, soft-tissue, and the prostate gland using (123)I-MIP-1072 and (123)I-MIP-1095, novel radiolabeled small molecules targeting prostate-specific membrane antigen. METHODS: Seven patients with a documented history of prostate cancer by histopathology or radiologic evidence of metastatic disease were intravenously administered 370 MBq (10 mCi) of (123)I-MIP-1072 and (123)I-MIP-1095 2 wk apart in a crossover trial design. (123)I-MIP-1072 was also studied in 6 healthy volunteers. Whole-body planar and SPECT/CT imaging was performed and pharmacokinetics studied over 2-3 d. Target-to-background ratios were calculated. Absorbed radiation doses were estimated using OLINDA/EXM. RESULTS: (123)I-MIP-1072 and (123)I-MIP-1095 visualized lesions in soft tissue, bone, and the prostate gland within 0.5-1 h after injection, with retention beyond 48 h. Target-to-background ratios from planar images averaged 2:1 at 1 h, 3:1 at 4-24 h, and greater than 10:1 at 4 and 24 h for SPECT/CT. Both agents cleared the blood in a biphasic manner; clearance of (123)I-MIP-1072 was approximately 5 times faster. (123)I-MIP-1072 was excreted in the urine, with 54% and 74% present by 24 and 72 h, respectively. In contrast, only 7% and 20% of (123)I-MIP-1095 had been renally excreted by 24 and 72 h, respectively. Estimated absorbed radiation doses were 0.054 versus 0.110 mGy/MBq for the kidneys and 0.024 versus 0.058 mGy/MBq for the liver, for (123)I-MIP-1072 and (123)I-MIP-1095, respectively. CONCLUSION: (123)I-MIP-1072 and (123)I-MIP-1095 detect lesions in soft tissue, bone, and the prostate gland at as early as 1-4 h. These novel radiolabeled small molecules have excellent pharmacokinetic and pharmacodynamic profiles and warrant further development as diagnostic and potentially when labeled with (131)I therapeutic radiopharmaceuticals.

Apolipoprotein E ε4 and age effects on florbetapir positron emission tomography in healthy aging and Alzheimer disease.

OBJECTIVES: Investigate apolipoprotein E ε4 (APOE4) gene and aging effects on florbetapir F18 positron emission tomography (PET) in normal aging and Alzheimer's disease (AD). METHODS: Florbetapir F18 PET images were analyzed from 245 participants, 18-92 years of age, from Avid Radiopharmaceutical's multicenter registered trials, including 86 younger healthy control volunteers (yHC), 61 older healthy control volunteers (oHC), 53 mild cognitive impairment (MCI) patients, and 45 AD dementia patients (DAT). Mean florbetapir standard uptake value ratios (SUVRs) were used to evaluate the effects of APOE4 carrier status, older age, and their interaction in each of these groups. RESULTS: In comparison with non-carriers, the APOE4 carriers in each of the oHC, MCI, and DAT groups had higher mean cortical-to-cerebellar florbetapir SUVRs, patterns of florbetapir PET elevations characteristic of DAT, and a higher proportion meeting florbetapir PET positivity criteria. Only the oHC group had a significant association between mean cortical florbetapir SUVRs and age. In cognitively normal adults, without regards to APOE4 genotype, amyloid began to increase at age 58 (95% confidence interval [CI]: 52.3-63.7), with a predicted typical age of florbetapir positivity occurring around age 71 years. Presence of the APOE4 gene reduced the age of predicted florbetapir positivity in normal aging to around age 56 years, approximately 20 years younger than non-carriers. INTERPRETATION: Cerebral amyloid deposition is associated with APOE4 carrier status in older healthy control subjects and symptomatic AD patients, and increases with age in older cognitively normal individuals. Amyloid imaging positivity appears to begin near age 56 years in cognitively intact APOE4 carriers and age 76 years in APOE4 non-carriers.

Predicting cognitive decline in subjects at risk for Alzheimer disease by using combined cerebrospinal fluid, MR imaging, and PET biomarkers.

PURPOSE: To assess the extent to which multiple Alzheimer disease (AD) biomarkers improve the ability to predict future decline in subjects with mild cognitive impairment (MCI) compared with predictions based on clinical parameters alone. MATERIALS AND METHODS: All protocols were approved by the institutional review board at each site, and written informed consent was obtained from all subjects. The study was HIPAA compliant. Alzheimer's Disease Neuroimaging Initiative (ADNI) baseline magnetic resonance (MR) imaging and fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) studies for 97 subjects with MCI were used. MR imaging-derived gray matter probability maps and FDG PET images were analyzed by using independent component analysis, an unbiased data-driven method to extract independent sources of information from whole-brain data. The loading parameters for all MR imaging and FDG components, along with cerebrospinal fluid (CSF) proteins, were entered into logistic regression models (dependent variable: conversion to AD within 4 years). Eight models were considered, including all combinations of MR imaging, PET, and CSF markers with the covariates (age, education, apolipoprotein E genotype, Alzheimer's Disease Assessment Scale-Cognitive subscale score). RESULTS: Combining MR imaging, FDG PET, and CSF data with routine clinical tests significantly increased the accuracy of predicting conversion to AD compared with clinical testing alone. The misclassification rate decreased from 41.3% to 28.4% (P < .00001). FDG PET contributed more information to routine tests (P < .00001) than CSF (P = .32) or MR imaging (P = .08). CONCLUSION: Imaging and CSF biomarkers can improve prediction of conversion from MCI to AD compared with baseline clinical testing. FDG PET appears to add the greatest prognostic information.

Amyloid-ß assessed by florbetapir F 18 PET and 18-month cognitive decline: a multicenter study.

OBJECTIVES: Florbetapir F 18 PET can image amyloid-ß (Aß) aggregates in the brains of living subjects. We prospectively evaluated the prognostic utility of detecting Aß pathology using florbetapir PET in subjects at risk for progressive cognitive decline. METHODS: A total of 151 subjects who previously participated in a multicenter florbetapir PET imaging study were recruited for longitudinal assessment. Subjects included 51 with recently diagnosed mild cognitive impairment (MCI), 69 cognitively normal controls (CN), and 31 with clinically diagnosed Alzheimer disease dementia (AD). PET images were visually scored as positive (Aß+) or negative (Aß-) for pathologic levels of ß-amyloid aggregation, blind to diagnostic classification. Cerebral to cerebellar standardized uptake value ratios (SUVr) were determined from the baseline PET images. Subjects were followed for 18 months to evaluate changes in cognition and diagnostic status. Analysis of covariance and correlation analyses were conducted to evaluate the association between baseline PET amyloid status and subsequent cognitive decline. RESULTS: In both MCI and CN, baseline Aß+ scans were associated with greater clinical worsening on the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog (p < 0.01) and Clinical Dementia Rating-sum of boxes (CDR-SB) (p < 0.02). In MCI Aß+ scans were also associated with greater decline in memory, Digit Symbol Substitution (DSS), and Mini-Mental State Examination (MMSE) (p < 0.05). In MCI, higher baseline SUVr similarly correlated with greater subsequent decline on the ADAS-Cog (p < 0.01), CDR-SB (p < 0.03), a memory measure, DSS, and MMSE (p < 0.05). Aß+ MCI tended to convert to AD dementia at a higher rate than Aß- subjects (p < 0.10). CONCLUSIONS: Florbetapir PET may help identify individuals at increased risk for progressive cognitive decline.

Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-ß plaques: a prospective cohort study.

BACKGROUND: Results of previous studies have shown associations between PET imaging of amyloid plaques and amyloid-ß pathology measured at autopsy. However, these studies were small and not designed to prospectively measure sensitivity or specificity of amyloid PET imaging against a reference standard. We therefore prospectively compared the sensitivity and specificity of amyloid PET imaging with neuropathology at autopsy. METHODS: This study was an extension of our previous imaging-to-autopsy study of participants recruited at 22 centres in the USA who had a life expectancy of less than 6 months at enrolment. Participants had autopsy within 2 years of PET imaging with florbetapir ((18)F). For one of the primary analyses, the interpretation of the florbetapir scans (majority interpretation of five nuclear medicine physicians, who classified each scan as amyloid positive or amyloid negative) was compared with amyloid pathology (assessed according to the Consortium to Establish a Registry for Alzheimer's Disease standards, and classed as amyloid positive for moderate or frequent plaques or amyloid negative for no or sparse plaques); correlation of the image analysis results with amyloid burden was tested as a coprimary endpoint. Correlation, sensitivity, and specificity analyses were also done in the subset of participants who had autopsy within 1 year of imaging as secondary endpoints. The study is registered with ClinicalTrials.gov, number NCT 01447719 (original study NCT 00857415). FINDINGS: We included 59 participants (aged 47-103 years; cognitive status ranging from normal to advanced dementia). The sensitivity and specificity of florbetapir PET imaging for detection of moderate to frequent plaques were 92% (36 of 39; 95% CI 78-98) and 100% (20 of 20; 80-100%), respectively, in people who had autopsy within 2 years of PET imaging, and 96% (27 of 28; 80-100%) and 100% (18 of 18; 78-100%), respectively, for those who had autopsy within 1 year. Amyloid assessed semiquantitatively with florbetapir PET was correlated with the post-mortem amyloid burden in the participants who had an autopsy within 2 years (Spearman ρ=0·76; p<0·0001) and within 12 months between imaging and autopsy (0·79; p<0·0001). INTERPRETATION: The results of this study validate the binary visual reading method approved in the USA for clinical use with florbetapir and suggest that florbetapir could be used to distinguish individuals with no or sparse amyloid plaques from those with moderate to frequent plaques. Additional research is needed to understand the prognostic implications of moderate to frequent plaque density. FUNDING: Avid Radiopharmaceuticals.

Extrarenal retroperitoneal angiomyolipoma mimicking metastatic melanoma: CT and FDG PET correlation.

A 38-year-old man with melanoma of the right flank underwent a staging 18F-fluoro-2-deoxyglucose (FDG) PET/CT scan, which demonstrated a hypermetabolic extrarenal mass in the left retroperitoneal space, concerning for metastatic melanoma. However, surgical pathology demonstrated an angiomyolipoma (AML). Although AMLs can rarely occur in an extrarenal location, extrarenal retroperitoneal AMLs are exceptional. AMLs have variable imaging appearances on multiple imaging modalities, including FDG PET, and can confound accurate diagnosis when in an extrarenal location. This case demonstrates the only known FDG PET description of an extrarenal retroperitoneal AML and highlights the challenge in accurate diagnosis based on FDG PET findings.

Impact of 18F-FDG PET used after initial treatment of cancer: comparison of the National Oncologic PET Registry 2006 and 2009 cohorts.

UNLABELLED: Since 2006, the National Oncologic PET Registry has collected prospective data on (18)F-FDG PET performed for cancer indications in Medicare beneficiaries under the coverage-with-evidence-development (CED) policy of the Centers for Medicare & Medicaid Services. In April 2009, coverage for PET performed to inform the initial treatment strategy of most solid tumors was expanded by the Centers for Medicare & Medicaid Services, but they continued to require CED for subsequent treatment strategy evaluations for many cancers. METHODS: For all years, we assessed National Oncologic PET Registry data for bladder, kidney, pancreas, prostate, stomach, small cell lung, uterine, and all other cancers that required CED. We compared clinical profiles and changes in intended management by interval (before or after April 2009, designated as the 2006 and 2009 cohorts) for PET scans performed for restaging or suspected recurrence (2006, n = 30,911; 2009, n = 54,747) or for chemotherapy monitoring (2006, n = 10,234; 2009, n = 15,611). RESULTS: There were slight differences between time periods but little difference by cancer type or patient age within a time period. For restaging or suspected recurrence, comparing the 2006 and 2009 cohorts, total change in intended management for all cancer types was about 33% in those younger than 65 y and about 35% in those older than 65 y (range by cancer type, 31%-41%). The referring physician impression of disease extent (restaging) or prognosis (chemotherapy monitoring) after PET was similar between cohorts. In the 2009 cohort, PET for chemotherapy monitoring was associated with a 25% increase in plans to continue therapy and a complementary decline in plans to adjust therapy. The greatest management impact of PET was during chemotherapy monitoring in the 2009 cohort, where a post-PET prognosis judged to be worse than before PET was associated with a plan to discontinue that therapy in 90% and to change to a different therapy in 65%. CONCLUSION: Our data demonstrate a similar impact of PET on planned management of cancer patients before and after the 2009 expansion of coverage. These results strongly suggest it is unlikely that new useful information will be obtained by extending the coverage of certain cancer types and indications only under CED. Future research on advanced imaging in the management of patients with cancer should focus on optimal sequencing and frequency of PET and other imaging modalities.

Impact of consolidation radiation therapy in stage III-IV diffuse large B-cell lymphoma with negative post-chemotherapy radiologic imaging.

PURPOSE: While consolidation radiation therapy (i.e., RT administered after chemotherapy) is routine treatment for patients with early-stage diffuse large B-cell lymphoma (DLBCL), the role of consolidation RT in stage III-IV DLBCL is controversial. METHODS AND MATERIALS: Cases of patients with stage III-IV DLBCL treated from 1991 to 2009 at Duke University, who achieved a complete response to chemotherapy were reviewed. Clinical outcomes were calculated using the Kaplan-Meier method and were compared between patients who did and did not receive RT, using the log-rank test. A multivariate analysis was performed using Cox proportional hazards model. RESULTS: Seventy-nine patients were identified. Chemotherapy (median, 6 cycles) consisted of anti-CD20 antibody rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; 65%); cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP; 22%); or other (13%). Post-chemotherapy imaging consisted of positron emission tomography (PET)/computed tomography (CT) (73%); gallium with CT (14%); or CT only (13%). Consolidation RT (median, 25 Gy) was given to involved sites of disease in 38 (48%) patients. Receipt of consolidation RT was associated with improved in-field control (92% vs. 69%, respectively, p = 0.028) and event-free survival (85% vs. 65%, respectively, p = 0.014) but no difference in overall survival (85% vs. 78%, respectively, p = 0.15) when compared to patients who did not receive consolidation RT. On multivariate analysis, no RT was predictive of increased risk of in-field failure (hazard ratio [HR], 8.01, p = 0.014) and worse event-free survival (HR, 4.3, p = 0.014). CONCLUSIONS: Patients with stage III-IV DLBCL who achieve negative post-chemotherapy imaging have improved in-field control and event-free survival with low-dose consolidation RT.

Variable-time positron emission tomography leg protocol to equalize noise for positron emission tomography/computed tomography acquisitions.

OBJECTIVES: Positron emission tomography protocols conventionally use a constant scan time per bed position (BP). It may be optimal to spend more time scanning some body sections, particularly the more attenuating sections. The relatively consistent tapering of legs may allow a single, variable-time protocol that could reduce or redistribute time and equalize image quality throughout the leg. Reducing the total scan time will limit the opportunity for motion, which can reduce imaging artefacts and improves image fusion, will improve a patient's experience, and will yield the biggest gains in time for the tallest patients. METHODS: Leg dimensions were studied in 55 adult positron emission tomography/computed tomography scans. Image quality versus size was parameterized using bottle phantoms (diameters, 4.5-19.7 cm) filled with identical 18F-fluorodeoxyglucose concentrations, positioned as legs and imaged. An exponential relationship of diameter to noise was fit to the data, which defined the noise-equalizing, variable-time protocol. RESULTS: Of 55 patient leg studies, 94.5% (52/55) had leg diameters that were less than ± 7.5% of the mean leg diameter for other patients of similar height. To equalize noise throughout the leg, relative scan times from superior to inferior as a function of BP are (1, 0.65, 0.45, 0.36, 0.30, and 0.25). CONCLUSION: Variable time compared with a constant-time protocol can require 75% less time for some BPs and half the total acquisition time. A variable-time protocol to reduce time has been implemented.

Use of florbetapir-PET for imaging beta-amyloid pathology.

CONTEXT: The ability to identify and quantify brain ß-amyloid could increase the accuracy of a clinical diagnosis of Alzheimer disease. OBJECTIVE: To determine if florbetapir F 18 positron emission tomographic (PET) imaging performed during life accurately predicts the presence of ß-amyloid in the brain at autopsy. DESIGN, SETTING, AND PARTICIPANTS: Prospective clinical evaluation conducted February 2009 through March 2010 of florbetapir-PET imaging performed on 35 patients from hospice, long-term care, and community health care facilities near the end of their lives (6 patients to establish the protocol and 29 to validate) compared with immunohistochemistry and silver stain measures of brain ß-amyloid after their death used as the reference standard. PET images were also obtained in 74 young individuals (18-50 years) presumed free of brain amyloid to better understand the frequency of a false-positive interpretation of a florbetapir-PET image. MAIN OUTCOME MEASURES: Correlation of florbetapir-PET image interpretation (based on the median of 3 nuclear medicine physicians' ratings) and semiautomated quantification of cortical retention with postmortem ß-amyloid burden, neuritic amyloid plaque density, and neuropathological diagnosis of Alzheimer disease in the first 35 participants autopsied (out of 152 individuals enrolled in the PET pathological correlation study). RESULTS: Florbetapir-PET imaging was performed a mean of 99 days (range, 1-377 days) before death for the 29 individuals in the primary analysis cohort. Fifteen of the 29 individuals (51.7%) met pathological criteria for Alzheimer disease. Both visual interpretation of the florbetapir-PET images and mean quantitative estimates of cortical uptake were correlated with presence and quantity of ß-amyloid pathology at autopsy as measured by immunohistochemistry (Bonferroni ρ, 0.78 [95% confidence interval, 0.58-0.89]; P <.001]) and silver stain neuritic plaque score (Bonferroni ρ, 0.71 [95% confidence interval, 0.47-0.86]; P <.001). Florbetapir-PET images and postmortem results rated as positive or negative for ß-amyloid agreed in 96% of the 29 individuals in the primary analysis cohort. The florbetapir-PET image was rated as amyloid negative in the 74 younger individuals in the nonautopsy cohort. CONCLUSIONS: Florbetapir-PET imaging was correlated with the presence and density of ß-amyloid. These data provide evidence that a molecular imaging procedure can identify ß-amyloid pathology in the brains of individuals during life. Additional studies are required to understand the appropriate use of florbetapir-PET imaging in the clinical diagnosis of Alzheimer disease and for the prediction of progression to dementia.

Uric acid is a danger signal of increasing risk for osteoarthritis through inflammasome activation.

Uric acid (UA) is known to activate the NLRP3 (Nacht, leucine-rich repeat and pyrin domain containing protein 3) inflammasome. When activated, the NLRP3 (also known as NALP3) inflammasome leads to the production of IL-18 and IL-1ß. In this cohort of subjects with knee osteoarthritis (OA), synovial fluid uric acid was strongly correlated with synovial fluid IL-18 and IL-1ß. Synovial fluid uric acid and IL-18 were strongly and positively associated with OA severity as measured by both radiograph and bone scintigraphy, and synovial fluid IL-1ß was associated with OA severity but only by radiograph. Furthermore, synovial fluid IL-18 was associated with a 3-y change in OA severity, on the basis of the radiograph. We conclude that synovial fluid uric acid is a marker of knee OA severity. The correlation of synovial fluid uric acid with the two cytokines (IL-18 and IL-1ß) known to be produced by uric acid-activated inflammasomes and the association of synovial fluid IL-18 with OA progression, lend strong support to the potential involvement of the innate immune system in OA pathology and OA progression.

Impact of dedicated brain PET on intended patient management in participants of the national oncologic PET Registry.

PURPOSE: This study seeks to assess the impact of dedicated brain positron emission tomography (PET) with 2-deoxy-2-[(18)F]fluoro-D-glucose on intended management of patients with primary and metastatic brain tumors. PROCEDURES: We analyzed demographic characteristics and evaluated change in intended management after PET, using previously described metrics, for patients in the National Oncologic PET Registry (NOPR) undergoing dedicated brain PET. For cases of primary brain tumors, comparisons to the overall NOPR cohort were made. PATIENT PROFILE: Between December 2006 and April 2009, 509 dedicated brain PET scans were done on 479 patients--367 (72.1%) for suspected or proven primary brain tumors and 142 (27.9%) for brain metastases. Compared with the overall NOPR cohort, subjects in the dedicated brain cohort were younger (41.3% less than 65 years vs. 10.5% overall, p < 0.0001) and more frequently had functional limitations from their cancers (78.6% vs. 62.3% overall; odds ratio (OR) 2.2, 95% CI 1.8-2.8). RESULTS: The pre-PET patient management plans in the primary brain tumor and metastasis subgroups were similar. A pre-PET plan of tissue biopsy was slightly more frequent than one of the treatments (31.3% vs. 28.6%) in the primary brain tumor subgroup and was more common than in the overall NOPR cohort (14.2%; OR 2.8, 95% CI 2.2-3.5). Changes from treatment to non-treatment also were more frequent than in the overall NOPR cohort (13.4% vs. 7.7%; OR 1.9, 95% CI 1.3-2.5). CONCLUSIONS: Among NOPR patients, dedicated brain PET was associated with similar net changes in intended management as in the overall NOPR cohort. However, brain PET patients were younger, more likely to be symptomatic, and less likely to have a change in management from non-treatment to treatment as a post-PET plan.