Salvage Radiotherapy Management Decisions in Postprostatectomy Patients with Recurrent Prostate Cancer Based on 18F-Fluciclovine PET/CT Guidance.

Imaging with novel PET radiotracers has significantly influenced radiotherapy decision making and radiation planning in patients with recurrent prostate cancer (PCa). The purpose of this analysis was to report the final results for management decision changes based on 18F-fluciclovine PET/CT findings and determine whether the decision change trend remained after completion of accrual. Methods: Patients with detectable prostate-specific antigen (PSA) after prostatectomy were randomized to undergo either conventional imaging (CI) only (arm A) or CI plus 18F-fluciclovine PET/CT (arm B) before radiotherapy. In arm B, positivity rates on CI and 18F-fluciclovine PET/CT for detection of recurrent PCa were determined. Final decisions on whether to offer radiotherapy and whether to include only the prostate bed or also the pelvis in the radiotherapy field were based on 18F-fluciclovine PET/CT findings. Radiotherapy decisions before and after 18F-fluciclovine PET/CT were compared. The statistical significance of decision changes was determined using the Clopper-Pearson (exact) binomial method. Prognostic factors were compared between patients with and without decision changes. Results: All 165 patients enrolled in the study had standard-of-care CI and were initially planned to receive radiotherapy. Sixty-three of 79 (79.7%) patients (median PSA, 0.33 ng/mL) who underwent 18F-fluciclovine PET/CT (arm B) had positive findings. 18F-Fluciclovine PET/CT had a significantly higher positivity rate than CI did for the whole body (79.7% vs. 13.9%; P < 0.001), prostate bed (69.6% vs. 5.1%; P < 0.001), and pelvic lymph nodes (38.0% vs. 10.1%; P < 0.001). Twenty-eight of 79 (35.4%) patients had the overall radiotherapy decision changed after 18F-fluciclovine PET/CT; in 4 of 79 (5.1%), the decision to use radiotherapy was withdrawn because of extrapelvic disease detected on 18F-fluciclovine PET/CT. In 24 of 75 (32.0%) patients with a final decision to undergo radiotherapy, the radiotherapy field was changed. Changes in overall radiotherapy decisions and radiotherapy fields were statistically significant (P < 0.001). Overall, the mean PSA at PET was significantly different between patients with and without radiotherapy decision changes (P = 0.033). Conclusion:18F-Fluciclovine PET/CT significantly altered salvage radiotherapy decisions in patients with recurrent PCa after prostatectomy. Further analysis to determine the impact of 18F-fluciclovine PET/CT guidance on clinical outcomes after radiotherapy is in progress.

Anti-3-18F-FACBC (18F-Fluciclovine) PET/CT of Breast Cancer: An Exploratory Study.

UNLABELLED: The purpose of this study was to explore the uptake of the synthetic amino acid analog PET radiotracer anti-3-(18)F-FACBC ((18)F-fluciclovine) in breast lesions with correlation to histologic and immunohistochemical characteristics. METHODS: Twelve women with breast lesions underwent 45-min dynamic PET/CT of the thorax after intravenous administration of 366.3 ± 14.8 (337.44-394.05) MBq of (18)F-fluciclovine. Uptake in the primary lesions at 4 representative time points (5, 17, 29, and 41 min) after injection were correlated with histologic, imaging, and clinical findings. The significance of differences in SUVmax and tumor-to-background ratios between malignant and benign tissue were calculated. Correlations of activity to histologic and immunohistochemical cancer subtypes were made including Ki-67 intensity and Nottingham grade (NG). RESULTS: There were 17 breast lesions (4 benign, 13 malignant) including 7 of 13 invasive ductal, 5 of 13 invasive lobular, and 1 of 13 metaplastic carcinomas. There was a significant difference in mean SUVmax ± SD of malignant (6.2 ± 3.2, 6.0 ± 3.2, 5.7 ± 2.8, and 5.6 ± 3.0) versus benign (1.3 ± 0.6, 1.2 ± 0.5, 1.2 ± 0.6, and 1.1 ± 0.5) lesions at 5, 17, 29, and 41 min, respectively (all P ≤ 0.0001). Tumor-to-background (aorta, normal breast, and marrow) ratios were also significantly higher in malignant than benign breast lesions (all P ≤ 0.02). The highest (18)F-fluciclovine activity seems to be present in triple-negative and NG3 subtypes. Across time points, quantitative Ki-67 had weak positive correlation with SUVmax (R1 = 0.48 [P = 0.03], R2 = 0.44 [P = 0.03], R3 = 0.46 [P = 0.03], R4 = 0.43 [0.06]). In 7 patients, (18)F-fluciclovine PET visualized locoregional and distant spread including that of lobular cancer, though identification of hepatic metastases was limited by physiologic background activity. CONCLUSION: The uptake characteristics of (18)F-fluciclovine are reflective of the histologic and immunohistochemical characteristics in suspected breast lesions with greater activity in malignant versus benign etiology. The data from this exploratory study may be useful to design future studies using (18)F-fluciclovine PET for breast tumor imaging as well as for detection of locoregional and distant spread.

Recurrent prostate cancer detection with anti-3-[(18)F]FACBC PET/CT: comparison with CT.

PURPOSE: To compare the diagnostic performance of the synthetic amino acid analogue PET radiotracer anti-3-[(18)F]FACBC (fluciclovine) with that of CT in the detection of recurrent prostate carcinoma. METHODS: This was a retrospective analysis of 53 bone scan-negative patients with suspected recurrent prostate carcinoma who underwent fluciclovine PET/CT and routine clinical CT within 90 days of each other. The correlation between imaging findings and histology and clinical follow-up was evaluated. Positivity rates and diagnostic performance were calculated for fluciclovine PET/CT and CT. RESULTS: Of 53 fluciclovine PET/CT and 53 CT examinations, 41 (77.4 %) and 10 (18.9 %), respectively, had positive findings for recurrent disease. Positivity rates were higher with fluciclovine PET/CT than with CT at all prostate-specific antigen (PSA) levels, PSA doubling times and original Gleason scores. In the prostate/bed, fluciclovine PET/CT was true-positive in 31 and CT was true-positive in 4 of 51 patients who met the reference standard. In extraprostatic regions, fluciclovine PET/CT was true-positive in 12 and CT was true-positive in 3 of 41 patients who met the reference standard. Of the 43 index lesions used to prove positivity, 42 (97.7 %) had histological proof. In 51 patients with sufficient follow-up to calculate diagnostic performance in the prostate/bed, fluciclovine PET/CT demonstrated a sensitivity of 88.6 %, a specificity of 56.3 %, an accuracy of 78.4 %, a positive predictive value (PPV) of 81.6 %, and a negative predictive value (NPV) of 69.2 %; the respective values for CT were 11.4 %, 87.5 %, 35.3 %, 66.7 % and 31.1 %. In 41 patients with sufficient follow-up to calculate diagnostic performance in extraprostatic regions, fluciclovine PET/CT demonstrated a sensitivity of 46.2 %, a specificity of 100 %, an accuracy of 65.9 %, a PPV of 100 %, and an NPV of 51.7 %; the respective values for CT were 11.5 %, 100 %, 43.9 %, 100 % and 39.5 %. CONCLUSION: The diagnostic performance of fluciclovine PET/CT in recurrent prostate cancer is superior to that of CT and fluciclovine PET/CT provides better delineation of prostatic from extraprostatic recurrence.

Reproducibility and reliability of anti-3-[¹8F]FACBC uptake measurements in background structures and malignant lesions on follow-up PET-CT in prostate carcinoma: an exploratory analysis.

PURPOSE: The aim of this study is to examine the reproducibility of anti-1-amino-3-[(18)F]fluorocyclobutane-1-carboxylic acid (anti-3-[(18)F]FACBC) quantitative measurements in key background structures and untreated malignant lesions. PROCEDURES: Retrospective review of 14 patients who underwent follow-up anti-3-[(18)F]FACBC positron emission tomography-X-ray computed tomography (PET-CT) for prostate carcinoma recurrence. Standard uptake values (SUV) were measured in both original and follow-up scans in key background structures and untreated malignant lesions. Absolute and percent mean difference in SUV between scans and interclass correlation coefficients (ICC) were also computed. RESULTS: Mean (±SD, range) scan interval was 17.4 months (±7.1, 4-29). %Mean difference in SUVmean was <20 % in background structures with low absolute differences. ICCs were >0.6 except for early-phase blood pool (ICC = 0.4). SUVmax in malignant lesions without interim therapy increased or remained stable over time. CONCLUSIONS: Despite variable time interval between scans, FACBC PET-CT demonstrates acceptable reproducibility in key background structures. Untreated malignant lesions showed stable or increased uptake over time. A formal test-retest study is planned.

Anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid: physiologic uptake patterns, incidental findings, and variants that may simulate disease.

UNLABELLED: Anti-1-amino-3-(18)F-fluorocyclobutane-1-carboxylic acid ((18)F-FACBC) is a synthetic amino acid analog PET radiotracer undergoing clinical trials for the evaluation of prostate and other cancers. We aimed to describe common physiologic uptake patterns, incidental findings, and variants in patients who had undergone (18)F-FACBC PET. METHODS: Sixteen clinical trials involving 611 (18)F-FACBC studies from 6 centers, which included dosimetry studies on 12 healthy volunteers, were reviewed. Qualitative observations of common physiologic patterns, incidental uptake, and variants that could simulate disease were recorded and compared with similar observations in studies of the healthy volunteers. Quantitative analysis of select data and review of prior published reports and observations were also made. RESULTS: The liver and pancreas demonstrated the most intense uptake. Moderate salivary and pituitary uptake and variable mild to moderate bowel activity were commonly visualized. Moderate bone marrow and mild muscle activity were present on early images, with marrow activity decreasing and muscle activity increasing with time. Brain and lungs demonstrated activity less than blood pool. Though (18)F-FACBC exhibited little renal excretion or bladder uptake during the clinically useful early imaging time window, mild to moderate activity might accumulate in the bladder and interfere with evaluation of adjacent prostate bed and seminal vesicles in 5%-10% of patients. Uptake might also occur from benign processes such as infection, inflammation, prostatic hyperplasia, and metabolically active benign bone lesions such as osteoid osteoma. CONCLUSION: Common physiologic uptake patterns were similar to those noted in healthy volunteers. The activity in organs followed the presence of amino acid transport and metabolism described with other amino acid-based PET radiotracers. As with other PET radiotracers such as (18)F-FDG, focal nonphysiologic uptake may represent incidental malignancy. Uptake due to benign etiologies distinct from physiologic background also occurred and could lead to misinterpretations if the reader is unaware of them.

Anti-3-[(18)F]FACBC positron emission tomography-computerized tomography and (111)In-capromab pendetide single photon emission computerized tomography-computerized tomography for recurrent prostate carcinoma: results of a prospective clinical trial.

PURPOSE: We prospectively evaluated the amino acid analogue positron emission tomography radiotracer anti-3-[(18)F]FACBC compared to ProstaScint® ((111)In-capromab pendetide) single photon emission computerized tomography-computerized tomography to detect recurrent prostate carcinoma. MATERIALS AND METHODS: A total of 93 patients met study inclusion criteria who underwent anti-3-[(18)F]FACBC positron emission tomography-computerized tomography plus (111)In-capromab pendetide single photon emission computerized tomography-computerized tomography for suspected recurrent prostate carcinoma within 90 days. Reference standards were applied by a multidisciplinary board. We calculated diagnostic performance for detecting disease. RESULTS: In the 91 of 93 patients with sufficient data for a consensus on the presence or absence of prostate/bed disease anti-3-[(18)F]FACBC had 90.2% sensitivity, 40.0% specificity, 73.6% accuracy, 75.3% positive predictive value and 66.7% negative predictive value compared to (111)In-capromab pendetide with 67.2%, 56.7%, 63.7%, 75.9% and 45.9%, respectively. In the 70 of 93 patients with a consensus on the presence or absence of extraprostatic disease anti-3-[(18)F]FACBC had 55.0% sensitivity, 96.7% specificity, 72.9% accuracy, 95.7% positive predictive value and 61.7% negative predictive value compared to (111)In-capromab pendetide with 10.0%, 86.7%, 42.9%, 50.0% and 41.9%, respectively. Of 77 index lesions used to prove positivity histological proof was obtained in 74 (96.1%). Anti-3-[(18)F]FACBC identified 14 more positive prostate bed recurrences (55 vs 41) and 18 more patients with extraprostatic involvement (22 vs 4). Anti-3-[(18)F]FACBC positron emission tomography-computerized tomography correctly up-staged 18 of 70 cases (25.7%) in which there was a consensus on the presence or absence of extraprostatic involvement. CONCLUSIONS: Better diagnostic performance was noted for anti-3-[(18)F]FACBC positron emission tomography-computerized tomography than for (111)In-capromab pendetide single photon emission computerized tomography-computerized tomography for prostate carcinoma recurrence. The former method detected significantly more prostatic and extraprostatic disease.

Near-elimination of folate-deficiency anemia by mandatory folic acid fortification in older US adults: Reasons for Geographic and Racial Differences in Stroke study 2003-2007.

BACKGROUND: The United States implemented mandatory folic acid fortification of enriched cereal grains in 1998. Although several studies have documented the resulting decrease in anemia and folate deficiency, to our knowledge, no one has determined the prevalence of folate-deficiency anemia after fortification. OBJECTIVE: We determined the prevalence of folate deficiency and folate-deficiency anemia within a sample of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. DESIGN: The REGARDS cohort is a prospective cohort of 30,239 black and white participants living in the contiguous United States. We measured serum folate concentrations in a random sample of 1546 REGARDS participants aged ≥50 y with baseline hemoglobin and red blood cell mean corpuscular volume measurements. Folate deficiency was defined as a serum folate concentration <6.6 nmol/L (<3.0 ng/mL), and anemia was defined as a hemoglobin concentration <13 g/dL in men and <12 g/dL in nonpregnant women (WHO criteria). Folate-deficiency anemia was defined as the presence of both folate deficiency and anemia. RESULTS: The mean hemoglobin concentration was 13.6 g/dL, and 15.9% of subjects had anemia. The median serum folate concentration was 34.2 nmol/L (15.1 ng/mL), and only 2 of 1546 participants 0.1%) were folate deficient. Both subjects were African American women with markedly elevated C-reactive protein concentrations, macrocytosis, and normal serum cobalamin concentrations; only one subject was anemic. Overall, the prevalence of folate-deficiency anemia was <0.1% (1 of 1546 subjects). CONCLUSION: Our data suggest that, after mandatory folic acid fortification, the prevalence of folate-deficiency anemia is nearly nonexistent in a community-dwelling population in the United States.

Valproate prescriptions for nonepilepsy disorders in reproductive-age women.

BACKGROUND: Scientific evidence has consistently shown taking valproate during pregnancy increases risks of congenital malformations and cognitive impairment. As such, elimination of its use would be an important step in birth defects prevention. There are guidelines discouraging its use among women with epilepsy, but none exists for women without epilepsy, nor is the prevalence of valproate for nonepilepsy indications known. METHODS: Using de-identified data from the National Hospital and Ambulatory Medical Care Surveys (1996-2007), we examined individual prescriptions for reproductive-age adolescent girls and adult women ages 15 to 44 years in the United States, and estimated the number of antiepileptic drug and valproate prescriptions in the aggregate. We classified our study population using International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes, as women with epilepsy and women without epilepsy. The prevalence of antiepileptic drug and valproate prescriptions among women without epilepsy was estimated as prescriptions per 1000 patient visits for every 3-year time interval and the overall study period. RESULTS: We found 83% of valproate prescriptions were issued to women without epilepsy and 74% of these were for psychiatric diagnoses. The prevalence of antiepileptic drug prescriptions among women without epilepsy tripled during the study period (10.3 [1996-1998] vs. 34.9 [2005-2007] per 1000 patient visits), whereas valproate prescriptions remained relatively stable (3.1 [1996-1998] vs. 3.7 [2005-2007] per 1000 patient visits). CONCLUSION: Most women of reproductive age who receive a valproate prescription do not have epilepsy. Valproate prescriptions did not decline, despite increasing knowledge of its teratogenicity. Reducing valproate use among women of reproductive age, especially among those who use the drug for psychiatric indications, would prevent birth defects and cognitive deficits.