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A phase 1b study evaluating the effect of elacestrant treatment on estrogen receptor availability and estradiol binding to the estrogen receptor in metastatic breast cancer lesions using 18F-FES PET/CT imaging.
Jager, A, de Vries, EGE, der Houven van Oordt, CWM, Neven, P, Venema, CM, Glaudemans, AWJM, Wang, Y, Bagley, RG, Conlan, MG, Aftimos, P
Breast cancer research : BCR. 2020;(1):97
Abstract
BACKGROUND Elacestrant is an oral selective estrogen receptor (ER) degrader. This phase 1b open-label, non-randomized study (RAD1901-106) was initiated to determine the effect of elacestrant on the availability of ER in lesions from postmenopausal women with ER+ advanced breast cancer (ABC) using 16α-18F-fluoro-17β-estradiol positron emission tomography with low-dose computed tomography (FES-PET/CT). METHODS Eligible patients were postmenopausal women with ER+, HER2- ABC; tumor progression after ≥ 6 months of 1-3 lines of endocrine treatment for ABC; and measurable or evaluable disease. Two 8-patient cohorts were enrolled: one treated with 400 mg elacestrant once daily (QD) and one treated with 200 mg elacestrant QD with dose escalation to 400 mg QD after 14 days. Elacestrant was dosed continuously until progressive disease, toxicity, or withdrawal. FES-PET/CT was performed pre-dose at baseline and 4 h post-dose on day 14. The primary endpoint was the percentage difference in FES uptake in tumor lesions (maximum 20) after 14 days of treatment compared to baseline. Overall response was investigator-assessed by Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1. RESULTS Patients (n = 16; median age, 53.5 years) had ABC with a median 2.5 prior lines of endocrine therapy. Median reduction in tumor FES uptake from baseline to day 14 was 89.1% (Q1, Q3: 75.1%, 94.1%) and was similar in both cohorts (89.1% [Q1, Q3: 67.4%, 94.2%], 200/400 mg and 88.7% [Q1, Q3: 79.5%, 94.1%], 400 mg). Residual ER availability (> 25% persistence in FES uptake) on day 14 was observed in 3 patients receiving 200/400 mg (3/78, 37.5%) and 1 patient receiving 400 mg (1/8, 12.5%). The overall response rate (ORR) was 11.1% (1 partial response), and clinical benefit rate (CBR) was 30.8%. Median percentage change in FES uptake did not correlate with ORR or CBR. Adverse events occurring in > 20% of the patients were nausea (68.8%), fatigue (50.0%), dyspepsia (43.8%), vomiting (37.5%), and decreased appetite, dysphagia, and hot flush (31.3% each). Most events were grade 2 in severity. CONCLUSION Elacestrant 200 mg and 400 mg QD greatly reduced ER availability measured by FES-PET/CT. In a heavily pretreated population, elacestrant was associated with antitumor activity. TRIAL REGISTRATION ClinicalTrials.gov, NCT02650817 . Registered on 08 January 2016.
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Diagnostic performance of 18F-choline PET-CT in prostate cancer.
Samper Ots, P, Luis Cardo, A, Vallejo Ocaña, C, Cabeza Rodríguez, MA, Glaria Enríquez, LA, Couselo Paniagua, ML, Olivera Vegas, J
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. 2019;(6):766-773
Abstract
OBJECTIVES To evaluate the diagnostic performance of 18F-choline PETCT in staging prostate cancer (PC) and whether the use of this imaging modality changes the therapeutic decision in patients previously staged by conventional imaging. The secondary aim was to determine the prognostic factors associated with positive choline PETCT findings in both detection of disseminated disease and in changes in the therapeutic indication. MATERIALS AND METHODS Multicentre, retrospective, observational study of 269 patients diagnosed with PC. Mean age was 69 ± 9.2 years. Of the 269 patients, 62 (23%) had high-risk localized PC (group 1), 118 (43.9%) biochemical failure after radical prostatectomy (group 2), and 89 (33.1%) biochemical failure after radiotherapy (group 3). None of the patients showed clear evidence of distant disease on computed tomography or bone scans. The following potential prognostic factors were assessed: PSA level at diagnosis; primary and secondary Gleason; Gleason score (GS); clinical and pathologic T and N stage; number of positive cylinders in the biopsy; presence of vascular or lymphatic invasion; status of surgical margins; androgen deprivation therapy (ADT); time to biochemical recurrence; and PSA, PSA doubling time (PSADT), and PSA velocity (PSAV) at failure. Univariate and multivariate analyses were performed, and receiver-operating curves calculated. RESULTS The mean PSA by groups was, group 1: 31.22 ng/ml, group 2: 2.52 ng/ml and group 3: 5.85 ng/ml. The tumor detection rate with 18F-choline PETCT was 74% (group 1: 85.5%, group 2: 55.1% and group 3: 91%). Prognostic factors for positive 18F-choline PETCT were identified only in group 2: PSA at failure and PSADT. 18F-choline PETCT changed the therapeutic indication in 62.8% (group 1: 71%, group 2: 55.2% and group 3: 70.1%). The prognostic factors for a change in treatment were identified only in group 1: secondary Gleason ≤ 4 and GS ≤ 7 and in group 2: PSA at failure, PSA nadir after surgery and pathologic stage N0. 18F-choline PETCT identified lymph node and/or metastatic disease in 32.7% (group 1: 25.8%, group 2: 29.7% and group 3: 41.6%). Prognostic factors for detecting lymph node/metastasis were identified in the group 2: PSA failure ≥ 1.37 ng/ml and PSADT < 4 months and in the group 3: PSADT < 4.6 months and time to failure < 5 years. CONCLUSION These findings support the clinical use de 18F-choline PET-CT in staging high-risk patients with a secondary Gleason ≤ 4 and GS ≤ 7, in restaging patients with biochemical recurrence after RP if PSA at failure ≥ 1.37 ng/ml or PSADT ≤ 4 months and in patients with biochemical failure after RT, if PSADT ≤ 4.6 months and time to failure < 5 years, because it determines a change in the therapeutic indication.
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The clinical value of imaging in primary cutaneous lymphomas: Role of high resolution ultrasound and PET-CT.
Mandava, A, Koppula, V, Wortsman, X, Catalano, O, Alfageme, F
The British journal of radiology. 2019;(1095):20180904
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Abstract
BACKGROUND Primary cutaneous lymphoma is a rare extranodal non-Hodgkin's lymphoma confined to the skin. The data on the imaging findings of primary cutaneous lymphomas are largely lacking and the current diagnosis is based on clinical and histopathological examination. With the advances in dermatological ultrasound and molecular imaging, newer perspectives in the evaluation of cutaneous lymphomas are available. OBJECTIVE To review and describe the imaging findings in patient's with the diagnosis of primary cutaneous lymphoma. METHODS A multicentric, retrospective observational study was undertaken in four countries to review the high resolution ultrasonography (HRUS) and fluorine 18-fludeoxyglucose positron emission tomography-computed tomography (PET-CT) imaging findings. RESULTS We had 41 patients, Female:Male 1:4.1; mean age, 57 years; range, 13-94 years. High resolution ultrasonography of the primary cutaneous lesions revealed thickening of the dermis in all the cases and the lesions were hypoechoic without any calcifications or central necrosis. The sonographic appearances of the lesions were categorised into focal infiltrative, nodular, pseudonodular, and diffusely infiltrative patterns. Nodular and pseudonodular lesions were predominant in B cell lymphomas, while diffusely infiltrative lesions were more common in T-cell lymphomas. On colour Doppler imaging, the lesions were hypervascular. Whole body 18F-fludeoxyglucose PET-CT imaging of the patients revealed increased uptake of the metabolite in the lesions. CONCLUSION Sonographic patterns based on high resolution ultrasonography provide early clues to the non-invasive diagnosis of primary cutaneous lymphomas and PET-CT is the recommended modality of imaging for staging and follow-up. ADVANCES IN KNOWLEDGE High resolution ultrasound with colour Doppler and PET-CT imaging are complimentary to the clinical diagnosis of primary cutaneous lymphomas.
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Prospective comparative study of 18F-sodium fluoride PET/CT and planar bone scintigraphy for treatment response assessment of bone metastases in patients with prostate cancer.
Fonager, RF, Zacho, HD, Langkilde, NC, Fledelius, J, Ejlersen, JA, Hendel, HW, Haarmark, C, Moe, M, Mortensen, JC, Jochumsen, MR, et al
Acta oncologica (Stockholm, Sweden). 2018;(8):1063-1069
Abstract
AIM: To compare 18F-sodium fluoride positron emission tomography/computed tomography (NaF PET/CT) and 99mTc-labelled diphosphonate bone scan (BS) for the monitoring of bone metastases in patients with prostate cancer undergoing anti-cancer treatment. MATERIAL AND METHODS Data from 64 patients with prostate cancer were included. The patients received androgen-deprivation therapy (ADT), next-generation hormonal therapy (NGH) or chemotherapy. The patients had a baseline scan and 1-3 subsequent scans during six months of treatment. Images were evaluated by experienced nuclear medicine physicians and classified for progressive disease (PD) or non-PD according to the Prostate Cancer Working Group 2 (PCWG-2) criteria. The patients were also classified as having PD/non-PD according to the clinical and prostate-specific antigen (PSA) responses. RESULTS There was no difference between NaF PET/CT and BS in the detection of PD and non-PD during treatment (McNemar's test, p = .18). The agreement between BS and NaF PET/CT for PD/non-PD was moderate (Cohen's kappa 0.53, 95% confidence interval 0.26-0.79). Crude agreement between BS and NaF PET/CT for the assessment of PD/non-PD was 86% (89% for ADT, n = 28; 88% for NGH, n = 16, and 80% for chemotherapy, n = 20). In most discordant cases, BS found PD when NaF PET/CT did not, or BS detected PD on an earlier scan than NaF PET/CT. Biochemical progression (27%) occurred more frequently than progression on functional imaging (BS, 22% and NaF PET/CT, 14%). Clinical progression was rare (11%), and almost exclusively seen in patients receiving chemotherapy. CONCLUSION There was no difference between NaF PET/CT and BS in the detection of PD and non-PD; however, BS seemingly detects PD by the PCWG-2 criteria earlier than NaF-PET, which might be explained by the fact that NaF-PET is more sensitive at the baseline scan.
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Predictive and prognostic potential of volume-based metabolic variables obtained by a baseline 18F-FDG PET/CT in breast cancer with neoadjuvant chemotherapy indication.
Garcia-Vicente, AM, Pérez-Beteta, J, Amo-Salas, M, Molina, D, Jimenez-Londoño, GA, Soriano-Castrejón, AM, Pena Pardo, FJ, Martínez-González, A
Revista espanola de medicina nuclear e imagen molecular. 2018;(2):73-79
Abstract
AIM: To investigate the usefulness of metabolic variables using 18F-FDG PET/CT in the prediction of neoadjuvant chemotherapy (NC) response and the prognosis in locally advanced breast cancer (LABC). MATERIAL AND METHODS Prospective study including 67 patients with LABC, NC indication and a baseline 18F-FDG PET/CT. After breast tumor segmentation, SUV variables (SUVmax, SUVmean and SUVpeak) and volume-based variables, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), were obtained. Tumors were grouped into molecular phenotypes, and classified as responders or non-responders after completion of NC. Disease-free status (DFs), disease-free survival (DFS), and overall survival (OS) were assessed. A univariate and multivariate analysis was performed to study the potential of all variables to predict DFs, DFS, and OS. RESULTS Fourteen patients were classified as responders. Median±SD of DFS and OS was 43±15 and 46±13 months, respectively. SUV and TLG showed a significant correlation (p<0.005) with the histological response, with higher values in responders compared to non-responders. MTV and TLG showed a significant association with DFs (p=0.015 and p=0.038 respectively). Median, mean and SD of MTV and TLG for patients with DFs were: 8.90, 13.73, 15.10 and 33.78, and 90.54 and 144.64, respectively. Median, mean and SD of MTV and TLG for patients with non-DFs were: 16.72, 29.70 and 31.09 and 90.89, 210.98 and 382.80, respectively. No significant relationships were observed with SUV variables and DFs. Volume-based variables were significantly associated with OS and DFS, although in multivariate analysis only MTV was related to OS. No SUV variables showed an association with the prognosis. CONCLUSION Volume-based metabolic variables obtained with 18F-FDG PET/CT, unlike SUV based variables, were good predictors of both neoadjuvant chemotherapy response and prognosis.
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How common is isolated cardiac sarcoidosis? Extra-cardiac and cardiac findings on clinical examination and whole-body 18F-fluorodeoxyglucose positron emission tomography.
Juneau, D, Nery, P, Russo, J, de Kemp, RA, Leung, E, Beanlands, RSB, Birnie, DH
International journal of cardiology. 2018;:189-193
Abstract
BACKGROUND Sarcoidosis is a systemic inflammatory disease which can involve nearly any organ. Clinically manifest cardiac involvement occurs in perhaps 5% of patients with sarcoidosis. The reported prevalence of isolated cardiac sarcoidosis (CS) varies widely with reported rates of 27-54%. The explanation for this variability is likely multi-factorial but perhaps mostly related to the diagnostic method(s) for assessing extra-cardiac involvement. The primary aim of this study was to assess the rate of isolated CS in a homogeneous, prospectively recruited cohort of patients with clinically manifest CS, using whole body FDG PET-CT imaging as a gold standard. A secondary aim was to describe the extent and distribution of extra-cardiac sarcoidosis at the time of first presentation of clinically manifest CS. METHODS Patients were prospectively recruited at the time of first presentation with cardiac symptoms. All patients underwent whole-body and cardiac 18F-FDG PET-CT. All patients were examined for presence of skin sarcoidosis and were assessed by an ophthalmologist. RESULTS 31 patients were included (mean age 56±8years, 17 female, 100% Caucasian). Patients had limited extra-cardiac involvement (mean of 2.2 organs) however using the most precise definition, only 1/31 (3.2%) patients had isolated CS. There were marked differences in right ventricular (RV) and atrial involvement between patients presenting with CS as first presentation compared to patients presenting initially with extra-cardiac disease. CONCLUSIONS Most patients had limited extra-cardiac involvement at the time of presentation of manifest CS however, isolated CS, using the proposed gold standard, was only observed in one patient.
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Quantitative Assessment of Early [18F]Sodium Fluoride Positron Emission Tomography/Computed Tomography Response to Treatment in Men With Metastatic Prostate Cancer to Bone.
Harmon, SA, Perk, T, Lin, C, Eickhoff, J, Choyke, PL, Dahut, WL, Apolo, AB, Humm, JL, Larson, SM, Morris, MJ, et al
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2017;(24):2829-2837
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Abstract
Purpose [18F]Sodium fluoride (NaF) positron emission tomography (PET)/computed tomography (CT) is a promising radiotracer for quantitative assessment of bone metastases. This study assesses changes in early NaF PET/CT response measures in metastatic prostate cancer for correlation to clinical outcomes. Patients and Methods Fifty-six patients with metastatic castration-resistant prostate cancer (mCRPC) with osseous metastases had NaF PET/CT scans performed at baseline and after three cycles of chemotherapy (n = 16) or androgen receptor pathway inhibitors (n = 40). A novel technology, Quantitative Total Bone Imaging, was used for analysis. Global imaging metrics, including maximum standardized uptake value (SUVmax) and total functional burden (SUVtotal), were extracted from composite lesion-level statistics for each patient and tracked throughout treatment. Progression-free survival (PFS) was calculated as a composite end point of progressive events using conventional imaging and/or physician discretion of clinical benefit; NaF imaging was not used for clinical evaluation. Cox proportional hazards regression analyses were conducted between imaging metrics and PFS. Results Functional burden (SUVtotal) assessed midtreatment was the strongest univariable PFS predictor (hazard ratio, 1.97; 95% CI, 1.44 to 2.71; P < .001). Classification of patients based on changes in functional burden showed stronger correlation to PFS than did the change in number of lesions. Various global imaging metrics outperformed baseline clinical markers in predicting outcome, including SUVtotal and SUVmean. No differences in imaging response or PFS correlates were found for different treatment cohorts. Conclusion Quantitative total bone imaging enables comprehensive disease quantification on NaF PET/CT imaging, showing strong correlation to clinical outcomes. Total functional burden assessed after three cycles of hormonal therapy or chemotherapy was predictive of PFS for men with mCRPC. This supports ongoing development of NaF PET/CT-based imaging biomarkers in mCRPC to bone.