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1.
Cancers (Basel) ; 13(17)2021 Aug 27.
Article in English | MEDLINE | ID: mdl-34503133

ABSTRACT

Although anti-CD38 monoclonal antibodies have improved the prognosis of relapsed/refractory multiple myeloma (RRMM), some patients still experience early relapses with poor outcomes. This present study evaluated the predictive value of FDG PET/CT parameters for RRMM prior to initiating anti-CD38 treatment. We included 38 consecutive RRMM patients who underwent a PET/CT scan treated at our institution at relapse. The median PFS was 12.5 months and the median OS was not reached. 42% of the patients had an initial ISS score of 1, 37% of 2, and 21% of 3. The presence of >3 focal lesions (FLs, n = 19) and the ISS score were associated with inferior PFS (p = 0.0036 and p = 0.0026) and OS (p = 0.025 and p = 0.0098). Patients with >3 FLs had a higher initial ISS score (p = 0.028). In multivariable analysis, the ISS score and >3 FLs were independent prognostic factors for PFS (p = 0.010 and p = 0.025 respectively), and combined they individualized a high-risk group with a median PFS and OS of 3.1 months and 8.5 months respectively vs. not reached for the other patients. The presence of >3 FLs on PET was predictive of survival outcomes in patients with RRMM treated using CD38 targeted therapy. Combined with the initial ISS, an ultra-high-risk RRMM population can thus be identified.

2.
JAMA Oncol ; 4(2): 217-224, 2018 Feb 01.
Article in English | MEDLINE | ID: mdl-29121144

ABSTRACT

IMPORTANCE: Androgen receptor-signaling inhibitor (ARSi) drugs prolong life in metastatic castration-resistant prostate cancer (mCRPC), but such tumors eventually become resistant and progress. Comprehensive positron emission tomography/computed tomography (PET/CT) imaging using fluoro-2-D-deoxyglucose F 18 ([18F]-FDG) for glycolysis (Glyc) and fluorodihydrotestosterone F 18 ([18F]-FDHT) for androgen receptor (AR) expression determine heterogeneity of imaging phenotypes, which may be useful in distinguishing patients who will benefit from ARSi drugs from those who need alternative treatments. OBJECTIVE: To test the hypothesis that PET/CT-based assessments of AR expression and glycolytic activity would reveal heterogeneity affecting prognosis. DESIGN, SETTING, AND PARTICIPANTS: Between April 6, 2007, and October 4, 2012, patients with mCRPC underwent imaging with both [18F]-FDG and [18F]-FDHT at Memorial Sloan Kettering Cancer Center. The patients were naive to ARSi treatment with enzalutamide or abiraterone acetate and were referred during documented disease progression. Image-directed biopsy determined the presence or absence of prostate cancer at positive imaging sites. INTERVENTIONS: PET/CT imaging was performed with [18F]-FDHT and [18F]-FDG; select individual lesions were biopsied to correlate imaging phenotype with histologic findings. MAIN OUTCOMES AND MEASURES: All metabolically active lesions were interpreted as [18F]-FDHT-positive (AR1) or [18F]-FDHT-negative (AR0) and as [18F]-FDG-positive (Glyc1) or [18F]-FDG-negative (Glyc0). Correlation was performed with overall survival for both individual lesion imaging phenotype as well as patient-specific imaging phenotype. RESULTS: The mean (SD) age of the 133 patients was 68 (8.6) years. Imaging phenotypes of 2405 PET/CT-positive lesions (median, 12.0 per patient) included 1713 (71.2%) AR1Glyc1, 386 (16.0%) AR1Glyc0, and 306 (12.7%) AR0Glyc1. On multivariate analysis, each phenotype had an independent negative impact effect on survival, most pronounced for AR0Glyc1 lesions (hazard ratio [HR], 1.11; 95% CI, 1.05-1.16; P < .001), followed by AR1Glyc1 lesions (HR, 1.05; 95% CI, 1.03-1.06; P < .001) and AR1Glyc0 lesions (HR, 1.03; 95% CI, 1.00-1.05; P = .048). When sorted by lesion type, 4 patient-specific groups emerged: (1) concordant, with all AR1Glyc1 (34 patients [25.6%]); (2) AR predominant, with AR1Glyc1 and varying numbers of AR1Glyc0 (33 [24.8%]); (3) Glyc predominant, with AR1Glyc1 and varying numbers of AR0Glyc1 (40 [30.1%]); and (4) mixed, with AR1Glyc1 plus a mixture of varying numbers of AR1Glyc0 and AR0Glyc1 (26 [19.5%]). CONCLUSIONS AND RELEVANCE: Heterogeneity of PET/CT imaging phenotype has clinical relevance on a lesion and individual patient level. With regard to mCRPC lesions, most express ARs, consistent with initial benefit of ARSi drugs. On a patient basis, 49% (groups 3 and 4) had at least 1 AR0Glyc1 lesion-the imaging phenotype with the most negative effect on survival, possibly due to ARSi resistance.


Subject(s)
Biomarkers, Tumor/metabolism , Glycolysis/physiology , Positron Emission Tomography Computed Tomography , Prostatic Neoplasms, Castration-Resistant/diagnosis , Prostatic Neoplasms, Castration-Resistant/metabolism , Receptors, Androgen/metabolism , Adenocarcinoma/diagnosis , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/analysis , Fluorodeoxyglucose F18/pharmacokinetics , Humans , Immunohistochemistry , Male , Middle Aged , Multimodal Imaging , Neoplasm Metastasis , Prognosis , Prostatic Neoplasms, Castration-Resistant/pathology , Receptors, Androgen/analysis
3.
Leuk Lymphoma ; 57(12): 2820-2826, 2016 12.
Article in English | MEDLINE | ID: mdl-27118302

ABSTRACT

Primary bone diffuse large B-cell lymphoma (PB-DLBCL) is a rare DLBCL location variant. We treated 76 PB-DLBCL patients by immuno-chemotherapy, resulting in an 84% sustained complete remission rate and a 78.9% survival over a 4.7-year median follow-up period. Ann Arbor stage IV and high age-adjusted international prognostic index were predictive of adverse outcome in univariate analysis. In multivariate analysis using a Cox model, only aa-IPI predicted long-term survival. While based on a limited number of cases, we suggested that radiotherapy may be useful as a consolidation modality in PB-DLBCL. We also suggested that positron emission tomography/CT scan should be interpreted with caution due to a persistent [18F]fluorodeoxyglucose [18FDG] uptake of bone lesions even after remission in some in PB-DLBCL patients. Our study based on a homogeneous cohort of PB-DLBCL patients confirmed the favorable outcome of this DLBCL variant and support the implementation of prospective clinical trials in this disease.


Subject(s)
Bone Neoplasms/diagnosis , Bone Neoplasms/therapy , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Neoplasms/mortality , Combined Modality Therapy/methods , Female , France , Humans , Lymphoma, Large B-Cell, Diffuse/mortality , Male , Middle Aged , Neoplasm Staging , Positron Emission Tomography Computed Tomography , Randomized Controlled Trials as Topic , Retrospective Studies , Survival Analysis , Treatment Outcome
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