fluorocholine and Prostatic-Neoplasms--Castration-Resistant

The role of 18F-choline positron emission tomography/computed tomography (FCH-PET/CT) in patients with metastatic castration-resistant prostate cancer (mCRPC) has been firmly established in recent years. We analyzed the prognostic value of functional parameters such as mean standardized uptake volume (SUVmean), maximum standardized uptake volume (SUVmax), metabolic total volume (MTV; the volume of interest consisting of all spatially connected voxels within a fixed threshold of 40% of the SUVmax), and total lesion activity (TLA: the product of MTV and mean standardized uptake value) estimated with FCH-PET/CT in mCRPC patients in progression after docetaxel and treated with new antiandrogen receptor therapies, abiraterone or enzalutamide.. We retrospectively studied 94 mCRPC patients, mean age 74 years (range 42-90), previously treated with docetaxel who were treated with either abiraterone (n = 52) or enzalutamide (n = 42). An FCH-PET/CT was performed at baseline, and patients were evaluated on a monthly basis for serological PSA response and every 3 months for radiological response. We measured MTV, SUVmean, SUVmax and TLA for each lesion and analyzed the sum of MTV (SMTV), SUVmean (SSUVmean), SUVmax (SSUVmax) and TLA (STLA) values for a maximum of 20 lesions. Univariate analysis was used to correlate these data with PFS and OS.. Semiquantitative parameters of FCH-PET/CT play a prognostic role in mCRCP patients treated with abiraterone or enzalutamide.

Topics: Adult; Aged; Aged, 80 and over; Androstenes; Benzamides; Choline; Humans; Male; Middle Aged; Neoplasm Metastasis; Nitriles; Phenylthiohydantoin; Positron Emission Tomography Computed Tomography; Prognosis; Prospective Studies; Prostatic Neoplasms, Castration-Resistant; Reproducibility of Results; Retrospective Studies

This study investigated the prognostic significance of metabolically active tumor volume (MATV) measurements applied to (18)F-fluorocholine PET/CT in castration-resistant prostate cancer (CRPC).. (18)F-fluorocholine PET/CT imaging was performed on 30 patients with CRPC. Metastatic disease was quantified on the basis of maximum standardized uptake value (SUV(max)), MATV, and total lesion activity (TLA = MATV × mean standardized uptake value). Tumor burden indices derived from whole-body summation of PET tumor volume measurements (i.e., net MATV and net TLA) were evaluated as variables in Cox regression and Kaplan-Meier survival analyses.. Net MATV ranged from 0.12 cm(3) to 1,543.9 cm(3) (median, 52.6 cm(3)). Net TLA ranged from 0.40 to 6,688.7 g (median, 225.1 g). Prostate-specific antigen level at the time of PET correlated significantly with net MATV (Pearson r = 0.65, P = 0.0001) and net TLA (r = 0.60, P = 0.0005) but not highest lesional SUV(max) of each scan. Survivors were followed for a median 23 mo (range, 6-38 mo). On Cox regression analyses, overall survival had a significant association with net MATV (P = 0.0068), net TLA (P = 0.0072), and highest lesion SUV(max) (P = 0.0173) and a borderline association with prostate-specific antigen level (P = 0.0458). Only net MATV and net TLA remained significant in univariate-adjusted survival analyses. Kaplan-Meier analysis demonstrated significant differences in survival between groups stratified by median net MATV (log-rank P = 0.0371), net TLA (log-rank P = 0.0371), and highest lesion SUV(max) (log-rank P = 0.0223).. Metastatic prostate cancer detected by (18)F-fluorocholine PET/CT can be quantified on the basis of volumetric measurements of tumor metabolic activity. The prognostic value of (18)F-fluorocholine PET/CT may stem from this capacity to assess whole-body tumor burden. With further clinical validation, (18)F-fluorocholine PET-based indices of global disease activity and mortality risk could prove useful in patient-individualized treatment of CRPC.

Topics: Aged; Aged, 80 and over; Choline; Humans; Male; Middle Aged; Multimodal Imaging; Multivariate Analysis; Neoplasm Metastasis; Positron-Emission Tomography; Prognosis; Prostatic Neoplasms, Castration-Resistant; Survival Analysis; Tomography, X-Ray Computed; Tumor Burden; Whole Body Imaging

We investigated the role of 18F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT) in the early evaluation of abiraterone and outcome prediction in patients with metastatic castration-resistant prostate cancer (CRPC).. Forty-three patients with metastatic CRPC progressing after docetaxel received abiraterone 1,000 mg daily with prednisone 5 mg twice daily. Patients were evaluated monthly for serological PSA response and safety. FCH-PET/CT was done at baseline and after 3 to 6 weeks. Univariate and multivariate Cox regression models addressed potential predictors of progression-free survival (PFS) and overall survival (OS).. Declines in PSA level of ≥50% were seen in 21 of 43 (49%) patients. Forty-two patients were evaluable for FCH-PET/CT response. FCH-PET/CT bone flare was observed in 4 of 42 (10%) evaluable patients. In univariate analysis, PSA decline and FCH-PET/CT response predicted PFS, while PSA decline and FCH-PET/CT (progression vs non progression) predicted OS. In multivariate analysis, only FCH-PET/CT (progression vs nonprogression) remained significant for PFS and OS (p = 0.022 and p = 0.027, respectively).. Early FCH-PET/CT can predict clinical outcome in CRPC beyond PSA response. These data support further studies on FCH-PET/CT for abiraterone monitoring and outcome prediction in patients with CRPC.

Topics: Aged; Androstenes; Antineoplastic Agents; Choline; Disease-Free Survival; Drug Resistance, Neoplasm; Humans; Image Interpretation, Computer-Assisted; Male; Middle Aged; Multimodal Imaging; Positron-Emission Tomography; Prostatic Neoplasms, Castration-Resistant; Radioisotopes; Tomography, X-Ray Computed

Metastatic involvement of the larynx is rare due to the absence of vessels within the cartilaginous tissue. The probability of metastatic spread increases with aging as a result of larynx ossification. The secondary involvement of larynx is more frequently associated with melanoma and renal cell carcinoma. Few observations have been reported also in prostate cancer patients, usually associated with advanced disease and diffuse metastatic bone involvement. We report a case of an 83-year-old man with castration-resistant prostate cancer in whom a metastasis to the thyroid cartilage was the only site of relapse.

Topics: Aged; Carcinoma; Choline; Copper Radioisotopes; Head and Neck Neoplasms; Humans; Male; Neoplasm Metastasis; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms, Castration-Resistant; Radiopharmaceuticals; Thyroid Cartilage

The aim of the study was to assess the correlation between metabolic response measured through positron emission tomography-computed tomography (PET-CT) with

Topics: Aged; Aged, 80 and over; Alpha Particles; Bone and Bones; Bone Neoplasms; Choline; Feasibility Studies; Fluorine Radioisotopes; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms, Castration-Resistant; Radioisotopes; Radium; Retrospective Studies; Treatment Outcome

This study aims to predict hematological toxicity induced by Ra therapy. We investigated the value of metabolically active bone tumor volume (MBTV) and total bone lesion activity (TLA) calculated on pretreatment fluorine-18-fluorocholine (F-FCH) PET/CT in castrate-resistant prostate cancer (CRPC) patients with bone metastases treated with Ra radionuclide therapy.. F-FCH PET/CT imaging was performed in 15 patients with CRPC before treatment with Ra. Bone metastatic disease was quantified on the basis of the maximum standardized uptake value (SUV), total lesion activity (TLA=MBTV×SUVmean), or MBTV/height (MBTV/H) and TLA/H. F-FCH PET/CT bone tumor burden and activity were analyzed to identify which parameters could predict hematological toxicity [on hemoglobin (Hb), platelets (PLTs), and lymphocytes] while on Ra therapy. Pearson's correlation was used to identify the correlations between age, prostate-specific antigen, and F-FCH PET parameters.. MBTV ranged from 75 to 1259 cm (median: 392 cm). TLA ranged from 342 to 7198 cm (median: 1853 cm). Patients benefited from two to six cycles of Ra (n=56 cycles in total). At the end of Ra therapy, five of the 15 (33%) patients presented grade 2/3 toxicity on Hb and lymphocytes, whereas three of the 15 (20%) patients presented grade 2/3 PLT toxicity.Age was correlated negatively with both MBTV (r=-0.612, P=0.015) and TLA (r=-0.596, P=0.018). TLA, TLA/H, and MBTV/H predicted hematological toxicity on Hb, whereas TLA/H and MBTV/H predicted toxicity on PLTs at the end of Ra cycles. Receiver operating characteristic curve analysis allowed to define the cutoffs for MBTV (915 cm) and TLA (4198 cm) predictive for PLT toxicity, with an accuracy of 0.92 and 0.99.. Tumor bone burden calculation is feasible with F-FCH PET/CT with freely available open-source software. In this pilot study, baseline F-FCH PET/CT markers (TLA, MBTV) have shown abilities to predict Hb and PLT toxicity after Ra therapy and could be explored for patient selection and treatment optimization.

Topics: Aged; Aged, 80 and over; Blood; Bone Neoplasms; Choline; Humans; Male; Middle Aged; Pilot Projects; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms, Castration-Resistant; Radium

We present 3 cases of patients with castration-resistant prostate cancer and bone metastases treated with Ra, belonging to our prospective and multicenter ChoPET-Rad study. All patients underwent clinical, hematological, and biochemical monitoring between each Ra administration. Initial and follow-up F-fluorocholine PET/CT and Tc-biphosphonate bone scintigraphy were performed previously and after the third Ra administration. Both techniques correctly established the response to treatment, in agreement to the biochemical response, although differences in the disease expression (concordant and discordant patterns) were found because of the different radiotracer biodistribution and molecular information derived from them.

Topics: Aged; Bone Neoplasms; Choline; Humans; Male; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms, Castration-Resistant; Radium; Treatment Outcome

Two patients with castrate-resistant prostate cancer and symptomatic skeletal metastases underwent F-fluorocholine PET/CT prior to treatment with Ra-dichloride to reveal additional active lesions in the prostate gland and lymph nodes. Subsequent scans performed at the midpoint and end of Ra-dichloride therapy showed resolution of this soft tissue activity alongside declining bone lesion activity. Concomitant increases in plasma interleukin 6 were detected, suggesting that immune system activation may have mediated the soft tissue response. Abscopal effects usually encountered with external beam radiotherapy may also be occurring with Ra-dichloride therapy.

Topics: Aged, 80 and over; Choline; Disease Progression; Humans; Male; Neoplasm Metastasis; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms, Castration-Resistant; Radioisotopes; Radium; Treatment Outcome

The association between choline uptake and androgen receptor (AR) expression is suggested by the upregulation of choline kinase-alpha in prostate cancer. Recently, detection of AR aberration in cell-free DNA as well as early 18F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT) were associated with outcome in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone and enzalutamide. We aimed to make a direct comparison between circulating AR copy number (CN) and choline uptake at FCH-PET/CT. We analysed 80 mCRPC patients progressing after docetaxel treated with abiraterone (n = 47) or enzalutamide (n = 33). We analysed AR CN from plasma samples using digital PCR and Taqman CN assays and total lesion activity (TLA) and metabolic tumor volume (MTV) on FCH-PET/CT at baseline. A meaningful correlation was showed among AR gain and TLA/MTV compared to AR non-gained cases (P = 0.001 and P = 0.004, respectively), independently from type of treatment. Multivariate analysis revealed that AR CN and only TLA were associated with both shorter PFS (P < 0.0009 and P = 0.026, respectively) and OS (P < 0.031 and P = 0.039, respectively). AR gain appeared significantly correlated with choline uptake represented mainly by TLA. Further prospective studies are warranted to better address this pathway of AR-signalling and to identify multiplex biomarker strategies including plasma AR and FCH-PET/CT in mCRPC patients.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Androstenes; Antineoplastic Combined Chemotherapy Protocols; Benzamides; Biomarkers, Tumor; Chlorine; Choline; Docetaxel; Gene Dosage; Humans; Male; Middle Aged; Nitriles; Phenylthiohydantoin; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms, Castration-Resistant; Receptors, Androgen; Signal Transduction

Measurements of metabolically active tumor volume (MATV) can be applied to (18)F-fluorocholine PET/CT to quantify whole-body tumor burden. This study evaluated the serial application of these measurements as systemic treatment response markers and predictors of disease progression in patients with castration-resistant prostate cancer (CRPC).. Forty-two patients completed sequential (18)F-fluorocholine PET/CT scans before and 1-3 mo after starting treatment for CRPC. Whole-body tumor segmentation was applied to determine net MATV from each scan. Changes in net MATV were evaluated as predictors of time to prostate-specific antigen (PSA) progression by Kaplan-Meier and proportional hazards regression analysis.. Treatments consisted of chemotherapy in 16 patients, antiandrogens in 19 patients, (223)Ra-dichloride in 5 patients, and sipuleucel-T in 2 patients. A significant MATV response (defined as a ≥30% decrease in net MATV) was observed in 20 patients on the basis of in-treatment PET/CT performed an average of 51 d (median, 49 d) into treatment. Significantly longer times to PSA progression were observed in patients who exhibited an MATV response (418 d vs. 116 d, P = 0.0067). MATV response was associated with a hazard ratio of 0.246 (P = 0.0113) for PSA progression, which remained significant when adjusted for treatment type.. Significant changes in whole-body tumor burden can be measured on (18)F-fluorocholine PET/CT over the course of contemporary treatments for CRPC. In this study, these changes were found to be predictive of PSA progression as a potential surrogate marker of treatment outcome. Because (18)F-fluorocholine PET/CT can also be used for localizing resistant tumors, this modality can potentially complement other measures of response in the precision management of advanced prostate cancer.

Topics: Aged; Androgen Antagonists; Antineoplastic Agents; Cancer Vaccines; Choline; Combined Modality Therapy; Disease Progression; Humans; Kaplan-Meier Estimate; Male; Positron Emission Tomography Computed Tomography; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radiopharmaceuticals; Radium; Tissue Extracts; Tumor Burden; Whole Body Imaging

We investigated the role of (18)F-methylcholine (FCH) PET/CT in the early evaluation of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide.. The study group comprised 36 patients with a median age of 72 years (range 48-90 years) who were treated with enzalutamide 160 mg once daily after at least one chemotherapeutic regimen with docetaxel. Patients were evaluated monthly for serological prostate-specific antigen (PSA) response. FCH PET/CT was performed at baseline and repeated after 3-6 weeks. Univariate and multivariate Cox regression models addressed potential predictors of progression-free survival (PFS) and overall survival (OS).. At a median follow-up of 24.2 months (range 1.8-27.3 months), 34 patients were evaluable for early FCH PET/CT evaluation of response, and of these 17 showed progressive disease (PD) and 17 had stable disease or a partial response. A decrease in PSA level of more than 50% was observed in 21 patients. Early FCH PET/CT PD predicted radiological PD 3 months in advance of CT in 12 of 18 patients (66%) and was discordant with the decrease in PSA level in 13 patients. In 6 of these, biochemical PD was confirmed in 2 months. In multivariate analysis, only decrease in PSA level and FCH PET/CT were significant predictors of PFS (p = 0.0005 and p = 0.029, respectively), whereas decrease in PSA level alone was predictive of OS (p = 0.007).. This is one of the first studies to evaluate the role of FCH PET/CT as an early predictor of outcome in mCRPC patients treated with enzalutamide. Our preliminary results suggest that the combination of FCH PET/CT and decrease in PSA level could be a valid tool to predict PFS in mCRPC patients. PSA remains the single most important prognostic factor, while FCH PET/CT does not add more information on OS beyond that obtained from PSA. Further studies in larger populations are needed to confirm these data and to clarify the role of FCH PET/CT in predicting response to enzalutamide in mCRPC patients.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Benzamides; Choline; Humans; Male; Middle Aged; Multimodal Imaging; Neoplasm Metastasis; Nitriles; Phenylthiohydantoin; Positron-Emission Tomography; Prostatic Neoplasms, Castration-Resistant; Radiopharmaceuticals; Tomography, X-Ray Computed

Several treatments are proposed for castration-resistant prostate cancer (CRPC) at the metastatic stage. Monitoring of response using serum prostate-specific antigen (PSA) levels (sPSA) can be insufficient at this stage. Imaging has been proposed, in particular, nuclear medicine functional imaging and MRI, since response of predominant bone metastases is hardly evaluable on CT. Our aim was to evaluate in patients with CRPC with bone metastases, before and after various treatment lines, the evolution of sPSA, whole-body 18F-fluorocholine (FCH) PET/CT and spine MRI (sMRI) that has been proposed for detection of imminent malignant spinal cord compression.. We retrospectively gathered a pilot series of 10 patients with CRPC metastatic to bone who had 47 PSA assays, FCH PET/CT, and spine-MRI (sMRI) performed concomitantly as routine examinations, before the beginning and at the end of 37 therapeutic intervals (TIs). Blinded reading of FCH PET/CT and sMRI was performed to evaluate visually whether or not the disease has been progressing (new lesions, greater size, or greater uptake intensity of known lesions) between the initial and the final examination of each TI.. Visual interpretations limited to spine FCH (sFCH) PET/CT and sMRI were in accordance for 34 TIs (92%): 14 progressions and 20 nonprogressions. In 2 cases, sFCH did not detect lesions visible on sMRI: one epiduritis and one 6-mm lesion. In 1 case, MRI missed a lesion in the sacrum that was detected on sFCH. When whole-body FCH (wbFCH) PET/CT was taken into account, the agreement with sMRI was limited to 29 TIs (78%). The 8 discrepant cases were all wbFCH positive and sMRI negative, that is, a significantly higher frequency of positivity for wbFCH (P < 0.008). Serum PSA levels increased by more than 25% during 21 TIs, whereas no progression was visible in 8 TIs on sMRI and in 2 TIs on wbFCH. In 5 TIs, sPSA decreased by more than 50%, and progression was never detected on imaging.. In detecting progression in patients with CRPC metastatic to bone, results of spine imaging with sMRI and sFCH PET/CT were highly correlated, whereas wbFCH PET/CT showed significantly more progression statues comparing to sMRI alone related to the exploration of other parts of the skeleton and of soft tissue.

Topics: Aged; Aged, 80 and over; Bone Neoplasms; Choline; Fluorine Radioisotopes; Humans; Magnetic Resonance Imaging; Male; Multimodal Imaging; Pilot Projects; Positron-Emission Tomography; Prostatic Neoplasms, Castration-Resistant; Radiopharmaceuticals; Spinal Cord; Tomography, X-Ray Computed; Whole Body Imaging