[18F]NaF PET/CT imaging biomarkers of progression-free survival in metastatic prostate cancer.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 277-277
Author(s):  
Stephanie Harmon ◽  
Tim Perk ◽  
Jens C. Eickhoff ◽  
Mary Jane Staab ◽  
Peter L. Choyke ◽  
...  

277 Background: 18F-Sodium Fluoride (NaF) PET/CT has been shown to be superior to 99mTc-MDP SPECT in detection of bone metastases and shows great promise to reliably measure functional changes in bone. This study assesses the relationship of Progression Free Survival (PFS) with NaF PET/CT measures in patients with metastatic Castration-Resistant Prostate Cancer (CRPC). Methods: 55 CRPC patients had NaF PET/CT scans performed at baseline, which was repeated at week 9 if receiving taxane-based therapy (N = 16) or week 12 if receiving androgen-signaling pathway (AR) inhibitors (N = 39). Bone lesions were identified using a novel technique allowing for extraction and tracking of PET metrics from individual lesions at every timepoint. Cox proportional hazard regression analyses were conducted to evaluate associations between imaging metrics and PFS. Results: Median PFS was 8.3 months (range 1.0-30.3+). The strongest predictor of PFS in univariate analysis was total functional burden (SUVtotal) (P < 0.0001) during treatment for all patients. Predictors of PFS differed between both treatment cohorts of patients (Table 1), including number of lesions, fraction of skeletal involvement, and average lesion activity (SUVmean). Maximum PSA benefit (percent decrease) during the first 12 weeks of therapy was highly predictive of PFS in the AR-directed cohort of patients (HR = 1.012 , P = 0.0005), as was change in the number of lesions (HR = 1.01, P = 0.03). Conclusions: There is indication thattotal functional burden of disease during treatment with taxane or AR-directed therapy is a strong predictor of PFS. In addition, change in number of lesions was predictive of treatment efficacy. This supports ongoing development of NaF PET/CT based imaging biomarkers in mCRPC. Clinical trial information: NCT01516866. [Table: see text]

2021 ◽  
Vol 11 ◽  
Author(s):  
Juan Briones ◽  
Maira Khan ◽  
Amanjot K. Sidhu ◽  
Liying Zhang ◽  
Martin Smoragiewicz ◽  
...  

BackgroundBoth Docetaxel (DOC) and Abiraterone (ABI) improve the survival of men with metastatic, castration sensitive prostate cancer (mCSPC). However, the outcome among mCSPC patients is highly variable, while there is a lack of predictive markers of therapeutic benefit. Furthermore, there is limited data on the comparative real-world effectiveness of adding DOC or ABI to androgen deprivation therapy (ADT).MethodsWe conducted a retrospective analysis of 121 mCSPC patients treated at Odette Cancer Centre (Toronto, ON, Canada) between Dec 2014 and Mar 2021 (DOC n = 79, ABI n = 42). The primary endpoint studied was progression free survival (PFS), defined as the interval from start of ADT to either (i) biochemical, radiological, or symptomatic progression, (ii) start of first-line systemic therapy for castration-resistant prostate cancer (CRPC), or (iii) death, whichever occurred first. To identify independent predictive factors for PFS in the entire cohort, a Cox proportional hazard model (stepwise selection) was applied. Overall survival (OS) was among secondary endpoints.ResultsAfter a median follow-up of 39.6 and 25.1 months in the DOC and ABI cohorts, respectively, 79.7% of men in the DOC and 40.5% in the ABI group experienced a progression event. PFS favored the ABI cohort (p = 0.0038, log-rank test), with 78.0% (95%CI 66.4–91.8%) of ABI versus 67.1% (57.5–78.3%) of DOC patients being free of progression at 12 months. In univariate analysis superior PFS was significantly related to older age at diagnosis of mCSPC, metachronous metastatic presentation, low-volume (CHAARTED), and low-risk (LATITUDE) disease, ≥90% PSA decrease at 3 months (PSA90), and PSA nadir ≤0.2 at 6 months. Age (HR = 0.955), PSA90 (HR = 0.462), and LATITUDE risk stratification (HR = 1.965) remained significantly associated with PFS in multivariable analysis. OS at 12 months was 98.7% (96.3–100%) and 92.7% (85.0–100%) in the DOC and ABI groups (p = 0.97), respectively.ConclusionsIn this real-world group of men undergoing treatment intensification with DOC or ABI for mCSPC, we did not find a significant difference in OS, but PFS was favoring ABI. Age at diagnosis of mCSPC, PSA90 at 3 months and LATITUDE risk classification are predictive factors of PFS in men with mCSPC.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17582-e17582
Author(s):  
Daniel Herrero Rivera ◽  
Ignacio Duran ◽  
Laura Marcos Kovandzic ◽  
Javier Puente ◽  
Begona Mellado ◽  
...  

e17582 Background: Cabazitaxel is a semi-synthetic derivative of a natural taxoid approved for the treatment of mCRPC patients (pts) after failure to docetaxel. Despite its proven efficacy, there is variability in the response, progression-free survival (PFS) and overall survival (OS) of pts. Changes in the genetic constitution of the individual such as the SNPs could explain this variability. The aim of this study was to evaluate the impact of certain SNPs in cabazitaxel activity. Methods: Clinical data from 67 mCRPC pts treated with cabazitaxel between March 2011 and October 2016 were collected. DNA was isolated from formalin fixed paraffin-embedded tumor samples. 56 SNPs in 5 genes related with metabolism and/or mechanism of action of cabazitaxel (CYP3A4, CYP3A5, ABCB1, TUBB1, CYP2C8) were chosen based on their Minor Allele Frequency, linkage disequilibrium and information from dbSNP and analyzed by TaqMan OpenArray (Lifetech). The presence/absence of mutant alleles of the selected SNPs was correlated with clinical features, progression free survival (PFS) and overall survival (OS) of prostate cancer. Chi-square test and Kaplan-Meier with log-rank test were used for statistical analyses. Results: The median age was 61 years (range 44-82). 56.7% (n = 38) had a Gleason score ≥8 and 94% had received docetaxel in first line. Type of response to cabazitaxel was associated with median OS (Partial response = 24.35 months, Stable disease = 11.16 months, Progression disease = 5.8 months; p= 0.045). Univariate analysis, showed worsed OS at 1 year for wild type status of SNP rs151352 (OR = 4, 95%CI 1.27-12.58, p= 0.029). In addition, two SNPs (rs11773597, rs1202186) were associated with radiological response to cabazitaxel ( p= 0.031 and p= 0.030 respectively). Other 7 SNPs (rs11773597, rs2235040, rs1045642, rs1419745, rs1202170, rs6949448, rs11572093) were associated ( p<0.05) with Gleason score, pain, PSA doubling time, febrile neutropenia and asthenia. Conclusions: A particular SNP profile could be predictive of efficacy and related with toxicity in mCRPC population treated with cabazitaxel after progression to docetaxel. These outcomes become particularly relevant in patient selection given the recent results of the CARD trial.


2021 ◽  
Vol 38 (6) ◽  
Author(s):  
Luca Triggiani ◽  
Rosario Mazzola ◽  
Davide Tomasini ◽  
Alessio Bruni ◽  
Giulia Alicino ◽  
...  

AbstractThe aim of the present study was to explore the potential impact of upfront metastases-directed therapy (MDT) in terms of prolongation of castration-sensitive phase in a series of oligorecurrent castration-sensitive prostate cancer (PC) patients. The present article is a multicenter retrospective study. The population of interest was castrate-sensitive oligorecurrent PC, defined as the presence of 1–3 uptakes in non-visceral sites such as bones or nodes detected by means of 18F-Choline PET/CT or 68-Gallium PSMA PET/CT. Primary endpoint was the time to castration resistance. Secondary endpoints were ADT-free survival, local progression-free survival, and overall survival. Eighty-two patients and 118 lesions were analyzed. The median time to castration resistance for the entire population of the study was 49 months (95% CI 43.6–54.4 months). The 1- and 2-year TTCR-free survival rates were 94% and 82%, respectively. At the time of analysis, 52 patients were still in the castration-sensitive phase of the disease. In this cohort of patients, the median ADT-free survival was 20 months (range 3–69 months). On the other hand, during follow-up 30 patients switched to the castration-resistant phase of disease. In this last group of patients, the median ADT-free survival was 20 months (range 4–50 months). After the ADT administration, the median castration-sensitive phase was 29 months (range 5–71 months). Castration resistance generally occurs at a median follow-up of 24–36 months following ADT. In the current study, upfront MDT does not decrease the time from initiation of ADT to castration resistance.


Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1099
Author(s):  
Fadi Khreish ◽  
Mona Wiessner ◽  
Florian Rosar ◽  
Zaidoon Ghazal ◽  
Amir Sabet ◽  
...  

At present, little is known about the molecular imaging-based response assessment of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy with 177Lutetium (177Lu-PSMA-617 RLT) in metastatic castration-resistant prostate cancer (mCRPC). Our study evaluated the response to RLT using both molecular imaging and biochemical response assessments, and their potential prediction of progression-free survival (PFS). Fifty-one consecutive patients given two cycles of RLT at 6-week intervals were analyzed retrospectively. 68Ga-PSMA-11 PET/CT was obtained about 2 weeks prior to the first and 4–6 weeks after the second cycle. Molecular imaging-based response using SUVpeak and tumor-to-liver ratio (TLR) was determined by modified PERCIST criteria. ∆TLR and ∆SUV were significantly correlated with ∆PSA (p < 0.001, each). After a median follow-up of 49 months, the median PFS (95% CI) was 8.0 (5.9–10.1) months. In univariate analysis, responders showing partial remission (PRPSA and PRTLR) had significantly (p < 0.001, each) longer PFS (median: 10.5 and 9.3 months) than non-responders showing either stable or progressive disease (median: 4.0 and 3.5 months). Response assessment using SUVpeak failed to predict survival. In multivariable analysis, response assessment using TLR was independently associated with PFS (p < 0.001), as was good performance status (p = 0.002). Molecular imaging-based response assessment with 68Ga-PSMA-11 PET/CT using normalization of the total lesion PSMA over healthy liver tissue uptake (TLR) could be an appropriate biomarker to monitor RLT in mCRPC patients and to predict progression-free survival (PFS) of this treatment modality.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ana María García Vicente ◽  
Mariano Amo-Salas ◽  
Javier Cassinello Espinosa ◽  
Roberto Gómez Díaz ◽  
Ángel Soriano Castrejón

AbstractTo assess the predictive and prognostic aim of interim and end-treatment 18F-fluorocholine PET/CT (FCH-PET/CT) and 99mTc-methilen diphosphonate bone scintigraphy (BS) in patients with castration-resistant prostate cancer and bone metastases (CRPC-BM) treated with Radium 223 dichloride (223Ra). Prospective and multicentre ChoPET-Rad study including 82 patients with CRPC-BM. Baseline, after 3 (interim) and 6 doses (end-treatment) BS and FCH PET/CT were performed in patients who meet the study criteria. Clinical variables, imaging and clinical progression were obtained and their association with progression free survival (PFS), and overall survival (OS) was studied. Agreement between BS and FCH PET/CT response was assessed using Kappa (K) analysis. Median of PFS and OS was 3 and 16 months, respectively. Agreement between interim BS and FCH PET/CT was weak (K: 0.28; p = 0.004). No agreement was observed between end-treatment diagnostic studies. Interim and end-treatment FCH PET/CT were related to PFS (p = 0.011 and p < 0.001, respectively). Therapeutic failure and interim BS and FCH PET/CT showed association with OS (p < 0.001, p = 0.037 and p = 0.008, respectively). Interim and end-treatment FCH PET/CT were good predictors of biochemical progression in patients treated with 223Ra. Therapeutic failure and progression in interim BS or FCH PET/CT were adverse factors for OS.


2019 ◽  
Vol 8 (8) ◽  
pp. 1169 ◽  
Author(s):  
Jeong Won Lee ◽  
Myung Jin Ban ◽  
Jae Hong Park ◽  
Sang Mi Lee

The purpose of this study was to assess the relationship between F-18 fluorodeoxyglucose (FDG) uptake in bone marrow (BM) on positron emission tomography/computed tomography (PET/CT) and survival in patients with head and neck squamous cell carcinoma (HNSCC). We retrospectively enrolled 157 HNSCC patients who underwent staging FDG PET/CT and subsequent treatment. On PET/CT, primary tumor metabolic characteristics, mean FDG uptake of BM (BM SUV), and BM-to-liver uptake ratio (BLR) were measured. The prognostic significance of FDG uptake of BM for predicting disease progression-free survival and distant failure-free survival was assessed using a Cox proportional hazards regression model. In univariate analysis for disease progression-free survival, increased BM SUV and BLR were associated with poor survival. In multivariate analysis, BLR (p = 0.044; hazard ratio, 1.96), TNM stage (p = 0.014; hazard ratio, 2.87) and maximum FDG uptake of the primary tumor (p = 0.046; hazard ratio, 2.38) were independently associated with disease progression-free survival. For distant failure-free survival, BLR, TNM stage, tumor size, and metabolic parameters of the primary tumor showed prognostic significance in univariate analysis. However, none of the variables showed significance in multivariate analysis. FDG uptake of BM in HNSCC patients might be a significant predictor for disease progression-free survival. Further studies with large patient population are needed to validate the results.


2021 ◽  
Author(s):  
Ana Maria Garcia Vicente ◽  
Mariano Amo-Salas ◽  
Javier Cassinello Espinosa ◽  
Roberto Gomez Diaz ◽  
Angel Soriano Castrejon

Abstract AimTo assess the predictive and prognostic aim of interim and end-treatment 18F-fluorocholine PET/CT (FCH-PET/CT) and 99mTc-methilen diphosphonate bone scintigraphy (BS) in patients with castration-resistant prostate cancer and bone metastases (CRPC-BM) treated with Radium 223 dichloride (223Ra). Methods: Prospective and multicentre ChoPET-Rad study including 82 patients with CRPC-BM. Baseline, after 3 (interim) and 6 doses (end-treatment) BS and FCH PET/CT were performed in patients who meet the study criteria. Clinical variables, imaging and clinical progression were obtained and their association with progression free survival (PFS), and overall survival (OS) was studied. Agreement between BS and FCH PET/CT response was assessed using Kappa (K) analysis.Results:Median of PFS and OS was 3 and 16 months, respectively. Agreement between interim BS and FCH PET/CT was weak (K: 0.28; p=0.004). No agreement was observed between end-treatment diagnostic studiesInterim and end-treatment FCH PET/CT were related to PFS (p=0.011 and p<0.001, respectively). Therapeutic failure and interim BS and FCH PET/CT showed association with OS (p<0.001, p=0.037 and p=0.008, respectively).Conclusions: Interim and end-treatment FCH PET/CT were good predictors of biochemical progression in patients treated with 223Ra. Therapeutic failure and progression in interim BS or FCH PET/CT were adverse factors for OS.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Paul Rogowski ◽  
Christian Trapp ◽  
Rieke von Bestenbostel ◽  
Nina-Sophie Schmidt-Hegemann ◽  
Run Shi ◽  
...  

Abstract Background The aim of this work was to investigate the outcome of metastasis-directed radiotherapy (MDT) in prostate cancer patients with bone metastases following current ESTRO/EORTC subclassifications for oligometastatic disease. Methods Clinical data of 80 consecutive oligometastatic patients with 115 bone lesions receiving MDT between 2011 and 2019 were retrospectively evaluated. Hormone-sensitive (77.5%) and castrate-resistant (22.5%) patients were included. MDT was delivered with conventional fractionated or stereotactic body radiotherapy (SBRT) techniques. Kaplan–Meier method, log rank test, as well as Cox regression were used to calculate local control (LC) and biochemical and clinical progression-free survival (bPFS/cPFS). Results At the time of MDT 31% of patients had de-novo synchronous oligometastatic disease, 46% had de-novo metachronous oligorecurrence after primary treatment and 23% had either de-novo oligoprogressive disease, repeat oligometastatic disease or induced oligometastatic disease. The median BED3 was 93.3 Gy (range 75.8–95.3 Gy). Concomitant ADT was administered in 69% of patients. After a median follow-up of 23 months the median bPFS and cPFS were 16.5 and 21.5 months, respectively. The 2-year LC rate was 98.3%. In multivariate analysis, age ≤ 70 (HR = 2.60, 95% CI 1.20–5.62, p = 0.015) and concomitant ADT (HR = 0.26, 95% CI 0.12–0.58, p = 0.001) significantly correlated with cPFS. Category of oligometastatic disease and hormone-sensitivity were predictive for cPFS in univariate analysis. Of 45 patients with biochemical relapse, nineteen patients (42.2%) had repeat oligometastatic disease. Fourteen patients (31%) underwent a second course of MDT. No patients experienced grade ≥ 3 toxicities. Conclusions MDT is safe and offers high local control rates in bone oligometastases of prostate cancer. At 2 years after treatment, more than 2 out of 5 patients are progression-free. Trial registration Retrospectively registered.


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