Quantitative total bone imaging (QTBI) in patients with metastatic castration-resistant prostate cancer (CRPC) using NaF PET/CT.

180 Background: CRPC is frequently associated with the development of osseous metastases. While imaging allows treatment response determination in soft tissue metastasis, its application in bony metastasis is limited to staging. Methods: QTBI is an innovative tool that allows extraction of comprehensive functional information in all osseous metastases, as well as treatment response in individual lesions, using 18F-Sodium Fluoride (NaF) PET/CT. We completed a multi-center trial assessing the performance characteristics (test-retest) and responsiveness of QTBI as an imaging biomarker of treatment response in men with metastatic CRPC to bone treated with either a taxane-based or androgen-signaling pathway directed therapy. Results: 54 patients have been enrolled from three academic centers. Potential imaging biomarkers of treatment response have been identified. Here we present initial data regarding the inter-lesional response heterogeneity and implications. Conclusions: Changes in SUVmax, SUVtotal, and SUVmean reflect quantifiable PET measurements that are complementary, but may have different meaning depending on the treatment administered (cytotoxic vs cytostatic). Relying on one measure alone can be misleading, particularly when assessing treatment response. For example, some lesions may experience a decrease in SUVmax, while simultaneously having an increase in SUVtotal. This implies that the therapy decreased the max functional activity of the lesion, but the overall functional burden of the lesion increased analogous to “slowing down” progression. This is in contrast with lesions that decrease (increase) in both SUVmax and SUVtotal, which would imply decreased activity and burden (increased activity and burden). We will show data representative of the above along with clinical outcomes in support of this conclusion, as well as the implications of treatment response heterogeneity in the clinical outcome. In summary, QTBI provides a unique tool in understanding the dynamics of treatment response, allowing newer trial designs that can explore combination, sequence, and the issue of continuing treatment beyond progression with existing therapies. Clinical trial information: NCT01516866.

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Comparison of NaF and FDG PET/CT for Assessment of Treatment Response in Castration-Resistant Prostate Cancers With Osseous Metastases

Clinical Genitourinary Cancer ◽

10.1016/j.clgc.2014.07.001 ◽

2015 ◽

Vol 13 (1) ◽

pp. e7-e17 ◽

Cited By ~ 18

Author(s):

Urban Simoncic ◽

Scott Perlman ◽

Glenn Liu ◽

Mary Jane Staab ◽

Jane Elizabeth Straus ◽

...

Keyword(s):

Treatment Response ◽

Fdg Pet ◽

Castration Resistant ◽

Osseous Metastases ◽

Pet Ct ◽

Prostate Cancers ◽

Fdg Pet Ct

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Exploring Spatial-Temporal Changes in 18F-Sodium Fluoride PET/CT and Circulating Tumor Cells in Metastatic Castration-Resistant Prostate Cancer Treated With Enzalutamide

Journal of Clinical Oncology ◽

10.1200/jco.20.00348 ◽

2020 ◽

Vol 38 (31) ◽

pp. 3662-3671

Author(s):

Christos E. Kyriakopoulos ◽

Elisabeth I. Heath ◽

Anna Ferrari ◽

Jamie M. Sperger ◽

Anupama Singh ◽

...

Keyword(s):

Prostate Cancer ◽

Treatment Response ◽

Bone Lesion ◽

Specific Antigen ◽

Standardized Uptake Value ◽

Ct Scans ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Pet Ct ◽

Psa Progression

PURPOSE Intrapatient treatment response heterogeneity is under-recognized. Quantitative total bone imaging (QTBI) using 18F-NaF positron emission tomography/computed tomography (PET/CT) scans is a tool that allows characterization of interlesional treatment response heterogeneity in bone. Understanding spatial-temporal response is important to identify individuals who may benefit from treatment beyond progression. PATIENTS AND METHODS Men with progressive metastatic castration-resistant prostate cancer (mCRPC) with at least two lesions on bone scintigraphy were enrolled and treated with enzalutamide 160 mg daily (ClinicalTrials.gov identifier: NCT02384382 ). 18F-NaF PET/CT scans were obtained at baseline (PET1), week 13 (PET2), and at the time of prostate-specific antigen (PSA) progression, standard radiographic or clinical progression, or at 2 years without progression (PET3). QTBI was used to determine lesion-level response. The primary end point was the proportion of men with at least one responding bone lesion on PET3 using QTBI. RESULTS Twenty-three men were enrolled. Duration on treatment ranged from 1.4 to 34.1 months. In general, global standardized uptake value (SUV) metrics decreased while on enzalutamide (PET2) and increased at the time of progression (PET3). The most robust predictor of PSA progression was change in SUVhetero (PET1 to PET3; hazard ratio, 3.88; 95% CI, 1.24 to 12.1). Although overall functional disease burden improved during enzalutamide treatment, an increase in total burden (SUVtotal) was seen at the time of progression, as measured by 18F-NaF PET/CT. All (22/22) evaluable men had at least one responding bone lesion at PET3 using QTBI. CONCLUSION We found that the proportion of progressing lesions was low, indicating that a substantial number of lesions appear to continue to benefit from enzalutamide beyond progression. Selective targeting of nonresponding lesions may be a reasonable approach to extend benefit.

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Assessment of the viability and treatment response of bone metastases in patients with metastatic castration-resistant prostate cancer using choline PET/CT

Medicine ◽

10.1097/md.0000000000026206 ◽

2021 ◽

Vol 100 (23) ◽

pp. e26206

Author(s):

Kazuhiro Kitajima ◽

Shingo Yamamoto ◽

Yusuke Kawanaka ◽

Hisashi Komoto ◽

Kimihiro Shimatani ◽

...

Keyword(s):

Prostate Cancer ◽

Bone Metastases ◽

Treatment Response ◽

Castration Resistant Prostate Cancer ◽

Choline Pet ◽

Castration Resistant ◽

Pet Ct

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The prognostic power of 18F-FDG PET/CT extends to estimating systemic treatment response duration in metastatic castration-resistant prostate cancer (mCRPC) patients

Prostate Cancer and Prostatic Diseases ◽

10.1038/s41391-021-00391-8 ◽

2021 ◽

Author(s):

Matteo Bauckneht ◽

Francesco Bertagna ◽

Maria Isabella Donegani ◽

Rexhep Durmo ◽

Alberto Miceli ◽

...

Keyword(s):

Prostate Cancer ◽

Treatment Response ◽

Fdg Pet ◽

Prognostic Value ◽

Systemic Treatment ◽

Response Duration ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Pet Ct ◽

Fdg Pet Ct

Abstract Background We aimed to test whether the prognostic value of 18 F‐Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT) in metastatic castration-resistant prostate cancer (mCRPC) extends to the estimation of systemic treatment response duration. Methods mCRPC patients submitted to FDG-PET/CT in four Italian centers from 2005 to 2020 were retrospectively enrolled. Clinical and biochemical data at the time of imaging were collected, and SUV max of the hottest lesion, total metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were calculated. The correlation between PET- and biochemical-derived parameters with Overall Survival (OS) was analysed. The prediction of treatment response duration was assessed in the subgroup submitted to FDG-PET/CT in the six months preceding Chemotherapy (namely Docetaxel or Cabazitaxel, 24 patients) or Androgen-Receptor Targeted Agents (ARTA, namely Abiraterone or Enzalutamide, 20 patients) administration. Results We enrolled 114 mCRPC patients followed-up for a median interval lasting 15 months. While at univariate analysis, prostate-specific antigen (PSA), Alkaline Phosphatase (ALP), MTV, and TLG were associated with OS, at the multivariate Cox regression analysis, the sole MTV could independently predict OS (p < 0.0001). In the subgroup submitted to FDG-PET/CT before the systemic treatment initiation, PSA and TLG could also predict treatment response duration independently (p < 0.05). Of note, while PSA could not indicate the best treatment choice, lower TLG was associated with higher success rates for ARTA but had no impact on chemotherapy efficacy. Conclusions FDG-PET/CT’s prognostic value extends to predicting treatment response duration in mCRPC, thus potentially guiding the systemic treatment selection.

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Neuroendocrine secretory profiles are not associated with treatment response to Lu-177-PSMA-617 radioligand therapy in patients with advanced metastatic castration-resistant prostate cancer

10.1055/s-0040-1708342 ◽

2020 ◽

Author(s):

T Derlin ◽

R Werner ◽

C Henkenberens ◽

TL Ross ◽

FM Bengel

Keyword(s):

Prostate Cancer ◽

Treatment Response ◽

Castration Resistant Prostate Cancer ◽

Radioligand Therapy ◽

Castration Resistant

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Comparison of pretherapeutic osseous tumor volume and standard hematology for prediction of hematotoxicity after PSMA-targeted radioligand therapy

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-021-05412-1 ◽

2021 ◽

Author(s):

Liam Widjaja ◽

Rudolf A. Werner ◽

Tobias L. Ross ◽

Frank M. Bengel ◽

Thorsten Derlin

Keyword(s):

Multivariate Analysis ◽

Tumor Volume ◽

Predictive Performance ◽

Castration Resistant Prostate Cancer ◽

Operating Characteristics ◽

Predictive Capability ◽

Radioligand Therapy ◽

Castration Resistant ◽

Pet Ct ◽

Late Stages

Abstract Purpose Hematotoxicity is a potentially dose-limiting adverse event in patients with metastasized castration-resistant prostate cancer (mCRPC) undergoing prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT). We aimed to identify clinical or PSMA-targeted imaging-derived parameters to predict hematological adverse events at early and late stages in the treatment course. Methods In 67 patients with mCRPC scheduled for 177Lu-PSMA-617 RLT, pretherapeutic osseous tumor volume (TV) from 68Ga-PSMA-11 PET/CT and laboratory values were assessed. We then tested the predictive capability of these parameters for early and late hematotoxicity (according to CTCAE vers. 5.0) after one cycle of RLT and in a subgroup of 32/67 (47.8%) patients after four cycles of RLT. Results After one cycle, 10/67 (14.9%) patients developed leukocytopenia (lymphocytopenia, 39/67 [58.2%]; thrombocytopenia, 17/67 [25.4%]). A cut-off of 5.6 × 103/mm3 for baseline leukocytes was defined by receiver operating characteristics (ROC) and separated between patients with and without leukocytopenia (P < 0.001). Baseline leukocyte count emerged as a stronger predictive factor in multivariate analysis (hazard ratio [HR], 33.94, P = 0.001) relative to osseous TV (HR, 14.24, P = 0.01). After four cycles, 4/32 (12.5%) developed leukocytopenia and the pretherapeutic leukocyte cut-off (HR, 9.97, P = 0.082) tended to predict leukocytopenia better than TV (HR, 8.37, P = 0.109). In addition, a cut-off of 1.33 × 103/mm3 for baseline lymphocytes separated between patients with and without lymphocytopenia (P < 0.001), which was corroborated in multivariate analysis (HR, 21.39, P < 0.001 vs. TV, HR, 4.57, P = 0.03). After four cycles, 19/32 (59.4%) developed lymphocytopenia and the pretherapeutic cut-off for lymphocytes (HR, 46.76, P = 0.007) also demonstrated superior predictive performance for late lymphocytopenia (TV, HR, 5.15, P = 0.167). Moreover, a cut-off of 206 × 103/mm3 for baseline platelets separated between patients with and without thrombocytopenia (P < 0.001) and also demonstrated superior predictive capability in multivariate analysis (HR, 115.02, P < 0.001 vs.TV, HR, 12.75, P = 0.025). After four cycles, 9/32 (28.1%) developed thrombocytopenia and the pretherapeutic cut-off for platelets (HR, 5.44, P = 0.048) was also superior for the occurrence of late thrombocytopenia (TV, HR, 1.44, P = 0.7). Conclusions Pretherapeutic leukocyte, lymphocyte, and platelet levels themselves are strong predictors for early and late hematotoxicity under PSMA-directed RLT, and are better suited than PET-based osseous TV for this purpose.

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