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  • Springer Science and Business Media LLC  (3)
  • 2020-2024  (3)
  • 1
    In: Journal of Translational Medicine, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2023-02-03)
    Abstract: Metastatic castration-resistant prostate cancer remains a challenging condition to treat. Among the available therapeutic options, the androgen receptor signaling inhibitors abiraterone acetate plus prednisone (AA) and enzalutamide (Enza), are currently the most used first-line therapies in clinical practice. However, validated clinical indicators of prognosis in this setting are still lacking. In this study, we aimed to evaluate a prognostic model based on the time of metastatic disease presentation (after prior local therapy [PLT] or de-novo [DN] ) and disease burden (low volume [LV] or high-volume [HV] ) at AA/Enza onset for mCRPC patients receiving either AA or Enza as first-line. Methods A cohort of consecutive patients who started AA or Enza as first-line treatment for mCRPC between January 1st, 2015, and April 1st, 2019 was identified from the clinical and electronic registries of the 9 American and European participating centers. Patients were classified into 4 cohorts by the time of metastatic disease presentation (PLT or DN) and volume of disease (LV or HV; per the E3805 trial, HV was defined as the presence of visceral metastases and/or at least 4 bone metastases of which at least 1 out the axial/pelvic skeleton) at AA/Enza onset. The endpoint was overall survival defined as the time from AA or Enza initiation, respectively, to death from any cause or censored at the last follow-up visit, whichever occurred first. Results Of the 417 eligible patients identified, 157 (37.6%) had LV/PLT, 87 (20.9%) LV/DN, 64 (15.3%) HV/PLT, and 109 (26.1%) HV/DN. LV cohorts showed improved median overall survival (59.0 months; 95% CI, 51.0–66.9 months) vs. HV cohorts (27.5 months; 95% CI, 22.8–32.2 months; P = 0.0001), regardless of the time of metastatic presentation. In multivariate analysis, HV cohorts were confirmed associated with worse prognosis compared to those with LV (HV/PLT, HR = 1.87; p = 0.029; HV/DN, HR = 2.19; P = 0.002). Conclusion Our analysis suggests that the volume of disease could be a prognostic factor for patients starting AA or Enza as first-line treatment for metastatic castration-resistant prostate cancer, pending prospective clinical trial validation.
    Type of Medium: Online Resource
    ISSN: 1479-5876
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2118570-0
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  • 2
    In: Cancer Immunology, Immunotherapy, Springer Science and Business Media LLC, Vol. 70, No. 12 ( 2021-12), p. 3679-3692
    Abstract: Debate is around the optimal immunization regimen for cancer vaccines since too intense vaccination schedules may exhaust reactive lymphocytes. GX301 is a telomerase-based cancer vaccine whose safety and immunological effects were tested in a phase I trial applying an eight administrations schedule. Main objective of this study was to comparatively analyse safety and immunological response to three GX301 regimens in metastatic castration-resistant prostate cancer patients with response/disease stability after docetaxel chemotherapy. This was a multicentre, randomized, parallel-group, open-label trial registered with EudraCT (2014-000095-26) and ClinicalTrials.gov (NCT02293707, 2014). Ninety-eight patients were randomized to receive either eight (regimen 1), four (regimen 2) or two (regimen 3) vaccine administrations. Sixty-three patients were assessable for the primary immunological end-point. Vaccine-specific immune responses were evaluated by intracellular staining for IFN, elispot and cytotoxic assay at 90 and 180 days from baseline. No major side effects were recorded. A 54% overall immune responder rate was observed with 95% of patients showing at least one vaccine-specific immune response. Rate of immunological responders and number of immunizations were proportionally related, suggesting superiority of regimens 1 and 2 over regimen 3. Overall survival did not differ among regimens in both immunological responders and non-responders and was inversely associated ( P  = 0.002) with increase in the number of circulating CD8 + T regulatory cells at 180 days. These data indicate that GX301 cancer vaccine is safe and immunogenic in metastatic castration-resistant prostate cancer patients. Schedules with high number of administrations should be preferred in future studies due to their better immunological outcome.
    Type of Medium: Online Resource
    ISSN: 0340-7004 , 1432-0851
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 1458489-X
    detail.hit.zdb_id: 195342-4
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  • 3
    In: Annals of Nuclear Medicine, Springer Science and Business Media LLC, Vol. 36, No. 4 ( 2022-04), p. 373-383
    Abstract: Androgen deprivation therapy alters body composition promoting a significant loss in skeletal muscle (SM) mass through inflammation and oxidative damage. We verified whether SM anthropometric composition and metabolism are associated with unfavourable overall survival (OS) in a retrospective cohort of metastatic castration-resistant prostate cancer (mCRPC) patients submitted to 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG PET/CT) imaging before receiving Radium-223. Patients and methods Low-dose CT were opportunistically analysed using a cross-sectional approach to calculate SM and adipose tissue areas at the third lumbar vertebra level. Moreover, a 3D computational method was used to extract psoas muscles to evaluate their volume, Hounsfield Units (HU) and FDG retention estimated by the standardized uptake value (SUV). Baseline established clinical, lab and imaging prognosticators were also recorded. Results SM area predicted OS at univariate analysis. However, this capability was not additive to the power of mean HU and maximum SUV of psoas muscles volume. These factors were thus combined in the Attenuation Metabolic Index (AMI) whose power was tested in a novel uni- and multivariable model. While Prostate-Specific Antigen (PSA), Alkaline Phosphatase (ALP), Lactate Dehydrogenase and Hemoglobin, Metabolic Tumor Volume, Total Lesion Glycolysis and AMI were associated with long-term OS at the univariate analyses, only PSA, ALP and AMI resulted in independent prognosticator at the multivariate analysis. Conclusion The present data suggest that assessing individual 'patients' SM metrics through an opportunistic operator-independent computational analysis of FDG PET/CT imaging provides prognostic insights in mCRPC patients candidates to receive Radium-223. Graphical abstract
    Type of Medium: Online Resource
    ISSN: 0914-7187 , 1864-6433
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2039738-0
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