Serial [F-18]-FDHT-PET to predict bicalutamide efficacy in patients with androgen receptor positive metastatic breast cancer

Background: The androgen receptor (AR) is a potential target in metastatic breast cancer (MBC), and 16 beta-[F-18]-fluoro-5 alpha-dihydrotestosterone positron emission tomography ([F-18]-FDHT-PET) can be used for noninvasive visualisation of AR. [F-18]-FDHT uptake reduction during AR-targeting therapy reflects AR occupancy and might be predictive for treatment response. We assessed the feasibility of [F-18]-FDHT-PET to detect changes in AR availability during bicalutamide treatment and correlated these changes with treatment response. Patients and methods: Patients with AR thorn MBC, regardless of oestrogen receptor status, received an [F-18]-FDHT-PET at baseline and after 4-6 weeks bicalutamide treatment. Baseline [F-18]-FDHT uptake was expressed as maximum standardised uptake value. Percentage change in tracer uptake, corrected for background activity (SUVcor), between baseline and follow-up PET scan (% reduction), was assessed per-patient and lesion. Clinical benefit was determined in accordance with Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 or clinical evaluation (absence of disease progression for >= 24 weeks). Results: Baseline [F-18]-FDHT-PET in 21 patients detected 341 of 515 lesions found with standard imaging and 21 new lesions. Follow-up [F-18]-FDHT- PET was evaluable in 17 patients with 349 lesions, showing a decrease in median SUVcor from 1.3 to 0.7 per-patient and lesion (P <0.001). Median % reduction per-patient was - 45% and per-lesion -39%. In patients with progressive disease (n Z 11), median % reduction was -30% versus -53% for patients who showed clinical benefit (in accordance with RECIST (n = 3) or clinical evaluation (n = 3); P Z 0.338). Conclusion: In this feasibility study, a bicalutamide-induced reduction in [F-18]-FDHT uptake could be detected by follow-up [F-18]-FDHT-PET in patients with AR thorn MBC. However, this change could not predict bicalutamide response. (C) 2020 The Authors. Published by Elsevier Ltd

The Impact of Age on Outcome of Embryonal and Alveolar Rhabdomyosarcoma Patients.:A Multicenter Study

Background: The prognosis of rhabdomyosarcoma (RMS) in children and adolescents has improved since the introduction of multi-agent chemotherapy. However, outcome data of adults with RMS are scarce. This multicenter retrospective study investigated the effect of age on outcome of RMS. Patients and Methods: Data were collected from three Dutch University Medical Centers between 1977-2009. The effect of age and clinical prognostic factors on relapse-free and disease-specific survival (DSS) were analyzed. Results: Age as a continuous variable predicted poor survival in multivariate analysis. Five-year DSS was highest for non-metastatic embryonal RMS, followed by non-metastatic alveolar RMS and was poor in metastatic disease. Higher age correlated with unfavorable histological subtype (alveolar RMS) and with metastatic disease at presentation in embryonal RMS. In non-metastatic embryonal RMS and in all alveolar RMS, higher age was an adverse prognostic factor of outcome. Conclusion: This study indicates that age is a negative predictor of survival in patients with embryonal and alveolar RMS

New insights in tailored treatment of gastrointestinal stromal tumours

Gastrointestinal strornal tumours (GISTs) are mesenchymal neoplasms that arise in the wall of the gastrointestinal tract. GISTs represent a continuum trom incidentally discoverd srnall modules with a benign or extremely low malignant potential to large to large highly malignant sarcomas. Characteristically, virtually all GISTS (>95 percent) overexpress the receptor tyrosine kinase and proto-oncogene KIT, which is used as an immunophenotypical marker for the diagnosis ot GIST. Moreover, oncogenic mutations that eiffect KIT or, much less often, the closely related platelet-derived growth factor receptor a (PDGFRA), have been detected in 85-90 percent of GISTs. These mutations result in ligand-independent, constitutive activation of these receptors leading to activation of cellular signal transduction cascades involved in cellular proliferation and survival. KIT and PDGFRA mutations are mutually exclusive and play fundamentalrole in the development of GIST. The tyrosine kinase inhibitor imatinib blocks the activity of KIT and PDGFRA. It has become the standard first-line treatment of patients with unresectable or metastasized GIST. Imatinib therapy resillts in high objective response and disease stabilisation rates but none of the patients are cured with this compound. The same holds t rue for second-line treatment with sunitinib , a tyrosine kinase inhibitor of KIT, PDGFR but also vascular endothelial growth factor (VEGFR) and FMS-like tyrosine kinase 3 (FLT3), of which clinical benefit, i.e. response and disease stabilisation, has been described but which is effective just as imatinib for a limited periocl of time. Therefore, new therapeutic strategies need to be developed.

The Impact of Age on Outcome of Embryonal and Alveolar Rhabdomyosarcoma Patients.: A Multicenter Study

Background: The prognosis of rhabdomyosarcoma (RMS) in children and adolescents has improved since the introduction of multi-agent chemotherapy. However, outcome data of adults with RMS are scarce. This multicenter retrospective study investigated the effect of age on outcome of RMS. Patients and Methods: Data were collected from three Dutch University Medical Centers between 1977-2009. The effect of age and clinical prognostic factors on relapse-free and disease-specific survival (DSS) were analyzed. Results: Age as a continuous variable predicted poor survival in multivariate analysis. Five-year DSS was highest for non-metastatic embryonal RMS, followed by non-metastatic alveolar RMS and was poor in metastatic disease. Higher age correlated with unfavorable histological subtype (alveolar RMS) and with metastatic disease at presentation in embryonal RMS. In non-metastatic embryonal RMS and in all alveolar RMS, higher age was an adverse prognostic factor of outcome. Conclusion: This study indicates that age is a negative predictor of survival in patients with embryonal and alveolar RMS