RESUMO
Advanced prostate cancer (aPC) in Black men was reported to present with aggressive features and to be associated with poor prognosis. Herein, we compared the cell-free DNA (cfDNA) genomic landscape of aPC in Black vs White men. Patients (pts) with aPC from 6 academic institutions and available cfDNA comprehensive genomic profiling (CGP) were included. Association between mutated genes and race was evaluated using Barnard's test and a Probabilistic Graphical Model (PGM) machine learning approach. Analysis included 743 aPC pts (217 Black, 526 White) with available cfDNA CGP. The frequency of alterations in the androgen receptor gene was significantly higher in Black vs White men (55.3% vs 35% respectively, P < .001). Additionally, alterations in EGFR, MYC, FGFR1, and CTNNB1 were present at higher frequencies in Black men. PGM analysis and Barnard's test were concordant. Findings from the largest cohort of Black men with aPC undergoing cfDNA CGP may guide further drug development in these men.
Assuntos
Ácidos Nucleicos Livres , Neoplasias da Próstata , Ácidos Nucleicos Livres/genética , Receptores ErbB , Genômica , Humanos , Masculino , Neoplasias da Próstata/genética , Receptores Androgênicos/genéticaRESUMO
PURPOSE: Prostate cancer is a heterogeneous disease with variable clinical outcomes. Despite numerous recent approvals of novel therapies, castration-resistant prostate cancer remains lethal. A "real-world" clinical-genomic database is urgently needed to enhance our characterization of advanced prostate cancer and further enable precision oncology. METHODS: The Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort (PROMISE) is a consortium whose aims are to establish a repository of de-identified clinical and genomic patient data that are linked to patient outcomes. The consortium structure includes a (1) bio-informatics committee to standardize genomic data and provide quality control, (2) biostatistics committee to independently perform statistical analyses, (3) executive committee to review and select proposals of relevant questions for the consortium to address, (4) diversity/inclusion committee to address important clinical questions pertaining to racial disparities, and (5) patient advocacy committee to understand patient perspectives to improve patients' quality of care. RESULTS: The PROMISE consortium was formed by 16 academic institutions in early 2020 and a secure RedCap database was created. The first patient record was entered into the database in April 2020 and over 1000 records have been entered as of early 2021. Data entry is proceeding as planned with the goal to have over 2500 patient records by the end of 2021. CONCLUSIONS: The PROMISE consortium provides a powerful clinical-genomic platform to interrogate and address data gaps that have arisen with increased genomic testing in the clinical management of prostate cancer. The dataset incorporates data from patient populations that are often underrepresented in clinical trials, generates new hypotheses to direct further research, and addresses important clinical questions that are otherwise difficult to investigate in prospective studies.
Assuntos
Neoplasias da Próstata , Genômica , Humanos , Masculino , Oncologia , Medicina de Precisão , Estudos Prospectivos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapiaRESUMO
BACKGROUND/AIM: To describe clinical features, radiotherapy (RT), and symptom outcomes in cancer patients with cranial nerve palsies associated with clival metastases. PATIENTS AND METHODS: This is a retrospective review of patients with primary metastatic cancers who developed clival metastases and received RT (2000-2020). RESULTS: Of the 44 patients with primary cancers (manly breast, prostate and multiple myeloma cancers) and distal clival metastases, 32 patients (73%) also had cervical spine metastases. Of the 23 RT-treated patients, 65% and 35% received clivus only and whole brain RT, respectively. Post-RT symptom improvement was observed in patients with diplopia (5/6; 83%), headache (8/10; 80%), chin numbness (2/4; 50%), blurry vision (2/5; 40%), lateral gaze deficit (2/6; 33%), and tongue deviation (1/4; 25%). CONCLUSION: Early detection and cranial nerve examination, in addition to RT treatment, should be considered in patients with breast, prostate, and multiple myeloma cancers, who developed cervical spine metastases.