Treatment Response Assessment According to Updated PROMISE Criteria in Patients with Metastatic Prostate Cancer Using an Automated Imaging Platform for Identification, Measurement, and Temporal Tracking of Disease.

Background And Objective: Prostate-specific membrane antigen (PSMA) molecular imaging is widely used for disease assessment in prostate cancer (PC). Artificial intelligence (AI) platforms such as automated Prostate Cancer Molecular Imaging Standardized Evaluation (aPROMISE) identify and quantify locoregional and distant disease, thereby expediting lesion identification and standardizing reporting. Our aim was to evaluate the ability of the updated aPROMISE platform to assess treatment responses based on integration of the RECIP (Response Evaluation Criteria in PSMA positron emission tomography-computed tomography [PET/CT]) 1.

Molecular Hallmarks of Prostate-specific Membrane Antigen in Treatment-naïve Prostate Cancer.

Background And Objective: We characterized tumor prostate-specific membrane antigen (PSMA) levels as a reflection of cancer biology and treatment sensitivities for treatment-naïve prostate cancer.

Methods: We first correlated PSMA positron emission tomography (PET) maximum standardized uptake values (SUVmax) in primary prostate cancer with tumor FOLH1 (PSMA RNA abundance) to establish RNA as a proxy (n = 55). We then discovered and validated molecular pathways associated with PSMA RNA levels in two large primary tumor cohorts.

Significant changes in macrophage and CD8 T cell densities in primary prostate tumors 2 weeks after SBRT.

Background: Radiotherapy impacts the local immune response to cancers. Prostate Stereotactic Body Radiotherapy (SBRT) is a highly focused method to deliver radiotherapy often used to treat prostate cancer. This is the first direct comparison of immune cells within prostate cancers before and after SBRT in patients.

High-dose per Fraction Radiotherapy Induces Both Antitumor Immunity and Immunosuppressive Responses in Prostate Tumors.

Purpose: The use of high-dose per fraction radiotherapy delivered as stereotactic body radiotherapy is a standard of care for prostate cancer. It is hypothesized that high-dose radiotherapy may enhance or suppress tumor-reactive immunity. The objective of this study was to assess both antitumor and immunosuppressive effects induced by high-dose radiotherapy in prostate cancer coclinical models, and ultimately, to test whether a combination of radiotherapy with targeted immunotherapy can enhance antitumor immunity.

The intraprostatic immune environment after stereotactic body radiotherapy is dominated by myeloid cells.

Background: Hundreds of ongoing clinical trials combine radiation therapy, mostly delivered as stereotactic body radiotherapy (SBRT), with immune checkpoint blockade. However, our understanding of the effect of radiotherapy on the intratumoral immune balance is inadequate, hindering the optimal design of trials that combine radiation therapy with immunotherapy. Our objective was to characterize the intratumoral immune balance of the malignant prostate after SBRT in patients.

Phase 1 Trial of Stereotactic Body Radiation Therapy Neoadjuvant to Radical Prostatectomy for Patients With High-Risk Prostate Cancer.

Purpose: This study aimed to evaluate the feasibility and safety of prostate stereotactic body radiation therapy (SBRT) neoadjuvant to radical prostatectomy (RP) in a phase 1 trial. The primary endpoint was treatment completion rate without severe acute surgical complications. Secondary endpoints included patient-reported quality of life and physician-reported toxicities.

Interference with DNA repair after ionizing radiation by a pyrrole-imidazole polyamide.

Pyrrole-imidazole (Py-Im) polyamides are synthetic non-genotoxic minor groove-binding small molecules. We hypothesized that Py-Im polyamides can modulate the cellular response to ionizing radiation. Pre-treatment of cells with a Py-Im polyamide prior to exposure to ionizing radiation resulted in a delay in resolution of phosphorylated γ-H2AX foci, increase in XRCC1 foci, and reduced cellular replication potential.