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Simple Summary: This research investigates the identification of tumor-specific serological biomarkers for the early diagnosis of glioblastoma multiforme (GBM) recurrence using peripheral whole blood samples in a minimally invasive approach known as "liquid biopsy". Our results indicate that gene expression analysis can detect changes in transcriptional (mRNAs) and post-transcriptional (small RNAs) levels after surgery and upon tumor recurrence. This prospective study aims to develop a diagnostic tool complementary to MRI modalities in the clinical follow-up, helping to track tumor progression/recurrence and to make clinical decisions. GBM WHO CNS Grade 4 represents a major challenge for oncology due to its aggressive behavior. Conventional imaging has restrictions in detecting tumor recurrence. This prospective study aims to identify gene-based biomarkers in whole blood instead of isolating exosomes for the early detection of tumor recurrence. Blood samples (n = 33) were collected from seven GBM patients at time points before and after surgery as well as upon tumor recurrence. Four tumor tissue samples were assessed in parallel. Next-generation sequencing (NGS), including mRNA-seq and small RNA-seq, was used to analyze gene expression profiles in blood samples and tumor tissues. A novel filtering pipeline was invented to narrow down potential candidate genes. In total, between 6–93 mRNA and 1–19 small RNA candidates could be identified among the seven patients. The overlap of genes between the patients was minimal, indicating significant inter-individual variance among GBM patients. In summary, this prospective study supports the applicability of gene expression measurements in whole blood for the detection of tumor recurrence. It might provide an alternative to the challenging workflow of liquid biopsy after laborious exosome isolation from whole blood. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with metastasized, castration-resistant prostate cancer can be treated locally with radioactive radium-223, which usually comprises six cycles. We wanted to know whether this treatment affects immune function. We performed cell culture experiments with white blood cells from the patients and added components of microorganisms. We tested the ability of the cells to proliferate and produce two cytokines (interferon-gamma and interleukin-10) that are important for the balance of the immune system. Our data in 21 patients indicate that the immune cells show impairment in their defense against microorganisms after treatment. As determined by bone scintigraphy, a reduction in tumor burden was observed in 67% of patients. Interestingly, even before treatment, the number of cells producing interleukin-10, an anti-inflammatory cytokine, was an indicator of tumor burden at the end of treatment. Thus, a blood test can help assess whether the treatment is likely to be successful. Previous data indicate that one cycle of treatment with radium-223 (223Ra) did not significantly impair lymphocyte function in patients with metastasized, castration-resistant prostate cancer. The aim of the current study was to assess in 21 patients whether six cycles of this therapy had an effect on lymphocyte proliferation and interferon-γ and interleukin (IL)-10 ELISpot results. Lymphocyte proliferation after stimulation with microbial antigens and the production of interferon-γ continuously decreased after six cycles of radionuclide therapy, reaching statistical significance (p < 0.05) at months 1, 2, 4, and/or 6 after therapy. One month after the last cycle of therapy, 67% of patients showed a decrease in tumor burden. The tumor burden correlated negatively with IL-10 secretion at baseline, e.g., after stimulation with tetanus antigen (p < 0.0001, r = −0.82). As determined by receiver operating characteristic (ROC) curve analysis, tetanus-specific IL-10 spots at baseline had the highest predictive value (p = 0.005) for tumor burden at month 6, with an area under the curve (AUC) of 0.90 (sensitivity 100%, specificity 78%). In conclusion, we observed an additive effect of treatment with 223Ra on immune function and found that IL-10 secretion at baseline predicted tumor burden at month 6 after treatment. [ABSTRACT FROM AUTHOR]

223 Ra, a targeted α-therapy, is approved for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) who have bone metastases. In the phase 3 ALSYMPCA study, 223 Ra prolonged survival and improved quality of life versus placebo. Our real-world study, PARABO, investigated pain and bone pain-related quality of life in patients with mCRPC and symptomatic bone metastases receiving 223 Ra in clinical practice. Methods: PARABO was a prospective, observational, noninterventional single-arm study conducted in nuclear medicine centers across Germany (NCT02398526). The primary endpoint was a clinically meaningful pain response (≥2-point improvement from baseline for the worst-pain item score in the Brief Pain Inventory-Short Form). Results: The analysis included 354 patients, who received a median of 6 223 Ra injections (range, 1-6). Sixty-seven percent (236/354) received 5-6 injections, and 33% (118/354) received 1-4 injections. Of 216 patients with a baseline worst-pain score of more than 1, 59% (128) had a clinically meaningful pain response during treatment. Corresponding rates were 67% (range, 98/146) with 5-6 223 Ra injections versus 43% (range, 30/70) with 1-4 injections, 60% (range, 60/100) in patients with no more than 20 lesions versus 59% (range, 65/111) in those with more than 20 lesions, and 65% (range, 69/106) in patients without prior or concomitant opioid use versus 54% (range, 59/110) in those with prior or concomitant opioid use. Mean subscale scores (pain severity and pain interference) on the Brief Pain Inventory-Short Form improved during treatment. Conclusion: 223 Ra reduced pain in patients with mCRPC and symptomatic bone metastases, particularly in patients who received 5-6 injections. The extent of metastatic disease did not impact pain response., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)