Practical Guidance on [177Lu]Lu-PSMA-617 Treatment, Including Radiation Safety, Adverse Event Monitoring, and Patient Counseling.

BACKGROUND: The approval of the prostate-specific membrane antigen (PSMA)-targeted radio-ligand therapy [177Lu]Lu-PSMA-617 represents a shift toward precision medicine-based treatments for metastatic castration-resistant prostate cancer. OBJECTIVES: This review aims to provide practical advice and clinical considerations for working with [177Lu]Lu-PSMA-617; particularly, regarding the role of nurses in managing radiation safety, monitoring and reporting of adverse events, and counseling patients receiving this therapy. METHODS: Clinical data, protocols, and guidelines are summarized alongside real-world insights to provide practical recommendations for nurses caring for patients treated with [177Lu]Lu-PSMA-617. FINDINGS: Nurses coordinate safe care for patients receiving [177Lu]Lu-PSMA-617 by facilitating communication among physicians, managing logistic concerns, monitoring for adverse events related to treatment, providing education, and counseling patients and caregivers throughout treatment.

Plain language summary of the HERO study comparing relugolix with leuprolide for men with advanced prostate cancer.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of a research study (known as a clinical trial) called HERO. The HERO study compared how well relugolix and leuprolide worked in lowering blood testosterone to sustained castration levels in men with advanced prostate cancer. Sustained castration is a blood testosterone level below 50 ng/dl from Day 29 through 48 weeks of treatment. WHAT WERE THE RESULTS?: Researchers looked at 930 adult men with advanced prostate cancer: 622 of these men took relugolix (by mouth once daily) and 308 received leuprolide (injected every 3 months). The HERO study showed that more men taking relugolix (97%) achieved sustained castration through 48 weeks than men receiving leuprolide (89%). This decrease in testosterone also happened more quickly in men taking relugolix. In 184 men who were followed up for 90 days after completing treatment, blood levels of testosterone returned to normal in more men who took relugolix than men who received leuprolide. Side effects were similar among men taking relugolix or receiving leuprolide, and most were identified as mild or moderate in terms of how bad they were. WHAT DO THE RESULTS OF THE STUDY MEAN?: In men with advanced prostate cancer and compared with those receiving leuprolide, more men taking relugolix had lower levels of blood testosterone. ClinicalTrials.gov NCT number: NCT03085095.

Outcomes of a randomized controlled trial assessing a smartphone Application to reduce unmet needs among people diagnosed with CancEr (ACE).

BACKGROUND: Smartphone technology represents an opportunity to deliver practical solutions for people affected by cancer at a scale that was previously unimaginable, such as information, appointment monitoring, and improved access to cancer support services. This study aimed to determine whether a smartphone application (app) reduced the unmet needs among people newly diagnosed with cancer. METHODS: A single blind, multisite randomized controlled trial to determine the impact of an app-based, 4-month intervention. Newly diagnosed cancer patients were approached at three health service treatment clinics. RESULTS: Eighty-two people were randomized (intervention; n = 43 and control; n = 39), average age was 59.5 years (SD: 12.9); 71% female; 67% married or in a de facto relationship. At baseline, there were no differences in participants' characteristics between the groups. No significant effects, in reducing unmet needs, were demonstrated at the end of intervention (4-month) or 12-month follow-up. Overall, 94% used the app in weeks 1-4, which decreased to 41% in weeks 13-16. Mean app use time per participant: Cancer Information, 6.9 (SD: 18.9) minutes; Appointment Schedule, 5.1 (SD: 9.6) minutes; Cancer Services 1.5 minutes (SD: 6.8); Hospital Navigation, 1.4 (SD: 2.8) minutes. CONCLUSIONS: Despite consumer involvement in the design of this smartphone technology, the app did not reduce unmet needs. This may have been due to the study being underpowered. To contribute to a meaningful understanding and improved implementation of smartphone technology to support people affected by cancer, practical considerations, such as recruitment issues and access to, and confidence with, apps, need to be considered. Australian New Zealand Clinical Trials Registration (ACTRN) Trial Registration: 12616001251415; WEF 7/9/2016.

Rapid development of sensitive, high-throughput, quantitative and highly selective mass spectrometric targeted immunoassays for clinically important proteins in human plasma and serum.

OBJECTIVES: The aim of this study was to develop high-throughput, quantitative and highly selective mass spectrometric, targeted immunoassays for clinically important proteins in human plasma or serum. DESIGN AND METHODS: The described method coupled mass spectrometric immunoassay (MSIA), a previously developed technique for immunoenrichment on a monolithic microcolumn activated with an anti-protein antibody and fixed in a pipette tip, to selected reaction monitoring (SRM) detection and accurate quantification of targeted peptides, including clinically relevant sequence or truncated variants. RESULTS: In this report, we demonstrate the rapid development of MSIA-SRM assays for sixteen different target proteins spanning seven different clinically important areas (including neurological, Alzheimer's, cardiovascular, endocrine function, cancer and other diseases) and ranging in concentration from pg/mL to mg/mL. The reported MSIA-SRM assays demonstrated high sensitivity (within published clinical ranges), precision, robustness and high-throughput as well as specific detection of clinically relevant isoforms for many of the target proteins. Most of the assays were tested with bona-fide clinical samples. In addition, positive correlations, (R2 0.67-0.87, depending on the target peptide), were demonstrated for MSIA-SRM assay data with clinical analyzer measurements of parathyroid hormone (PTH) and insulin growth factor 1 (IGF1) in clinical sample cohorts. CONCLUSIONS: We have presented a practical and scalable method for rapid development and deployment of MS-based SRM assays for clinically relevant proteins and measured levels of the target analytes in bona fide clinical samples. The method permits the specific quantification of individual protein isoforms and addresses the difficult problem of protein heterogeneity in clinical proteomics applications.

Very late stent thrombosis approximately 7 years after deployment and one-week cessation of dual antiplatelet therapy.

This work describes the longest reported interval between drug-eluting stent (DES) placement and very late stent thrombosis (VLST). A 69-year-old male presented with substernal chest pain associated with ST-segment myocardial infarction (STEMI) after having a DES deployed 6.9 years (2506 days) prior. The patient's medical history revealed several risk factors for VLST. The patient suspended clopidogrel therapy in preparation for elective cystoscopy approximately 10 days before presenting.

Use of selected reaction monitoring mass spectrometry for the detection of specific MHC class I peptide antigens on A3 supertype family members.

The development of peptide-based vaccines that are useful in the therapeutic treatment of melanoma and other cancers ultimately requires the identification of a sufficient number of antigenic peptides so that most individuals, regardless of their major histocompatibility complex (MHC)-encoded class I molecule phenotype, can develop a cytotoxic T lymphocyte (CTL) response against one or more peptide components of the vaccine. While it is relatively easy to identify antigenic peptides that are presented by the most prevalent MHC class I molecules in the population, it is problematic to identify antigenic peptides that are presented by MHC class I molecules that have less frequent expression in the population. One manner in which this problem can be overcome is by taking advantage of known MHC class I supertypes, which are groupings of MHC class I molecules that bind peptides sharing a common motif. We have developed a mass spectrometric approach which can be used to determine if an antigenic peptide is naturally processed and presented by any given MHC class I molecule. This approach has been applied to the A3 supertype, and the results demonstrate that some, but not all, A3 supertype family-associated peptides can associate with all A3 supertype family members. The approach also demonstrates the shared nature of several newly identified peptide antigens. The use of this technology negates the need to test peptides for their ability to stimulate CTL responses in those cases where the peptide is not naturally processed and bound to the target MHC class I molecule of interest, thus allowing resources to be focused on the most promising vaccine candidates.

Smac is required for cytochrome c-induced apoptosis in prostate cancer LNCaP cells.

Release of cytochrome c from mitochondria to cytosol has been identified as one of the central events of apoptosis. Direct injection of cytochrome c induces apoptosis in some but not in all cell types. We observed that LNCaP prostate cancer cells failed to undergo apoptosis induced by cytochrome c microinjections. Microinjection of cytochrome c with another mitochondrial protein, Smac, was sufficient to activate caspases, however. Smac is believed to function as a neutralizer of caspase inhibitors, and mass spectrometry analysis identified XIAP as a predominant Smac binding protein in LNCaP cells. These findings are consistent with a requirement for a release of Smac from mitochondria to enable caspase activation in prostate cells. Indeed, translocation of Smac from mitochondria to cytosol was observed in LNCaP cells that undergo apoptosis and was inhibited by epidermal growth factor, which is a survival factor for these cells. These results further emphasize the central role of mitochondria in the regulation of apoptosis in prostate cancer cells.