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ProBio is the first outcome-adaptive platform trial in prostate cancer utilizing a Bayesian framework to evaluate efficacy within predefined biomarker signatures across systemic treatments. Prospective circulating tumor DNA and germline DNA analysis was performed in patients with metastatic castration-resistant prostate cancer before randomization to androgen receptor pathway inhibitors (ARPIs), taxanes or a physician's choice control arm. The primary endpoint was the time to no longer clinically benefitting (NLCB). Secondary endpoints included overall survival and (serious) adverse events. Upon reaching the time to NLCB, patients could be re-randomized. The primary endpoint was met after 218 randomizations. ARPIs demonstrated ~50% longer time to NLCB compared to taxanes (median, 11.1 versus 6.9 months) and the physician's choice arm (median, 11.1 versus 7.4 months) in the biomarker-unselected or 'all' patient population. ARPIs demonstrated longer overall survival (median, 38.7 versus 21.7 and 21.8 months for taxanes and physician's choice, respectively). Biomarker signature findings suggest that the largest increase in time to NLCB was observed in AR (single-nucleotide variant/genomic structural rearrangement)-negative and TP53 wild-type patients and TMPRSS2-ERG fusion-positive patients, whereas no difference between ARPIs and taxanes was observed in TP53-altered patients. In summary, ARPIs outperform taxanes and physician's choice treatment in patients with metastatic castration-resistant prostate cancer with detectable circulating tumor DNA. ClinicalTrials.gov registration: NCT03903835 ., Competing Interests: Competing interests A.C., A.D., B.L., M.P., S.J., S.D., M.B., A.K., C.S., J.V.W., M.H.E., L.P., E.J., J.S., P.S., M.N.V., M.O., S.V.B., M.A., I.V., E.E., J.D., D.L., M.S. and J.O. declare no competing interests. The following authors declare having received honoraria (privately or to institution/employer) from the following companies: MSD/Merck (B.S. and G.E.); Janssen-Cilag (B.S., B.D.L., A.M., C.T.K. and J.L.); AstraZeneca (B.D.L., C.T.K. and J.L.); ESMO (B.D.L.); Astellas (B.Y.A.); Pfizer (B.Y.A., H.G. and J.L.); BMS (BY.A. and W.D.R.); Ipsen (B.Y.A.); Johnson & Johnson Innovative Medicine (W.D.R.); Gilead (G.E.); Roche (G.E.); Pierre Fabre (G.E.); and Amgen (C.T.K.). The following authors declare having performed consulting or advisory roles for the following companies: Astellas (BS., A.U., D.D.M. and H.G.); Janssen-Cilag (B.S., P.O., A.U., H.G. and D.D.M.); BMS (B.S.); MSD/Merck (B.S., A.U., D.D.M. and P.O.); Bayer (B.S., P.O., H.G., A.M. and D.D.M.); AAA (P.O.); Novartis (P.O.); Pierre Fabre (A.U.); Pfizer (A.U. and D.D.M.); Roche (A.U.); Gilead (G.E.); Elicera Therapeutics (G.E).; XNK Therapeutics AB (G.E.); Sprint Bioscience AB (G.E.); Accord (H.G.); and AstraZeneca (H.G., D.D.M. and J.L.). The following authors declare having received research grants or sponsoring of trials from the following companaies: Bayer (P.O,. A.U. and N.L.); Janssen-Cilag (H.G.); AstraZeneca (H.G.); Merck (A.U. and W.D.R.); Pierre Fabre (A.U.); Ipsen (W.D.R. and N.L.); Johnson & Johnson Innovative Medicine (W.D.R.); and Roche Diagnostics (D.D.M.). The following authors declare having an unpaid membership in a (non-)governmental organization or advocacy organization: COMPERMED (B.D.L.); PSA Vlaanderen vzw (B.D.L. and C.G.); Swiss Urology (A.M.); Swedish Cancer Society (G.E.); and EAU Guidelines Urethral Stricture Panel (N.L.). The following authors declare having stock ownership or board membership: A3P AB (H.G. and M.E.); ClinSight AB (M.E.); Lighthouse Precision Oncology AB (B.D.L., J.L., M.M., R.B. and V.C.). The following authors declare having patents: J.L. and M.M. have filed a Swedish Patent Application (no. 2350786-6), ‘Method of identifying and adjusting for systematic variability in DNA abundance measurements’, which is applied in the current study to identify copy number alterations. However, the method will be made freely available under a GPL 3.0 license (https://github.com/ClinSeq/jumble/)., (© 2024. The Author(s).)

Purpose: Evaluate the efficacy of a novel skincare product for the management of chemotherapy-related dermatological toxicities., Methods: A monocentric, prospective, interventional, open-label, pretest-posttest, single-group study with cancer patients receiving chemotherapy (n = 100) was set up. All enrolled patients applied the emollient daily to their face and body for three weeks. The severity of the skin reactions was evaluated by a researcher using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 at baseline and end of the trial. Patient-reported outcomes (PROs) included the frequency and severity of skin symptoms (Numerical rating scale, NRS), quality of life (QoL; Skindex-16 and Dermatology Life Quality Index), Patient Benefit Index (PBI), and treatment satisfaction. PROs were collected at baseline, weekly, and at the end of the trial., Results: According to the CTCAE and NRS, the novel emollient significantly improved the severity and frequency of xerosis and pruritus (Ps ≤ .001). A significant reduction in the NRS score for frequency of erythema was measured (p < .001). The frequency and severity of burning and pain did not change. Regarding the patients' QoL, no beneficial effect of the skin care product was measurable. 44% of the patients experienced at least one patient-relevant treatment benefit. 87% of the patients were satisfied with the emollient and would recommend it., Conclusions: This study shows that the novel emollient significantly reduced chemotherapy-induced skin toxicity, more specifically xerosis and pruritus without hampering patient's QoL. Future research is needed to make definite conclusions using a study design including a control group and a long-term follow-up., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: This study aimed to determine whether single nucleotide polymorphisms (SNPs) in genes involved in DNA repair or metabolism of taxanes or platinum could predict toxicity or response to first-line chemotherapy in ovarian cancer., Methods: Twenty-six selected SNPs in 18 genes were genotyped in 322 patients treated with first-line paclitaxel-carboplatin or carboplatin mono-therapy. Genotypes were correlated with toxicity events (anemia, neutropenia, thrombocytopenia, febrile neutropenia, neurotoxicity), use of growth factors and survival., Results: The risk of anemia was increased for variant alleles of rs1128503 (ABCB1, C > T; p = 0.023, OR = 1.71, 95% CI = 1.07-2.71), rs363717 (ABCA1, A > G; p = 0.002, OR = 2.08, 95% CI = 1.32-3.27) and rs11615 (ERCC1, T > C; p = 0.031, OR = 1.61, 95% CI = 1.04-2.50), while it was decreased for variant alleles of rs12762549 (ABCC2, C > G; p = 0.004, OR = 0.51, 95% CI = 0.33-0.81). Likewise, increased risk of thrombocytopenia was associated with rs4986910 (CYP3A4, T > C; p = 0.025, OR = 4.99, 95% CI = 1.22-20.31). No significant correlations were found for neurotoxicity. Variant alleles of rs2073337 (ABCC2, A > G; p = 0.039, OR = 0.60, 95% CI = 0.37-0.98), rs1695 (ABCC1, A > G; p = 0.017, OR = 0.55, 95% CI 0.33-0.90) and rs1799793 (ERCC2, G > A; p = 0.042, OR = 0.63, 95% CI 0.41-0.98) associated with the use of colony stimulating factors (CSF), while rs2074087 (ABCC1, G > C; p = 0.011, OR = 2.09, 95% CI 1.18-3.68) correlated with use of erythropoiesis stimulating agents (ESAs). Homozygous carriers of the rs1799793 (ERCC2, G > A) G-allele had a prolonged platinum-free interval (p = 0.016)., Conclusions: Our data reveal significant correlations between genetic variants of transport, hepatic metabolism, platinum related detoxification or DNA damage repair and toxicity or outcome in ovarian cancer.

Symptomatic exercise-associated hyponatremia (EAH), which is relatively common among marathon runners, is an uncommon event among ultra-endurance athletes. A 44-year-old man presented to the emergency department with increased thirst after successfully completing a 100-mile mountain bike race in Leadville, Colorado. Initial laboratory tests revealed a blood sodium level of 116 mEq/L. The primary etiologic factor in EAH is fluid consumption in excess of fluid losses in prolonged exertion. Early diagnosis and management is crucial to prevent cerebral and pulmonary edema.

Objectives: The annual incidence of out-of-hospital cardiac arrest (OOHCA) in the United States is approximately 6 per 10,000 population and survival remains low. Relatively little is known about the performance characteristics of a two-tiered emergency medical services (EMS) system split between fire-based basic life support (BLS) dispersed from fixed locations and hospital-based advanced life support (ALS) dispersed from nonfixed locations. The objectives of this study were to describe the incidence of OOHCA in Denver, Colorado, and to define the prevalence of survival with good neurologic function in the context of this particular EMS system., Methods: This was a retrospective cohort study using standardized abstraction methodology. A two-tiered hospital-based EMS system for the County of Denver and 10 receiving hospitals were studied. Consecutive adult patients who experienced nontraumatic OOHCA from January 1, 2003, through December 31, 2004, were enrolled. Demographic, prehospital arrest characteristics, treatment data, and survival data using the Utstein template were collected. Good neurologic survival was defined by a Cerebral Performance Categories (CPC) score of 1 or 2., Results: During the study period, 1,985 arrests occurred. Of these, 715 (36%) had attempted resuscitation by paramedics and constitute our study sample. The median age was 65 years (interquartile range = 52-78 years), 69% were male, 41% had witnessed arrest, 25% had bystander cardiopulmonary resuscitation (CPR) performed, and 30% had ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) as their initial rhythm. Of the 715 patients, 545 (76%) were transported to a hospital, 223 (31%) had return of spontaneous circulation (ROSC), 175 (25%) survived to hospital admission, 58 (8%) survived to hospital discharge, and 42 (6%, 95% confidence interval [CI] = 4% to 8%) had a good neurologic outcome., Conclusions: Out-of-hospital cardiac arrest survival in Denver, Colorado, is similar to that of other United States communities. This finding provides the basis for future epidemiologic and health services research in the out-of-hospital and ED settings in our community.