Phase III trial of long-term adjuvant androgen deprivation after neoadjuvant hormonal cytoreduction and radiotherapy in locally advanced carcinoma of the prostate: the Radiation Therapy Oncology Group Protocol 92-02.

PURPOSE: Radiation Therapy Oncology Group (RTOG) Protocol 92-02 was a randomized trial testing long-term (LT) adjuvant androgen deprivation (AD) after initial AD with external-beam radiotherapy (RT) in patients with locally advanced prostate cancer (PC; T2c-4) and with prostate-specific antigen level less than 150 ng/mL. PATIENTS AND METHODS: Patients received a total of 4 months of goserelin and flutamide, 2 months before and 2 months during RT. A radiation dose of 65 to 70 Gy was given to the prostate and a dose of 44 to 50 Gy to the pelvic lymph nodes. Patients were randomly assigned to receive no additional therapy (short-term [ST]AD-RT) or 24 months of goserelin (LTAD-RT); 1,554 patients were entered onto the study. RESULTS: The LTAD-RT arm showed significant improvement in all efficacy end points except overall survival (OS; 80.0% v 78.5% at 5 years, P =.73), compared with the STAD-RT arm. In a subset of patients not part of the original study design, with tumors assigned Gleason scores of 8 to 10 by the contributing institutions, the LTAD-RT arm had significantly better OS (81.0% v 70.7%, P =.044). There was a small but significant increase in the frequency of late radiation grades 3, 4, and 5 gastrointestinal toxicity ascribed to the LTAD-RT arm (2.6% v 1.2% at 5 years, P =.037), the cause of which is not clear. CONCLUSION: The RTOG 92-02 trial supports the addition of LT adjuvant AD to STAD with RT for T2c-4 PC. In the exploratory subset analysis of patients with Gleason scores 8 to 10, LT adjuvant AD resulted in a survival advantage.     

Evaluating the Effect of a COVID-19 Predictive Model to Facilitate Discharge: A Randomized Controlled Trial

Background  We previously developed and validated a predictive model to help clinicians identify hospitalized adults with coronavirus disease 2019 (COVID-19) who may be ready for discharge given their low risk of adverse events. Whether this algorithm can prompt more timely discharge for stable patients in practice is unknown. Objectives  The aim of the study is to estimate the effect of displaying risk scores on length of stay (LOS). Methods  We integrated model output into the electronic health record (EHR) at four hospitals in one health system by displaying a green/orange/red score indicating low/moderate/high-risk in a patient list column and a larger COVID-19 summary report visible for each patient. Display of the score was pseudo-randomized 1:1 into intervention and control arms using a patient identifier passed to the model execution code. Intervention effect was assessed by comparing LOS between intervention and control groups. Adverse safety outcomes of death, hospice, and re-presentation were tested separately and as a composite indicator. We tracked adoption and sustained use through daily counts of score displays. Results  Enrolling 1,010 patients from May 15, 2020 to December 7, 2020, the trial found no detectable difference in LOS. The intervention had no impact on safety indicators of death, hospice or re-presentation after discharge. The scores were displayed consistently throughout the study period but the study lacks a causally linked process measure of provider actions based on the score. Secondary analysis revealed complex dynamics in LOS temporally, by primary symptom, and hospital location. Conclusion  An AI-based COVID-19 risk score displayed passively to clinicians during routine care of hospitalized adults with COVID-19 was safe but had no detectable impact on LOS. Health technology challenges such as insufficient adoption, nonuniform use, and provider trust compounded with temporal factors of the COVID-19 pandemic may have contributed to the null result. Trial registration  ClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT04570488","term_id":"NCT04570488"}}NCT04570488.     

Stem cell plasticity: a new image of the bone marrow stem cell

The central tenet of stem cell biology is that within tissues there reside stem cells with the capacity for both self-renewal and terminal differentiation to the multiple lineages of that tissue. Over the last few years, numerous studies have challenged this paradigm by showing that tissue stem cells can differentiate to unexpected cell lineages, suggesting an enormous plasticity of differentiation. The hematopoietic stem cell, which resides within bone marrow and gives rise to all blood cells, has been the focal point of these efforts. However, recent studies have disputed the notion of hematopoietic stem cell plasticity. In truth, stem cell plasticity, strictly defined, has yet to be rigorously proven. Both animal models to carefully address outstanding issues and pilot clinical trials to explore the therapeutic potential will be key elements to advance science for the benefit of patients.     

Pregnancy testing

Immunoassays have virtually replaced bioassays for detection of pregnancy. Slide and tube tests are applicable in most clinical situations. Because of its sensitivity, radioimmunoassay is ideal for diagnosis of early and ectopic pregnancies.     

Ex Vivo Expansion or Manipulation of Stem Cells to Improve Outcome of Umbilical Cord Blood Transplantation

The outcome of umbilical cord blood transplantation for adult patients with hematologic malignancies now rivals that of matched unrelated donor transplantation. However, delayed hematopoietic and immunologic recovery remains a source of significant morbidity and mortality. Multiple strategies are now being studied to overcome these limitations. One strategy involves ex vivo expansion of the umbilical cord blood unit prior to transplantation. A second strategy involves exposure of the umbilical cord blood graft to compounds aimed at improving homing and engraftment following transplantation. Such a strategy may also address the problem of slow hematopoietic recovery as well as the increased risk of graft failure. Many of these strategies are now being tested in late phase multi-center clinical trials. If proven cost-effective and efficacious, they may alter the landscape of donor options for allogeneic stem cell transplantation.     

Insulin pump therapy

Preview

How successful is insulin pump therapy in normalizing the blood glucose level? Does it have great advantages over conventional insulin injection therapy? Who are the best candidates for it? In answering these and other questions, Dr Horwitz looks at the experience that has accumulated with use of this major innovation in diabetes therapy.