Weekly EBM Update 8.27.18

Association of Broad-Based Genomic Sequencing With Survival Among Patients With Advanced Non–Small Cell Lung Cancer in the Community Oncology Setting (JAMA 8/2018)

The concept of broad-based genomic sequencing has made up an integral component of what is known as “precision” medicine—use of biomarker assessment to tailor cancer therapy to an individual. This concept is particularly attractive in an era where specific genetic mutations are identified and targeted with benefit to clinically relevant patient outcomes. In the specific case of advanced non-small cell lung cancer, for example, testing for mutations in EGFR and ALK are now standard of care as they predict efficacy of potential therapeutic options. Broad-based genetic screening, then, is an attempt to test many cancer genes (in this case, >30) that may have additional predictive or prognostic benefit. The National Comprehensive Cancer Network recommends such broad-based genomic sequencing as a method to uncover rare driver mutations and/or candidates for clinical trials. Nevertheless, in NSCLC populations, prior studies have failed to produce convincing evidence that routine use of broad-based genomic screening improves survival in a population, except for one retrospective study for which EGFR/ALK were included in the study group.

The study conducted by Presley, et. al, in JAMA therefore set out to assess whether the use of a broad-based genomic screen connotes any mortality benefit above the standard-of-care EGFR and ALK mutation testing. Consistent with past results, the authors were unable to find any statistically significant survival benefit in the population. They identified that less than 5% of patients who underwent broad-based genomic sequencing-informed treatment for a non-EGFR or ALK mutation. They did acknowledge that the initial, unadjusted survival estimates favored broad-based genomic sequencing, but found that immunotherapy use was independently associated with both factors and may have served as a confounder. Criticism of broad genomic sequencing includes the assertion that simply being assigned to genetic-directed therapy is not a proof of benefit, and that high costs associated with widespread use of these genomic screens and then subsequent targeted therapies may be out-of-reach for many community-treated patients and unsustainable in the long run.

Take Home: At the present, broad based genomic sequencing to identify additional mutations associated with NSCLC does not appear to have an effect on overall mortality in patients with non-small cell lung cancer.

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Assessment of the Safety of Discharging Select Patients Directly Home From the Intensive Care Unit A Multicenter Population-Based Cohort Study (JAMA IM 8/2018)

We have all been faced with difficult discharge and disposition decisions in the past, but one of the most difficult decisions is whether or not a patient in the intensive care unit is ready for direct discharge home, or needs to be first transferred to the medical ward prior to discharge. For many patients, transfer to the ward is necessary for issues related to rehabilitation, continued medical therapy, or to observe the trajectory of the frail patient. However, a select subgroup of patients may be able to discharge directly from the ICU. The Authors of this study evaluated the healthcare utilization and clinical outcomes of select patients admitted to the ICU who were discharged directly from the unit, compared to a control cohort of patients who were first transferred to the floor prior to discharge. The patients were matched based on propensity scores in an attempt to minimize the effects of confounding. The authors analyzed 6,732 patients admitted to 9 ICU’s. 14% of patients were discharged home, while 86% were transferred to the ward. The most common admitting diagnoses discharged home were overdose, pneumonia, and trauma/orthopedic injuries. The most common ICU admitting diagnoses discharged home were overdose, withdrawal, seizures, or metabolic coma. Patients discharged home had a significantly shorter length of hospital stay compared to those transferred to the ward (3.3 days vs. 9.2 days, p-value: < 0.001). Additionally, there was no difference in 30-day hospital readmission rates between groups (discharged home: 10% vs. transferred to ward: 11%). 4% of patients in both groups died in the year following discharge. The only factors with statistically significant increased risk for hospital readmission were being discharged from a hospital where ≥ 1 patient was directly discharged per week, and leaving against medical advice (HR 1.17, and 1.79 respectively)

Take Home: For select patients admitted to the ICU (notably those with admission diagnoses of overdose, withdrawal, seizures, or metabolic coma), direct discharge home may be reasonable. Direct discharge home for these diagnoses is associated with a 30-day readmission and 1-year mortality similar to propensity score matched controls who were transferred to the floor prior to discharge.

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