Context: In Cushing disease, the association between the rate of serum cortisol decline and recurrent disease after corticotroph adenoma removal has not been adequately characterized.Objective: To analyze postoperative serum cortisol and recurrence rates in Cushing disease.Methods: Patients with Cushing disease and pathology-confirmed corticotroph adenoma were retrospectively studied. Cortisol halving time was estimated using exponential decay modeling. Halving time, first postoperative cortisol, and nadir cortisol values were collected using immediate postoperative inpatient laboratory data. Recurrence and time-to-recurrence were estimated and compared among cortisol variables.Results: A total of 320 patients met inclusion/exclusion criteria for final analysis, and 26 of those patients developed recurrent disease. Median follow-up time was 25 months (95% CI, 19-28 months), and 62 patients had ≥ 5 years follow-up time. Higher first postoperative cortisol and higher nadir were associated with increased risk of recurrence. Patients who had a first postoperative cortisol ≥ 50 µg/dL were 4.1 times more likely to recur than those with a first postoperative cortisol < 50 µg/dL (HR 4.1, 1.8-9.2; P = .0003). Halving time was not associated with recurrence (HR 1.7, 0.8-3.8, P = .18). Patients with a nadir cortisol ≥2 µg/dL were 6.6 times more likely to recur than those with a nadir cortisol of < 2 µg/dL (HR 6.6, 2.6-16.6, P < .0001).Conclusion: Postoperative nadir serum cortisol is the most important cortisol variable associated with recurrence and time-to-recurrence. Compared to first postoperative cortisol and cortisol halving time, a nadir < 2 µg/dL showed the strongest association with long-term remission and typically occurs within the first 24 to 48 hours after surgery.

BACKGROUND: Glioblastoma (GBM) is driven by various genomic alterations. Next-generation sequencing (NGS) could yield targetable alterations that might impact outcomes. The goal of this study was to describe how NGS can inform targeted therapy (TT) in this patient population. METHODS: The medical records of patients with a diagnosis of GBM from 2017 to 2019 were reviewed. Records of patients with recurrent GBM and genomic alterations were evaluated. Objective response rates and disease control rates were determined. RESULTS: A total of 87 patients with GBM underwent NGS. Forty percent (n = 35) were considered to have actionable alterations. Of these 35, 40% (n = 14) had their treatment changed due to the alteration. The objective response rate (ORR) of this population was 43%. The disease control rate (DCR) was 100%. The absolute mean decrease in contrast-enhancing disease was 50.7% (95% CI 34.8–66.6). CONCLUSION: NGS for GBM, particularly in the recurrent setting, yields a high rate of actionable alterations. We observed a high ORR and DCR, reflecting the value of NGS when deciding on therapies to match genomic alterations. In conclusion, patient selection and the availability of NGS might impact outcomes in select patients with recurrent GBM.

Introduction: In older patients with axis fractures, the survival benefit from surgery is unclear due to high baseline mortality. Comparative effectiveness research can provide evidence from population level cohorts. Propensity weighting is the preferred methodology for reducing bias when analyzing national administrative cohort data for these purposes but has not yet been utilized for this important surgical conundrum. We estimate the effect of surgery on mortality after isolated acute traumatic axis fracture in older adults. Materials and Methods: We used a retrospective population-based cohort of Medicare patients and generated a propensity score-weighted nonsurgical cohort and compared mortality with and without surgery. This balanced the comorbid conditions of the treatment groups. Incident fractures were defined using a predetermined algorithm based on enrollment, code timing, and billing location. The primary outcome was adjusted all-cause 1-year mortality. Results: From 12 372 beneficiaries with 1-year continuous enrollment and a coded axis fracture, 2676 patients met final inclusion/exclusion criteria. Estimated incidence was 16.5 per 100 000 person-years overall in 2014 (95% confidence interval [CI]: 15.0-18.0) and was stable from 2008 through 2014. Patients with axis fracture had a mean age of 82.8 years, 30.2% were male, and 91.9% were Caucasian. Mortality was 3.8 times higher (CI 3.6-4.1) compared with the general population of older US adults. Propensity-weighted mortality at 1 year for nonsurgical patients was 26.7 of 100 (CI: 24.5-29.0). Mortality for surgical patients was significantly lower (19.7/100; CI 14.5-25.0). Risk difference was 7.0 fewer surgical deaths per 100 patients (CI: 1.3-12.7). Surgical patients aged 65 to 74 years had the largest difference in mortality with 11.2 fewer deaths per 100 (CI: 1.1-21.3). Discussion: Patients with axis fractures are predominantly older Caucasian women and have a higher mortality rate than the general population. Propensity-weighted mortality at 1-year was lower in the surgical patients with the largest risk difference occurring in patients 65 to 74 years old. Conclusions: Surgery may provide an independent survival benefit in patients aged 65 to 75 years, and the mortality difference diminishes thereafter.