Laveena Chhatwani

Increased Resource Use in Lung Transplant Admissions in the Lung Allocation Score Era

RATIONALE In 2005, the lung allocation score (LAS) was implemented to prioritize organ allocation to minimize waiting-list mortality and maximize 1-year survival. It resulted in transplantation of older and sicker patients without changing 1-year survival. Its effect on resource use is unknown. OBJECTIVES To determine changes in resource use over time in lung transplant admissions. METHODS Solid organ transplant recipients were identified within the Nationwide Inpatient Sample (NIS) data from 2000 to 2011. Joinpoint regression methodology was performed to identify a time point of change in mean total hospital charges among lung transplant and other solid-organ transplant recipients. Two temporal lung transplant recipient cohorts identified by joinpoint regression were compared for baseline characteristics and resource use, including total charges for index hospitalization, charges per day, length of stay, discharge disposition, tracheostomy, and need for extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS A significant point of increased total hospital charges occurred for lung transplant recipients in 2005, corresponding to LAS implementation, which was not seen in other solid-organ transplant recipients. Total transplant hospital charges increased by 40% in the post-LAS cohort (

Adjuvant Treatment of Resected Lung Cancer

569,942 [

Phase I and pharmacokinetic study of bexarotene in combination with gefitinib in the third-line treatment of non-small-cell lung cancer: brief report.

53,229] vs.

Lung transplantation following death by drowning: a review of the current literature

407,489 [

Adjuvant Chemotherapy for Resected Non-Small Cell Lung Cancer

28,360]) along with an increased median length of stay, daily charges, and discharge disposition other than to home. Post-LAS recipients also had higher post-transplant use of extracorporeal membrane oxygenation (odds ratio, 2.35; 95% confidence interval, 1.56-3.55) and higher incidence of tracheostomy (odds ratio, 1.52; 95% confidence interval, 1.22-1.89). CONCLUSIONS LAS implementation is associated with a significant increase in resource use during index hospitalization for lung transplant.

A phase I dose-escalation and pharmacokinetic study of enzastaurin and erlotinib in patients with advanced solid tumors.

Lung cancer is the leading cause of cancer mortality worldwide, and efforts to improve outcomes of patients with this disease require a multidisciplinary approach. While surgical resection is the optimal treatment for early stage lung cancer, the high rates of recurrence after resection pose a distinct challenge. In recent years, substantial evidence has accumulated to support adjuvant chemotherapy in Stage II and III non-small cell lung cancer (NSCLC). A recent meta-analysis of large clinical trials of cisplatin-based adjuvant chemotherapy for resected NSCLC showed that the 5-year survival benefit in favor of chemotherapy was 5.3% (hazard ratio for death, 0.89; 95% confidence interval, 0.82-0.96; P = 0.005). The use of adjuvant chemotherapy in Stage I NSCLC remains controversial. Current and future efforts are being directed toward identification of prognostic and predictive markers to select patients at highest risk for recurrence, and of chemotherapeutic agents to which their tumors are most likely to respond. The role of targeted therapies, including those directed at the epidermal growth factor receptor and vascular endothelial growth factor in adjuvant treatment, is currently under investigation. At this time, there are no data to support the routine use of adjuvant radiation treatment, except in cases in which surgical margins are positive.

Combined Lung-Liver Transplantation: The United States Experience

Gefitinib (an epidermal growth factor receptor tyrosine kinase inhibitor) and bexarotene (a rexinoid) affect similar oncogenic pathways and are both metabolized through cytochrome P450 CYP3A4. We studied the combination of bexarotene and gefitinib in the third-line treatment of advanced non-small-cell lung cancer to examine pharmacokinetic interactions and establish the maximum tolerated dose. This was a single-institution, nonrandomized, open-label, phase I clinical trial with a standard 3+3 dose escalation. Three patients were enrolled at each dose level on the basis of pharmacokinetic analysis with dose level 1 including gefitinib (Iressa) 250 mg oral daily and bexarotene (Targretin) 400 mg/m2 oral daily and dose level +1 including gefitinib 500 mg oral daily and bexarotene 400 mg/m2 oral daily. Patients received gefitinib alone for 2 weeks to allow for steady state and thereafter, bexarotene was added. In dose level 1, two of three patients had undetectable gefitinib levels at day 15 for unknown reasons. However, the peak levels on day 29 for all three patients receiving 250 mg of gefitinib with bexarotene are lower than published peak levels. Among the three patients in dose level +1, ∼40% lower gefitinib plasma concentrations were noted on day 29 compared with day 15 along with a mean 44% reduction in area under the plasma concentration–time curve from 0 to 24 h (AUC0–24). Bexarotene appears to lower the C max and AUC0–24 of gefitinib through cytochrome P450 CYP3A4. Our results have pharmacokinetic implications for ongoing trials that combine bexarotene with other small molecules in the era of personalized cancer therapy.

THE UTILITY OF PARAMETRIC RESPONSE MAPPING IN PULMONARY GRAFT VS HOST DISEASE FOLLOWING HEMATOPOIETIC STEM CELL TRANSPLANT

While multiple donor characteristics have been cited as ideal for lung transplantation, there are minimal widely accepted exclusion criteria. One criterion that many centers view with hesitation is death by drowning. However, recent literature suggests such donors may result in acceptable outcomes following transplantation. This review highlights a case of a patient who underwent a successful bilateral lung transplant from a donor following a drowning event. A review of the current literature is presented, concluding with a new proposed set of favorable donor criteria following death by drowning.