It is unclear if clinician risk stratification has changed with time. The aim of this study was to assess the temporal change in the concordance between patient presenting risk and the intensity of ...evidence-based therapies received for non–ST-segment elevation acute coronary syndromes over a 9-year period. Data from 3,562 patients with non–ST-segment elevation acute coronary syndromes enrolled in the Australian and New Zealand population of the Global Registry of Acute Coronary Events (GRACE) from 1999 to 2007 were analyzed. Patients were stratified to risk groups on the basis of the GRACE risk score for in-hospital mortality. Main outcome measures included in-hospital use of widely accepted evidence-based medications, investigations, and procedures. Invasive management was consistently higher in low-risk patients than in intermediate- or high-risk patients (coronary angiography 66.7% vs 63.5% vs 35.3%, p <0.001; percutaneous coronary intervention 31.1% vs 22.0% vs 12.9%, p <0.001). Absolute rates of angiography and percutaneous coronary intervention in the high-risk group remained 24% and 15% lower compared to the low-risk group in the most recent time period (2005 to 2007). In-hospital use of thienopyridine, low–molecular weight heparin, and glycoprotein IIb/IIIa inhibitors showed a similar inverse relation with risk. Prescription of aspirin, β blockers, statins, and angiotensin receptor blockers was inversely related to risk before 2004, although this inverse relation was no longer present in the most recent time period (2005 to 2007). Only in-hospital use of unfractionated heparin showed use concordant with patient risk status. In conclusion, despite an overall increase in the uptake of evidence-based therapies, most investigations and treatments are not targeted on the basis of patient risk. Clinician risk stratification remains suboptimal compared to objective measures of patient risk.
To report toxicity and early survival data for IDEAL-CRT, a trial of dose-escalated concurrent chemoradiotherapy (CRT) for non-small cell lung cancer.
Patients received tumor doses of 63 to 73 Gy in ...30 once-daily fractions over 6 weeks with 2 concurrent cycles of cisplatin and vinorelbine. They were assigned to 1 of 2 groups according to esophageal dose. In group 1, tumor doses were determined by an experimental constraint on maximum esophageal dose, which was escalated following a 6 + 6 design from 65 Gy through 68 Gy to 71 Gy, allowing an esophageal maximum tolerated dose to be determined from early and late toxicities. Tumor doses for group 2 patients were determined by other tissue constraints, often lung. Overall survival, progression-free survival, tumor response, and toxicity were evaluated for both groups combined.
Eight centers recruited 84 patients: 13, 12, and 10, respectively, in the 65-Gy, 68-Gy, and 71-Gy cohorts of group 1; and 49 in group 2. The mean prescribed tumor dose was 67.7 Gy. Five grade 3 esophagitis and 3 grade 3 pneumonitis events were observed across both groups. After 1 fatal esophageal perforation in the 71-Gy cohort, 68 Gy was declared the esophageal maximum tolerated dose. With a median follow-up of 35 months, median overall survival was 36.9 months, and overall survival and progression-free survival were 87.8% and 72.0%, respectively, at 1 year and 68.0% and 48.5% at 2 years.
IDEAL-CRT achieved significant treatment intensification with acceptable toxicity and promising survival. The isotoxic design allowed the esophageal maximum tolerated dose to be identified from relatively few patients.
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