CA-CANCER J CLIN ：血栓栓塞预示胰腺癌不良预后

Andrew Epstein, MD, professor in the division of gastrointestinal medical oncology at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York City, and colleagues conducted a review of patients with pancreatic cancer to assess the impact and timing of TE on survival and to examine associations between other clinical variables and risk of TE.

Using an institutional electronic application, investigators identified patients with pancreatic cancer who were treated with chemotherapy at MSKCC from January 1, 2000 through December 31, 2009. Any patient records found by the electronic application to have a diagnosis code indicating TE were then manually reviewed for data. In addition, to verify the accuracy of the electronic application in selecting records relevant to this study, 50 randomly selected charts from patients with pancreatic cancer but no coded TE event were reviewed manually and none were found to have had a TE. Eight patients who were diagnosed with a TE more than 3 months before the diagnosis of pancreatic cancer were excluded from analyses.

The median survival of the 1915-patient cohort was 13.7 months, and 690 patients (36%) had at least one TE recorded. Of the 690 patients with TE, 614 (89%) had a non–catheter-related deep vein thrombosis and/or pulmonary embolism. An arterial TE occurred in 30 patients (4.4%). A total of 638 patients (92.5%) had locally advanced or metastatic disease when their first TE was diagnosed.

After adjusting for pancreatic surgery, having a TE significantly increased the risk of death during the follow-up interval with a hazard ratio (HR) of 2.6 (P < .01). Not surprisingly, patients who underwent surgery had significantly longer survival than those who did not undergo surgery (HR, 0.42; P < .01). The 134 patients who developed a TE within 1.5 months from the diagnosis of pancreatic cancer had a significantly higher risk of death than patients who did not develop a TE within 1.5 months of their cancer diagnosis (HR, 2.1; P < .01).

“It is not a new observation to find that TE is common in pancreatic cancer, but this study helps to define the incidence. The main new finding is that patients with an early TE had clearly worse outcomes,” says corresponding author Eileen O'Reilly, MD, associate member of the gastrointestinal oncology service at MSKCC and an associate professor at the Weill Cornell Medical College of Cornell University.

Time to the diagnosis of TE was significantly shorter in patients who received erythropoiesis-stimulating agents (ESAs) versus those who did not. Having a low body mass index (BMI) (< 18.5 kg/m²) compared with a normal BMI was associated with a significantly longer time to thrombosis (HR, 0.6; P < .01), but having an overweight or obese BMI (> 25 kg/m²) compared with a normal BMI was not associated with time to thrombosis.

Investigators found no significant effect of a lower hemoglobin level, higher white blood cell count, higher platelet count, or elevated activated partial thromboplastin time values. Time to thrombosis, however, was significantly shorter for patients with elevated international normalized ratio (INR) values (HR, 1.22; P < .01)

In a multivariate Cox regression analysis of overall survival controlling for standard clinical variables such as age and sex as well as variables that were found in the study to be significantly associated with time to thrombosis on bivariate analysis, having a TE was associated with an increased risk of death (HR, 2.83). Gender or ESA administration had no effect, but an older age at diagnosis and an elevated INR were associated with significantly worse survival.