Patterns of spread and prognostic implications of lung cancer metastasis in an era of driver mutations

[摘要] BackgroundIn the present study, we examined the pattern of metastatic spread in patients with advanced nonsmall- cell lung cancer (nsclc) and the effect ofEGFRmutations. MethodsPatients were identified from a provincial cancer registry, and individual medical records were reviewed. Patients were included if they had stage iv nsclc and underwent diagnosticEGFRmutation testing. Patients were divided intoEGFRmutation-positive ( EGFR+ ) andEGFRwild type (wt) cohorts. The primary endpoint was the cumulative incidence for each metastatic site: lung, bone, brain, liver, adrenal glands, distant nodes, and other. Cumulative incidence curves were estimated using a competing-risks method. The secondary outcome was survival. ResultsOf the 543 identified patients, 121 (22.3%) tested asEGFR+,and 422 (77.7%) tested asEGFRwt. The incidence of brain (39.2% vs. 28.2%,p= 0.038) and lung (61.2% vs. 51.0%,p= 0.048) metastasis was higher in theEGFR+cohort than in theEGFRwt cohort. In theEGFR+cohort, a higher incidence of liver metastasis was associated with the exon 21 mutation subtype than with the exon 19 deletion subtype [23% vs. 7%,p< 0.01; hazard ratio (hr): 3.47]. Median survival was significantly longer for theEGFR+cohort than for theEGFRwt cohort (22.4 months vs. 7.9 months,p< 0.001). In multivariable analysis, brain (hr: 1.73), liver (hr: 1.69), and bone (hr: 1.89) metastases were associated with worse survival. ConclusionsRates of lung and brain metastases are higher inEGFRmutation carriers, even when adjusted for differences in survival. Brain, liver, and bone metastases are independent negative prognostic factors for survival.

[学科分类] 肿瘤学

[关键词] EGFR;lung cancer;metastasis behavior;population studies