The Significance Of Pro-gastrin Releasing Peptide(ProGRP) For Small Cell Lung Cancer Using A Second EGFR-TKI Afer A Severe AE Related To A First EGFR-TKI In NSCLC

Objective To evaluate the clinical value of Pro-gastrin Releasing Peptide (ProGRP) for small cell lung cancer (SCLC). To evaluate the clinical value of Elecsys(?) ProGRP immunoassay in Chinese patients. Methods Serum and plasma levels of ProGRP were respectively measured by both Elecsys(?) and ARCHITECT assays in healthy subjects, benign diseases subjects, malignant diseases except for lung cancer subjects, non-small cell lung cancer (NSCLC) subjects and small cell lung cancer (SCLC) subjects. All the subjects were recruited by the Peking Union Medical College Hospital (PUMCH) from March to October2013. The correlation between the ARCHITECT and the cobas(?) assays and the relationship between serum and plasma samples on the cobas(?) assay were analyzed. The receiver operating characteristic curve (ROC) was used to set the cutoff value and the areas under ROC (ROC-AUC) of ProGRP measuring by Elecsys(?) assay. The NSCLC and SCLC patients’serum NSE levels were measured at the same time. The ROC curve was used to set the cutoff value and ROC-AUC of NSE. The sensitivities and specificities of ProGRP and NSE were analyzed for diagnosing SCLC. Monitor the ProGRP levels of SCLC cohort patients and gather the evaluation results of CT scans during the chemotherapy. Results1. The ARCHITECT and cobas(?) ProGRP assays showed good correlation in plasma ProGRP concentrations. The bias of the results detected by the two diagnostic methods can be accepted clinically. Good correlation between serum ProGRP concentrations and plasma ProGRP concentrations was also demonstrated on the cobas(?) assay. The bias of the detection results of two samples can be accepted clinically.2. The serum levels of ProGRP in SCLC group were significantly higher than those in the healthy group, benign diseases group, malignant diseases except for lung cancer group and NSCLC group (p<0.001). The levels of ProGRP in limited-disease small cell lung cancer (LD-SCLC) and extensive-disease small cell lung cancer (ED-SCLC) were not significant difference (p=0.856).3. Using the subjects of healthy group as control to draw the ROC curve, the cutoff value of ProGRP was74.44pg/ml. The sensitivity of ProGRP to diagnose SCLC was96.0%, the specificity97.2%. Using the subjects of benign diseases group as control to draw the ROC curve, the cutoff value of ProGRP was109.30pg/ml. The sensitivity of ProGRP to diagnose SCLC was96.0%, the specificity100%. Using the subjects of malignant diseases except for lung cancer group as control to draw the ROC curve, the cutoff value of ProGRP was115.6pg/ml. The sensitivity of ProGRP to diagnose SCLC was92.0%, the specificity94.1%. Using the subjects of NSCLC group as control to draw the ROC curve, the cutoff value was115.6pg/ml. The sensitivity of ProGRP to diagnose SCLC was92.0%, the specificity95.6%. Using the other four groups except for SCLC patients as control to draw the ROC curve, the cutoff value of ProGRP was93.79pg/ml. The sensitivity of ProGRP to diagnose SCLC was96.0%, specificity96.4%.4. Using the subjects of NSCLC group as control to draw the ROC curves, the ROC-AUC of ProGRP (0.976) was statistically higher than that of NSE (0.873)(p=0.01). The sensitivities of ProGRP and NSE were92.0%and52%respectively when their specificity was95.6%. The combining detection of the two tumor markers had no significant influence on sensitivity, but the specificity is dramatically dropped.5. The detection results of ProGRP were in accordance with the CT evaluation results during the chemotherapy. Conclusions Good correlation between serum and plasma ProGRP concentrations was demonstrated on the cobas(?) assay. ProGRP is a better tumor marker than NSE for the diagnosis of SCLC. It is an important index to evaluate the effect of chemotherapy. The new small-molecule epidermal growth factor receptor tyrosine kinase inhibitors are widely used in the treatment of NSCLC patients in recent years. EGFR-TKIs not only have proven survival benefit in EGFR positive NSCLC patients, but also have significantly improved their life qualities. The common toxic and side effects of EGFR-TKIs include acne-like rash, diarrhea and nausea etc. The uncommon toxic and side effects are hepatotoxicity and alopecia etc. The rare toxic and side effect is interstitial lung disease. It is controversial that using a second EGFR-TKI is appropriate after a severe AE related to a first EGFR-TKI in NSCLC. Two typical cases demonstrated here hinted us that when one EGFR-TKI was forced to stop because of the intolerant toxic and side effects in the treatment of EGFR positive NSCLC, another EGFR-TKI may not cause the same toxic and side effects.