Search

Background: Epithelial growth factor receptor tyrosine kinase inhibitor (EGFR TKI) revolutionize the standard of care for advanced non-small cell lung cancer (NSCLC) harboring sensitive EGFR mutation. Liver toxicity is the dose-limiting factor for TKI but its importance is largely overlooked. Here the relationship between the elevation of transaminase and progression-free survival (PFS) was explored. Methods: This was a retrospective study where patients with advanced NSCLC were screened. And those treatment-naïve and with sensitive EGFR mutation who were prescribed with EGFR TKI were enrolled. The highest level of transaminase (alanine aminotransferase, ALT, and aspartate transaminase, AST) during the treatment course was recorded. Results: Totally 208 patients were recruited, and most of them (48.6%) took gefitinib. The whole cohort achieved a median PFS of 11.2 months (95%CI: 10.0-12.3 m). 73 (35.1%) patients had elevated transaminase and most was attributed to gefitinib (n=43, 42.5%). Specifically, ALT was elevated in 65 patients (31.3%) while AST in 24 patients (11.5%). Again, gefitinib was associated with more cases of ALT (40.6%) and AST (17.8%) elevation. The elevation of AST was not related to PFS (P=0.259, HR=0.751, 95%CI: 0.464-1.214). Interestingly, those with normal ALT level had a longer PFS (12.6m, 95%CI: 10.6-14.5 m) than those with elevated ALT (9.5m 95%CI: 7.9-11.0 m, P=0.025, HR=0.682, 95%CI: 0.488-0.953). The inverse relationship was confirmed in the COX regression analysis (P=0.047). Conclusion: This study revealed the side effects of elevated ALT was inversely related to the PFS of EGFR TKI treatment. The liver impairment by TKI should not be overlooked., (Creative Commons Attribution License)

Backgrounds: Targeted therapy for lung cancer depends on the genetic testing. Liquid biopsy provides a valuable source for the genetic testing. However, direct evidence was lacking for whether liquid biopsy could guide the targeted therapy. Methods: In this retrospective study, the admitted patients from Jan 2015 to Feb 2016 were screened through a pre-established database. Patients with metastatic, pathologically-confirmed, and treatment naïve non-small cell lung cancer who were prescribed with epithelial growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) from the guidance of liquid biopsy were enrolled (Liquid group). The mutation status in tumors was not mandatory. During the same period, patients medicated with TKI based on tumor samples were included in the Control group. They were enrolled in an age-, gender-, performance-, smoking-, and histology-matched manner. Results: We screened 536 patients and enrolled 26 patients in the Liquid group. Another 26 patients were enrolled in a 1:1 ratio in the Control group. In the Liquid group, a high consistence (84.6%) in EGFR mutation status between liquid and tumor was observed. The best response was partial response in 19 patients (73.1 %), and followed by stable disease in 6 patients (23.1 %). The median progression-free survival was 10.0 months (95%CI: 4.2-15.8 months). In the Control group, a similar disease control rate (88.4%, P=0.603) and comparable PFS (8.6 months, 95% CI: 7.6-10.4 months, P=0.714, HR=0.657, 95% CI: 0.309-1.396) was found. In the Liquid group, 3 of 4 patients with discordant results between tumor and liquid biopsy showed treatment responses favoring the liquid biopsy. Conclusion: This study provided direct evidence supporting the liquid biopsy for guiding the targeted therapy for lung cancer., (Creative Commons Attribution License)

The primary aim of this study was to evaluate the relationship of single nucleotide polymorphisms (SNPs) in ribosomal protein SA (RPSA) gene with colorectal cancer (CRC). A case-control study including 388 controls and 387 patients with CRC was conducted in a Chinese population. Information about socio-demography and living behavior factors was collected by a structured questionnaire. Three SNPs (rs2133579, rs2269349, rs7641291) in RPSA gene were genotyped by Illumina SnapShot method. Multiple logistic regression models were used for assessing the joint effects between tea consumption and SNPs on CRC. The subjects with rs2269349 CC genotype had a decreased risk for CRC (OR=0.60; 95%CI = 0.37-0.99), compared with TT/CT genotype after adjustment for covariates. A similar association of rs2269349 with rectal cancer was observed (OR=0.49; 95%CI=0.24-1.00). Further analyses indicated that this SNP could modify the protective effect of tea drinking on CRC. Among the subjects with rs2269349 TT/CT or rs2133579 AA/GA, there was a marginal significantly lower risk of CRC (OR and 95%CI: 0.63 and 0.39-1.01 for rs2269349; 0.64 and 0.40-1.02 for rs2133579) in tea-drinking subjects in comparison to non-tea-drinking subjects. Mutants in the RPSA gene might be associated with genetic susceptibility to CRC and influence the protective effect of tea consumption in the Chinese population.