Poor prognosis of NSCLC located in lower lobe is partly mediated by lower frequency of EGFR mutations

Abstract

It is controversial whether a tumor located in the lower lobe is related with worse outcome of non-small cell lung cancer (NSCLC). This study aimed to clarify the prognostic role of primary tumor location in NSCLC. Patients newly diagnosed with NSCLC in a tertiary referral hospital from January 2011 to December 2014 were followed up for 5 years. Of the 2,289 NSCLC cases, 911 (39.8%) cases pertained to lower lobe cancers. Patients with lower lobe cancer showed a higher all-cause mortality rate than those with non-lower lobe cancer (48.6% vs. 40.3%, p < 0.001). Patients with lower lobe cancer had a lower proportion of adenocarcinoma histology and epidermal growth factor receptor (EGFR) mutations. Furthermore, compared to patients with non-lower lobe cancer, those with lower lobe cancer had a higher level of tumor markers (neuron-specific enolase and cytokeratin fragment 21-1). Mediation analysis revealed that the association between lower lobe cancer and higher all-cause mortality could be explained by an indirect pathway through EGFR mutations (percent mediated = 17.3%, p = 0.005). The sensitivity analysis for adenocarcinoma patients showed similar results (percent mediated = 18.8%, p = 0.021). Lower lobe cancer is associated with a higher all-cause mortality risk in patients with NSCLC, which is partly mediated by a lower proportion of EGFR mutations.

Quantification of the spatial distribution of primary tumors in the lung to develop new prognostic biomarkers for locally advanced NSCLC

“…In locally advanced NSCLC, lower lung lobe locations have been associated with significantly poorer outcome compared to other lung lobe locations for patients treated with chemoradiotherapy 2 as well as for patients treated with definitive radiation therapy 20 . For resectable stage IIIA NSCLC patients, contradicting results have been reported 3 , 19 , 21 . Proximity of lower lobe tumors favors to spread to the subcarinal station or contralateral hilar lymph nodes, causing in particular in advanced tumor stage a spread to central airway or mediastinum 3 .…”

“…More commonly, tumor location was studied in relation to lobe location. Primary tumors located in the lower lobe were significantly associated with higher mortality rate in 2,289 NSCLC patients of all stages and treated with curative intent or palliative intent with surgery, radiotherapy or chemotherapy (48.6% vs. 40.3%, p < 0.001) 19 . In locally advanced NSCLC, lower lung lobe locations have been associated with significantly poorer outcome compared to other lung lobe locations for patients treated with chemoradiotherapy 2 as well as for patients treated with definitive radiation therapy 20 .…”

“…No clear and distinct outcome association of tumor location was observed for surgically treated patients. Tumor location as a prognostic factor is regarded controversial also due to unknown underlying mediating factors such as histology or possibly mutation status differences between patient groups 17 , 19 , 27 . Further studies are needed to interpret the origin of the differences in spatial distribution.…”

Uncovering interpretable potential confounders in electronic medical records

“…The covariate can point to NSCLC on the lower left node of the lung. Studies have observed that lung cancer on the lower lobe or lower left lobe has worse survival [41, 42]. The covariate could be pointing to a severe conditions related to lung and other problems that indicate poor overall health.…”

Yu-Ping-Feng Formula Exerts Antilung Cancer Effects by Remodeling the Tumor Microenvironment through Regulating Myeloid-Derived Suppressor Cells

“…In recent years, due to the promotion of smoking cessation education, early screening work, and the progress Gr- Evidence-Based Complementary and Alternative Medicine of treatment fields (such as targeted therapy, immunotherapy, etc. ), the mortality rate of lung cancer has shown a rapid trend of decline [26]. However, the current five-year survival rate remains low.…”