Stage III non-small cell lung cancer (NSCLC) includes a highly heterogeneous group of patients with differences in the extent and localization of disease. Many aspects of stage III disease are controversial. The data supporting treatment approaches are often subject to a number of limitations, due to the heterogeneous patient populations involved in the trials. Furthermore, the definition of stage III disease has changed over time, and early studies were frequently inadequately powered to detect small differences in therapeutic outcome, were not randomized, or had a limited follow-up times. Major improvements in therapy, including the use of more active chemotherapy agents and refinements in radiation and surgical techniques, also limit the interpretation of earlier clinical trials. Lastly, improvements in pretreatment staging have led to reclassification of patients with relatively minimal metastatic disease as stage IV rather than stage III, leading to an apparent increase in the overall survival of both stage III and IV patients. Median overall stage III NSCLC survival ranges from 9 to 34 months. Higher survival rates are observed in younger Caucasian women with good performance status, adenocarcinoma, mutations, stage IIIA, and in patients with multidisciplinary-team-based diagnoses.
Polymorphisms in DNA repair pathways may play a relevant role in lung cancer survival in never-smokers. Furthermore, they could be implicated in the response to chemotherapy and toxicity of platinum agents. The aim of this study was to evaluate the influence of various genetic polymorphisms in the BER and NER DNA repair pathways on survival and toxicity in never-smoker LC patients. The study included never-smokers LC cases diagnosed from 2011 through 2019, belonging to the Lung Cancer Research In Never Smokers study. A total of 356 never-smokers cases participated (79% women; 83% adenocarcinoma and 65% stage IV). Survival at 3 and 5 years from diagnosis was not associated with genetic polymorphisms, except in the subgroup of patients who received radiotherapy or chemo-radiotherapy, and presented with ERCC1 rs3212986 polymorphism. There was greater toxicity in those presenting OGG1 rs1052133 (CG) and ERCC1 rs11615 polymorphisms among patients treated with radiotherapy or chemo-radiotherapy, respectively. In general, polymorphisms in the BER and NER pathways do not seem to play a relevant role in survival and response to treatment among never-smoker LC patients.
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