Clinical-pathological and molecular characterization of long-term survivors with advanced non-small cell lung cancer

Objective:Long-term survivors(LS)of non-small cell lung cancer(NSCLC)without driver alterations,displaying an overall survival(OS)of more than 3 years,comprise around 10%of cases in several series treated with chemotherapy.There are classical prognosis factors for these cases[stage,Eastern Cooperative Oncology Group(ECOG),etc.],but more data are required in the literature.In this multi-center study,we focused on LS of advanced NSCLC with OS above 36 months to perform a clinical-pathological and molecular characterization.Methods:In the first step,we conducted a clinical-pathological characterization of the patients.Afterwards,we carried out a genetic analysis by comparing LS to a sample of short-term survivors(SS)(with an OS less than 9 months).We initially used whole-genome RNA-seq to identify differentiating profiles of LS and SS,and later confirmed these with reverse transcription-polymerase chain reaction(RT-PCR)for the rest of the samples.Results:A total of 94 patients were included,who were mainly men,former smokers,having adenocarcinoma(AC)-type NSCLC with an ECOG of 0-1.We obtained an initial differential transcriptome expression,displaying 5 over-and 33 under-expressed genes involved in different pathways:namely,the secretin receptor,surfactant protein,trefoil factor 1(T FF1),serpin,Ca-channels,and Tolllike receptor(TLRs)families.Finally,RT-PCR analysis of 40(20 LS/20 SS)samples confirmed that four genes(surfactant proteins and SFTP)were significantly down-regulated in SS compared to LS by using an analysis of covariance(ANCOVA)model:SFTPA1(P=0.023),SFTPA2(P=0.027),SFTPB{P=0.02),and SFT PC(P=0.047).Conclusions:We present a sequential genetic analysis of a sample of NSCLCLS with no driver alterations,obtaining a differential RNA-seq/RT-PCR profile showing an abnormal expression of SF genes.

New challenges in the combination of radiotherapy and immunotherapy in non-small cell lung cancer

Immunotherapy has represented one of the main medical revolutions of recent decades,and is currently a consolidated treatment for different types of tumors at different stages and scenarios,and is present in a multitude of clinical trials.One of the diseases in which it is most developed is non-small cell lung cancer.The combination of radiotherapy and immunotherapy in cancer in general and lung cancer in particular currently represents one of the main focuses of basic and clinical research in oncology,due to the synergy of this interaction,which can improve tumor response,resulting in improved survival and disease control.In this review we present the biochemical and molecular basis of the interaction between radiotherapy and immunotherapy.We also present the current clinical status of this interaction in each of the stages and cases of non-small cell lung cancer,with the main results obtained in the different studies both in terms of tumor response and survival as well as toxicity.Finally,we mention the main studies underway and the challenges of this interaction in the coming years,including how these treatments should be combined to achieve the greatest efficacy with the fewest possible side effects(dose,type of radiotherapy and drugs,sequence of treatments).