Analysis of tumor-draining vein secretome: A direct access to tumor-derived extracellular vesicles in surgical lung cancer patients

Tumor-secreted extracellular vesicles(EVs)participate in the metastasis process through different mechanisms,including the preparation of the pre-metastatic niche to grant circulating tumor cells(CTCs)implantation and growth.The study of the metastasis process through the analysis of CTCs and tumor-derived EVs is difficult because of the dilution grade of these elements in peripheral blood.In early-stage lung cancer patients,the tumor-secreted products are even more diluted.An attractive strategy in surgical lung cancer patients is to purify them from a pulmonary tumor-draining vein where they are enriched.The information obtained from the analysis of EVs and CTCs purified from this source could give more accurate information about tumor biology and could be an important source of biomarkers to identify patients at high risk of relapse after curative surgery.

Pathological response to neoadjuvant therapy with chemotherapy vs chemoradiotherapy in stage III NSCLC-contribution of IASLC recommendations

BACKGROUND Neoadjuvant treatment(NT)with chemotherapy(Ch)is a standard option for resectable stage III(N2)NSCLC.Several studies have suggested benefits with the addition of radiotherapy(RT)to NT Ch.The International Association for the Study of Lung Cancer(IASLC)published recommendations for the pathological response(PHR)of NSCLC resection specimens after NT.AIM To contribute to the IASLC recommendations showing our results of PHR to NT Ch vs NT chemoradiotherapy(ChRT).METHODS We analyzed 67 consecutive patients with resectable stage III NSCLC with positive mediastinal nodes treated with surgery after NT Ch or NT ChRT between 2013 and 2020.After NT,all patients were evaluated for radiological response(RR)according to Response Evaluation Criteria in Solid Tumours criteria and evaluated for surgery by a specialized group of thoracic surgeons.All histological samples were examined by the same two pathologists.PHR was evaluated by the percentage of viable cells in the tumor and the resected lymph nodes.RESULTS Forty patients underwent NT ChRT and 27 NT Ch.Fifty-six(83.6%)patients underwent surgery(35 ChRT and 21 Ch).The median time from ChRT to surgery was 6 wk(3-19)and 8 wk(3-21)for Ch patients.We observed significant differences in RR,with disease progression in 2.5%and 14.8%of patients with ChRT and Ch,respectively,and partial response in 62.5%ChRT vs 29.6%Ch(P=0.025).In PHR we observed≤10%viable cells in the tumor in 19(54.4%)and 2 cases(9.5%),and in the resected lymph nodes(RLN)30(85.7%)and 7(33.3%)in ChRT and Ch,respectively(P=0.001).Downstaging was greater in the ChRT compared to the Ch group(80%vs 33.3%;P=0.002).In the univariate analysis,NT ChRT had a significant impact on partial RR[odds ratio(OR)12.5;95%confidence interval(CI):1.21-128.61;P=0.034],a decreased risk of persistence of cancer cells in the tumor and RLN and an 87.5%increased probability for achieving downstaging(OR 8;95%CI:2.34-27.32;P=0.001).CONCLUSION We found significant benefits in RR and PHR by adding RT to Ch as NT.A longer follow-up is necessary to assess the impact on clinical outcomes.