Circulating biomarkers and outcomes in advanced non-small cell lung cancer patients treated with anti-PD1 (program death 1 receptor) monoclonal antibodies.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20592-e20592
Author(s):  
Mary J. Fidler ◽  
Marta Batus ◽  
Imad Tarhoni ◽  
Selina Sayidine ◽  
Cristina L. Fhied ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune System ◽  
T Cell ◽  
Pilot Study ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Prognostic Value ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

e20592 Background: Current evaluation of immunohistochemical expression of PDL-1 (program death receptor 1 ligand) can select some non-small cell lung cancer (NSCLC) patients who may benefit from anti-PD1 directed therapy. It is an imperfect marker and there is little information about systemic modulation of the immune system on therapy. In this study we explored the prognostic value of baseline circulating immune checkpoint and inflammatory molecules in advanced non-small cell lung cancer (NSCLC) patients receiving anti-PD1 therapy. Methods: Prospectively collected serum from advanced NSCLC patients receiving nivolumab or pembrolizumab were evaluated with the MILLIPLEX Human High Sensitivity T-cell (17-plex) and ProcartaPlex Human Immuno-Oncology Checkpoint (14-plex) panels on our Luminex FlexMAP 3D. Biomarker level cutoffs were optimized and evaluated against progression-free survival (PFS) and overall survival (OS) using log-rank analysis. Results: 21 cases were enrolled in this pilot study: 72% Caucasian, 61% female, 24% never-smokers. IL-10 was found to have a significant association with both PFS (p = 0.0055) and OS (p = 0.024), with levels below 3.32 pg/mL being associated with a superior clinical outcome. We also found IL-2 and IL-6 to have significant associations with PFS (p = 0.033 and 0.040, respectively), again, with low levels being associated with a superior outcome. Neither of these had significant associations with OS. Low circulating levels of the T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) protein were associated with superior PFS (p = 0.036), and a weak trend (p = 0.19) for OS. Conclusions: In this small exploratory pilot study we identified several circulating molecules associated with inflammation and immune system regulation that may have prognostic value for anti-PD-1 therapy. Notably, TIM-3 is a Th1-specific protein associated with macrophage activation and is also a component of T-cell exhaustion along with LAG3 and PD-1. Additional studies to follow up on these findings in larger cohorts are underway.

scholarly journals P2-095: Prognostic value of the determination of K-ras mutations plasma in advanced non-small cell lung cancer (NSCLC) patients

2007 ◽  
Vol 2 (8) ◽  
pp. S528-S529
Author(s):  
Rafael Sirera ◽  
Carlos Camps ◽  
José-Luis González-Larriba ◽  
Juan Lao ◽  
R García-Gómez ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Prognostic Value ◽  
Small Cell ◽  
Small Cell Lung ◽  
Ras Mutations ◽  
Nsclc Patients

scholarly journals Prognostic Roles of mRNA Expression of S100 in Non-Small-Cell Lung Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Ying Liu ◽  
Jian Cui ◽  
Yun-Liang Tang ◽  
Liang Huang ◽  
Cong-Yang Zhou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Mrna Expression ◽  
Cell Lung Cancer ◽  
Prognostic Value ◽  
Smoking Status ◽  
S100 Protein ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

The S100 protein family is involved in cancer cell invasion and metastasis, but its prognostic value in non-small-cell lung cancer (NSCLC) has not been elucidated. In the present study we investigated the prognostic role of mRNA expression of each individual S100 in NSCLC patients through the Kaplan–Meier plotter (KM plotter) database. Expression of 14 members of the S100 family correlated with overall survival (OS) for all NSCLC patients; 18 members were associated with OS in adenocarcinoma, but none were associated with OS in squamous cell carcinoma. In particular, high mRNA expression level of S100B was associated with better OS in NSCLC patients. The prognostic value of S100 according to smoking status, pathological grades, clinical stages, and chemotherapeutic treatment of NSCLC was further assessed. Although the results should be further verified in clinical trials our findings provide new insights into the prognostic roles of S100 proteins in NSCLC and might promote development of S100-targeted inhibitors for the treatment of NSCLC.

Surrogates of response to treatment of non-small cell lung cancer with immunotherapy: Toxicity and leukocyte ratios—Experience of a center.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21052-e21052
Author(s):  
Alba Moratiel Pellitero ◽  
Ines Ruiz Moreno ◽  
Mara Cruellas ◽  
Natalia Alonso Marin ◽  
Maitane Ocáriz ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune System ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Neutrophil To Lymphocyte Ratio ◽  
Small Cell Lung ◽  
Lymphocyte Ratio ◽  
Nsclc Patients ◽  
Worse Prognosis

e21052 Background: Immunotherapy is proposed as a therapeutic novelty in metastatic non-small cell lung cancer (NSCLC), in many cases already in front line. It presents different adverse effects than traditional schemes, due to the stimulation of the immune system. There is a possible relationship between toxicity and response. Neutrophil-to-lymphocyte ratio (NLR) as a possible predictive factor of response. Objectives: Evaluating the response according to the toxicity degree in NSCLC patients in real clinical practice. Analyze whether pretreatment NLR high patients have a worse prognosis. Methods: Observational, retrospective, analytical, single-center study. HCULB stage IV NSCLC patients with inmunotherapy treatment during 2016-2018. Descriptive and multivariate analysis. Toxicity grade: CTCAE version 4.0. Response assessment: RECIST 2.0 and immunorelated criteria. Toxicity degree and response (global and individualized results according to treatment and histology). Neutrophil-to-lymphocyte ratio and response. Results: N = 43 patients (35 men, 8 women). Average age 64 years. Response: 3 complete response (CR) (toxicity ≥2), 13 partial response (PR) (toxicity ≥1), 13 stable disease (SD), 12 progression (P) (only 4 toxicity and ≤2), 2 not evaluated. Hypothyroidism as the most common irAE. Relationship between toxicity and response: the absence of irAEs conditions worse prognosis p < 0.05. Histology: 25 adenocarcinoma [18 with irAES (1 CR, 7 PR, 8 SD,) and 7 without (1 SD, 5 P, 1 no ev.)]; 17 squamous [13 with irAES (1 CR, 6 PR, 4 SD) and 4 without (3 P, 1 no ev.)]; 1 adenosquamous with irAES and CR. Drug: Atezolizumab N = 8 [6 with irAES (2 PR, 3 SD, 1 P) and 2 without (both P)], Nivolumab N = 16 [9 with irAES (1 CR, 3 PR, 3 SD, 2 P) and 7 without (1 SD, 4 P, 2 no ev.)], Pembrolizumab N = 19 [17 with irAEs (2 CR, 8 PR, 6 SD, 1 P) and 2 without (both P)]. Significant positive correlation between toxicity and response (p < 0.001) R = 0.067, (CI 99% 0.378-0.837), regardless of histology and drug. It is observed a better response in those patients who presented a NRL close to 3 or less at the beginning of treatment. On the contrary, it is observed that subjects with NRL greater than 4 obtained worse results when they were treated with immunotherapy. Conclusions: The appearance of irAES like a response indicator of immune system, seem to conditione better evolution. In contrast, the absence of toxicity predicts a worse prognosis. Further studies with a larger sample are needed to confirm our findings about the predictive value of NLR and optimize therapeutic regimens if necessary.

Abstract A31: Predictive and prognostic value of KRAS mutations in advanced non-small cell lung cancer (NSCLC) patients treated with chemotherapy

2012 ◽  
Vol 18 (3 Supplement) ◽  
pp. A31-A31
Author(s):  
Wouter W. Mellema ◽  
Anne-Marie C. Dingemans ◽  
Egbert F. Smit ◽  
Jules Derks ◽  
Daniëlle A.M. Heideman ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Prognostic Value ◽  
Small Cell ◽  
Small Cell Lung ◽  
Kras Mutations ◽  
Nsclc Patients ◽  
Predictive And Prognostic Value

scholarly journals Neoantigen vaccination induces clinical and immunologic responses in non-small cell lung cancer patients harboring EGFR mutations

2021 ◽  
Vol 9 (7) ◽  
pp. e002531
Author(s):  
Fenge Li ◽  
Ligang Deng ◽  
Kyle R Jackson ◽  
Amjad H Talukder ◽  
Arjun S Katailiha ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cell ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Cell Responses ◽  
Clinical Responses ◽  
Nsclc Patients

BackgroundNeoantigen (NeoAg) peptides displayed at the tumor cell surface by human leukocyte antigen molecules show exquisite tumor specificity and can elicit T cell mediated tumor rejection. However, few NeoAgs are predicted to be shared between patients, and none to date have demonstrated therapeutic value in the context of vaccination.MethodsWe report here a phase I trial of personalized NeoAg peptide vaccination (PPV) of 24 stage III/IV non-small cell lung cancer (NSCLC) patients who had previously progressed following multiple conventional therapies, including surgery, radiation, chemotherapy, and tyrosine kinase inhibitors (TKIs). Primary endpoints of the trial evaluated feasibility, tolerability, and safety of the personalized vaccination approach, and secondary trial endpoints assessed tumor-specific immune reactivity and clinical responses. Of the 16 patients with epidermal growth factor receptor (EGFR) mutations, nine continued TKI therapy concurrent with PPV and seven patients received PPV alone.ResultsOut of 29 patients enrolled in the trial, 24 were immunized with personalized NeoAg peptides. Aside from transient rash, fatigue and/or fever observed in three patients, no other treatment-related adverse events were observed. Median progression-free survival and overall survival of the 24 vaccinated patients were 6.0 and 8.9 months, respectively. Within 3–4 months following initiation of PPV, seven RECIST-based objective clinical responses including one complete response were observed. Notably, all seven clinical responders had EGFR-mutated tumors, including four patients that had continued TKI therapy concurrently with PPV. Immune monitoring showed that five of the seven responding patients demonstrated vaccine-induced T cell responses against EGFR NeoAg peptides. Furthermore, two highly shared EGFR mutations (L858R and T790M) were shown to be immunogenic in four of the responding patients, all of whom demonstrated increases in peripheral blood neoantigen-specific CD8+ T cell frequencies during the course of PPV.ConclusionsThese results show that personalized NeoAg vaccination is feasible and safe for advanced-stage NSCLC patients. The clinical and immune responses observed following PPV suggest that EGFR mutations constitute shared, immunogenic neoantigens with promising immunotherapeutic potential for large subsets of NSCLC patients. Furthermore, PPV with concurrent EGFR inhibitor therapy was well tolerated and may have contributed to the induction of PPV-induced T cell responses.

scholarly journals Targeting lactate dehydrogenase a improves radiotherapy efficacy in non-small cell lung cancer: from bedside to bench

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yang Yang ◽  
Yu Chong ◽  
Mengyuan Chen ◽  
Wumin Dai ◽  
Xia Zhou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Lactate Dehydrogenase ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Prognostic Value ◽  
Small Cell ◽  
Atp Depletion ◽  
Small Cell Lung ◽  
Nsclc Patients

Abstract Background Lactate dehydrogenase A (LDHA) is overexpressed and associated with poor prognosis in many kinds of cancer. In the current study, we evaluated the prognostic value of LDHA expression in non-small cell lung cancer (NSCLC), and tested whether LDHA inhibition might improve radiotherapy efficacy in NSCLC. Methods LDHA expression was investigated in NSCLC patients, using online database and further verified by immunohistochemistry. The prognostic value of LDHA was evaluated using Kaplan–Meier plotter database. In vitro, two NSCLC cell lines were pretreated with oxamate, an inhibitor of LDHA, and colony formation method was performed to determine cellular radiosensitivity. Comet assay was used to detect DNA damage after irradiation. Flow cytometry was applied to test cell cycle progression and apoptosis, and monodansylcadaverine (MDC) staining was used to examine cell autophagy. Results Both mRNA and protein levels of LDHA expression were up-regulated in NSCLC tissues. High LDHA expression was a poor prognostic factor and associated with radioresistance in NSCLC patients. LDHA inhibition by oxamate remarkably increased radiosensitivity in both A549 and H1975 cancer cells, and enhanced ionizing radiation (IR)-induced apoptosis and autophagy, accompanied by cell cycle distribution alternations. Furthermore, LDHA inhibition induced reactive oxygen species (ROS) accumulation and cellular ATP depletion, which might increase DNA injury and hinder DNA repair activity. Conclusions Our study suggests that inhibition of LDHA may be a potential strategy to improve radiotherapy efficacy in NSCLC patients, which needs to be further tested by clinical trials.

Targeting Lactate Dehydrogenase A Improves Radiotherapy Efficacy in Non-Small Cell Lung Cancer: From Bedside to Bench

2021 ◽  
Author(s):  
Yang Yang ◽  
Yu Chong ◽  
Mengyuan Chen ◽  
Wumin Dai ◽  
Xia Zhou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Prognostic Value ◽  
Small Cell ◽  
Atp Depletion ◽  
Small Cell Lung ◽  
Poor Prognostic Factor ◽  
Nsclc Patients

Abstract BackgroundLDHA is overexpressed in many kinds of cancer, and associated with poor prognosis. In the current study, we evaluated the prognostic value of LDHA expression in non-small cell lung cancer (NSCLC), and tested whether LDHA inhibition might improve radiotherapy efficacy in NSCLC.MethodsLDHA mRNA expression was investigated in NSCLC patients, using online database and further verified by immunohistochemistry. The prognostic value of LDHA was evaluated using Kaplan-Meier plotter database. In vitro, two NSCLC cell lines were pretreated with oxamate, an inhibitor of LDHA, and colony formation method was performed to determine cellular radiosensitivity. Comet assay was used to detect DNA damage after irradiation. Flow cytometry was applied to test cell cycle progression and apoptosis, and autophagy was examined by monodansylcadaverin (MDC) staining.ResultsBoth mRNA and protein levels of LDHA expression were up-regulated in NSCLC tissues. High LDHA expression was a poor prognostic factor and associated with radioresistance in NSCLC patients. LDHA inhibition by oxamate remarkably increased radiosensitivity in both A549 and H1975 cancer cells, and enhanced ionizing radiation (IR)-induced apoptosis and autophagy, accompanied by cell cycle distribution alternations. Furthermore, LDHA inhibition induced reactive oxygen species (ROS) accumulation and cellular ATP depletion, which might increase DNA injury and hinder DNA repair activity.ConclusionsOur study suggests inhibition of LDHA may be a potential strategy to improve radiotherapy efficacy in NSCLC patients, which needs to be further tested by clinical trials.

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