scholarly journals Kinetics of plasma cfDNA predicts clinical response in non-small cell lung cancer patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaorong Zhou ◽  
Chenchen Li ◽  
Zhao Zhang ◽  
Daniel Y. Li ◽  
Jinwei Du ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Prognostic Biomarker ◽  
Tumor Burden ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Nsclc Patients ◽  
Kinetics Of

AbstractTyrosine kinase inhibitors (TKIs), VEGF/VEGF receptor inhibitors (VEGFIs) and immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced cancers including non-small-cell lung cancer (NSCLC). This study aims to evaluate the utility of plasma cell-free DNA (cfDNA) as a prognostic biomarker and efficacy predictor of chemotherapy (CT) with or without these precision therapies in NSCLC patients. Peripheral cfDNA levels in 154 NSCLC patients were quantified before and after the first target cycle of chemotherapy. The correlations of cfDNA with tumor burden, clinical characteristics, progression-free survival (PFS)/disease-free survival (DFS), objective response ratio (ORR), and therapy regimens were analyzed respectively. Baseline cfDNA, but not post-chemotherapeutic cfDNA, positively correlates with tumor burden. Notably, cfDNA kinetics (cfDNA Ratio, the ratio of post-chemotherapeutic cfDNA to baseline cfDNA) well distinguished responsive individuals (CR/PR) from the non-responsive (PD/SD). Additionally, cfDNA Ratio was found negatively correlated with PFS in lung adenocarcinoma (LUAD), but not lung squamous-cell carcinoma (LUSC) which may be due to a limited number of LUSC patients in this cohort. LUAD patients with low cfDNA Ratio have prolonged PFS and improved ORR, compared to those with high cfDNA Ratio. When stratified by therapy regimen, the predictive value of cfDNA Ratio is significant in patients with chemotherapy plus VEGFIs, while more patients need be included to validate the value of cfDNA Ratio in other regimens. Thus, the kinetics of plasma cfDNA during chemotherapy may function as a prognostic biomarker and efficacy predictor for NSCLC patients.

Follow up analysis by exosomal miRNAs in EGFR mutated non-small cell lung cancer (NSCLC) patients during osimertinib (AZD9291) treatment: A potential prognostic biomarker tool.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e23035-e23035 ◽  
Author(s):  
Marco Giallombardo ◽  
Jorge Jorge Chacartegui ◽  
Pablo Reclusa ◽  
Jan P. Van Meerbeeck ◽  
Riccardo Alessandro ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Prognostic Biomarker ◽  
Small Cell ◽  
Small Cell Lung ◽  
Exosomal Mirnas ◽  
Nsclc Patients ◽  
Egfr Mutated

Clinical impact of targetable gene alterations on therapeutic outcomes in stage II/III locally advanced non-small cell lung cancer patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9038-9038
Author(s):  
Yoshitaka Zenke ◽  
Shingo Matsumoto ◽  
Terufumi Kato ◽  
Shingo Miyamoto ◽  
Takuma Imakita ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Survival Rate ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Stage Ii ◽  
Small Cell Lung ◽  
Free Survival ◽  
Nsclc Patients ◽  
Gene Alterations

9038 Background: The clinical significance of genetic alterations in stage II/III non-small cell lung cancer (NSCLC) patients has not yet been clarified. We have prospectively analyzed NSCLC patients for cancer-related gene alterations and have followed up clinical course of the patients, establishing a large-scale clinico-genomic database in our nationwide genome screening project (LC-SCRUM-Japan). Methods: Submitted tumor samples were subjected to a targeted next-generation sequencing (NGS) system, Oncomine™ Comprehensive Assay. Therapeutic and prognostic data were collected and updated every year. Results: Since March 2015 to May 2019, 5166 non-squamous NSCLC patients from 263 institutions had been enrolled in the LC-SCRUM-Japan, and 754 of them were diagnosed as stage II/III. The median age of the 754 patients was 67 years (range, 21-92), and 503 (67%) were male, 595 (79%) smokers and 631 (84%) stage III. Of 640 available samples, 258 (40%) had targetable gene alterations, comprising 106 KRAS mut, 42 EGFR mut, 29 BRAF mut, 20 MET ex14skip/amp, 16 ALK fus, 12 ROS1 fus, 11 ERBB2 ex20ins, 8 RET fus, 7 EGFR ex20ins, 5 AKT1 mut, 1 NRG1 fus, 1 FGFR2/3 fus. In patients who received surgery (n = 159), 3-year disease-free survival rate was worse in patients with targetable gene alterations than in those without (40% vs 58% months; p = 0.03). In patients who received cytotoxic chemo-radiotherapy (n = 148), the response rate was similar in patients with targetable gene alterations and those without (70% vs. 77%); however, 3-year progression-free survival rate tended to be shorter in patients with targetable gene alterations than in those without (19% vs 35%; p = 0.08). Conclusions: In stage II/III NSCLC, the total frequency of targetable gene alterations was similar to that previously evaluated in our stage IV cohort (45%), and the current standard therapies showed early progression in the targetable gene-altered patients. A novel effective multimodality treatment in combination with targeted therapies is needed for this population.

Efficacy of afatinib in the clinical practice: Final results of the GIDEON study in EGFR mutated non-small cell lung cancer (NSCLC) in Germany.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21636-e21636
Author(s):  
Wolfgang M. Brueckl ◽  
Martin Reck ◽  
Harald Schäfer ◽  
Cornelius Kortsik ◽  
Tobias Gaska ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Clinical Routine ◽  
Free Survival ◽  
Nsclc Patients ◽  
Egfr Mutated

e21636 Background: Afatinib is an irreversible ErbB family blocker, which is approved for the treatment of advanced non-small cell lung cancer (NSCLC) patients with activating EGFR mutations. Here we report the final results of the prospective non-interventional study (NIS) GIDEON, which was initiated to investigate the efficacy and tolerability of afatinib in the daily clinical routine in Germany. Methods: EGFR-mutated NSCLC patients were treated with afatinib according to label until progression, death or discontinuation. Efficacy (progression-free survival (PFS) rate at 12 months, objective response rate, ORR; disease control rate, DCR; progression-free survival, PFS and overall survival, OS) was prospectively assessed by investigators. Data about tolerability were collected during routine treatment. Results: In total, 161 patients were enrolled at 41 sites in Germany, 152 patients received at least one dose of afatinib (treated set; TS) and 146 patients were treated according to the protocol (PPS). The majority of patients for the entire TS had exon 19 deletions (64.5%), followed by L858R point mut. (22.4%) and uncommon mut. (exon 18-21 point mut.; 13.1%). The primary objective was PFS-rate at 12 months, which was 50.2% in the PPS. Median PFS amounted to 12.2 months. ORR and DCR were 74.6% and 91.5% in the PPS, respectively. Median OS was 30.4 months with 1- and 2-year survival rates of 79.1% and 57.7%, respectively. Among pat. with uncommon EGFR-mut., the 12-months PFS rate was 40.2% with a mPFS of 10.7 months. ORR and DCR were 83.3% and 91.7%, respectively. The most frequent documented adverse drug reactions (ADRs) were diarrhea and rash/acne with 13.8% and 7.2% of grade 3 but no grade 4 or higher. Conclusions: Afatinib is a standard therapy for patients with activating EGFR mut. in Germany. The final results of this prospective NIS confirm the robust clinical data for afatinib in the clinical routine setting, including patients with uncommon exon 18-21 point mutations. Clinical trial information: NCT02047903.

scholarly journals Kinetics of Plasma cfDNA Predicts Clinical Response in Non-Small Cell Lung Cancer Patients

2020 ◽  
Author(s):  
Xiaorong Zhou ◽  
Chenchen Li ◽  
Zhao Zhang ◽  
Daniel Y. Li ◽  
Jinwei Du ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Prognostic Biomarker ◽  
Checkpoint Inhibitors ◽  
Tumor Burden ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
Kinetics Of

AbstractBackgroundTyrosine Kinases Inhibitors (TKIs), VEGF/VEGF receptor inhibitors (VEGFIs, bevacizumab) and immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced cancer including non-small-cell lung cancer (NSCLC). Cell-free DNA (cfDNA) has been adapted as a convenient liquid biopsy that reflects characteristics of the status of both the primary and metastatic tumors, assisting in personalized medicine. This study aims to evaluate the utility of cfDNA as a prognostic biomarker and efficacy predictor of chemotherapy with or without these precision therapies in NSCLC patients.MethodsPeripheral cfDNA levels were quantified in 154 patients with NSCLC before (baseline) and after (post-chemotherapy) the first target cycle of chemotherapy. These patients were divided into four subgroups receiving chemotherapy only, chemotherapy plus TKIs, chemotherapy plus VEGFIs, and chemotherapy plus immune checkpoint inhibitors (ICIs), respectively. The correlations of cfDNA with tumor burden, clinical characteristics, progression-free survival (PFS), objective response ratio (ORR), and therapy regimens were analyzed.ResultsBaseline cfDNA, but not post-chemotherapy, positively correlates with tumor burden. cfDNA Ratio (post-chemotherapy/baseline) well distinguished responsive individuals (CR/PR) from non-responsive patients (PD/SD). Additionally, cfDNA Ratio was found to be negatively correlated with PFS in lung adenocarcinoma (LUAD), but not in lung squamous-cell carcinoma (LUSC). LUAD patients with low cfDNA Ratio benefit significantly including prolonged PFS and improved ORR, compared with those with high cfDNA Ratio. When stratified by therapy regimen, the predictive value of cfDNA Ratio is significant in patients with chemotherapy plus VEGFIs.ConclusionThe kinetics of plasma cfDNA during the chemotherapy may function as a prognostic biomarker and efficacy predictor for NSCLC patients.

scholarly journals Identification of Circulating miR-762 as a Novel Diagnostic and Prognostic Biomarker for Non-Small Cell Lung Cancer

2020 ◽  
Vol 19 ◽  
pp. 153303382096422
Author(s):  
Lei Chen ◽  
Yunxia Li ◽  
Jingshu Lu
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Prognostic Biomarker ◽  
Clinical Stage ◽  
Small Cell ◽  
Proliferative Capacity ◽  
Healthy Individuals ◽  
Small Cell Lung ◽  
Nsclc Patients

Background: MicroRNAs (miRNAs) have been demonstrated to play critical roles in tumorigenesis of non-small cell lung cancer (NSCLC), and circulating miRNAs are a valuable source of biomarkers for the clinical management of NSCLC. The aim of this study was to determine the value of serum miR-762 as a diagnostic and prognostic biomarker for NSCLC. Methods: We examined circulating miR-762 expression in 148 NSCLC patients and 60 healthy individuals using the quantitative real-time polymerase chain reaction (qRT-PCR). The effect of miR-762 downregulation on the proliferative capacity of NSCLC cells were also explored. Results: The serum miR-762 levels were significantly upregulated in NSCLC patients compared to the healthy individuals. Receiver operating characteristics (ROC) curve analysis revealed that circulating miR-762, carcinoembryonic antigen (CEA), CYFRA21-1 and a combination of these 3 biomarkers yield the areas under the curve (AUC) of 0.874, 0.826, 0.41 and 0.969, respectively. Interestingly, circulating miR-762 identified the NSCLC patients at the clinical stage I from healthy controls with an AUC value of 0.920. In addition, serum miR-762 expression was significantly correlated with clinical stage, lymph node metastasis, histological grade and gefitinib-resistance. The survival analysis showed that NSCLC patients in the high serum miR-762 group suffered worse overall survival and relapse-free survival than those in the low serum miR-762 group. The multivariate Cox proportional hazards regression analysis revealed high circulating miR-762 was an independent unfavorable prognostic factor. Downregulation of miR-762 significantly suppressed the proliferative capacity of NSCLC cells in vitro, and bioinformatic analysis of the potential downstream targets of miR-762 identified many important cancer-associated pathways. Conclusions: In conclusion, serum miR-762 might serve as a promising diagnostic and prognostic biomarker for the NSCLC.

scholarly journals Postoperative Radiotherapy for Patients With Resectable Stage III-N2 Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Tianyu Lei ◽  
Jing Li ◽  
Hao Zhong ◽  
Huibo Zhang ◽  
Yan Jin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Postoperative Radiotherapy ◽  
Meta Analysis ◽  
Small Cell ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Free Survival ◽  
Nsclc Patients

PurposeFor resectable cases of stage III-N2 non-small cell lung cancer (NSCLC), the best treatment after surgery is still uncertain. The effect of postoperative radiotherapy (PORT) is controversial. Thus, we performed this updated meta-analysis to reassess the data of PORT in stage III-N2 NSCLC patients, to figure out whether these patients can benefit from PORT.MethodsWe conducted searches of the published literature in EMBASE, PubMed, and the Cochrane Library for relevant randomized control trials (RCTs) comparing PORT group with the non-PORT group in NSCLC patients at stage III-N2. These studies allowed the prior chemotherapy in the treatment. We extracted the data from these articles and used the hazard ratios (HRs) and their 95% confidence intervals (CIs) as summary statistics for estimating the effect of PORT on overall survival (OS), disease-free survival (DFS), local-regional recurrence-free survival (LRFS).ResultThe analyses of seven randomized controlled trials (1,318 participants) show no benefit of PORT on survival (HR, 0.87; 95% CI, 0.71 to 1.07; p = 0.18) but a significantly different effect of PORT on DFS (HR, 0.83; 95% CI, 0.71 to 0.97; p = 0.02) and LRFS (HR, 0.64; 95% CI, 0.50 to 0.81; p = 0.0003). There is not enough evidence of a difference in the effect on survival by the utility of chemotherapy along with PORT though subgroup analysis of no chemotherapy group, concurrent chemoradiotherapy and sequential chemoradiotherapy group. Even in trials with 3D-CRT radiation technique, the pooled analysis shows no benefit of PORT on survival in patients with stage III-N2 NSCLC (data is not shown).ConclusionOur findings illustrate that in the postoperative treatment for patients with stage III-N2 NSCLC, PORT contributes to a significantly increased DFS and LR and may not associate with an improved OS, indicating a cautious selection.

scholarly journals Stereotactic Radiotherapy for Ultra-Central Lung Oligometastases in Non-Small-Cell Lung Cancer

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 885
Author(s):  
Mauro Loi ◽  
Davide Franceschini ◽  
Luca Dominici ◽  
Ciro Franzese ◽  
Ilaria Chiola ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Grade 3 ◽  
Nsclc Patients ◽  
The Impact

Background: Stereotactic body radiotherapy (SBRT) in ultra-central (UC) lung tumors, defined in the presence of planning target volume (PTV) overlap or direct tumor abutment to the central bronchial tree or esophagus, may be correlated to a higher incidence of severe adverse events. Outcome and toxicity in oligometastatic (≤3 metastases) non-small-cell lung cancer (NSCLC) patients receiving SBRT for UC tumors were evaluated. Methods: Oligometastatic NSCLC patients treated with SBRT for UC were retrospectively reviewed. Local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS) were calculated. Incidence and grade of toxicity were evaluated. Statistical analysis was performed to assess the impact of clinical and treatment-related variables on outcome and toxicity occurrence. Results: Seventy-two patients were treated to a median biologically effective dose (BED) of 105 (75–132) Gy10. Two-year LC, DMFS, PFS, and OS were 83%, 46%, 43%, and 49%. BED>75 Gy10 was correlated to superior LC (p = 0.02), PFS (p = 0.036), and OS (p < 0.001). Grade ≥3 toxicity rate was 7%, including one fatal esophagitis. No variables were correlated to DMFS or to occurrence of overall and grade ≥3 toxicity. Conclusions: SBRT using dose-intensive schedules improves outcome in NSCLC patients. Overall toxicity is acceptable, although rare but potentially fatal toxicities may occur.

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