Mutational landscape of early-stage non-small cell lung cancer patients using a 451 gene panel.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20048-e20048
Author(s):  
Guanxian Mao ◽  
Peng Xuxing ◽  
Wu Hao ◽  
Wang Junbing ◽  
Liu Suyue ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Detection Rate ◽  
Early Stage ◽  
Small Cell ◽  
Driver Mutations ◽  
Small Cell Lung ◽  
Early Stage Nsclc ◽  
Nsclc Patients

e20048 Background: Many studies have reported mutation landscapes of non-small cell lung cancer (NSCLC), but most of the data were from advanced-stage patients. This study reports the mutation landscape of early-stage NSCLC patients. Methods: Many studies have reported mutation landscapes of non-small cell lung cancer (NSCLC), but most of the data were from advanced-stage patients. This study reports the mutation landscape of early-stage NSCLC patients. Results: In all, 74 tDNA and ctDNA samples were analyzed. A total of 285 mutations were identified, including 174 in tDNA and 111 in plasma ctDNA. Genes with the highest -frequencies of mutations in tDNA were EGFR, TP53, KMT2B, BRAF, PIK3CA, CDKN2A, and KRAS,while TP53, EGFR, NOTCH3, PIK3CA, andATM were the genes with the highest frequencies of mutations in ctDNA. The detection rate of driver mutations in tDNA and ctDNA, respectively, were: 42.9% (15/35) and 12.8% (5/39) for EGFR, 5.7% (2/35) and 2.6% (1/39) for ALK, 5.7% (2/35) and 2.6% (1/39) for ERBB2, 11.4% (4/35) and 0%)0/39) for BRAF,5.7% (2/35) and 0%)0/39) for RET, 37% (13/35) and 23.1% (9/39) for TP53. Conclusions: In all, 74 tDNA and ctDNA samples were analyzed. A total of 285 mutations were identified, including 174 in tDNA and 111 in plasma ctDNA. Genes with the highest -frequencies of mutations in tDNA were EGFR, TP53, KMT2B, BRAF, PIK3CA, CDKN2A, and KRAS,while TP53, EGFR, NOTCH3, PIK3CA, andATM were the genes with the highest frequencies of mutations in ctDNA. The detection rate of driver mutations in tDNA and ctDNA, respectively, were: 42.9% (15/35) and 12.8% (5/39) for EGFR, 5.7% (2/35) and 2.6% (1/39) for ALK, 5.7% (2/35) and 2.6% (1/39) for ERBB2, 11.4% (4/35) and 0% )0/39) for BRAF,5.7% (2/35) and 0% )0/39) for RET, 37% (13/35) and 23.1% (9/39) for TP53.

scholarly journals Circulating serum exosomal miR-20b-5p and miR-3187-5p as efficient diagnostic biomarkers for early-stage non-small cell lung cancer

2020 ◽  
Vol 245 (16) ◽  
pp. 1428-1436
Author(s):  
Zhi-Jun Zhang ◽  
Xing-Guo Song ◽  
Li Xie ◽  
Kang-Yu Wang ◽  
You-Yong Tang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Small Cell ◽  
Small Cell Lung ◽  
Diagnostic Biomarkers ◽  
Non Invasive ◽  
Early Stage Nsclc ◽  
Nsclc Patients

Circulating exosomal microRNAs (ExmiRNAs) provide an ideal non-invasive method for cancer diagnosis. In this study, we evaluated two circulating ExmiRNAs in NSCLC patients as a diagnostic tool for early-stage non-small lung cancer (NSCLC). The exosomes were characterized by qNano, transmission electron microscopy, and Western blot, and the ExmiRNA expression was measured by microarrays. The differentially expressed miRNAs were verified by RT-qPCR using peripheral blood specimens from NSCLC patients ( n = 276, 0 and I stage: n = 104) and healthy donors ( n = 282). The diagnostic values were measured by receiver operating characteristic (ROC) analysis. The results show that the expression of both ExmiR-20b-5p and ExmiR-3187-5p was drastically reduced in NSCLC patients. The area under the ROC curve (AUC) was determined to be 0.818 and 0.690 for ExmiR-20b-5p and ExmiR-3187-5p, respectively. When these two ExmiRNAs were combined, the AUC increased to 0.848. When the ExmiRNAs were administered with either carcinoembryonic antigen (CEA) or cytokeratin-19-fragment (CYFRA21-1), the AUC was further improved to 0.905 and 0.894, respectively. Additionally, both ExmiR-20b-5p and ExmiR-3187-5p could be used to distinguish early stages NSCLC (0 and I stage) from the healthy controls. The ROC curves showed that the AUCs were 0.810 and 0.673, respectively. Combination of ExmiR-20b-5p and ExmiR-3187-5p enhanced the AUC to 0.838. When CEA and CYFRA21-1 were administered with the ExmiRNAs, the AUCs were improved to 0.930 and 0.928, respectively. In summary, circulating serum exosomal miR-20b-5p and miR-3187-5p could be used as effective, non-invasive biomarkers for the diagnosis of early-stage NSCLC, and the effects were further improved when the ExmiRNAs were combined. Impact statement The high mortality of non-small cell lung cancer (NSCLC) is mainly because the cancer has progressed to a more advanced stage before diagnosis. If NSCLC can be diagnosed at early stages, especially stage 0 or I, the overall survival rate will be largely improved by definitive treatment such as lobectomy. We herein validated two novel circulating serum ExmiRs as diagnostic biomarkers for early-stage NSCLC to fulfill the unmet medical need. Considering the number of specimens in this study, circulating serum exosomal miR-20b-5p and miR-3187-5p are putative NSCLC biomarkers, which need to be further investigated in a larger randomized controlled clinical trial.

scholarly journals Tumor-Derived Exosomal miR-620 as a Diagnostic Biomarker in Non-Small-Cell Lung Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Youyong Tang ◽  
Zhijun Zhang ◽  
Xingguo Song ◽  
Miao Yu ◽  
Limin Niu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Area Under The Curve ◽  
Small Cell ◽  
Small Cell Lung ◽  
Early Stage Nsclc ◽  
Noninvasive Biomarker ◽  
Nsclc Patients

Background. Evidence has suggested the functional role of exosomal miRNAs in cancer diagnosis. This study aimed to determine whether the serum exosomal biomarkers can improve the diagnosis of patients with non-small-cell lung cancer (NSCLC). Materials and Methods. The exosomes were extracted from the serum of NSCLC patients (n = 235) and healthy donors (n = 231) using ultracentrifugation and then were evaluated by using transmission electron microscopy, qNano, and western blotting. The serum exosomal miRNA expression was validated using qPCR. Results. Exosomal miR-620 was significantly reduced in NSCLC and early-stage NSCLC patients ( P < 0.0001 ) when compared to that of healthy controls, with an area under the curve (AUC) of 0.728 and 0.707, respectively. Exosomal miR-620 expression showed an association with drinking ( P = 0.008 ) and distant metastasis ( P = 0.037 ). Additionally, the downregulated exosomal miR-620 showed association with chemotherapeutic effect ( P = 0.044 ). Conclusion. These findings suggest the serum exosomal miR-620 as a promising diagnostic and prognostic noninvasive biomarker in NSCLC patients.

scholarly journals Molecular profile of KRAS G12C-mutant colorectal and non-small-cell lung cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Luiz Henrique Araujo ◽  
Bianca Mendes Souza ◽  
Laura Rabelo Leite ◽  
Sabrina A. F. Parma ◽  
Natália P. Lopes ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Driver Mutations ◽  
Molecular Profile ◽  
Common Mutation ◽  
Small Cell Lung ◽  
The South ◽  
Nsclc Patients

Abstract Background KRAS is the most frequently mutated oncogene in cancer, however efforts to develop targeted therapies have been largely unsuccessful. Recently, two small-molecule inhibitors, AMG 510 and MRTX849, have shown promising activity in KRAS G12C-mutant solid tumors. The current study aims to assess the molecular profile of KRAS G12C in colorectal (CRC) and non-small-cell lung cancer (NSCLC) tested in a clinical certified laboratory. Methods CRC and NSCLC samples submitted for KRAS testing between 2017 and 2019 were reviewed. CRC samples were tested for KRAS and NRAS by pyrosequencing, while NSCLC samples were submitted to next generation sequencing of KRAS, NRAS, EGFR, and BRAF. Results The dataset comprised 4897 CRC and 4686 NSCLC samples. Among CRC samples, KRAS was mutated in 2354 (48.1%). Most frequent codon 12 mutations were G12D in 731 samples (14.9%) and G12V in 522 (10.7%), followed by G12C in 167 (3.4%). KRAS mutations were more frequent in females than males (p = 0.003), however this difference was exclusive of non-G12C mutants (p < 0.001). KRAS mutation frequency was lower in the South and North regions (p = 0.003), but again KRAS G12C did not differ significantly (p = 0.80). In NSCLC, KRAS mutations were found in 1004 samples (21.4%). As opposed to CRC samples, G12C was the most common mutation in KRAS, in 346 cases (7.4%). The frequency of KRAS G12C was higher in the South and Southeast regions (p = 0.012), and lower in patients younger than 50 years (p < 0.001). KRAS G12C mutations were largely mutually exclusive with other driver mutations; only 11 NSCLC (3.2%) and 1 CRC (0.6%) cases had relevant co-mutations. Conclusions KRAS G12C presents in frequencies higher than several other driver mutations, and may represent a large volume of patients in absolute numbers. KRAS testing should be considered in all CRC and NSCLC patients, independently of clinical or demographic characteristics.

scholarly journals Reduction of Elevated Plasma Osteopontin Levels With Resection of Non–Small-Cell Lung Cancer

2010 ◽  
Vol 28 (6) ◽  
pp. 936-941 ◽  
Author(s):  
Justin D. Blasberg ◽  
Harvey I. Pass ◽  
Chandra M. Goparaju ◽  
Raja M. Flores ◽  
Suzie Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Small Cell ◽  
Enzyme Linked Immunosorbent Assay ◽  
Small Cell Lung ◽  
Early Stage Nsclc ◽  
Independent Cohort

Purpose Plasma osteopontin (OPN) levels in advanced non–small-cell lung cancer (NSCLC) correlate with therapeutic response and survival, but the utility of plasma OPN for diagnosis and monitoring of early-stage NSCLC has not been investigated. We hypothesize that plasma OPN levels are elevated in early-stage NSCLC and decrease with resection. Patients and Methods Presurgery plasma OPN levels (in ng/mL) were measured by enzyme-linked immunosorbent assay (ELISA) in a discovery set of 60 patients with early-stage NSCLC and were compared with data from 56 cancer-free smokers. Presurgery OPN was validated in an independent cohort of 96 patients with resectable NSCLC. The presurgery levels in the latter cohort were compared with matched postsurgery levels. Perioperative OPN levels were correlated with demographics, tumor characteristics, and perioperative events. OPN was monitored during follow-up. Results Discovery set presurgery NSCLC OPN (271 ± 31 ng/mL) was higher than smokers (40 ± 2 ng/mL; P = .001). Presurgery OPN was similar in the NSCLC validation cohort (324 ng/mL ± 20 ng/mL; P = .134). Postsurgery OPN (256 ng/mL ± 21 ng/mL) measured at mean of 9.8 weeks (range, 2 to 46 weeks) was lower than presurgery OPN (P = .005). Time from surgery significantly impacted postsurgery OPN: OPN ≤ 6 weeks postsurgery (303 n/mL ± 26 ng/mL) was higher than OPN greater than 6 weeks postsurgery (177 ng/mL ± 29 ng/mL; P = .003). Multivariate analysis noted correlations between albumin and creatinine to presurgery OPN and use of thoracotomy to postsurgery OPN. Recurrence rate was 5% at 29 weeks mean follow-up. OPN at recurrence was elevated from postsurgery nadir. Conclusion Plasma OPN levels are elevated in early-stage NSCLC. They are reduced after resection and appear to increase with recurrence. Plasma OPN may have utility as a biomarker in early-stage NSCLC.

The mutation profile of genes related to primary resistance to EGFR-TKI in early NSCLC.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21014-e21014
Author(s):  
Jiangang Ye ◽  
Qi Zhang ◽  
Xing Zhang ◽  
Huijuan Qin ◽  
Minqi Tian
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Gene Mutations ◽  
Clinical Information ◽  
Small Cell ◽  
Small Cell Lung ◽  
Primary Resistance ◽  
Nsclc Patients

e21014 Background: In targeted therapy for patients with advanced non-small cell lung cancer (NSCLC), approximately 30% of NSCLC patients with EGFR mutations develop primary resistance at the beginning of treatment with TKIs. However, the knowledge of primary resistance in early-stage NSCLC patients with EGFR positve remains poorly understood. Methods: Mutations of nine genes that may be related to primary resistance EGFR TKIs in advanced non-small cell lung cancer were chosen through pubmed and other databases including EGFR T790M, EGFR 20ins, PIK3CA, KRAS, BRAF, ERBB2 amplification, MET amplification, PTEN deletion and BCL2L11 deletion. Gene mutations related to primary resistance in patients with early-stage lung cancer (I-IIIA) from the TCGA database were analyzed. Results: According to TCGA database, there were 1089 patients with NSCLC of which 585 were lung adenocarcinoma and 504 lung were squamous cell carcinoma. A number of 46 EGFR-sensitive (19del / L858R) mutations were observed in adenocarcinoma, of which the clinical information of which 44 cases harbored competed clinical information including 39 patients with early stage could be identified as follows,1 patient in stage I, 11 patients in stage IA, 8 patients in stage IB, 7 patients in stage IIA, 4 patients in stage IIB, 8 patients in stage IIIA, 1 patient in stage IIIB and 4 patients in stage IV, respectively. Among the 39 cases of early non-small cell lung cancer with EGFR-sensitive mutations, 2 case of EGFR T790M mutations (5.12%), 2 case of PIK3CA (5.12%), 2 case of BRAF (5.12%), 11 case of MET (DUP) (28.2 %), 8 case of ERBB2 (DUP) (20.5%) and 5 case of PTEN (Del) (12.8%) mutations were observed respectively. Meanwhile, none of primary resistance gene mutations could be found in non-small cell lung squamous cell cancer(0/1). Conclusions: The presence of different mutation frequency in the primary resistance genes associated with EGFR TKIs in patients with early NSCLC was proved. Our study suggested it was necessary for patients to test mutations in primary resistance genes before accepted the adjuvant and neoadjuvant therapy using TKIs. As a retrospective study with a relatively small population, the conclusions of this study needed to be verified with a larger sample.

scholarly journals Stereotactic Body Radiation Therapy Mitigates Radiation Induced Lymphopenia in Early Stage Non-Small Cell Lung Cancer

2020 ◽  
Author(s):  
Mark McLaughlin ◽  
Morshed Alam ◽  
Lynette Smith ◽  
Jeffrey Ryckman ◽  
Chi Lin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Radiation Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Stereotactic Body Radiation Therapy ◽  
Early Stage ◽  
Small Cell ◽  
Small Cell Lung ◽  
Early Stage Nsclc ◽  
Radiation Induced

Abstract Background Radiation-induced lymphopenia (RIL) occurs during treatment with conventional radiation in multiple organ sites. Development of RIL portends poor prognosis. Stereotactic body radiation therapy (SBRT) spares RIL in pancreatic cancer, but has not been examined in other sites commonly treated with SBRT. This work examines if SBRT similarly spares RIL in patients with non-small cell lung cancer (NSCLC). Methods Retrospective analysis was done at a single institution on 40 distinct cases of SBRT for early stage NSCLC from 2006-2017. Incidentally collected lymphocyte counts collected within 6 months of SBRT treatment were analyzed to determine if RIL occurred. The presence of RIL was correlated with location of initial failure and survival endpoints. Kaplan-Meier curves were constructed with significance defined at the level p = 0.05. Results RIL was observed in 35% of the analyzed patients. Patterns of failure and survival data were comparable to prior SBRT literature. There was no observed association in two year local, nodal, or distant failure, progression free survival, or overall survival based on the presence of RIL. Conclusions SBRT spares RIL in NSCLC compared to historical rates observed with conventionally fractionated radiation. As understanding of the role of the immune system in cancer control continues to evolve, the importance of RIL sparing techniques take on increasing importance. This study represents the first analysis of RIL sparing in SBRT in an early stage NSCLC cohort without the confounding influence of chemotherapy.

scholarly journals ASCO 2021—selection of personal highlights in early stage non-small cell lung cancer

2021 ◽  
Author(s):  
Gudrun Absenger ◽  
Andreas Pircher
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Early Stage ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Adjuvant Setting ◽  
Small Cell Lung ◽  
Early Stage Nsclc

SummaryThis article intends to summarize personal non-small cell lung cancer (NSCLC) highlights of the virtual ASCO 2021 meeting. Immunotherapy is now a mainstay of advanced stage NSCLC treatment and there are several ongoing studies investigating the role of immunotherapy in early stage NSCLC. At ASCO 2021 the first data on atezolizumab in the adjuvant setting were presented and give a positive signal that immunotherapy will also become an option for patient in early stage NSCLC. Furthermore, overall survival (OS) updates of two studies investigating the effects of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in the adjuvant setting of EGFR-mutated NSCLC patients were presented. In conclusion ASCO 2021 provided the lung cancer community with inspiring new data especial in early stages and challenges the community with integration of these data into our daily clinical routine.

scholarly journals Factors influencing patient satisfaction after treatments for early-stage non-small cell lung cancer

2021 ◽  
Author(s):  
Cecilia Pompili ◽  
Sanjush Dalmia ◽  
Finn McLennan Battleday ◽  
Zoe Rogers ◽  
Kate Absolom ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Decision Making ◽  
Patient Satisfaction ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Small Cell ◽  
Small Cell Lung ◽  
Early Stage Nsclc ◽  
Patient Reported

Abstract Purpose Patient-reported outcome measures, including satisfaction with treatment decisions, provide important information in addition to clinical outcomes, survival and decision-making in lung cancer surgery. We investigated associations between preoperative clinical and socio-demographic factors and patient-reported satisfaction 6 weeks after radical treatment for early-stage non-small cell lung cancer (NSCLC). Methods We conducted a sub-group analysis of the prospective observational longitudinal study of 225 participants in two treatment groups—surgical (VATS) and radiotherapy (SABR). The Patient Satisfaction Questionnaire-18 (PSQ-18) was used to measure patient satisfaction 6 weeks after treatment. Clinical variables, Index of Multiple Deprivation decile and Decision self-efficacy scores were used in regression analysis. Variables with a p level < 0.1 were used as independent predictors in generalised linear logistic regression analyses. Results As expected, the two groups differed in pre-treatment clinical features. The SABR group experienced more grade 1–2 complications than the VATS group. No differences were found between the groups in any subscale of the PSQ-18 questionnaire. Patients experiencing complications or living in more deprived areas were more satisfied with care. Properative factors independently associated with patient satisfaction were the efficacy in decision-making and age. Conclusion We showed that efficacy in treatment decision-making and age was the sole predictor of patient satisfaction with their care after radical treatment for early-stage NSCLC. Patients from more deprived areas and patients who suffered complications reported greater subsequent satisfaction. Involving patients in their care may improve satisfaction after treatment for early-stage NSCLC.

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