scholarly journals Does the Waiting Period for Genetic Tests Affect the Prognosis in Chemotherapy-Treated de novo Metastatic Non-Small Cell Lung Cancer Patients without a Driver Mutation?

2020 ◽  
pp. 1-7
Author(s):  
Serdar Arici ◽  
Abdullah Sakin ◽  
Ruhper Cekin ◽  
Saban Secmeler ◽  
Nurgül Yasar ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
De Novo ◽  
Small Cell ◽  
Driver Mutations ◽  
Small Cell Lung ◽  
Metastatic Nsclc ◽  
Group A ◽  
Nsclc Patients

<b><i>Introduction:</i></b> The length of the necessary waiting period to test driver mutations may generate anxiety in patients and clinicians. For this reason, an investigation was conducted to determine whether the duration between diagnosis and the start of first-line chemotherapy (DDC) in non-small cell lung cancer (NSCLC) patients without driver mutations has an impact on prognosis. <b><i>Methods:</i></b> The study included 303 de novo metastatic NSCLC patients without a driver mutation and patients were divided into 2 groups according to DDC: ≤30 days (group A) or &#x3e;30 days (group B). The determinant factors for progression-free survival (PFS) and overall survival (OS) were examined by Cox regression analysis. <b><i>Results:</i></b> The mean DDC was calculated as 38.2 ± 54.5 days. The number of patients in group A and B were 183 and 120, respectively. The median PFS in groups A and B was 5.0 and 6.0 months (<i>p</i> = 0.268) and the median OS was 10.0 and 11 months, respectively (<i>p</i> = 0.341). Univariate and multivariate analyses revealed that DDC was not a factor associated with PFS and OS. <b><i>Conclusion:</i></b> Our results show that a higher DDC was not associated with a worse prognosis in metastatic NSCLC patients without driver mutations. In this context, it is safer for patients and their physicians to wait for test results before starting chemotherapy.

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 Efficacy and safety of PD-1/PD-L1 inhibitors plus nab-paclitaxel for patients with non-small cell lung cancer who have progressed after platinum-based chemotherapy

2020 ◽  
Vol 12 ◽  
pp. 175883592093688
Author(s):  
Fan Zhang ◽  
Di Huang ◽  
Lei Zhao ◽  
Tao Li ◽  
Sujie Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Monotherapy Group ◽  
Small Cell Lung ◽  
Metastatic Nsclc ◽  
Platinum Based Chemotherapy ◽  
Paclitaxel Group ◽  
Nsclc Patients

Background: Immunotherapy combined with platinum-based chemotherapy is now the standard first-line treatment for non-small cell lung cancer (NSCLC) patients. However, limited evidence exists to show the efficacy of immunotherapy plus taxanes for patients who have progressed after platinum-based chemotherapy. Methods: The immunotherapy naïve patients with metastatic NSCLC who received anti-PD-1/PD-L1 monotherapy or combined with nab-paclitaxel after prior platinum-based chemotherapy from 2015 to 2018 in PLA General Hospital were identified. The progression-free survival, overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety were assessed. Results: Of 57 patients, 40 were treated with anti-PD-1/PD-L1 monotherapy and 17 were treated with anti-PD-1/PD-L1 plus nab-paclitaxel. With a median OS follow-up of 16.3 months, the nab-paclitaxel group showed significantly longer OS compared with the immune monotherapy group (median, 28.6 months versus 15.9 months, log-rank p = 0.020). When adjusted by covariates in COX proportional regression model, both the treatment group [ p = 0.009, hazard ratio (HR) 0.361; 95% confidence interval (CI) 0.168–0.773] and performance status ( p = 0.003, HR 0.372; 95% CI 0.192–0.721) demonstrated independent association with the longer OS from combination therapy. In addition, ORR was 23.5% (4/17) in the immune checkpoints inhibitors (ICIs) plus nab-paclitaxel group versus 13.5% (5/37) in immune monotherapy group ( p = 0.439), with a DCR of 88.2% (15/17) and 59.5% (22/37) ( p = 0.034), respectively. The incidence of grade 3/4 adverse events was 23.5% (4/17) in the combination group and 2.5% (1/40) in the immune monotherapy group. Conclusion: PD-1/PD-L1 inhibitor plus nab-paclitaxel resulted in significantly longer OS and higher response versus ICI single agent in metastatic NSCLC patients who have progressed after platinum-based chemotherapy. These findings need to be further explored by prospective studies.

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 ALK Mutation Status in EGFR-negative Non-small-cell Lung Cancer Patients in Bulgaria

Folia Medica ◽  
2018 ◽  
Vol 60 (3) ◽  
pp. 397-401
Author(s):  
Slaveyko N. Djambazov ◽  
Toni Y. Vekov ◽  
Evgeni V. Mekov ◽  
Georgi S. Slavchev ◽  
Rosen E. Petkov ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Driver Mutations ◽  
Small Cell Lung ◽  
Alk Rearrangement ◽  
Lung Cancer Patients ◽  
Anaplastic Lymphoma ◽  
Nsclc Patients

Abstract Background: Patients with non-small-cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) rearrangement mutation are found to be 3–13%. Aim: To evaluate the prevalence of ALK mutations in EGFR-negative NSCLC patients in Bulgaria. Materials and methods: One hundred and thirty-two patients with EGFR-negative NSCLC were examined for ALK mutation analysis between January and June 2016. Data were obtained from patients’ register of four major oncological hospitals in Bulgaria. Results: Data were available for 124 (93.9%) patients, tumor mass was insufficient for analysis in 8 (6.1%) patients. Most of the patients were with adenocarcinoma (82 patients, 62.1%); 11 patients (8.3%) were with squamous histology and 2 patients (1.5%) were with other type of NSCLC. Histology data were missing in 37 patients (28.0%). ALK mutation was confirmed in 5 patients (3.8%), 119 (90.2%) patients had ALK wild type. ALK positive patients were with adenocarcinoma (n=3), squamous cell carcinoma (n=1) and other type (n=1) NSCLC. All ALK mutations were observed in never smokers (n=3) and former smokers (n=2). Conclusion: The present study is the first of this kind in Bulgaria – it investigates the prevalence of ALK mutation rate in EGFR-negative NSCLC patients, which was found to be 3.8%. The presence of EGFR, ALK or other driver mutations is a prerequisite for targeted therapy and thus needs to be accurately assessed in NSCLC.

Breast cancer

2018 ◽  
Author(s):  
Jim Cassidy ◽  
Donald Bissett ◽  
Roy A. J. Spence OBE ◽  
Miranda Payne ◽  
Gareth Morris-Stiff ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Symptom Relief ◽  
Small Cell ◽  
Driver Mutations ◽  
Small Cell Lung ◽  
Presenting Symptoms ◽  
Metastatic Nsclc ◽  
Symptoms And Signs

Thoracic cancer examines the epidemiology, aetiology, and role of screening and prevention in the reduction of deaths from lung cancer, the majority caused by cigarette smoking. The pathology and genetics of lung cancer, with particular note of the driver mutations, are followed by the symptoms and signs of the disease. Appropriate investigations are described to stage the tumour. The optimum treatment for localised non-small cell lung cancer (NSCLC) is surgical resection, followed in some cases by adjuvant chemotherapy. However, most cases present with disease too advanced for surgery, and for these chemotherapy and radiotherapy are appropriate. Metastatic NSCLC can be treated with platinum based doublet chemotherapy with modest palliative benefits. Metastatic NSCLC with specific driver mutations are amenable to control by targeted therapy. Locally advanced NSCLC is often treated with similar chemotherapy and radiotherapy, ideally administered concurrently, to achieve symptom relief but also improved survival rates. Short course simple radiotherapy offers symptom relief in patients not fit for chemotherapy. Patients with localised NSCLC who are not fit for surgery, may benefit from radical radiotherapy, particularly stereotactic radiotherapy. Small cell lung cancer (SCLC) is characterised by almost universal systemic spread, so that surgery is rarely appropriate. Staging is similar to NSCLC, and chemotherapy is the mainstay of treatment, usually cisplatin or carboplatin combined with etoposide. When possible, this is combined with concurrent thoracic irradiation covering all radiological sites of disease. Prophylactic cranial irradiation reduces the risk of CNS disease. Malignant pleural mesothelioma is caused by occupational asbestos exposure. Symptoms and signs, investigation and staging, and management are discussed. Thymic tumours, their pathology, presenting symptoms including paraneoplastic syndromes, investigation, staging and treatment are reviewed.

Is survival improving in stage IV non-small cell lung cancer?

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6577-6577
Author(s):  
A. E. Birnbaum ◽  
T. Ng ◽  
B. O'Connor ◽  
A. Plette ◽  
D. Berz
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Stage Iv ◽  
The United States ◽  
Small Cell ◽  
Small Cell Lung ◽  
Metastatic Nsclc ◽  
Time Period ◽  
Nsclc Patients

6577 Background: Non small cell lung cancer (NSCLC) represents the number one cause of cancer mortality in the United States. Over several decades clinical research has focused on the development of new, more active chemotherapeutic drugs to improve survival. Over the time period from 1994 to 2003 six drugs have been approved for the treatment of metastatic NSCLC. We are presenting a population based analysis of the survival in patients with metastatic NSCLC in the US from 1981–1990, 1991–1997 and 1998–2003. We also provide a pharmaco-economic view of this observation. Methods: We analyzed the SEER (Surveillance, Epidemiology, and End Results) program database for cancer specific survival rates in stage IV NSCLC patients who were diagnosed between 1980 and 2003 in the SEER catchment geographic areas. The primary exposure of interest was the year of diagnosis. Results: We identified 52,086 eligible patients in total. 8,950, 21,111 and 18,712 patients were diagnosed 1981 to1990, 1991 to 1997 and 1998 to 2003 respectively. The cox proportional hazard ratios were 0.97 (95% CI 0.94–0.99) and 0.85 (0.83–0.88) for the time periods 1991 to 1997 and 1998 to 2003, respectively, using the time period from 1981 to1990 as reference. This subtle increase in survival was strictly paralleled by increasing costs for the medical care of this patient population. Conclusions: The survival of stage IV NSCLC patients seems to be mildly improving, what is paralleled by increasing cost for the care of those patients. [Table: see text] No significant financial relationships to disclose.

scholarly journals Concurrent T790M and L858R mutations in treatment-naïve metastatic non-small-cell lung cancer: A therapeutic challenge – Current treatment strategies and promising therapies of the future in a nutshell

2017 ◽  
Vol 03 (01) ◽  
pp. 087-091
Author(s):  
M. Babu ◽  
K. Babu ◽  
K. Lokesh ◽  
L. Rajeev ◽  
Gita Bhat
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
De Novo ◽  
Treatment Plan ◽  
Small Cell ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Metastatic Nsclc ◽  
Treatment Naïve

AbstractDe novo (pretreatment) epidermal growth factor receptor T790M mutation in non-small-cell lung cancer (NSCLC) is rare when detected by standard genotyping methods. We present a case of concurrent de novo T790M and L858R mutations detected by direct sequencing in treatment-naïve metastatic NSCLC. This case is worthy of mention as the presence of this mutation has a bearing on the choice of treatment. This article aims to evaluate the clinical outcome for metastatic NSCLC with de novo T790M mutation and formulate an optimum treatment plan in this clinical scenario. The novel targeted therapy agents have also been reviewed.

Tumor-associated exosomal miRNA biomarkers to differentiate metastatic vs. nonmetastatic non-small cell lung cancer

2020 ◽  
Vol 58 (9) ◽  
pp. 1535-1545 ◽  
Author(s):  
Ning Wang ◽  
Wei Guo ◽  
Xingguo Song ◽  
Lisheng Liu ◽  
Limin Niu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Expression Profiles ◽  
Small Cell ◽  
Potential Candidate ◽  
Small Cell Lung ◽  
Diagnostic Biomarkers ◽  
Metastatic Nsclc ◽  
Nsclc Patients

AbstractBackgroundExosomal microRNAs (miRNAs) are proposed to be excellent candidate biomarkers for clinical applications. However, little is known about their potential value as diagnostic biomarkers for metastatic non-small cell lung cancer (NSCLC).MethodsIn this study, microarrays were used to determine distinct miRNA profiles of plasma exosomes in a discovery cohort of healthy donors, metastatic NSCLC and nonmetastatic NSCLC patients. Three potential candidate miRNAs were selected based on the differential expression profiles. The discovery set data were validated by quantitative real-time polymerase chain reaction using a validation cohort.ResultsNSCLC patients (n = 80) and healthy controls (n = 30) had different exosome-related miRNA profiles in plasma. Results demonstrated that the level of let-7f-5p was decreased in plasma exosomes of NSCLC patients (p < 0.0001). Further analysis of three differentially expressed miRNAs revealed that miR-320a, miR-622 and let-7f-5p levels could significantly segregate patients with metastatic NSCLC from patients with nonmetastatic NSCLC (p < 0.0001, p < 0.0001 and p = 0.023, respectively). In addition, the combination of let-7f-5p, CEA and Cyfra21-1 generated an area under the curve (AUC) of 0.981 for the diagnosis of NSCLC patients, and the combination of miR-320a, miR-622, CEA and Cyfra21-1 had an AUC of 0.900 for the diagnosis of patients with metastatic NSCLC.ConclusionsThis novel study demonstrated that plasma exosomal miRNAs are promising noninvasive diagnostic biomarkers for metastatic NSCLC.

scholarly journals Co-Occurring Potentially Actionable Oncogenic Drivers in Non-Small Cell Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Yiming Zhao ◽  
Shuyuan Wang ◽  
Zhengyu Yang ◽  
Yu Dong ◽  
Yanan Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
First Generation ◽  
Kinase Inhibitors ◽  
De Novo ◽  
Treatment Strategies ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

BackgroundSeveral oncogenic drivers in non-small cell lung cancer (NSCLC) are considered actionable with available or promising targeted therapies. Although targetable drivers rarely overlap with each other, there were a minority of patients harboring co-occurring actionable oncogenic targets, whose clinical characteristics and prognosis are not yet clear.MethodsA total of 3,077 patients with NSCLC who underwent molecular analysis by NGS were included, and their demographic and clinical data were retrospectively collected.ResultsOur study found that the frequency of NSCLC patients harboring co-occurring potentially actionable alterations was approximately 1.5% (46/3077); after excluding patients with EGFR-undetermined mutations, the incidence was 1.3% (40/3077); 80% (37/46) harbored both EGFR mutations and other potentially actionable drivers such as MET amplification (21.6%; 8/37) and alterations in ERBB2 including mutations (27%; 10/37) and amplification (21.6%; 8/37); other combinations of potentially actionable drivers including alterations in ERBB2, KRAS, MET, ALK, and RET were also identified. Additionally, de novo MET/ERBB2 amplification in patients harboring EGFR-mutant NSCLC treated with first-generation EGFR tyrosine kinase inhibitors (TKIs) was associated with shorter PFS (p &lt; 0.05). The efficacy of TKIs in NSCLC patients harboring other co-occurring potentially actionable drivers varied across different molecular subtypes.ConclusionsApproximately 1.5% of NSCLCs harbored co-occurring potentially actionable oncogenic drivers, commonly involving EGFR mutations. Co-occurring actionable targets may impact the efficacy of TKIs; therefore, future clinical trials in these patients should be anticipated to tailor the combination or sequential treatment strategies.

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