scholarly journals The Prognostic Effect of KRAS Mutations in Non-Small Cell Lung Carcinoma Revisited: A Norwegian Multicentre Study

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4294
Author(s):  
Sissel Gyrid Freim Wahl ◽  
Hong Yan Dai ◽  
Elisabeth Fritzke Emdal ◽  
Thomas Berg ◽  
Tarje Onsøien Halvorsen ◽  
...  
Keyword(s):  
Kras Mutation ◽  
Clinical Characteristics ◽  
Small Cell Lung Carcinoma ◽  
Progression Free Survival ◽  
Small Cell ◽  
Prognostic Impact ◽  
Small Cell Lung ◽  
Kras Mutations ◽  
Cell Lung Carcinoma ◽  
Kras Status

Background: due to emerging therapeutics targeting KRAS G12C and previous reports with conflicting results regarding the prognostic impact of KRAS and KRAS G12C in non-small cell lung cancer (NSCLC), we aimed to investigate the frequency of KRAS mutations and their associations with clinical characteristics and outcome. Since mutation subtypes have different preferences for downstream pathways, we also aimed to investigate whether there were differences in outcome according to mutation preference for the Raf, PI3K/Akt, or RalGDS/Ral pathways. Methods: retrospectively, clinicopathological data from 1233 stage I–IV non-squamous NSCLC patients with known KRAS status were reviewed. KRAS’ associations with clinical characteristics were analysed. Progression free survival (PFS) and overall survival (OS) were assessed for the following groups: KRAS wild type (wt) versus mutated, KRAS wt versus KRAS G12C versus KRAS non-G12C, among KRAS mutation subtypes and among mutation subtypes grouped according to preference for downstream pathways. Results: a total of 1117 patients were included; 38% had KRAS mutated tumours, 17% had G12C. Among KRAS mutated, G12C was the most frequent mutation in former/current smokers (45%) and G12D in never smokers (46%). There were no significant differences in survival according to KRAS status, G12C status, among KRAS mutation subtypes or mutation preference for downstream pathways. Conclusion: KRAS status or KRAS mutation subtype did not have any significant influence on PFS or OS.

Real-world evidence in the treatment of metastatic non-small cell lung cancer in a single institution of Colombia in the period August 2015 to August 2018.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18204-e18204
Author(s):  
Luis Eduardo Pino ◽  
Aylen Vanessa Ospina Serrano ◽  
Ivan Camilo Triana
Keyword(s):  
Lung Cancer ◽  
Clinical Characteristics ◽  
Egfr Mutation ◽  
Small Cell Lung Carcinoma ◽  
Target Therapy ◽  
Stage Iv ◽  
Small Cell ◽  
Small Cell Lung ◽  
Alk Rearrangement ◽  
Cell Lung Carcinoma

e18204 Background: In Colombia, lung cancer is the first cause of mortality. However, there is a large gap in terms of the information available regarding the characteristics and survival of these patients in the country. Methods: This is an observational, descriptive study of a cohort of patients with stage IV non-small cell lung carcinoma who initiated medical treatment at Fundación Santa Fe de Bogotá, a high complexity hospital. We analyzed clinical characteristics, oncogenic addiction expression, PDL1 expression, treatments, progression free survival (PFS), overall survival (OSm) and treatment related complications. Results: Twenty-six patients were included during the 3 years. The OSm for all the cohort was 19.6 months(m). In the group without PDL-1 expression and negative for oncogenic addiction that received treatment with chemotherapy the OSm was 16.9m and the PFS 9.6m. The OSm for the group with EGFR mutation that received target therapy was 24,7m and the PFS 13.11m. The patients with ALK rearrangement treated with target therapy had an OSm 17m and PFS 5m. The group with expression greater than 50% for PDL-1 that received only immunotherapy OSm was 9.5m and PFS 9m, and in the group with expression for PDL-1 between 1-49% the median OSm and PFS has not been reached. In relation with grade 3 toxicity, 7% of patients that received chemotherapy had kidney failure, 7% emesis and 15% hyporexia. Patients that received target therapy 9% had diarrhea and 9% hepatotoxicity. 9% of patients with bevacizumab presented bleeding and 8% of patients with immunotherapy had autoimmune colitis, in all these cases the medication was suspended. Hypothyroidism was the most frequent complication with the immunotherapy, and it was resolved with substitution therapy. Conclusions: Clinical characteristics and outcomes of this cohort were similar to other lung cancer patients series. Factors like cigarette, nutritional status and ECOG were no significant in the survival. 34,6% of patients had EGFR mutation and 7% had ALK rearrangements. Related to PDL1 we found 26% expresser patients. The highest OS and PFS was for the group with the EGFR mutation and for the group with PDL-1 expression between 1-49%.

Therapeutic impact of mutation subtypes and concomitant STK11 mutations in KRAS–mutated non-small cell lung cancer (NSCLC): A result of nationwide genomic screening project (LC-SCRUM-Japan).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9589-9589 ◽  
Author(s):  
Yutaro Tamiya ◽  
Yoshitaka Zenke ◽  
Shingo Matsumoto ◽  
Naoki Furuya ◽  
Tomohiro Sakamoto ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kras Mutation ◽  
Progression Free Survival ◽  
Genetic Alterations ◽  
Small Cell ◽  
Small Cell Lung ◽  
Kras Mutations ◽  
Genomic Screening

9589 Background: KRAS mutations are one of the common oncogene drivers in non-small cell lung cancer (NSCLC), and the development of several targeted drugs for KRAS-mutated NSCLC is now ongoing. However, the clinical impact of KRAS mutation subtypes or concomitant other gene mutations in NSCLC patients (pts) remains unclear. Methods: In a nationwide genomic screening project (LC-SCRUM-Japan), we have prospectively analyzed lung cancer pts for genetic alterations and tumor mutation burden (TMB) by next-generation sequencing system, and for PD-L1 expression by immunohistochemistry (22C3 antibody). The therapeutic efficacy and survival of KRAS-mutated non-squamous (non-sq) NSCLC pts were evaluated using a clinico-genomic database of the LC-SCRUM-Japan. Results: A total of 5166 non-sq NSCLC pts enrolled from 2015 to 2019. KRAS mutations were detected in 794 pts (15%; G12C/G12D/G12V/G12A/G13X/others = 232/186/165/66/61/84). Among the 794 pts, TMB and PD-L1 expression were analyzed in 128 and 79, respectively, and 218 received PD-1/PD-L1 inhibitors (IO) after 1st-line chemotherapy. The median age was 66 years (range, 29-89). 142 pts (65%) were male and 172 (78%) were smokers. Concomitant STK11 mutations were detected in 33 pts (15%) with no difference in the mutation frequency among KRAS mutation subtypes. KRAS G12C was significantly associated with high TMB (≥ 10 mut/Mb) (p = 0.03), and KRAS G12C or G12V with high PD-L1 expression (≥ 50%) (p = 0.02). In pts who received IO, median progression-free survival (mPFS) was significantly longer in pts with KRAS G12C or G12V than in those with other KRAS mutations (4.7 vs 2.0 months, hazard ratio (HR) 0.58 [95%CI 0.43-0.78], p < 0.01). Among pts with KRAS G12C or G12V, mPFS of IO was significantly shorter in pts with concomitant STK11 mutations than in those without (1.8 vs. 5.7 months, HR 1.97 [95%CI 1.06-3.41], p = 0.02). These correlations were not observed in platinum-containing chemotherapy (Plt-CTx). There were also no significant differences in IO and Plt-CTx efficacies between with and without other concomitant mutations, such as TP53, RB1, CDKN2A and PTEN mutations. Conclusions: Non-sq NSCLC pts with KRAS G12C/V were more sensitive to IO therapies than those with other KRAS mutations, but KRAS G12C/V-positive pts with concomitant STK11 mutations were less sensitive than those without. These results could be highly informative in the development of novel targeted therapies for KRAS-mutated NSCLC.

scholarly journals Cryptococcal Endocarditis in a Woman with Metastatic Non-Small Cell Lung Cancer: A Case Report and Review of the Literature

2020 ◽  
pp. 1-5
Author(s):  
Tony Kurian ◽  
Tony Kurian ◽  
Jason Peng ◽  
Courtney Regan Wagner ◽  
Fritzie S. Albarillo
Keyword(s):  
Kinase Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Replacement Surgery ◽  
History Of ◽  
Epidermal Growth

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have demonstrated improved progression-free survival benefits and decreased treatment-related side effects, and therefore are now considered first-line of treatment of EGFR mutated, metastatic non-small cell lung carcinoma (NSCLC). Cryptococcal endocarditis is an extremely rare clinical entity with only seven reported cases in the literature. Prior cases were seen in patients with a history of rheumatic heart disease or prior valve replacement surgery. Little is known regarding the natural history and optimal management of Cryptococcal endocarditis, given the limited available data. We present a case of Cryptococcal endocarditis and meningitis in a patient with metastatic NSCLC receiving targeted therapy with an EGFR-TKI with no history of significant cardiac disease.

Genetic subtypes of large cell neuroendocrine carcinoma (LCNEC) to predict response to chemotherapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9061-9061 ◽  
Author(s):  
Jules Derks ◽  
Noémie Leblay ◽  
Robert Jan van Suylen ◽  
Erik Thunnissen ◽  
Michael den Bakker ◽  
...  
Keyword(s):  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Large Cell ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Netherlands Cancer Registry ◽  
Response To Chemotherapy

9061 Background: To treat LCNEC with non-small cell lung carcinoma type chemotherapy (NSCLC-ct, i.e. gemcitabine/taxanes or pemetrexed) or small cell lung carcinoma type (SCLC-ct, i.e. platinum-etoposide) is subject of debate. Molecular studies have identified two mutually exclusive subtypes in LCNEC, the co-mutated TP53 and RB1and the STK11/ KEAP1 (predominantly RB1 wildtype(wt)) group. We investigated if overall survival (OS) and progression free survival (PFS) correlates with targeted next-generation sequencing (TNGS) results in LCNEC treated with NSCLC-ct or SCLC-ct. Methods: For this population based retrospective cohort study all diagnoses of stage IV ct treated high grade neuroendocrine carcinomas (NEC, not being SCLC) were retrieved from the Netherlands Cancer Registry and Pathology Registry (PALGA) (2003-2012). Panel-consensus pathology revision of original tumor slides was performed on (N = 230) and TNGS for genes TP53, RB1, STK11 and KEAP1 analyzed with a multi-sample variant caller (Needlestack). Results: LCNEC was consensus diagnosed in 146/230 and 77 passed quality control for TNGS. Mean coverage was 2832x, a mutation(mt) in TP53 was present in 87%, RB1mt in 46%, STK11mt in 13% and KEAP1mt in 18% of sequenced LCNEC. RB1 was co-altered with TP53 in 94% of LCNEC; mutually exclusive to STK11mt (100%) but not KEAP1mt (57%). NSCLC-ct or SCLC-ct was specified in 92% of patients and RB1wt LCNEC treated with NSCLC-ct (n = 22) showed a trend to better OS compared to SCLC-ct (n = 13) (8.5 months (95% confidence interval (CI): [6.3-10.6]) vs. 5.8 [5.5-6.1] months, p = 0.055). Due to reported resistance in NECs we analyzed NSCLC-ct without pemetrexed-ct; OS was significantly longer for NSCLC-ct (n = 15) compared to SCLC-ct (9.6 [7.7-11.6] vs. 5.8 [5.5-6.1] months, p = 0.026). PFS of RB1wt NSCLC-ct treated patients was significantly longer than SCLC-ct (p = 0.044), without pemetrexed (p = 0.018). In patients with RB1mt LCNEC OS/PFS was not significantly different for NSCLC-ct vs. SCLC-ct. Conclusions: In LCNEC with RB1wt, NSCLC-ct correlates with a more favorable outcome compared to SCLC-ct. However, RB1mt LCNEC treated with NSCLC-ct do similarly worse as SCLC-ct. Prospective studies should be initiated.

Synchronous EGFR and KRAS mutations in non-small cell lung carcinoma

Pathology ◽  
2010 ◽  
Vol 42 ◽  
pp. S69
Author(s):  
Nathan T. Harvey ◽  
Nancy Lerda ◽  
Graeme Casey ◽  
Glenice Cheetham
Keyword(s):  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Small Cell Lung ◽  
Kras Mutations ◽  
Cell Lung Carcinoma

scholarly journals The Inhibition of Wnt Restrain KRASG12V-Driven Metastasis in Non-Small-Cell Lung Cancer

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 837
Author(s):  
Pei-Shan Hung ◽  
Ming-Hung Huang ◽  
Yuan-Yeh Kuo ◽  
James Chih-Hsin Yang
Keyword(s):  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Dominant Negative ◽  
Gene Set Enrichment Analysis ◽  
Dominant Negative Mutant ◽  
Small Cell Lung ◽  
Kras Mutations ◽  
Cell Lung Carcinoma ◽  
Wnt Inhibitor

The KRAS mutations have been an obstacle to identify therapeutic targets in cancer treatment. In this work, we clarified the distinct metastasis pattern of non-small-cell lung carcinoma (NSCLC) induced by KRASG12V/KRASG12D mutations and inhibited the KRASG12V mediated metastasis by Wnt inhibitor. First, we found that KRASG12V induced more aggressive phenotype in vitro and in vivo experiments. The Gene Set Enrichment Analysis (GSEA) results of H838 KRASG12V cells showed a significant negative correlation with RhoA-related signaling. Following this clue, we observed KRASG12D induced higher activation of RhoA and suppressed activation of Wnt/β-catenin in H838KRASG12D cells. The restored activation of Wnt/β-catenin in H838KRASG12D cells could be detected when expression with a dominant-negative mutant of RhoA or treatment with RhoA inhibitor. Furthermore, the Wnt inhibitor abolished the KRASG12V-induced migration. We elucidated the importance of the axis of RhoA/Wnt in regulatory NSCLC metastasis driven by KRAS mutations. Our data indicate that KRASG12V driven NSCLC metastasis is Wnt-dependent and the mechanisms of NSCLC metastasis induced by KRASG12V/KRASG12D is distinct.

The prognostic impact of quality of life assessed with the EORTC QLQ-C30 in inoperable non-small cell lung carcinoma treated with radiotherapy

2000 ◽  
Vol 55 (1) ◽  
pp. 19-25 ◽  
Author(s):  
Hans Langendijk ◽  
Neil K Aaronson ◽  
Jos M.A de Jong ◽  
Guul P.M ten Velde ◽  
Martin J Muller ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Prognostic Impact ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Eortc Qlq C30 ◽  
Eortc Qlq
Sign in / Sign up

Export Citation Format

Share Document