scholarly journals The frequency of EGFR And KRAS mutations in the Turkish population with non-small cell lung cancer and their response to erlotinib therapy

2018 ◽  
Vol 21 (2) ◽  
pp. 21-26 ◽  
Author(s):  
A Demiray ◽  
A Yaren ◽  
N Karagenç ◽  
F Bir ◽  
AG Demiray ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Survival Rate ◽  
Small Cell Lung Cancer ◽  
Kras Mutation ◽  
Median Overall Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Kras Mutations ◽  
Erlotinib Therapy

Abstract In this study, profiles of epidermal growth factor receptor (EGFR) and Kirsten ras sarcoma (KRAS) mutations and response to erlotinib therapy have been investigated in patients with non-small cell lung cancer (NSCLC). DNA from 300 patients with NSCLC was extracted from paraf-fin-embedded tissues. After the extracted DNA was sequenced by pyrosequencing method, a total of 97 (32.0%) patients out of 300 were detected to carry an EGFR mutation and 75 (25.0%) patients out of 300 carried a KRAS mutation; 20 (6.6%) patients were detected to carry both of EGFR and KRAS mutations. The EGFR mutations were found to be statistically significant in female patients (48.0 women vs. 28.0% men, non smokers (49.0 vs. 26.0%) and adenocarcinoma (37.8 vs. squamous 26.8%). The overall rate of survival in patients receiving erlotinib therapy than in patients who did not. In patients without the KRAS mutation, the median overall survival rate was 161 ± 30 weeks with erlotinib therapy and 90 ± 13 weeks in patients without erlotinib therapy. In patients having KRAS mutation, the median overall survival was 98 ± 16 weeks with erlotinib therapy and 34 ± 16 weeks with no erlotinib therapy. In our study, we once again demonstrated that the presence of these mutations affected response to erlotinib therapy. The KRAS mutations negatively affected survival rate with and without erlotinib therapy.

Driver mutations to predict for poorer outcomes in non-small cell lung cancer patients treated with concurrent chemoradiation and consolidation durvalumab.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8528-8528
Author(s):  
Yufei Liu ◽  
Zhe Zhang ◽  
Waree Rinsurongkawong ◽  
Xiuning Le ◽  
Carl Michael Gay ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Targeted Therapy ◽  
Small Cell Lung Cancer ◽  
Small Cell ◽  
Driver Mutation ◽  
Driver Mutations ◽  
Small Cell Lung ◽  
Kras Mutations ◽  
Mutation Status

8528 Background: The use of durvalumab after chemoradiation in locally advanced non-small cell lung cancer (NSCLC) patients significantly improves overall survival. However, it is unclear whether this benefit applies to all genetic subtypes of lung cancer. We hypothesize that patients with driver mutation NSCLC may derive less benefit from consolidation durvalumab. Methods: Using the Genomic Marker-Guided Therapy Initiative (GEMINI) database at MD Anderson, we identified 134 patients who were treated with chemoradiation followed by durvalumab for NSCLC. We segregated patients with driver mutations to targetable (EGFR, ALK translocation, ROS1 fusion, MET exon 14 skipping, RET fusion, and/or BRAF) (N = 24) and those driven by canonical KRAS mutations (N = 26). The rest (N = 84) had none of these mutations. We gathered demographic, treatment, and outcome data and compared progression-free survival (PFS) and overall survival (OS) using the Kaplan-Meier method. We used multivariate regression analysis to account for demographic and treatment variables. Results: For our cohort, median age at diagnosis was 64.8, 52% were female (n = 70), and median follow up was 1.5 years. 86% of patients have a history of smoking (n = 115). 21% had squamous cell histology (n = 28). 2 patients had stage IIA disease, 6 had stage IIB, 48 had stage IIIA, 56 had stage IIIB, 13 had stage IIIC, and 9 had stage IV. 73 patients had progression after durvalumab and 37 patients died. Patients with driver mutations had significantly worse median PFS compared to those without driver mutations (8.9 mo vs 26.6 mo; HR 2.62 p < 0.001). Patients with KRAS mutations had particularly poor PFS (Median 7.9 mo, HR 3.34, p < 0.001), while patients with targetable driver mutations trended to worse PFS (Median 14.5 mo, HR 1.96, p = 0.056). The median OS for the cohort was 4.8 yrs with no significant differences based on driver mutation status. On multivariate analysis, only driver mutation status was associated with PFS, but not OS. For patients with first progression, we found the targetable driver group to have significantly improved time to second objective progression (PFS2) compared to the KRAS (HR 0.28, p = 0.011) or non-mutated group (HR 0.38, p = 0.025). All patients in the targetable driver group received targeted therapy after first progression. Conclusions: Our results suggest that patients with driver mutations have worse PFS compared to patients without these mutations after chemoradiation. However, patients with targetable oncogene driver mutations have significantly improved prognosis after initial progression compared to the other groups, likely due to targeted therapy, suggesting that these therapies, including novel approaches towards KRAS mutants, should be further explored in this setting.

scholarly journals CMET-08. CEREBROSPINAL FLUID CARCINOEMBRYONIC ANTIGEN PREDICT PROGNOSIS IN LEPTOMENINGEAL METASTASIS FROM NON-SMALL CELL LUNG CANCER

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi52-vi52
Author(s):  
Junjie Zhen ◽  
Shaoqun Li ◽  
Lei Wen ◽  
Mingyao Lai ◽  
Linbo Cai
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Cerebrospinal Fluid ◽  
Small Cell Lung Cancer ◽  
Carcinoembryonic Antigen ◽  
Median Overall Survival ◽  
Leptomeningeal Metastasis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Serum Cea

Abstract BACKGROUND Leptomeningeal metastasis (LM) is a detrimental complication of patients with non-small cell lung cancer (NSCLC) and its incidence has increased due to recent improvements in survival. The aim of this study was to identify the clinicopathological features and prognostic factors related to overall survival in NSCLC patients with LM. METHODS Seventy-four consecutive patients diagnosed with LM from NSCLC between 2009 and 2018 in Guangdong Sanjiu Brain Hospital were retrospectively reviewed. RESULTS Median KPS at diagnosis of LM were 60 (range, 20–90). Forty-seven (63.5%) patients harboring epidermal growth factor receptor (EGFR) or anaplasticlymphoma kinase (ALK) mutation while other twenty-seven patients (36.5%) were wild type or unknown status. Local treatment for LM consisted of whole-brain radiotherapy (WBRT) (52.7%), ventriculoperitoneal (VP) shunt (6.8%) and external drainage (6.8%). Systematic therapy for LM included EGFR or ALK tyrosine kinase inhibitors (TKI) (59.5%), chemotherapy (40.5%) and bevacizumab (8.1%). The median overall survival from diagnosis of LM to death was 8.1 months (95% confidence interval: 5.2 to 11.0). Patients with high Cerebrospinal Fluid (CSF) carcinoembryonic antigen (CEA) level (＞50ng/ml) had worse prognosis compared with those low CSF CEA level (≤50ng/ml) ones (p=0.02). However, there was no significant difference in survival between patients with high serum CEA and those with low serum CEA (p=0.645). EGFR/ALK mutation and EGFR/ALK TKI after LM were also identified as variables that had prognostic influence on survival, while KPS, concurrent brain metastasis, WBRT and chemotherapy had no prognostic value for survival. CONCLUSION Median overall survival was higher than historical experience in this retrospective analysis. It is CSF CEA level, but not serum CEA level that correlated with prognosis for LM from NSCLC.

scholarly journals LPTO-07. CARCINOEMBRYONIC ANTIGEN OF CEREBROSPINAL FLUID PREDICT PROGNOSIS OF LEPTOMENINGEAL METASTASIS FROM NON-SMALL CELL LUNG CANCER

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i7-i7
Author(s):  
Junjie Zhen ◽  
Lei Wen ◽  
Shaoqun Li ◽  
Mingyao Lai ◽  
Cheng Zhou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Cerebrospinal Fluid ◽  
Small Cell Lung Cancer ◽  
Carcinoembryonic Antigen ◽  
Median Overall Survival ◽  
Leptomeningeal Metastasis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Serum Cea

Abstract BACKGROUND: Leptomeningeal metastasis (LM) is a detrimental complication of patients with non-small cell lung cancer (NSCLC) and its incidence has increased due to recent improvements in survival. The aim of this study was to identify the clinicolpathological features and prognostic factors related to overall survival in NSCLC patients with LM. METHODS: Seventy-four consecutive patients diagnosed with LM from NSCLC between 2009 and 2018 in Guangdong Sanjiu Brain Hospital were retrospectively reviewed. RESULTS: Median KPS at diagnosis of LM were 60 (range, 20–90). Forty-seven (63.5%) patients harboring epidermal growth factor receptor (EGFR) or anaplasticlymphoma kinase (ALK) mutation while other twenty-seven patients (36.5%) were wild type or unknown status. Local treatment for LM consisted of whole-brain radiotherapy (WBRT) (52.7%), ventriculoperitoneal (VP) shunt (6.8%) and external drainage (6.8%). Systematic therapy for LM included EGFR or ALK tyrosine kinase inhibitors (TKI) (59.5%), chemotherapy (40.5%) and bevacizumab (8.1%). The median overall survival from diagnosis of LM to death was 8.1 months (95% confidence interval: 5.2 to 11.0). Patients with high Cerebrospinal Fluid (CSF) carcinoembryonic antigen (CEA) level (＞50ng/ml) had worse prognosis compared with those low CSF CEA level (≤50ng/ml) ones (p=0.02). However, there was no significant difference in survival between patients with high serum CEA and those with low serum CEA (p=0.645). EGFR/ALK mutation and EGFR/ALK TKI after LM were also identified as variables that had prognostic influence on survival, while KPS, concurrent brain metastasis, WBRT and chemotherapy had no prognostic value for survival. CONCLUSION: Median overall survival was higher than historical experience in this retrospective analysis. It is CSF CEA level, but not serum CEA level that correlated with prognosis for LM from NSCLC.

scholarly journals Factors Affecting the Survival of Patients with Oligometastatic Non-Small-Cell Lung Cancer: A Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Yu Shi ◽  
Jianxin Yang ◽  
Ninghua Yao ◽  
Minghai Shao ◽  
Wenxiu Ding ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Sensitivity Analysis ◽  
Overall Survival ◽  
Survival Rate ◽  
Small Cell Lung Cancer ◽  
Meta Analysis ◽  
Small Cell ◽  
Overall Survival Rate ◽  
Small Cell Lung ◽  
Nsclc Patients

Background. The aim was to investigate the potential factors related with overall survival of oligometastatic non-small-cell lung cancer (NSCLC) patients. Methods. A literature search was conducted in databases including PubMed, Embase, and Cochrane library up to March 2017. The hazard radio (HR) as well as the corresponding 95% confidence interval (CI) were calculated, and all the statistics analysis was performed by the R 3.12. Heterogeneity was analyzed using I-squared and Cochran Q tests. Furthermore, sensitivity analysis was performed to evaluate the stability of results. Results. In total, 6 articles were included in the meta-analysis. Nodal status was significantly correlated with the overall survival rate of NSCLC oligometastatic patients (HR: 1.69, 95% CI: 1.23–2.32, Z=3.20, P=0.001). No significant relationship was found between overall survival rate of NSCLC oligometastatic patients and the indicators including sex, stage, smoker, age, and histology. Notably, sensitivity analysis on data evaluating relationship between patients survival and the stage and histology showed that results were reversed after removing one of the studies. Conclusions. Nodal status might be associated with the overall survival of oligometastatic NSCLC patients.

Vaccination of patients with advanced non-small cell lung cancer with an optimized cryptic hTERT peptide (Vx-001)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7642-7642
Author(s):  
K. Kosmatopoulos ◽  
E. Bolonaki ◽  
A. Kotsakis ◽  
E. Papadimitraki ◽  
D. Agouraki ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Median Overall Survival ◽  
Small Cell ◽  
Historical Control ◽  
Small Cell Lung ◽  
Skin Reactions ◽  
Local Skin

7642 Background: To evaluate the immunological and clinical efficacy of the optimized peptide TERT572Y (Vx-001) presented by HLA-A*0201 in patients with advanced non-small cell lung cancer (NSCLC). Methods: Twenty-two patients with residual (n=8) or progressive (n=14) advanced NSCLC following chemotherapy and/or radiotherapy received two subcutaneous injections of the optimized TERT572Y peptide followed by four injections of the native TERT572 peptide given every 3 weeks. Peptide-specific immune responses were monitored by Elispot assay and/or TERT572Y pentamer staining. Clinical outcome was compared with that of 22 case-matched historical control patients. Results: Thirteen (59%) out of 22 patients completed the vaccination program. Toxicity consisted primarily of local skin reactions. TERT572-specific CD8+ cells were detected in 16 (76.2%) out of 21 patients after the 2nd vaccination and 10 (90.9%) out of 11 patients after the 6th vaccination. Stable disease occurred in 8 (36.4%) patients with a median duration of 11.2 months. Patients with an early immunological response (n=16) had a significantly longer time to disease progression and overall survival than non-responders (n=5) (log-rank tests p=0.046 and p=0.012, respectively). The estimated median overall survival was 30.0 (range, 2.8–40.0) and 4.1 (range, 2.4–10.9) months for immunological responders and non-responders, respectively. Moreover, median overall survival was 30.6 months (95% CI:10.9–48.9) and 6.1 months (95% CI:4.4–7.8) for the vaccinated and case-matched historical control patients, respectively (p=0.074). Conclusions: TERT572Y peptide vaccine is well tolerated and effective in eliciting a specific T-cell immunity which seems to be associated with prolonged patients’ survival. No significant financial relationships to disclose.

Stereotactic bradiotherapy (SRT) for operable stage I non-small cell lung cancer: Is SRT comparable to surgery?

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7623-7623 ◽  
Author(s):  
H. Onishi ◽  
H. Shirato ◽  
Y. Nagata ◽  
M. Hiraoka ◽  
G. Kotaro ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Survival Rate ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Stage I ◽  
Overall Survival Rate ◽  
Small Cell Lung ◽  
Radical Treatment

7623 Background: Stereotactic radiotherapy (SRT) has been aggressively performed as a radical treatment for stage I non-small cell lung cancer (NSCLC) in Japan, however most cases were medically inoperable. In a large Japanese multi-institutional experience, we reviewed the treatment outcome of SRT for medically operable stage I NSCLC cases with the patients’ refusal to surgery. Methods: In 1995–2004, 86 medically operable patients with stage I NSCLC (median age, 74 years; 62 T1N0M0; 24 T2N0M0) were treated with SRT alone in 14 reliable institutions. Stereotactic three-dimensional treatment was performed using non-coplanar dynamic arcs or multiple static ports. A total dose of 20 to 72.5 Gy at the isocenter was administered in 1 to 10 fractions. Median calculated biological effective dose (BED) was 115 Gy (range, 100–153 Gy). The data was collected and analyzed in a retrospective manner. Results: During follow-up (median, 43 months), pulmonary complications of above grade 2 arose in 4 patients (5.8%). Local control rates at 3 and 5-year post SRT were 88.1% and 85.5%, respectively. Three and 5-year overall survival rates were 80.7% and 71.3%, respectively. Five-year overall survival rate for patients whose age was over 70 years (n=27) and under 70 years (n=58) were 74.3% and 69.6%, respectively. Five-year overall survival rate for stage IA (n=62) and IB (n=24) cases were 72.3% and 68.4%, respectively. Conclusions: SRT is safe and promising as a radical treatment for operable stage I NSCLC. The survival rate of SRT is potentially comparable to that of surgery. No significant financial relationships to disclose.

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.

Role of T0 status in overall survival for unresectable stage III non-small cell lung cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9026-9026
Author(s):  
Takefumi Komiya ◽  
Emily Powell ◽  
Charles Vu ◽  
Achuta Kumar Guddati
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Survival Rate ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Unresectable Stage ◽  
Stage Iii Nsclc

9026 Background: Occult (T0) primary non-small cell lung cancer (NSCLC) with mediastinal involvement is a known but rare clinical condition. Its prognosis has not been evaluated well in the literature. Methods: Using National Cancer Database (NCDB), cases diagnosed between 2004 and 2016 with unresectable clinical stage III NSCLC with N2 or N3 involvement were selected and assigned to T0 or T1-4 group according to AJCC staging version 6th or 7th. Clinical demographics including use of chemotherapy/immunotherapy in first course of treatment were collected. As validation, independent data using Surveillance, Epidemiology, and End Results Program (SEER) was analyzed accordingly. Survival analyses were conducted using Kaplan-Meier and log-rank tests. Results: A total of 458 and 84,263 cases met criteria for unresectable, N2/N3 stage III NSCLC with T0 and T1-4 status, respectively. T0 status was associated with younger age, recent diagnosis, adenocarcinoma histology, N3, and use of chemotherapy. Overall survival (OS) was improved in T0 over T1-4 group (p < 0.0001) with a five-year survival rate of 30.5% and 12.7%, respectively, with a validation with multivariate proportional hazard models. Propensity score matching analyses using all 458 patients in each group demonstrated a significant difference in OS (p < 0.0001). The difference was also significant in a subset of those who have undergone chemoradiation (p < 0.0001). Independent analysis using SEER data confirmed its superior survival of T0 over T1-4 with a five-year survival rate of 35.3% and 13.5%, respectively. Conclusions: Both NCDB and SEER analyses demonstrated better survival of T0 than T1-4 counterpart in the setting of unresectable stage III NSCLC, irrespective of chemotherapy status. This group may require a distinct assignment to new staging group after further investigation.

scholarly journals Characterization With KRAS Mutant Is a Critical Determinant in Immunotherapy and Other Multiple Therapies for Non-Small Cell Lung Cancer

2022 ◽  
Vol 11 ◽  
Author(s):  
Mo Shen ◽  
Rongbin Qi ◽  
Justin Ren ◽  
Dongqing Lv ◽  
Haihua Yang
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Kras Mutation ◽  
Biological Diversity ◽  
Small Cell ◽  
Small Cell Lung ◽  
Kras Mutations

Non-small cell lung cancer (NSCLC) is a frequent type of cancer, which is mainly characterized clinically by high aggressiveness and high mortality. KRAS oncoprotein is the most common molecular protein detected in NSCLC, accounting for 25% of all oncogenic mutations. Constitutive activation of the KRAS oncoprotein triggers an intracellular cascade in cancer cells, leading to uncontrolled cell proliferation of cancer cells and aberrant cell survival states. The results of multiple clinical trials have shown that different KRAS mutation subtypes exhibit different sensitivities to different chemotherapy regimens. Meanwhile, anti-angiogenic drugs have shown differential efficacy for different subtypes of KRAS mutated lung cancer. It was explored to find if the specificity of the KRAS mutation subtype would affect PD-L1 expression, so immunotherapy would be of potential clinical value for the treatment of some types of KRAS mutations. It was discovered that the specificity of the KRAS mutation affected PD-L1, which opened up immunotherapy as a potential clinical treatment option. After several breakthrough studies, the preliminary test data of many early clinical trials showed that it is possible to directly inhibit KRAS G12C mutation, which has been proved to be a targeted treatment that is suitable for about 10%–12% of patients with advanced NSCLC, having a significant impact on the prolongation of their survival and the improvement of their quality of life. This article reviews the latest progress of treatments for NSCLC with KRAS mutation, in order to gain insight into the biological diversity of lung cancer cells and their potential clinical implications, thereby enabling individualized treatment for patients with KRAS-mutant NSCLC.

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