The clinical characteristic and prognostic factors of leptomeningeal metastasis in patients with non-small-cell lung cancer: A retrospective study from one single cancer institute.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13502-e13502
Author(s):  
Weiwei Yan ◽  
Jinming Yu
Keyword(s):  
Prognostic Factors ◽  
Retrospective Study ◽  
Performance Status ◽  
Leptomeningeal Metastasis ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
Alk Rearrangement ◽  
Single Cancer ◽  
Nsclc Patients ◽  
Egfr Tkis

e13502 Background: Leptomeningeal metastasis (LM) is a detrimental complication of advanced NSCLC, and the optimal therapeutic approach for LM patients is in shortage. The retrospective study was to investigate clinical features and prognostic factors of NSCLC patients with LM. Methods: We retrospectively reviewed the records of NSCLC patients with LM at the Shandong Cancer Hospital and Institute between July 2014 and March 2018. Identified cases had pathology-proven NSCLC with either positive CSF cytology or LM enhancement by MRI. Results: One hundred and thirty-six NSCLC patients (58 men, 78 women) with LM were enrolled in the retrospective study, median age was 55 years (range, 29–89 years). Fifty-one patients harbored EGFR mutations and ALK rearrangement was detected in six patients. Treatment for LM consisted of EGFR-TKIs alone in 11 patients, WBRT alone in 19 patients, Chemotherapy (ChT) alone in 12 patients, EGFR-TKIs plus WBRT in 30 patients, WBRT plus ChT in 25 patients, and EGFR-TKIs plus ChT in 24 patients. The median progression free survival (PFSLM) was 3.9 months (95% CI, 3.178-4.622) and the median overall survival (OSLM) was 9.8 months (95% CI,7.5-12.1). A multivariate analysis indicated that KPS ≥ 80 (HR = 0.592, 95% CI:0.369-0.95; p = 0.03) and EGFR-TKIs (HR = 0.507, 95% CI:0.283-0.908; p = 0.022) after LM diagnosis were independent favourable predictors of survival, whereas smoking (HR = 1.181, 95 % CI:1.009-3.246; p = 0.047) was an independent predictor of poor survival. Conclusions: Patients with good performance status, non-smokers and the administration of EGFR-TKIs might improve clinical outcomes in NSCLC patients with LM.

Identification of a microRNA (miRNA) based signature for survival in advanced non-small cell lung cancer (NSCLC) patients (pts) treated with cisplatin-vinorelbine: A ELCWP study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18006-e18006
Author(s):  
Thierry Berghmans ◽  
Luc Willems ◽  
Marianne Paesmans ◽  
Lieveke Ameye ◽  
Jean-Jacques Lafitte ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Prognostic Score ◽  
Performance Status ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Cox's Regression ◽  
And Performance ◽  
A Prospective Study ◽  
Nsclc Patients

e18006 Background: Main prognostic factors for survival in NSCLC pts are stage and performance status (PS) while sex, histology and others are reported. However, these variables do not allow predicting individual prognosis, justifying further research. MiRNA are small non-coding RNAs regulating gene expression. As a secondary aim of a prospective study, we looked at the prognostic value of tumour miRNA on survival in NSCLC pts treated by cisplatin (60 mg/m2 D1) and vinorelbine (25 mg/m2, D1+8) 1st line chemotherapy. Methods: During the diagnostic bronchoscopy, a biopsy was lysed into Tripure Isolation Reagent (Roche Diagnostics) on ice, snap frozen and stored at -80°C. MiRNA expression was assessed using TaqMan Low Density Arrays (756 human miRNA panel, Applied Biosystems) and normalized using the delta delta CT method to RNU48 (SNORD48) CT value for every sample. Survival was measured from the registration date. Results: The main characteristics of 38 eligible pts were: median age 60 years, male 27 (71%), 80-100 Karnofsky PS in 26 (68%), adenocarcinoma 20 (53%), stage IV 30 (79%). At time of analysis, 25 pts were dead. After stepwise selection among 756 analysed miRNA, a combination of 4 miRNA including miR-200c, miR-424, miR-29c and miR-124 provided a prognostic signature for survival. Using a linear combination of the miRNA CT values with Cox's regression coefficients as weights, we constructed a prognostic score. With a cut-off of 52, the signature distinguished pts with good (n = 18) and poor (n = 20) prognosis with respective median survival of 47.3 months (95% CI 29.8-52.4) and 15.5 months (95% CI 9.1-22.8) (p <0.001; hazard ratio 21.1, 95% CI 4.7-94.9). The same signature discriminated pts with “good progression-free survival” (median 19.8 months; 95% CI 15.3-33.8) from the others (median 9.1 months; 95% CI 6.3-15.5) (p <0.001; hazard ratio 3.8, 95% CI 1.7-8.7). Conclusions: A 4 miRNA signature is associated with improved survival in patients with advanced stage NSCLC treated with 1st line cisplatin and vinorelbine. These results need confirmation in an independent cohort and the signature has to be compared to conventional prognostic factors.

EGFR-TKI benefit for NSCLC patients with EML4-ALK rearrangement.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18035-e18035
Author(s):  
Zhijie Wang ◽  
Jie Wang ◽  
Yi Long Wu ◽  
Hua Bai ◽  
Xu-Chao Zhang ◽  
...  
Keyword(s):  
Molecular Subtype ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
Alk Rearrangement ◽  
Mutant Type ◽  
Egfr Mutant ◽  
Nsclc Patients ◽  
Egfr Tki

e18035 Background: EML4-ALK rearrangement defines a new molecular subtype of non-small-cell lung cancer (NSCLC). To identify the biological profiles of these patients, we examined the clinico-pathologic characteristics and treatment outcomes of NSCLC patients based on EML4-ALK and EGFR mutations. Methods: Patients with stage IV NSCLC were screened for EML4-ALK rearrangement and EGFR mutations at Peking University Cancer Hospital. EML4-ALK was identified using fluorescent in situ hybridization (FISH) confirmed by immunohistochemistry (IHC), and EGFR mutations were determined using denaturing high-performance liquid chromatography (DHPLC). Results: Of the 151 patients screened, 113 had complete follow-up data as an analysis set. The incidence of EML4-ALK was 9.7% (11/113) using FISH, in which 10 cases had sufficient specimens for IHC confirmation and all were positive. Overall, EML4-ALK and EGFR mutations were largely mutually exclusive (p = 0.033), although two patients harbored concurrent mutations. EML4-ALK rearrangement was associated with resistance to EGFR-TKIs compared with the EGFR mutant type and WT/Nonrearrangement type (p = 0.001 for objective response rate; p = 0.004 for disease control rate; p = 0.021 for progression-free survival [PFS]). In terms of patients who received platinum-based doublet chemotherapy, no significant differences were observed in PFS between the EML4-ALK type, EGFR mutant type, and WT/Nonrearrangement type. Moreover, two patients with concurrent EML4-ALK and EGFR mutations had superior PFS after EGFR-TKI compared with single EML4-ALK-rearranged patients. Conclusions: This study presents several biological features of EML4-ALK NSCLC. It is largely mutually exclusive to EGFR mutations, resistant to EGFR-TKI. Coexistence of ALK rearrangement and EGFR mutation in patients with advanced NSCLC might represent a separate genotype with unique biological characteristics.

scholarly journals Prognostic Factors in Lung Adenocarcinoma with Bone Metastasis Treated with EGFR-TKIs

Medicina ◽  
2021 ◽  
Vol 57 (9) ◽  
pp. 967
Author(s):  
Tzu-Hsuan Chiu ◽  
Chun-Yu Lin ◽  
Meng-Heng Hsieh ◽  
Shu-Min Lin ◽  
Yueh-Fu Fang
Keyword(s):  
Prognostic Factors ◽  
Bone Metastasis ◽  
Lung Adenocarcinoma ◽  
Kinase Inhibitors ◽  
Performance Status ◽  
Progression Free Survival ◽  
Advanced Lung Cancer ◽  
First Line ◽  
Cancer Management ◽  
Egfr Tkis

Background and Objectives: Patients who have advanced lung cancer and bone metastasis (BM) often suffer from skeletal-related events (SREs) that lead to poor quality of life and poor prognosis. Our study aimed to investigate the prognostic factors in patients with BM from epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma. Materials and Methods: This retrospective study included 77 lung adenocarcinoma patients with synchronous BM. These patients had first-line EGFR tyrosine kinase inhibitors (EGFR-TKIs) between January 2017 and December 2019. Among them, 42 patients were treated with 120 mg of subcutaneous denosumab monthly. We investigated their baseline characteristics, cancer management, SREs, progression-free survival (PFS), and overall survival (OS). Results: The PFS in the patients treated with or without denosumab were 10.1 vs. 12.5 months (p = 0.971). The median OS was 26.9 vs. 29.5 months (p = 0.967) in no denosumab and denosumab groups, respectively. Univariate analyses showed benefit of afatinib in PFS and good performance status in OS. Conclusion: Those patients that took afatinib as first-line EGFR-TKIs had significantly longer PFS than those treated with other TKIs. Denosumab had no prognostic effect on PFS or OS.

TGFb expression as predictor of outcome in EGFR wild type (WT) metastatic non-small cell lung cancer (NSCLC) patients (PTS) treated with EGFR tyrosine kinase inhibitors (TKIs).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18104-e18104
Author(s):  
Giovanna Finocchiaro ◽  
Luca Toschi ◽  
Letizia Gianoncelli ◽  
Barbara Canal ◽  
Luca Rubino ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Progression Free Survival ◽  
Staining Intensity ◽  
Egfr Mutations ◽  
Study Cohort ◽  
Intrinsic Resistance ◽  
Alk Rearrangement ◽  
Primary Resistance ◽  
Metastatic Nsclc ◽  
Nsclc Patients

e18104 Background: Gefitinib and erlotinib have shown to be highly effective in pts harboring EGFR mutations, while the majority of EGFR wt pts does not respond to treatment.Preclinical data suggested that TGFb and HGF could affect response to TKIs. Aim of the present study is to investigate molecular predictors for primary resistance to TKIs in metastatic NSCLC pts. Methods: This retrospective study included 120 metastatic NSCLC patients treated with gefitinib (68/56.7%) or erlotinib (52/43.3%) in first line (20/16.7%) or after prior chemotherapy (100/83.4%) with at least one measurable lesion and availability of paraffin-embedded tumour tissue from primary cancer. Analyses included presence of mutations in EGFR and KRAS genes, assessment of ALK rearrangement by fluorescence in situ hybridization (FISH) and protein expression of HGF and TGFb by immunohistochemistry (IHC). Pts were grouped in IHC+ and IHC- according to staining intensity. Results: In the whole study cohort response rate (RR) was 9.2%, median progression free survival (PFS) 2.5 months, and overall survival (OS) 7.8 months. EGFR mutations were observed in 9.2% of pts and were significantly associated with better pts outcome. KRAS was mutated in 23.3% of pts without any correlation with clinical end points. ALK translocations were observed in 5 pts (4.2%), and none responded to treatment. IHC was successfully performed for HGF and TGFb in 95 and 75 pts respectively. No difference was seen in HGF+ (9/9.5%) vs HGF- pts in terms of RR, PFS and OS. TGFb+ pts (41/54.7%) had a significantly shorter OS than TGFb- pts (6.7 vs 10.3 months, p=0.020) although no difference in terms of RR and PFS was observed. When restricting survival analysis to EGFR wt/KRAS wt pts (n=80) TGFb+ subjects had a significantly worse PFS (1.9 vs 2.9 months, HR 2.16, CI 95% 1.18;3.95, p=0.013) and OS (5.3 vs 8.8 months, HR 2.07, CI 95% 1.10;3.91, p=0.025) when compared with the TGFb- group. Conclusions: Overexpression of TGFb is associated with a poor outcome in EGFR and KRAS wt pts treated with gefitinb or erlotinib. Prospective validation of the role of TGFb as a mediator of intrinsic resistance to EGFR TKIs in NSCLC is warranted.

Response to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) patients with de novo epidermal growth factor receptor (EGFR) T790M and S768I resistance mutations.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20557-e20557
Author(s):  
Deirdre Kelly ◽  
Lisa Mary Prior ◽  
Jack Patrick Gleeson ◽  
Lynda M. McSorley ◽  
Rachel Kearns ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stable Disease ◽  
De Novo ◽  
Objective Response ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
Resistance Mutations ◽  
Free Survival ◽  
Nsclc Patients ◽  
Egfr Tkis

e20557 Background: Patients with synchronous de novo EGFR sensitising and resistance mutations are rare. Little is known about the response of these patients to EGFR TKIs, especially in a Caucasian population. Methods: We identified NSCLC patients found to have EGFR mutations using PCR-based fragment length analysis, mass spectrometry-based genotyping (Sequenom), and Sanger sequencing using a large multi-institutional database. Baseline clinical characteristics, response rate, progression free survival (PFS) and overall survival (OS) were calculated. Results: From 2008-2015, we observed de novo synchronous EGFR sensitising and resistance mutations in 12 patients representing an overall incidence of 3.6% of EGFR mutants and 0.4% of all NSCLC patients tested. Seven patients were treated using EGFR TKI therapy with erlotinib. In all cases, T790M (n = 4,50%) or S768I (n = 4, 50%) occurred concurrently with another sensitising EGFR mutation, either L858R (n = 4, 34%) or exon 19 deletion (n = 8, 66%). Objective responses were seen in two patients (29%). Three further patients had stable disease lasting 6, 23 and 54 months respectively. The median progression-free survival was 24 months and the median overall survival was 34 months. All patients with baseline EGFR S768I mutations (n = 3) had an objective response or stable disease on erlotinib while two of four patients with T790M demonstrated de novo resistance. Conclusions: This is the largest Irish review of synchronous de novo EGFR mutations. The incidence of co-occurring EGFR mutations was 0.4% and erlotinib demonstrated activity in this cohort of patients. Ongoing trials will determine whether next-generation EGFR TKIs such as osimertinib are preferable as first-line therapy in these patients.

Biological and clinical prognostic factors in patients with advanced non-small-cell cancer (NSCLC) treated by erlotinib: Preliminary results of the ERMETIC cohort

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8079-8079
Author(s):  
J. Cadranel ◽  
M. Beau-Faller ◽  
A. Mauguen ◽  
S. Lizard ◽  
J. Madelaine ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Cox Model ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
Kras Mutations ◽  
Free Survival ◽  
Nsclc Patients ◽  
First Time ◽  
Egfr Tkis

8079 Background: Although it has been suggested that results of EGFR-IHC, EGFR-FISH and EGFR and KRAS mutations are predictive of EGFR-TKIs efficacy, they are not used in clinical practice. ERMETIC is a French NCI granted prospective study aiming to facilitate implementation of these biomarkers in France. Methods: After a preliminary phase of validation in 16 French centers, these biomarkers were studied in available tumor specimens collected from all consecutive NSCLC patients (pts) treated by erlotinib, for the first time. Patients were followed-up until progression or death. Demographic, clinical, pathological characteristics and biomarkers were studied by Cox model as predictors of progression free survival (PFS) and overall survival (OS). Results: 493 of the 530 enrolled pts between 02/07 and 03/08 are included in this analysis, among whom at least 357 (72%) tumor specimens were collected. 88% were Caucasians, 32% females; median age was 62 (33–93); 15% were never smoker, 67% former and 15% active. 18% were PS0, 51% PS1 and 31% PS2–3. 92% pts were metastatic and 66% had adenocarcinoma (ADC). Erlotinib (150 mg in 98% of pts) was given as first-, second- and third-or-more-line in 10, 45, 42% of pts, respectively. 94% of pts had received previous platin-based chemotherapy. With a 11.5 months (mo.) median of follow-up, PFS was 2.4 mo. and OS 5.6 mo., with a 30% 1-year OS. Clinical factors independently associated with shorter OS were: PS1 and PS2–3 (HR=1.79 and 4.3, p<.0001); histology other than ADC and squamous cell (HR=1.44 and 1.03, p=.05); 2 sites of metastasis and more (HR=1.60 and 1.82, p<.0001) and former and active smoking (HR=1.49 and 2.12, p=.002). In multivariate analysis, line of treatment was not prognostic. Conclusions: The study confirmed in a large cohort of advanced NSCLC treated by erlotinib the independent value of several prognostic factors. Prognostic values of EGFR-IHC, EGFR-FISH and EGFR and KRAS mutations will be reported at the meeting. [Table: see text]

Loss of 5'ALK leads to better response to crizotinib in sarcomas with ALK rearrangement.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e23554-e23554
Author(s):  
Bin Li ◽  
Yongbin Hu ◽  
Qiongzhi He ◽  
Jingchen Lu ◽  
Gengwen Huang ◽  
...  
Keyword(s):  
Karnofsky Performance Status ◽  
Performance Status ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Underlying Mechanism ◽  
Alk Rearrangement ◽  
Undifferentiated Sarcoma ◽  
Clinical Responses ◽  
Alk Positive ◽  
Nsclc Patients

e23554 Background: Crizotinib targets abnormal ALK activation, however, the clinical responses vary among patients with ALK rearrangement. A recent study showed that the NSCLC patients with 5'ALK loss have a favorable response to Crizotinib with doubled progression-free survival (PFS). We asked whether sarcoma patients with ALK rearrangement have a similar correlation between 5'ALK loss and clinical response to Crizotinib. Methods: The histopathologic diagnosis was made on H&E staining and IHC, including anti-ALK(D5F3). DNA isolated from FFPE materials was subjected to an NGS assay targeting 295 genes including ALK rearrangement. Results: 4 cases were detailed in Table. Case#1 is an inflammatory myofibroblastic tumor with a PLEKHH2-ALK rearrangement, which was previously reported in an NSCLC but not in sarcomas. Case #2 is an undifferentiated sarcoma with 2 ALK fusions, RANBP2-ALK and TMEM217-ALK, both in-frame fusions containing intact tyrosine kinase domains. The TMEM217-ALK is a novel fusion. Case#3 is a leiomyosarcoma with MYH9-ALK fusion, which was often seen in ALK-positive large B-cell lymphoma but not in sarcoma. Case #4 is an undifferentiated sarcoma with EML4-ALK fusion. All 4 cases had positive ALK IHC, consistent with the expression of ALK fusion proteins. Case#1 and #2 had a loss of 5' ALK, while case #3 and #4 retained the 5' ALK. All cases received and responded to Crizotinib therapy, with the Karnofsky Performance Status (KPS) improved from 30-60 score pre-therapy to 90-100 score after 3 months of Crizotinib. While Case#3 and #4, both retained the 5' ALK, relapsed at 9.4 m and 6.1 m, case#1 and #2, both lost 5' ALK, remain progression-free at 15m and 27m, respectively. The side effect was manageable with a grade II hepatic toxicity in only one patient. Conclusions: We report here 4 sarcomas with ALK rearrangement, including a novel fusion TMEM217-ALK. Two of these cases had a 5' ALK loss in addition to the 3' ALK rearrangement, and both had much longer PFS on Crizotinib therapy. The underlying mechanism deserved further investigation. Four fibrosarcomas with ALK rearrangements and their response to Crizotinib therapy.[Table: see text]

SHP2 Inhibition Benefits Epidermal Growth Factor Receptor mutated Non-Small Cell Lung Cancer Therapy

2020 ◽  
Vol 20 ◽  
Author(s):  
Leiming Xia ◽  
Lu Wen ◽  
Siying Wang
Keyword(s):  
Stem Cells ◽  
Synergistic Effects ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Combination Strategies ◽  
Lung Cancer Therapy ◽  
Src Homology ◽  
Nsclc Patients ◽  
Egfr Mutated ◽  
Egfr Tkis

: EGFR-TKIs are facing a big challenge of everlasting activated EGFR mutations which lack of effective binding sites, this barrier confers the dark sides that largely limited the outcome of NSCLC patients in clinic. Combination strategies show impressive anti-tumor efficacy comparing with EGFR-TKI mono-treatment, especially targeting both stem cells and non-stem cells. SHP2 (Src homology 2-containing phosphotyrosine phosphatase 2) plays an important role in regulating various malignant biology through hyper-activating intracellular pathways due to either over expression or catalytical mutation. Some pathways that SHP2 involved in were overlaps with EGFR downstream, and others were not subject to EGFR. Interestingly, SHP2 suppression was reported that can destroy the stemness of cancer. Therefore, we hypothesize SHP2 inhibitor might be an promising drug that could synergistically enhance or sensitize the anti-tumor efficacy of EGFR-TKIs in EGFR mutated NSCLC patients. Here, we summarized the mechanisms of SHP2 in regulating EGFR mutated NSCLC patients, attempted to reveal the potential synergistic effects of SHP2 inhibitor combined with EGFR-TKIs.

scholarly journals Molecular and Clinical Features of EGFR-TKI-Associated Lung Injury

2021 ◽  
Vol 22 (2) ◽  
pp. 792
Author(s):  
Tohru Ohmori ◽  
Toshimitsu Yamaoka ◽  
Koichi Ando ◽  
Sojiro Kusumoto ◽  
Yasunari Kishino ◽  
...  
Keyword(s):  
Lung Injury ◽  
Tyrosine Kinase ◽  
Performance Status ◽  
Cytotoxic Agents ◽  
Egfr Mutations ◽  
Poor Performance Status ◽  
Chronic Obstructive ◽  
Tki Treatment ◽  
Egfr Tki ◽  
Egfr Tkis

The tyrosine kinase activity of epidermal growth factor receptors (EGFRs) plays critical roles in cell proliferation, regeneration, tumorigenesis, and anticancer resistance. Non-small-cell lung cancer patients who responded to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) and obtained survival benefits had somatic EGFR mutations. EGFR-TKI-related adverse events (AEs) are usually tolerable and manageable, although serious AEs, including lung injury (specifically, interstitial lung disease (ILD), causing 58% of EGFR-TKI treatment-related deaths), occur infrequently. The etiopathogenesis of EGFR-TKI-induced ILD remains unknown. Risk factors, such as tobacco exposure, pre-existing lung fibrosis, chronic obstructive pulmonary disease, and poor performance status, indicate that lung inflammatory circumstances may worsen with EGFR-TKI treatment because of impaired epithelial healing of lung injuries. There is limited evidence from preclinical and clinical studies of the mechanisms underlying EGFR-TKI-induced ILD in the available literature. Herein, we evaluated the relationship between EGFR-TKIs and AEs, especially ILD. Recent reports on mechanisms inducing lung injury or resistance in cytokine-rich circumstances were reviewed. We discussed the relevance of cytotoxic agents or immunotherapeutic agents in combination with EGFR-TKIs as a potential mechanism of EGFR-TKI-related lung injury and reviewed recent developments in diagnostics and therapeutics that facilitate recovery from lung injury or overcoming resistance to anti-EGFR treatment.

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