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.

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.

Chemoimmunotherapy combination: Potential option for metastatic NSCLC patients with EGFR mutation resistant to osimertinib.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20618-e20618
Author(s):  
Bo Yang ◽  
Yaping Long ◽  
Yi Hu
Keyword(s):  
Egfr Mutation ◽  
Acquired Resistance ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
Combination Group ◽  
Metastatic Nsclc ◽  
Number Of Patients ◽  
Grade 3 ◽  
Egfr Mutant ◽  
Nsclc Patients

e20618 Background: Osimertinib has been emerged as the standard selection in EGFR T790M-positive NSCLC patients who failed prior treatment with EGFR TKIs. However, acquired resistance to osimertinib is a growing clinical challenge. Despite the significant antitumor activity of Chemoimmunotherapy (CIT) combinations in NSCLC, clinical benefit in patients with EGFR mutations has not been shown obviously. Our objective was to assess the effectiveness and tolerability of CIT for metastatic EGFR-mutant NSCLC patients with acquired resistance to Osimertinib. Methods: We conducted a retrospective study in patients with sensitizing EGFR-mutant NSCLC who were resistant to Osimertinib and received anti-PD1 immunotherapy combined with chemotherapy at Chinese PLA General Hospital. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and toxicities were examined. Results: Between Oct 2015 and Nov 2018, 11 patients were available for analysis, 45.5% male, 45.5% ECOG PS 0-1, median age 54 years, all pts who failed treatment with Osimertinib had received previously targeted therapies. In this CIT combination group, 6 [54.5%] of 11 pts received pembrolizumab and 5[54.5%] of 11 pts received Nivolumab anti-PD1 therapy, 8 [72.7%] of 11 pts received mono-chemotherapy and 3 [27.3%] of 11 pts received platinum-based doublet chemotherapy. The median PFS was 7.47 months (95% CI 3.04 to 11.89). Despite Median OS was not reached, the OS rate at one year was 6 [54.5%] of 11. The ORR was 5 [45.5%] of 11. Treatment-related adverse events (TRAE) of grade 3 or higher were reported in 6 [54.5%] of 11 patients. The most common grade 3 or worse TRAEs were fatigue (3 [27.3%] of 11) and anemia (3 [27.3%] of 11); The following ≥Grade 3 TRAEs occurred once: decreased neutrophil count, acute kidney injury, gastrointestinal bleeding. One patient discontinued treatment because of immune-associated gastroenteritis. Conclusions: In metastatic NSCLC patients with activating EGFR mutation resistant to Osimertinib, our single institution real-world experience in Chemoimmunotherapy combination shows promising activity and acceptable toxicity profile. Given the small number of patients studied, further clinical trials are warranted.

scholarly journals Neoadjuvant EGFR-TKI Therapy for EGFR-Mutant NSCLC in Traditionally Unresectable Patients

2021 ◽  
Author(s):  
Ke-Cheng Chen ◽  
Shuenn-Wen Kuo ◽  
Chen-Hao Hsiao ◽  
Jing-Shing Chen
Keyword(s):  
Thoracic Surgery ◽  
Lung Adenocarcinoma ◽  
Surgical Resection ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
Multidisciplinary Management ◽  
Advanced Stage ◽  
Nsclc Patients

Abstract IntroductionAdvanced stage non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations may have benefit from tyrosine kinase inhibitors (TKI). However, the role of multidisciplinary management including neoadjuvant TKI therapy and thoracic surgery is uncertain. This study assessed the possible impact of neoadjuvant TKI therapy and thoracic surgery in selected advanced stage patients.MethodsAdvanced stage of IIIB and IVA NSCLC patients were retrospectively reviewed from 2010 to 2013. Patients with EGFR mutations who received neoadjuvant TKI followed by surgical resection were included. All patients were followed up for 5 years or until death.ResultsThere were total 15 advanced stage lung adenocarcinoma patients in the study. 8 patients were stage IIIB and 7 were stage IVA. All tumor sizes significantly decreased after neoadjuvant TKI therapy (p value = 0.0002). 11 patients received adjuvant TKI therapy after surgical resection and others received adjuvant cisplatin-based chemotherapy. Progression-free survival was superior in the group of adjuvant TKI therapy than in the group of adjuvant chemotherapy (median 14 months versus 5.9 months, p value = 0.016). Overall survival (OS) was not different between two groups (p value = 0.755). In the group of adjuvant TKI therapy, median OS in patients harboring exon 19 deletion and exon 21 L858R was 60 months and 44.9 months, respectively (p value = 0.078). ConclusionTKI may decrease the size of EGFR mutation lung adenocarcinoma. A multidisciplinary management including neoadjuvant TKI therapy and thoracic surgery may be discussed in selected advanced stage lung adenocarcinoma.

An updated analysis of ICOGEN to demonstrate utility of a blood-based proteomic test to predict outcomes in EGFR TKI treated patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20655-e20655
Author(s):  
Yuankai Shi ◽  
Xiaohong Han ◽  
Li Zhang ◽  
Lieming Ding ◽  
Nicholas Dupuis ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Progression Free Survival ◽  
Therapeutic Benefit ◽  
Phase Iii ◽  
Egfr Mutations ◽  
Study Endpoint ◽  
Primary Study ◽  
Plasma Samples ◽  
Nsclc Patients ◽  
Test Result

e20655 Background: ICOGEN was a randomized Phase III clinical trial comparing two EGFR tyrosine kinase inhibitors (TKI), icotinib (I) and gefitinib (G), in EGFR gene mutation status unknown non-small-cell lung cancer (NSCLC) patients previously treated with platinum doublet chemotherapy. Plasma samples from study patients were retrospectively analyzed with a commercially-available blood-based proteomic test which has been shown to have prognostic and predictive properties in NSCLC. This study represents an updated analysis of ICOGEN to evaluate the ability of the test to predict outcome based on therapeutic regimen. Methods: Available pre-treatment plasma samples from ICOGEN were retrospectively analyzed with the proteomic test which classifies subjects as Good or Poor. Progression free survival (PFS ) and over-all survival (OS) were analyzed within treatment (TX) arms and test classification. Results: 352 subjects were evaluated, with 277(78.7%) classified as Good and 75(21.3%) classified as Poor. Among all patients evaluated with the proteomic test, the median PFS was 4.9 mo. and 2.3 mo. (HR [95% CI] 0.61 [0.46 – 0.81]; p = 0.0004) and median OS was 16.6 mo. and 5.5 mo. (HR [95% CI] 0.39 [0.29 – 0.50]; p < 0.0001) for the Good and Poor sub-groups, respectively. Association between test result and PFS was significant in patients treated with I (6.0 mo vs. 1.9 mo, HR = 0.43, p < 0.0001), but not significant in patients treated with G (3.7 mo vs. 2.5 mo, HR = 0.85, p = 0.429). Further evaluation demonstrated that the proteomic test predicted differential therapeutic benefit between icotinib and gefitinib for PFS (pint = 0.036). In OS, a significant association between test result and outcome was shown in both the I (16.3 mo vs. 4.0 mo, HR [95% CI] 0.27[0.19-0.39]; p < 0.0001) and G (16.6 mo vs. 7.0 mo, HR [95% CI] 0.51[0.35-0.76; p = 0.0008) arms, which trended towards prediction of differential therapeutic benefit between icotinib and gefitinib for OS (pint = 0.086). Conclusions: For ICOGEN’s primary study endpoint, the proteomic test was predictive of differential therapeutic benefit between icotinib and gefitinib in EGFR mutations status unknown NSCLC patients.

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.

scholarly journals Better Progression-Free Survival in Elderly Patients with Stage IV Lung Adenocarcinoma Harboring Uncommon Epidermal Growth Factor Receptor Mutations Treated with the First-line Tyrosine Kinase Inhibitors

Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 434 ◽  
Author(s):  
Ming-Ju Tsai ◽  
Jen-Yu Hung ◽  
Mei-Hsuan Lee ◽  
Chia-Yu Kuo ◽  
Yu-Chen Tsai ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
First Line ◽  
Free Survival ◽  
Younger Patients ◽  
Epidermal Growth

Patients with lung adenocarcinoma harboring common epidermal growth factor receptor (EGFR) mutations usually have a good response rate (RR) and longer progression-free survival (PFS) to EGFR tyrosine kinase inhibitors (TKIs). However, the treatment efficacy to uncommon EGFR mutations remains controversial. We, therefore, performed a retrospective study, screening 2958 patients. A total of 67 patients with lung adenocarcinoma harboring uncommon EGFR mutations were enrolled and 57 patients with stage IV diseases receiving a first-line EGFR TKI were included for further analyses. The patients were classified into 27 (47%) “a single sensitizing uncommon mutation”, 7 (12%) “multiple sensitizing mutations”, 5 (9%) “a sensitizing mutation and a resistant uncommon mutation”, and 18 (32%) “other resistant uncommon mutations”. No significant difference was noted in PFS or overall survival (OS) between groups. Patients receiving different first-line EGFR TKIs had similar PFS and OS. The elder patients had a significantly poorer performance status than the younger patients but a significantly longer PFS than the younger patients (median PFS: 10.5 vs. 5.5 months, p = 0.0320). In conclusion, this is the first study to identify that elderly patients with stage IV lung adenocarcinoma harboring uncommon EGFR mutation might have a longer PFS. Large-scale prospective studies are mandatory to prove our findings.

scholarly journals Prognostic Value of BIM Deletion in EGFR-Mutant NSCLC Patients Treated with EGFR-TKIs: A Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Fangfang Lv ◽  
Liang Sun ◽  
Qiuping Yang ◽  
Zheng Pan ◽  
Yuhua Zhang
Keyword(s):  
Kinase Inhibitors ◽  
Meta Analysis ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Deletion Polymorphism ◽  
Asian Populations ◽  
Egfr Mutant ◽  
Nsclc Patients ◽  
Egfr Tkis

Background. Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is inevitable in EGFR-mutant non-small-cell lung cancer (NSCLC) patients. A germline 2903 bp deletion polymorphism of Bcl-2-like protein 11 (BIM) causes reduced expression of proapoptotic BH3-only BIM protein and blocks TKI-induced apoptosis of tumor cells. Yet the association between the deletion polymorphism and response to EGFR-TKI treatment remains inconsistent among clinical observations. Thus, we performed the present meta-analysis. Methods. Eligible studies were identified by searching PubMed, Embase, and ClinicalTrials.gov databases prior to March 31, 2021. Hazard ratios (HRs) and 95% confidence intervals (CIs) of progression-free survival (PFS) and overall survival (OS) and odds ratios (ORs) and 95% CIs of objective response rate (ORR) and disease control rate (DCR) were calculated by using a random effects model. Sensitivity, metaregression, and publication bias analyses were also performed. Results. A total of 20 datasets (3003 EGFR-mutant NSCLC patients receiving EGFR-TKIs from 18 studies) were included. There were 475 (15.8%) patients having the 2903-bp intron deletion of BIM and 2528 (84.2%) wild-type patients. BIM deletion predicted significantly shorter PFS ( HR = 1.35 , 95% CI: 1.10-1.64, P = 0.003 ) and a tendency toward an unfavorable OS ( HR = 1.22 , 95% CI: 0.99-1.50, P = 0.068 ). Patients with deletion polymorphism had lower ORR ( OR = 0.60 , 95% CI: 0.42-0.85, P = 0.004 ) and DCR ( OR = 0.59 , 95% CI: 0.38-0.90, P = 0.014 ) compared with those without deletion. Conclusion. BIM deletion polymorphism may confer resistance to EGFR-TKIs and can be used as a biomarker to predict treatment response to EGFR-TKIs in EGFR-mutant NSCLC patients from Asian populations.

Clinical and molecular characteristics of advanced non-small cell lung cancer (NSCLC) patients (pts) with rapid progressive disease (RPD) on gefitinib therapy (G)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7592-7592
Author(s):  
M. J. Fidler ◽  
L. Buckingham ◽  
M. Gale ◽  
J. Coon ◽  
A. Mauer ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Objective Response ◽  
Gene Copy Number ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
Gene Copy ◽  
Molecular Characteristics ◽  
Kaplan Meier ◽  
G 12 ◽  
Nsclc Patients

7592 Background: Prognostic factors associated with better outcomes (EGFR mutations (mut), high EGFR gene copy number, never smoking) can be used to select pts for EGFR tyrosine kinase inhibitor (TKI) combination trials, but would exclude the majority of NSCLC pts. Excluding pts with the worst likely outcomes is another strategy that may result in more pts who could benefit from the combination of a TKI with other agents. Our objective was to identify clinical and molecular characteristics associated with RPD (=70 days) and shorter progression-free survival (PFS) in previously treated NSCLC pts receiving G. Methods: Consecutive Expanded Access Trial pts with >1 week G were included for analysis. Tissue from 87 pts was evaluated for EGFR, pAKT and PTEN protein expression by immunohistochemistry; 58 tumors were analyzed for mut and sum of CA dinucliotide repeats (ΣCA rpts) by SSCP, PCR and sequencing. Results: There were 150 pts; 77 female, median (md) age 67. Md follow-up was 5.8 months (mo). Objective response was 8% (2CR, 10PR, 56 SD, 82 RPD). Md Kaplan-Meier PFS and survival were 2.0 and 5.8 mo, respectively. See table for univariate results. Smoking, Mut-PTEN-, EGFR-PTEN- and EGFR-pAKT- tumors were associated with shorter PFS. Separate clinical and molecular multivariate models were developed. In logistic regressions, non-adenocarcinoma histology (N- A), p=0.004, =12 mo from diagnosis to G (dx-G =12 mo), p=0.0009, lack of mut (p=0.0298) and ΣCA rpts <34 (p=0.0622) were associated with RPD. In Cox regressions, N-A (p=0.0256), dx-G =12 mo (p=0.0166) and lack of mut (p=0.0298) were associated with shorter PFS. Conclusions: N-A, dx-G =12 mo and lack of mut were associated with RPD and shorter PFS in univariate and multivariate analyses. ΣCA rpts <34 and double-negative molecular combinations were also related to worse outcome. These clinical and molecular characteristics may warrant further study as exclusion criteria for TKI combination clinical trials. [Table: see text] [Table: see text]

Usefulness of cytological samples (CS) for the assessment of ALK rearrangements in non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18008-e18008 ◽  
Author(s):  
Maria D. Lozano ◽  
Tania Labiano ◽  
Maria I. Zudaire ◽  
Alfonso Gurpide ◽  
Javier Zulueta ◽  
...  
Keyword(s):  
Molecular Subtype ◽  
Egfr Mutations ◽  
Fish Analysis ◽  
Gene Rearrangements ◽  
Cell Block ◽  
Alk Rearrangement ◽  
Kras Mutations ◽  
Inhibitor Analysis ◽  
Dual Colour ◽  
Nsclc Patients

e18008 Background: ALK gene rearrangements define a new molecular subtype of NSCLC with response to Crizotinib, a dual MET and ALK inhibitor. Analysis of ALK rearrangements has been performed in biopsies or surgical specimens. However, advanced NSCLC is often diagnosed by FNA cytology obtained through minimally invasive techniques, and frequently CS are the only tumour sample available. We assessed the feasibility of determining ALK rearrangements in CS. Methods: We studied prospectively ALK rearrangements in 53 CS from 53 NSCLC patients (30 M/23 F) by FISH (Vysis dual colour break apart probe). We considered positive for ALK rearrangement when > 15% of cells show splits signals. Tumor samples were obtained by bronchoscopy -FNA in 26 cases (49.1%), EBUS-FNA in 7 (13.2%), EUS-FNA in 3 cases (5.7%), CT-FNA in 3 (5.7%), and direct FNA in 6 cases (11.3%). Two cavity fluids (3.8%), 4 imprints (7.5%), and 2 cellblocks received for consultation (3.8%) were also studied. FISH was performed on non-stained ThinPrep in 28 cases (52.8%), Papanicolau stained smears in 15 cases (28.3%), cell block in 9 cases (17%), and 1 stained ThinPrep. All cases were tested for EGFR and KRAS mutations. Correlation cytological/paraffin embedded samples was performed in 4 paired cases. Results: Thirty-seven samples(69.8%) were adequate for FISH analysis. Three cases (8.1%) had ALK rearrangements: non-smoker women with adenocarcinoma, two of them with signet ring cells. One case had a concurrent EGFR mutation in exon 21. FISH study was unsuccessful in 16 cases (30.2%):10 Papanicolau stained smears (62.5%), 5 unstained ThinPrep (31.3%), and 1 cell block. Nineteen ThinPrep slides were adequate for FISH analysis (86.4%) as well as 8 out of 9 cell blocks. Concordance rate in paired cases were 100%. Conclusions: Determination of ALK gene rearrangements in CS is feasible. It is mandatory an exquisite management and care of the samples to preserve quality. ThinPrep and cell blocks are the most suitable samples for FISH analysis, while Papanicolau stained smears provide poor results. Coexistence of ALK gene rearrangements and EGFR mutations was observed in one case, indicating that such alterations are not necessarily mutually exclusive.

Circulating tumor cells and T790M in metastatic non-small cell lung cancer patients with EGFR mutations and acquired resistance to TKI.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18127-e18127
Author(s):  
Kazutoshi Isobe ◽  
Yoshinobu Hata ◽  
Keita Sato ◽  
Keishi Sugino ◽  
Go Sano ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Acquired Resistance ◽  
Stage Iv ◽  
Distant Metastases ◽  
Egfr Mutations ◽  
Cellsearch System ◽  
Metastatic Nsclc ◽  
Nsclc Patients ◽  
Egfr Tki

e18127 Background: This study assessed correlations between the presence of circulating tumor cells (CTCs), detection of T790M in organs with metastases or circulating-free DNA (cfDNA), and prognosis in metastatic NSCLC patients with acquired resistance to EGFR-TKI. Methods: Metastatic NSCLC patients with activating EGFR mutations, who initially responded but subsequently experienced disease progression while on EGFR-TKI treatment, were defined as having ‘acquired resistance’. Blood samples were collected after development of such acquired resistance and CTCs were counted using the CellSearch system (Veridex). At the same time, T790M in affected organs or cfDNA was analyzed with cycleave real-time PCR assay and fragment analysis. Results: : Six men and 14 women with a mean age of 63.5 yrs (22-84) were enrolled. Histological subtypes were adenocarcinoma in 19 and squamous cell carcinoma in the remaining one. Clinical stages were stage IV in 14 and recurrence with distant metastases after surgical resection in 6. EGFR mutations in tumors at the primary site were G719C in 1, exon 19 deletion in 7, L858R in 10, and G791C + L858R in 2. CTCs were detected in 8 (40%). Numbers of CTCs (per 7.5 ml blood) were 1 in 4 cases, and 3, 4, 8, and 24 in 1 case each. Patients without CTCs survived significantly longer than those with CTCs (≥1 per 7.5 ml). Mean survival time from first detection of CTCs was 3.0 months in patients with CTCs and not reached in patients without CTCs (p < 0.001). T790M was detected in 6 cases (30%). T790M was found in 75% (n = 6/8) of patients without CTCs but in 0% (n = 0/12) of those with CTCs (p < 0.05). Conclusions: The presence of CTCs was correlated with poorly prognosis and lack of T790M in affected organs or cfDNA. The presence of CTCs was informative for distinguishing patients with or without T790M.

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