Prediction of the molecular status in non-small cell lung cancer based on metastatic pattern: A free webtool powered by artificial intelligence.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9535-9535
Author(s):  
Benjamin Besse ◽  
Alison Dormieux ◽  
Laura Mezquita ◽  
Renaud Monnet ◽  
Melodie Tazdait ◽  
...  
Keyword(s):  
Artificial Intelligence ◽  
Lung Metastases ◽  
Smoking Status ◽  
Stage Iv ◽  
Egfr Mutations ◽  
Molecular Testing ◽  
Free Access ◽  
Braf Mutations ◽  
Kras Mutations ◽  
Metastatic Pattern

9535 Background: Molecular characterization of metastatic lung adenocarcinomas is mandatory but might be hampered by the quantity of tissue, restricted access to molecular platforms or limited economical resources. Our aim was to develop a tool supported by the hypothesis that radiological patterns of pts could help predict the rate of positivity of the most common oncogenic drivers. Methods: We defined an algorithm based on a molecularly defined cohort of 656 pts with stage IV lung adenocarcinoma. Two radiologists centrally reviewed the baseline imaging. Clinical data were retrospectively collected. There were 135 EGFR mutations, 81 ALK fusions, 47 BRAF mutations, 141 KRAS mutations, and 146 pan-negative tumors for these 4 oncogenic drivers. Univariate correlation analyses were performed to define an algorithm predicting the molecular testing positivity based on the metastatic pattern. Subsequently, an online tool was developed. This study was approved by our institutional review board. Results: Metastatic patterns correlated with the genomic drivers when compared to the pan-negative group. In the EGFR group, pleural metastases were more frequent (32% vs. 20%; p = 0.021), whereas adrenal and node metastases less frequent (6% vs.23%; p < 0.001 and 11% vs. 23% respectively; p = 0.011). In the ALK group, there were more brain and lung metastases (respectively 42% vs. 29%; p = 0.043 and 37% vs. 24% respectively; p = 0.037). In the BRAF group, pleural and pericardial metastases were more common (47% vs. 20%; p < 0.001 and 11% vs. 3% respectively; p = 0.04) and bone metastases less common (21% vs. 42%; p = 0.011). Lymphangitis was more frequent in EGFR, ALK and BRAF groups (6%, 7% and 15% vs. 1%; p = 0,016, p = 0,009 and p < 0,001 respectively). A free online access to the algorithm is now available after registration at http//tactic-ct.fr. Physicians enter age, sex, smoking status and the sites of metastases at diagnosis (present/absent/unknown). A mutation score is calculated, reflecting the % of chance to find an oncogenic driver. On the website, contributors can also enter new cases and an artificial intelligence will refine the algorithm and expand the number of oncogenic drivers. Conclusions: Our free access tool allows establishing a hierarchy in the molecular testing based on simple clinical and radiological information. Continual learning from new cases entered in the database will increase the sensitivity of the tool. This tool might save time, tumor tissue, economical resources and accelerate access to personalized treatment.

The spectrum of genomic alterations in young adult non-small cell lung cancer (NSCLC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8077-8077
Author(s):  
Geoffrey R. Oxnard ◽  
Jennifer C. Heng ◽  
Stacy L. Mach ◽  
Peter C. Lo ◽  
Mohit Butaney ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Characteristics ◽  
Stage Iv ◽  
Egfr Mutations ◽  
Insertion Mutation ◽  
Braf Mutations ◽  
Genomic Alterations ◽  
Kras Mutations ◽  
Targeted Next Generation Sequencing ◽  
Undifferentiated Histology

8077 Background: Identification of targetable genomic alterations in patients (pts) with NSCLC can have a profound impact on treatment and clinical outcomes. Given the complexity and cost of comprehensive genomic testing, clinical characteristics enriching for targetable genomic alterations are of interest. We hypothesized that young adults with NSCLC would have a higher prevalence of targetable genomics alterations compared to the general NSCLC population. Methods: An institutional database of pts with NSCLC was reviewed in an IRB-approved fashion to identify subjects with age < 40 at diagnosis. Clinical characteristics and risk factors were reviewed. Tumor genotyping for alterations in EGFR, KRAS, ALK, BRAF, HER2, and ROS1was pursued as part of an institution-wide genomics protocol. Targeted next-generation sequencing (NGS) of wild-type cases is underway. Results: From 2032 subjects with NSCLC, we identified 70 diagnosed at an age < 40 (3.4%). Pt characteristics: median age 35 (range 20-39); 63% never-smokers, 33% with ≥10 pack-years; 74% adeno, 9% squam, 14% undifferentiated, 3% neuroendocrine; 19% had a family history of lung cancer; 61% stage IV at diagnosis. Median survival from date of advanced disease was 15.8 months. Genotyping was performed on 51 pts with adeno or undifferentiated histology: 14 with EGFR mutations (27%), 5 with KRAS mutations (10%), 8 with ALK rearrangements (16%), 0 with BRAF mutations, 1 with a HER2 insertion (2%), 1 with a ROS1 rearrangement (2%). Compared to a reference prevalence from the Lung Cancer Mutation Consortium (Kris et al, ASCO, 2011), KRAS mutations were less common (p=0.01) and ALK rearrangements were more common (p<0.01). NGS of 2 cases to date has identified one pt with a novel 21 base-pair insertion mutation in FGFR2, not present in germline tissue. Conclusions: 47% (CI: 33%-60%) of pts diagnosed with NSCLC under age 40 harbor a targetable alteration in EGFR, ALK, HER2, or ROS1. These patients may be enriched for targetable genotypes and deserving of a unique treatment approach, and additionally represent an attractive population for genomic discovery.Supported in part by the Bonnie J. Addario Lung Cancer Foundation and the Conquer Cancer Foundation of ASCO.

Feasibility and clinical impact of routine molecular testing of gastrointestinal (GI) cancers at a tertiary center with a multigene, next generation sequencing (NGS) panel.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 216-216
Author(s):  
Giacomo Bregni ◽  
Tiberio Sticca ◽  
Tugba Akin Telli ◽  
Silvia Camera ◽  
Ligia Ioana Craciun ◽  
...  
Keyword(s):  
Stage Iv ◽  
Needle Aspiration ◽  
Genetic Alterations ◽  
Clinical Impact ◽  
Molecular Testing ◽  
Routine Practice ◽  
Clinical Value ◽  
Braf Mutations ◽  
Kras Mutations ◽  
Tertiary Center

216 Background: High-throughput technologies have been increasingly used in research. Nevertheless, limited data are available on the feasibility and clinical value of these technologies in routine practice. Methods: All consecutive GI cancer patients (pts) who were tested with the 48-gene Truseq Amplicon Cancer Panel (Illumina) as part of routine practice at our Institution were identified from a prospectively maintained pathology database. Feasibility, results and impact on management decisions were analysed. Associations were tested with Fisher’s test. Results: From Apr 2014 to Jun 2019, 314 pts were tested. Sequencing was successful in 290 cases (92.4%; 234 colorectal (CRC), 21 gastro-esophageal, 17 bilio-pancreatic, 9 GIST, 4 appendix, 3 small intestine, 2 hepatocellular). In successful and failed cases, respectively, analyses were attempted on core biopsy (37.0% vs 66.7%), surgery (62.6% vs 16.7%), and fine needle aspiration (0.4% vs 12.4%) tumour samples (p < 0.001). Median turnaround time (TAT) was 12.5 days, reducing from 13 days in 2014 to 10 days in 2019. The majority of successfully tested pts (85.6%) had stage IV disease. TP53 was the most frequent mutation (45.9%), followed by APC (42.1%), KRAS (39.7%), PIK3CA (12.1%), SMAD4 (7.6%), BRAF (6.2%), and NRAS (5.5%). All other mutations were found in < 5% of cases. Excluding RAS/BRAF and KIT/PDGFR mutations, sequencing results impacted on the management of 4 (1.4%) pts. In 199 stage IV CRC pts, KRAS mutations were associated with lung (p = 0.020) and bone metastases (mts) (p = 0.008), NRAS mutations with liver mts (p = 0.021), BRAF mutations with peritoneal mts (p = 0.001), and APC mutations with lymph node mts (p = 0.006). Assuming a median of 25 samples per run, the estimated cost of NGS analysis per pt was €186. Conclusions: Low failure rate, short TAT and fair costs support feasibility of multi-gene NGS in routine practice. The clinical impact of this technology, however, is still limited but it could raise with the identification of new biologically relevant genetic alterations and the increased availability of novel therapeutics.

Lung Cancer in 2013: State of the Art Therapy for Metastatic Disease

2013 ◽  
pp. 339-346
Author(s):  
Frances A. Shepherd ◽  
Paul A. Bunn ◽  
Luis Paz-Ares
Keyword(s):  
Lung Cancer ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Stage Iv ◽  
Poor Performance ◽  
Initial Therapy ◽  
Egfr Mutations ◽  
Molecular Testing ◽  
Molecular Features ◽  
Platinum Doublet

Lung cancer is the leading worldwide cause of cancer death and the majority of patients present with metastatic stage IV disease. At diagnosis, clinical, histologic, and molecular features must be considered in therapeutic decision-making for systemic therapy. Molecular testing for at least epidermal growth factor receptor ( EGFR) and ALK should be performed in all patients before therapy. Platinum doublet chemotherapy may be considered for “fit” patients who do not have a molecular driver genetic abnormality. Bevacizumab can be considered for addition to the doublet in patients with nonsquamous cancers who have no contraindications. A pemetrexed combination is considered only in nonsquamous histology. Patients with EGFR mutations or ALK fusions should be treated with erlotinib or crizotinib, respectively, even in patients with tumor-related poor performance. The tyrosine-kinase inhibitors (TKIs) may be continued until multisite, symptomatic progression. For patients initially treated with a platinum doublet, maintenance chemotherapy with pemetrexed, erlotinib, gemcitabine, or possibly docetaxel is an option with selection based on clinical features, histology, type of initial therapy, and response to first-line therapy.

scholarly journals Analysis of Predictive Biomarkers in Patients With Lung Adenocarcinoma From Southern Brazil Reveals a Distinct Profile From Other Regions of the Country

2019 ◽  
pp. 1-9 ◽  
Author(s):  
Tiago F. Andreis ◽  
Bruno S. Correa ◽  
Fernanda S. Vianna ◽  
Fernanda De-Paris ◽  
Marina Siebert ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Predictive Biomarkers ◽  
Egfr Mutations ◽  
Southern Brazil ◽  
Braf Mutations ◽  
Kras Mutations ◽  
Histologic Subtype ◽  
Molecular Alterations ◽  
Common Histologic Subtype ◽  
L1 Protein

PURPOSE Adenocarcinoma is the most common histologic subtype of non–small-cell lung cancer, representing 40% of all diagnoses. Several biomarkers are currently used to determine patient eligibility for targeted treatments, including analysis of molecular alterations in EGFR and ALK, as well as programmed death-ligand 1 (PD-L1) protein expression. Epidemiologic data reporting the frequency of these biomarkers in Brazilian patients with lung adenocarcinoma (LUAD) are limited, and existing studies predominantly included patients from the southeast region of the country. MATERIALS AND METHODS The goal of this study was to investigate the frequency of somatic mutations in the EGFR, KRAS, NRAS, and BRAF genes, ALK, and PD-L1 expression in a series of Brazilian patients diagnosed with LUAD predominantly recruited from centers in southern Brazil. Molecular analysis of the EGFR, KRAS, NRAS, and BRAF genes was performed by next-generation sequencing using DNA extracted from tumor tissue. Immunohistochemistry was used to detect ALK and PD-L1 expression. RESULTS Analysis of 619 tumors identified KRAS mutations in 189 (30.2%), EGFR mutations in 120 (19.16%), and BRAF mutations in 19 (3%). Immunohistochemistry demonstrated ALK and PD-L1 expression in 4% and 35.1% of patients, respectively. CONCLUSION To our knowledge, this is the first study investigating the molecular epidemiology of patients with LUAD from southern Brazil and the largest assessing the frequency of multiple predictive biomarkers for this tumor in the country. The study also reveals a distinct mutation profile compared with data originating from other regions of Brazil.

Smoking history and frequency of somatic KRAS mutations in adenocarcinoma of the lung

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7573-7573
Author(s):  
V. A. Miller ◽  
G. J. Riely ◽  
M. G. Kris ◽  
D. Rosenbaum ◽  
J. Marks ◽  
...  
Keyword(s):  
Cigarette Smoking ◽  
Mutational Analysis ◽  
Smoking History ◽  
Egfr Mutations ◽  
Molecular Testing ◽  
Kras Mutations ◽  
Exon 2 ◽  
Significant Difference ◽  
Never Smokers ◽  
Lung Adenocarcinomas

7573 Background: Somatic mutations in the epidermal growth factor receptor (EGFR) gene are more common in patients with adenocarcinoma, especially those who smoked < 15 pack years (py). KRAS mutations are found in ∼25% of lung adenocarcinomas, most commonly in codons 12 and 13 of exon 2 (∼85%) and have been associated with poor prognosis in resected disease [Winton NEJM 2005] and resistance to EGFR tyrosine kinase inhibitors [Pao PLoS Med 2005]. KRAS mutations are uncommon in non-small cell lung cancer histologies other than adenocarcinoma. We sought to determine the association between quantitative measures of cigarette smoking and presence of KRAS mutations in lung adenocarcinomas. Methods: Standard direct sequencing techniques were used to identify KRAS codon 12 and 13 mutations in lung adenocarcinoma specimens from surgical resections between 2001 and 2006 and tumor specimens sent for KRAS molecular analysis in 2006. Surgical specimens were obtained from an institutional tumor bank. Detailed smoking history (age at first cigarette, packs per day, years smoked, years since quitting smoking) was obtained from the medical record and a patient-completed smoking questionnaire. Results: KRAS mutational analysis was performed on 408 lung adenocarcinomas from 242 women and 166 men. Median age was 68 (range 33–89). KRAS mutations were present in 19% (78/408, 95% CI 15 to 23%). The frequency of KRAS mutation was not associated with age or gender. The presence of KRAS mutations was not related to smoking history with 15% (9/61) of never smokers having KRAS mutations compared with 19% (51/275) of former smokers. When compared with never smokers, there was no significant difference in frequency of KRAS mutations for tumors from patients with 1–5 py (5%, p=0.44), 6- 10 py (12%, p=0.99), 11–15 py (25%, p=0.45), 16–25 py (16%, p=0.99), 26–50 py (25%, p=0.129), 51–75 py (20%, p=0.48), >75 py (20%, p=0.47) history of cigarette smoking. Conclusions: While the incidence of EGFR mutations has a strong inverse relationship with the amount of cigarettes smoked, allowing the selective molecular testing for EGFR mutations, the frequency of KRAS mutations cannot be predicted by age, gender, or smoking history. KRAS mutational analysis of all adenocarcinomas is required to reliably identify patients with KRAS mutations. No significant financial relationships to disclose.

Clinical characteristics of KRAS mutations in NSCLC and their impact on outcomes to first-line chemotherapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7588-7588
Author(s):  
Mohit Butaney ◽  
Jennifer Porter ◽  
Neal Ian Lindeman ◽  
Pasi A. Janne ◽  
Michael S. Rabin ◽  
...  
Keyword(s):  
Smoking Status ◽  
Egfr Mutations ◽  
Limited Information ◽  
Wild Type ◽  
First Line ◽  
Kras Mutations ◽  
Response To Chemotherapy ◽  
Significant Difference ◽  
The Impact ◽  
Line Chemotherapy

7588 Background: KRAS is one of the most commonly mutated oncogenes in non-small cell lung cancer (NSCLC). While the impact of EGFR mutations and EML4-alk translocations has been well-described, there is limited information about the impact of these somatic mutations on response to chemotherapy. Methods: We retrospectively reviewed the demographics and clinical outcomes of patients with KRAS mutations and compared these to patients who were KRAS wild-type (WT). Eligible pts received 1st-line IV chemo for stage IV NSCLC at DFCI and had known information about both KRAS and EGFR status. Since the biology and impact of EGFR mutations on response to chemo is well-described, we excluded such pts from the analysis. The primary endpoint was progression-free survival (PFS) with first-line chemo; secondary endpoints included radiographic response rate (RR) and overall survival (OS). Results: Between 2/05 and 8/11, there were 63 eligible KRAS pts and 97 eligible WT pts. The groups were similar in age (median 65yrs in both groups), % female (K 62, WT 54) race (K 89% white/6% black, 5% other; WT 86% white,/6% black/8% other), histology (K 90%adeno/8% NSCLC NOS; WT 86% adeno/9%NSCLC NOS), and % of pts receiving 1/2/3 agents in 1st line (K 11/56/33; WT 18/53/30). KRAS pts were less likely to be never or light smokers (4% vs 33% for WT). Nonsmokers were more likely to harbor KRAS transition rather than transversion mutations (3 transition, 1 transversion), while the converse held for smokers (51 transversions, 8 transitions). Median PFS was similar for KRAS vs WT (K .65 vs WT 4.8 months, p=0.81). RR (29% for both groups), disease control rates (K 73% vs WT 78%), and median OS (K 13.5 vs WT 12.1 months, p=.525) were also similar. Outcomes of KRAS pts to 2nd line chemotherapy (PFS 2.2, OS 8.6) are similar to those seen for WT patients in this setting. There was no significant difference in outcomes based on gender, smoking status, drug received (pemetrexed-based vs taxane based), or specific KRAS genotype. Conclusions: Pts with KRAS mutations experience similar outcomes to standard chemotherapy as those who are wild-type for EGFR and KRAS. Going forward, these data can serve as a reference for control arms of KRAS-specific randomized trials.

Predictors of delays in initiation of oral tyrosine kinase inhibitors (TKIs) in EGFR and ALK positive advanced non-small cell lung cancer (NSCLC).

2019 ◽  
Vol 37 (27_suppl) ◽  
pp. 134-134
Author(s):  
Bernardo H. L. Goulart ◽  
Shasank Chennupati ◽  
Kathryn Egan ◽  
Catherine R. Fedorenko ◽  
Scott David Ramsey
Keyword(s):  
Median Time ◽  
Language Processing ◽  
Cost Sharing ◽  
Cox Regression ◽  
Stage Iv ◽  
Egfr Mutations ◽  
Molecular Testing ◽  
Median Income ◽  
Delayed Initiation ◽  
Male Sex

134 Background: Molecular testing practices and cost-sharing policies may result in delayed initiation of TKI therapy. We assessed predictors of delayed initiation of TKIs in metastatic EGFR+ or ALK+ NSCLC. Methods: We identified patients with EGFR+ and ALK+ NSCLC diagnosed between 01/01/2010 and 12/31/2016 in the Washington State SEER registry using validated natural language processing methods. We linked registry records to commercial and Medicare (including part D) claims. Eligible patients had stage IV NSCLC, sensitizing EGFR mutations or ALK+ by FISH, ≥ 1 pharmacy claims for EGFR or ALK TKIs, and ≥12 months of insurance enrollment post-diagnosis. Potential predictors included age, sex, race, Census-level median household income, urban status, insurance type, comorbidity, histology, mutation type, and receipt of chemotherapy prior to first TKI claim (pre-TKI chemo). We defined time to TKI initiation as the interval from diagnosis to first pharmacy claim for EGFR or ALK TKIs. We fitted Cox regression models to identify predictors of delays in TKI initiation, defining covariates with a P < 0.05 in a final multivariate model as independently associated with delays. Results: For 122 patients (median age 70; 65% female; 74% White; median income $66,580; 98% metropolitan; 35% Medicare; 80% EGFR+; 12% using pre-TKI chemo), the median time to TKI initiation was 6.7 weeks (IQR = 3.9 to 14.0). Independent predictors of TKI delays included male sex (HR = 0.51; 95%CI = 0.34; 0.76); Medicare insurance (HR = 0.32; 95% CI = 0.20; 0.53) and pre-TKI chemo (HR = 0.37; 95% CI = 0.20; 0.66). Median time to TKI initiation was 9.7 vs. 5.8; 7.8 vs. 4.1; and 16.0 vs. 6.3 weeks in male vs. female, Medicare vs. commercial insurance, and pre-TKI chemo (yes vs no), respectively. Conclusions: Male sex, Medicare insurance, and chemotherapy prior to TKI are associated with delays in TKI initiation for EGFR+ and ALK+ stage IV NSCLC patients. Possible explanations include higher prevalence of smoking in males resulting in lower priority for molecular testing, high cost-sharing policies for TKIs in Medicare patients, and prolonged time to obtain molecular test results leading patients to start chemotherapy first.

scholarly journals Molecular Features and Clinical Outcomes of Extramedullary Plasmacytomas

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 398-398
Author(s):  
Rie Nakamoto-Matsubara ◽  
Valentina Nardi ◽  
Cristina Panaroni ◽  
Keertik Fulzele ◽  
Tomoaki Mori ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Chromosome 1 ◽  
Molecular Testing ◽  
Fish Analysis ◽  
Braf Mutations ◽  
Kras Mutations ◽  
Molecular Abnormalities ◽  
Molecular Features ◽  
Number Of Patients

Abstract The treatment of multiple myeloma (MM) continues to evolve with new drugs, resulting in dramatically improved outcomes. Despite these advances, MM remains an incurable disease, with Extraosseous/Extramedullary disease (EMD) playing a major role in the development of relapsed refractory disease. EMD is defined by the development of plasma cell neoplasms that arise in tissues other than bones. EMD can present at diagnosis or develop during the disease course of MM. Sometimes EMD can be solitary without bone marrow (BM) involvement. Determining the molecular underpinnings of EMD are critical to advance the care of such patients. A few reports suggest a possible role of Ras mutations in the intramedullary to extramedullary transition in a limited number of patients. Therefore, the molecular biology of developing EMD has not yet been clearly defined. We sought to identify molecular features of EMD and associated these with clinical outcomes. We analyzed samples from 443 MM patients who presented to Massachusetts General Hospital between 2013 and 2021. All patients voluntarily signed informed consent approved by the institutional review board for SNaPshot (molecular) testing. BM aspirate, biopsy and EMD tumor specimens underwent pathological analysis as well as FISH testing. The diagnosis of EMD was determined by either CT, PET-CT or MRI done as part of their clinical course. In some cases, EMD was confirmed by biopsy. Although there were some cases of EMD adjacent to bones, we strictly defined EMD as non-adjacent to bones based on imaging. Nucleic acids were extracted from BM and EMD samples obtained from MM patients. Multiplexed mutational analysis was done with primers designed to cover 111 genes including genes known to be oncogenic. SNaPshot was done and the threshold for allele frequencies was determined as 8% based on our laboratory cut-offs. The median follow-up of the entire MM population was 63.7 months (range 1 to 408). Overall, 96 of 443 patients (21.6%) developed EMD as previously defined. Sixty-five out of 96 patients had biopsy confirmed EMD, while 31 patients were diagnosed by imaging only. SNaPshot molecular testing was performed on 30 EMD samples from the 65 patients who had biopsies. Interestingly, all EMD samples except for 1 had either NRAS, KRAS, or BRAF mutations. There were 14 EMD samples with NRAS mutations, 6 with KRAS mutations, 4 with BRAF mutations, and 1 with both KRAS and BRAF mutations. All BRAF mutations coexisted with other mutations, such as TP53, ATM, and ARID1A whereas some of the NRAS and KRAS mutations were observed alone. Next SNaPshot was analyzed for 8 paired BM and EMD samples. Three BM samples were negative for NRAS mutations while all EMD samples were positive. Patients with KRAS/NRAS/BRAF mutations who developed EMD had poorer prognosis than non-EMD patients with KRAS/NRAS/BRAF mutations. In patients with KRAS mutations, the median overall survival (OS) was 36.9 months (EMD) vs not reached (non-EMD) (p&lt;0.01); and BRAF mutations, the median OS was 58.5 months (EMD) vs 112.4 months(non-EMD) (p=0.194). In patients with NRAS mutations, the median OS was 94.5 months(EMD) vs 124.5 months (non-EMD) (p=0.11). Average time from diagnosis of MM to developing EMD in 68 patients with longitudinal follow up was 41.6 months and average time from developing EMD to death in 54 patients with longitudinal follow-up was 7.6 months. There were significant differences in BM FISH analysis in KRAS/NRAS/BRAF mutation harboring EMD vs non-EMD; Chromosome 1 abnormalities (79.2% vs 34.2%), TP53 deletion (41.7% vs 22.4%) and hyperdiploidy (37.5% vs 67.1%). Our data suggest that KRAS/NRAS/BRAF mutations may play an important role in the development of EMD. These and other associated molecular abnormalities portend a poorer prognosis and may provide novel therapeutic insights. Disclosures Nardi: Loxo Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees. Yee: Amgen: Consultancy; Bristol Myer Squibb: Consultancy; Adaptive: Consultancy; GSK: Consultancy; Janssen: Consultancy; Oncopeptides: Consultancy; Sanofi: Consultancy; Takeda: Consultancy; Karyopharm: Consultancy. Branagan: Adaptive Biotechnologies: Consultancy; BeiGene: Consultancy; CSL Behring: Consultancy; Karyopharm: Consultancy; Pharmacyclics: Consultancy; Sanofi Genzyme: Consultancy. O'Donnell: Onocopeptide: Consultancy; Karyopharm: Consultancy; Janssen: Consultancy; Bristol Myer Squibb: Consultancy; Adaptive: Consultancy; Takeda: Consultancy. Raje: Celgene, Amgen, Bluebird Bio, Janssen, Caribou, and BMS: Other.

Association between different potential predictive markers from TRUST, a trial of erlotinib in non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7651-7651 ◽  
Author(s):  
E. Laack ◽  
C. Schneider ◽  
T. Gutjahr ◽  
E. Heinmöller ◽  
V. Lutz ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Smoking Status ◽  
Gene Copy Number ◽  
Predictive Markers ◽  
Egfr Mutations ◽  
Gene Copy ◽  
Tumor Type ◽  
Open Label ◽  
Kras Mutations ◽  
Tumor Patient

7651 Background: Recent studies have examined potential predictive markers in NSCLC patients (pts) treated with EGFR tyrosine kinase inhibitors. However, few data are available on inter-relationships between different markers. Clinical and molecular markers were analyzed for patients from TRUST, an open label, non-randomized trial initiated to provide erlotinib access to pts with advanced NSCLC. Methods: 393 German pts (99% Caucasian) with stage IIIb/IV NSCLC were included. Markers/characteristics assessed were: EGFR (282 pts) and phosphorylated MAPK (pMAPK; 109 pts) using immunohistochemistry (IHC; positive status was defined as: ≥10% of tumor cells with any membrane staining for EGFR; and H-score ≥200 for pMAPK), EGFR gene copy number (135 pts) using fluorescence in-situ hybridization (FISH), EGFR mutations (86 pts), KRAS mutations (108 pts), tumor type (281 pts), smoking status (392 pts) and gender (393 pts). Results: EGFR FISH+ pts were likely to also be EGFR IHC+: 92.9% (26/28) of EGFR FISH+ pts were EGFR IHC+, and 92.6% of EGFR IHC- pts were also EGFR FISH- (p<0.1). pMAPK expression status was not related to other markers. 15.7% (17/108) pts had KRAS and 7.0% (6/86) had EGFR mutations; no pts had mutations in both genes, indicating that these mutations might be mutually exclusive. Both KRAS mutations and histology were associated with smoking status. 94.1% (16/17) pts with KRAS mutations and 91.6% (87/95) pts with squamous-cell carcinoma were smokers. In female pts, the occurrence of adenocarcinoma was significantly higher (73.6% vs 55.4% in males; p<0.001), possibly influenced by a lower incidence of smokers in this group (51.3% vs 92.2% in males; p<0.001). Conclusions: The availability of a large number of tumor samples from the TRUST study, and assessment of a broad range of markers allows investigation of relationships between various tumor/patient characteristics. Understanding these complex inter-relationships may shed light on the role of each marker. Specific combinations of markers may prove useful in predicting clinical benefit from erlotinib. As the study is ongoing, additional data will be available and presented. No significant financial relationships to disclose.

Clinical features of patients with lung adenocarcinomas harboring BRAF V600E mutations.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8101-8101 ◽  
Author(s):  
Tongtong An ◽  
Jie Wang ◽  
Hua Bai ◽  
Zhijie Wang ◽  
Jun Zhao ◽  
...  
Keyword(s):  
Survival Rates ◽  
Multivariate Logistic Regression Analysis ◽  
Braf V600e ◽  
Chinese Patients ◽  
Smoking History ◽  
Egfr Mutations ◽  
Occurrence Rate ◽  
Braf Mutations ◽  
Kras Mutations ◽  
Lung Adenocarcinomas

8101 Background: To investigate the prevalence, distribution, and prognostic role of activating BRAF mutations in Chinese patients with lung adenocarcinomas (ADCs). Methods: This retrospective study included 192 lung ADCs (97 males 50.5%, 95 females 49.5%). BRAF gene mutations were screened using AmoyDx BRAF V600E mutations detection kit. Mutations of EGFR and KRAS gene were also analyzed. Results: BRAF mutations were present in 8(4.17%) lung ADCs patients. V600E mutations were significantly more prevalent in females (6 of 96; 6.25%) than in males (2 of 97; 2.06%), as indicated by multivariate logistic regression analysis. Other clinocopathologic parameters, including age, smoking history, and tumor stage, were not significantly associated with V600E BRAF mutations. V600E-mutated tumors were not associated with different progression-free and overall survival rates comparing with non V600E-mutated tumors in this study. The frequency of EGFR and KRAS mutations in all patients were 42.7%(82/192) and 8.3%(16/192), respectivelyBRAF and EGFR were concomitantly mutated in three tumors. All tumors with BRAF mutations were found to be negative for KRAS mutations. Conclusions: We report for the first time to our knowledge that V600E BRAF mutation has high concomitant occurrence rate with EGFR mutations in Chinese lung ADCs patients. BRAF mutations were found to be independently associated only with female gender.

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