scholarly journals Clinical Characteristics of Patients With Lung Adenocarcinomas Harboring BRAF Mutations

2011 ◽  
Vol 29 (15) ◽  
pp. 2046-2051 ◽  
Author(s):  
Paul K. Paik ◽  
Maria E. Arcila ◽  
Michael Fara ◽  
Camelia S. Sima ◽  
Vincent A. Miller ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Clinical Characteristics ◽  
Median Overall Survival ◽  
Smoking History ◽  
Egfr Mutations ◽  
Braf Mutations ◽  
Former Smokers ◽  
Lung Adenocarcinomas

Purpose BRAF mutations occur in non–small-cell lung cancer. Therapies targeting BRAF mutant tumors have recently been identified. We undertook this study to determine the clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. Patients and Methods We reviewed data from consecutive patients with lung adenocarcinoma whose tumors underwent BRAF, EGFR, and KRAS mutation testing as well as fluorescence in situ hybridization for ALK rearrangements. Patient characteristics including age, sex, race, performance status, smoking history, stage, treatment history, and overall survival were collected. Results Among 697 patients with lung adenocarcinoma, BRAF mutations were present in 18 patients (3%; 95% CI, 2% to 4%). The BRAF mutations identified were V600E (50%), G469A (39%), and D594G (11%). Mutations in EGFR were present in 24%, KRAS in 25%, and ALK translocations in 6%. In contrast to patients with EGFR mutations and ALK rearrangements who were mostly never smokers, all patients with BRAF mutations were current or former smokers (P < .001). The median overall survival of advanced-stage patients with BRAF mutations was not reached. In comparison, the median overall survival of patients with EGFR mutations was 37 months (P = .73), with KRAS mutations was 18 months (P = .12), and with ALK rearrangements was not reached (P = .64). Conclusion BRAF mutations occur in 3% of patients with lung adenocarcinoma and occur more commonly in current and former smokers. The incidence of BRAF mutations other than V600E is significantly higher in lung cancer than in melanoma.

Use of Cigarette-Smoking History to Estimate the Likelihood of Mutations in Epidermal Growth Factor Receptor Gene Exons 19 and 21 in Lung Adenocarcinomas

2006 ◽  
Vol 24 (11) ◽  
pp. 1700-1704 ◽  
Author(s):  
DuyKhanh Pham ◽  
Mark G. Kris ◽  
Gregory J. Riely ◽  
Inderpal S. Sarkaria ◽  
Tiffani McDonough ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Receptor Gene ◽  
Growth Factor Receptor ◽  
Smoking History ◽  
Egfr Mutations ◽  
Epidermal Growth ◽  
Former Smokers ◽  
Never Smokers ◽  
Lung Adenocarcinomas ◽  
Exon 19

Purpose Lung adenocarcinomas with mutations in exons 19 and 21 of the epidermal growth factor receptor gene (EGFR) demonstrate sensitivity to gefitinib or erlotinib. Investigators have reported an association between EGFR mutations and the amount and duration of cigarette smoking, with the highest incidence of mutations seen in never smokers. Methods EGFR exon 19 and 21 mutation status was determined in 265 tumor samples using direct sequencing, polymerase chain reaction (PCR), or PCR-based restriction fragment length polymorphism analysis. A detailed smoking history was obtained. Patients were categorized as never smokers (< 100 lifetime cigarettes), former smokers (quit ≥ 1 year ago), or current smokers (quit < 1 year ago). Results We detected EGFR mutations in 34 (51%) of 67 never smokers (95% CI, 38% to 64%), 29 (19%) of 151 former smokers (95% CI, 13% to 27%), and two (4%) of 47 current smokers (95% CI, 1% to 16%). Significantly fewer EGFR mutations were found in people who smoked for more than 15 pack-years (P < .001) or stopped smoking less than 25 years ago (P < .02) compared with individuals who never smoked. The number of smoking pack-years and smoke-free years predicted the prevalence of EGFR mutations (areas under receiver operating characteristic curve = 0.78 and 0.77, respectively). Conclusion The likelihood of EGFR mutations in exons 19 and 21 decreases as the number of pack-years increases. Mutations were less common in people who smoked for more than 15 pack-years or who stopped smoking cigarettes less than 25 years ago. These data can assist clinicians in assessing the likelihood of exon 19 and 21 EGFR mutations in patients with lung adenocarcinoma when mutational analysis is not feasible.

scholarly journals Simplified Molecular Classification of Lung Adenocarcinomas Based on EGFR, KRAS, and TP53 Mutations

2019 ◽  
Author(s):  
Roberto Ruiz-Cordero ◽  
Junsheng Ma ◽  
Abha Khanna ◽  
Genevieve Ray Lyons ◽  
Waree Rinsurongkawong ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Survival Data ◽  
Molecular Subtypes ◽  
Stage Iv ◽  
Molecular Classification ◽  
Smoking History ◽  
Egfr Mutations ◽  
Prognostic Features ◽  
Mutational Status

Abstract Introduction: Gene expression profiling has consistently identified three molecular subtypes of lung adenocarcinoma that have prognostic implications. To facilitate stratification of patients with this disease into similar molecular subtypes, we developed and validated a simple, mutually exclusive classification. Methods: Mutational status of EGFR, KRAS, and TP53 was used to define six mutually exclusive molecular subtypes. A development cohort of 283 cytology specimens of lung adenocarcinoma was used to evaluate the associations between the proposed classification and clinicopathologic variables including demographic characteristics, smoking history, fluorescence in situ hybridization and molecular results. For validation and prognostic assessment, 63 of the 283 cytology specimens with available survival data were combined with a separate cohort of 428 surgical pathology specimens of lung adenocarcinoma. Results: The proposed classification yielded significant associations between these molecular subtypes and clinical and prognostic features. We found better overall survival in patients who underwent surgery and had tumors enriched for EGFR mutations. Worse overall survival was associated with older age, stage IV disease, and tumors with co- mutations in KRAS and TP53. Interestingly, neither chemotherapy nor radiation therapy showed benefit to overall survival. Conclusions: The mutational status of EGFR, KRAS, and TP53 can be used to easily classify lung adenocarcinoma patients into six subtypes that show a relationship with prognosis, especially in patients who underwent surgery, and these subtypes are similar to classifications based on more complex genomic methods reported previously.

scholarly journals Simplified Molecular Classification of Lung Adenocarcinomas Based on EGFR, KRAS, and TP53 Mutations

2019 ◽  
Author(s):  
Roberto Ruiz-Cordero ◽  
Junsheng Ma ◽  
Abha Khanna ◽  
Genevieve Ray Lyons ◽  
Waree Rinsurongkawong ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Survival Data ◽  
Molecular Subtypes ◽  
Stage Iv ◽  
Molecular Classification ◽  
Smoking History ◽  
Egfr Mutations ◽  
Prognostic Features ◽  
Mutational Status

Abstract Background: Gene expression profiling has consistently identified three molecular subtypes of lung adenocarcinoma that have prognostic implications. To facilitate stratification of patients with this disease into similar molecular subtypes, we developed and validated a simple, mutually exclusive classification. Methods: Mutational status of EGFR, KRAS, and TP53 was used to define seven mutually exclusive molecular subtypes. A development cohort of 283 cytology specimens of lung adenocarcinoma was used to evaluate the associations between the proposed classification and clinicopathologic variables including demographic characteristics, smoking history, fluorescence in situ hybridization and molecular results. For validation and prognostic assessment, 63 of the 283 cytology specimens with available survival data were combined with a separate cohort of 428 surgical pathology specimens of lung adenocarcinoma. Results: The proposed classification yielded significant associations between these molecular subtypes and clinical and prognostic features. We found better overall survival in patients who underwent surgery and had tumors enriched for EGFR mutations. Worse overall survival was associated with older age, stage IV disease, and tumors with co-mutations in KRAS and TP53. Interestingly, neither chemotherapy nor radiation therapy showed benefit to overall survival. Conclusions: The mutational status of EGFR, KRAS, and TP53 can be used to easily classify lung adenocarcinoma patients into seven subtypes that show a relationship with prognosis, especially in patients who underwent surgery, and these subtypes are similar to classifications based on more complex genomic methods reported previously.

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.

Clinical characteristics and anti-PD-(L)1 treatment outcomes of KRAS-G12C mutant lung cancer compared to other molecular subtypes of KRAS-mutant lung cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9596-9596
Author(s):  
Kathryn Cecilia Arbour ◽  
Hira Rizvi ◽  
Andrew J. Plodkowski ◽  
Darragh Halpenny ◽  
Matthew David Hellmann ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Clinical Characteristics ◽  
Cox Proportional Hazards Model ◽  
Smoking History ◽  
Exact Test ◽  
Fisher's Exact Test ◽  
Fisher’S Exact Test ◽  
Baseline Characteristics ◽  
Direct Inhibitors

9596 Background: KRAS mutations are identified in approximately 30% of NSCLC. There are no FDA approved targeted therapies for patients with KRAS-mutant non-small cell lung cancer (NSCLC) but novel direct inhibitors of KRAS G12C have shown some activity in early phase clinical trials. We hypothesized that patients with KRAS-G12C mutations may have distinct clinical characteristics and responses to systemic therapies compared to patients with non-G12C subtypes. Methods: We identified patients with KRAS-mutant lung cancers who underwent next-generation sequencing with MSK-IMPACT, between January 2014 and December 2018. Baseline characteristics were compared with the Chi-square and Fisher’s exact test for categorical data and Wilcoxon rank-rum test for continuous data. Overall survival was calculated from time of diagnosis of metastatic/recurrent disease to date of death or last follow up, with left truncation to account for time of MSK-IMPACT. Overall survival was compared between groups using the Cox proportional-hazards model. Response evaluations where performed by independent thoracic radiologists according to RECIST 1. and compared between group with the Fisher’s exact test. Results: We identified 1194 patients with KRAS -mutant NSCLC, 772 with recurrent or metastatic disease. Of patients with advanced disease, 46% (352/772) had mutations in KRAS-G12C and 54% harbored non-G12C mutations (15% G12D, 16% G12V, 8% G12A, 4% G13D). Co-mutation patterns were similar with respect to KEAP1 (p=0.9) and STK11 (p=1.0). Patients with non-G12C mutations had a higher proportion of never smokers (10% vs 1.4% p<0.001). The median OS from diagnosis was 13 months for G12C and non-G12C patients (p=0.99). 45% (347/772) received 1L or 2L line treatment with PD-(L)1 inhibitor. RECIST measurements were available for 290/347 cases (84%). ORR with anti-PD-(L)1 treatment was 24% vs 28% in G12C vs non-G12C patients (p=0.5). In patients with PD-L1 50% (n=103), ORR was 39% for G12C vs 58% non-G12C patients (p=0.06). Conclusions: KRAS G12C mutations are present in 12% of patients with NSCLC and represent a relevant subtype of NSCLC given KRAS G12C inhibitors now in clinical development. Baseline characteristics including co-mutation patterns are similar between patients with G12C and non-G12C, except for smoking history. The efficacy of KRAS G12C direct inhibitors will need to be compared to other available therapies for KRAS mutant NSCLC (chemotherapy and PD-(L)1 inhibitors) to identify most effective therapeutic strategy.

Standard-Dose Osimertinib in EGFR-Mutated Non–Small-Cell Lung Adenocarcinoma With Leptomeningeal Disease

2021 ◽  
pp. 561-568
Author(s):  
Luke S. McLean ◽  
Wasek Faisal ◽  
Sagun Parakh ◽  
Steven C. Kao ◽  
Craig R. Lewis ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Median Overall Survival ◽  
Treatment Options ◽  
Eastern Cooperative Oncology Group ◽  
Small Cell ◽  
Leptomeningeal Disease ◽  
Small Cell Lung ◽  
Egfr Mutated

PURPOSE Leptomeningeal disease (LMD) in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma is associated with a poor prognosis and limited treatment options. Osimertinib is a potent third-generation EGFR tyrosine kinase inhibitor with confirmed CNS penetration. This study reports on outcomes of patients with EGFR-mutated non–small-cell lung cancer who developed LMD and were subsequently treated with osimertinib. METHODS We identified patients treated with osimertinib 80 mg PO daily under a compassionate access scheme across nine tertiary Australian institutes between July 2017 and July 2020. Patient demographics, tumor characteristics, and treatment history were collected. Median overall survival, median progression-free survival, disease control rates (DCR), and overall response rates (ORR) were assessed. Kaplan-Meier analysis was performed and descriptive statistics were used. RESULTS Thirty-nine patients were analyzed of which 74% were female. Exon 19 deletions (49%) and L858R point mutations (41%) were the most common EGFR mutations. Forty-nine percentage of patients were Eastern Cooperative Oncology Group 1. The median duration of osimertinib therapy was 6 months. The extracranial DCR and ORR were 60% and 54%, and the intracranial DCR and ORR were 68% and 53%, respectively. Median overall survival was 10.5 months (95% CI, 8.17 to 15.05 months). CONCLUSION There are limited treatment options for LMD in EGFR-positive lung cancer, and osimertinib at a dose of 80 mg daily is an active therapeutic option for these patients.

scholarly journals Simplified Molecular Classification of Lung Adenocarcinomas Based on EGFR, KRAS, and TP53 Mutations

2020 ◽  
Author(s):  
Roberto Ruiz-Cordero ◽  
Junsheng Ma ◽  
Abha Khanna ◽  
Genevieve Ray Lyons ◽  
Waree Rinsurongkawong ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Survival Data ◽  
Molecular Subtypes ◽  
Stage Iv ◽  
Molecular Classification ◽  
Smoking History ◽  
Egfr Mutations ◽  
Prognostic Features ◽  
Mutational Status

Abstract Background: Gene expression profiling has consistently identified three molecular subtypes of lung adenocarcinoma that have prognostic implications. To facilitate stratification of patients with this disease into similar molecular subtypes, we developed and validated a simple, mutually exclusive classification. Methods: Mutational status of EGFR , KRAS , and TP53 was used to define seven mutually exclusive molecular subtypes. A development cohort of 283 cytology specimens of lung adenocarcinoma was used to evaluate the associations between the proposed classification and clinicopathologic variables including demographic characteristics, smoking history, fluorescence in situ hybridization and molecular results. For validation and prognostic assessment, 63 of the 283 cytology specimens with available survival data were combined with a separate cohort of 428 surgical pathology specimens of lung adenocarcinoma. Results: The proposed classification yielded significant associations between these molecular subtypes and clinical and prognostic features. We found better overall survival in patients who underwent surgery and had tumors enriched for EGFR mutations. Worse overall survival was associated with older age, stage IV disease, and tumors with co-mutations in KRAS and TP53 . Interestingly, neither chemotherapy nor radiation therapy showed benefit to overall survival. Conclusions: The mutational status of EGFR , KRAS , and TP53 can be used to easily classify lung adenocarcinoma patients into seven subtypes that show a relationship with prognosis, especially in patients who underwent surgery, and these subtypes are similar to classifications based on more complex genomic methods reported previously.

Influence of smoking dose on the outcome of Japanse patients with non-small cell lung cancer who had gefitinib treatment

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19004-e19004
Author(s):  
K. Asami ◽  
M. Kawahara ◽  
S. Atagi ◽  
T. Kawaguchi ◽  
A. Kubo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Prognostic Factor ◽  
Egfr Mutation ◽  
Small Cell ◽  
Smoking History ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Significant Difference ◽  
Heavy Smokers

e19004 Background: Non-smoking history and epidermal growth factor receptor (EGFR) mutation are associated with increased sensitivity to gefitinib in non-small cell lung cancer (NSCLC). However, it is still unclear how much smoking dose is associated with survival and response to gefitinib among smokers. Methods: NSCLC patients (pts) with detailed smoking history who received gefitinib at our institution between 9/02 and 9/04 were reviewed. An analysis was conducted to the pts for association between smoking dose, EGFR mutations, performance status (PS), response and overall survival using multivariate analysis. Results: Data were available for 100 pts including 30 females and 70males. We expressed smoking dose as pack year (Py).The median dose of smoking was 32 Py (0.1–100 Py). We defined the group of <10 Py as light smokers(17 pts) and the other group of 10 Py or more as heavy smokers(83 pts). We detected 31(31%) EGFR mutation (median 14 Py 0.1–75 Py) with exon 18 / 19 /21 mutation;3/17/11 pts .Cox survival analysis showed that overall survival was preferably associated with small dose of smoking(<10 Py)(HR=0.505; [95% CI 0.277–0.921; P=0.013]), EGFR mutation(HR=0.452[95% CI 0.235–0.87;P=0.035])and PS;0–1(HR=0.347 [95% CI 0.207–0.583 P<0.001]). EGFR mutations were significantly more frequently observed in light (12/17:71%) than heavy smokers(19/83:23%) (p<0.001). Disease control rate(DCR) was significantly higher in light (13/17;76%;PR 6, SD 7) than heavy smokers(29/83;35%;PR 15, SD 14)(P=0.002), but there was not significant difference between those groups in terms of response rate (RR)(P=0.187). There were significant differences between pts with EGFR mutations (PR 13 SD 14; RR 42%,DCR 87%) and pts without EGFR mutations (PR 8 SD 15; RR 12%, DCR 33%) in terms of RR(P<0.001) and DCR(P<0.001). In pts with EGFR mutation, there was no significant difference between light and heavy smokers in terms of RR (light smokers 5/10, heavy smokers 8/21; P=0.701) and DCR (light smokers 10/10, heavy smokers17/21; P= 0.277). Conclusions: EGFR mutations were predictive factor and prognostic factor. Small dose of smoking (< 10 Py) was prognostic factor, however it was not a predictive factor of smokers with NSCLC. No significant financial relationships to disclose.

Frequency and clinical characterization of NSCLC patients harboring PIK3CA mutations identified within a regional screening network.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10526-10526
Author(s):  
Masyar Gardizi ◽  
Matthias Scheffler ◽  
Lukas Carl Heukamp ◽  
Marc Christiaan Allardt Bos ◽  
Kerstin Albus ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Smoking Status ◽  
Tnm Classification ◽  
Tumor Stage ◽  
High Load ◽  
Egfr Mutations ◽  
Braf Mutations ◽  
Pik3ca Mutations ◽  
Exon 9

10526 Background: PIK3CA mutations are a rare oncogenic event of potential therapeutic relevance in NSCLC. Here we report frequency and characteristics of patients with PIK3CA mutated lung tumors. Methods: Patients with NSCLC and PIK3CA mutations were identified within our regional Network for Molecular Screening in Lung Cancer. We further analyzed the presence of BRAF, KRAS, EGFR mutations as well as ALK translocation, ERBB2 and FGFR1 amplifications in PIK3CA mutated samples. Clinical data on age, sex, TNM classification and tumor stage, histological type, grading, overall survival, smoking status, comorbidity, BMI and secondary malignancies were retrieved from clinical charts in accordance with the local ethics committee. Results: PIK3CA mutations were detected with a frequency of 3.7% (24% exon 20,76% exon 9) in 1000 patients. Histologically 32% were defined as squamous cell carcinoma, 48% as adenocarcinoma and 18% other histological subtypes or NSCLC-NOS. Exon 9 mutations were present in the acinar and lepidic subtype, whereas exon 20 mutations were seen in the papillary and solid subtype. Cooccuring genetic lesions were observed in 16% (mutations in KRAS=2, EGFR=1, BRAF=1; FGFR1 amplification=2). 14 were female, 23 male with a mean age of 69 years. 21 of these patients were further clinically annotated. 11 patients presented with stage IIIb/IV eligible for palliative treatment and 10 stage I – IIIa eligible for surgical therapy +/- adjuvant therapy. All but 1 patient were smokers with an average BMI of 26,2kg/m2 with a typical high load of comorbidity mainly of cardiovascular diseases, 8 of 21 patients showed prior malignancies in their medical history. The median overall survival within this population has not been reached yet. Conclusions: Screening for PIK3CA mutations is feasible. A high proportion (38%) of patients with PIK3CA mutated lung cancer have prior malignancies and show a high load of comorbidity. Furthermore PIK3CA mutations are not exclusive to KRAS, EGFR or BRAF mutations or FGFR1 amplifications. Successful identification of patients with oncogenic lesions in lung cancer in a screening network might allow future personalized treatment of these patients.

ALK and MET genes in advanced lung adenocarcinomas: The Lung Cancer Mutation Consortium experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7589-7589 ◽  
Author(s):  
Marileila Varella-Garcia ◽  
Lynne D Berry ◽  
Pei-Fang Su ◽  
Wilbur A. Franklin ◽  
A. John Iafrate ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Gene Amplification ◽  
Therapy Response ◽  
Complete Response ◽  
Age At Diagnosis ◽  
Smoking History ◽  
Heavy Smoking ◽  
Cancer Mutation ◽  
Lung Adenocarcinomas

7589 Background: The Lung Cancer Mutation Consortium (LCMC) consisting of 14 US Cancer Centers was established to evaluate a panel of molecular mutations in advanced lung adenocarcinoma. ALK gene fusions and MET gene amplification were assessed by FISH in CLIA certified laboratories. Methods: Molecular tests were performed in stage IIIB or IV lung adenocarcinoma. To date, FISH assays have been completed in 901 patients for ALK (ALK break-apart, Abbott Molecular) and in 654 patients for MET (in house/Abbott Molecular reagents). ALK+ specimens were defined by split 3’ALK/5’ALK signals (gap >2 signal diameters) or single 3’ALK signals in >15% of tumor cells. MET gene amplification (MET+) was defined by ratio mean MET/mean CEP7 ≥2. Results: The ALK+ patient subset (N=75, 8.3%) compared to the ALK- had significantly lower age at diagnosis (52 vs. 60, p<0.001) and less frequent heavy smoking history (61% never-smokers among ALK+ vs. 31% among ALK-, p<0.001; pack-year for current/former smokers 17 vs. 40, p=0.003). Liver metastases were significantly more frequent among ALK+ than ALK- (23% vs.10%, p=0.004); no difference was detected in bone, brain and adrenal gland metastases. MET+ (N=29, 4.4%) was significantly associated with female sex (72% female among MET+ vs. 39% among MET-, p<0.001) and marginally more frequent in patients with adrenal metastasis; no difference was detected for age at diagnosis and smoking history. Follow-up on 73 ALK+ patients indicated that 56% received crizotinib as targeted therapy. Response was unknown in 8% and unreportable in 22% patients enrolled in ongoing randomized trials. Among patients with evaluable response, complete response, partial response, stable disease, and progressive disease were found respectively in 3%, 66%, 28%, and 3%. Conclusions: The LCMC successfully tested ALK and MET FISH in a large number of lung adenocarcinomas. It was demonstrated that directing positive patients to specific interventions is feasible, and that grouping of testing and trials within consortia may maximise relevant trial accrual in rare molecular subtypes. Supported by NCI-GO award. Submitted on behalf of the LCMC.

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