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M.A. Castro
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P1.02 - Poster Session with Presenters Present (ID 454)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.02-010 - Frequency of Uncommon EGFR Mutations in NSCLC in an Argentinean University Institution (ID 4405)
14:30 - 14:30 | Author(s): M.A. Castro
- Abstract
Background:
EGFR mutations are present in approximately 15% of NSCLC Caucasian patients, with a similar frequency described in Argentina.Exon 19 deletions and exon 21 L858R are consider common mutations (>90 %) that predict better progression free survival with EGFR-TKIs than with chemotherapy treatment. Most relevant uncommon mutations had a frequency ranged from 1.9% to 7.9% between different populations and their outcome, in general, is less favorable.
Methods:
We analyzed, retrospectively, our dataset of EGFR mutational status in the last two years with the objective to describe the frequency and characteristics of the patients with uncommon EGFR mutations in our population of NSCLC patients. The mutational analysis was performed on formalin fixed paraffin-embedded tissue blocks. EGFR exons 18 through 21 were amplified by PCR- based technology.
Results:
A total of 113 patients underwent EGFR testing since January 2014 until June 2016. Among them, 29 cases (25.7 %) harbored EGFR mutations. The exon 19 deletions (n=9; 8%) and L858R point mutation (n=6; 5.3%) accounted for the 51.7 % of EGFR mutated cases (13.3% of the population explored) while 48.3 % were uncommon mutations (12,4%). In the last group, mutations sites were: G719X in exon 18 (n=9; 8%), L861Q in exon 21 (n=2; 1.8%), INS20 in exon 20 (n=2; 1.8%) and S768I in exon 20 (n=1; 0.9%). All the 14 patients carrying EGFR uncommon mutations had adenocarcinoma histology. In addition, they were more frequently observed in men than in women (79% versus 21%) and in smokers than in nonsmokers (65% versus 45%). The mean age was 62.5 years. Most of the patients (n=11; 75.6%) had advanced disease (stage IIIB-IV) at diagnosis. No one had Asian ethnicity. Seven patients (50%) received EGFR-TKIs for first or second line treatment (4 erlotinib, 2 afatinib and 1 gefitinib). None of them showed sustained clinical benefit. At present, 7 out of 12 patients had died.
Conclusion:
Although the clinical characteristics of our cohort are similar to the data published, we noted a higher and unusual frequency of EGFR uncommon mutations especially exon 18 G719X.All cases treated with EGFR-TKIs showed poor sensitivity to therapy. Time to treatment and accessibility to appropriate therapy in this subgroup are important issues to explore in future reports from public institutions of our region.
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P2.01 - Poster Session with Presenters Present (ID 461)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.01-085 - Epigenetic Profile of Oligoprogressive versus Widespread Non-Small Cell Lung Cancer Patients (ID 4669)
14:30 - 14:30 | Author(s): M.A. Castro
- Abstract
Background:
Lung cancer is the worldwide leading cause of death from cancer. Epigenetic silencing of tumor suppressor genes (TSG) contributes to the development and progression of lung cancer. In this prospective study we assess the methylation profile of locally advanced and oligometastatic versus widespread metastatic Non-Small Cell Lung Cancer (NSCLC). We will determine the ability of a panel of tumor suppressor genes (TSG) to discriminate these clinical phenotypes
Methods:
Patients (≥18 years) were eligible for inclusion if they had histologically confirmed unresectable non-pretreated stage III/IV NSCLC. Paraffin-embedded blocks from patients from this study cohort were macro-dissected based on hematoxylin-eosin evaluations to ensure a minimum of 75% of tumor cells. DNA was extracted. Promoter methylation status of TSG (SFRP5, TIMP3, HLTF, RUNX3, ID4) will be evaluated by EpiTect Methyl II Signature PCR (Qiagen). Data analysis was done using integrated Excel-based templates, which provide gene methylation status as percentage unmethylated (UM) and percentage methylated (M) fraction of input DNA. Methylation levels were described as: ³1-19%: low methylation level, 20-59%: moderate methylation level and ³60%: high methylation level. Presence of intrathoracic disease and limited extrathoracic disease, (M1b, proposed 8th TNM edition) vs multiple metastatic disease (M1c) was described for clinical and molecular analysis.
Results:
From March 2015 to June 2016, 40 out of 60 sixty patients had enough tissue to be included. Intrathoracic disease was present in 19 patients (47.5%), M1b disease in 8(20%) and 13 patients (32.5%) had multiple extrathoracic disease. The methylation profile for intrathoracic disease was: SFRP5 was found in 4/19 patients (21.1%), ID4 7/19 (36.6%), HLTF 12/19 (63.2%), RUNX3 19/19 (100%) and TIMP3 10/19 (52.6%); for M1b disease: SFRP5 was found in 4/8 patients (50%), ID4 3/8 (37.5%), HLTF 6/8 (75%), RUNX3 6/8 (75%) and TIMP3 7/8 (87.5%); for M1c disease: SFRP5 6/13 patients (46.2%), ID4 9/13 (69.2%), HLTF 11/13 (84.6%), RUNX3 13/13 (100%) and TIMP3 8/13 (61.5%). Overall survival was shortened for the group of patients with methylation of ID4³20% (14.5 vs 19 months, p=0.010 Log Rank Test). In the subgroup analysis this difference was sustained for patients with oligoprogressive disease (Intrathoracic plus IVb) vs IVc (9.5 vs 17.5 months, p=0.05 Log Rank Test vs 14 vs 19 months , p=0.51, respectively)
Conclusion:
Although no definitive conclusions can be done because of the sample size, it seems that patients with methylation of ID4 of 20% or more have worse prognosis. ID4 could also help to differentiate oligometastatic vs widespread NSCLC
