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K. Madan
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P1.02 - Poster Session with Presenters Present (ID 454)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 2
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.02-028 - Detection of Oncogenic Drivers in Pleural Effusions and Archived FNA Smears of Pulmonary Adenocarcinoma (ID 5176)
14:30 - 14:30 | Author(s): K. Madan
- Abstract
Background:
Cytological materials are widely used in diagnosis and staging of lung cancer due to advanced stage of disease at the time of presentation. Mutational oncogenic drivers in pulmonary adenocarcinoma (ADC) include EGFR, Kras and Her-2/neu. We utilized archived FNA smears and pleural effusion samples of ADC for detection of oncogenic molecular drivers.
Methods:
Pleural fluids (36) and May Grunwald stained FNA smears (18) were used for mutation anaysis. Sanger sequencing and ARMS and Scorpions PCR performed. Each tumor sample was evaluated for all classes of genomic alterations, including base-pair substitutions, insertions/deletions, as well as intronic/CDS polymorphisms.
Results:
There were 31 males and 23 females, aged 18 to 82 years with mean age 65.5 years. A total of 9 patients (16.6%) were found positive for EGFR mutations (Table 1, Figure 1). EGFR exon 18 intronic poylmorphism was seen in 4 cases and EGFR exon 20 showed intronic and CDS polymorphism in most cases. However, none of the cases were found to be positive for EGFR, exon 18, 20, Kras and Her-2/neu mutation. Figure 1 Figure 2
Conclusion:
These findings verify the feasibility of analysis of oncogenic drivers in cytological specimens in advanced ADC. Stained aspiration smears can be used after establishing diagnosis and checking adequacy of the specimen.
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P1.02-038 - Over- Expression of Epidermal Growth Factor Receptor 1 (EGFR1) Gene in Serum of Adenocarcinoma Lung at a Tertiary Level Centre in North India (ID 5583)
14:30 - 14:30 | Author(s): K. Madan
- Abstract
Background:
Epidermal growth factor receptor (EGFR) is a cell surface protein that binds to epidermal growth factor. Over expression of EGFR1 in tumor tissue has been observed in upto 65% of advanced non small cell lung cancer, and has shown promising prognostic potential. In this study, we compared the EGFR1 gene expression in serum adenocarcinoma lung with healthy controls.
Methods:
We analyzed 61 newly diagnosed patients of adenocarcinoma lung and 50 healthy controls. RNA was isolated from blood serum of all subjects and real time PCR (RT- PCR) was performed after complementary DNA (cDNA) synthesis. The level of EGFR1 expression in serum was calculated by relative quantification method and expressed as fold-increase compared to compared with controls. Expression levels were also correlated with various clinico- pathological parameters.
Results:
Out of 61 patients, 42 were males. The mean (SD) age of the entire group was 54.5 (11.5) years. Most of the patients (79%) had stage IV disease. 23 (38%) patients were current/ ex- smokers, with median pack years of 10 (range, 0.5- 100). Majority of patients had KPS of 90 (51%) and ECOG 1 (74%) respectively. Activating mutations in EGFR were observed in the tissue of 14 (21.3%) of 61 patients; of these, 9 were exon- 19 deletions and 4 were exon- 21 point mutations. In the patients, a 19.66 mean- fold increase in serum EGFR gene expression was observed compared to healthy controls. No significant association was found between EGFR expression and other variables i.e., sex, age, smoking habit, performance status, stage of disease and EGFR mutation status.
Conclusion:
Serum EGFR1 gene was over expressed by >16 fold in advanced adenocarcinoma lung compared to healthy controls. The association of EGFR expression with other clinical disease characteristics needs further exploration.
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P3.01 - Poster Session with Presenters Present (ID 469)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.01-025 - Primary Pulmonary Sarcomas: An Entity Lost in Misdiagnosis (ID 5930)
14:30 - 14:30 | Author(s): K. Madan
- Abstract
Background:
Primary pulmonary sarcomas are very rare with an incidence rate of <0.5% of all lung malignancies. Their low incidence has impeded comprehensive evaluation of their association with smoking, definitive diagnostic and treatment-regimes. They are often misdiagnosed, both on radiology as well as on fine-needle-aspirate/small-biopsies. We present a series of primary pulmonary sarcomas diagnosed over the last two and a half years.
Methods:
All cases of primary pulmonary sarcomas (2014-2016) were retrieved and reviewed.
Results:
A total of 21 sarcomas were identified. The most common was synovial sarcoma. Four exceptionally rare cases included pulmonary-artery intimal sarcoma, primary pulmonary myxoid sarcoma, malignant peripheral nerve-sheath tumor and follicular dendritic-cell sarcoma. The clinical and pathology details of which are provided in table1. The patients were distributed over a wide-age range (range:9-65 years, median:34 years) with a male-preponderance (M:F=2.2:1). Radiological features were non-specific except in case1(table1). Histopathology revealed spindle-cell tumor in all cases(figure1) and an extensive immunohistochemical-panel and cytogenetic testing was required to clinch the diagnosis. Figure 1 Figure 2
Conclusion:
This is a series of primary thoracic sarcomas with a highlight on four extremely rare cases which bring to light their unique clinical, radiological, histopathological and immunohistochemical findings. Awareness of such entities is essential for proper diagnosis, appropriate molecular-testing and treatment.
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-037 - Does Tissue EGFR Mutation Status Predict Treatment Response and Mortality in Adenocarcinoma Lung? (ID 4836)
14:30 - 14:30 | Author(s): K. Madan
- Abstract
Background:
Targeted therapy with tyrosine kinase inhibitors (TKI) in EGFR positive patients is associated with superior response rates in Caucasian and East Asian populations. Whether similar response is observed in Asian Indians with lung cancer is not yet clear. We aimed to compare the response rates and survival between EGFR positive and negative patients with advanced adenocarcinoma lung at a tertiary level centre in North India.
Methods:
Treatment naive patients of adenocarcinoma lung were recruited. All patients underwent complete staging and tissue EGFR mutation analysis using DNA extraction and Polymerase chain reaction. EGFR positive patients were treated with oral Gefitinib 250 mg once daily and EGFR negative patients with 3-weekly cycles of platinum based doublet chemotherapy. Treatment response was evaluated after 3 months of Gefitinib or after 4 cycles of chemotherapy using CT-PET scan and categorized as Complete metabolic remission (CR), partial response (PR), stable disease (SD), and progressive disease (PD). The proportion of responders (CR + PR) and non-responders (SD+PD), and short term survival at 3 months were compared between EGFR positive and negative patients.
Results:
59 patients completed response evaluation at 3 months / 4 cycles. These included 41 males (59.5%), with a mean (SD) age 55.9 (11.2) years. Majority (89.4%) had metastatic stage IV disease. 34 patients (67.5%) were current or previous smokers, with median smoking index of 400 (range, 0-1500). 76% patients had KPS of 80 or above, and 78% had ECOG of 0-1. Overall, 17 patients (29.3%) were tissue EGFR positive for either of exons 18, 19, or 21. The 3-month outcomes in EGFR positive and negative groups were: complete response – 1.6% vs 0 %, partial response - 61 % vs 24.4%, stable disease – 5.6% vs 26.8%, progressive disease – 11.1% vs 17.1%, and mortality in 16.7% vs 31.7% respectively. EGFR positive group had higher responders compared to EGFR negative patients (p=0.002) although mortality rate did not differ significantly.
Conclusion:
EGFR mutation positive patients treated upfront with TKI are more likely to show objective response at three months and demonstrate a trend towards lower mortality compared to EGFR negative patients treated with conventional chemotherapy.
