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R. Guleria



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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
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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): R. Guleria

      • 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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    P1.06 - Poster Session with Presenters Present (ID 458)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P1.06-011 - Altered Body Composition and Fat Loss in Advanced Non-Small Cell Lung Cancer (ID 4212)

      14:30 - 14:30  |  Author(s): R. Guleria

      • Abstract

      Background:
      Assessment of body composition, including fat mass and fat%, is a useful measure of nutritional status in cancer and may help guide nutritional interventions. However, these abnormalities have not been well documented in lung cancer. We aimed to study alterations in parameters of body composition in Non small cell lung cancer (NSCLC).

      Methods:
      A retrospective chart review was conducted of all newly diagnosed patients with NSCLC. Age and sex matched healthy controls were recruited prospectively. Disease staging was done according to the American Joint Committee on Cancer (7th edition). Performance status was asssessed using the Karnofsky performance Scale(KPS), and the Eastern Cooperative Oncology Group (ECOG). Details of body composition including basal Metabolic Rate (BMR), total body water (TBW), fat mass, and Fat-free mass (FFM) were calculated by bioelectric impedance method using TANITA TBF 300 body composition analyzer.

      Results:
      A total of 256 patients (83.6% males) and 211 controls (81.5% males) were studied. The mean (SD) age of patients was 54.5(9.0) years, median smoking index was 598 (range, 0-2500) and mean duration of symptoms was 158.3(91.7) days. Median KPS was 80 (range, 40-100). Majority had Stage IV disease (54.7%), followed by Stage III (41.4%) and Stage II (3.9%). All measured components of body composition were significantly lower in NSCLC compared to controls (Table).Among patients with normal body weight (BMI 18.5 – 25 kg/m[2]), the TBW and FFM were significantly lower compared to their healthy counterparts. Figure 1



      Conclusion:
      NSCLC is associated with significant malnutrition and altered body composition, especially reduction in the percentage of body fat. Nutritional interventions must, therefore, be tailored accordingly for these patients.

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    P2.01 - Poster Session with Presenters Present (ID 461)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Biology/Pathology
    • Presentations: 2
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      P2.01-007 - Detection of Promoter DNA Methylation of APC, DAPK, and GSTP1 Genes in Tissue Biopsy and Matched Serum of Advanced Stage Lung Cancer Patients (ID 5595)

      14:30 - 14:30  |  Author(s): R. Guleria

      • Abstract

      Background:
      Promoter DNA hypermethylation is a well characterized epigenetic event and has been linked with early stages of lung carcinogenesis through inactivation of tumor suppressor genes. In this study, we studied the methylation status of APC, DAPK, and GSTP1 genes in tissue biopsy and serum of lung cancer patients and cancer-free controls.

      Methods:
      In this prospective study, 160 primary lung cancer patients and 70 cancer-free controls undergoing bronchoscopy for benign disease were recruited. DNA was isolated from tissue biopsy and serum of all the subjects and methylation-specific PCR of APC, DAPK, and GSTP1 was carried out after bisulfite conversion. Association of DNA methylation with various clinico-pathological parameters and survival was determined in lung cancer patients.

      Results:
      The methylation rates of APC, DAPK, and GSTP1 in tissue biopsy were 83.1%, 83.1%, and 78.1% for lung cancer patients and 72.9%, 70%, and 70% for cancer-free controls. The methylation rates of APC, DAPK, and GSTP1 in serum were 52.5%, 30.6%, and 65.6% for lung cancer patients and 14.3%, 18.6%, and 30% for cancer-free controls. In lung cancer patients, all three genes were methylated at significantly higher frequency in tissue biopsy than matched serum samples. No significant correlation was observed between methylation of any of three genes with clinico-pathological parameters, including survival.

      Conclusion:
      Present study did not demonstrating any evidence suggesting the role of promoter DNA methylation of APC, DAPK, and GSTP1 in lung carcinogenesis. However, follow-up of cancer-free controls, who were positive for DNA methylation, is required to confirm their role in early stages of lung carcinogenesis.

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      P2.01-011 - Identification of Differentially Expressed Circulating miRNAs in the Serum of NSCLC Patients Using next Generation Sequencing (ID 4016)

      14:30 - 14:30  |  Author(s): R. Guleria

      • Abstract

      Background:
      Aberrant expression of miRNAs has been found in human cancers and has not only been used as diagnostic, prognostic, and predictive biomarkers, but also as potential therapeutic target. In this study, we compared the expression profile of miRNAs in the serum of NSCLC patients with that of non-malignant respiratory disease patients and healthy controls.

      Methods:
      For this prospective pilot study, a total of 10 subjects were recruited, 2 each of lung adenocarcinoma (ADC), squamous cell carcinoma (SQC), pulmonary tuberculosis (TB), chronic obstructive pulmonary disease (COPD), and healthy controls, from Outpatient Department of Pulmonary Medicine and Sleep Disorders, AIIMS, New Delhi. Approximately 5 ml. of peripheral blood was collected; serum was separated and total RNA was isolated using miRNeasy serum/plasma kit (QIAGEN). Small RNAs were purified from total RNA; libraries of 18 to 50 nt small RNAs were prepared with the TruSeq RNA Library Prep Kit (Illumina), and mature miRNAs were profiled using illumina TruSeq Sequencing Chemistry on illumina HiSeq 2000 next generation sequencing (NGS) platform. Quality check was performed and high quality raw data was mapped on to miRBase database. The expression profile of miRNAs in each subject was analyzed using miRNAkey software and fold change was performed to identify differentially expressed miRNAs in NSCLC as compared to controls.

      Results:
      Using NGS, we were able to detect 1074, 1013, 299, 268, and 907 known miRNAs in the serum of lung ADC, SQC, TB, COPD and healthy controls, respectively. A number of miRNAs, such as let-7, miR-10b-5p, miR-15a-5p, miR-23b-5p, miR-92a-3p, miR-148b-3p, miR-185-3p, miR-192-5p, miR-320a, miR-329-3p, miR-342-3p, miR-375, miR-449a, miR-486-5p, miR-497-5p, miR-584-3p, miR-1908-5p, and miR-3195 were found to be downregulated, while miR-10a-5p, miR-148a-3p, and miR-197-3p were found to be upregulated in NSCLC as compared to non-malignant respiratory disease controls and healthy controls (>2 fold change; p<0.05). Further, few miRs, including miR-93-3p, miR-130b-5p, miR-196b-5p, miR-337-3p, miR-378f, miR-382-5p, miR-424-3p, and miR-1271-3p were found to be specifically expressed in NSCLC.

      Conclusion:
      A number of miRNAs were found to be dysregulated in the serum of NSCLC patients than controls. The present study is being continued in a larger set of subjects to validate the findings & also the expression patterns of target genes of differentially expressed miRNAs is being analyzed by real-time reverse-transcriptase PCR to find their relevance in lung carcinogenesis. This may prove to be useful for developing non-invasive diagnostic and prognostic tools as well as tools to monitor therapeutic efficacy in NSCLC.

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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
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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): R. Guleria

      • 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.