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Sita Andarini



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    MA 04 - Advocacy: Listen to the Patients (ID 655)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Patient Advocacy
    • Presentations: 1
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      MA 04.12 - Discussant - MA 04.09, MA 04.10, MA 04.11 (ID 10864)

      12:10 - 12:25  |  Presenting Author(s): Sita Andarini

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    P1.02 - Biology/Pathology (ID 614)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P1.02-065 - Histone Deacetylase Inhibition Alters Stem Cell Phenotype in Gefitinib-Resistant Lung Cancer Cells with EGFR Mutation (ID 7401)

      09:30 - 09:30  |  Author(s): Sita Andarini

      • Abstract

      Background:
      Cancer stem cells (CSCs) are epigenetically altered by histone deacetylase (HDAC), resulting in chromatin condensation. We have reported that gefitinib-resistant-persisters (GRP) population within non-small cell lung cancer (NSCLC) cells possesses CSCs features. The purpose of this study is to examine the role of HDAC in the gefitinib-resistant lung CSC.

      Method:
      We used HDAC1, HDAC2, and HDAC5 as markers of chromatin compaction in GRP of EGFR-mutant NSCLC cells PC9 and HCC827. Gefitinib-resistant tumor (GRT) was established by obtaining the remaining tumor in PC9-injected NOG mice after two weeks of gefitinib treatment. Quantitative real-time PCR were performed to analyze gene expressions. immunofluorescence and fluorescence-immunohistochemistry were performed to analyze protein expressions in the NSCLC cell lines and in vivo biopsy specimens, respectively. HDAC inhibitor Trichostatin-A was used to study the impact on the sensitivity of GRP to gefitinib and the implication on the CSC features.

      Result:
      PC9-GRP and HCC827-GRP cells expressed high level of HDAC1, HDAC2, and HDAC5. GRT also showed upregulation of HDAC1 compared to naïve PC9 tumor. Inhibition of HDAC reduced CSC-related factors and, reduced sphere formation of GRP, and increased sensitivity to gefitinib. Specimens from lung cancer patients with acquired resistance to gefitinib displayed high expression of HDAC1.

      Conclusion:
      HDAC is implicated in the CSC phenotype and is involved in the resistance to EGFR-TKI in NSCLC. Inhition of HDAC could be considered to reverse acquired resistance of EGFR-mutant to EGFR-TKI that is mediated by CSC.

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    P1.03 - Chemotherapy/Targeted Therapy (ID 689)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Chemotherapy/Targeted Therapy
    • Presentations: 1
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      P1.03-024 - Efficacy of Carboplatin-Vinorelbine in Advanced NSCLC Patients at Persahabatan Hospital, Jakarta - Indonesia (ID 8426)

      09:30 - 09:30  |  Author(s): Sita Andarini

      • Abstract

      Background:
      Combination of platinum-based and third generation drugs such as vinorelbine chemotherapy are frequently used as paliative chemotherapy for Non-small cell lung cancer (NSCLC) patients in Indonesia especially in Persahabatan Hospital. But there is still no data about the efficacy and tolerability of carboplatin-vinorelbine regimen. This study was conducted to evaluate the efficacy and toxicity of this regimen as first line chemotherapy for advanced NSCLC patients in Persahabatan Hospital.

      Method:
      This study was an observational study in advanced NSCLC patients who receive carboplatin-vinorelbine regimen as first line chemotherapy. subjects were recruited between 1[st] January 2015 to 30[th ]March 2017. Clinical data regarding the histological type, staging, side effect of chemotherapy, RECIST and survival were recorded.

      Result:
      Thirty eight subjects were recruited in this study of which carboplatin 5 AUC on day 1 and vinorelbine 30mg/m[2 ]on day 1 and 8 were administered as a combination therapy. This regimen has a good efficacy with overall response rate (ORR) 12,5% and clinical benefit rate (CBR) 87,5%. The overall survival (OS) 34,2% with median of survival time 387 days (12,9 moths) and progression free survival (PFS) 323 days (10,7 months). We found grade 1 anemia (38,4%) and grade 2 nausea vomiting (57,9%) as hematological and non-hematological toxicity that frequently occured in this study. Two cases of grade 2 gastrointestinal bleeding were observed but the subjects still be able to continue the chemotherapy soon after recovery. Mild phlebitis were observed in 65.7% cases ( 24 subjects) and moderate phlebitis in 2.6% (1 subject) as procedural complication of this chemotherapy regimen.

      Conclusion:
      Combination of carboplatin and vinorelbine as first line chemotherapy has a good efficacy and tolerability for advanced NSCLC subjects.

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    P2.03 - Chemotherapy/Targeted Therapy (ID 704)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Chemotherapy/Targeted Therapy
    • Presentations: 2
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      P2.03-031 - Efficacy of Gefitinib and Radiotherapy Combination in Lung Adenocarcinoma (ID 9160)

      09:30 - 09:30  |  Author(s): Sita Andarini

      • Abstract

      Background:
      Combinations of gefitinib and radiotherapy have been observed to have synergistic and anti-proliferative effects on lung cancer in vitro, but clinical studies were limited. In clinical setting, patients who presented with respiratory difficulties like SVCS, radiotherapy should be given immediately to address the emergency while waiting for the results of EGFR mutation test.

      Method:
      We did a preliminary study to evaluate the efficacy of gefitinib and radiotherapy combination in lung adenocarcinoma in Persahabatan National Respiratory Refferal Hospital Jakarta Indonesia. Subjects were consecutively recruited between January 2013 to December 2016

      Result:
      Thirty one lung adenocarcinoma with EGFR mutations were enrolled. Most of them were male (51.61%) with median age of 54.5 years old (range 38-70 years old). Epidermal Growth Factor Reseptor (EGFR) mutation characteristics were on exon 21 L858R (61.30%); exon 21 L861Q (16.12%) and exon 19 deletion (22.58%). Radiotherapy were given at doses between 30-60 Gy. Among these subjects, Progression Free Survival (PFS) were 185 days (CI95%; 123.69-246.30), 1 year survival rate (1-ysr) was 45.2%. and overall survival (OS) are 300 days (CI95%;130.94-469.06). There were no grade 3/4 hematological and non hematological toxicities recorded. The most frequent Grade 1 and 2 non hematological toxicities were skin rash, diarrhea, paranochia and monoliasis and might be related to TKI.

      Conclusion:
      The combination of TKI with radiation may be considered in subjects with respiratory distress.

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      P2.03-049 - Pulmonary Adenoid Cystic Carcinoma with EGFR Activating Mutation and Responds Well with Tyrosine Kinase Inhibitor  (ID 9813)

      09:30 - 09:30  |  Author(s): Sita Andarini

      • Abstract

      Background:
      Adenoid cystic carcinoma (ACC) is an rare form of malignant neoplasm that arises from secretory glands in salivary glands of the head and neck but cases primary from respiratory tract is rare. Epidermal Growth Factor Receptor activating mutation is common in lung adenocarcinoma in Asian and responded well with Tyrosine Kinase Inhibitor.

      Method:
      We present the case of a 48 year old female complaining chest pain and shortness of breath.

      Result:
      The patient was referred to the hospital due to chest pain and shortness of breath since 4 months. Initial CXR showed pulmonary mass and chest CT scan showed giant pulmonary mass but no nodes enlargement. Lobectomy were performed and histopathology evaluation showed adenoid cystic carcinoma. The patient underwent radiotherapy chemotherapy. Four months later the symptoms increased and tumor grow. EGFR mutation were done and positive for activating mutation (exon 19 deletion) and Gefitinib were started. The patient was stable for 1 year with gefitinib with minor side effects.

      Conclusion:
      EGFR mutation testing should be considered in a rare pulmonary mass such as adenoid cystic carcinoma.

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    P3.01 - Advanced NSCLC (ID 621)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 3
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      P3.01-032 - Preliminary study of  Lung Cancer Adenocarcinoma  with De-novo EGFR T790M Mutation in Persahabatan Hospital-Jakarta, Indonesia. (ID 9179)

      09:30 - 09:30  |  Author(s): Sita Andarini

      • Abstract

      Background:
      De-novo EGFR T790M mutations are rare, occurs less than 5% in the world and resistant to EGFR-TKI treatment. In Persahabatan Hospital, patients with De novo EGFR T790M mutations are given systemic chemotherapy with or without radiotherapy. No data on clinical profiles and 6 months survival rate in this group. the purpose of this preliminary study is to evalaute clincal profiles and 6 months survival of EGFR-T790M mutation in lung adenocarcinoma in Persahabtan Hospital Jakarta Indonesia.

      Method:
      Subjects was recruited consecutively from lung cancer Adenocarcinoma with De-novo EGFR T790M mutations. EGFR mutation is routinely assesed in lung adenocarcinoma in Persahabatan Hospital using PCR-High Resollution Melting, RFLP Analysis and direct sequencing. Subjects' clinical characteristics (race, age, gender), smoking habits, family history of malignancy, occupation, date at diagnosis (through anatomic pathology examination), complete diagnosis, stage, performance status, metastasis, chemotherapy and radiotherapy, RECIST evaluation, date of death were recorded.

      Result:
      Fourteen subjects were elligible and included in this study of which 9 subjects were male (64,2%), 5 subjects female (35,7%). Smoking status were 8 subject were smoker (57,1%), never smoke (35,7%), ex smokers (7,14%). Two subjects ( 14.2%) has family history of malignancy. All subjects were stage 4 with 42.8% pleural effusion (6 subjects), 21.4% pleural effusion and bone metastasis (3 subjects), 21.4% ( 3 subjects) with distant lymph nodes metastasis, 7.2% brain metastasis ( 1 subjects), 7.14% brain and bone metastasis. Mutation in ONLY exon 20 T790M 85,7% ( 12 subjects); double mutation did exist with Exon 19 ins/del and exon 20 T790M (1 subject); exon 19 ins/del and exon 20 T790M (1 subject); exon 21 L861Q and exon 20 T790M in 1 subject. Systemic chemotherapy were done in 9 subjects (64,3%), systemic chemotherapy and radiotherapy were done in 5 subject (35,7%). Six months survival rates in this group was 50%; and 1 year survival were 21,42%; Interestingly 4 subjects (28,6%) survived more than 1 year.

      Conclusion:
      De-novo EGFR T790M mutations are rare (< 5%). The presence double mutation ie. De-novo EGFR T790M mutations and other activating EGFR mutation did exist. these group has variable clinical responses with chemotherapy and warrant further investigation.

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      P3.01-053 - Detection of Common EGFR Mutation in Cytological Smears Using Reversed Dot Blot (RDB) Hybridization Method (ID 9765)

      09:30 - 09:30  |  Author(s): Sita Andarini

      • Abstract
      • Slides

      Background:
      Epidermal growth factor receptor (EGFR) mutation can predict the response to EGFR tyrosine kinase inhibitor (TKI) in non small cell lung cancer (NSCLC). In this study, we determined the limit of detection of different methods, such as sequencing, restriction frament length polymorphism (RFLP), high resolution melting (HRM) and reversed dot blot (RDB) hybridization to detect for EGFR mutation detection.

      Method:
      Mutation detections of exons19 and 21 in EGFR gene were performed using sequencing, restriction fragment length polymorphism (RFLP) and high resolution melting (HRM) analysis method. Moreover, we also developed Reversed Dot Blot(RDB) method hybridization as an alternative procedure. Genomic DNA of H1975, HCT116 cell line as well as specially designed oligonucleotides were used to determine the limit of detection of these procedures. We also determine the sensitivity and specificity of RDB method compared to existing methods.

      Result:
      Limit of detection of each method was determined by titration of mutant allele in wildtype background. HRM analysis and RFLP were able to detect mutation in samples containing 6.25% to 12.5% mutated DNA.Limit of detection of RDB method was around 12.5%. Analysis of 40 patients had shown that the specificity for to detect mutations in exon 19 and 21 was 100% and 89.5% and the sensitivity for both exon was 62.5%.

      Conclusion:
      RDB method maybe used as an alternative method to standard procedure such as sequencing. This method is specific, but need further improvement to increase its sensitivity.

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      P3.01-054 - Urinary ct-DNA Testing of EGFR Common Mutation in Non-Small Cell Lung Cancer Patients (ID 9780)

      09:30 - 09:30  |  Author(s): Sita Andarini

      • Abstract
      • Slides

      Background:
      The existence of circulating tumor DNA (ct-DNA) in urine as a noninvasive and alternative sample to tissue biopsy has been promising. However, it still has some challenges. Common mutations of epidermal growth factor receptor (EGFR), such as L858R in exon 21 mutation has been used to predict lung cancer treatment response to tyrosine kinase inhibitors (TKI). The study aimed to demonstrate that DNA from urine can be detected using simple methods with high sensitivity, enabling early Non-Small Cell Lung Cancer (NSCLC) detection from these noninvasive samples.

      Method:
      Cytological smear and urine samples from 59 NSCLC patients had been collected and processed to obtain genomic DNA. EGFR common mutations in exon 21 were analyzed using polymerase chain reactions (PCR) and restriction fragment length polymorphism (RFLP) methods that having analytical sensitivity of detecting 3% EGFR mutant alleles. Diagnostic sensitivity and specificity test was used to evaluate the feasibility of urine as source of noninvasive samples compared with cytological samples.

      Result:
      We were able to detect EGFR exon 21 L858R mutations in 17 of 59 (28,81%) urine samples while 27 of 59 (45,76%) cytological samples were EGFR positive mutations. Agreement between urine and cytological slide was 45.76%. Diagnostic sensitivity and specificity were 22,22% and 65.62% respectively.

      Conclusion:
      EGFR mutation of lung cancer patients were detected from urine using RFLP methods. In this study, mutation rate in urine (28,81%) was similar to mutation rate from plasma (22%) of Asian Lung cancer patients as described Han, B et al 2015. However, poor sensitivity (22.22%) and specificity (65.62%) of urinary ctDNA L858R analysis may not lead to treatment decision. More in-depth studies focusing on urine collection techniques and more sensitive technology may lead to useful application of urine as an alternative noninvasive liquid biopsy sample for NSCLC detection.

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    P3.11 - Patient Advocacy (ID 727)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Patient Advocacy
    • Presentations: 1
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      P3.11-001 - Factors Correlated With Time and Cost Diagnostic Lung Cancer (ID 10138)

      09:30 - 09:30  |  Author(s): Sita Andarini

      • Abstract

      Background:
      Most of lung cancer patients diagnosed in advanced stage. The reasons for the delay of the diagnosis might be from patient and/or health care system. Currently, Indonesia, as a developing country in Asia, has National Health Insurance System (Jaminan Kesehatan Nasional) of which the patients is feasibly referred to the referral hospital without worrying the cost. In Persahabatan Hospital-the National Referral for Respiratory Diseases many cases have diagnostic delayed that might contribute to the prognosis. We had been conducting a study to evaluate diagnostic time and diagnostic cost to diagnose lung cancer.

      Method:
      We conducted an observational study in Persahabatan Hospital Jakarta of which newly diagnosed lung cancer patients were reviewed. We evaluated the time and cost needed from the first visit until definitive diagnosis by histopatology obtained. We also evaluated the factors that have correlated with time and cost of lung cancer diagnosis.

      Result:
      One hundred and ten subjects were enrolled in this study. Eighty four (76,36%) were male and 26 (23,64%) were female. The median age was 57 years old with range 26 to 86 years old. Data have shown that 53 (48,2%) subjects were diagnosed under target time ( less than 2 weeks) but 57 subjects (51,8%) had diagnostic time more than 2 weeks. The median time of diagnostic was 15 days with the range of 1 to 68 days. Diagnostic delay was correlated with: early stage of the diseases, good performance status, no financial resource. The median cost of diagnosis was 13.025.381 Rupiahs ( around 1000 US$) with range Rp. 1.083.000,- to Rp156.285.000,- ( <100US$ to 11.000 US$). Subject who came with advanced stage, poor performance status, had complication of lung cancer and reffered to private hospitals had higher diagnostic cost.

      Conclusion:
      Median diagnostic time of lung cancer in Persahabatan Hospital Jakarta Indonesia was 15 days ranging from 1 to 86 days. Diagnostic time correlated with stage at admission, performance status at admission and financial support. The median cost of diagnosis was Rp. 13.025.381,- ( around 1000 US$) with the range of Rp. 1.083.000,- to Rp156.285.000,- ( < 100US$ to 10.000 US$). Cost of lung cancer diagnosis correlated with stage at admission, performance status at admission, source of financial support and complication related to lung cancer.