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"Latar belakang: Insulin-like growth factor 1 receptor(IGF1R) diekspresikan pada banyak tumor solidtermasuk kanker paru dan peningkatan aktivasi IGF1R mencerminkan progresivitas kanker. Epithelial-mesenchymal transition (EMT) merupakan salah satu mekanisme yang digunakan sel kanker untuk bermetastasis dan menyebabkan perburukan pasien. Kondisi lingkungan mikroseperti hipoksia dapat menginduksi EMT. Tujuan penelitian ini adalah untuk menentukan peran aktivasi IGF1R pada EMT yang diinduksi hipoksia pada kanker paru dan untuk menguji apakah inhibisi IGF1R dapat mencegah EMT pada sel kanker paru yang hipoksik.Metode: Sel kanker paru, yaitu A549, dipajankan pada lingkungan hipoksia untuk menilai ekspresi genotipe dan fenotipe EMT. Analisis ekspresi gen dilakukan dengan quantitative real-time PCR (qPCR)dan fenotipe sel dipelajari dengan penilaian morfologi, scratch wound assay dan imunofloresen. Hasil: Sel-sel yang hipoksik menunjukkan perubahan morfologi menjadi berbentuk spindle, peningkatan motilitas sel, penurunan ekspresi E-cadherin dan peningkatan ekspresi fibronektin dan vimentin yang mencerminkan fenomena EMT. Hipoksia juga mengakibatkan peningkatan ekspresi insulin-like growth factor 1 (IGF1), IGF1-binding protein 3 (IGFBP3) dan IGF1R, namun transforming growth factor β (TGFβ) tidak meningkat. Inhibisi hypoxia-inducible factor 1α (HIF1α) dengan YC-1 menekan aktivasi IGF1R dan menurunkan ekspresi IGF1 dan IGFBP3 pada sel yang hipoksik.Lebih lanjut, inhibisi IGF1R dengan AEW541 pada keadaan hipoksia mengembalikan ekspresi E-cadherin dan menurunkan ekspresi penanda mesenkimal fibronektin dan vimentin.Akhirnya, stimulasi sel normoksik dengan IGF1 menginduksi terjadinya EMT.Kesimpulan: Hasil penelitian ini mengindikasikan peran aktivasi IGF1R dalam terjadinya EMT yang diinduksi keadaan hipoksia dan inhibisi IGF1R bisa mencegah fenomena EMT. Temuan dalam penelitian ini memperlihatkan potensi pencegahan progresivitas kanker yang distimulasi hipoksia dan dimediasi EMT dengan terapi target IGF1R.

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Introduction: Insulin-like growth factor 1 receptor (IGF1R) is expressed in many types of solid tumors including non-small cell lung cancer (NSCLC), and enhanced activation of IGF1R is thought to reflect cancer progression.Epithelial-mesenchymal transition (EMT) has been established as one of the mechanisms responsible for cancer progression and metastasis, and microenvironment conditions, such as hypoxia, have been shown to induce EMT. The purposes of this study were to address the role of IGF1R activation in hypoxia-induced EMT in NSCLC and to determine whether inhibition of IGF1R might reverse hypoxia-induced EMT.Methods: Human NSCLC cell line A549 was exposed to hypoxia to investigate the expression of EMT-related genes and phenotypes. Gene expression analysis was performed by quantitative real-time PCR (qPCR) and cell phenotypes were studied by morphology assessment, scratch wound assay, andimmunofluorescence.Results: Hypoxia-exposed cells exhibited a spindle-shaped morphology with increased cell motility reminiscent of EMT, and demonstrated the loss of E-cadherin and increased expression of fibronectin and vimentin. Hypoxia also led to increased expression of IGF1, IGF binding protein-3 (IGFBP3), and IGF1R, but not transforming growth factor β1 (TGFβ1). Inhibition of hypoxia-inducible factor-1α (HIF1α) with YC-1 abrogated activation of IGF1R, and reduced IGF1 and IGFBP3 expression in hypoxic cells. Furthermore, inhibition of IGF1R using AEW541 in hypoxic condition restored E-cadherin expression, and reduced expression of fibronectinand vimentin. Finally, IGF1 stimulation of normoxic cells induced EMT.Conclusions: Our findings indicated that hypoxia induced EMT in NSCLC cells through activation of IGF1R, and that IGF1R inhibition reversed these phenomena. These results suggest a potential role for targeting IGF1R in the prevention of hypoxia-induced cancer progression and metastasis mediated by EMT."

"Latar Belakang: Tingginya angka kejadian kanker paru menyebabkan diperlukan pemanfaatan suatu penanda biologis spesifik kanker paru untuk menilai progresifitas penyakit. Transforming growth factor-β adalah protein yang disekresi untuk meregulasi proliferasi, diferensiasi dan kematian dari berbagai jenis sel. Semua jenis sel kekebalan termasuk sel B, sel T, sel dendritik dan makrofag mensekresi TGF-β. Jenis TGF-β yang terbanyak adalah TGF-β1. Diperlukan pengukuran kadar TGF-β1 serum darah tepi sebagai faktor prognostik pada kanker paru khususnya KPKBSK stage lanjutMetode: Penelitian ini merupakan studi perbandingan dengan disain potong lintang pada pasien kanker paru yang telah tegak diagnosis dan bersedia diambil serum darah tepi untuk pemeriksaan kadar TGF-β1 serum menggunakan Human TGF-β1 Quantikine ELISA kit dari R D. Kadar TGF-β1 serum diukur pada 68 subjek yang terdiri dari 30 subjek kelompok kanker paru dan 38 subjek kelompok bukan kanker paru.Hasil: Kadar TGF-β1 serum pada kelompok kanker paru meningkat signifikan lebih tinggi dibandingkan kelompok bukan kanker paru (median; min-max) (3601.85; 2006.87-14995.25 pg/mL vs 2510.11; 646.31-5584.07 pg/mL) (P = 0.000). Tidak ditemukan hubungan antara kadar TGF-β1 serum dengan jenis kelamin, umur, riwayat merokok, gejala klinis, gambaran bronkoskopi, jenis sitologi/histopatologi, KPKBSK stage lanjut, dan status tampilan umum. Median Survival Time (95% CI) TGF-β1 < 3601.85 pg/mL adalah 9.7 (2.4-16.9) bulan sedangkan TGF-β1 ≥ 3601.85 pg/mL adalah 16.7 (7.7-25.7) bulan. Over all survival TGF-β1 13.3 (5.8-20.8) bulanKesimpulan: Kadar TGF-β1 serum meningkat pada kelompok kanker paru dibandingkan kelompok bukan kanker paru. Kadar TGF-β1 serum belum dapat digunakan sebagai marker prognostik kanker paru.

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Beckground: The high incidence rate of lung cancer leads to the utilization of a specific biological marker of lung cancer to assess disease progression. Transforming growth factor-β is a secreted protein to regulate the proliferation, differentiation and death of different cell types. Types of immune cells are B cells, T cells, dendritic cells and macrophages secreting TGF-β. The most common type of TGF-β is TGF-β1. Therefore, measurement of serum level of TGF-β1 as a prognostic factors in lung cancer, especially advanced stage NSCLC, to assess progressivity of lung cancer is needed. Method: This study is a comparative study with cross-sectional design in lung cancer patients who had been diagnosed and were willing to be taken for examination of peripheral blood serum levels of TGF-β1 using the Quantikine Human TGF-β1 ELISA kit from R&D system. TGF-β1 serum levels were measured in 68 subjects consisted of 30 subjects with lung cancer group and 38 subjects controlled group. Result: Serum level of TGF-β1 in lung cancer group increased significantly higher than control group (median; min-max) (3601.85; 2006.87-14995.25 pg/mL vs. 2510.11; 646.31-5584.07 pg/mL) (P = 0.000). There was no association between serum level of TGF-β1 with gender, age, smoking history, clinical symptoms, bronchoscopy, cytology/histopathology, advanced stage of NSCLC, and performance status. Median Survival Time (95% CI) TGF-β1 <3601.85 pg/mL was 9.7 (2.4-16.9) months while TGF-β1 ≥ 3601.85 pg/mL was 16.7 (7.7-25.7) months. Over all survival TGF-β1 13.3 (5.8-20.8) months. Conclusion: Serum level of TGF-β1 is higher in the lung cancer group compared to controlled group. Serum TGF-β1 levels can not be used as a prognostic markers of lung cancer."

"Latar belakang : Terapi target baru golongan EGFR-TKi telah direkomendasikan sebagai terapi lini pertama untuk pasien KPKBSK non skuamosa dengan mutasi EGFR positif. Belum tersedia data di Indonesia tentang efikasi dan toksisitas terapi target baru EGFR-TKi pada pasien KPKBSK dengan mutasi EGFR positif dibandingkan dengan kemoradioterapi pada EGFR wild type di RSUP Persahabatan Jakarta.Metode : Disain penelitian ini kohort retrospektif melalui resume medis pasien KPKBSK non skuamosa di RSUP Persahabatan periode Januari 2010 sampai Juli 2014. Teknik pengambilan sampel adalah consequtive sampling. Jumlah sampel 61 pasien yang terdiri dari 31 pasien KPKBSK non skuamosa dengan mutasi EGFR positif yang diberikan terapi target baru EGFR-TKi dan 30 pasien dengan EGFR wild type yang diberikan kemoradioterapi.Hasil : Karakteristik pasien KPKBSK non skuamosa dengan mutasi EGFR yang positif adalah laki-laki sebanding dengan perempuan, bukan perokok, mutasi delesi di ekson 19 sebanding dengan mutasi L858R di ekson 21, angka tahan hidup 1 tahun 48,37%, rata-rata time to progression 284 hari sedangkan pasien EGFR wild type adalah laki-laki lebih dominan, perokok, angka tahan hidup 1 tahun 33,3% dan rata-rata time to progression 210 hari dan overall survival 293 hari. Uji T independen menunjukan terdapat hubungan yang bermakna antara terapi target baru EGFR-TKi dengan lama time to progression (p=0,028). Toksisitas yang sering ditemukan pada terapi target baru EGFR-TKi adalah mual- muntah (6,8%) diare (16,2%), alopesia (3,2%) dan kelainan kulit kemerahan (12,9%) sedangkan pada kelompok kemoradioterapi toksisitas yang ditemukan adalah anemia (13,3%), leukopenia (6,7%) dan trombositopenia (3,3%).Kesimpulan : Pasien KPKBSK non skuamosa dengan mutasi EGFR yang positif dan diberikan terapi target baru EGFR-TKi memiliki time to progression yang lebih lama dan toksisitas yang dapat ditoleransi.

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Background: The new targeted therapy of EGFR-TKi has been recommended as first-line therapy for patients with NSCLCC non-squamous with mutated EGFR. There are no data about the efficacy and toxicity of the new targeted therapy of EGFR-TKi in NSCLC non-squamous with mutated EGFR compared with chemotradiotherapy in wild type at Persahabatan Hospital, Jakarta.

Methods: The design of study are retrospective cohort through medical records of NSCLC non-squamous patients in the Department of Pulmonology and Respiratory Persahabatan Hospital in January 2010 to July 2014. The sampling technique is consequtive sampling. The number of samples are 61 patients consisted of 31 patients with NSCLC non-squamous with mutated EGFR treated the new targeted therapy of EGFR-TKi and 30 patients with EGFR wild type treated chemoradiotherapy.

Results: The characteristics of NSCLC non-squamous patients with positive mutated EGFR are male compared to women, non-smokers, a deletion mutation in exon 19 L858R mutation comparable with in exon 21, 1-year survival 41,9%, mean time to progression is 284 days and patients of wild-type mutation are more dominant in males, smokers, 1-year survival 33,3% and mean time to progression is 210 days and overall survival is 293 days . The independent t test showed a significant relationship between the new targeted therapy with EGFR-TKi and TTP (p = 0.028). The most common adverse events in the EGFR-TKi group are nausea and vomitus 96,8%), diarrhea (16,2%), alopecia (3,2%) and rash (12,9%) and in the chemotherapy group, anemia (13,3%), leucopenia (6,7%) and thrombocytopenia (3,3%).

Conclusions: The EFGR-TKi for patients with advanced non small cell lung cancer who are selected on the basis of EGFR mutations improve time to progression with acceptable toxicity."

"[ABSTRAKPendahuluan. Kanker paru jenis karsinoma bukan sel kecil (KPKBSK) terdiri dari nonskuamosa dan skuamosa. Kanker paru jenis karsinoma bukan sel kecil nonskuamosa adalah adenokarsinoma dan karsinoma sel besar. Saat ini terapi kanker paru sangat berkembang dari agen kemoterapi sampai terapi target terutama EGFR-TKI. Penelitian ini bertujuan untuk menilai angka tahan hidup pasien KPKSBK nonskuamosa yang mendapat kemoterapi lini pertama dibandingkan terapi EGFR-TKI di RSUP Persahabatan.Metode. Penelitian ini adalah penelitian retrospektif antara tahun 2010 sampai 2013 dari rekam medis pasien KPKBSK non skumosa yang mendapatkan kemoterapi lini pertama dan EGFR-TKI. Pasien dikemoterapi dengan platinum baseddan EGFR-TKI diterapi gefitinib 1x250 mg/hari atau erlotinib 1x150 mg/hari. Angka tahan hidup dinilai dari mulai tegak diagnosis sampai pasien meninggal atau saat penelitian dihentikan.Hasil. Dari 96 sampel KPKBSK non skuamosa terdiri dari 48 pasien yang mendapat kemoterapi lini pertama dan 48 pasien yang diterapi EGFR-TKI. Berdasarkan karakteristik pasien, usia terbanyak adalah 40-60 tahun (kemoterapi 32 (66,7%) dan EGFR-TKI 31 (64,6%) dengan jenis kelamin laki-laki yang mendominasi (kemoterapi 25(52,1%), EGFR-TKI 27 (56,2%). Pasien merokok yang mendapat kemoterapi lini pertama 41,7% dan EGFR-TKI 56,3% dengan IB terbanyak untuk kemoterapi (IB ringan 27,1%) dan untuk EGFR-TKI (IB sedang 22,9%). Jenis histologi adenokarsinoma 95,8% dengan dominasi stage IV 89,6% (kemoterapi 91,7% dan EGFR-TKI 87,5%) disertai tampilan status 2 59,4%. Angka tahan hidup pasien (ATH) 6 bulan 74%, ATH 1 tahun 22,90% dan ATH 2 tahun 6,20%. Masa tengah tahan hidup (MTTH) pasien yang mendapat EGFR-TKI lebih lama sedikit dibandingkan yang mendapat kemoterapi lini pertama (263 hari versus 260 hari.Kesimpulan. Masa tahan hidup 1 tahun pasien KPKBSK non skuamosa yang diterapi EGFR-TKI sedikit lebih lama dibandingkan kemoterapi lini pertama (263 hari vs 260 hari). Sedangkan ATH 1 tahun pasien kemoterapi lini pertama lebih besar dibandingkan EGFR-TKI (25% vs 20,8%). Faktor yang paling mempengaruhi angka tahan hidup adalah stage dengan nilai p<0,05.

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ABSTRACT Introduction. Lung cancer is the type of non-small cell carcinoma (NSCLC) consists of non-squamous and squamous. Non-small cell lung cancer of non squamous types consist of adenocarcinoma and large cell carcinoma. Currently, lung cancer therapy is highly developed of chemotherapeutic agents to targeted therapy especially EGFR-TKI. This study aims to assess the survival rate of NSCLC patients of non-squamous type who receive first line chemotherapy and those who recieve EGFR-TKI therapy at Persahabatan hospital.Methods. This study is a retrospective study between 2010 to 2013 from the medical records of NSCLC patients of non-squmous type who receive first-line chemotherapy and thise who recieve EGFR-TKI.Patients with platinum-based chemotherapy and EGFR-TKI with gefitinib therapy 1x250 mg/day or erlotinib 1x150mg/day. Survival rate assessed from start to erect the diagnosis until the patient dies or when the study is discontinued.Result. From 96 subject of NSCLC patients with non-squamous type consisted of 48 patients who receive first-line chemotherapy, and 48 patients are treate with EGFR-TKI. Based on the characteristics of the patients, most are 40-60 years old (chemotherapy 32 (66.7%) and EGFR-TKI 31 (64.6%) with the male gender that dominates (chemotherapy 25 (52.1%), EGFR-TKI 27 (56.2%). Smoking patients who received first-line chemotherapy are 41.7% and 56.3% of EGFR-TKIs with chemotherapy highest IB (mild IB 27.1%) and for EGFR-TKI (moderate IB are 22.9%). 95.8% of adenocarcinoma histology type with a predominance of stage IV 89.6% (91.7% for chemotherapy and EGFR-TKI 87.5%) with performance status 2 59.4% . Survival rate of patients are 74% for 6 months survival, 1 year survival rate is 22.90% and 2 years survival rate of 6.20%. Median period of survival rate in patients who receiving EGFR-TKI longer than they received first-line chemotherapy (263 days versus 260 days).Conclusion. Median survival rate of non-squamous NSCLC that treated by EGFR-TKI is longer than first-line chemotherapy (263 days vs 260 days). Although 1 year survival rate first-line chemotherapy in patients is greater than EGFR-TKI (25% vs 20.8%). The factors that most influence the survival rate is stages with p value<0.05.;Introduction. Lung cancer is the type of non-small cell carcinoma (NSCLC) consists of non-squamous and squamous. Non-small cell lung cancer of non squamous types consist of adenocarcinoma and large cell carcinoma. Currently, lung cancer therapy is highly developed of chemotherapeutic agents to targeted therapy especially EGFR-TKI. This study aims to assess the survival rate of NSCLC patients of non-squamous type who receive first line chemotherapy and those who recieve EGFR-TKI therapy at Persahabatan hospital.Methods. This study is a retrospective study between 2010 to 2013 from the medical records of NSCLC patients of non-squmous type who receive first-line chemotherapy and thise who recieve EGFR-TKI.Patients with platinum-based chemotherapy and EGFR-TKI with gefitinib therapy 1x250 mg/day or erlotinib 1x150mg/day. Survival rate assessed from start to erect the diagnosis until the patient dies or when the study is discontinued.Result. From 96 subject of NSCLC patients with non-squamous type consisted of 48 patients who receive first-line chemotherapy, and 48 patients are treate with EGFR-TKI. Based on the characteristics of the patients, most are 40-60 years old (chemotherapy 32 (66.7%) and EGFR-TKI 31 (64.6%) with the male gender that dominates (chemotherapy 25 (52.1%), EGFR-TKI 27 (56.2%). Smoking patients who received first-line chemotherapy are 41.7% and 56.3% of EGFR-TKIs with chemotherapy highest IB (mild IB 27.1%) and for EGFR-TKI (moderate IB are 22.9%). 95.8% of adenocarcinoma histology type with a predominance of stage IV 89.6% (91.7% for chemotherapy and EGFR-TKI 87.5%) with performance status 2 59.4% . Survival rate of patients are 74% for 6 months survival, 1 year survival rate is 22.90% and 2 years survival rate of 6.20%. Median period of survival rate in patients who receiving EGFR-TKI longer than they received first-line chemotherapy (263 days versus 260 days).Conclusion. Median survival rate of non-squamous NSCLC that treated by EGFR-TKI is longer than first-line chemotherapy (263 days vs 260 days). Although 1 year survival rate first-line chemotherapy in patients is greater than EGFR-TKI (25% vs 20.8%). The factors that most influence the survival rate is stages with p value<0.05.;Introduction. Lung cancer is the type of non-small cell carcinoma (NSCLC) consists of non-squamous and squamous. Non-small cell lung cancer of non squamous types consist of adenocarcinoma and large cell carcinoma. Currently, lung cancer therapy is highly developed of chemotherapeutic agents to targeted therapy especially EGFR-TKI. This study aims to assess the survival rate of NSCLC patients of non-squamous type who receive first line chemotherapy and those who recieve EGFR-TKI therapy at Persahabatan hospital.Methods. This study is a retrospective study between 2010 to 2013 from the medical records of NSCLC patients of non-squmous type who receive first-line chemotherapy and thise who recieve EGFR-TKI.Patients with platinum-based chemotherapy and EGFR-TKI with gefitinib therapy 1x250 mg/day or erlotinib 1x150mg/day. Survival rate assessed from start to erect the diagnosis until the patient dies or when the study is discontinued.Result. From 96 subject of NSCLC patients with non-squamous type consisted of 48 patients who receive first-line chemotherapy, and 48 patients are treate with EGFR-TKI. Based on the characteristics of the patients, most are 40-60 years old (chemotherapy 32 (66.7%) and EGFR-TKI 31 (64.6%) with the male gender that dominates (chemotherapy 25 (52.1%), EGFR-TKI 27 (56.2%). Smoking patients who received first-line chemotherapy are 41.7% and 56.3% of EGFR-TKIs with chemotherapy highest IB (mild IB 27.1%) and for EGFR-TKI (moderate IB are 22.9%). 95.8% of adenocarcinoma histology type with a predominance of stage IV 89.6% (91.7% for chemotherapy and EGFR-TKI 87.5%) with performance status 2 59.4% . Survival rate of patients are 74% for 6 months survival, 1 year survival rate is 22.90% and 2 years survival rate of 6.20%. Median period of survival rate in patients who receiving EGFR-TKI longer than they received first-line chemotherapy (263 days versus 260 days).Conclusion. Median survival rate of non-squamous NSCLC that treated by EGFR-TKI is longer than first-line chemotherapy (263 days vs 260 days). Although 1 year survival rate first-line chemotherapy in patients is greater than EGFR-TKI (25% vs 20.8%). The factors that most influence the survival rate is stages with p value<0.05.;Introduction. Lung cancer is the type of non-small cell carcinoma (NSCLC) consists of non-squamous and squamous. Non-small cell lung cancer of non squamous types consist of adenocarcinoma and large cell carcinoma. Currently, lung cancer therapy is highly developed of chemotherapeutic agents to targeted therapy especially EGFR-TKI. This study aims to assess the survival rate of NSCLC patients of non-squamous type who receive first line chemotherapy and those who recieve EGFR-TKI therapy at Persahabatan hospital.Methods. This study is a retrospective study between 2010 to 2013 from the medical records of NSCLC patients of non-squmous type who receive first-line chemotherapy and thise who recieve EGFR-TKI.Patients with platinum-based chemotherapy and EGFR-TKI with gefitinib therapy 1x250 mg/day or erlotinib 1x150mg/day. Survival rate assessed from start to erect the diagnosis until the patient dies or when the study is discontinued.Result. From 96 subject of NSCLC patients with non-squamous type consisted of 48 patients who receive first-line chemotherapy, and 48 patients are treate with EGFR-TKI. Based on the characteristics of the patients, most are 40-60 years old (chemotherapy 32 (66.7%) and EGFR-TKI 31 (64.6%) with the male gender that dominates (chemotherapy 25 (52.1%), EGFR-TKI 27 (56.2%). Smoking patients who received first-line chemotherapy are 41.7% and 56.3% of EGFR-TKIs with chemotherapy highest IB (mild IB 27.1%) and for EGFR-TKI (moderate IB are 22.9%). 95.8% of adenocarcinoma histology type with a predominance of stage IV 89.6% (91.7% for chemotherapy and EGFR-TKI 87.5%) with performance status 2 59.4% . Survival rate of patients are 74% for 6 months survival, 1 year survival rate is 22.90% and 2 years survival rate of 6.20%. Median period of survival rate in patients who receiving EGFR-TKI longer than they received first-line chemotherapy (263 days versus 260 days).Conclusion. Median survival rate of non-squamous NSCLC that treated by EGFR-TKI is longer than first-line chemotherapy (263 days vs 260 days). Although 1 year survival rate first-line chemotherapy in patients is greater than EGFR-TKI (25% vs 20.8%). The factors that most influence the survival rate is stages with p value<0.05., Introduction. Lung cancer is the type of non-small cell carcinoma (NSCLC) consists of non-squamous and squamous. Non-small cell lung cancer of non squamous types consist of adenocarcinoma and large cell carcinoma. Currently, lung cancer therapy is highly developed of chemotherapeutic agents to targeted therapy especially EGFR-TKI. This study aims to assess the survival rate of NSCLC patients of non-squamous type who receive first line chemotherapy and those who recieve EGFR-TKI therapy at Persahabatan hospital.Methods. This study is a retrospective study between 2010 to 2013 from the medical records of NSCLC patients of non-squmous type who receive first-line chemotherapy and thise who recieve EGFR-TKI.Patients with platinum-based chemotherapy and EGFR-TKI with gefitinib therapy 1x250 mg/day or erlotinib 1x150mg/day. Survival rate assessed from start to erect the diagnosis until the patient dies or when the study is discontinued.Result. From 96 subject of NSCLC patients with non-squamous type consisted of 48 patients who receive first-line chemotherapy, and 48 patients are treate with EGFR-TKI. Based on the characteristics of the patients, most are 40-60 years old (chemotherapy 32 (66.7%) and EGFR-TKI 31 (64.6%) with the male gender that dominates (chemotherapy 25 (52.1%), EGFR-TKI 27 (56.2%). Smoking patients who received first-line chemotherapy are 41.7% and 56.3% of EGFR-TKIs with chemotherapy highest IB (mild IB 27.1%) and for EGFR-TKI (moderate IB are 22.9%). 95.8% of adenocarcinoma histology type with a predominance of stage IV 89.6% (91.7% for chemotherapy and EGFR-TKI 87.5%) with performance status 2 59.4% . Survival rate of patients are 74% for 6 months survival, 1 year survival rate is 22.90% and 2 years survival rate of 6.20%. Median period of survival rate in patients who receiving EGFR-TKI longer than they received first-line chemotherapy (263 days versus 260 days).Conclusion. Median survival rate of non-squamous NSCLC that treated by EGFR-TKI is longer than first-line chemotherapy (263 days vs 260 days). Although 1 year survival rate first-line chemotherapy in patients is greater than EGFR-TKI (25% vs 20.8%). The factors that most influence the survival rate is stages with p value<0.05.]"

"Latar Belakang: Usia lanjut dan hubungannya dengan kesintasan kanker paru karsinoma bukan sel kecil sudah diteliti sebelumnya, namun kesintasannya di rumah sakit di Indonesia belum diteliti. Belum banyak penelitian lain yang memperhitungkan faktor perancu antara lain derajat keparahan penyakit, status fungsional, komorbiditas, dan indeks massa tubuh dalam meneliti pengaruh pertambahan usia dengan kesintasan kanker paru karsinoma bukan sel kecil. Tujuan: Mengetahui adakah perbedaan kesintasan satu tahun pasien kanker paru karsinoma bukan sel kecil usia lanjut dan bukan usia lanjut yang diterapi di semua stadium dengan mempertimbangkan functional status, indeks massa tubuh, dan komorbiditas. Metode: Kohort retrospektif dengan pendekatan analisis kesintasan terhadap 227 pasien kanker paru karsinoma bukan sel kecil yang berobat jalan maupun rawat inap di RS Cipto Mangunkusumo dan RS Kanker Dharmais tahun 2002-2012, terbagi 2 kelompok berdasarkan usia saat diagnosis (<60 tahun dan >60 tahun). Kurva Kaplan-Meier digunakan untuk mengetahui kesintasan satu tahun masingmasing kelompok. Analisis bivariat menggunakan uji log-rank, analisis multivariat menggunakan cox proportional hazard regression. Besarnya hubungan variabel usia dengan kesintasan dinyatakan dengan crude HR dan IK 95% serta adjusted HR dan IK 95% setelah dimasukkan variabel perancu. Hasil dan Pembahasan: Terdapat 227 pasien adalah kanker paru karsinoma bukan sel kecil yang diterapi dimana karakteristik kedua kelompok (<60 tahun dan >60 tahun) sebanding kecuali jenis kelamin, merokok, ada tidaknya komorbiditas, dan jumlah komorbiditas. Persentase mortalitas satu tahun adalah 68,0% dan 61,9% untuk kelompok usia <60 dan >60 tahun dengan median kesintasan 8 dan 9 bulan bulan. Analisis bivariat tidak menunjukkan hubungan bermakna antara usia dengan kesintasan satu tahun. Simpulan: Tidak ada pengaruh usia terhadap kesintasan satu tahun pasien kanker paru karsinoma bukan sel kecil yang diterapi di RS Cipto Mangunkusumo dan RS Kanker Dharmais di semua stadium dengan mempertimbangkan functional status, indeks massa tubuh, dan komorbiditas.

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Background: Old age and its relations to non-small cell lung carcinoma survival has been studied before but its survival in Indonesia has not been studied before. Not many studies that have considered confounders, such as stage, functional status, comorbidities and body mass index, in the study between advancing age and non-small cell lung cancer carcinoma survival.

Aim: To evaluate differences of treated non-small cell lung carcinoma one year survival between non-elderly and elderly considering stages, functional status, body mass index and comorbidities.

Methods: Retrospective cohort design and survival analysis were used to 227 patients with non-small cell lung cancer that being treated at Cipto Mangunkusumo Hospital and Dharmais Cancer Hospital between 2002 and 2012 that divided into 2 groups according to age at diagnosis (<60 years and >60 years). Kaplan-Meier curve was used to evaluate the one year survival of each group. Bivariate analysis was conducted using log-rank test, multivariate analysis was conducted using cox proportional hazard regression. The extend of relation between advancing age and survival was expressed with crude HR with 95% CI and adjusted HR with 95% CI after adjusting for confounders.

Results and Discussion: There were 227 non-small cell lung carcinoma being treated whereas the characteristics between two groups (<60 years and >60 years) were the same except for sex, smoking status, comorbidities and number of comorbidities. One year mortality percentage were 68.0% and 61.9% to <60 years and >60 years groups, respectively, with the survival median of 8 and 9 months. Bivariate analysis didn’t find statistically significant relation between age and one year survival.

Conclusion: Age didn’t influence one year survival of treated non-small cell lung carcinoma at Cipto Mangunkusumo Hospital and Dharmais Cancer Hospital considering stage, functional status, comorbidities and body mass index."

"[ABSTRAKLatar belakang: Kasus baru dan kematian kanker paru semakin meningkat. Rokok tembakau sangat berperan tetapi hanya 15% yang menderita kanker paru. Oleh karena itu faktor genetik diduga berperan pada kanker paru. Penelitian-penelitian kohort selama ini menunjukan hubungan bermakna risiko kanker paru dengan riwayat kanker di keluarga. Tujuan: Tujuan utama dari penelitian ini adalah untuk menentukan proporsi subjek kanker paru dengan riwayat kanker pada keluarga.Metode: Penelitian ini adalah studi observasi deskriptif potong lintang dengan subjek kanker paru yang berobat jalan maupun inap di RSUP Persahabatan Jakarta 1 Januari 2013 sampai 31 Mei 2015.Hasil: Subjek penelitian 380 dengan komposisi laki-laki lebih banyak dibandingkan perempuan (72,9% banding 27,1%) dengan median 56 tahun dan nilai minimum dan maksimum 20-86 (66) tahun. Sebanyak 65.3% subjek adalah perokok. Dari total subjek yang merokok, 33,2% termasuk perokok dengan Indeks Brickman (IB) sedang. Jenis sel kanker terbanyak adalah masuk kelompok Kanker Paru Karsinoma Bukan Sel Kecil (KPKBSK) yaitu adenokarsinoma 73,4%. Sebagian besar subjek terdiagnosis pada stage lanjut baik pada kelompok KPKBSK maupun Kanker Paru Karsinoma Sel Kecil (KPKSK). Proporsi subjek dengan riwayat kanker keluarga sebesar 8,2% dengan subjek laki-laki lebih besar dibandingkan perempuan (5,8% dibandingkan 2,4%). Nilai minimum-maksimum usia 35-72 tahun, median 55 tahun. Subjek yang merokok hanya ditemukan pada laki-laki sebanyak 71% dan jenis kanker terbanyak adenokarsinoma 71%. Hubungan keluarga 1 orang lebih banyak ditemukan dibandingkan lebih 1 orang (64,4% banding 35,6%) dengan dominasi ayah (25,8%). Jenis kanker keluarga paling banyak bukan kanker paru dibandingkan kanker paru (85,4% banding 14,6%). Kesimpulan: Proporsi subjek kanker paru dengan riwayat kanker pada keluarga adalah 8,2%. Subjek dengan 1 anggota keluarga yang memiliki kanker paling banyak 64,4% dengan dominasi ayah 25,8%. Jenis kanker paru dengan riwayat kanker keluarga terbanyak adenokarsinoma 71%. Jenis kanker keluarga lebih banyak adalah bukan kanker paru 85,4%.

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ABSTRACTBackground: The new cases and mortality of lung cancer are increasing. Smoking tobacco have a role play but only 15% smokers are suffering from lung cancer. Therefore, genetic factors thought to play a role in lung cancer. Many studies show a significant association with the risk of lung cancer in the family history of cancer.Objective: To determine the proportion of lung cancer?s subjects with a cancer history in the family.Methods: Using cross-sectional a descriptive observational study with the outpatient and inpatient lung cancer?s subject at Persahabatan Hospital, Jakarta started from January 1st, 2013 until April 30th, 2015.Results: The total subject of the study are 380 with the composition of men higher than women (72.9% vs 27.1 %) with a median is 56 and a minimum-maximum age is 20-86 (66). From those subjects, 65.3% are smokers with the most moderate IB is 33.2%. The most type cancer cells in group of Non Small Cell Lung Cancer Carcinoma (NSCLCC) is adenocarcinoma (73.4%). Most subjects diagnosed at an advanced stage either in groups of NSCLCC or Small Cell Lung Cancer Carcinoma (SCLCC). The subject?s proportion with the family cancer history is 8.2% in which male subjects are larger than females (5.8% vs 2.4%). A minimum-maximum age is 35-72 (37) and median 55. Smoker is only found in male 71% and the most type cancer cells is adenocarcinoma 71%. Family relation of the subjects found that 1 person is much more found than more 1 person (64.4% vs 35.6%) with dominated by father (25,8%). The type of cancer in the family is non lung cancer higher than lung cancer (85,4% vs 14,6%).Conclusions: The proportion of subjects with lung cancer in their family cancer is 8.2%. The most type family relation of the subjects is 1 person 64,4% with dominated by father 25,8%. The most type lung cancer cells which have family history cancer is adenocarcinoma 71%. The most type of cancer in the family is non lung cancer 64.4%.;Background: The new cases and mortality of lung cancer are increasing. Smoking tobacco have a role play but only 15% smokers are suffering from lung cancer. Therefore, genetic factors thought to play a role in lung cancer. Many studies show a significant association with the risk of lung cancer in the family history of cancer.Objective: To determine the proportion of lung cancer?s subjects with a cancer history in the family.Methods: Using cross-sectional a descriptive observational study with the outpatient and inpatient lung cancer?s subject at Persahabatan Hospital, Jakarta started from January 1st, 2013 until April 30th, 2015.Results: The total subject of the study are 380 with the composition of men higher than women (72.9% vs 27.1 %) with a median is 56 and a minimum-maximum age is 20-86 (66). From those subjects, 65.3% are smokers with the most moderate IB is 33.2%. The most type cancer cells in group of Non Small Cell Lung Cancer Carcinoma (NSCLCC) is adenocarcinoma (73.4%). Most subjects diagnosed at an advanced stage either in groups of NSCLCC or Small Cell Lung Cancer Carcinoma (SCLCC). The subject?s proportion with the family cancer history is 8.2% in which male subjects are larger than females (5.8% vs 2.4%). A minimum-maximum age is 35-72 (37) and median 55. Smoker is only found in male 71% and the most type cancer cells is adenocarcinoma 71%. Family relation of the subjects found that 1 person is much more found than more 1 person (64.4% vs 35.6%) with dominated by father (25,8%). The type of cancer in the family is non lung cancer higher than lung cancer (85,4% vs 14,6%).Conclusions: The proportion of subjects with lung cancer in their family cancer is 8.2%. The most type family relation of the subjects is 1 person 64,4% with dominated by father 25,8%. The most type lung cancer cells which have family history cancer is adenocarcinoma 71%. The most type of cancer in the family is non lung cancer 64.4%., Background: The new cases and mortality of lung cancer are increasing. Smoking tobacco have a role play but only 15% smokers are suffering from lung cancer. Therefore, genetic factors thought to play a role in lung cancer. Many studies show a significant association with the risk of lung cancer in the family history of cancer. Objective: To determine the proportion of lung cancer’s subjects with a cancer history in the family. Methods: Using cross-sectional a descriptive observational study with the outpatient and inpatient lung cancer’s subject at Persahabatan Hospital, Jakarta started from January 1st, 2013 until April 30th, 2015.Results: The total subject of the study are 380 with the composition of men higher than women (72.9% vs 27.1 %) with a median is 56 and a minimum-maximum age is 20-86 (66). From those subjects, 65.3% are smokers with the most moderate IB is 33.2%. The most type cancer cells in group of Non Small Cell Lung Cancer Carcinoma (NSCLCC) is adenocarcinoma (73.4%). Most subjects diagnosed at an advanced stage either in groups of NSCLCC or Small Cell Lung Cancer Carcinoma (SCLCC). The subject’s proportion with the family cancer history is 8.2% in which male subjects are larger than females (5.8% vs 2.4%). A minimum-maximum age is 35-72 (37) and median 55. Smoker is only found in male 71% and the most type cancer cells is adenocarcinoma 71%. Family relation of the subjects found that 1 person is much more found than more 1 person (64.4% vs 35.6%) with dominated by father (25,8%). The type of cancer in the family is non lung cancer higher than lung cancer (85,4% vs 14,6%).Conclusions: The proportion of subjects with lung cancer in their family cancer is 8.2%. The most type family relation of the subjects is 1 person 64,4% with dominated by father 25,8%. The most type lung cancer cells which have family history cancer is adenocarcinoma 71%. The most type of cancer in the family is non lung cancer 64.4%.]"

"ABSTRAK Tesis ini menilai efikasi dan toksisiti Erlotinib/Gefitinib sebagai terapi lini kedua pada pasien KPKBSK yang mengalami progresifitas. Ini adalah sebuah penelitiankohor retrospektif antara tahun 2009 sampai 2013 dari rekam medis pasienKPKBSK yang mengalami progresifitas. Respons (subjektif, semisubjektif danobjektif) dievaluasi setiap bulan. Toksisiti dinilai setiap minggu sejak pemberianErlotinib/Gefitinib berdasarkan kriteria WHO. Hasil evaluasi respons objektif,tidak ada pasien yang memberikan respons komplit. Best overall response ratedari 31 pasien, 48,8% menetap, 22,6% perburukan,12,9% respons sebagian dan6,5% tidak dinilai/inevaluable. Pada penilaian respons semisubjektif didapatkan19.4% peningkatan berat badan, 51,6% penurunan berat badan dan 29,0%menetap. Waktu tengah tahan hidup mencapai 18 bulan, rerata masa tahan hidup1 tahunan 80,6% dan masa tahan hidup keseluruhan 6,50%. Data menunjukkantidak ada timbul toksisiti hematologi berat (grade ¾) dan data penilaian toksisitinon hematologi sangat jarang timbul toksisiti berat (grade ¾). Efikasi monoterapiEGFR-TKI (Erlotinib/Gefitinib) cukup tinggi dengan toksisiti yang ditimbulkantidak berat. Dengan demikian Erlotinib/Gefitinib sebagai terapi lini kedua cukupbaik.ABSTRACT This thesis assesses the efficacy and toxicity of Erlotinib/Gefitinib as a second

line therapy in NSCLC patients. This is a retrospective cohort study between 2009

and 2013 from the medical records of patients who experienced progression

NSCLC. Therapeutic response was evaluated every month. Toxicity assessed

every month since giving Erlotinib/Gefitinib according to WHO?s criteria. Results

of objective response evaluation none of the patients complete response. Best

overall response rate of 31 patients with the most stable response are 48.8%. Most

semisubjective response obtained are 51.6% weight loss. The middle survival time

reached 18 month, the mean 1 year survival time are 80.6% and a 6.50% overall

survival. The data showed no hematologic toxicity arise severe (grade ¾) and

non-hematological toxicity very rarely arise severe toxicity. The efficacy of EGFR

TKI monotherapy (Erlotinib/Gefitinib) is high enough with toxicity cause not

severe. Thus Erlotinib/Gefitinib as second-line therapy is quite good. ;This thesis assesses the efficacy and toxicity of Erlotinib/Gefitinib as a second

line therapy in NSCLC patients. This is a retrospective cohort study between 2009

and 2013 from the medical records of patients who experienced progression

NSCLC. Therapeutic response was evaluated every month. Toxicity assessed

every month since giving Erlotinib/Gefitinib according to WHO?s criteria. Results

of objective response evaluation none of the patients complete response. Best

overall response rate of 31 patients with the most stable response are 48.8%. Most

semisubjective response obtained are 51.6% weight loss. The middle survival time

reached 18 month, the mean 1 year survival time are 80.6% and a 6.50% overall

survival. The data showed no hematologic toxicity arise severe (grade ¾) and

non-hematological toxicity very rarely arise severe toxicity. The efficacy of EGFR

TKI monotherapy (Erlotinib/Gefitinib) is high enough with toxicity cause not

severe. Thus Erlotinib/Gefitinib as second-line therapy is quite good. "