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"Latar Belakang: Kanker paru menjadi penyebab kematian utama akibat keganasan pada laki-laki sebesar 31% dan perempuan sebesar 27%. Pada pasien adenokarsinoma paru dengan mutasi pada exon 20 T790M memberikan respons yang buruk terhadap terapi EGFR-TKI generasi pertama maupun generasi kedua. Tujuan: Mengetahui profil serta angka tahan hidup 1 tahun pasien kanker paru jenis Adenokarsinoma dengan mutasi exon 20 T790M primer. Metode: Penelitian menggunakan desain kohort terhadap pasien-pasien adenokarsinoma paru stadium IV dengan mutasi exon 20 T790M primer dari bulan September 2015 sampai Desember 2017 di RSUP Persahabatan. Variabel yang diteliti adalah karakteristik klinis dan angka kesintasanberdasarkan kurva Kaplan Meier. Hasil analisis dinyatakan berbeda bermakna apabila nilai p<0,05. Hasil: Didapatkan 27 subjek penelitian dengan rerata usia 58,5 tahun dan berjenis kelamin laki-laki (70,6%). Keluhan utama berupa sesak napas (73,5%) dan nyeri dada (55,9%). Mutasi genetik tunggal pada Exon 20 T790M (64,7%), sedangkan mutasi Exon 20 T790M dengan Exon 21 L858R (11,8%) dan mutasi Exon 20 T790M dengan 21 L861Q (8,8%). Organ target metastasis adalah efusi pleura (73,5%), tulang (26,5%) dan otak (20,6%). Angka kesintasan 360 dan 990 hari sebesar 35% dan 20% dengan median kesintasan sebesar 213 hari. Kesimpulan: Mutasi exon 20 T790M pada adenokarsinoma paru memegang peranan penting terhadap kesintasan dan prediktor responsterhadap terapi yang diberikan.

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Background: Lung cancer causes mortality in men (31%) and in women (27%). Lung adenocarcinoma patients with exon 20 T790Mepidermal growth factor receptor(EGFR) mutation showed poor response to the first generation and second generation of EGFR tyrosine kinase inhibitor (TKI) therapy.

Purpose: This study aims to reveal the characteristics and one year survival rate of lung adenocarcinoma patients with primary exon 20 T790M EGFR mutations treated at Persahabatan Hospital Jakarta, Indonesia.

Methods: The cohort study involved patients with primary exon 20 T790M EGFR mutation between September 2015 to December 2017 in Persahabatan Hospital Jakarta, Indonesia. The survival rate was observed from Kaplan Meier estimator curve and was statistically analyzed.

Results: There were 27 subjects with mean age of 58.5 years and were predominated male (70.6%). The most common chief complaints were shortness of breath (73.5%) and chest pain (55.9%). The EGFR mutations detected were exon 20 T790M (64.7%), exon 20 T790M with exon 21 L858R (11.8%) and exon 20 T790M with exon 21 L861Q (8.8%). Metastatic target organs were pleural effusions (73.5%), bone (26.5%) and brain (20.6%). Survival rate of 360 and 990 days was 35% and 20% respectively with median survival rate was 213 days.

Conclusion: Exon 20 T790M EGFR mutation in lung adenocarcinoma was revealed to be an important factor in survival and in predicting response to EGFR TKI chemotherapy."

"Latar Belakang: Jumlah kasus KPKBSK diperkirakan 85% dari seluruh kasus kanker paru dan 40% diantaranya adalah jenis adenokarsinoma. Sebanyak 10%-30% pasien adenokarsinoma mengalami mutasi EGFR dan mendapatkan terapi EGFR-TKI. Mayoritas pasien KPKBSK memiliki respons dan toleransi baik terhadap terapi EGFR- TKI tetapi sebagian kecil pasien mengalami penyakit paru interstisial akibat EGFR- TKI. Penelitian ini bertujuan untuk mengetahui proporsi gambaran penyakit paru interstisial pada pasien KPKBSK dengan terapi EGFR-TKI di RSUP Persahabatan.Metode: Penelitian ini merupakan penelitian observasional analitik dengan pendeketan kohort retrospektif yang dilakukan bulan Januari 2021 hingga Juni 2022. Subjek penelitian adalah pasien KPKBSK yang mendapatkan terapi EGFR-TKI. Subjek penelitian dipilih sesuai kriteria inklusi dan eksklusi. Pengambilan data melalu data sekunder berupa rekam medis dan hasil CT scan toraks pasien yang kontrol di poliklinik onkologi RSUP Persahabatan.Hasil: Pada penelitian ini diperoleh 73 subjek penelitian, pasien KPKBSK dengan mutasi EGFR yang mendapatkan terapi EGFR-TKI di RSUP Persahabatan. Sebanyak 12 dari 73 subjek penelitian mengalami gambaran ILD yang dievaluasi berdasarkan CT scan toraks RECIST I dan II dengan karakteristik jenis kelamin laki-laki (22,2%), kelompok usia 40-59 tahun (19,4%), perokok (24,1%), indeks brinkman berat (42,9%) dan mendapatkan terapi afatinib (26,1%). Proporsi gambaran ILD pada pasien KBPKBSK dengan terapi EGFR-TKI adalah opasitas retikular (58,3%), parenchymal band (33,3%), ground-glass opacities (25%), traction bronchiectasis (25%) dan crazy paving pattern (8,3%). Hasil analisis bivariat dan multivariat menunjukkan tidak terdapat perbedaan antara faktor-faktor seperti jenis kelamin, usia, jenis EGFR-TKI, riwayat merokok, indeks brinkman, riwayat penyakit paru dan tampilan status terhadap gambaran ILD.Kesimpulan: Gambaran ILD pada pasien KPKBSK dengan terapi EGFR-TKI meliputi opasitas retikular, parenchymal band, ground-glass opacities, traction bronchiectasis dan crazy paving pattern. Tidak terdapat perbedaan bermakna secara statistik antara faktor-faktor yang memengaruhi terhadap gambaran ILD.

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Background: The number of cases of NSCLC is estimated around 85% of all lung cancer cases and 40% among them are adenocarcinoma. Approximately 10%-30% of adenocarcinoma patients have EGFR mutations and receive EGFR-TKI therapy. The majority of NSCLC patients have a good response and tolerance to EGFR-TKI therapy, but a small group of patients experience EGFR-TKI induced interstitial lung disease. This study aims to determine the proportion of features of interstitial lung disease ini NSCLC patients treated with EGFR-TKI at Persahabatan Hospital.

Methods: This study was an analytic observational with a retrospective cohort approach that was conducted from January 2021 until June 2022. The subject were NSCLC patients who received EGFR-TKI treatment. The inclusion and exclusion criteria were used to determine which subjects will be included in the study. Data collection through secondary data from medical record and chest CT scan results of patients controlled at oncology polyclinic at Persahabatan Hospital.

Result : In this study, there were 73 subjects of NSCLC with EGFR mutations and received EGFR-TKI therapy at Persahabatan Hospital. There were 12 out of 73 subjects had ILD features which were evaluated based on RECIST I and II chest CT scan with predominant of male (22.2%), age group 40-59 years old (19.4%), smokers (24.1%), severe Brinkman index (42.9%) and received afatinib (26.1%). The proportion of ILD features in NSCLC patients with EGFR-TKI therapy are reticular opacities (58.3%), parenchymal bands (33.3%), ground-glass opacities (25%), traction bronchiectasis (25%) and crazy paving pattern (8.3%). The results of bivariate and multivariate analyzes showed that there was no differences between factors such as sex, age, type of GEFR-TKI, smoking history, Brinkman index, history of lung disease and performance status with features of ILD.

Conclusion: Features of ILD in NSCLC patients with EGFR-TKI therapy include reticular opacities, parenchymal bands, ground-glass opacities, traction bronchiectasis and crazy paving pattern. There is no statistically significa"

"Latar belakang: Terapi target dengan EGFR TKI merupakan terapi utama untuk kanker paru, khususnya KPKBSK. Selain permasalahan efektivitas harga, permasalahan lain terkait penggunaan EGFR TKI adalah resistansi primer dan sekunder seperti T790M, C797S dan insersi ekson 20. Penelitian in silico QSAR berbasis machine learning dan molecular docking dapat mempercepat penemuan senyawa EGFR TKI baru berbasis senyawa fitokimia.Metode: Penelitian ini adalah penelitian in silico untuk mengembangkan model QSAR berbasis machine learning yang dilanjutkan dengan molecular docking untuk penapisan senyawa fitokimia yang memiliki efek EGFR TKI terhadap mutasi T790M, C797S dan insersi ekson 20. Model machine learning dibuat untuk memprediksi nilai IC50 berdasarkan struktur kimia senyawa. Data pembelajaran berasal dari pangkalan data ChEMBL, data senyawa fitokimia dari KEGG, dan data makromolekul dari RCSB PDB. Simulasi molecular dynamics dilakukan untuk memvalidasi lebih lanjut hasil molecular docking.Hasil: Didapatkan 8627 senyawa EGFR TKI dari ChEMBL, yang dibagi menjadi set pembelajaran dan set uji dengan rasio 9:1. Model machine learning dengan algoritma LGBM berhasil dikembangkan dengan nilai R2 sebesar 73%. Lima senyawa fitokimia dengan nilai IC50 prediksi terbaik adalah orobol, norswertianin, isokaempferide, isoathyriol, dan norathyriol. Kelima senyawa memiliki profil farmakokinetik dan toksikologi yang cukupbaik. Hasil molecular docking menunjukkan norswertianin memiliki kemampuan ikatan terbaik terhadap EGFR mutasi T790M dan T790M/C797S/L858R, sedangkan orobol terhadap mutasi T790M/C797S dan insersi ekson 20. Kedua senyawa dapat membentuk ikatan yang stabil pada simulasi molecular dynamics.Kesimpulan: Model QSAR berbasis machine learning dengan algoritma LGBM dapat digunakan untuk memprediksi nilai IC50 EGFR TKI senyawa berdasarkan struktur kimianya. Senyawa fitokimia dapat digunakan sebagai dasar pengembangan EGFR TKI baru. Senyawa norswertianin dan orobol memiliki potensi terbesar sebagai EGFR TKI yang efektif untuk mutasi T790M, C797S dan insersi ekson 20.

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Background: Targeted therapy with EGFR TKI has been the mainstay of lung cancer treatment, especially NSCLC. Besides the poor cost-effectiveness, primary and secondary resistances, such as T790M, C797S, and exon 20 insertion mutation, have been problematic in EGFR TKI clinical utilization. In silico research, such as machine learning-based QSAR dan molecular docking, has the potential to hasten the discovery of novel EGFR TKI based on phytochemicals.

Method: This study is an in silico research to develop a machine learning-based QSAR model, followed by molecular docking experiments for virtual screening of phytochemicals that have bioactivity as EGFR TKI against T790M, C797S, and exon 20 insertion mutation. A machine learning model will be developed to predict IC50 based on chemical structure. The learning set is sourced from the ChEMBL database, phytochemical data from KEGG, and macromolecule data from RCSB PDB. Molecular dynamic simulation is carried out to validate the molecular docking result further.

Results: A total of 8627 compounds was procured from ChEMBL database, which was split into training and test sets with a ratio of 9:1. LGBM based machine learning model with considerable accuracy can be developed, with R2 of 73%. The five compounds with the best predicted IC50 value was orobol norswertianin, isokaempferide, isoathyriol, and norathyriol. All compounds possess a good pharmacokinetics and toxicology profile. The molecular docking result showed that norswertianin has the best binding affinity against EGFR with T790M and T790M/C797S/L8568R. Orobol has the best binding affinity against EGFR with T790M/C797S and exon 20 insertion. Both compounds can form a stable binding in molecular dynamics simulation.

Conclusions: Machine learning-based QSAR model utilizing the LGBM algorithm can predict IC50 value as EGFR TKI based on the compound’s chemical structure. Phytochemicals can be used as the basis for novel EGFR TKI. Norswertianin and orobol have the best EGFR TKI potential against T790M, C797S, and exon 20 insertion mutations."

"World Health Organization (WHO) menyebutkan bahwa kanker paru telah menjadi satu diantara penyebab kematian utama di seluruh dunia. Prognosis kanker paru merupakan yang paling buruk diantara jenis kanker lainnya. Studi ini bertujuan untuk mengetahui perbandingan kesintasan dan risiko kematian pada pasien Kanker Paru Karsinoma Sel Kecil (KPKSK) dan Kanker Paru Karsinoma Bukan Sel Kecil (KPKBSK) di Rumah Sakit Umum Pusat Persahabatan sejak Januari 2021 hingga Desember 2023 dan di foloow-up hingga September 2024 menggunakan desain kohort retrospektif. Variable yang di analisis pada penelitian ini meliputi jenis histologi, usia, jenis kelamin, ras/suku, status pekerjaan, status perkawinan, Tingkat Pendidikan, derajat merokok, jenis pasien, performance status, lateralitas tumor, clinical stage dan penatalaksanaan. Dari 938 pasien kanker paru yang dianalisis, 6.29% adalah KPKSK dan sisanya 93.71% adalah KPKBSK. Dengan median overall survival (OS) pada KPKSK adalah 142 hari dan pada KPKBSK adalh 298 hari setelah terdiagnosa selama tiga tahun pengamatan. Pada final model dikatuhi bahwa usia, derajat merokok, performance statusserta tatalaksana bermakna secara statistic terhadap risiko kematian pada pasien kanker paru setelah dikontrol variable confounding (p<0.05). Terdapat interaksi antara usia ≥60 dan jenis histologi KPKBSK yang bermakna secara statistic terhadap penurunan risiko kematian sebesar 59% setelah dikontrol oleh variable confounding (aHR 0.41 95% CI 0.26 – 0.66 p=0.000) dibandingkan dengan pasien KPKSK. Hasil penelitian ini diharapkan dapat memberikan informasi untuk klinisi dan menjadi referensi penelitian selanjutnya.

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According to the World Health Organization (WHO), lung cancer is one of the leading causes of death worldwide. The prognosis of lung cancer is the worst among other cancers. This study aims to compare survival and risk of death in patients with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) at Persahabatan General Hospital from January 2021 to December 2023 and follow-up until September 2024 using a retrospective cohort design. The variables analysed in this study included histology type, age, gender, race/ethnicity, employment status, marital status, education level, smoking status, patient type, performance status, tumour laterality, clinical stage and treatment. Of the 938 lung cancer patients analysed, 6.29% had SCLC and the remaining 93.71% had NSCLC. The median overall survival (OS) in SCLC is 142 days and in NSCLC is 298 days after diagnosed during three years of observation. In the final model, it was found that age, smoking level, performance status and treatment were statistically significant on the risk of death in lung cancer patients after controlling for confounding variables (p <0.05). There was an interaction between age ≥60 and histology type of NSCLC which was statistically significant on decrease the risk of death by 59% after controlling for confounding variables (aHR 0.41 95% CI 0.26 - 0.66 p = 0.000) compared to SCLC patients. The results of this study are expected to inform clinicians and provide a reference for further research."

"[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: Kanker paru menduduki peringkat ketiga sebagai penyebab kematian utama akibat keganasan di Indonesia, 85% di antaranya adalah kanker paru karsinoma bukan sel kecil (KPKBSK). Pasien kanker paru rentan terhadap infeksi oportunistik, termasuk kriptokokosis, yaitu infeksi jamur Cryptococcus. Penelitian tentang data klinis dan keberadaan Cryptococcus pada pasien KPKBSK di Indonesia masih terbatas. Salah satu metode untuk mendeteksi keberadaan Cryptococcus adalah pemeriksaan serologi Lateral Flow Assay (LFA). Tujuan: Penelitian ini bertujuan untuk mengetahui profil klinis pasien KPKBSK dan kaitannya dengan hasil pemeriksaan LFA Cryptococcus di RSUP Persahabatan. Metode: Penelitian dengan disain potong lintang ini dilakukan pada pasien KPKBSK yang belum dikemoterapi di RSUP Persahabatan yang memenuhi kriteria inklusi. Data klinis pasien diperoleh dari anamnesis dan pemeriksaan fisik yang diambil dari rekam medis, selanjutnya dilakukan pemeriksaan LFA Cryptococcus di laboratorium Parasitologi FKUI. Hasil: Dari 77 subjek yang memenuhi kriteri inklusi, terdapat 48 (62,3%) pasien laki-laki, dengan rerata usia 59,4 tahun. Data klinis lain menunjukkan IMT 18,5-22,9 kg/m2 (53,2%), status tampilan 1 (42,9%), perokok aktif (61,0%), Indeks Brinkman ringan (42,9%), adenokarsinoma (75,3%), stadium IIIB-IV (79,2%). Riwayat komorbid yang ditemukan adalah TB (13,0%), asma/PPOK (1,3%), DM (16,9%), dan penyakit lainnya (31,2%). Proporsi hasil pemeriksaan LFA Cryptococcus positif adalah 11,7%. Tidak ditemukan hubungan bermakna antara profil klinis dengan keberadaan Cryptococcus pada pasien KPKBSK. Simpulan: Proporsi keberadaan Cryptococcus pada pasien KPKBSK yang belum dikemoterapi adalah 11,7%. Profil klinis terbanyak berupa IMT 18,5-22,9 kg/m2, status tampilan 1, perokok aktif, Indeks Brinkman ringan, jenis keganasan adenokarsinoma, dan stadium IIIB-IV. Riwayat komorbid meliputi TB, asma/PPOK, DM, dan penyakit lain. Tidak ditemukan hubungan antara profil klinis dengan keberadaan Cryptococcus pada subjek penelitian.

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Background: Lung cancer is the third of leading cause of death due to malignancy in Indonesia. Eighty-five percent of them were non-small cell lung cancer (NSCLC). Lung cancer patients are prone to have the opportunistic infections, such as cryptococcosis. However, the clinical data on the exictance of Cryptococcus in NSCLC patients in Indonesia are scarce. One of the methods to detect Cryptococcus in those patients is the Lateral Flow Assay (LFA) serology test.

Aim: The study aimed to determine the association between the clinical profile of NSCLC patients with the Cryptococcal LFA test results at Persahabatan Hospital, Jakarta.

Methods: This cross-sectional study was conducted on naïve NSCLC patients at Persahabatan Hospital Jakarta, who met the inclusion criteria. The clinical data were obtained from history taking and physical examination from the medical records. Furthermore, the Cryptococcal LFA serology test was conducted at laboratory of Parasitology Department, Faculty of Medicine Universitas Indonesia.

Results: Of the 77 subjects, there were 48 male patients (62.3%), and the mean age was 59.4 years old. The most common clinical profile of NSCLC patients were BMI of 18.5-22.9 kg/m2 (53.2%), performance status 1 (42.9%), active smokers (61.0%), mild Brinkman Index (42.9%), adenocarcinoma (75.3%), and cancer stage of IIIB-IV (79.2%). The comorbidities of those patients were TB (13.0%), asthma/COPD (1.3%), DM (16.9%), and other diseases (31.2%). The proportion of positive Cryptococcal LFA test results was 11.7%. There was no significant association between the clinical profiles and the presence of Cryptococcus.

Conclusion: The proportion of the Cryptococcus existance in naïve NSCLC patients was 11.7%. The most common clinical profiles were BMI of 18.5-22.9 kg/m2, performance status 1, active smokers, mild Brinkman Index, adenocarcinoma histology type, and lung cancer stage at IIIB-IV. The comorbidities of those patients were TB, asthma/COPD, DM, and other diseases. No association was found between the clinical profile of those patients and the presence of Cryptococcus."

"Pendahuluan: Saat ini, rejimen kemoterapi berbasis platinum dengan dua jenis obat seperti paklitaksel-karboplatin dan pemetreksat-karboplatin merupakan terapi lini pertama pasien adenokarsinoma paru dengan mutasi epidermal growth factor receptor (EGFR) negatif. Di rumah sakit Persahabatan, kedua rejimen tersebut banyak digunakan dan dijamin pembiayaannya oleh Badan Penyelenggara Jaminan Sosial Kesehatan (BPJS). Dengan harga pemetreksat yang lebih mahal dan efektivitas yang belum diketahui, perlu dilakukan suatu kajian farmakoekonomi. Studi ini bertujuan untuk mengetahui profil efikasi, toksisitas, dan biaya paklitaksel-karboplatin dibandingkan pemetreksat-karboplatin.Metode: penelitian ini merupakan studi potong lintang, menggunakan data rekam medis. Pasien adenokarsinoma paru mutasi EGFR negatif yang pertama kali didiagnosa dan diterapi dengan paklitaksel-karboplatin atau pemetreksat-karboplatin dimasukkan ke dalam kriteria inklusi. Analisis farmakoekonomi dilakukan berdasarkan keluaran klinis yang terdiri dari efektivitas dan biaya medis langsung. Efektivitas dinilai berdasarkan overall response rate (ORR).Hasil: Rekam medis dari 21 pasien paklitaksel-karboplatin dan 21 pasien pemetreksat-karboplatin berhasil dievaluasi. Efektivitas kedua rejimen kemoterapi secara statistik tidak berbeda bermakna yang dilihat dari ORR (P=0,739). Toksisitas hematologi yang sering dialami oleh kedua kelompok adalah anemia, neutropenia, leukopenia derajat 1-2. Anemia, leukopenia, dan neutropenia derajat 3 lebih sering terjadi pada kelompok paklitaksel-karboplatin. Toksisitas nonhematologi kedua kelompok adalah mual muntah, rambut rontok, dengan neuropati perifer lebih banyak dialami kelompok paklitaksel-karboplatin. Melihat hal tersebut, pasien pada kelompok pemetreksat-karboplatin mengalami toksisitas lebih sedikit dibandingkan kelompok paklitaksel-karboplatin. Dari perhitungan analisis minimalisasi biaya diperoleh hasil bahwa biaya rerata per pasien dengan rejimen paklitaksel-karboplatin lebih murah Rp. 10.986.257,55 atau 50,25%, dibandingkan pemetreksat-karboplatin.Kesimpulan: tidak ada perbedaan efektivitas antara kedua rejimen. Biaya rerata per pasien dengan rejimen paklitaksel-karboplatin lebih murah dibandingkan pemetreksat-karboplatin. Diperlukan penelitian prospektif dengan jumlah subjek yang lebih besar dan melibatkan banyak rumah sakit.

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Background: At present, platinum-based chemotherapy regimens with two types of drugs such as paclitaxel-carboplatin and pemetrexed-carboplatin are first-line therapy for pulmonary adenocarcinoma patients with negative epidermal growth factor receptor (EGFR) mutations. At Persahabatan Hospital, the two regimens are widely used and guaranteed by National Health Insurance. With the price of pemetrexed which is more expensive and the effectiveness is unknown, it is necessary to do a pharmacoeconomic study. This study aimed to determine the efficacy, toxicity, and cost profile of paclitaxel-carboplatin compared to pemetrexed-carboplatin.

Methods: This s is a cross-sectional study, using medical record data. Patients with pulmonary adenocarcinoma negative EGFR mutations first diagnosed and treated with paclitaxel-carboplatin or pemetrexed-carboplatin were included. A pharmacoeconomic analysis is performed on the basis of clinical outcomes consisting of effectiveness and direct medical costs. Effectiveness was assessed based on the overall response rate (ORR).

Results: Medical records from 21 patients with paclitaxel-carboplatin and 21 patients with pemetrexed-carboplatin were successfully evaluated. The effectiveness of the two chemotherapy regimens was not significantly different, which was seen from the ORR (P = 0.739). The most common hematologic toxicity experienced of the two groups are anemia, neutropenia, leukopenia grade 1-2. Anemia, leukopenia and neutropenia grade 3 are more common in paclitaxel-carboplatin group. The nonhematological toxicity of the two groups was nausea vomitus, hair loss, with peripheral neuropathy more experienced by paclitaxel-carboplatin group. Seeing this, patients in pemetreksat-carboplatin group experienced less toxicity compared to paclitaxel-carboplatin group. From the calculation of cost minimization analysis the results showed that the average cost per patient with pulmonary adenocarcinoma negative EGFR mutation with paclitaxel-carboplatin regimen was cheaper Rp. 10.986.257,55 or 50,25%, compared to pemetrexed-carboplatin.

Conclusion: there was no difference in effectiveness between the two regimens. The average cost per patient with paclitaxel-carboplatin regimen was cheaper compared to pemetrexed-carboplatin. A prospective study is required with a larger number of study subjects and involves many hospitals."

"Kanker paru-paru merupakan jenis kanker yang paling banyak diderita dan paling mematikan di dunia. Tipe kanker paru-paru paling banyak diderita merupakan kanker paru-paru non-sel-kecil (NSCLC). Senyawa flavonoid digunakan sebagai inhibitor protein reseptor faktor pertumbuhan epidermal (EGFR) dalam penelitian ini karena memiliki kemampuan bioaktivitas dan bioavailabilitas yang berpotensi sebagai obat antikanker. Penelitian ini menggunakan pendekatan in silico untuk menemukan senyawa flavonoid yang dapat menghambat protein reseptor EGFR secara efektif untuk dijadikan kandidat obat melalui desain obat berbasis fragmen. Beberapa metode komputasi yang digunakan adalah metode Protein-Ligand Interaction Fingerprint (PLIF), penentuan titik farmakofor, simulasi penambatan molekul, serta uji farmakologi dan toksisitas. Setelah dilakukan screening secara virtual melalui penambatan dengan protein EGFR (PDB. 1M17) menggunakan data flavonoid berasal dari basis data pubchem yang berjumlah 25.189 didapat dua fragmen terbaik yang memiliki tiga ikatan hidrogen untuk dilakukan fragment growing dan dari penambatan molekul senyawa hasil fragment growing yang berjumlah 25.600 diperoleh sepuluh senyawa terbaik, dengan parameter ΔGbinding lebih kecil dibanding standar erlotinib yaitu -8,8536 dan nilai RMSD lebih kecil dari 2,0 Å. Ligan tersebut diuji farmakologi dan prediksi toksisitas diperoleh dua senyawa sebagai kandidat inhibitor EGFR yaitu compound 980 dan compound 760 yang memiliki inhibisi CYP yang lebih sedikit dibanding standar dan tidak bersifat toksik untuk organ hati. Berdasarkan hasil tersebut maka compound 980 dan compound 760 dapat menjadi inhibitor EGFR yang potensial.

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Lung cancer is the most suffered and deadly type of cancer in the world. The most common type of lung cancer is non-small cell lung cancer (NSCLC). Flavonoid compounds are used as epidermal growth factor receptor (EGFR) protein inhibitors in this study because they have the potential for bioactivity and bioavailability as anticancer drugs. This study uses an in silico approach to find flavonoid compounds that can effectively inhibit EGFR receptor proteins to be drug candidates through fragment-based drug design. Some computational methods used are the Protein-Ligand Interaction Fingerprint (PLIF) method, pharmacophore point determination, molecular tethering simulation, and pharmacology and toxicity tests. After a virtual screening with EGFR protein (PDB. 1M17) used flavonoid data from the pubchem database with totat number 25,189 is obtained the two best fragments that have three hydrogen bonds to do fragment growing and from molecular docking simulation of compound molecules from fragment growing totaling 25,600 is obtained the ten best compounds, with the parameter ΔGbinding smaller than the erlotinib standard which is -8.8536 and an RMSD value smaller than 2.0 Å. The ligand was tested pharmacologically and the the toxicity was predicted is obtained two compounds as EGFR inhibitor candidates namely compound 980 and compound 760, which had less CYP inhibition than standard and were not toxic to liver. Based on these results, compound 980 and compound 760 can be potential EGFR inhibitors.

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"Latar Belakang : Pasien kanker paru rentan terhadap infeksi jamur. Candida dan Aspergillus merupakan jenis jamur paling banyak yang menyebabkan infeksi jamur pada pasien kanker. Penelitian ini bertujuan untuk mengetahui profil klinis, spektrum jamur dan imunoglobulin G spesifik Aspergillus pada pasien kanker paru yang belum dikemoterapi di RSUP Persahabatan.Metode : Penelitian ini berdesain potong lintang. Subjek penelitian adalah pasien KPKBSK yang sudah tegak jenis dan belum dikemoterapi yang berobat di RSUP Persahabatan. Dahak dan serum diperiksakan biakan jamur dan IgG spesifik Aspergillus di Departemen Parasitologi Fakultas Kedokteran Universitas Indonesia. Hasil biakan jamur dan IgG spesifif Aspergillus dianalisis untuk mengetahui hubungannya dengan demografi.Hasil : Subjek penelitian sebanyak 77 pasien. Hasil biakan dahak yang tumbuh jamur sebanyak 76 subjek (98,7%). Jumlah isolat jamur yang tumbuh ≥ dua spesies sebanyak 35 pasien (45,5%). Isolat jamur yang paling banyak tumbuh adalah Candida albicans (72,3%) dan Aspergillus niger (33,8%). Hasil IgG spesifik Aspergillus pada subjek penelitian yang positif sebanyak 22,1%. Terdapat hubungan bermakna antara umur dan leukosit dengan IgG spesifik Aspergillus dan antara umur dan jenis kelamin dengan biakan Aspergillus.Kesimpulan : Isolat jamur yang ditemukan di antaranya adalah Candida albicans, Aspergillus niger, Aspergillus flavus, Aspergillus fumigatus, Penicillium spp. Candida glabrata, Candida paraspillosis, Candida tropicalis dan Candida kruseii. Terdapat hasil IgG spesifik Aspergillus positif pada subjek penelitian sebanyak 22,1%. Umur dan nilai leukosit berhubungan dengan IgG spesifik Aspergillus dengan nilai (p = 0,048) dan (p = 0,014), sedangkan umur dan jenis kelamin berhubungan dengan biakan Aspergillus dengan nilai (p = 0,027) dan (p = 0,035).

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Background: Lung cancer patients are prone to fungal infections. Candida and Aspergillus are the most common cause of fungal infections in cancer patients. This study aimed to determine the clinical profile, fungal detection spectrum and level of Aspergillus specific immunoglobulin-G (igG) of new lung cancer patients prior to chemotherapy at Persahabatan Hospital.

Methods: We performed a cross-sectional study, involving NSCLC patients in Persahabatan Hospital whose type of cancer had been established and had not received chemotherapy as subjects. Sputum and serum of the patients was examined for fungus and Aspergillus specific IgG cultures in the Department of Parasitology Faculty of Medicine, Universitas Indonesia. The results of Aspergillus specific fungi and IgG were analyzed to determine their relationship with demographics.

Results: The study included 77 patients as subjects. Sputum culture detected fungi growth in 76 subjects (98.7%). Fungal isolates that grew ≥ 2 species were present in 35 patients (45.5%). Candida albicans (72.3%) and Aspergillus niger (33.8%) were found from the cultures. Positive Aspergillus specific IgG was present in 22.1% of the subjects. There was a significant relationship between age, leukocytes concentration, and level of Aspergillus specific IgG and between age, sex and Aspergillus culture.

Conclusion: The fungi isolates in this study were Candida albicans, Aspergillus niger, Aspergillus flavus, Aspergillus fumigatus, Penicillium spp. Candida glabrata, Candida paraspillosis, Candida tropicalis and Candida kruseii. Aspergillus specific IgG results were positive in 22.1% of subjects. Age and leukocyte value are associated with Aspergillus specific IgG with (p=0.048) and (p=0.014), and age and sex are associated with Aspergillus culture with (p=0.027) and (p=0.035)."

"Latar Belakang: Mutasi Epidermal Growth Factor Receptor (EGFR) merupakan prediktor keberhasilan terapi TKI pada non-small cell lung cancer (NSCLC). Ras Asia, perempuan, bukan perokok, tipe histologis adenokarsinoma adalah karakteristik klinikopatologis yang diketahui memiliki asosiasi dengan mutasi EGFR pada NSCLC. Di Indonesia belum pernah dilakukan penelitian yang membuktikan asosiasi tersebut di tengah keterbatasan sumber daya dan fasilitas pemeriksaan biomolekuler untuk medeteksi mutasi EGFR.Metode: Desain studi adalah potong lintang. Subjek dikumpulkan secara konsekutif dari pasien adenokarsinoma paru stadium lanjut Rumah Sakit Umum Pusat Nasional Cipto Mangunkusumo dan Rumah Sakit Dharmais Pusat Kanker Nasional yang memeriksakan status mutasi EGFR di Laboratorium Kalbe Genomics dalam kurun waktu Januari 2010 hingga Desember 2013. Dari rekam medis pasien ditelusuri data umur, jenis kelamin, status merokok, diagnosis dan status mutasi EGFR. Uji chi-square dilanjutkan regresi logistik digunakan untuk menilai asosiasi jenis kelamin dan status merokok terhadap status mutasi EGFR.Hasil: Studi melibatkan 51 subjek dan didapatkan proporsi mutasi EGFR sebesar 47,1% (IK 95% = 33,4% – 60,8%). Uji bivariat menunjukkan perempuan (RO=4,80; IK 95%=1,12-20,61) dan bukan perokok (RO=4,00; IK 95%=1,23-13,06) memiliki asosiasi dengan mutasi EGFR, namun pada uji multivariat hanya status bukan perokok yang masih bermakna (RO=4,00; IK 95%=1,22-13,06).Simpulan: Proporsi mutasi EGFR pada kelompok pasien adenokarsinoma paru stadium lanjut 47,1%. Hanya status bukan perokok yang memiliki asosiasi independen dengan mutasi EGFR.

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Background: Epidermal Growth Factor Receptor (EGFR) mutation is predictor for successful TKI therapy in non-small cell lung cancer (NSCLC) patient. Asian, women, non-smoker, and histology of adenocarcinoma are the clinicopathological characteristics associated with EGFR mutation in NSCLC patient. In Indonesia, no research has been performed to confirm association between those characteristics while the resources and facilities to detect EGFR mutation are lacking.

Method: A cross sectional study was performed in Cipto Mangunkusumo National Referral Hospital and Dharmais Hospital National Cancer Center from January 2010 to December 2013. Subjects were collected consecutively from advanced lung adenocarcinoma patients who underwent examination for EGFR mutation in Kalbe Genomics Laboratory during study period. From medical records, information about age, gender, smoking status, diagnosis, and EGFR mutation status were collected. Chi square and logistic regression analysis were performed to assess association between variables.

Results: From 51 subjects participated in this study, proportion of EGFR mutation was 47.1% (CI 95% = 33,4% – 60,8%). Bivariate analysis revealed that women (OR=4,80; CI 95%=1,12-20,61) and non-smoker (OR=4,00; CI 95%=1,23-13,06) were associated with EGFR mutation. While in multivariate analysis, non-smoker status was the only significant clinical factor associated with EGFR mutation (OR=4.00; CI 95%=1.22-13.06).

Conclusion: Proportion of EGFR mutation in advanced lung adenocarcinoma patients is 47,1%. Non-smoker status is the only clinical factor associated with EGFR mutation."