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Marscha Iradyta Ais

Proporsi gambaran penyakit paru interstisial pada pasien kanker paru karsinoma bukan sel kecil dengan terapi epidermal growth factor receptor tyrosine kinase inhibitor di RSUP Persahabatan = The proportion of interstial lung disease features in patients with non small cell lung cancer treated with epidermal growth factor receptors tyrosine kinase inhibitor at Persahabatan Hospital

"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.

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"

Jakarta: Fakultas Kedokteran Universitas Indonesia, 2023

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UI - Tugas Akhir Universitas Indonesia Library

Kasum Supriadi

Angka tahan hidup pasien kanker paru kelompok bukan sel kecil non skuamosa yang mendapat terapi target Epidermal Growth Factor Receptor-Tyrosin Kinase Inhibitor dan yang mendapat kemoterapi lini pertama di Rumah Sakit Persahabatan = The survival rate of non squamous by non small cell lung carcinoma patiens who are given by target therapy Epidermal Growth Facttor Receptor-Tyrosin Kinase Inhibitors and those given by first line kemotheraphy treatment at Persahabatan Hospital

"[ABSTRAK

Pendahuluan. 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.

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.

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.

Jakarta: Fakultas Kedokteran Universitas Indonesia, 2014

T58765

UI - Tesis Membership Universitas Indonesia Library

Moulid Hidayat

Peran Quiescent Lung Cancer Stem Cell (CSC) dalam Prosesresistans terhadap Agen Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) pada Adenokarsinoma Paru dengan Mutasi EGFR Positif = Role of Quiescent Lung Cancer Stem Cells in Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR- TKI) Resistance in EGFR-Mutant Lung Adenocarcinoma

"Latar Belakang: Beberapa bukti menunjukkan bahwa quiescent cancer stem cell (CSC) terlibat dalam resistans terhadap gefitinib pada adenokarsinoma paru sebagai mekanisme nonmutasi. Kami sebelumnya telah mempublikasikan bahwa gefitinib- resistant persister (GRP) mengekspresikan stemness factor dengan level yang tinggi dan memiliki ciri khas fenotip CSC. Studi terbaru menunjukkan bahwa FBXW7, merupakan jenis protein F-box, memainkan peran penting dalam pemeliharaan quiescent CSC dengan memediasi degradasi protein c-MYC melalui proses ubiquination. Tujuan dari penelitian ini adalah untuk mengetahui peran FBXW7 dalam resistans terhadap gefitinib pada adenokarsinoma paru dengan mutasi EGFR.

Metode: Cell line dari sel adenokarsinoma paru, PC9, yang mengandung mutasi sensitif EGFR dipajankan pada gefitinib dengan konsentrasi tinggi untuk mengembangkan GRP. Kami mencoba melakukan abrogasi ekspresi gen FBXW7, dan mengevaluasi sensitivitasnya terhadap gefitinib dan populasi CD133-positive stem cell di GRP. Kami juga memasukkan plasmid FUCCI melalui proses infeksi lentiviral ke dalam sel dan kemudian menyelidiki siklus sel dan sel pada fase G0 dalam GRP. Selanjutnya, kami telah mengembangkan model gefitinib-resistant tumor (GRT) dengan menyuntikkan sel PC9 ke dalam mencit NOG diikuti dengan pemberian gefitinib setelah pertumbuhan tumor, dan mengevaluasi ekspresi mRNA dan ekspresi protein dari penanda terkait quiescence, FBXW7 in vivo.

Hasil: GRP menunjukkan ekspresi yang tinggi dari penanda cancer stem cell, CD133 dan penanda terkait quiescence, FBXW7 dan ekspresi c-MYC yang rendah pada tingkat protein secara in vitro. Analisis siklus sel menunjukkan bahwa mayoritas GRP berada pada fase G0/G1. TIndakan abrogasi gen FBXW7 menurunkan populasi sel CD133-positive di GRPs. Abrogasi FBXW7 juga meningkatkan kerentanan sel terhadap gefitinib, membalikkan populasi sel fase G0/G1 menjadi sel S/G2/M, dan menurunkan jumlah sel GRP. Secara in vivo, pada GRT setelah pengobatan gefitinib menunjukkan ekspresi FBXW7 yang tinggi dan ekspresi c-MYC yang rendah. Kami juga menemukan bahwa ekspresi FBXW7 dalam sel CD133-positive meningkat dan ekspresi c-MYC menurun pada mencit dan pada 9 dari 14 spesimen tumor dari pasien adenokarsinoma paru dengan mutasi EGFR resistan terhadap gefitinib.

Kesimpulan: Temuan ini menunjukkan bahwa FBXW7 dapat memainkan peran penting dalam pemeliharaan quiescence pada gefitinib-resistant lung CSC pada adenokarsinoma paru dengan mutasi positif EGFR

Background: Accumulating evidence indicates that quiescent cancer stem cells (CSCs) are involved in the resistance to gefitinib in non-small cell lung cancer (NSCLC) as non-mutational mechanism. We have previously reported that gefitinib-resistant persisters (GRPs) highly expressed stemness factors and had characteristic features of the CSCs phenotype. Recent studies demonstrate that FBXW7, a type of F-box protein, plays an important role in the maintenance of quiescent CSC by mediating the degradation of c-MYC protein by ubiquination. The aim of this study is to figure out the role of FBXW7 in the resistance to gefitinib in lung adenocarcinoma with EGFR mutation.
Methods: lung adenocarcnoma cell lines, PC9, harboring sensitive-EGFR mutation were exposed to high concentration of gefitinib in order to develop GRPs. We tried to knockdown FBXW7 gene expression, and evaluated their sensitivity to gefitinib and CD133-positive stem cell population in GRPs. We also introduced FUCCI plasmid via lentiviral infection in the cells and then investigated the cell cycle and G0-phase cells in GRPs. Furthermore, we established gefitinib-resistant tumor (GRT) model by injecting PC9 cells into NOG-mice followed by gefitinib administration after tumor growth, and evaluated mRNA and protein expression of quiescence-related markers including FBXW7 in vivo.
Results: In vitro, GRPs showed high expression of stem cell marker CD133 and quiescence-related markers including FBXW7 and low expression of c-MYC at protein level. Cell cycle analysis revealed that majority of GRPs existed in G0/G1 phase. Silencing of FBXW7 gene reduced CD133-positive cell population in GRPs. Knockdown of FBXW7 also increased susceptibility of cells to gefitinib, reversed population of G0/G1 cells to G2/S/M cells, and decreased cell number of GRPs. In vivo, GRTs after gefitinib treatment revealed high expression of FBXW7 and low expression of c-MYC. We also found that FBXW7 expression in CD133-positive cells was increased and c-MYC expression was decreased in mice and in 9 out of
14 tumor specimens from EGFR-mutant lung adenocarcinoma patients with acquired resistance to gefitinib.
Conclusion: These findings suggest that FBXW7 plays a pivotal role in the maintenance of quiescence in gefitinib-resistant lung CSCs in EGFR mutation- positive lung adenocarcinoma."

Jakarta: Fakultas Kedokteran Universitas Indonesia, 2020

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UI - Tugas Akhir Universitas Indonesia Library

Riyadi Sutarto

Kapasitas difusi paru terhadap karbon monoksida (DLCO) pada pasien adenokarsinoma paru yang mendapat EGFR-TKI di Rumah Sakit Umum Pusat Persahabatan Jakarta, Indonesia = Lung diffusion capacity of lung adenocarcinoma patients treated with the epidermal growth factor receptor-tyrosine kinase inhibitors in Persahabatan Hospital Jakarta, Indonesia

"Latar belakang : Efek potensial EGFR-TKI terhadap fungsi paru belum diinvestigasi secara mendalam. Penelitian ini bertujuan untuk menilai efek pemberian EGFR TKI terhadap fungsi paru terutama nilai DLCO.

Metode : Penelitian berlangsung secara prospektif dari September 2018 hingga Juni 2019 di Rumah Sakit Persahabatan Jakarta. Terdapat 20 subjek adenokarsinoma paru dengan mutasi tunggal di exon 19/21 yang dapat menyelesaikan pemeriksaan DLCO baik sebelum mendapat EGFR TKI dan setelah tiga bulan terapi.

Hasil : Penelitian ini mendapatkan peningkatan bermakna nilai rerata KVP prediksi dari 60,6% menjadi 68,25% (p=0,03), nilai rerata VEP1 Prediksi dari 59,7% menjadi 67,05% (p=0,036), nilai rerata DLCO dari 11,55 ml/menit/mmHg menjadi 13,72 ml/menit/mmHg (p=0,004) dan DLCO prediksi dari 53,4% menjadi 63,85% (p=0,03). Peningkatan nilai rerata DLCO prediksi paling besar pada kelompok dengan hasil RECIST partial response yaitu sebesar 16,43% (p=0,056).

Kesimpulan : Terapi EGFR TKI selama tiga bulan pada subyek adenokarsinoma paru dengan mutasi tunggal exon19/21 dapat meningkatkan fungsi paru secara bermakna baik nilai KVP prediksi, VEP1 prediksi, DLCO, dan DLCO prediksi.

Background : The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are drugs of choice in non-small cell lung cancer possessing EGFR mutation. Its effect on the lung function is not well understood. This study aims to assess lung function using the lung diffusion capacity (DLCO) test in lung cancer patients treated with EGFR-TKIs. ming

Method :

This prospective study included lung cancer patients treated with EGFR-TKIs at Persahabatan Hospital Jakarta, Indonesia, between September 2018 andGrowt June 2019. The study recruited 20 lung adenocarcinoma patients presented with a single mutation at exon 19 or 21 as subjects in the process. Their DLCO was examined before and three months after receiving EGFR-TKI. Subjects were grouped according to the Response Evaluation Criteria in Solid Tumors (RECIST) assessment.

Results: There was an increase in predicted FVC from 60.60% to 68.25% (p=0.03), predicted FEV1 from 59.7% to 67.05% (p=0.036%), DLCO from 11.5 mL/minute/mmHg to 13.72 mL/minute/mmHg (p=0.004), and predicted DLCO from 53.4% to 63.85% (p=0.03) during the therapy. The largest increase of predicted DLCO was shown in RECIST group of partial response (16.43%, p=0.056) Conclusion: This study found an improvement in lung function (predicted FVC, predicted FEV1, DLCO, and predicted DLCO) among lung adenocarcinoma subjects exhibiting single mutation at exon 19 or 21 after three months of EGFR-TKIs treatment."

Jakarta: Fakultas Kedokteran Universitas Indonesia, 2019

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UI - Tugas Akhir Universitas Indonesia Library

Hapsari Retno Dewanti

Profil dan angka tahan hidup 1 tahun kanker paru bukan sel kecil (kpkbsk) jenis adenokarsinoma paru dengan mutasi epidermal growth factor receptor (egfr) exon 20 t790m primer di rsup persahabatan = The characteristics and one year survival of lung adenocarcinoma patients with primary exon 20 t790m epidermal growth factor receptor mutation treated at persahabatan hospital Jakarta, Indonesia

"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.

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."

Jakarta: Fakultas Kedokteran Universitas Indonesia, 2018

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UI - Tugas Akhir Universitas Indonesia Library

Muhammad Resa

Desain inhibitor Epidermal Growth Factor Receptor (EGFR) dari senyawa flavonoid berbasis fragment-based drug design sebagai obat potensial untuk terapi kanker paru-paru non-sel-kecil = Epidermal growth factor receptor (egfr) inhibitor design from flavonoid compounds based on fragment-based drug design as a potential drug for non-small-cell lung cancer therapy

"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.

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.
"

Depok: Fakultas Matematika dan Ilmu Pengetahuan Alam Universitas Indonesia, 2020

T54605

UI - Tesis Membership Universitas Indonesia Library

Widya Angasreni

Analisis terapi afatinib pada adenokarsinoma paru dengan mutasi epidermal growth factor receptor (EGFR) di RSUP Persahabatan = Therapy analysis of afatinib in lung adenocarcinoma with epidermal growth factor receptor mutation (EGFR) at Persahabatan Hospital

"Latar Belakang: Kanker paru merupakan kanker terbanyak kedua yang terdiagnosis dan menjadi penyebab terbanyak kematian akibat kanker. Pemberian afatinb sebagai terapi target Epidermal Growth Factor Receptor (EGFR)-Tyrosine Kinase Inhibitor (TKI saat ini telah menjadi terapi standar untuk pasien adenokarsinoma paru dengan mutasi EGFR di Indonesia, termasuk di RSUP Persahabatan. Penelitian ini dilakukan untuk menganalisis pemberian terapi afatinib pada pasien adenokarsinoma paru dengan mutasi EGFR di RSUP Persahabatan.

Metode: Desain penelitian ini adalah kohort retrospektif menggunakan data rekam medis fisik dan elektronik, dilakukan di Poli Onkologi RSUP Persahabatan, dengan teknik total sampling. Subjek penelitian adalah pasien adenokarsinoma paru dengan mutasi EGFR yang mendapatkan afatinib pada Januari 2018-Desember 2021 di Poli Onkologi RSUP Persahabatan yang memenuhi kriteria penelitian.

Hasil: Didapatkan 116 subjek penelitian, pasien adenokarsinoma paru dengan mutasi EGFR yang mendapatkan afatinib di RSUP Persahabatan dengan karakteristik lebih banyak laki-laki (52,6%), kelompok usia <65 tahun (80,2%), suku Jawa (81,9%), tanpa faktor risiko keganasan di keluarga (82,8%). Saat terdiagnosis subjek penelitian lebih banyak dengan stage IVA (75%), metastasis pleura (59,5%), mutasi EGFR delesi ekson 19 (53,4%) status tampilan 0-1 (75,9%) dan metastasis otak didapatkan pada 19% subjek. Nilai median progression free survivival (PFS) subjek penelitian yang mendapat afatinib adalah 13 bulan (95%IK 10,5-15,5 bulan), dan nilai median overall survival (OS) adalah 17 bulan (95%IK 14,9-19,1 bulan). Angka tahan hidup satu tahun yang didapat 65,1% dan Objective Respons Rate (ORR) adalah 36,1%. Sebanyak 35,3% subjek mendapatkan penurunan dosis afatinib 20 mg atau 30 mg. Toksisitas nonhematologi tersering pada pada penelitian ini adalah diare (74,1%), diikuti oleh stomatitis (61,2%), ruam kulit (59,5%) dan paronikia (49,1%).

Kesimpulan: Afatinib sebagai terapi lini pertama memberikan luaran yang cukup baik untuk pasien adenokarsinoma paru dengan mutasi EGFR di RSUP Persahabatan dengan efek samping samping nonhematologi yang dapat dikelola. Riwayat penurunan dosis afatinib tidak memengaruhi angka kesintasan.

Background: Lung cancer is the second most diagnosed cancer and the most common cause of death from cancer. Afatinib as targeted therapy with Epidermal Growth Factor Receptor (EGFR)-Tyrosine Kinase Inhibitor (TKI) has now become standard therapy for lung adenocarcinoma patients with EGFR mutations in Indonesia, including at RSUP Persahabatan. This study was conducted to analyze the administration of afatinib therapy in lung adenocarcinoma patients with EGFR mutations at Persahabatan General Hospital.
Metode: Design of the study was retrospective cohort using secondary data, physical and electronic medical records at Oncology Clinic Persahabatan Hospital with total sampling technique. Subject of this study were medical records of lung adenocarcinoma patients with EGFR mutation and received afatinib therapy by January 2018- December 2021 which met the inclusion criteria.
Results: There were 116 subjects of lung adenocarcinoma with EGFR mutation and received afatinib at Persahabatan Hospital, with predominant of male (52,6%), age <65 years old (80,2%), Javanese (81,9%), without history of cancer in family (82,8%). Most of subjects are diagnosed as lung adenocarcinoma at stage IVA (75%), with most of them have pleural metastases (59,5%), EGFR mutation with exon 19 deletion (53,4%), performa status 0-1 (75,9%), and brain metastases were found in 19% of subject. The median progression free survival (PFS) of subjects was 13 months (95% CI 10.5-15.5 months), and the median overall survival (OS)was 17 months (95% CI 14.9- 19.1 months). The one-year survival rate was 65.1% and the Objective Response Rate (ORR) was 36,1%. As many as 35.3% of subjects had adjustment dose of afatinib to 20 mg or 30 mg The most common non-hematological toxicity found was diarrhea (74.1%), followed by stomatitis (61.2%), skin rash (59.5%) and paronychia (49.1%).
Conclusion: Afatinib as a first-line therapy provides a good outcome for lung adenocarcinoma patients with EGFR mutations at Persahabatan General Hospital with manageable non-hematological adverse events. History of adjustment dose of afatinib did not affect survival rate."

2023

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UI - Tesis Membership Universitas Indonesia Library

Putu Ayu Diah P S

Efikasi dan toksisiti kemoterapi karboplatin-vinorelbin pada pasien kanker paru jenis karsinoma bukan sel kecil (KPKBSK) stage lanjut di RSUP Persahabatan = Efficacy and toxicity of carboplatin vinorelbine chemotherapy in advanced non small cell lung cancer (NSCLC) patients at Persahabatan Hospital

"ABSTRAK

Latar Belakang : Paduan kemoterapi berbasis platinum dengan generasi ketiga khususnya karboplatin-vinorelbin sudah sering digunakan sebagai kemoterapi paliatif pada pasien KPKBSK stage lanjut di Indonesia khususnya Rumah Sakit Umum Pusat RSUP Persahabatan namun sampai saat ini belum terdapat data mengenai efikasi dan toksisiti paduan kemoterapi ini di RSUP Persahabatan.Metode : Desain penelitian ini adalah survey observasional retrospektif pada pasien KPKBSK stage lanjut IIIB dan IV yang menjalani kemoterapi lini I di RSUP Persahabatan dengan paduan kemoterapi karboplatin-vinorelbin sejak 1 Januari 2015 sampai 30 Maret 2017.Hasil : Total subjek dalam penelitian ini adalah 38 pasien yang mendapatkan paduan kemoterapi Karboplatin AUC-5 pada hari ke-1 dan vinorelbin 30 mg/m2 pada hari ke1 dan ke-8. Paduan kemoterapi karboplatin-vinorelbin mempunyai efikasi yang baik dengan Objective overall response rate ORR 12,5 dan clinical benefit rate CBR 87,5 . Overall survival OS pada penelitian ini adalah 34,2 dengan masa tengah tahan hidup 387 hari 12,9 bulan dan progression free survival 323 hari 10,7 bulan. Toksisiti hematologi dan nonhematologi yang paling sering terjadi adalah anemia derajat 1 38,4 dan keluhan mual, muntah derajat 2 57,9 . Pada penelitian ini terdapat 2 kasus perdarahan saluran cerna derajat 2 namun pasien masih dapat melanjutkan kemoterapi. Kami juga mendapatkan komplikasi tindakan kemoterapi berupa phlebitis ringan pada 24 pasien 65,7 dan phlebitis sedang pada 1pasien 2,6 .Kesimpulan: Paduan karboplatin-vinorelbin sebagai kemoterapi lini I memiliki efikasi yang baik serta efek toksisiti yang masih dapat ditoleransi sehingga aman diberikan pada pasien KPKBSK stage lanjut. Kata kunci: efikasi, toksisiti, hematologi, nonhematologi, objective overall response rate, clinical benefit rate, overall survival, MTTH, TTP, PFS

ABSTRAK

Background Combination of platinum base and third generation drugs Carboplatin and vinorelbine chemotherapy are frequently used as paliative chemotherapy for Non small cell lung cancer NSCLC patients in Indonesia especially in Persahabatan Hospital. But there are still no data about the activity and tolerability of this regiment in Persahabatan Hospital. This study is conducted to evaluate the efficacy and toxicity of this regiment as first line chemotherapy for advanced NSCLC patients in Persahabatan Hospital.Method This study is an observational survey retrospective study for advanced NSCLC patientswho receive carboplatin vinorelbine regiment as fisrt line chemotherapy since 1st January 2015 to 30th March 2017.Result We observea total of 38 patients who receive carboplatin 5 AUC on day 1 and vinorelbine 30mg m2 on day 1 and 8. This regiment has a good efficacy with overall response rate ORR 12,5 and clinical benefit rate CBR 87,5 . The overall survival OS is 34,2 with median of survival time 387 days 12,9 moths and PFS 323 days 10,7 moths . We found grade 1 anemia 38,4 and grade 2 nausea vomiting 57,9 as hematological and non hematological toxicity that frequently occur in this study. We found 2 cases of grade 2 gastrointestinal bleeding but the patients are still able to continue the chemotherapy after doing some correction for the haemoglobin Hb . We also found mild phlebitis in 24 patients 65,7 and 1 moderate phlebitis in 1 patient 2,6 as procedural complication of this chemotherapyConclusion Combination ofcarboplatin and vinorelbine as first line chemotherapy has a good efficacy and tolerability for advanced NSCLC patients. Key word efficacy, toxicity, haematological, non hematological, overall objective response rate ORR , clinical benefit rate CBR , overall survival OS , median time of survival, time to progression TTP and progression free survival PFS ."

2017

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UI - Tugas Akhir Universitas Indonesia Library

Muhammad Ali Asdar

Efikasi gefitinib dan erlotinib pada pasien adenokarsinoma paru dengan mutasi gen epidermal growth factor receptor di Rumah Sakit Rujukan Respirasi Nasional Persahabatan Jakarta = Efficacy of gefitinib and erlotinib for lung adenocarcinoma with epidermal growth factor receptor mutation in Persahabatan Hospital Jakarta

"Pendahuluan: Tyrosine Kinase Inhibitors (TKIs) sangat efektif terhadap Kanker

Paru jenis Karsinoma Bukan Sel Kecil (KPKBSK) dengan mutasi Epidermal

Growth Factor Receptor (EGFR). Gefitinib dan Erlotinib adalah generasi pertama

EGFR-TKI untuk pengobatan KPKBSK dengan mutasi EGFR. Obat-obat ini telah

tersedia melalui asuransi kesehatan di Indonesia untuk pasien Adenokarsinoma

paru dengan mutasi EGFR. Data mengenai efikasi dan toksisitas EGFR-TKI saat

ini belum tersedia di Indonesia.

Metode: Kami melakukan analisis observasional kohort retrospektif pada pasien

Adenokarsinoma paru dengan mutasi EGFR di RSUP Persahabatan, Jakarta

Indonesia dari Januari 2015 sampai dengan Desember 2017. Kami meninjau

rekam medis 331 pasien dengan diagnosis Adenokarsinoma paru dengan mutasi

EGFR stage lanjut yang diobati dengan EGFR-TKI generasi pertama. Sebanyak

192 subjek yang memenuhi kriteria inklusi.

Hasil: Subjek yang mendapatkan Gefitinib (n=132) dan Erlotinib (n=60). Median

progression free survival (PFS) sebanding antara Gefitinib dan Erlotinib (9,0 dan

7,0 bulan, interval kepercayaan 95% [IK] 0,57-1,07, p=0,126). Median Overall

survival (OS) dan angka tahan hidup 1 tahun masing-masing kelompok adalah

44,5 vs 39,5 bulan (95% IK 0,35-1,29, p=0,670) dan 92% berbanding 92%

(p=0,228). Terdapat toksisitas termasuk diare, paronikia, skin rash dan stomatitis

yang diamati tetapi tidak ada perbedaan yang bermakna pada toksisitas derajat 3

atau 4 antara kedua kelompok (p=0,713).

Kesimpulan: Kedua EGFR-TKIs generasi pertama sebanding dalam PFS dan OS,

meskipun Gefitinib terlihat lebih tinggi, tetapi secara statistik tidak bermakna dan

keduanya memiliki toksisitas yang sebanding dan dapat ditoleransi.

Introductions: Tyrosine kinase inhibitors (TKIs) are effective against non-small

cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR)

mutation. Gefitinib and erlotinib are the first-generation EGFR-TKIs

recommended as first-line treatments for NSCLC with EGFR mutations and are

available through Universal Health Coverage in Indonesia for lung

adenocarcinoma patients with EGFR mutations. However, the efficacy and safety

data of EGFR-TKIs are unavailable in Indonesia.

Methods: We did a retrospective cohort analysis of the patients of lung

adenocarcinoma with EGFR mutations treated in Persahabatan Hospital Jakarta,

Indonesia, between January 2015 and December 2017. We reviewed the records

of 331 patients with advanced stage lung adenocarcinoma with EGFR mutation

treated with the first-generation EGFR-TKIs. The subjects were 192 patients who

met the inclusion criteria.

Results: Subjects were receiving gefitinib (n=132) and erlotinib (n=60). Median

progression-free survival (PFS) was comparable between gefitinib and erlotinib

(9.0 vs 7.0 months, 95% confidence interval [CI] 0.57-1.07, p=0.126). The

median overall survival (OS) and 1-year survival were 44.5 vs 39.5 months

(95%CI 0.35-1.29, p=0.228; and 92% vs 92%, p=0.228, respectively). Reported

toxicities were diarrhea, paronychia, rash, and stomatitis but not of significant

difference between grade 3 or 4 toxicities (p=0.713).

Conclusions: The PFS and OS of the first-generation EGFR-TKIs were

comparable, although gefitinib PFS and OS was shown to be better, but without

significance. Both gefitinib and erlotinib had comparable and tolerable adverse

effects"

Jakarta: Fakultas Kedokteran Universitas Indonesia, 2019

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UI - Tugas Akhir Universitas Indonesia Library

Sarifuddin

Analisis korelasi transforming growth factor 1 (TGF B-1) serum pada pasien kanker paru jenis karsinoma bukan sel kecil (KPKBSK) stage lanjut = The correlation analysis of transforming growth factor 1 (TGF B-1) serum in advanced non small cell lung cancer (NSCLC) patients

"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 lanjut

Metode: 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) bulan

Kesimpulan: 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.

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."

Jakarta: Fakultas Kedokteran Universitas Indonesia, 2018

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