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"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."

"Pendahuluan: Tyrosine Kinase Inhibitors (TKIs) sangat efektif terhadap KankerParu jenis Karsinoma Bukan Sel Kecil (KPKBSK) dengan mutasi EpidermalGrowth Factor Receptor (EGFR). Gefitinib dan Erlotinib adalah generasi pertamaEGFR-TKI untuk pengobatan KPKBSK dengan mutasi EGFR. Obat-obat ini telahtersedia melalui asuransi kesehatan di Indonesia untuk pasien Adenokarsinomaparu dengan mutasi EGFR. Data mengenai efikasi dan toksisitas EGFR-TKI saatini belum tersedia di Indonesia.Metode: Kami melakukan analisis observasional kohort retrospektif pada pasienAdenokarsinoma paru dengan mutasi EGFR di RSUP Persahabatan, JakartaIndonesia dari Januari 2015 sampai dengan Desember 2017. Kami meninjaurekam medis 331 pasien dengan diagnosis Adenokarsinoma paru dengan mutasiEGFR stage lanjut yang diobati dengan EGFR-TKI generasi pertama. Sebanyak192 subjek yang memenuhi kriteria inklusi.Hasil: Subjek yang mendapatkan Gefitinib (n=132) dan Erlotinib (n=60). Medianprogression free survival (PFS) sebanding antara Gefitinib dan Erlotinib (9,0 dan7,0 bulan, interval kepercayaan 95% [IK] 0,57-1,07, p=0,126). Median Overallsurvival (OS) dan angka tahan hidup 1 tahun masing-masing kelompok adalah44,5 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 stomatitisyang diamati tetapi tidak ada perbedaan yang bermakna pada toksisitas derajat 3atau 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 dankeduanya memiliki toksisitas yang sebanding dan dapat ditoleransi.

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Introductions: Tyrosine kinase inhibitors (TKIs) are effective against non-smallcell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR)mutation. Gefitinib and erlotinib are the first-generation EGFR-TKIsrecommended as first-line treatments for NSCLC with EGFR mutations and areavailable through Universal Health Coverage in Indonesia for lungadenocarcinoma patients with EGFR mutations. However, the efficacy and safetydata of EGFR-TKIs are unavailable in Indonesia.Methods: We did a retrospective cohort analysis of the patients of lungadenocarcinoma with EGFR mutations treated in Persahabatan Hospital Jakarta,Indonesia, between January 2015 and December 2017. We reviewed the recordsof 331 patients with advanced stage lung adenocarcinoma with EGFR mutationtreated with the first-generation EGFR-TKIs. The subjects were 192 patients whomet the inclusion criteria.Results: Subjects were receiving gefitinib (n=132) and erlotinib (n=60). Medianprogression-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). Themedian 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). Reportedtoxicities were diarrhea, paronychia, rash, and stomatitis but not of significantdifference between grade 3 or 4 toxicities (p=0.713).Conclusions: The PFS and OS of the first-generation EGFR-TKIs werecomparable, although gefitinib PFS and OS was shown to be better, but withoutsignificance. Both gefitinib and erlotinib had comparable and tolerable adverseeffects"

"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.

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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."

"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 : Mutasi pada gen Epidermal Growth Factor Receptor (EGFR) berhubungan dengan karsinogenesis Adenokarsinoma paru terutama pada usia muda yang tidak terpajan cukup lama oleh rokok sebagai karsinogen. Penelitian ini untuk mengetahui profil mutasi gen EGFR dan angka tahan hidup pasien adenokarsinoma paru usia muda. Metode: Penelitian observasional kohort retrospektif dan prospektif pada Adenokarsinoma paru usia muda yakni usia <45 tahun dibandingkan dengan usia yang lebih tua. Data diambil dari catatan medis rumah sakit umum pusat Persahabatan Jakarta 2012-2013 dan dilakukan observasi progresivitas dan kematian selama 2 tahun pasca tegak diagnosis. Hasil: Total pasien Adenokarsinoma paru adalah 218 orang terdiri dari 65 orang usia muda dan 153 orang usia tua. Karakteristik Adenokasrsinoma paru usia muda adalah perempuan (58,3%), bukan perokok (66,7%), stage lanjut (98,5%), status tampilan WHO ≤2, metastasis ke luar rongga toraks (43,1%). Proporsi mutasi EGFR positif pada usia muda lebih tinggi dibandingkan usia tua (70,8%vs51%; p=0,007). Mutasi gen EGFR usia muda terdiri dari 36,9% delesi ekson 19; 30,8% mutasi ekson 21 L858R; 3,1% mutasi ekson 21 L861Q dan 29,2% wild type. Masa tengah tahan hidup Adenokarsinoma paru usia muda dengan EGFR positif yang diberikan EGFR tyrosine kinase inhibitor adalah 652 hari (590-713 hari, IK 95%) dengan angka tahan hidup 1 tahun adalah 87,5% dan masa bebas penyakit adalah 345 hari (IK 95%, 323-366 hari). Delesi ekson 19 memberikan masa bebas penyakit yang lebih baik dibandingkan dengan mutasi ekson 21 (RR 2,361; IK 95% 1,126-4,952; p=0,023). Masa tengah tahan hidup Adenokarsinoma paru usia muda dengan mutasi EGFR wild type yang mendapat kemo/kemoradioterapi adalah 515 hari (IK 95%, 487-542) dengan angka tahan hidup 1 tahun adalah 70,7% dan masa bebas penyakit adalah 202 hari (IK 95%, 137-266 hari). Kesimpulan: Profil mutasi gen EGFR pada Adenokarsinoma paru usia muda sangat penting dalam pemilihan terapi lini pertama sehingga dapat meningkatkan angka tahan hidup.

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Introduction: Epidermal Growth Factor Receptor (EGFR) mutation is associated with Lung Adebocarcinoma carcinogenesis particularly in young patients which don?t have long exposure to smoke as carcinogen. This study investigate Profile of Epidermal Growth Factor Receptor Mutation and Survival in Young Patients with lung Adenocarcinoma.

Method: Retrospective and prospective observational cohort study in lung Adenocarcinoma <45 years old compare with olders. Data are taken from medical record Persahabatan hospital Jakarta 2012-2013 and we observed for progressivity and mortality in 2 years since diagnosis.

Results: A total 218 lung Adenocarcinoma consists of 65 young patients and 153 olders. Young lung Adenocarcinomas are female (58,3%), nonsmokers (66,7%), advanced stage (98,5%), performance status WHO ≤2, extrathoracic metastatics (43,1%). EGFR mutation in youngers are higher than olders (70,8%vs51%; p=0,007). Mutation in young patients consists are 36,9% exon 19 deletion; 30,8% exon 21 L858R mutation; 3,1% exon 21 L861Q mutation and 29,2% wild type. Overall survival (OS) young patients with EGFR mutation positive treated with EGFR tyrosine kinase inhibitor are 652 days (95% CI, 590-713 days), 1 year survival is 87,5% and progression free survival (PFS) are 345 days (95% CI, 323-366 days). Exon 19 deletion give higher PFS than exon 21 (RR 2,361; IK 95% 1,126-4,952; p=0,023). Overall survival young patients with EGFR wild type treated with conventional chemotherapy are 515 days (487-542 days, 95%), 1 year survival is 70,7% and their PFS are 202 days (137-266 days, 95% CI).

Conclusion: EGFR mutation profile in young lung Adenocarcinoma is important to choose first line therapy so that can increase their survival."

"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.

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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. mingMethod :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."

"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"

"[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: 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

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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."