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Latar Belakang. Tingkat kekambuhan dan toksisitas terapi merupakan masalah pada kanker serviks. Antibodi monoklonal sebagai terapi target menunjukkan peran menjanjikan dalam pengobatan kanker. Penelitian ini bertujuan untuk menganalisis efek imunologis pada pemberian radiasi bersama mAb h-R3 pada pasien kanker serviks.

Metode. Penelitian ini merupakan penelitian eksperimental yang dilakukan dalam dua tahun. Subjek dibagi menjadi dua kelompok, mendapat terapi radiasi dengan/tanpa mAb h-R3. Uji terhadap sel imun (sel NK CD56⁺, sel T CD4⁺, dan sel T CD8⁺) dilakukan pada darah perifer dan jaringan tumor untuk menilai efek imunologis dan respons terapi pada masing-masing kelompok. Analisis dilakukan dalam tiga waktu: sebelum terapi (pre terapi) untuk menilai kondisi awal, satu minggu setelah pemberian mAb h-R3 yang pertama (saat terapi) untuk menilai pengaruh mAb h-R3, dan setelah radiasi eksterna selesai sebelum brakhiterapi I (pasca terapi) untuk menilai pengaruh pemberian radiasi dengan atau tanpa mAb h-R3.

Hasil. Terdapat 22 subjek, stadium IIB hingga IIIB dengan rerata usia 51,2 ± 7,7 tahun. Didapatkan rasio sel NK CD56⁺ pre dan saat terapi di jaringan tumor pada kelompok mAb h-R3 lebih tinggi (p<0,05), menunjukkan pengaruh mAb h-R3 terhadap sel NK CD56⁺. Pengaruh tersebut terlihat juga pada jumlah sel T CD4⁺ dan CD8⁺ pre dan saat terapi di sirkulasi dan jaringan tumor, kelompok mAb mengalami peningkatan dengan perbedaan yang signifikan di sirkulasi antar dua kelompok (p<0,05). Pengaruh pemberian radiasi bersama mAb h-R3 terlihat dalam perbandingan antara pre dan pasca terapi, walaupun sel imun dalam sirkulasi pada kedua kelompok menurun, namun kelompok mAb h-R3 tetap memiliki jumlah lebih tinggi. Terdapat korelasi antara peningkatan jumlah sel NK CD56⁺ dengan penurunan volume tumor. Berdasarkan RECIST, kelompok mAb h-R3 memiliki respons lebih baik (p<0,05) dengan complete response 63,6% vs 18,2% pada kelompok kontrol.

Kesimpulan. mAb h-R3 meningkatkan jumlah sel imun secara sistemik maupun lokal, pemberian radiasi bersama mAb h-R3 menghasilkan respons imunitas seluler yang lebih baik sehingga meningkatkan respons terapi.

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Introduction. Rate of recurrences and toxicity of therapy remain as problems in cervical cancer. Monoclonal antibody as targeted therapy has showed a promising role in cancer treatment. This study aims to analyze the immunological response of radiation and mAb h-R3 in cervical cancer treatment.

Methods. This was an experimental study conducted in two years. Subjects were divided into two groups, one group received radiation with mAb h-R3 and the other received radiation only. Cellular immunity tests (NK CD56⁺ cell, CD4⁺ T cell, and CD8⁺ T cell) were performed on peripheral blood and tumor tissue to determine the immunological effect and tumor response on each group. Analyses were performed at 3 period: before treatment (pre therapy) as baseline, one week after first administration of mAb h-R3 (during therapy) to measure effect of mAb h-R3, and after external radiation before first brachytherapy (after therapy) to measure effect of radiation with or without mAb h-R3.

Result. There were 22 subjects, stage IIB to IIIB, with the mean age of 51.2 ± 7.7 years. The ratio of tumor tissue NK CD56⁺ cells pre- and during-therapy in mAb h-R3 group were higher (p<0.05), showing the effect of mAb h-R3 to NK CD56⁺ cells. Number of T CD4⁺ and CD8⁺ cells pre- and during-therapy in peripheral blood and tumor tissue in mAb h-R3 group increased with significant difference in peripheral blood between two groups (p<0.05). Radiation and mAb h-R3 effect were shown in pre- and post-therapy ratio, although all immune cells were decreased, mAb h-R3 group still have higher number of cells. There was a correlation between the increment of NK CD56⁺ cells with tumor volume reduction. Based on RECIST criteria, mAb h-R3 group have better response (p<0.05) than control group (complete response: 63.6% vs 18.2%).

Conclusion. mAb h-R3 increases the number of immune cells both systemically and locally, radiotherapy and mAb h-R3 have better immune response which will increase the therapeutic response.

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"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."

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

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

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

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

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

"Kanker payudara adalah jenis kanker yang memiliki kasus baru terbanyak dan penyebab kematian tertinggi di kalangan wanita. Hal tersebut menjadikan pemahaman mengenai konsep pengobatan presisi (precision medicine) perlu dikembangkan, salah satunya dengan penggunaan kultur primer dari jaringan kanker pasien. Epidermal growth factor receptor (EGFR) telah dilaporkan umum digunakan sebagai marker prognostik kanker payudara melalui deteksi protein menggunakan metode immunohistokimia (IHK). Namun, metode tersebut memiliki kekurangan dalam menjadi acuan penentuan terapi adjuvant. Penggunaan kultur primer sebagai pengganti cell lines dalam penelitian kanker perlu terus dikembangkan karena lebih mewakili karakteristik fenotipe dan genotipe dari jaringan kanker in vivo. Oleh sebab itu, penelitian ini bertujuan untuk mengetahui tingkat ekspresi relatif gen EGFR pada sampel kultur primer dan jaringan asalnya serta mengetahui perbandingan ekspresi relatif gen EGFR pada sampel jaringan jinak dan jaringan ganas kanker payudara. Metode yang digunakan, yaitu melalui deteksi mRNA gen EGFR dengan semi kuantitatif RT-PCR pada dua pasien yang mewakili jaringan jinak dan ganas. Hasil penelitian menunjukkan tidak terdapat perbedaan signifikan antara ekspresi EGFR pada kultur primer dan jaringan asal, serta ekspresi EGFR pada jaringan ganas lebih tinggi dibandingkan dengan jaringan jinak. Berdasarkan hasil yang diperoleh, dapat disimpulkan bahwa kultur primer dapat dijadikan model alternatif dalam penelitian kanker, serta EGFR dapat dijadikan marker potensial dalam menentukan tingkat agresivitas kanker payudara.

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Breast cancer is a type of cancer that has a highest rate of incidence as well as mortality among women. This makes the understanding of the concept of precision medicine need to be continuously developed, in wich one of the methods is through using primary cultures from patient's tissue. It has been reported that epidermal growth factor receptor (EGFR) is commonly used as a prognostic marker of breast cancer through protein detection using the Immunohistochemical (IHC) method. However, this method has shortcomings in being a reference for determining adjuvant therapy. The use of primary culture as a subtitute cell lines in cancer research needs to be developed due to its more representative of the phenotype and genotype characteristics of cancer tissue in vivo. Therefore, this study aims to determine the relative expression level of the EGFR gene in primary culture sample and its tissue origin as well as comparing the relative expression of the EGFR gene in samples of benign tissue and malignant tissue of breast cancer. The method used is the detection of EGFR gene mRNA with semi-quantitative RT-PCR in two patients representing benign and malignant tissues. The results showed that there was no significant difference between EGFR expression in primary culture and tissue of origin, and EGFR expression in malignant tissue was higher than in benign tissue. Hence, it can be concluded that primary culture can be used as an alternative model in cancer research, and EGFR can be used as a potential marker in determining aggressiveness level of breast cancer."

"Latar belakang: Penderita kanker ovarium umumnya datang berobat pada stadium lanjut, sehingga kekambuhan pasca pembedahan dan pemberian kemoterapi mencapai 70-80%. EGFR mengaktifkan jalur sinyal yang menginduksi onkogenesis dan proliferasi sel. Tujuan penelitian ini adalah untuk menganalisis peran EGFR dalam patogenesis tumor serosum ovarium dan peluangnya untuk digunakan sebagai penanda keganasan.Metode: Penelitian ini menggunakan metode potong lintang. Sampel terdiri atas 15 kasus tumor jinak, 15 kasus borderline dan 15 kasus adenokarsinoma di Departemen Patologi Anatomik FKUI/RSCM tahun 2008-2012. Dilakukan pulasan imunohistokimia EGFR dan penilaian dengan H score.Hasil: Terdapat perbedaan ekspresi EGFR yang bermakna antara kelompok tumor serosum jinak (H score = 15), borderline (H score = 60) dan adenokarsinoma (H score = 120), dengan p=0,000.Kesimpulan. Ekspresi EGFR pada tumor serosum ovarium meningkat seiring peningkatan derajat keganasan.

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Background: Most of ovarian cancer patients are diagnosed in already advanced stage, therefore 70-80% of cases having recurrence after surgical staging and chemotherapy. EGFR activates signaling pathways which induce oncogenesis and cell proliferation. The aim of this study is to analyze the role of EGFR in the pathogenesis of serous ovarian tumors and its possibility to be used as a malignant marker.Methods: This was a cross-sectional study on each 15 cases of benign, borderline and malignant serous ovarian tumors from Anatomical Pathology Department FMUI/CMH in 2008-2012. EGFR status was assessed by immunohistochemistry technique and the expression was evaluated using H score.Results: There was significant difference between EGFR expression in benign (H score = 15), borderline (H score = 60) and malignant serous ovarian tumors (H score = 120), p=0,000.Conclusion: The EGFR immunoexpression was increased along with the higher degree of serous ovarian tumor malignancy."

"Latar Belakang: Kanker Nasofaring (KNF) salah satu pilihan terapinya adalah kemoterapi neoajuvan. Respon kemoterapi ini, di pengaruhi oleh Epidermal Growth Factor Receptor(EGFR), faktor yang berperan pada pertumbuhan dan invasif tumor. Tujuan dari penelitian ini adalah untuk mengetahui perbandingan tingkat ekspresi EGFR dengan respon kemoterapi neoajuvan dan tingkat ekstensif tumor primer. Penelitian ini merupakan studi potong lintang deskriptif, dilakukan penilaian respon kemoterapi neoajuvan dan tingkat ekstensif tumor primer, pada pasien KNF yang telah mendapat kemoterapi dan dilakukan pemeriksaan ekspresi EGFR. Hasil penelitian: Proporsi ekspresi EGFR pada kanker nasofaring untuk ekspresi negatif, positif dan kuat, berturut-turut sebesar (10%), (70%) dan (20%). Pasien yang respon terhadap kemoterapi neoajuvan adalah 23 pasien (76,6%) dan tidak respon 7 pasien (23,4%). Kelompok pasien yang memberikan respon terhadap kemoterapi, 15 pasien ( 50%) memiliki intensitas EGFR yang lemah. Pasien dengan tingkat ekstensif T3-T4 , mempunyai ekspresi EGFR lebih besar dibandingkan T1-T2 tumor. Kesimpulan : Proporsi ekspresi EGFR pada kanker nasofaring di Indonesia sebesar 90 persen. Kemoterapi neoajuvan lebih respon pada tumor dengan ekspresi EGFR positif dan intensitas EGFR yang lemah. Tumor dengan tingkat ekstensif yang lebih tinggi, mempunyai ekspresi EGFR lebih tinggi.

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Background: Neoadjuvan chemotherapy is one option of treatment for nasopharyngeal cancer (NPC). The response of chemotherapy influenced by EGFR expression. EGFR is important factor for the growth and tumors invasion. Purpose of the study is compare of the EGFR expression level with response of neoadjuvan chemotherapy and extensive level of the primary tumor. The methods is cross-sectional descriptive study that assessment of response to neoadjuvan chemotherapy and extensive level of the primary tumor. The NPC patients who have received chemotherapy is examined of EGFR expression.

Result of the study is the proportion of EGFR expression in NPC for negative, positive and strong expression is 10%, 70%, and 20% respectively. Patients who responses to neoadjuvan chemotherapy are 23 patients(76.6%) and non-responses 7 patients (23.4%). The group patients who responses to chemotherapy, 15 patients (50%) have EGFR weak intensity. Patients with T3-T4 tumors (56,6%) have EGFR expression is greater than T1-T2 tumors(44,4%).

Conclusion: The proportion of EGFR expression in NPC in Indonesia is 90 percent. Neoajuvan chemotherapy is more response in tumors with positive EGFR expression and weak intensity. Tumors with high extensive levels have higher EGFR expression."

"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."