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"Latar balakang. Sekitar 75% kanker leher rahim datang ke rumah sakit dalam stadium lanjut. Terapi utama kanker serviks stadium lanjut adalah radioterapi. Kombinasi terapi radiasi dengan kemoterapi ternyata tidak menghasilkan respons terapi yang lebih baik, tetapi bahkan menimbulkan efek samping yang lebih berat dibandingkan terapi radiasi saja. Perubahan pola makan saat ini, diduga berpengaruh pada respons terapi. Rasio asupan Polyunsaturated Fatty Acids (PUFA) n-6 : n-3 sekitar 1-2 : 1 dapat melawan pertumbuhan kanker. Beberapa publikasi melaporkan bahwa PUFA n-3 (AL n-3) mempunyai efek pro-apoptosis, anti-inflamasi, anti-proliferatif dan anti-angiogenik. Penelitian ini bertujuan untuk mengetahui apakah suplementasi nutrisi tinggi PUFA bersamaan dengan terapi radiasi dapat meningkatkan respons tumor pada kanker serviks stadium lanjut. Metode. Penelitian ini merupakan Randomized Clinical Trial, double blind pada pasien kanker serviks stadium lanjut, jenis karsinoma sel skuama yang hanya mendapat terapi radiasi di Departemen Radioterapi, Rumah Sakit Cipto Mangunkusumo (RSCM), Jakarta. Subjek penelitian diambil secara konsekutif, melalui randomisasi dibagi dua kelompok, yaitu kelompok perlakuan dan kontrol. Selama radiasi subjek penelitian mendapat suplementasi nutrisi mengandung isokalori dan isoprotein dengan rasio AL n-6 : n-3 = 1,27 : 1 dan kontrol. Selama perlakuan dilakukan evaluasi setiap lima kali radiasi, meliputi BB dan efek samping radiasi akut. Parameter yang dinilai adalah respons klinis, respons histopatologis serta perubahan kadar PGE2 dan VEGF serum.Hasil. Sebanyak 31 subjek dari 45 subjek dapat menyelesaikan penelitian. Sebelum perlakuan, status sosio-demografi, pola asupan AL n-6 dan n-3, status gizi dan klinis tidak didapatkan perbedaan bermakna. Setelah perlakuan, didapatkan penurunan kadar PGE2 serum pada kelompok perlakuan, sedangkan kelompok kontrol mengalami kenaikan (p = 0,127). Penurunan kadar VEGF kelompok perlakuan lebih besar dibanding kontrol (p = 0,626). Respons klinis dan respons histopatologis kelompok perlakuan lebih baik dibanding kontrol, dengan kemaknaan masing-masing p = 0,172 dan p = 0,169. Secara statistik belum didapatkan perbedaan yang bermakna pada penurunan kadar PGE2 dan VEGF serum, respons klinis dan respons histopatologis, tetapi didapat kemaknaan klinis yang nyata pada kelompok perlakuan dibanding kontrol. Analisis statistik gabungan dari respons klinis, respons histopatologis, kadar PGE2 dan VEGF serum didapatkan respons tumor total yang bermakna (p = 0,048).Kesimpulan. Suplementasi nutrisi tinggi PUFA dengan rasio asam lemak n-6 : n- 3 = 1,27 : 1 pada kanker serviks stadium lanjut bersama terapi radiasi memberikan respons tumor total yang lebih baik.

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Background. Approximately 75% of uterine cervical cancer came to the hospital in an advanced stage. Primary therapy of advanced cervical cancer is radiotherapy. The combination of radiotherapy with chemotherapy did not give better outcomes, but even cause more severe side effects than radiotherapy. Changes in dietary intake at this time, are supposed to influence the response to therapy. The ratio of n-6 to n-3 polyunsaturated fatty acids (PUFA) about 1-2: 1 can fight cancer growth. Several publications stated that n-3 PUFA has pro- apoptotic effect, anti-inflammatory, anti-proliferative and anti-angiogenic. This study aimed to examine whether radiotherapy combined with daily nutritional supplements enriched PUFA enhance tumor response in advanced cervical cancer.

Method. This study was a double-blind Randomized Clinical Trial (RCT) in patients with advanced squamous cell cervical cancer, received radiation only as control group, and those who received nutritional supplementation containing isocaloric and isoprotein with ratio of n-6 : n-3 PUFA = 1.27: 1 as treatment group. This study was performed in the Department of Radiotherapy Dr. Cipto Mangunkusumo General Hospital (RSUPNCM), Jakarta. Evaluation was done every five times radiation, including Karnofsky Perfomance Scale, body weight and side effects of acute radiation. Parameters assessed were clinical and hematological response, histopathological response and changes in the levels of PGE2 and VEGF serum.

Results. A total of 31 subjects from 45 subjects participated the study completely. Prior to treatment, socio-demographic status, patterns of n-6 and n-3 PUFA, clinical and nutritional status were analyzed, no significant differences were noted. After treatment, a decrease in serum PGE2 levels in the treatment group was found, while in the control group increased (P = 0.127). VEGF in the treatment group declined higher than controls (P = 0.626). Treatment group showed significant better clinical response and histopathological responses compared to the control group (p = 0.172 and p = 0.169). No significant differences were found in the reduction of PGE2 and VEGF serum levels, clinical response and histopathological response, although from clinical standpoint there is a better significant response in the treatment group than the control. The combined statistical analysis of clinical response, histopathological response, PGE2 and VEGF serum levels obtained total tumor response (P = 0.048).

Conclusion. Nutritional supplementation enriched PUFA (ratio of n-6: n-3 PUFA = 1.27 : 1) in advanced cervical cancer receiving radiotherapy gives better total tumor response."

"Tujuan : Untuk mengetahui pengaruh kadar hemoglobin, kadar hematokrit dan transfusi selama radiasi terhadap respon tumor dan kesintasan pada pasien kanker serviks stadium lanjut lokal (FIGO IIB-IIIB) yang menjalani terapi radiasi. Metode : Dilakukan studi kohort retrospektif terhadap pasien kanker serviks stadium IIB-IIIB yang memenuhi kriteria inklusi-eksklusi, yang berobat di Departemen Radioterapi RSCM periode Januari 2007 - Desember 2011, dianalisa dan dibandingkan respon tumor dan kesintasan antara kadar hemoglobin <11g/dL dengan ≥11g/dL, kadar hematokrit ≤35% dengan >35%, pasien yang ditransfusi dan tidak ditransfusi selama radiasi. Hasil : Respon tumor komplit pada kadar Hb sebelum radiasi <11g/dL dibandingkan dengan ≥11g/dL adalah 77,1% vs 70,2% p=0,34 ; kesintasan 3 tahun 84% vs 75% p=0,42. Respon tumor komplit pada kadar Hb selama radiasi <11g/dL dibandingkan dengan ≥11g/dL adalah 81,3% vs 67,9% p= 0,049 ; kesintasan 3 tahun 82% vs 79% p=0,05. Respon tumor komplit pada kadar Ht sebelum radiasi ≤35% dibandingkan dengan >35% adalah 71,7% vs 75,8% p=0,65 ; kesintasan 3 tahun 86% vs 78% p>0,05. Respon tumor komplit pada kadar Ht selama radiasi ≤35% dibandingkan dengan >35% adalah 72,7% vs 72,7% p=1,00 ; kesintasan 3 tahun 78% vs 87% p=>0,05. Kesintasan 3 tahun pada pasien yang ditransfusi dibandingkan dengan yang tidak ditransfusi 80% vs 84% p=0,95. Kesimpulan : Penelitian ini menunjukkan perbedaan yang bemakna pada pengaruh kadar hemoglobin rerata selama radiasi terhadap respon tumor dan kesintasan, pengaruh kadar hematokrit sebelum dan rerata selama radiasi terhadap respon tumor dan kesintasan.

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Aim : To determine the effect of hemoglobin level, hematocrit level and transfusion during radiation on tumor response and survival rate in patients with locally advanced cervical cancer (FIGO IIB-IIIB) who underwent radiation therapy.

Methods : A retrospective cohort study has done on cervical cancer patients stage IIB-IIIB who met the inclusion-exclusion criteria, which is treated in the Department of Radiotherapy RSCM period January 2007 - December 2011, were analyzed and compared to tumor response and survival rate between hemoglobin level <11g / dL with ≥11g / dL, hematocrit level ≤35% to> 35%, patients with blood transfused or not during radiation.

Results : Complete tumor response in Hb levels before radiation <11g / dL compared with ≥11g / dL was 77.1% vs. 70.2% p = 0.34; 3-year survival rate 84% vs. 75% p = 0.42. Complete tumor response in hemoglobin levels during radiation <11g / dL compared with ≥11g / dL was 81.3% vs. 67.9% p = 0.049; 3-year survival rate 82% vs. 79% p = 0.05. Complete tumor response in hematocrit levels before radiation ≤35% compared to> 35% was 71.7% vs. 75.8% p = 0.65; 3-year survival rate 86% vs. 78% p> 0.05. Complete tumor response in hematocrit levels during radiation ≤35% compared to> 35% was 72.7% vs. 72.7% p = 1.00; 3-year survival rate 78% vs. 87% p => 0.05. 3-year survival rate in patients who were not transfused transfused compared with 80% vs. 84% p = 0.95.

Conclusions : This study shows that differences in the influence of mean hemoglobin levels during radiation on tumor response and survival rate, the influence of mean hematocrit levels before and during radiation on tumor response and survival rate."

"Kanker serviks merupakan salah satu kanker terbanyak pada perempuan dengan jumlah kasus dan kematian yang bermakna, terutama di negara-negara berkembang seperti Indonesia. Penelitian terbaru menyoroti peran mikroRNA (miRNA) dalam karsinogenesis, terutama miR-21 yang terlibat dalam berbagai jenis kanker pada perempuan, termasuk kanker serviks. Selain itu, miR-145, LATS1, dan NF-κB dipercaya memiliki peran dalam radioresistensi. Penelitian ini bertujuan untuk membuktikan pengaruh konsentrasi miR-21, miR-145, Large Tumor Suppressor 1 (LATS1), dan Nuclear Factor Kappa B (NF-kB) serta usia terhadap respons kemoradiasi pada pasien kanker serviks stadium lanjut lokal. Penelitian ini menggunakan desain potong lintang analitik yang dilakukan di Rumah Sakit Cipto Mangunkusumo dari bulan Juli 2017 sampai Juni 2023. Sampel jaringan dari biopsi serviks diambil dan diperiksa menggunakan real-time reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) untuk mendeteksi miR-21 dan miR-145, serta ELISA untuk mendeteksi konsentrasi LATS1 dan NF-kB sebelum pasien menerima terapi kemoradiasi. Pemeriksaan ultrasonografi kemudian dilakukan kembali untuk menilai respons radiasi dengan menggunakan kriteria RECIST 1.1. Dari 140 subjek, ditemukan gambaran histopatologi karsinoma sel skuamosa pada 119 (85%) sampel, dengan distribusi kanker serviks stadium IIIB pada 102 (72,9%) subjek dan stadium IVA pada 38 (27,1%) subjek. Ekspresi miR- 21 di atas cut-off lebih banyak ditemukan pada subjek yang radioresisten (p = 0,010; AUC = 67,6%). Ekspresi miR-145 dan LATS1 di atas cut-off lebih banyak ditemukan pada kelompok radioresisten, masing-masing dengan p = 0,132 (AUC = 38,8%) dan p = <0,001 (AUC = 32,7%). Ekspresi NF-kB di bawah cut-off ditemukan lebih banyak pada kelompok radioresisten (p = 0,009; AUC = 61%), dan usia di bawah cut-off juga lebih banyak ditemukan pada kelompok radioresisten (p = 0,138; AUC = 39,2%). Penelitian ini menunjukkan bahwa ekspresi miR-21 dan LATS1 pra-kemoradiasi yang tinggi serta ekspresi NF-κB yang rendah berhubungan dengan terjadinya radioresistensi. Sebaliknya, konsentrasi miR-145 dan usia tidak berhubungan dengan radioresistensi, sehingga dapat disimpulkan bahwa miR-21 memiliki potensi sebagai biomarker radioresisten pada pasien kanker serviks stadium lanjut lokal dan pemeriksaan kombinasi tidak disarankan.

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Cervical cancer is one of the most common cancers in women with a significant number of cases and deaths, especially in developing countries such as Indonesia. Recent research highlights the role of microRNAs (miRNAs) in carcinogenesis, particularly miR-21, which is involved in various types of cancer in women, including cervical cancer. In addition, miR-145, LATS1 and NF-κB also considered to play a role in radioresistance. This study aims to determine the influence of miR- 21, miR-145, Large Tumor Suppressor 1 (LATS1), Nuclear Factor Kappa B (NF- κB), and age on chemoradiation response in locally advanced cervical cancer patients. This study used an analytical cross-sectional design conducted at Cipto Mangunkusumo Hospital from July 2017 to June 2023. Cervical biopsy tissue samples were collected and examined using real-time reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) to detect miR-21 and miR-145, and ELISA to measure LATS1 and NF-κB concentrations before patients underwent chemoradiation therapy. Ultrasound examination was then re-performed to assess radiation response using RECIST 1.1 criteria. This research obtained a total of 140 samples with histopathological subtype of squamous cell carcinoma found in 119 (85%) samples, with cervical cancer stage IIIB in 102 (72.9%) subjects and stage IVA in 38 (27.1%) subjects. Expression of miR-21 above the cut-off was more prevalent in radioresistant patients (p = 0.010; AUC = 67.6%). Expression of miR-145 and LATS1 above the cut-off were found to be higher in the radioresistant group with p = 0.132 (AUC = 38.8%) and p = <0.001 (AUC = 32.7%), respectively. NF-κB expression below the cut-off were found to be higher in the radioresistant group (p = 0.009; AUC = 61%), and age below the cut-off were also found to be higher in the radioresistant group (p = 0.138; AUC = 39.2%). This study showed that high expression of miR-21 and LATS1 pre-chemoradiation and low expression of NF-κB pre-chemoradiation were all associated with radioresistance, while miR- 145 concentration and age were not associated with radioresistance. This study concluded that miR-21 had the potential to be used as a radioresistant biomarker in patients with local advanced-stage cervical cancer and combination testing was not suggested."

"Latar Belakang: Kelahiran preterm adalah kelahiran sebelum usia kehamilan 37 minggu lengkap. Secara global, kelahiran preterm menyebabkan morbiditas dan mortalitas bayi yang tinggi. Laporan World Health Organization (WHO) tahun 2010, Indonesia saat ini termasuk dalam 10 besar negara dengan jumlah kelahiran preterm terbanyak yaitu 15,5 per 100 kelahiran hidup. Berbagai faktor dihubungkan dengan penyebab terjadinya kelahiran preterm, termasuk salah satunya adanya defisiensi asam lemak tidak jenuh rantai panjang selama kehamilan.Tujuan: Mengetahui kadar asam lemak tidak jenuh rantai panjang (ALA, EPA, DHA, LA dan AA) pada ibu hamil dengan kelahiran preterm dan aterm.Metode: Penelitian dilakukan dengan uji potong-lintang dengan subjek penelitianibu hamil preterm dan aterm yang melakukan persalinan di RSUPN Dr. Cipto Mangunkusumo dan RS Budi Kemuliaan Jakarta pada Juli hingga Desember 2019.Hasil: Diperoleh 60 subjek penelitian dengan 30 subjek pada masing-masing kelompok. Hasil dengan kategori rendah didapatkan pada kelompok preterm dengan median kadar ALA 47 μmol/L, AA 491 μmol/L dengan perbedaan yang bermakna dengan kelompok aterm (p=0,03 dan p=0,01). Indeks omega-3 pada masing-masing kelompok juga rendah yaitu 2,5% pada preterm dan 3% pada aterm.Kesimpulan: Terdapat perbedaan yang bermakna antara kadar ALA dan AA pada ibu yang mengalami kelahiran preterm dan aterm. Tidak terdapat perbedaan yang bermakna kadar EPA, DHA, LA, indeks omega-3, rasio omega-6/ omega-3, dan rasio AA/EPA pada ibu yang mengalami kelahiran preterm dan aterm.

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Background: Approximately 15 million babies were born prematurely every year with one million of them dying from preterm birth complications. Indonesia was among the top 10 countries worldwide with the highest number of preterm births, which was 15.5 preterm births per 100 live births. In recent years, several studies have been investigating the role of nutrition in reducing the risk of preterm birth, one that seems promising is long-chain unsaturated fatty acids (LCPUFA). This study was conducted to determine LCPUFA status in pregnant women who undergo preterm and term births in Jakarta, Indonesia.Objective: To determine the levels of long-chain unsaturated fatty acids (ALA, EPA, DHA, LA dan AA) in pregnant women undergoing preterm and term birth.Method: A descriptive study was conducted on 30 pregnant women in each group who experienced preterm and term births at Cipto Mangunkusumo and Budi Kemuliaan Hospital Jakarta between July and December 2019. Maternal blood plasma was examined by measuring the concentration of alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid (LA), arachidonic acid (AA), omega-3 index, omega-6/ omega-3, and AA/ EPA ratio.Result: The median levels of ALA and AA were low in the preterm birth group with significant differences between the two groups (p= 0,03 and p= 0,01). The median total concentrations of ALA, EPA, DHA, LA, AA, omega-3 index, omega-6/ omega-3, and AA/EPA ratio in preterm birth group were as follows: 47 μmol/L, 18,5 μmol/L, 262 μmol/L, LA 3382 μmol/L, 491 μmol/L, 2,5%, 13 and 26,5. While in the term birth group were as follows 58,5 μmol/L, 19 μmol/L, 262 μmol/L, LA 3382 μmol/L, 491 μmol/L, 2,5%, 13 and 26,5. The median concentration of EPA and DHA on both groups were in a normal range. Most of the subjects had a low omega-3 index, 86,7% from total subjects in preterm and 66,7% in term group.Conclusion: There are significant differences between ALA and AA concentration in women who experienced preterm and term birth. There were no significant differences in levels of EPA, DHA, LA, omega-3 index, omega-6/ omega-3 ratio, and AA/EPA ratio between the two groups."

"Latar Belakang : Kanker paru karsinoma bukan sel kecil (KPKBSK) merupakan jenis kanker paru yang terbanyak. Kesintasan kanker paru terutama ditentukan oleh jenis dan stage kanker. Pada jenis dan stage yang sama masih terdapat perbedaan kesintasan. Inflamasi telah lama diketahui sebagai faktor yang memengaruhi kesintasan pada pasien KPKBSK. Pemeriksaan profil leukosit merupakan pemeriksaan yang murah, cepat dan rutin dikerjakan. Terdapat beberapa penelitian di luar negeri yang meneliti hubungan rasio neutrofil limfosit, rasio trombosit limfosit dan rasio limfosit monosit namun dengan hasil dan titik potong yang beragam. Metode : Penelitian ini menggunakan metode kohort retrospektif pada 148 pasien KPKBSK stage lanjut dengan mutasi epidermal growth factor receptor (EGFR) wild type atau tidak diketahui yang berobat ke RSRRN Persahabatan antara tahun 2018-2019, yang mendapatkan kemoterapi minimal 2 siklus. Dilakukan pencatatan data profil leukosit berupa RNL, RTL dan RLM sebelum menjalani kemoterapi pertama, kemudian diikuti respons klinis berupa kesintasan PFS dan OS. Analisis hubungan antar variabel menggunakan uji korelasi Spearman dan analisis kesintasan menggunakan kurva Kaplan Meier. Hasil : Sampel penelitian 148 pasien KPKBSK stage IIIB-IV dengan proporsi laki-laki 107 orang (72,3%) dan perempuan 41 orang (27,7%). Median usia 57 tahun (16-77 tahun). Didapatkan kanker paru jenis karsinoma sel skuamosa (KSS) sebanyak 83 (56,1%), adenokarsinoma 62 (41,9%) dan adenoskuamosa 3 (2%) dengan performance status (PS) 0-2. Terdapat hubungan yang bermakna antara RNL, RTL dan RLM dengan PFS dan OS. Pasien dengan RNL≥4 memiliki PFS yang lebih rendah (HR=1,689, IK95%:1,189-2,399, p=0,003) dan OS lebih rendah (HR=2,028, IK95%:1,423-2,891, p<0,001). Pasien dengan RTL≥125 memiliki PFS yang lebih rendah (HR=2,229, IK95%:1,226-4,053, p=0,009) dan OS lebih rendah (HR=2,286, IK95%:1,259-4,148, p=0,007). Pasien dengan RLM≥2,5 memiliki PFS yang lebih tinggi (HR=0,464, IK95%:0,316 - 0,682, p<0,001) dan OS lebih tinggi (HR=0,383, IK95%:0,259 - 0,565, p<0,001) Kesimpulan : Nilai RNL, RTL dan RLM memiliki hubungan dengan PFS dan OS pada pasien KPKBSK stage lanjut yang mendapatkan kemoterapi. Baik RNL, RTL maupun RLM dapat digunakan sebagai faktor prognostik pada pasienKPKBSK stage lanjut yang mendapatkan kemoterapi Kata kunci Kemoterapi, KPKBSK, prognosis, rasio neutrofil limfosit (RNL), rasio trombosit limfosit (RTL), rasio limfosit monosit (RLM)

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Background : Non small cell lung cancer (NSCLC) is the most common type of lung cancer. Lung cancer survival is mainly determined by the type and stage of cancer. At the same type and stage, there are still differences in survival. Inflammation has long been recognized as a factor that affects survival in patients with NSCLC. Examination of the leucocyte profile is an inexpensive, fast and routine examination. There are several studies that examine the relationship between the ratio of neutrophil to lymphocytes (NLR), the ratio of platelets to lymphocytes (PLR) and the ratio lymphocytes to monocyte (LMR) but with varying results and cut points. Methods : This study used a retrospective cohort method on 148 advanced stage NSCLC patients with wild type or unknown mutations of epidermal growth factor receptor (EGFR) who were treated at RSRRN Persahabatan between 2018-2019, who received at least 2 cycles of chemotherapy. Leukocyte profile data were recorded in the form of NRL, PLR and LMR before undergoing the first chemotherapy, followed by clinical responses in the form of PFS and OS survival. Analysis of the relationship between variables using the Spearman correlation test and survival analysis using the Kaplan Meier curve. Results : Total sample was 148 NSCLC patients IIIB-IV with the proportion of 107 men (72,3%) and 41 women (27,7%). The median age was 57 years (16-77 years). There were 83 (56,1%) squamous cell carcinoma (SCC) cases, 62 (41,9%) adenocarcinoma cases and 3 (2%) adenosquamous cases with performance status (PS) of 0-2. There is a significant relationship between NLR, PLR and LMR with PFS and OS. Patients with NLR≥4 had lower PFS (HR=1,689, 95% CI:1,189-2,399, p=0,003) and lower OS (HR=2,028, 95% CI:1,423-2,891, p<0,001). Patients with PLR≥125 had lower PFS (HR=2,229, 95% CI:1,226-4,053, p=0,009) and lower OS (HR=2,286, 95% CI:1,259-4,148, p=0,007). Patients with LMR≥2,5 had higher PFS (HR=0,464, 95% CI: 0,316-0.682, p<0,001) and higher OS (HR=0,383, 95% CI: 0,259-0,565, p<0,001) Conclusion : NLR, PLR and LMR values ​​were associated with PFS and OS in advanced stage NSCLC patients receiving chemotherapy. Both NLR, PLR and LMR could be used as prognostic factors in advanced stage NSCLC patients receiving chemotherapy"

"Tujuan. Penelitian ini bertujuan untuk mengetahui profil Treg (ditunjukkan oleh Foxp3), CD4, dan CD8 pada kanker serviks stadium lanjut lokal dan dampaknya terhadap progresivitas tumor dan respons radiasi. Metode. Setelah disetujui oleh komite penelitian, kami mengumpulkan data pasien kanker serviks stadium lanjut lokal yang menjalani radioterapi, di RSCM, Jakarta, pada Januari 2018 – Desember 2020. Subjek penelitian harus memiliki pencitraan pra dan paska radiasi dan spesimen blok parafin untuk memenuhi syarat dalam penelitian ini. Profil Foxp, CD4, dan CD8, akan dianalisis dengan imunohistokimia dengan penghitungan jumlah sel. Respons radiasi akan dianalisa dengan kriteria RECIST 1.1. Semua informasi klinis pasien yang diperlukan akan dikumpulkan dari rekam medis elektronik. Hasil. Kami menemukan bahwa sebagian besar pasien memiliki karsinoma sel skuamosa (93%), stadium IIIC (48%), dan menjalani radiasi saja (72%). Evaluasi RECIST menunjukkan 62% pasien memiliki respons lengkap, 28% respons parsial, dan 10% respons buruk (penyakit stabil dan progresif). Kami dapatkan median jumlah sel CD4 =29 (7 – 154), CD8 = 30 (6 – 227), dan Foxp3 = 36 (2 – 156). Tidak ada hubungan bermakna antara jumlah sel limfosit CD4, CD8, dan Foxp3 dengan volume tumor, dengan p = 0.858; p = 0.975, dan p = 0.723 masing masing. Tidak ada hubungan bermakna dengan dimensi terbesar tumor dengan p = 0.481, p = 0.480, dan p = 0.792 masing masing. Tidak ada pula hubungan bermakna antara jumlah sel limfosit CD4, CD8, dan Foxp3 dengan respons radiasi dengan p = 0.964, p = 0.296, dan p = 0.787 masing masing. Namun kami mendapatkan korelasi positif yang kuat dan bermakna pada jumlah sel tumor pada stroma, CD 4 - CD8 (r = 0.580, p=0.001); CD4 - Foxp3 (r = 0.699, p < 0.001), dan CD8 - Foxp3 (r = 0.652, p < 0.001). Kesimpulan. Sebagian besar pasien kanker stadium lanjut lokal yang menjalani radiasi memiliki respons lengkap. Tidak didapatkan hubungan bermakna antara jumlah sel limfosit CD4, CD8, dan Foxp3 dengan volume tumor, dimensi terbesar tumor, dan respons radiasi. Terdapat korelasi yang kuat dan signifikan antar sel imun (CD4-CD8, CD4-Foxp3, dan CD8-Foxp3) pada lingkungan stroma.

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Aims: This study aims to determine profile of Treg (shown by Foxp3), CD4, and CD8 in locally advanced cervical cancer and the impact to tumor progressivity and radiation response. Method. After been approved by the institution research committee, we collect data of locally advanced of cervical cancer patients who underwent radiotherapy, at RSCM, Jakarta, in January 2018 – December 2020. Studies subjects must have pre and post irradiation imaging and paraffin block specimen to be eligible in this study. Profile of Foxp, CD4, and CD8, will be analyzed by immunohistochemistry, by counting the number of cells, and radiation response will be analyzed by RECIST 1.1 criteria. All necessary patient’s clinical information will be collected from electronic medical record. Result. We found that most of the patients had squamous cell carcinoma (93%), stage IIIC (48%), and underwent radiation alone (72%). RECIST evaluation showed 62% of patients had a complete response, 28% a partial response, and 10% had a poor response (stable and progressive disease). We found median CD4 cell counts = 29 (7 – 154), CD8 = 30 (6 – 227), and Foxp3 = 36 (2 – 156). There was no significant relationship between the number of CD4, CD8, and Foxp3 lymphocytes with tumor volume, with p = 0.858; p = 0.975, and p = 0.723 respectively. There was no significant relationship with the dimensions of the largest tumor with p = 0.481, p = 0.480, and p = 0.792, respectively. There was no significant relationship between the number of CD4, CD8, and Foxp3 lymphocytes with radiation response with p = 0.964, p = 0.296, and p = 0.787, respectively. However, we found a strong and significant positive correlation in the number of tumor cells in the stroma, CD4 - CD8 (r = 0.580, p = 0.001); CD4 - Foxp3 (r = 0.699, p < 0.001), and CD8 - Foxp3 (r = 0.652, p < 0.001). Conclusion. Most locally advanced cancer patients who undergo radiation have a complete response. There are no significant relationships between the number of CD4, CD8, and Foxp3 lymphocytes with tumor volume, largest tumor dimensions, and radiation response. There is a strong and significant correlation between immune cells (CD4-CD8, CD4-Foxp3, and CD8-Foxp3) in the stromal environment."

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Karsinoma sel skuamosa rongga mulut (KSS-RM) merupakan keganasan yang

menempati urutan ke-6 dari seluruh kasus kanker di dunia. Pembedahanmerupakan terapi utama KSS-RM namun pada KSS-RM lanjut lokal,pembedahan merupakan tantangan bagi dokter bedah karena struktur anatomiyang rumit dan dampaknya terhadap kualitas hidup penderita Oleh karena itudipikirkan pemberian kemoterapi neoadjuvan (KN) pada KSS-RM stadium lanjutlokal untuk mengecilkan tumor. Kemoresistensi merupakan masalah pemberianKN pada KSS-RM stadium lanjut lokal akibat microenvironment yang hipoksikditandai dengan peningkatan ekspresi HIF-1α. Kemoresistensi juga diregulasi olehmiR-210 serta peningkatan ekspresi penanda sel punca CD44 dan CD133.Melatonin memiliki efek antioksidan kuat dan efek onkostatik sehinggadiharapkan dapat memperbaiki kondisi hipoksia tumor.Penelitian ini merupakan uji klinis dengan desain paralel acak tersamarpembanding plasebo, yang dilaksanakan pada bulan Juni 2017 hingga Juli 2018,bertujuan untuk mengetahui efektivitas melatonin dalam meningkatkan responsklinis penderita KSS-RM stadium lanjut lokal yang diberikan kemoterapineoadjuvan dan apakah melatonin dapat memperbaiki hipoksia yang ditandaidengan penurunan ekspresi HIF-1α, miR-210, CD44, dan CD133. Sebanyak 50pasien KSS-RM stadium lanjut lokal dari RSCM dan RSKD dirandomisasi.Sebanyak 25 pasien mendapat kombinasi melatonin dan KN (taksan, sisplatin,dan 5-fluorourasil) dan 25 pasien lainnya mendapat KN saja. Sebanyak 25 pasienyang menyelesaikan protokol penelitian (13 pasien kelompok melatonin dan 12pasien kelompok plasebo). Perubahan ekspresi HIF-1α, miR-210, CD44, danCD133 yang diukur dari jaringan biopsi sebelum terapi dan jaringan biopsi/eksisiluas pasca terapi, menggunakan metode qRT-PCR absolute quantification. Selainitu untuk menilai respons klinis digunakan RECIST 1.1 sebelum dan sesudah KN.Melatonin 20 mg perhari menurunkan ekspresi HIF-1α (p = 0,301), miR-210 (p =0,767), dan CD44 (p = 0,103) namun tidak bermakna jika dibandingkan plasebo.Ekspresi CD133 meningkat pada kedua kelompok melatonin dan plasebo (p =0,301) walaupun tidak bermakna. Melatonin 20 mg perhari selama 1 minggusebelum KN pertama dimulai sampai KN selesai tidak memberikan perbedaanrespons positif yang bermakna pada dua kelompok. Penurunan konsentrasi HIF-1a dan CD133 tidak diikuti penurunan persentase sisa tumor. Pada kelompokmelatonin, ekspresi CD44 dan miR-210 menurun diikuti penurunan persentasesisa tumor yang tidak bermakna dibandingkan plasebo. Pada kelompok yangmendapat melatonin, persentase sisa tumor 21,35% lebih rendah dibandingkankelompok plasebo meskipun tidak berbeda bermakna (p = 0,531).

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Squamous cell carcinoma of the oral cancer (OSCC) is the sixth most common

malignancy of all malignant tumors. Surgery is the mainstay of treatment for oralcavity cancers. Surgery in locally advanced OSCC presents many challengesprimarily because the head and neck region have many critical structures that canbe damaged by tumor or treatment. Damage to these structures can result insignificant structural, cosmetic and functional deficits that negatively impactquality of life. Therefore, it is thought that neoadjuvant chemotherapy (KN) inlocal advanced stage OSCC is to shrink the tumor. The chemoresistancy is aproblem of KN administration in locally advanced OSCC due to a hypoxicmicroenvironment characterized by increased expression of HIF-1α. Thechemoresistancy is also regulated by miR-210 as well as increased expression ofCD44 and CD133 stem cell markers. Melatonin has powerful antioxidant effectsand oncostatic effects that are expected to improve tumor hypoxia.This study is a double-blind, randomized clinical trial, which was carried out inJune 2017 to July 2018 to determine the effectiveness of melatonin in improvingthe clinical response of locally advanced OSCC patients given neoadjuvantchemotherapy and whether melatonin can improve hypoxia marked by decreasedexpression of HIF-1α, miR-210, CD44, and CD133. Only 25 patients hadcompleted the study protocol, 13 in melatonin group and 12 in placebo group. Thedifference in HIF-1α, miR-210, CD44, and CD133 expression were measured as adelta concentration using absolute quantification qRT-PCR. The concentration ofthe biomolecular markers within the tumor tissue taken from the first biopsy (pretreatment)were determined using qRT-PCR then subtracted from theconcentration of biomarkers taken from the second biopsy. The clinical responsewas assessed using RECIST 1.1.The administration of melatonin 20 mg/day decreased the expression of HIF-1α(p = 0,301), miR-210 (p = 0,767), and CD44 (p = 0,103) but not statisticallysignificant. CD133 expression increased in both group melatonin and placebo (p= 0,301). Melatonin 20 mg per day for 1 week before NC was started until NCwas completed did not give a significant difference in positive responses in thetwo groups. The decrease concentrations of HIF-1 and CD133 were not followedby a decrease in the percentage of remaining tumors. The melatonin groupshowed a decrement in CD44 and miR-210 followed by a decrement in thepercentage of remaining tumors that were not significant compared to placebo. Inthis study, melatonin did not increase the clinical response although there is21.35% decrement in tumor mass in melatonin group compare (p = 0,531).

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"Pendahuluan: Kanker payudara kanker dengan prevalensi, morbiditas dan mortalitas terbanyak di dunia. Kemoterapi neoadjuvan merupakan terapi sistemik pada kanker yang ditujukan untuk meningkatkan prognosis pasien. Proses imunologi dan inflamasi berperan dalam prognosis tumor. Beberapa indikator inflamasi antara lain neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), dan platelet-lymphocyte ratio (PLR). Penelitian ini ditujukan untuk menganalisa NLR, PLR, dan LMR terhadap respons klinis kanker payudara stadium lokal lanjut.Metode: Desain penelitian ini adalah cross-sectional yang ditujukan untuk menilai hubungan NLR, LMR, dan PLR terhadap respons klinis dengan metode WHO. Penelitian ini akan dilakukan di RSCM pada wanita dengan kanker payudara stadium lokal lanjut yang menjalani kemoterapi neoajuvan RSCM tahun 2016-2021. Pengumpulan data akan dilakukan secara konsekutif (consecutive sampling) pada rekam medis.Hasil: Pada penelitian ini didapatkan 84 subjek penelitian dengan usia rerata 50 tahun dan stadium klinis T4. Pada penelitian ini didapatkan nilai median NLR sebesar 2,62, PLR sebesar 186,9 dan LMR sebesar 3,78 pada populasi sampel. Analisis bivariat antara NLR, LMR, dan PLR dengan respons klinis didapatkan tidak bermakna secara statistik (p>0,05) dengan nilai OR 1,3 (CI95% 0,7-2,2), 0,81 (CI95% 0,04-1,4), dan 1,06 (CI95% 0,5-1,9) secara berurutan. Terdapat hubungan yang bermakna antara NLR dengan kejadian mortalitas 1 tahun (p<0,05) dengan nilai OR 2,27 (CI95% 1,1-4,5).Kesimpulan: Penelitian ini tidak mendapatkan adanya hubungan antara NLR, LMR, dan PLR dengan respons klinis pada kanker payudara lokal lanjut pasca KNA di RSCM.

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Introduction: Breast cancer is one of the most prevalent cancer around the globe with significant morbidity and mortality. Neoadjuvant chemotherapy is a systemic therapy with the aim of reducing the size of tumor, including breast cancer. The role of immunologic and inflammatory process has been reported as a prognostic factors in breast cancer including neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), and platelet-lymphocyte ratio (PLR). We aimed to analyze the role NLR, PLR, and LMR to the clinical response of locally advanced breast cancer after neoadjuvant chemotherapy regimen.

Methods: We used cross-sectional research design for this study with the aim of observe the relation between NLR, LMR, and PLR and clinical response of neoadjuvant chemotherapy. We conducted this study in Cipto Mangunkusumo General Hospital. Our subjects include women with locally advanced breast cancer that has been treated with neoadjuvant chemotherapy between 2016-2021. We collected the subject consecutively using medical record as the primary data source.

Result: We obtained 84 subjects with the mean age of 50 years and clinical stage of T4. The median of NLR, LMR, and PLR were 2.62, 186.9, and 3.78 consecutively. Bivariate analysis of NLR, LMR, dan PLR with clinical response showed no significant association with the odd ratio of 1,3 (CI95% 0,7-2,2), 0,81 (CI95% 0,04-1,4), and 1,06 (CI95% 0,5-1,9) consecutively. We found significant association between NLR and 1 year mortality rate with the odd ratio of 2,27 (CI95% 1,1-4,5).

Conclusion: We found no correlation between NLR, LMR, and PLR with clinical response after neoadjuvant chemotherapy in locally advanced breast cancer."

"Tujuan: Membandingkan distribusi dosis respon akhir RE dan efek samping akut RE teknik konvensional dan teknik konformal pada kasus kanker serviks lokal lanjut Metode Dilakukan studi kohort retrospektif terhadap pasien kanker serviks II B dan III B yang mendapat RE pra brakiterapi di Dept Radioterapi RSCM. Hasil: Didapat 51 pasien menjalani RE teknik konvensional 25 dengan Cobalt 60 26 dengan Linac dan 29 pasien menjalani teknik konformal Sesuai ketentuan ICRU 50 dan 62 prescribed dose dan cakupan volume target teknik konvensional Cobalt lebih kecil p 0 001 dan 1 kasus dari 25 pasien mendapatkan PTV 95 Prescribed dose dan cakupan volume target teknik konvensional Linac lebih besar p 0 001 dibanding teknik konformal Rerata conformity index teknik konvensional sebesar 2 dan teknik konformal 1 02 p 0 001 Dosis dan volume pada buli rektosigmoid dan bowel teknik konvensional lebih besar p 0 001 Respon komplit akhir RE teknik konvensional adalah 42 dan teknik konformal adalah 58 p 0 001 Faktor independen respon akhir RE yaitu stadium FIGO dini dan ukuran tumor sebelum RE kecil le 4cm Pada semua kasus tidak didapatkan efek samping akut lokal yang berat RTOG grade 3 4 Proporsi efek samping ringan RTOG grade 1 2 pada gastrointestinal vesikourinaria dan kulit lebih banyak pada teknik konvensional secara berurutan 72 Vs 28 p 0 002 78 Vs 22 p 0 003 dan 78 Vs 22 p 0 01. Kesimpulan: RE teknik konformal lebih unggul dibanding teknik konvensional dalam distribusi prescribed dose dan cakupan volume target atau organ kritis yang berdampak pada respon tumor akhir RE dan efek samping.

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Purpose: To compare the dose distribution acute tumor response and acute side effects between conventional and conformal techniques EBRT in locally advanced uterine cervical cancerMethods and materials Retrospective cohort study was done in stage II B and III B uterine cervical cancer underwent EBRT before brachytherapy in Dept Radioterapi RSUPN Cipto Mangunkusumo.

Results: Fifety one patients underwent conventional technique EBRT and 29 patients of conformal technique EBRT The average of target prescribed dose and volume coverage of 2 techniques EBRTwas in accordance with criteria of ICRU 50 and 62 smaller p 0 001 only 1 case of Cobalt conventional technique EBRT showed PTV 95 Conformity index of conventional technique EBRT was 2 and conformal technique EBRT was 1 02 p 0 001 Dose and volume of vesicourinary rectosigmoid and distal large bowel of conventional technique EBRT was greater p 0 001 Complete response of conventional technique was 42 and conformal technique was 58 p 0 001 Independent factors were early FIGO stage and tumor size before EBRT le 4cm There were no severe acute side effects RTOG grade 3 4 in both groups Acute side effects RTOG grade 1 2 of conventional techniques was more than conformal gastrointestinal vesikourinaria and skin respectively 72 vs 28 p 0 002 78 vs 22 p 0 003 and 78 vs 22 p 0 01.

Conclusion: Conformal technique EBRT was superior to conventional technique EBRT in prescribed dose distribution target volume coverage and organ at risk dose that impact on acute tumor response and side effects "

"Kanker ovarium memiliki mortalitas mencapai 70%, dan 85% dari pasien yang datang pada kondisi stadium lanjut. Sebanyak > 80% pasien stadium lanjut merespons pada kemoterapi lini pertama yang menggunakan obat berbasis platinum, namun median kesintasan bebas penyakitnya (disease-free survival) hanya mencapai 18 bulan, sebagian besar merupakan pasien kambuh, dan tidak merespons pada kemoterapi lini berikutnya. Pada moda moda kemoresistensi, yang paling dapat diintervensi adalah adanya sel punca kanker (CSC) pada jaringan kanker ovarium pasien. Kemoresistensi pada CSC memiliki beberapa mekanisme berbeda, salah satunya adalah tingginya aktivitas protein ATM dan ATR yang dapat bersifat kompetitif terhadap obat berbasis platinum dalam berikatan dengan DNA. Selama ini, telah banyak penelitian eksperimental yang menarget CSC kanker ovarium, namun penelitian terbaru menggunakan RNA microarray menemukan bahwa gen ADAM19 diekspresikan secara eksklusif pada CSC kanker ovarium sehingga dapat digunakan sebagai marker spesifik. Oleh karena itu, penelitian ini ditujukan untuk mengeksplorasi kemoresistensi pada CSC kanker ovarium dari jaringan segar pasien dan korelasinya dengan ekspresi gen ATM dan ATR, serta mengonfirmasi ekspresi gen ADAM19 sebagai marker spesifik subpopulasi CSC kanker ovarium yang dipilah menggunakan metode MACS dengan penanda CD133. Dari 67 pasien subjek penelitian yang diambil dan dikultur jaringan metastasisnya, dua di antaranya dapat dikultur tanpa batas, menghasilkan kultur dengan dominan sel epitel, dan tidak mengalami senescence. Setelah itu, sel-sel kultur dipilah menggunakan MACS dengan penanda CD133 untuk mendapatkan CSC, kemudian diuji menggunakan metode pembuatan sferoid, RT-qPCR, dan uji kemoresistensi. Dari pembentukan sferoid yang dilakukan pada tiga jenis sel yang digunakan, yakni lini sel SKOV3, serta kultur primer OV1 dan OVM1, ditemukan secara konsisten bahwa jumlah sferoid yang didapatkan pada kultur CSC CD133+ lebih banyak dibandingkan main population (MP) dan CD133-. Dari RT-qPCR juga ditemukan secara konsisten bahwa seluruh ekspresi gen ATM, ATR, NANOG, ADAM19, Ki-67, dan kaspase-3 pada CSC CD133+ lebih tinggi dibandingkan MP dan CD133. Pada uji kemoresistensi terhadap kemoterapi karboplatin, didapatkan bahwa sel CD133+ juga lebih kemoresisten dibandingkan dengan MP dan CD133-. Berdasarkan uji korelasi Spearman Rho, ekspresi gen ATM dan ATR berkorelasi positif sedang menuju sangat kuat dengan sifat kemoresistensi terhadap karboplatin. Pada akhir penelitian, disimpulkan bahwa CSC dengan CD133+ memiliki kemampuan proliferasi yang lebih tinggi dengan ekspresi gen Ki-67 yang meningkat, memiliki stemness yang lebih kuat terlihat pada ekspresi gen Nanog-nya yang lebih tinggi, dan memiliki kemampuan kemoresistensi yang lebih besar ditunjukkan oleh ekspresi gen ATM dan ATR-nya yang tinggi serta berkorelasi positif dengan hasil uji kemoresistensi.

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Ovarian cancer has a mortality rate of up to 70% where 85% of patients present at an advanced stage. More than 80% of advanced stage patients respond to first-line chemotherapy using platinum-based drugs, but the median disease-free survival is only 18 months. Most patients relapse, and do not respond to subsequent lines of chemotherapy. In the chemoresistance modes, the easiest way to intervene is through the presence of cancer stem cells (CSC) in the patient's ovarian cancer tissue. Chemoresistance in CSC has several different mechanisms, one of which is the high activity of ATM and ATR proteins that can be competitive against platinum-based drugs in binding to DNA. So far, there have been many experimental studies targeting ovarian cancer CSCs, but a recent study using RNA microarray found that ADAM19 gene expression is expressed exclusively in ovarian cancer CSCs so that it can be used as a specific marker. Therefore, this study aimed to explore chemoresistance in ovarian cancer CSC from fresh patient’s tissue and its correlation with ATM and ATR gene expression, as well as to confirm ADAM19 gene expression as a specific marker for ovarian cancer CSC subpopulations sorted using the MACS method with the CD133 marker. Out of 67 patients who were the subjects of the study, the samples were taken and cultured for their metastatic tissues, 2 of them could be cultured indefinitely, could produce cultures with a predominance of epithelial cells, and did not experience senescence. After that, the culture cells were sorted using MACS with the CD133 marker to obtain CSC, then tested using the spheroid preparation method, RT-qPCR, and chemoresistance test. From the spheroid culture performed on the 3 types of cells used, namely the SKOV3 cell line, as well as OV1 and OVM1 primary cultures, it was found consistently that the number of spheroids obtained in CD133+ CSC cultures was higher than the main population (MP) and CD133-. From RT-qPCR it was also found consistently that all genes expression ATM, ATR, NANOG, ADAM19, Ki-67, and Caspase-3 in CD133+ CSCs were higher than MP and CD133. In the chemoresistance test to carboplatin chemotherapy, it was found that CD133+ cells were also more chemoresistant than MP and CD133-. Based on the Spearman Rho correlation test, ATM and ATR gene expression had a moderately strong positive correlation with chemoresistance to carboplatin. At the end of the study, it was concluded that CSCs with CD133+ had a higher ability to proliferate with increased expression of the Ki-67 gene, had stronger stemness as seen in the higher expression of the NANOG gene, and had greater chemoresistance ability as indicated by the expression of the ATM gene. and high ATR and positively correlated with chemoresistance test results."