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"Latar belakang: Karsinoma nasofaring (KNF) merupakan penyakit genetik multifaktorial, bersifat endemik dan mempunyai perbedaan signifikan dalam distribusi geografi s. Selain faktor virus Epstein Barr (EBV), insiden KNF juga dipengaruhi oleh faktor genetik seperti polimorfi sme gen reseptor sel T lokus β (TCR-β). Penelitian ini bertujuan untuk mengetahui hubungan polimorfi sme gen TCR-β dengan suseptibilitas individu untuk berkembang menjadi KNF pada populasi Indonesia. Metode: Penelitian dilakukan dengan teknik PCR-RFLP menggunakan enzim restriksi Bgl II pada gen TCR-β. Analisis PCR-RFLP gen TCR-β digunakan untuk mendeterminasi alotip gen TCR-β pada penderita KNF dan kontrol dan pada kelompok etnis Cina dan pribumi dalam populasi Indonesia. Hasil: Hasil penelitian menunjukkan bahwa distribusi alotip gen TCR-β pada penderita KNF dan kontrol tidak berbeda bermakna (p > 0,05). Frekuensi alel A meningkat pada penderita KNF. Distribusi alotip gen TCR-β antara etnis Cina dan kelompok pribumi tidak memperlihatkan perbedaan bermakna (p> 0,05). Kesimpulan: Distribusi alel gen TCR-β antara kelompok KNF dengan kelompok kontrol tidak menunjukkan perbedaan. Distribusi alel gen TCR-β antara etnis Cina dan pribumi tidak menunjukkan perbedaan. Polimorfi sme gen TCR-β tidak berhubungan dengan KNF dan etnis pada populasi Indonesia.

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AbstractBackground: Nasopharyngeal carcinoma (NPC) is a multifactorial genetic disease, characteristically endemic and shows considerable differences in its geographical distribution. Besides infection with EBV, genetic factors such as polymorphisms of TCR-β gene contribute to the incidence of NPC. This study investigates the association of TCR-β gene polymorphisms with individual susceptibility to develop NPC in Indonesian ethnic groups. Methods: The study was carried out by the PCR-RFLP method using Bgl II restriction enzyme to digest TCR-β gene. The PCR-RFLP analysis of TCR-β gene was used to determine allotypes of TCR-β gene in NPC patients and control among ethnic Chinese and indigenous groups in the population of Indonesia. Results: The results indicate that the distribution of TCR-β gene allotypes between NPC patients and controls are not signifi cantly different (p > 0.05); however, the frequency of A allele tends to increase in NPC patients. The distribution of TCR-β gene allotypes between Chinese ethnic group was not signifi cantly different from indigenous groups (p > 0.05). Conclusion: The distribution of TCR-β gene allele between NPC group and control groups showed no difference. The distribution of TCR-β gene between ethnic Chinese and indigenous groups showed no difference. Polymorphisms of TCR-β gene are not associated with NPC and ethnic groups in Indonesian population. "

"AbstrakNasopharyngeal carcinoma (NPC) is the most frequent head and neck malignancy in Indonesia. Misdiagnosis of NPC is common because of unspecific symptoms as unilateral ear complaint. This case reminds doctors of the early symptoms of NPC and of other factors which lead to misdiagnosis and addresses also patients and their families. Reported is a 44 years old man with unilateral ear disorder that had been treated by otorhinolaryngologists, an ophthalmologist, a neurologist, and dentist first, but diagnosed with nasopharyngeal carcinoma stage IVA (T4N1M0) one year later. NPC has unspecific early symptoms such as unilateral ear disorder. Primarily doctors, but also patients and their families should be aware of unilateral ear complaint."

"Penelitian ini bertujuan untuk memverifikasi dosis radiasi radioterapi pada kasus kanker payudara dan kanker nasofaring (KNF). Percobaan dilakukan dengan menggunakan Linac Varian Trilogy radiasi foton berenergi 6 MV. Detektor yang digunakan dalam penelitian ini adalah film gafchromic, MatriXX 2D array, TLD, dan EPID. Film gafchromic dan TLD ditempatkan dalam phantom rando untuk mengevaluasi distribusi dosis pada volume target, sedangkan untuk mendapatkan hasil registrasi film gafchromic dan MatriXX 2D array ditempatkan dalam Multi Cube, dan dilakukan juga penyinaran pada EPID. Hasil perbedaan distribusi dosis teknik IMRT dan VMAT antara film dengan dosis preskripsi TPS pada KNF PTV70 adalah 6,87% dan 8,55%, pada KNF PTV50 adalah 14,43% dan 4,65%, sedangkan pada kanker payudara 11,98% dan 12,10%. Perbedaan nilai dosis antara TLD dengan dosis preskripsi TPS teknik IMRT dan VMAT pada KNF PTV50 sebesar 1,76% dan 1,60%, dan pada kanker payudara sebesar 7,06% dan 3,36%. Selisih perbedaan nilai gamma indeks teknik IMRT dan VMAT pada KNF sebesar -0,09% dan -1,65% antara film dan MatriXX, dan 5,13% dan 1,43% antara film dengan EPID. Pada kanker payudara selisih perbedaan nilai gamma indeks teknik IMRT dan VMAT sebesar 0,51% dan 0,19% antara film dengan MatriXX, dan 2,28% dan 4,38% antara film dengan EPID. Verifikasi dosis radioterapi dan registrasi citra pada kasus kanker payudara dan KNF dapat dilakukan menggunakan film gafchromic, TLD, MatriXX 2D array, dan EPID.

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This study was aimed to verify the radiation dose in the case of breast cancer and nasopharyngeal carcinoma (NPC). The experiments were performed using a Varian Trilogy Linac at 6 MV photon radiation and gafchromic films, Matrixx 2D Array, TLD, and EPID detectors. Gafchromic films and TLD were inserted into rando phantom to measures the dose on target volume and organ at risk. In order to evaluated the gamma index, gafchromic films and Matrixx 2D array were placed in the Multi Cube, and was irradiated with EPID in position. Results of the dose distribution differences on IMRT and VMAT between film and TPS on NPC PTV70 was 6.87% and 8.55%, the NPC PTV50 was 14.43% and 4.65%, and for breast cancer was 11,98% and 12,10%. The dose differences between TLD and TPS on IMRT and VMAT for NPC PTV50 was 1.76% and 1.60%, and the breast cancer was 7.06% and 3.36%. Gamma index differences on IMRT and VMAT technique on NPC was -0.09% and -1.65% between film and MatriXX, and 5.13% and 1.43% between films and EPID. In breast cancer the gamma index differences on IMRT and VMAT was 0.51% and 0.19% between films and MatriXX, and 2.28% and 4.38% between films and EPID. Radiotherapy dose verification and image registration for breast cancer and NPC was done using gafchromic film, TLD, MatriXX 2D array, and EPID."

"Latar belakang: kanker nasofaring (KNF) adalah keganasan yang umum dijumpai pada nasofaring. Cukup banyak bukti menunjukkan adanya keterkaitan KNF dengan sistem kekebalan tubuh. Tidak semua subset sel T merupakan sel T efektor. Sel T regulator (TReg) yang merupakan salah satu subset dari sel T, memiliki peran penting dalam mengatur imunitas anti tumor. Sampai saat ini belum dapat disimpulkan bahwa keberadaan sel TReg pada lokasi tumor pasti akan memicu pertumbuhan tumor. Akan tetapi, adanya sel T CD4+ dan CD8+ tentunya berpengaruh terhadap kontrol perkembangan tumor. Studi ini bertujuan untuk menilai karakterisitik CD4, CD8 dan FOXP3 pada pasien KNF dan hubungannya terhadap agresivitas tumor.Metode: penelitian ini merupakan studi kohort prospektif. Sel TReg dinilai menggunakan marker FOXP3. Jumlah protein CD4, CD8 dan FOXP3 pada jaringan biopsi tumor dideteksi dan diukur dengan ELISA. Volume tumor primer dan volume total metastasis kelenjar getah bening regional didapatkan dari proses delineasi dengan pencitraan 3D. Spearmen-rho test digunakan untuk menilai korelasi antara CD4, CD8 dan FOXP3 dengan volume tumor primer dan volume total metastasis kelenjar getah bening regional.Hasil: Sebanyak 23 subjek penelitian (14 pria dan 9 wanita) terkumpul berdasarkan kriteria inklusi dan eksklusi. Stadium KNF terbanyak pada studi ini adalah stadium IV (AJCC edisi ke-8). Analisis dengan uji Spearman menunjukkan korelasi kuat antara konsentrasi protein FOXP3 dan volume tumor primer (p=0.02, r=0.60), dan juga antara konsentrasi protein CD8 dan volume tumor primer (p=0.00, r=0.81). Menariknya, juga ditemukan korelasi antara konsentrasi CD8 dan FOXP3 (p=0.00, r=0.85). Tidak ditemukan korelasi antara konsentrasi protein CD4, CD8 dan FOXP3 dengan volume total metastasis kelenjar getah bening regional. Tidak ditemukan juga korelasi antara konsentrasi FOXP3 dan stadium KNF. Sayangnya, belum dapat disimpulkan hubungan antara konsentrasi FOXP3 dan respons terapi pada penelitian ini.Kesimpulan: Keberadaan sel TReg berpengaruh terhadap agresivitias lokal tumor yang ditandai dengan peningkatan volume massa tumor primer. Korelasi antar konsentrasi CD4, CD8 dan FOXP3 memberikan gambaran interaksi dan mekanisme respons imunitas tubuh dalam menjaga keseimbangan antara sel T efektor dan sel T regulator.

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Background: nasopharyngeal cancer (NPC) is a common malignancy found in the nasopharynx area. There is quite a lot of evidence showing a link between NPC and the immune system. Regulatory T cells (TReg), a subset of T cells, have an essential role in regulating anti-tumor immunity. It has not been confirmed that TReg cells at the tumor site will trigger tumor growth. However, the presence of CD4+ and CD8+ T cells certainly affects the control of tumor growth. This study aims to assess the characteristics of CD4, CD8, and FOXP3 in NPC patients and their relationship with tumor aggressiveness.

Methods: a prospective cohort study was conducted on 23 subjects (14 men and 9 women) based on the inclusion and exclusion criteria. TReg cells were assessed using the FOXP3 marker. The number of CD4, CD8, and FOXP3 proteins in tumor biopsy tissue was detected and measured by ELISA kit (MBS2702975, MBS165145, MBS162054). The volume of the primary tumor and the total volume of regional lymph node metastases were obtained from the delineation process based on 3D imaging. Spearmen-rho test was used to assess the correlation of CD4, CD8, and FOXP3 with primary tumor volume and total volume of regional lymph node metastases.

Results: A total of 23 study subjects (14 men and 9 women) were collected based on the inclusion and exclusion criteria. The most common NPC stage in this study was stage IV (AJCC 8th edition). Analysis by the Spearman-rho test showed a strong correlation between; concentration of FOXP3 protein and primary tumor volume (p=0.02, r=0.60) and the concentration of CD8 protein and primary tumor volume (p=0.00, r=0.81). Interestingly, a correlation was also found between the concentration of CD8 protein and FOXP3 (p=0.00, r=0.85). There was no correlation between CD4, CD8, and FOXP3 proteins and the total volume of regional lymph node metastases. There was also no correlation between FOXP3 concentration and NPC stage. Unfortunately, it is impossible to conclude the relationship between FOXP3 concentration and treatment response in this study.

Conclusions: the presence of TReg cells affects the local aggressiveness of the tumor, which is characterized by an increase in the volume of the primary tumor. The correlation between CD4, CD8, and FOXP3 concentrations provides an overview of the interactions and mechanisms of the body's immune response to maintain a balance between effector T cells and regulatory T cells."

"Latar Belakang: Ekspresi PD-L1 sering ditemukan pada keganasan yang terkait dengan virus Epstein-Barr (EBV) seperti karsinoma nasofaring. Studi terbaru menunjukkan bahwa keganasan terkait EBV memiliki tingkat ekspresi PD-L1 yang tinggi. Tetapi mekanisme yang mendasari regulasi PD-L1 dan EBV terhadap ekstensi tumor masih kurang dipahami. Beberapa literatur menghubungkan parameter ini dengan tumor stadium lanjut dan prognosis buruk. Studi ini akan menilai konsentrasi PD-L1 dan DNA EBV pada jaringan tumor, pada pasien kanker nasofaring di populasi Indonesia yang dikumpulkan secara konsekutif dan dikorelasikan dengan ekstensivitas tumor. Metode: Kami menggunakan imunohistokimia dan ELISA untuk menilai PD-L1 dan reaksi rantai polimerase (PCR) juga dilakukan untuk menilai konsentrasi DNA EBV (EBNA-1 sebagai primer). Delineasi tumor dilanjutkan dengan perhitungan volumetrik menggunakan Eclipse Treatment Planning System. Semua pemeriksaan dilakukan pra terapi. Kami memperoleh data kuantitatif dan kualitatif. Kurva korelasi didapatkan menggunakan uji korelasi Pearson.  Hasil: Tidak ada korelasi antara DNA EBV dan ekstensivitas kanker nasofaring dengan ekspresi PD-L1 positif (p = 0,371). Lebih lanjut, tidak ada korelasi antara DNA EBV dan PD-L1.  Kesimpulan: Berapapun banyaknya tumor viral load DNA EBV dan konsentrasi PD-L1 tidak akan berpengaruh pada ekstensivitas tumor. Ini adalah studi pendahuluan.

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Background: PD-L1 expression is often found in malignancies associated with Epstein-Barr virus (EBV) such as nasopharyngeal carcinoma. Recent studies shown that EBV-related malignancies have high levels of PD-L1 expression. But the mechanism underlying the regulation of PD-L1 and EBV DNA against tumor extension is still poorly understood. Some literature links this parameter with advanced tumors and poor prognosis. This study will assess tumor tissue PD-L1 and EBV DNA concentrations in nasopharyngeal cancer patients in the Indonesian population collected consecutively and correlate with tumor extensivity. 

Methods: We used immunohistochemical and ELISA to assess PD-L1 and polymerase chain reaction is also performed to assess the EBV DNA concentrations (EBNA-1 as primary). Tumor volume delineation continued with volumetric calculation using Eclipse treatment planning system. All examinations were carried out pre therapy. Quantitative and qualitative data was obtained. Correlation curves were estimated using the Pearson correlation test. 

Results: There was no correlation between EBV DNA and nasopharyngeal cancer extension with positive PD-L1 expression (p = 0.371). Furthermore, there is also no correlation existed between the EBV DNA copy and PD-L1. 

Conclusion: No matter how much tumor EBV DNA viral load and PD-L1 concentrations had no effect on tumor extensivity. This is a preliminary study."

"Pendahuluan: Malnutrisi dan hipoksia merupakan faktor yang mempengaruhi kegagalan terapi pada KNF stadium lokal lanjut. Kadar albumin merupakan salah satu pemeriksaan status nutrisi. Hipoksia menyebabkan radioresistensi terhadap radiasi.Tujuan dari penelitian ini adalah mengetahui korelasi antara kadar albumin praradiasi, hipoksia terhadap respon radiasi. Metode penelitian: Penelitian ini merupakan studi kohort retrospektif menggunakan data sekunder terhadap 40 pasien kanker nasofaring stadium lokal lanjut yang memenuhi kriteria inklusi di Departemen Radioterapi dan Departemen Patologi Anatomi RSUP Dr Cipto Mangunkusumo dari Desember 2012 sampai Agustus 2013. Dilakukan pencatatan kadar albumin praradiasi, berat badan serta CT scan sebelum dan sesudah radiasi. Kemudian dilakukan analisa HIF1α dengan pulasan imunohistokimia. Sel yang positif hipoksia dihitung per 10 lapang pandang besar. Setelah itu, dilakukan penilaian respon radiasi berdasarkan kriteria Recist. Hasil: Rerata kadar albumin praradiasi sebesar 3,9 +/- 0,5 g/dL, dan median persentase hipoksia sel yaitu 24,7(1-100)%. Tidak terdapat hubungan yang bermakna antara kadar albumin praradiasi terhadap respon radiasi (p≥0,05). Terdapat hubungan yang bermakna anatara hipoksia terhadap respon radiasi (p<0,05). Korelasi antara kadar albumin praradiasi dan hipoksia menunujukkan korelasi yang lemah dan tidak bermakna (r=-0,24, p=0,324). Kesimpulan: Hasil penelitian ini memperlihatkan bahwa albumin praradiasi tidak berhubungan dengan respon radiasi pada KNF stadium lokal lanjut. Terbukti bahwa hipoksia meningkatkan radioresistensi dan menurunkan respon radiasi. Tidak terdapat korelasi antara albumin praradiasi dan hipoksia.

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Introduction: Malnutrion and hypoxia had been shown to cause irradiation failure. Albumin is one of the nutritional status examination. Hypoxia caused radioresistance to irradiation. The purpose of this study was to evaluate the correlation of albumin, hypoxia towards radiation response in locally advanced nasopharyngeal carcinoma.

Methods: This is a retrospective cohort study using secondary data from Departement of Radiotheraphy and Departement of Pathology Cipto Mangunkusomo hospital of 40 patients locally advanced nasopharyngeal cancer who meet the inclusion criteria from December 2012 to August 2013. Albumin preirradiation, body weight and CT scan before and after radiation were recorded. We examined the expression of HIF1 α by immunohistochemistry staining. Hypoxia cell was asessed by cell counting. Radiation response was determined by Recist criteria.

Results: The mean of serum albumin is 3.9 + / - 0.5 g /dL, and the median percentage of hypoxia was 24,7(1-100)%. There was no statistically significant relationship between albumin and radiation response (p≥0.05). There was a statistically significant relationship between hypoxia and radiation response (p<0,05). There were no correlation between albumin and hypoxia (r=-0,24, p=0,324).

Conclusion: This study showed that there was no correlation between albumin preirradiation and response in locally advanced nasopharyngeal cancer. It was proven that hypoxia increased radioresistance in locally advanced nasopharyngeal cancer. There was no correlation between albumin preirradiation and hypoxia."

"Malnutrisi pada kanker nasofaring (KNF) disebabkan oleh peradangan, sel tumor dan efek kemoradioterapi. Malnutrisi dikaitkan dengan penurunan kualitas hidup, fungsi fisik, dan kelangsungan hidup. Pemberian nutrisi pasien KNF yang menjalani radioterapi (RT) memperbaiki status gizi, kapasitas fungsional, dan prognosis keseluruhan. Pasien KNF dengan kaheksia, usia 29 - 67 tahun, tiga pria dan satu wanita yang menjalani kemoradioterapi. Diberikan nutrisi sesuai kebutuhan energi, makronutrien, mikronutrien, dan nutrien spesifik. Pemantauan pasien di awal, hingga RT selesai, pada keluhan terkait terapi, analisis asupan, antropometri, komposisi tubuh, kapasitas fungsional, dan pemeriksaan CRP. Didapatkan penurunan asupan pada empat pasien saat RT, tetapi meningkat lagi pada tiga pasien setelah pemasangan NGT. Satu pasien dengan peningkatan berat badan (BB), sedangkan 3 pasien lainnya BB menurun 2,2-13% pasca RT. Tiga pasien dengan CRP meningkat pada awal RT, tetapi hanya 1 pasien dengan CRP kembali normal. Massa otot meningkat pada 3 pasien setelah RT. Tiga pasien mengalami perbaikan skor ECOG pasca RT, dan satu pasien dengan skor ECOG tetap stabil. Pemasangan NGT dapat mempertahankan asupan pasien. Terapi nutrisi memperbaiki penurunan BB, tetapi tidak terlihat kaitan dengan CRP, massa otot dan kapasitas fungsional karena faktor lain.

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Malnutrition in nasopharyngeal carcinoma (NPC) is induced by inflammation, tumor cells and the effects of chemoradiotherapy. Malnutrition is associated with decrease in quality of life, physical function and survival. Nutritional therapy to NPC who underwent radiotherapy (RT) improves nutritional status, functional capacity, and prognosis. NPC cachexic patients, ages 29 - 67 years, three male and one female, all underwent chemoradiotherapy. Nutrition therapy start with planning of energy, macronutrient, micronutrient and specific nutrients needs. Patients monitoring start from the the beginning, until completed RT, related to therapy, intake analysis, anthropometry, body composition, functional capacity, and C-Reactive Protein (CRP) examination. Decrease intake in four patients during RT, but it increased in three patients after NGT insertion. One patient increase body weight (BW), while other 3 patients dropped BW 2.2-13% post-RT. Three patients increase in CRP at the start of RT, but only 1 CRP patient returned to normal. Muscle mass increased in 3 patients after RT. Three patients had improved ECOG scores after RT, and one patient with ECOG scores remained stable. Insertion of NGT can maintain patient intake. Nutritional therapy maintains BW, but does not appear to be related to CRP, muscle mass and functional capacity due to other factors."

"Karsinoma nasofaring (KNF) merupakan penyakit endemis di Indonesia dengan tingkat mortalitas yang tinggi. Salah satu penyebab mortalitas adalah metastasis jauh. VEGF-A terbukti berperan pada kejadian metastasis jauh KNF, namun penelitian yang membahas hubungan langsung keduanya masih terbatas. Selain VEGF, terdapat jalur pensinyalan lain terkait VEGF yang mungkin berperan dalam kejadian metastasis jauh, yaitu jalur pensinyalan Hippo. Protein Yes-Associated Protein (YAP) adalah downstream efektor utama dari jalur pensinyalan ini. Dengan dilakukan pulasan YAP serta dievaluasi hubungan antara YAP dengan VEGF-A diharapkan hasilnya dapat memberikan informasi mengenai potensi biomarker sebagai indikator prognostik kejadian metastasis jauh KNF. Penelitian menggunakan metode analitik observasional dengan uji Chi-square dan korelasi koefisien kontingensi. Terdapat perbedaan ekspresi YAP yang bermakna pada kelompok KNF dengan dan tanpa metastasis jauh (p<0,001). Terdapat perbedaan bermakna ekspresi VEGF-A pada kelompok KNF dengan dan tanpa metastasis jauh (p<0,001). Ekspresi YAP yang tinggi berhubungan dengan peningkatan ekspresi VEGF-A (p=0,001). Terdapat korelasi signifikan antara peningkatan ekspresi YAP dan peningkatan ekspresi VEGF-A dengan kekuatan lemah (C=0,397, p=0,01). Terdapat perbedaan bermakna koekspresi YAP tinggi dan VEGF-A tinggi (double co-high-expression) antara kelompok KNF dengan dan tanpa metastasis jauh (p<0,001). Penelitian ini mendukung sifat onkogenik YAP. YAP dan VEGF-A dapat menjadi biomarker potensial untuk memprediksi kejadian metastasis jauh KNF.

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Nasopharyngeal carcinoma (NPC) is an endemic disease in Indonesia with a high mortality rate. Distant metastasis is one of the leading causes of death. Although VEGF-A has been found to play a role in distant NPC metastasis, research on the relationship between the two is still limited. Another VEGF-related pathway, the Hippo pathway, may be involved in distant metastasis. Yes-Associated Protein (YAP) is the main downstream effector of this signaling pathway. It is expected that performing YAP marker and studying the relationship between YAP and VEGF-A, would provide data on the possibility of biomarkers that may be used as a prognostic predictor of the occurrence of distant metastasis in NPC. An observational analytic study was conducted—statistical analysis using SPSS 25.0 with Chi-square and contingency coefficients test. There was a significant difference in YAP expression between NPC with and without distant metastasis (p<0.001). The expression of VEGF-A differed significantly between NPC with and without distant metastasis (p<0.001). There was a significant relationship between YAP and VEGF-A (p=0.001) and a weak correlation (C 0.397, p=0.01). There was a significant difference in the double co-high-expression group between the KNF with and without distant metastasis (p<0.001). This study highlights YAP's oncogenic role in NPC, suggesting that YAP and VEGF-A might be potential biomarkers to predict distant metastasis in NPC."