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Abstrak :
ABSTRAK
Latar belakang: Seminoma testis yang gagal sembuh dengan penatalaksanaan konvensional memiliki prognosis buruk. Beberapa kejadian rekuren setelah dilakukan kemoterapi juga ditemukan. Programmed Death Ligand-1 (PD-L1) terekspresi pada berbagai keganasan dan tumor infiltrating lymphocytes(TILs) serta telah diketahui perannya sebagai faktor prognostik. Penelitian ini dilakukan untuk mengetahui peran ekspresi PD-L1 pada seminoma testisdalam menentukanoverall survival(OS) danprogression free survival(PFS).

Bahan dan cara: Penelitian ini merupakan penelitiankohort retrospektif dengan desain analisis kesintasan. Data klinis diambil dari rekam medis RSUPN Cipto Mangunkusumo sejak Januari 2011-Desember 2016 yang diobservasi selama 2 tahun. Data histopatologik diambil dari Departemen Patologi Anatomik RSUPN Cipto Mangunkusumoyang kemudian dilakukan pulasan imunohistokimia PD-L1.

Hasil: Terdapat hubungan yang bermakna antara ekspresi PD-L1 pada sel tumor dengan 2-yearOS (p=0,023) dan PFS (p=0,002) padaseminoma testis.Tidak terdapat hubungan yang bermakna antara ekspresi PD-L1 pada TILs dengan 2-year OS (p=0,235) dan PFS (p=0,111). Terdapat hubungan bermakna antara ekspresi PD-L1 pada sel tumor dan ekspresi PD-L1 pada TILs dengan PFS (p=0,019). Terdapat hubungan yang bermakna antara stadiumdengan 2-yearOS (p=0,010)dan PFS (p=0,000)serta metastasis kelenjar getah beningpada 2-yearOS (p=0,010)dan PFS (p=0,000).

Kesimpulan: Ekspresi PD-L1 pada sel tumor seminoma testis berhubungan dengan OS dan PFS, tetapi hubungan tersebut tidak ditemukan pada TILs.

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ABSTRACT
Background: The prognosis of testicular seminoma who failed to be cured with conventional therapy is poor. Several recurrent events after chemotherapy were also found. PD-L1 is expressed in various types of malignancy and tumor infiltrating lymphocytes (TILs) and its role is known as a prognostic factor. This study was conducted to determine the role of PD-L1 expressionseminomain determining overall survival (OS) and progression free survival(PFS).

Materials and Methods: Thisis aretrospective cohort study with survival analysis. Clinical datawere obtained from medical record in RSUPN Cipto Mangunkusumo since January 2011-December 2016 and observed for 2 years. Histopathological datawere obtained from Anatomical Pathology Department and PD-L1 immunohistochemistry staining were performed.

Results: Asignificant correlation between PD-L1 expression in tumor cells with 2-year OS (p=0,023) and PFS(p=0,002) intesticular seminoma was found. Nosignificant correlation between PD-L1 expression in TILs with 2-year OS (p=0,235)and PFS (p=0,111).We also found significant correlations between PD-L1 expression in tumor cells and TILs with PFS (p=0,019). A significant correlation between stage with 2-year OS (p=0,010)and PFS (p=0,000) and lymph node metastases with 2-year OS (p=0,010) and PFS (p=0,000)

Conclusion: PD-L1 expression in tumor cells testicular seminoma were significantly correlated with OS and PFS. There were no statistically significant associations between PD-L1 expression in TILs with OS and PFS.

Abstrak :
Latar Belakang: Limfoma Hodgkin merupakan keganasan yang mencakup 1% kasus kanker keseluruhan. Adapun overall survival (OS) pasien limfoma Hodgkin dalam lima tahun mencapai 90%. Namun, progression-free survival (PFS) limfoma Hodgkin hanya mencapai 70-90% dalam kurun waktu 25 bulan. Setelah mengalami progresivitas, pasien mengalami penurunan PFS setelah mendapat terapi lini kedua. Sehingga, perlu diketahui faktor-faktor prediktor yang mempengaruhi PFS pasien limfoma Hodgkin. Tujuan: Mengetahui faktor-faktor prognostik PFS dua tahun pasien limfoma Hodgkin. Metode: Penelitian ini menggunakan desain kohort retrospektif yang melibatkan pasien limfoma Hodgkin yang teregistrasi dari tahun 2011-2021 di Rumah Sakit Umum Pusat Nasional Dokter Cipto Mangunkusumo. Faktor-faktor prognostik yang diteliti adalah stratifikasi risiko, skor prognosis internasional, kadar trombosit, laktat dehidrogenase, indeks komorbiditas Charlson, dan waktu sejak diagnosis hingga terapi. Analisis multivariat terhadap PFS dua tahun dilakukan menggunakan model regresi Cox. Hasil: Terdapat 115 subjek yang disertakan dalam penelitian dengan median usia 29 tahun, kadar trombosit 393.000 sel/L, LDH 340 IU/L, dan waktu sejak diagnosis hingga terapi enam minggu. Sebagian besar subjek penelitian adalah kelompok stadium lanjut (53,91%), total skor prognosis internasional 0-3 (69,57%), dan total skor indeks komorbiditas Charlson 0-1 (75,65%). Angka PFS dua tahun pasien limfoma Hodgkin di RSCM sebesar 59,13%. Hasil analisis bivariat menunjukkan waktu sejak diagnosis hingga terapi yang tidak memiliki kemaknaan secara statistik dengan HR 0,83 (IK 95% 0,42-1,59, p=0,57). Analisis multivariat menghasilkan tiga faktor prognostik independen, yakni stadium lanjut (HR 7,85 IK 95% 3,01-20,47, p<0,01), trombosit >450.000 sel/L (HR 2,77 IK 95% 1,49-5,16, p<0,01), dan LDH baik 250-500 IU/L (HR 2,57 IK 95% 1,01-3,63, p=0,04) maupun >500 IU/L (HR 3,06 IK 95% 1,20-7,82, p=0,02). Sistem skor berdasarkan ketiga variabel tersebut memiliki diskriminasi yang baik (AUROC 0,879, IK 95% 0,816-0,942, p <0,01). Kesimpulan: Stadium lanjut, trombosit >450.000 sel/L, dan LDH 250 IU/L merupakan faktor-faktor prognostik PFS dua tahun pada pasien limfoma Hodgkin. ......Background: Hodgkin's lymphoma is a malignancy that accounts for 1% of all cancer cases. The overall survival (OS) of Hodgkin's lymphoma patients in five years reaches 90%. However, progression-free survival (PFS) for Hodgkin's lymphoma only reaches 70-90% within 25 months. After experiencing progression, patients experienced a decrease in PFS after receiving second-line therapy. So, it is necessary to know the predictor factors that influence the PFS of Hodgkin's lymphoma patients. Aim: To determine prognostic factors for two-year PFS in Hodgkin's lymphoma patients. Methods: This study used a retrospective cohort design involving Hodgkin's lymphoma patients registered from 2011-2021 at Dokter Cipto Mangunkusumo National General Hospital. The prognostic factors studied were risk stratification, international prognosis score, platelet levels, lactate dehydrogenase, Charlson comorbidity index, and time from diagnosis to therapy. Multivariate analysis of two-year PFS was performed using Cox regression models. Results: There were 115 subjects included in the study with a median age of 29 years, platelet levels of 393,000 cells/L, LDH 340 IU/L, and time from diagnosis to therapy of six weeks. Most of the research subjects were in the advanced stage group (53.91%), the total international prognosis score was 0-3 (69.57%), and the total Charlson comorbidity index score was 0-1 (75.65%). The two-year PFS rate for Hodgkin's lymphoma patients at RSCM was 59.13%. The results of bivariate analysis showed that the time from diagnosis to therapy was not statistically significant with HR 0.83 (95% CI 0.42-1.59, p=0.57). Multivariate analysis yielded three independent prognostic factors, namely advanced stage (HR 7.85, 95% CI 3.01-20.47, p<0.01), platelets >450,000 cells/L (HR 2.77, 95% CI 1.49-5.16, p<0.01), and LDH either 250-500 IU/L (HR 2.57, 95% CI 1.01- 3.63, p=0.04) or >500 IU/L (HR 3.06 95% CI 1.20-7.82, p=0.02). The scoring system based on these three variables had good discrimination (AUROC 0.879, 95% CI 0.816- 0.942, p <0.01). Conclusion: Advanced stage, platelets >450,000 cells/L, and LDH >250 IU/L are prognostic factors for two-year PFS in Hodgkin's lymphoma patients.

Abstrak :
Latar Belakang: Kanker nasofaring (KNF) merupakan jenis keganasan yang paling umum terjadi di wilayah kepala dan leher di Indonesia. Saat ini, terjadi pergeseran paradigma ke konsep tumor microenvironment, yang menekankan pentingnya penanda biologis. Rasio limfosit monosit (RLM) mencerminkan Tumor-Infiltrating Lymphocytes (TIL) dan Tumor- Associated Macrophages (TAM). Namun, temuan penelitian tentang RLM, TIL CD8, dan TAM CD163 sebagai prediktor untuk Progression-Free Survival (PFS) masih kontroversial. Belum ada penelitian yang menyelidiki hubungan antara marker-marker ini dan PFS 3 tahun pada pasien KNF stadium lokal lanjut di Indonesia. Tujuan: Mengetahui PFS 3 tahun pada pasien KNF stadium lokal lanjut dan mengetahui hubungan antara RLM, TIL, dan TAM dengan PFS 3 tahun. Metode: Studi kohort retrospektif yang dilakukan di Rumah Sakit Cipto Mangunkusumo (RSCM) selama periode Januari 2015 hingga 2020. Kami menghimpun data mengenai karakteristik demografis pasien, menghitung RLM, dan pewarnaan imunohistokimia untuk TAM CD163 dan TIL CD8 pada blok biopsi jaringan. Analisis penentuan nilai titik potong dilakukan melalui kurva receiver operating curve (ROC) untuk ketiga ini. Setelahnya, kami melakukan analisis terhadap ketiga parameter tersebut terkait PFS 3 tahun dengan menggunakan kurva Kaplan-Meier dan uji log rank. Untuk mengatasi variabel perancu, dilakukan uji Cox Regression. Hasil: Didapatkan persentase PFS 3 tahun KNF stadium lokal lanjut sebesar 46,7%. Nilai titik potong terbaik untuk RLM, CD163, dan CD8 berturut – turut adalah 1,82, 1,96, dan 47,5%. Berdasarkan analisis bivariat dan multivariat, didapatkan RLM ≤ 1,82 (aHR 1,785, IK95% 1,057 – 3,018), CD163 ≥196 (aHR 6,126, IK95% 3,382 – 11,097), dan CD8 ≤47,5% (aHR 2,099, IK95% 1,232 – 3,575). Simpulan: Nilai RLM dan TIL CD8 yang tinggi berhubungan dengan PFS 3 tahun yang baik, sedangkan TAM CD163 yang tinggi berhubungan dengan PFS 3 tahun yang buruk pada pasien KNF lokal lanjut. ......Background: Nasopharyngeal cancer (NPC) is the most common malignancy in the head and neck region in Indonesia. Recently, there has been a paradigm shift towards the concept of the tumor microenvironment, emphasizing the significance of biological markers. The lymphocyte-to-monocyte ratio (LMR) reflects Tumor-Infiltrating Lymphocytes (TILs) and Tumor-Associated Macrophages (TAMs). However, findings on LMR, CD8 TILs, and CD163 TAMs as predictors for Progression-Free Survival (PFS) remain controversial. No study has yet investigated the relationship between these markers and 3-year PFS in patients with advanced local-stage NPC in Indonesia. Objective: To determine the 3-year PFS in patients with advanced local-stage NPC and to ascertain the relationship between LMR, TILs, and TAMs with 3-year PFS. Methods: A retrospective cohort study was conducted at Cipto Mangunkusumo Hospital (RSCM) from January 2015 to 2020. We gathered data on patient demographic characteristics, calculated LMR, and performed immunohistochemical staining for CD163 TAMs and CD8 TILs on tissue biopsy blocks. The determination of cutoff values was performed using receiver operating curve (ROC) analysis for all three. Subsequently, we analyzed these parameters in relation to 3-year PFS using Kaplan-Meier curves and log-rank tests. Cox Regression analysis was conducted to adjust for confounding variables. Results: The 3-year PFS rate for advanced local-stage NPC was found to be 46.7%. The optimal cutoff values for LMR, CD163, and CD8 were 1.82, 1.96, and 47.5%, respectively. Based on bivariate and multivariate analyses, we found LMR ≤ 1.82 (aHR 1.785, 95% CI 1.057 – 3.018), CD163 ≥196 (aHR 6.126, 95% CI 3.382 – 11.097), and CD8 ≤47.5% (aHR 2.099, 95% CI 1.232 – 3.575). Conclusion: High LMR and CD8 TIL values are associated with favorable 3-year PFS, while high CD163 TAM values are associated with poor 3-year PFS in patients with advanced local-stage NPC.