Tesis

Pengaruh Faktor Inflamasi terhadap Respons Tumor dan Tingkat Kesintasan Pasien Kanker Serviks Stadium Lanjut Lokal yang Mendapatkan Terapi Kemoradiasi dan Brakiterapi: Studi Kohort Berbasis Rasio Neutrofil-Limfosit = The Influence of Inflammation Factor towards Tumor Response and Overall Survival in Locally Advanced Cervical Cancer Patients Receiving Chemoradiotherapy and Brachytherapy: A Cohort Study based on NeutrophilLymphocyte Ratio.

Pendahuluan: Tingginya prevalensi infeksi HPV16/18 dapat menjadi faktor yang memengaruhi perbedaan karakteristik respons inflamasi pada pasien kanker serviks di Indonesia, direpresentasikan oleh rasio neutrofil-limfosit (NLR). Namun, batas nilai cut-off NLR masih bervariasi. Studi ini bertujuan untuk membuktikan pengaruh NLR sebagai salah satu penanda inflamasi terhadap respons tumor dan tingkat kesintasan 3-tahun pasien kanker serviks stadium lanjut lokal di Indonesia. Metode: Studi ini merupakan studi kohort retrospektif pada pasien kanker serviks stadium lanjut lokal (IIB – IVA) di RSUPN Dr. Cipto Mangunkusumo, Jakarta (RSCM) yang telah selesai mendapatkan terapi kemoradiasi dan brakiterapi pada tahun 2019 – 2021. Data karakteristik klinis, karakteristik tumor, parameter hematologi, dan faktor pemberian terapi dikumpulkan dari rekam medis. Penanda inflamasi berupa rasio neutrofil-limfosit (NLR), rasio platelet-limfosit (PLR), dan rasio limfosit-monosit (LMR) dihitung dari parameter hematologi. Nilai cut-off NLR ditentukan dari kurva ROC. Tingkat kesintasan diperkirakan sesuai metode Kaplan-Meier. Analisis bivariat dan multivariat dilakukan untuk mengetahui faktor yang memengaruhi respons tumor dan tingkat kesintasan 3-tahun. Hasil: Nilai cut-off NLR yang optimal adalah 5,25. Pada studi ini, terdapat 73 pasien dengan NLR rendah dan 57 pasien dengan NLR rendah. Sekitar 66,9% pasien yang mencapai respons komplit, yang dipengaruhi oleh NLR (HR 2,89; 95% CI 1,16 – 7,23; p = 0,043), terapi kemoradiasi konkuren (HR 3,98; 95% CI 1,68 – 9,41; p = 0,002), dan overall treatment time (OTT) (HR 1,02; 95% CI 1,01 – 1,04; p = 0,003). Secara keseluruhan, tingkat kesintasan 3-tahun mencapai 62,3% dengan rata-rata 28,31 bulan. Tingkat kesintasan 3-tahun dipengaruhi oleh NLR (HR 1,79; 95% CI 1,01 – 3,18; p = 0,046) dan terapi kemoradiasi konkuren (HR 1,91; 95% CI 1,05 – 3,48; p = 0,034). Pasien dengan respons komplit pasca terapi memiliki tingkat kesintasan yang lebih baik. Kesimpulan: NLR dan terapi kemoradiasi merupakan faktor prognosis independen terhadap respons tumor dan tingkat kesintasan 3-tahun pada pasien kanker serviks stadium lanjut lokal. Sementara itu, OTT memengaruhi respons tumor, namun tidak memengaruhi tingkat kesintasan 3-tahun.
Kata kunci: inflamasi, kanker serviks, rasio neutrofil-limfosit, respons tumor, tingkat kesintasan


Introduction: The high prevalence of HPV16/18 infection might be associated with the different characteristics of inflammatory response among cervical cancer patients in Indonesia, represented by the neutrophil-lymphocyte ratio (NLR). However, the cut-off value of NLR was still varied. This study aimed to reveal the influence of NLR as an inflammatory marker toward tumor response and 3-year overall survival (OS) in patients with locally advanced cervical cancer in Indonesia. Methods: We conducted a retrospective cohort study of locally advanced (IIB – IVA) cervical cancer patients in Dr. Cipto Mangunkusumo Hospital, Jakarta, who completed chemoradiotherapy and brachytherapy from 2019 to 2021. We collected data regarding clinical characteristics, tumor characteristics, hematologic parameters, and therapy-related factors from medical records. Inflammatory markers, including neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR), were calculated from hematologic parameters. The ROC curve determined the cut-off value of NLR. The 3-year OS was estimated by the Kaplan-Meier method. We conducted bivariate and multivariate analyses to investigate factors contributing to the tumor response and 3-year OS. Results: The optimal cut-off value of NLR was 5.25. This study included 73 patients with high NLR and 57 with low NLR. About 66.9% patients achieved complete response after chemoradiotherapy, associated NLR (HR 2.89; 95% CI 1.16 – 7.23; p = 0.043), concurrent chemoradiotherapy (CCRT) (HR 3.98; 95% CI 1.68 – 9.41; p = 0.002), and overall treatment time (OTT) (HR 1.02; 95% CI 1.01 – 1.04; p = 0.003). Overall, the 3-year OS reached 62.3% with a mean of 28.31 months. The 3- year OS was associated with (HR 1.79; 95% CI 1.01 – 3.18; p = 0.046) and CCRT (HR 1.91; 95% CI 1.05 – 3.48; p = 0.034). Moreover, patients who achieved complete responses had better survival rates. Conclusion: NLR and CCRT were independent prognostic factors for tumor response and 3-year OS in locally advanced cervical cancer patients. Meanwhile, OTT was associated with tumor response but not with 3-year OS.
Keywords: cervical cancer, inflammation, neutrophil-lymphocyte ratio, survival, tumor response