Nilai Prognostik Neutropenia Pasca Kemoterapi Awitan Dini Terhadap Kesintasan Pasien Kanker Payudara Triple Negative di RSUP Dr Sardjito

HERDIFITRIANNE SAINTISSA YANUARISTI, Dr. dr. Ibnu Purwanto, Sp. PD-KHOM; dr. Mardiah Suci Hardianti, Ph.D, Sp. PD-KHOM

2021 | Skripsi | S1 KEDOKTERAN

Latar Belakang: Kanker payudara adalah kanker yang paling banyak ditemukan pada wanita di dunia, termasuk di Indonesia dan RSUP Dr Sardjito. Kanker payudara triple negative (triple negative breast cancer, selanjutnya disebut TNBC) adalah subtipe kanker payudara paling umum kedua di Indonesia, yang menunjukkan gambaran histopatologis negatif pada reseptor hormonal dan HER2, sehingga pilihan perawatan TNBC masih terbatas pada pembedahan, radioterapi, dan kemoterapi. Kemoterapi, sebagai opsi yang paling disarankan, menekan sistem hematopoietik sehingga dikaitkan dengan terjadinya neutropenia. Neutropenia yang diinduksi kemoterapi (chemotherapy-induced neutropenia / CIN) adalah toksisitas hematologi yang paling serius dari kemoterapi sitotoksik kanker. Di sisi lain, CIN yang dibagi menjadi awitan dini (siklus 1-2 kemoterapi) dan awitan akhir (siklus >3) berdasarkan waktu terjadinya, diperkirakan dapat menjadi faktor prognostik baik terhadap kesintasan pasien kanker. Tujuan: Mengetahui apakah kondisi neutropenia pasca kemoterapi awitan dini berpengaruh terhadap angka overall survival (OS) 2 tahun pada pasien TNBC di RSUP Dr Sardjito. Metode: Penelitian ini merupakan studi observasional analitik, dengan desain kohort retrospektif. Sumber data adalah registri klinis pasien TNBC di Instalasi Kanker Tulip RSUP Dr. Sardjito Yogyakarta tahun 2014-2018. Penelitian ini menggunakan analisis kesintasan yang berupa overall survival (OS) dengan indikator CIN yang dijadikan sebagai variabel bebas yang selanjutnya akan diuji pengaruhnya terhadap kesintasan pasien (variabel terikat). Subjek penelitian didapat melalui teknik sampling konsekutif. Kesintasan dianalisis menggunakan kurva Kaplan-Meier dan dibandingkan dengan uji log-rank, diikuti dengan analisis univariat pada model cox-proportional hazard. Hasil: Neutropenia awitan dini yang diinduksi kemoterapi (CIN early-onset) terdapat pada 52 pasien (56,7%) dari total 97 pasien penelitian. Pasien yang meninggal berjumlah 37 (21 pada kelompok neutropenia dan 16 pada kelompok non-neutropenia), dan pasien yang hidup pada akhir penelitian berjumlah 60 (34 pada neutropenia dan 26 pada non-neutropenia) (P=0,993) yang mengindikasikan hubungan tidak signifikan antara neutropenia dan luaran. Pada uji Log-rank didapatkan bahwa hasil 2-year survival CIN sebesar 60,2% dengan rata-rata waktu kesintasan 41,079+3,42 bulan dan median waktu kesintasan 46 bulan (p=0,488). Analisis kesintasan dengan model cox-regression menunjukkan bahwa neutropenia memengaruhi OS dengan 20,6% risiko luaran kematian lebih rendah, namun tidak bermakna secara statistik (HR 0,794; IK 95%: 0,414 - 1,524; P= 0,489). Dari hasil analisis bivariat dan multivariat variabel perancu, hanya status anemia pre-kemoterapi yang memiliki pengaruh signifikan (P= 0,037). Kesimpulan: Neutropenia pasca kemoterapi awitan dini bukan merupakan faktor prognostik independen terhadap luaran pasien TNBC di Instalasi Kanker Tulip, RSUP Dr Sardjito. Kata Kunci: Triple negative breast cancer, faktor prognostik, neutropenia.

Background: Breast cancer is the most common cancer among women worldwide, including in Indonesia and Dr. Sardjito Hospital. The most common breast cancer subtype found in Indonesia is Luminal A, followed by the triple - negative subtype. Triple negative breast cancer (TNBC) is a type of breast cancer that shows negative histopathological features at hormonal receptors and HER2, making treatment options for TNBC to be limited to surgery, radiotherapy and chemotherapy. Chemotherapy, as the most preferred option, suppresses the hematopoietic system and the patient's immune mechanisms, and is therefore associated with neutropenia. Chemotherapy-induced neutropenia (CIN) is the most serious hematologic toxicity of cancer chemotherapy. Based on the time of occurrence, CIN is divided into early onset and late onset, which is thought to be a prognostic factor for the survival of cancer patients. Objective: Identifying the impact of chemotherapy-induced neutropenia towards the 2-year overall survival (OS) rate in TNBC patients at Dr. Sardjito General Hospital. Method: This research used an analytic observational method, with a retrospective cohort design, using data that was obtained from the clinical registry of TNBC patients at the Tulip Cancer Center, Dr. Sardjito Hospital Yogyakarta from 2014-2018. This study used a survival analysis in the form of overall survival (OS) with early-onset CIN as the independent variable, which will then be tested for its relation to the patients' survival (dependent variable). The sampling technique used was consecutive sampling. Patients' survival was analyzed using the Kaplan-Meier curve and compared with the log-rank test, followed by univariate analysis on a cox-proportional hazard model. Results: Early onset chemotherapy-induced neutropenia was present in 42 patients (43.3%) out of the total 97 study patients. There were 37 patients who died (21 in the neutropenic group and 16 in the non-neutropenic group), and 60 patients alive at the end of the study (34 in neutropenia and 26 in non-neutropenia) (P = 0.993) indicating an insignificant relationship between neutropenia and output. In the Log-rank test, it was found that the 2-year survival result was 60.2% with mean survival time 41,079+3,42 months and median survival time 46 months (p = 0.488). The survival analysis using the cox-regression model showed that CIN affected OS (HR 0,794; 95% CI: 0.414 - 1.524; P = 0.489), but it was not statistically significant. From the results of the univariate analysis of several parameters including age, body mass index, clinical stage, histological type, type of surgery, chemotherapy regimen, and pre-chemotherapy anemia, only pre-chemotherapy anemia status had a significant effect (P = 0.037). Conclusion: Early onset chemotherapy-induced neutropenia is not an independent prognostic factor for the outcome of TNBC patients at the Tulip Cancer Installation, Dr. Sardjito Hospital. Keywords: Neutropenia, early onset chemotherapy-induced neutropenia, triple negative breast cancer, survival rate

Kata Kunci : Triple negative breast cancer, faktor prognostik, neutropenia, early onset chemotherapy-induced neutropenia, survival rate