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"Latar belakang: Instabilitas mikrosatelit (MSI) adalah keadaan hipermutabilitas genetik akibat gangguan perbaikan mismatch DNA yang berhubungan karsinogenesis dan progresifitas tumor.MSI berperan dalam sistem DNA Damage Response (DDR) yang mempengaruhi berhentinya siklus sel, perbaikan double strand break (DSB), dan apoptosis. MSI telah diketahui dikaitkan dengan respons yang baik pada kanker kolorektal, atau respons buruk pada kanker endometrium. Peran MSI pada kanker serviks belum jelas karena belum banyak studi tentang hal tersebut. Metode : dua puluh sembilan secara konsekutif total sampling jaringan kanker serviks di RSCM diperiksa dengan Imuhohistokimia dan pasien telah menjalani radioterapi di RSCM pada Januari 2018 hingga desember 2020 . Hasil : kami mendapatkan 3,4% defective-Mismatch Repair/ dMMR dan 96,6% proficient-mismatch repair/pMMR. satu protein MSH6 termutasi.dan protein lainnya normal. karena keterbatasan sampel MSI positif, belum dapat disimpulkan hubungan MSI dengan respon radioterapi dan stadium kanker (p>0.999) Kesimpulan: MSI ditemukan pada kanker serviks stadium lanjut lokal di Indonesia dalam jumlah lebih sedikit dari MSS dengan prevalensi yang sepadan dengan studi sebelumnya.

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Background: Microsatellite instability (MSI) is a state of genetic hypermutability due to impaired DNA mismatch repair associated with carcinogenesis and tumor progression. MSI plays a role in the DNA Damage Response (DDR) system that affects cell cycle arrest, double strand break (DSB) repair, and apoptosis. MSI has been known to be associated with a good response in colorectal cancer, or a poor response in endometrial cancer. The role of MSI in cervical cancer is not clear because there are not many studies on it. Methods: Twenty-nine samples consecutively total sampling of cervical cancer tissue at the RSCM were examined by immunohistochemistry and the patients had undergone radiotherapy at the RSCM from January 2018 to December 2020. Results: we got 3.4% dMMR, 96.6% pMMR, one MSH6 protein was mutated, and the other proteins were normal. Due to the limited number of positive MSI samples, it is not possible to conclude the relationship between MSI and radiotherapy response and cancer stadium (p>0.999). Conclusion: MSI was found in locally advanced cervical cancer in Indonesia in less number than MSS with a prevalence commensurate with previous studies."

"Latar belakang: Pada kanker nasofaring, tingginya angka kegagalan metastasis jauh paska terapi masih menimbulkan masalah. Sehingga, penelitian mengenai penggunaan terapi sistemik novel pada kanker nasofaring seperti imunoterapi perlu dilakukan. Terdapat beberapa biomarker yang dapat diperiksa untuk dapat memprediksi respon dari pemberian imunoterapi, salah satunya adalah microsatellite instability (MSI). Mikrosatelit merupakan area pada DNA yang memiliki banyak pengulangan kodon, sehingga rentan terjadi gangguan coding dan mengakibatkan akumulasi mutasi. Pada keadaan normal, kerusakan ini akan diperbaiki dengan sistem mismatch repair. Namun, jika terdapat gangguan atau mutasi terkait sistem ini, atau yang disebut dengan deficient mismatch repair (dMMR), akan menghasilkan fenotipe MSI. Pada kanker kolorektal dan endometrium. Namun sampai saat ini, hanya terdapat 3 penelitian yang melakukan pemeriksaan status MSI pada kanker nasofaring. Penelitian ini bertujuan untuk melihat gambara status MSI pada pasien kanker nasofaring pada pasien di RSCM, Indonesia.Metode: Penelitian ini merupakan penelitian eksploratif dengan 36 subjek penelitian. Dilakukan pemeriksaan status instabilitas mikrosatelit menggunakan pemeriksaan berbasis polymerase chain reaction (PCR) Idylla MSI. Dilakukan pula pemeriksaan MMR menggunakan pemeriksaan berbasis imunohistokimia (IHK) menggunakan 4 antibodi untuk mendapatkan keselerasan antara pemeriksaan MSI dan MMR pada pasien kanker nasofaring di RSCM.Hasil : Menggunakan pemeriksaan Idylla MSI, ditemukan MSI pada 2 dari 36 pasien (5,6%) dan dMMR menggunakan pemeriksaan IHK pada 3 dari 36 pasien (8,34%). Hasil yang konsisten ditemukan pada 2 metode pemeriksaan sebesar 96,97%.Kesimpulan: Pada kanker nasofaring ditemukan frekuensi MSI yang rendah baik menggunakan pemeriksaan IHK dan Idylla MSI. Ditemukan keselerasan yang tinggi antara pemeriksaan berbasis IHK dan pemeriksaan berbasis PCR Idylla MSI.

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Background: Despite high probability of local control after treatment, high rate of distant metastases-failure still pose as problem in the management of locally advanced nasopharyngeal carcinoma. Thus, research for novel systemic therapies for nasopharyngeal cancer, such as immunotherapy, needs to be done. There are several biomarkers that may predict the response to immunotherapy, one of which is microsatellite instability (MSI) phenotype. Microsatellites defined by areas in DNA that are prone to mutations due to repetition of 1-3 nitrogen base. However, under normal circumstances, there are repair systems that can identify and correctly repairs DNA mutations in microsatellite area, a system called mismatch repair (MMR) system. Microsatellite instability is a condition of accumulating mutations in microsatellite area due to defect in MMR system. In colorectal and endometrial cancer, MSI are known as one of prognostic and predictive markers, especially with the usage of immunotherapy immune checkpoint blockade PD-1/PD-L1. To this date, only 3 studies are available in exploring the role of MSI in nasopharyngeal cancer, and no study was done in Indonesia. We conduct this study to assess the MSI status of Indonesia's nasopharyngeal cancer patients in Ciptomangunkusumo Hospital.

Methods: This is the first explorative study in exploring the role of MSI in Indonesia's nasopharyngeal cancer patients. A total of 36 subjects were recruited, and both MSI assessment using immunohistochemistry (IHC) and polymerase chain reaction (PCR) Idylla MSI was done on all study subjects.

Results: MSI was found in 2 patients (5,6%) using PCR based Idylla MSI, and dMMR was found in 3 patients (8,34%). Consistent results between IHC and PCR based MSI assessment was found in 32 patients (96,97%).

Conclusion: MSI was a rare event in Indonesia's nasopharyngeal cancer patients. High concordance was found between IHC and PCR MSI assessment in nasopharyngeal cancer."

"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."

"ABSTRAK

Tujuan: Untuk mengetahui gambaran transposisi ovarium sebagai upaya proteksi fungsi ovarium pada pasien kanker serviks yang menjalani radioterapi

Metode: Penelitian ini merupakan penelitian cohort, before–after study pada pasien-pasien kanker serviks dan kanker vagina stadium IB, IIA, IIB, IIIA, dan IIIB yang akan menjalankan radioterapi dan dilakukan transposisi ovarium. Penelitian dilakukan di Rumah Sakit Cipto Mangunkusumo (RSCM) dan Rumah Sakit Umum Persahabatan (RSUP) sejak 1 Januari 2011 sampai 31 Maret 2014. Luaran yang diukur adalah perubahan kadar Anti Mullerian Hormone (AMH), Follicle Stimulating Hormone (FSH), dan skor keluhan hidup terkait menopause.

Hasil: Terdapat 16 subyek penelitian, namun hanya 12 orang subyek yang dilakukan transposisi ovarium dan menyelesaikan radioterapi. Efek proteksi transposisi ovarium sangat rendah (8,3%) dimana hanya satu dari 12 orang yang tidak mengalami penurunan kadar AMH setelah radioterapi. Sisanya mengalami penurunan kadar AMH setelah radioterapi yang bermakna (T-test berpasangan p=0,037). Kadar FSH meningkat sesudah radioterapi (T-test berpasangan p= 0,015). Skor keluhan hidup meningkat setelah dilakukan radioterapi (T-test berpasangan p<0,001). Faktor penyebab efek proteksi transposisi ovarium yang rendah karena sebagian besar subyek memiliki kadar awal AMH yang rendah. Rekomendasi penelitian ini adalah memperketat proses seleksi transposisi ovarium, yaitu usia ≤ 35 tahun, kadar AMH > 0,3 ng/ml, dan kadar FSH≤ 12 mIU/ml.

Kesimpulan: Transposisi ovarium memiliki efek proteksi fungsi ovarium yang rendah (8,3%). Hal itu dapat disebabkan karena sebagian besar subyek memiliki kadar AMH yang rendah sebelum terapi.

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ABSTRAK

Objective: To know the effect of ovarian transposition in protecting ovarian function in cervical cancer patients undergoing radiotherapy

Methodology: This cohort study was before–after study in patients who had cervical or vaginal cancer stage IB, IIA, IIB, IIIA, and IIIB who underwent ovarian transposition before radiotherapy. This study was done in Cipto Mangunkusumo Hospital and Persahabatan satellite hospital since 1 January 2011 until 31 March 2014. The level of Anti Mullerian Hormone (AMH), Follicle Stimulating Hormone (FSH), and menopause symptom score were evaluated before and after radiotherapy.

Result: There were 16 patients who underwent ovarian transposition but only 12 patients completed radiotherapy. The protective effect of ovarian transposition was low, only one among 12 subjects (8.3%) did not experience decreased level of AMH. Ten subjects had significantly decreased AMH level after radiotherapy (paired T-test, p=0.037). FSH level was significantly increased after radiotherapy (paired T-test p=0.015). Menopause symptoms scores were increased after radiotherapy (paired T-test p<0.001). This study recommended the tighter selection criteria for patients undergoing ovarian transposition such as, age younger than 35 years old, AMH level > 0,3 ng/ml, and FSH level≤ 12 mIU/ml.

Conclusion: Ovarian transposition had low protective effect (8.3%) and it might be caused by the low level of AMH in most subjects before radiotherapy

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"Tujuan: Membahas perhitungan Tingkat Utilisasi Radioterapi optimal (TURo), aktual (TURa) serta kebutuhan tidak terpenuhi (kesenjangan) antar keduanya untuk kanker serviks dan ovarium di Indonesia. Metodologi: Studi deskriptif desain potong lintang, metode total sampling dengan mengambil data sekunder dari registrasi kanker dan/atau rekam medis internal RS partisipan yang memiliki pusat radioterapi di Indonesia tahun 2019. Hasil: Dari 33 RS partisipan total data kanker serviks dan ovarium adalah 4937 dan 1583. Rata-rata pasien berusia 48-52 tahun (7-91 tahun). Domisili pasien sebagian besar dari Pulau Jawa. Stadium III adalah yang terbanyak untuk kedua kanker serviks (39,4%) dan ovarium (20,8%). Tatalaksana kanker serviks didominasi oleh radioterapi saja dan radioterapi-kemoterapi (28,5% dan 27,4%), sementara kanker ovarium terbanyak adalah kemoterapi-pembedahan (43,8%). Nilai TURo, TURa, dan kebutuhan tidak terpenuhi untuk kanker serviks yaitu 97,2% (90,9-97,4%), 61,24%, dan 36,7% (32,62-37,13%) dan untuk kanker ovarium 1,89% (1,39-4,60%), 4,83%, dan -155,56% (-247,48%-(-5)%). Kesimpulan: TUR masih memiliki kesenjangan yang cukup besar antara aktual dan optimal pada kanker serviks. Sebaliknya, kanker ovarium terkesan adanya utilisasi berlebihan namun kesenjangan terlihat pada eskalasi cakupan yang lebih luas. Diperlukan usaha peningkatan aktualisasi TUR mendekati nilai optimalnya. Faktor-faktor yang mempengaruhi TUR harus dieksplorasi secara universal meliputi segi pasien, klinisi dan sistem kesehatan.

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Purpose: To discuss the calculation of the optimal and actual Radiotherapy Utilization Rate (RURo and RURa) and unmet need (gap) between the two RUR for cervical and ovarian cancer in Indonesia. Methodology: This is a descriptive cross-sectional study with total sampling by taking secondary data from cancer registry and/or medical records of participating hospitals with radiotherapy centers in Indonesia in 2019.

Results: Out of the 33 participating hospitals, the total data on cervical and ovarian cancer were 4937 and 1583. The mean age was 48-52 years old (7-91). Most of the patients were from Java Island. Stage III was the most common for both cancers, 39.4% and 20.8%. The management of cervical cancer was dominated by radiotherapy alone and radiotherapy-chemotherapy (28.5% and 27.4%), while ovarian cancer most were chemotherapy-surgery (43.8%). RURo, RURa, and unmet needs for cervical cancer were 97.2% (90.9-97.4%), 61.24% and 36.7% (32.62-37.13%) and for ovarian cancer were 1.89% (1.39-4.60%), 4.83%, and -155.56% (-247.48%-(-5)%). Conclusion: RUR for cervical cancer still has a sizeable gap between actual and optimal. On the other hand, ovarian cancer gives the impression of overutilization but the gap was seen when escalating wider coverage. Efforts are needed to increase actualization rate close to its optimal value. The factors that affect RUR should be explored universally including the patient, clinician and health system aspects."

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Respons radiasi kanker serviks diduga dapat ditingkatkan dengan pemilihan waktu radiasi tetap yang berpola sirkadian karena dianggap sesuai dengan fase radiosensitif G₂-M sel kanker. Daur sirkadian dan melatonin dianggap berperan dalam radiosensitivitas. Dihipotesiskan respons radiasi pagi hari maupun efek samping radiasi pagi hari akan lebih baik dibanding sore hari.

Penelitian ini merupakan uji klinis dengan perolehan subjek secara berurutan. Alokasi pilihan waktu radiasi pada pagi (06.00–08.00) dan sore (16.00–18.00) hari dengan randomisasi blok tiap enam subjek terpisah antara stadium II dan III. Data diperoleh menggunakan metode open label. Pengukuran data klinis seperti ukuran tumor, respons klinis, dan efek samping dilakukan oleh dua dokter independen yang terlatih. Dilakukan pengukuran kadar melatonin dan fase G₂-M siklus sel di institusi resmi. Respons baik dan buruk ditetapkan berdasarkan kriteria WHO sedangkan efek samping ada atau tidak, ditetapkan berdasarkan kiriteria RTOG.

Penyinaran di waktu pagi menunjukkan respons klinis lebih baik dibandingkan sore (p 0,025; 95% IK:1,27–33,08; adj OR: 6,48) untuk respons pascaradiasi maupun 2–4 minggu pascaradiasi (p 0,048; 95% IK 1,02–47,81; adj OR 6,98). Kadar Hb awal dan ukuran klinis tumor berpengaruh secara bermakna terhadap respons baik pascaradiasi maupun respons baik 2–4 minggu pascaradiasi. Dalam hal efek samping, pilihan waktu radiasi tidak menunjukkan hasil yang bermakna, namun kadar melatonin praradiasi berpengaruh, khususnya efek samping kulit (p 0,006; 95% IK 1,66–18,99; adj OR 5,62). Variabel yang bermakna memengaruhi efek samping terapi pada gastrointestinal adalah overall treatment time (p 0,031; 95% IK 1,19–39,93; adj OR 6,89), sedangkan untuk genitourinaria adalah PA diferensiasi (p 0,015; 95% IK 1,51–46,37; adj OR 8,36), penurunan berat badan (p 0,025; 95% IK 1,22–18,30; adj OR 4,72), dan nyeri sebelum radiasi (p 0,017; 95% IK 1,31–15,32; adj OR 4,47).

Simpulan: Respons radiasi kanker serviks uteri yang diradiasi pagi hari lebih baik daripada yang diradiasi sore hari, namun efek samping radiasi pagi hari tidak berbeda bermakna dibandingkan sore hari. Belum dapat dipastikan pengaruh besarnya proporsi fase G₂-M terhadap respons klinis radiasi. Ada kecenderungan pengaruh kadar melatonin pagi hari terhadap respons klinis radiasi dan terbukti kadar melatonin berpengaruh pada efek samping kulit.

Kata kunci: kanker serviks, melatonin, radiosensitivitas, siklus sel, sirkadian

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The radiation response of cervical cancer can be enhanced by the choice of a fixed radiation time of circadian pattern because it is considered to be in accordance with the radiosensitive phase of G₂-M cancer cells. Circadian cycles and melatonin are thought to play a role in radiosensitivity. It is hypothesized that the response and side effects of morning radiation will be better than the afternoon.

This study was an RCT (randomized clinical trials) with consecutive sampling. Treatment allocation for radiation time in the morning (06.00–08.00) and afternoon (16.00–18.00) were determined by block randomization for every six subjects based on the stage (II and III). The data was obtained with an open label method. Measurement of clinical data such as tumor size, clinical response, and side effects were carried out by two-trained independent physicians. Measurement of melatonin levels and G₂-M phases of cell cycle were carried out in official institution. Good and poor responses were set based on WHO criteria while the side effects were determined based on the RTOG criteria.

Morning radiation showed a better post-radiation and 2–4 weeks post-radiation clinical response compared with afternoon (p 0.025; 95% CI:1.27–33.08; adj OR: 6.48 and p 0.048; 95%CI 1.02–47.81; adj OR 6.98, respectively). The initial Hb level and clinical size of the tumor had a significant effect on good response both post-radiation and 2-4 weeks post-radiation. In regards to the side effects, radiation time did not show significant results in causing side effects, but pre-radiation melatonin level did on skin (p 0.006; 95%CI 1.66–18.99; adj OR 5.62). The significant variable in influencing gastrointestinal side effects was overall treatment time (p 0.031; 95%CI 1.19–3.93; adj OR 6.89), whereas for genitourinaria were differentiation of histopathology (p 0.015; 95%CI 1.51–46.37; adj OR 8.36), weight loss (p 0.025; 95%CI 1.22–18.30; adj OR 4.72), and presence of pain pre-radiation (p 0.017; 95%CI 1.31–15.32; adj OR 4.47).

Conclusion: The radiation response of irradiated uterine cervical cancer is better in the morning than the afternoon. Nevertheless, the side effects of morning radiation do not differ significantly compared to the afternoon. The influence of the G₂-M phase proportion on the clinical response to radiation cannot be ascertained. The level of melatonin in the morning might affect the radiation response and affect the side effects on skin.

Keywords: cell cycle, cervical cancer, circadian, melatonin, radiosensitivity.

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"Tujuan : Mengetahui pengaruh penerapan protokol buli di RSCM terhadap dosimetri dan toksisitas radiasi usus pada pasien kanker serviks saat menjalani radiasi eksterna. Metode : Penelitian adalah penelitian kohort retrospektif pada 236 subjek penelitian yang menjalankan radioterapi eksterna di IPTOR RSCM pada tahun 2019 – 2021. Subjek terbagi menjadi tiga kategori menurut perlakuan yaitu pasien tanpa protokol buli sebanyak 84 pasien, dengan protokol buli 300 - <500 mL sebanyak 35 pasien dan protokol buli 500 mL sebanyak 67 pasien. Uji normalitas menggunakan Kolmogorov-Smirnov, perbandingan rerata menggunakan Kruskal Wallis dan Mann Whittney. Perbandingan nominal kategorik menggunakan chi square. Analisis multivariat menggunakan regresi linier dan regresi logistik Hasil : Pasien tanpa diberikan instruksi protokol buli volume buli yang cenderung lebih kecil yaitu median 83,5 mL (min-maks) (29,2 – 570) dibandingkan dengan yang diberikan instruksi protokol buli 300 - <500 mL yaitu median (min-maks) 91,5 mL (25,6 – 409,4) dan yang diberikan instruksi protokol buli 500 mL yaitu 125 mL (15-462) (P=0,014). Protokol buli juga berpengaruh terhadap proporsi pasien dengan V45 bowel bag <195 mL, dimana pasien dengan protokol buli 11,12% mencapai V45 bowel bag <195mL, sedangkan pasien tanpa protokol buli hanya 3,2% yang mencapai V45 bowel bag <195 mL (P=0,04. CI 95%). Kesimpulan : Protokol buli yang telah diterapkan di IPTOR RSCM terlihat mempunyai pengaruh terhadap volume buli dan volume bowel bag namun tidak menunjukkan pengaruh terhadap toksisitas akut gastrointestinal bawah.

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Objective: To determine the effect of bladder protocol at RSCM to the irradiated bowel volume and acute bowel toxicity in cervical cancer patients underwent external beam radiotherapy. Methods: This was a retrospective cohort study on 236 cervical cancer patients who underwent external radiotherapy at IPTOR RSCM in 2019-2021. Subjects were divided into three bladder protocol categories. Patients without bladder protocol (n=84), with 300 - <500 mL bladder protocol (n=85) and with 500 mL bladder protocol (n=67). Normality test using Kolmogorov-Smirnov, mean comparison using Kruskal Wallis and Mann Whittney. Comparison of categorical nominal using chi square. Multivariate analysis using linear regression and logistic regression. Results: Patients without bladder protocol had a smaller bladder volume, which median (min-max) was 83.5 mL (29.2 – 570) compared to those who were given a bladder protocol instruction of 300 - <500 mL which was 91, 5 mL (25.6 – 409.4) and those given 500 mL bladder protocol which median value was 125 mL (15-462) (P=0.014. 95% CI). Bladder protocol also caused more patients to achieve V45 bowel bag <195 mL which was 11.12% compared to those without bladder protocol which was 3,2% (P=0.04). Conclusion: The bladder protocol that has been applied at IPTOR RSCM seems to influence the bladder volume and bowel bag volume but did not show an effect on acute lower gastrointestinal toxicity.

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"ABSTRAK Latar Belakang: Prognosis dan tatalaksana kanker kolorektal sangat dipengaruhi olehstadiumnya. Pada tahun 2012, the European Society for Medical Oncology mempublikasikan pedoman yang menyarankan evaluasi terhadap microsatellite instability MSI untuk menentukan perjalanan penyakit kanker kolorektal. Penelitian ini bertujuan untuk menginvestigasi faktor prognostik MSI-H pada kadar kesintasan 3 tahun. Metode: Penelitian ini menggunakan data sekunder dari penelitian sebelumnya oleh Setyaningsih, dkk. yang berjudul ldquo;Penelitian Microsattelite Instability Melalui Ekspresi PMS2 dan MSH6 serta Tumor-Infiltrating Lymphocyte pada Kanker Kolorektal Kiri dan Kanan rdquo;. Kami memasukkan total 90 pasien yang didiagnosis sebagai kanker kolorektal yang menjalani bedah reseksi dari tahun 2008 hingga 2013 di RSUPN Cipto Mangunkusumo. Kami menganalisa status MSI sebagai faktor prognosis untuk menentukan kadar kesintasan 3 tahun yang disesuaikan dengan ukuran dan tipe tumor, metastasis, dan umur pasien. Hasil: Dari 90 pasien, 47 orang dapat dilakukan follow up. Mayoritas pasien didiagnosis dengan kanker kolorektal stadium III n=29; 61,7 , 8 pasien didiagnosis sebagai stadium IV, 9 pasien didiagnsosis sebagai stadium II, dan 1 pasien didiagnosis dengan stadidum I. Kesintasan tiga tahun untuk pasien MSI-H adalah 33,3 , 22,2 , dan 20 untuk stadium II, III, dan IV; dibandingkan dengan kesintasan tiga tahun untuk pasien MSI-L yaitu 0 , 5 , dan 0 p = 0,003 . Selain itu, berdasarkan analisis multivariate, kami menemukan bahwa MSI-L memiliki hazard ratio 2,421 1,991-2,851 dibandingkan dengan MSI-H p = 0,004 . Kesimpulan: MSI-H adalah faktor prognosis yang penting untuk menentukan kesintasan tiga tahun pada pasien kanker kolorektal. Kami menemukan bahwa pasien dengan MSI-H memiliki prognosis yang lebih baik dibandingkan dengan pasien MSI-L. Temuan ini sejalan dengan pedoman dan penelitian sebelumnya yang menyarankan penggunaan MSI untuk menentukan perjalanan penyakit dan pilihan terapi pada pasien kanker kolorektal.

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ABSTRACT Background The prognosis and treatment of colorectal cancer is based on its stadium. Due to its features, the prognosis stage II colorectal cancer is still considered inexact with the survival rates ranging from 87,5 in stage IIA to 58.4 in stage IIC.The European Society for Medical Oncology published a guideline in 2012 which suggests that microsatellite instability MSI should be evaluated to determine the course of the colorectal cancer. This study is aimed to investigate prognostic factor of MSI ndash H for 3 years survival rates. Method This study used secondary data from a previous study performed by Setyaningsih, et al. titled ldquo Penelitian Microsattelite Instability Melalui Ekspresi PMS2 dan MSH6 serta Tumor Infiltrating Lymphocyte pada Kanker Kolorektal Kiri dan Kanan rdquo . We included a total of 90 patients diagnosed with colorectal cancer who underwent resection surgery from 2008 to 2013 in RSUPN Cipto Mangunkusumo. We analyzed the MSI status as a prognosticfactor to determine 3 years survival rate, adjusted with the size and types of the tumor, metastasis, and age. Results Among 90 patients, 47 have been followed up. The median age was 47 years. The majority of the patients was diagnosed with stage III colorectal cancer n 29 61.7 , 8 patients were diagnosed with stage IV, 9 patients were diagnosed with stage II colorectal cancer, and 1 patient was diagnosed with stage I colorectal cancer. Three years survival rates for patients with MSI H are 33.3 , 22.2 , and 20 for stage II, III, and IV respectively, compared to 5 years survical rates for MSI L patients which are 0 , 5 , and 0 p 0.003 . Futhermore, with multivariate analysis, we found that MSI L has 2.421 1.991 2.851 hazard ratio compared to MSI H p 0.004 . Conclusions MSI H is an important prognostic factor to determine 3 years survival rate in colorectal cancer patients.We found that patient with MSI H have more favourable prognosis compared to MSI L patients This findings complements previous guidelines and studies which suggested the use of MSI to determine the disease course and treatment options in colorectal cancer."