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Soehartati Argadikoesoemo Gondhowiardjo
"Karsinoma Nasofaring (KNF) merupakan salah satu jenis keganasan yang sering ditemukan di Indonesia.' Data yang diperoleh dari registrasi kanker berdasarkan Patologi di Indonesia pada tahun 1991 menunjukkan adanya 1059 (5,6%) kasus KNF di antara 18,770 kasus keganasan. Hal ini menempatkan KNF pada urutan ke empat setelah karsinoma mulut rahim, payudara, dan kulit.
Di Sub.Bagian Radioterapi Fakultas Kedokteran Universitas Indonesia (FKUI) I Rumah Sakit Umum Pusat Nasional - Cipto Mangunkusumo (RSUPN-CM) dalam kurun waktu 5 tahun, periode 1980 - 1984, terdapat 748 pasien KNF. Angka ini menyatakan bahwa KNF merupakan kasus ke tiga terbanyak setelah keganasan mulut rahim dan payudara. Sejumlah 74,5% kasus datang pada stadium IV, 18,6% kasus pada stadium III dan hanya 6,9% di antaranya yang berada pada stadium I dan 1I.' Data dari Bagian Telinga, Hidung dan Tenggorok (THT) FKUII RSUPN-CM memperlihatkan bahwa KNF merupakan kasus keganasan terbanyak (71,8%) dari semua jenis keganasan THT yang dijumpai.
Jenis keganasan ini sangat jarang ditemukan di daratan Eropa dan Amerika Utara, yaitu dengan angka kejadian kurang dari 1 di antara 100,000 penduduk. Sebaliknya, di daerah Asia Timur dan Tenggara didapatkan angka kejadian yang tinggi, bahkan angka kejadian tertinggi di dunia terdapat di propinsi Cina Tenggara, yaitu sebesar 40-50 kasus KNF di antara 100.000 penduduk."
Jakarta: Fakultas Kedokteran Universitas Indonesia, 1998
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UI - Disertasi Membership  Universitas Indonesia Library
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Irwan Ramli
"

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


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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Depok: Fakultas Kedokteran Universitas Indonesia, 2019
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UI - Disertasi Membership  Universitas Indonesia Library
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Sawitri Darmiati
"[ABSTRAK
Latar belakang: Respons tumor setelah pemberian sitostatik sebagai kemoterapi neoajuvan pada pasien kanker payudara masih belum memuaskan dan respons tumor baru dapat dinilai setelah siklus ke-3; untuk mengurangi efek samping sitostatik dan penghematan biaya bagi yang tidak respons dibutuhkan faktor prediksi respons tumor lebih awal.
Tujuan penelitian: Untuk mengetahui apakah perubahan rasio choline/water pada pemeriksaan magnetic resonance spectroscopy (MRS) dapat digunakan sebagai faktor prediksi awal respons tumor pasien kanker payudara yang memperoleh sitostatik sebagai kemoterapi neoajuvan dan menganalisis korelasi persentase perubahan rasio choline/water eksternal dengan internal.
Bahan dan cara: Penelitian dilaksanakan di Rumah Sakit Umum Pusat Nasional Cipto Mangunkusumo (RSCM) pada bulan Agustus 2011 sampai April 2014. Subjek memperoleh sitostatik sebagai kemoterapi neoajuvan. Pemeriksaan MRI/MRS 1,5 T dilakukan sebelum sitostatik I, 20 atau 21 hari setelah sitostatik I dan setelah sitostatik III, menggunakan program syngo-GRACE untuk MRS. Tumor diukur berdasarkan RECIST 1.1. Respons tumor ≥ 30% dinyatakan positif, dan < 30% dinyatakan negatif. Hasil: Diperoleh 40 subjek dengan kanker payudara ukuran tumor ≥ 5 cm tanpa ulkus respons tumor positif 47,5%, peningkatan rasio choline/water eksternal 35% dan choline/water internal 42,5%. Peningkatan rasio choline/water eksternal pada MRS I- MRS II pada hari ke-20 atau ke-21 setelah pemberian sitostatik 1 menunjukkan respons tumor positif, RR=0,49 (IK 0,26-0,90) terutama untuk stadium < IIIC. Pada peningkatan rasio choline/water internal RR=0,54 (IK 0,28-1,04) dan penurunan nilai Apparent Diffusion Coefficient (ADC) RR= 0,51 (IK 0,23-1,13), didapatkan hubungan yang sama tetapi lebih lemah. Didapatkan pula korelasi sedang arah positif antara persentase perubahan rasio choline/water eksternal dengan persentase perubahan rasio choline/water internal (r=0,572, p=0,000). Derajat keganasan, Ki67, Bcl2 dan MVD tidak dapat digunakan sebagai faktor prediksi respons tumor. Pada Ki67 sama dengan atau lebih dari 14%, masih diperoleh repons tumor positif sedangkan pada Ki67 kurang dari 14%, tidak ditemukan respon tumor positif.
Simpulan: Peningkatan rasio choline/water eksternal pada MRS I-MRS II pada hari ke-20 atau ke-21 setelah pemberian sitostatik 1 sebagai kemoterapi neoajuvan dapat memprediksi pengecilan tumor setelah sitostatik III sama dengan atau lebih besar dari 30% terutama untuk stadium < IIIC. Perubahan rasio choline/water eksternal dan internal dapat digunakan untuk memprediksi respons tumor setelah pemberian sitostatik.;

ABSTRACT
Background : Cytostatics administration as neoadjuvant chemotherapy does not provided satisfactory tumor response in breast cancer patients and could be asses after 3rd cycle. To minimize the side effects and cost of cytostatics, early predictive factor of tumor response following neoadjuvant therapy in breast cancer patients is required. Objectives: The purpose of this study was, to asses of choline/water ratio by using
magnetic resonance spectroscopy (MRS) as an early predictive factor of cytostatics response after neoadjuvant therapy in breast cancer patients, secondly to analyze the correlation between external choline/water ratio and internal choline/water ratio.
Material and method: This study was conducted at Cipto Mangunkusumo National General Hospital since August 2011 to April 2014. Subjects received cytostatics as neoadjuvant chemotherapy underwent MRI/MRS prior to cytostatics I, 20/21 days after having cytostatics I and after cytostatics III. MRI 1.5 T was used for MRI examination and syngo-GRACE program for MRS. Tumor measurement was based on RECIST 1.1, tumor response of ≥ 30% is considered positive, and < 30% is considered negative.
Results: Among 40 non-ulcerating breast cancer subjects with tumor size of more or equal to 5 cm, 47.5% show positive response. MRS I and II showed escalation of external choline/water ratio on days 20/21 after the introduction of cytostatic I as neoadjuvant treatment, which could be used to predict tumor shrinkage after cytostatic III as high as 30% or more, RR = 0.49 (CI 0.26 - 0.90), especially for < IIIC stage. Changes of internal choline/water ratio, RR= 0.54 (CI 0.28 - 1.04) and Apparent Diffusion Coefficient (ADC) changes, RR= 0.51 (CI 0.23-1.13) show similar result but less related. A positive moderate correlation between changes of external choline/water ratio and changes of internal choline/water ratio is seen (r=0,572, p=0,000). No correlation between degree of malignancy, Bcl2, Ki67 dan MVD with tumor response. Changes of choline/water ratio combined with Ki67 higher than or equal with 14% could give positive tumor response, on the other hand, declining of choline/water ratio combined with Ki67 less than 14%, no positive tumor response could be found. Conclusion: Increased of external choline/water ratio on MRS I-MRS II on day 20 or 21 following cytostatic 1 as neoadjuvant chemotherapy can predict tumor shrinkage following cytostatic III of equal or more than 30%, especiallyfor < IIIC stage. Changes of external and internal choline/water ratio could be used to predict tumor response following cytostastic administration., Background : Cytostatics administration as neoadjuvant chemotherapy does not provided satisfactory tumor response in breast cancer patients and could be asses after 3rd cycle. To minimize the side effects and cost of cytostatics, early predictive factor of tumor response following neoadjuvant therapy in breast cancer patients is required. Objectives: The purpose of this study was, to asses of choline/water ratio by using
magnetic resonance spectroscopy (MRS) as an early predictive factor of cytostatics response after neoadjuvant therapy in breast cancer patients, secondly to analyze the correlation between external choline/water ratio and internal choline/water ratio.
Material and method: This study was conducted at Cipto Mangunkusumo National General Hospital since August 2011 to April 2014. Subjects received cytostatics as neoadjuvant chemotherapy underwent MRI/MRS prior to cytostatics I, 20/21 days after having cytostatics I and after cytostatics III. MRI 1.5 T was used for MRI examination and syngo-GRACE program for MRS. Tumor measurement was based on RECIST 1.1, tumor response of ≥ 30% is considered positive, and < 30% is considered negative.
Results: Among 40 non-ulcerating breast cancer subjects with tumor size of more or equal to 5 cm, 47.5% show positive response. MRS I and II showed escalation of external choline/water ratio on days 20/21 after the introduction of cytostatic I as neoadjuvant treatment, which could be used to predict tumor shrinkage after cytostatic III as high as 30% or more, RR = 0.49 (CI 0.26 - 0.90), especially for < IIIC stage. Changes of internal choline/water ratio, RR= 0.54 (CI 0.28 - 1.04) and Apparent Diffusion Coefficient (ADC) changes, RR= 0.51 (CI 0.23-1.13) show similar result but less related. A positive moderate correlation between changes of external choline/water ratio and changes of internal choline/water ratio is seen (r=0,572, p=0,000). No correlation between degree of malignancy, Bcl2, Ki67 dan MVD with tumor response. Changes of choline/water ratio combined with Ki67 higher than or equal with 14% could give positive tumor response, on the other hand, declining of choline/water ratio combined with Ki67 less than 14%, no positive tumor response could be found. Conclusion: Increased of external choline/water ratio on MRS I-MRS II on day 20 or 21 following cytostatic 1 as neoadjuvant chemotherapy can predict tumor shrinkage following cytostatic III of equal or more than 30%, especiallyfor < IIIC stage. Changes of external and internal choline/water ratio could be used to predict tumor response following cytostastic administration.]"
2014
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UI - Disertasi Membership  Universitas Indonesia Library