Pasien-pasien kanker serviks yang dilakukan kemoradiasi dan brachiterapi di RSUP H. Adam Malik Medan Januari 2019

BAB 1 PENDAHULUAN

Pendahuluan 1 Kanker Serviks Kanker Serviks adalah kanker paling sering menyebabkan kematian keempat pada wanita dengan perkiraan kasus baru pada tahun 2018 yang mewakili 6,6% dari semua kanker wanita. Sekitar 90% kematian akibat kanker serviks terjadi di negara-negara berpenghasilan rendah dan menengah.

Pendahuluan 2 Epidemiologi Kanker Serviks Urutan ke 5 40% keganasan kasus kanker serviks kematian kanker serviks Kanker di Indonesia menempati urutan kelima tertinggi penyebab kematian Lebih dari 40% keganasan pada wanita Indonesia merupakan kanker ginekologi Sekitar kasus kanker serviks baru didiagnosis setiap tahun di Indonesia (perkiraan untuk tahun 2018) kematian kanker serviks terjadi setiap tahun di Indonesia

Terapi 3 Kanker Serviks Adjuvan Radioterapi (RT) atau Kemoradiasi Ajuvan Radioterapi (RT) atau Kemoradiasi dilakukan bila terdapat faktor risiko yaitu metastasis KGB, metastasis parametrium, batas sayatan tidak bebas tumor, deep stromal invasion, LVSI dan faktor risiko lainnya. Hanya ajuvan radiasi eksterna (EBRT) bila metastasis KGB saja. Apabila tepi sayatan tidak bebas tumor / closed margin, maka radiasi eksterna dilanjutkan dengan brakhiterapi metastasis KGB saja. Apabila tepi sayatan tidak bebas tumor / closed margin, maka radiasi eksterna dilanjutkan dengan brakhiterapi. Brachytherapy Brachytherapy adalah satu-satunya metode yang ditunjukkan dosis tinggi yang dibutuhkan untuk mengendalikan kanker serviks, tanpa menyebabkan efek samping yang tidak diinginkan

BAB II TUJUAN DAN MANFAAT

TUJUAN UMUM 4 Mengetahui prevalensi pasien-pasien kanker serviks yang dilakukan kemoradiasi dan brakiterapi di RSUP HAM pada tahun 2017

1 2 3 Tujuan Khusus 5 Karakteristik pasien Jenis kemoterapi, jumlah, dosis Luaran pasien kanker serviks Mengetahui karakteristik pasien- pasien kanker serviks yang dilakukan kemoradiasi dan brakiterapi di RSUP HAM pada tahun 2017 Mengetahui jenis kemoterapi, jumlah dan dosis radiasi serta jumlah brakiterapi yang dilakukan pada pasien – pasien kanker serviks di RSUP HAM dari tahun 2017 Mengetahui luaran pasien – pasien kanker serviks yang dilakukan kemoradiasi dan brakiterapi di RSUP HAM pada tahun 2017

MANFAAT 6 Memberikan informasi mengenai karakteristik pasien-pasien kanker serviks yang dilakukan kemoradiasi dan brakiterapi Sebagai rujukan tambahan bagi peneliti lain mengenai karakteristik pasien-pasien kanker serviks yang dilakukan kemoradiasi dan brakiterapi

BAB III METODOLOGI

METODOLOGI 7 Data diambil dari registrasi kanker dan SIRS RSUP H.Adam Malik Medan, kemudian dilakukan penyaringan pada kasus kanker serviks dan hanya pada pasien yang dilakukan kemoradiasi dan brakiterapi. Kemudian data yang kurang dilengkapi dari Rekam Medis dan bagian Radioterapi RSUP H.Adam Malik Medan.

BAB IV TINJAUAN PUSTAKA

Epidemiologi kasus baru kanker serviks kematian akibat kanker serviks 13,4 / / Pada tahun 2018, menurut perkiraan GLOBOCAN, terdapat sekitar kasus baru kanker serviks di seluruh dunia tahun 2018, ada sekitar kematian akibat kanker serviks di seluruh dunia Tingkat insidensi kasar dilaporkan tertinggi yaitu 13,4 / / tahun pada tahun 2015 dan terendah yaitu 0,14 / / tahun pada tahun 2006 di Cina Usia tingkat insidensi standar dilaporkan tertinggi yaitu / / tahun di Zimbabwe pada tahun 2000 dan terendah yaitu 0,11 / / tahun di Cina pada tahun 2006

Epidemiologi 9 Gambar 2 Insidensi Kematian Penderita Kanker Serviks per wanita Gambar 1 Insidensi Kejadian Kanker Serviks per wanita

Radioterapi 10 Radioterapi menggunakan sinar berenergi tinggi yang bertujuan untuk merusak serta membunuh sel kanker pada serviks, parametrial, dan kelenjar limfe di pelvis. Kanker serviks stadium IIB, III, IV sebaiknya diobati dengan radioterapi. Metode radioterapi disesuaikan dengan tujuannya yaitu tujuan pengobatan kuratif, paliatif atau adjuvan. Radioterapi dengan dosis kuratif hanya akan diberikan pada stadium I sampai III B. Apabila sel kanker sudah keluar rongga panggul, maka radioterapi hanya bersifat paliatif yang diberikan secara selektif pada stadium IV A. Radioterapi ajuvan diberikan atau diindikasikan pada pasien pasca histerektomi radikal pada stadium IA-IIA atas dasar indikasi stratifikasi resiko tinggi

Radiasi Eksternal 1 Prinsip kerja dari radioterapi adalah kematian sel yang ditandai dengan kerusakan DNA. Kerusakan DNA ini dapat disebabkan oleh efek langsung ke DNA maupun efek tidak langsung dengan ionisasi air di sitoplasma yang menghasilkan radikal bebas yang bersifat toksik terhadap DNA. Radiasi eksterna pada kanker serviks dapat diberikan dengan berbagai teknik konvensional 2 dimensi, konformal 3 dimensi, intensity modulated radiation therapy (IMRT) dan volumetric modulated radiation therapy (VMAT). Gambar 4 Target radiasi dalam foto simulator untuk radioterapi konvensional 2 dimensi untuk lapangan antero-posterior dan postero-anterior

BRACHYTHERAPY 12 Brachytherapy adalah pengobatan radiasi dengan mendekatkan sumber radiasi ke tumor primer Brakiterapi pada kanker serviks merupakan metode brakiterapi intrakaviter. Brakiterapi intrakaviter ini menggunakan aplikator tandem dan ovoid atau ring. Aplikator tandem dimasukkan ke dalam cerviks uteri di mana ujungnya sampai fundus uteri, sedangkan aplikator ovoid atau ring menempel pada fornix. Digunakan dalam kombinasi dengan EBRT, brachytherapy dapat memberikan hasil yang lebih baik daripada EBRT saja. Dosis yang diberikan untuk tujuan kuratif adalah sekurang-kurangnya 70 Grey (Gy). Selain itu teknik brachytherapy bermanfaat untuk tumor yang bersifat hipoksik atau memiliki daya proliferasi lambat karena secara kontinyu memberikan radiasi

Efek Samping Radioterapi 13 Kanker Serviks Pada pasien usia muda dan stadium awal, pembedahan lebih disukai daripada radioterapi karena dapat mempreservasi fungsi ovarium dan mempertahankan fungsi vagina, karena dosis rendah radioterapi terhadap ovarium dapat mengakibatkan infertilitas dan kehilangan fungsi endokrin. Efek Samping Akut Pruritus Deskuamasi Hiperpigmentasi pada kulit Nyeri berkemih Tenesmus dan hematochezia Efek Samping Lambat Striktur uretra Stenosis vagina Proktitis radiasi

Prognosis Kanker Serviks 14 Berdasarkan stadium kanker (5-years survival rate) Prognosis kanker serviks adalah buruk. Prognosis yang buruk tersebut dihubungkan dengan % kanker serviks terdiagnosis pada stadium invasif, stadium lanjut, bahkan stadium terminal. Stadium I Stadium II Stadium III Stadium IV 90 % 60-80% 50% 30%

Chapter V Result and Discussion

Result 15 Table I. Distribution of patients by age In table 1 shows the most patients aged 50 – 60 years, that is 38 people (49,3%). While the number of patients under 40 years is 8 people (10,4%) and patients aged years are 31 people (40,3%). Conducted research on the characteristics of cervical cancer involving 77 patients enrolled in the cancer registration information system in RSUP H. Adam Malik Hospital and SIRS from Januari 2017 until December 2017

Result 16 Table II. Distribution of patients based on parity In table II it was found that the majority of patients were multiparous as many as 64 patients (83,1%), while 1 patients (1,3%) were nullipara and 12 person (15,6%) was primiparous.

Result 17 Table III. Distribution of patients by stage In table III it can be seen that the majority of patients have reached stage IIIB as many as 51 people (66,2%), while patients in stage IIB were 20 people (26%). Stage IB2 and IIA2 were 1 patient (1,3%), IIIA and IVB were 2 patients (2,6%).

Result 18 Table IV. Duration of Diagnose It is known in the table IV above that, the total time to diagnose was  7 days for 59 patients (76,6%) and > 7 days for 18 patients (23,4%).

Result 19 Table V. Types of Radiotherapy It is known in the table above that, the types of radiotherapy was ERBT for 48 patients (62,3%) and ERBT plus brachytherapy as many as 24 patient (31,2%) and 5 patients (6,5%) was not perfomed radiotherapy.

Result 20 Table VI. Frequency of REBT It is known in the table above that, the frequency of ERBT was 25 – 28 times for 43 patients (59,7%) and  20 times as many as 19 patient (26,4%) and 10 patients (13,9%) was perfomed >28 ERBT.

Result 21 Table VII. Dose of ERBT It is known in the table above that, the most given dose for ERBT was  Gy for 58 patients (80,6%) and 52 Gy ERBT

Result 22 Table VIII. Duration of Radiotherapy It is known in the table above that, the duration of ERBT was 5 – 10 weeks for 58 patients (66,7%) and 1 – 4 weeks as many as 14 patient (19,4%), 11 – 15 weeks for 7 patients (9,7%) and 3 patients (4,2%) was perfomed >15 weeks ERBT. For brachytherapy, 21 patients (87,5%) had 1 – 4 weeks of brachytheraphy and only 3 patients had 5 – 10 weeks of brachytheraphy.

Result 23 Tabel IX. Stage of Cancer and Chemotherapy It is known in the table above that, the most stage of cancer who had chemotherapy was stage IIIB for 12 patients (25%) had 3 – 4 times chemotherapy and stage IIB for 12 patients (25%) had 5 times chemotherapy. 4 patients (8,3%) with cervical cancer stage IIB and IIIB who had 1 – 2 times of chemotherapy. Then as mach as 7 patients (14,6%) with cervical cancer stage IIB and IIIB who had 1 – 2 times of chemotherapy. Just 1 patient with stage IBA and IIIA had 5 times of chemotheraphy.

Result 24 Table X. Total Time the first diagnose to Chemo - Radiotherapy It is known in the table above that, total time the first diagnose to Chemo - Radiotherapy was 5 – 10 weeks for 20 patients (41,6%) and 1 – 4 weeks as many as 10 patient (20,8%), 11 – 15 weeks for 13 patients (27,2%), 16 – 20 weeks for 2 patients (4,2%) and >20 weeks for 3 patients (6,2%). For ERBT plus BT, 11 patients (45,8%) had 11 – 15 weeks total time, 7 patients (29,2%) had 5 – 10 weeks, 4 patients (16,7%) had 16 – 20 weeks and only 2 patients had >20 weeks total time for all.

Result 25 Table XI. Outcome to ERBT It is known in the table above that, response cancer to ERBT was complete for 19 patients (39,6%), cancer become progressive happened to 3 patients (6,2%), cancer had partial response just to 1 patient (2,1%). The most outcome can’t be evaluated because of lost of follow up for 25 patients (52,1%).

Result 26 Table XII. Outcome to ERBT + Brachytherapy It is known in the table above that, response cancer to ERBT plus Brachytherapy was complete for 15 patients (62,5%), cancer become progressive happened to 3 patients (6,2%), cancer had partial response just to 1 patient (2,1%). Then lost of follow up just for 5 patients (20,8%).

Result 27 Table XIII. Reccurence Free Survival It is known in the table above that, no reccurency 34 patients (81%), recurrent ≤6 months 2 patient s(4,7%), 6 – 12 months 5 patients (11,9), and > 12 months 1 patient (2,4%).

Discussion 28 Cervical cancer is the second most common female cancer in women aged 15 to 44 years in Indonesia. The highest incidence was in years (87.02%) with peak incidence in years (21.12%). 1,274 patients had multiparity status (74.55%). There were 336 patients identified at the initial stage (19.66%) and 1,373 patients at the final stage (80.34%). Tumor size of ≥ 4 cm was found in 535 patients (31.30%) and > 4 cm in 1,174 patients (68.70%). According to research by the Parazzini, the most parity of cervical cancer is 2 by 27%. Increased risk of cervical cancer in accordance with increasing parity with relative risk (RR) Based on this study 80.34% of patients were presented at an advanced stage. Radiotherapy plays an important role in the management of locally advanced cervical cancer. It provides local control at a range from 58–87%, however, intrapelvic recurrences occur 23% of the time in stage II-B and 41% of the time in stage IIIB. The highest recurrence distribution occurs in the lateral parametrium at 92%. Complete response after external radiation is a predictor of treatment success. 14 Various studies by Eifel P et al. and Rose et al. concluded that chemoradiation administration would improve survival and prevent recurrence compared to radiotherapy alone. The standard regimen for chemoradiation is cisplatin 40 mg / m2 every week for 5 times given with external radiotherapy.

Discussion 29 Cervical carcinoma Brachytherapy (BT) is a standard component of radical radiation therapy for cervical cancer. The local control rates, survival rates, and treatment-related complications in patients with Stage III cervical cancer treated with HDR or LDR and those treated with concomitant chemotherapy are examined. Patients with Stage III cervical cancer treated with EBRT and brachytherapy have a local control rate of >50% in most series. Selected patients with Stage III cervical carcinoma who have an adequate response to EBRT and concomitant chemotherapy may be treated with HDR brachytherapy. Study by Li et al found that with a median follow-up of 47 months (range: 10–61 months), the group which had pelvic EBRT with brachytherapy had a significantly improved 5-year PFS rate (P = 0.044), but no significant difference in 5- year overall survival was found between the two groups (P = 0.437). In patients treated without brachytherapy, the most common site of relapse was the pelvis. No significant differences were found regards to acute and chronic radiation toxicities, including myelosuppression, dermatitis, enterocolitis, proctitis and cystitis (P = 0.485, 0.875, 0.671, and respectively) between the groups of pelvic EBRT with and without vaginal brachytherapy Study by Pereira et al, found that patients unable to receive platinum-based CCRT had the worst outcome, and their responses were inferior to patients who received EBRT. The challenges of treating women with locally advanced cervical cancer in a low-resource setting are multifactorial and include treatment delays, the lack of brachytherapy and the unpredictable availability of chemotherapy

Conclusion 30 Based on the results as the characteristics, most patients aged years, that is 38 people (49,3%). While the number of patients under 40 years is 8 people (10,4%) and patients aged years are 31 people (40,3%). And the majority of patients were multiparous as many as 64 patients (83,1%), while 1 patients (1,3%) were nullipara and 12 person (15,6%) was primiparous Based on stage of cervical cancer, majority of patients have reached stage IIIB as many as 51 people (66,2%), while patients in stage IIB were 20 people (26%). Stage IB2 and IIA2 were 1 patient (1,3%), IIIA and IVB were 2 patients (2,6%). the total time to diagnose was  7 days for 59 patients (76,6%) and > 7 days for 18 patients (23,4%). The types of radiotherapy was ERBT for 48 patients (62,3%) and ERBT plus brachytherapy as many as 24 patient (31,2%) and 5 patients (6,5%) was not perfomed radiotherapy

Conclusion 31 The frequency of ERBT was 25 – 28 times for 43 patients (59,7%). The most given dose for ERBT was  Gy for 58 patients (80,6%). The most duration of ERBT was 5 – 10 weeks for 58 patients (66,7%). The most stage of cancer who had chemotherapy was stage IIIB for 12 patients (25%) had 3 – 4 times chemotherapy and stage IIB for 12 patients (25%) had 5 times chemotherapy. The frequency of Brachytherapy was 7 Gy to all of patient Total time the first diagnose to Chemo - Radiotherapy was 5 – 10 weeks for 20 patients (41,6%) and 1 – 4 weeks as many as 10 patient (20,8%), 11 – 15 weeks for 13 patients (27,2%) Response cancer to ERBT was complete for 19 patients (39,6%), cancer become progressive happened to 3 patients (6,2%). The most outcome can’t be evaluated because of lost of follow up for 25 patients (52,1%). Response cancer to ERBT plus Brachytherapy was complete for 15 patients (62,5%), cancer become progressive happened to 3 patients (6,2%) For RFS, this study had no reccurency 34 patients (81%), recurrent ≤6 months 2 patient s(4,7%), 6 – 12 months 5 patients (11,9), and > 12 months 1 patient (2,4%).

Recommendation 32 More accurate data in medical record and operating record. Education the patients not to discontinue therapy and keep continuous follow up after complete treatment.

Thank you very much ! Any Questions?