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4. Osteo Sarcoma

OSTEO SARCOMA

Oleh Dr H Subagyo SpB – SpOT

 

BAB I

PENDAHULUAN

Jaringan tulang rangka dewasa dibentuk oleh empat komponen, yaitu tulang, tulang rawan, jaringan ikat, dan sumsum tulang, dimana dari keempat komponen ini dapat timbul neoplasma. Dengan demikian, neoplasma tulang dapat diklasifikasikan atau digolongkan secara histologis menurut macam sel asal neoplasma, jadi didapat neoplasma golongan osteogenik/fibrogenik, dan miogenik, serta neoplasma golongan lain.  1

Berikut adalah klasifikasi dari lesi pada tulang yang menyerupai neoplasma. 2

  1. Osteogenic
  2. Osteoma (ivory exostosis)
  3. Single osteochondroma (osteocaltilage inous exostosis)
  4. Multiple osteochondromata (multiple hereditary exostoses)
  5. Osteoid osteoma
  6. Benign osteoblastoma (giant osteoid osteoma)
  7. Chondrogenic
    • Enchondroma
    • Multiple enchondromata (ollier’s dyschondroplasia)
    • Fibrogenic
    • Subperiosteal cortical defect (metaphyseal fibrous defect)
    • Nonosteogenic fibroma (nonossifiying fibroma)
    • Monostotic fibrous dysplasia
    • Polyostotic fibrous dysplasia
    • Osteofibrous dysplasia (campanacci syndrome)
    • “Brown tumor” (hyperparathyroidism)
      • Angiogenic
      • Angioma of bone (hemangioma and lymphangioma)
      • Aneurysmal bone cyst (ABC)
      • Uncertain origin
      • Simple bone cyst (unicameral bone cyst) (UBC)

Berikut adalah klasifikasi dari neoplasma primer pada tulang (true primary neoplasma of the bone).

  1. Osteogenic
  2. Osteosarcoma (osteogenic sarcoma)
  3. Surface osteosarcoma (paraosteal sarcoma; periosteal sarcoma)
  4. Chondrogenic
  5. Benign chondroblastoma
  6. Chondromyxoid fibroma
  7. Chondrosarcoma
  8. Fibrogenic
  9. Fibrosarcoma of bone
  10. Malignant fibrous histiocytoma of bone
  11. Angiogenic
  12. Angiosarcoma of bone
  13. Myelogenic
  14. Myeloma of bone (multiple myeloma)
  15. Ewing’s sarcoma (Ewing’s tumor)
  16. Hodgkin’s lymphoma of bone
  17. Non hodgkin’s lymphoma (reticulum cell sarcoma)
  18. Skeletal reticuloses (langerhans’ cell hostiocytoses)
  19. Leukemia
  20. Uncertain origin
  21. Giant cell tumor of the bone (osteoclastoma)

 

 BAB II

JOINT ANATOMY AND PHYSIOLOGY

Diarthrodial joint merupakan tempat terjadinya suatu pemisahan yang sempurna antara jaringan-jaringan penyambung. Diarthrodial joint terdiri dari cairan synovial yang melumasi dua lapisan kartilago sendi sehingga mencegahnya untuk saling bergesek satu dengan yang lain. Kartilago sendi unik dalam koefisien gesek di antara dua permukaan sendinya dengan jumlah cairan synovial yang normal, diperkirakan 10 kali lebih kecil bila dibandingkan dengan koefisien gesek di antara dua blok es. Hal ini memungkinkan adanya pergerakan bebas. 5

Jumlah kartilago sendi yang dicapai hingga pertumbuhan sempurna (usia pertengahan remaja) merupakan jumlah total yang akan dimiliki seseorang hingga akhir massa hidupnya. Sekali kartilago sendi ini mengalami kerusakan, maka tidak akan dapat diganti. Perbaikan kartilago (fibrokartilago) dapat terlihat serupa dan bahkan memiliki kemiripan komponen tetapi tidak identik dengan kartilago sendi, tetapi tidak memiliki mekanisme untuk mempertahankan beban berat pada permukaan sendi. Terlebih, fibrokartilago akan bertahan hingga beberapa tahun selama masih terdapat tekanan yang melintasi sendi normal. Penelitian masih terus dilanjutkan untuk mengetahui kartilago dalam hubungannya untuk mengganti bagian sendi yang rusak sebelum sendi tersebut mengalami kerusakan menyeluruh. 5

Kartilago sendi tersusun dari kartilago hyaline dimana 60 - 80 % di antaranya merupakan air. Sisa komposisinya terdiri dari makromolekul (kolagen, proteoglycan, dan protein nonkolagen), dimana secara keseluruhan komposisinya berupa asam amino dan gula. Kolagen tipe II membentuk sekitar 95 % kolagen pada kartilago sendi.

Terdapat tiga proteoglycan utama pada kartilago sendi dimana semuanya terdiri dari rantai polisakarida dengan inti protein. Dua proteoglycan yang lebih besar dapat sebagai uggrecan, bersama air, mengisi rongga interfibrillar dan kartilago merupakan komponen mekanisnya. Satu bagian terutama terdiri dari chondroitin sulfate dan lainnya berupa keratin sulfite. Bagian yang lebih kecil terutama terdiri dari sulfate. 5,6

Kartilago sendi terbagi menjadi empat zona atau lapisan, yaitu : 6

  1. Superficial (gliding).
  2. Middle (transitional).
  3. Deep (radial).
  4. Calcified.

Masing-masing zona memiliki pengaturan, komponen kolagen dan proteoglikan, serta fungsi sendiri. Gangguan yang terjadi pada berbagai lapisan tersebut dapat menyebabkan kartilago sendi tidak dapat menjalankan fungsinya (malfunction). Terdapat banyak protein minor pada kartilago sendi yang penting untuk fungsi normal kartilago. 5

Kemampuan kartilago yang sangat terbatas untuk dapat memperbaiki diri sangat berbeda dengan tulang. Tulang memiliki kemampuan untuk memperbaiki tidak hanya setelah tulang mengalami kerusakan ataupun luka namun juga pada saat tidak adanya jaringan parut (scar). Kartilago tidak dapat memiliki kemampuan untuk menyembuhkan diri. Luka yang terjadi pada kartilago sendi akan diikuti dengan respons dari chondrocyte, namun respons ini sangat terbatas dan tidak akan diikuti dengan penyembuhan terhadap luka-luka yang terjadi. 5

Jika luka, termasuk laserasi, yang terjadi superficial dan tidak mengenai tulang subchondral, maka tidak akan terdapat penyembuhan secara klinis. Jika luka hingga mengenai tulang subchondral maka akan terjadi perdarahan, dan akan menimbulkan adanya respons penyembuhan; meskipun demikian, kartilago yang mengalami penyembuhan tidak identik bila dibandingkan dengan kartilago sendi asli dan tidak memiliki fungsi yang sama karena kartilago restorative ini mengalami penyembuhan dengan cepat dan tidak dapat menahan tekanan yang normal ditimbulkan oleh sendi. 5

 

BAB III

WHAT IS CANCER


Berbagai organ dan jaringan tubuh dibentuk oleh blok-blok kecil pembangun yang disebut dengan "sel". Sel-sel ini di berbagai bagian tubuh yang berbeda memberikan perbedaan dalam rupa maupun fungsinya. Namun, kebanyakan dari sel-sel tersebut memiliki kesamaan dalam hal memperbanyak diri.

 Sel secara terus-menerus akan berubah menjadi lebih tua dan akhirnya mati, selanjutnya akan terbentuk sel-sel baru yang akan menggantikannya. Normalnya, pembelahan dan pertumbuhan sel terkontrol dengan tertib dan rapi. Namun, bila untuk berbagai alasan proses ini menjadi tidak terkontrol, maka sel-sel tersebut akan terus-menerus membelah, membentuk sel­sel abnormal yang nantinya akan membentuk suatu "gumpalan" yang disebut "tumor". Tumor ini dapat jinak ataupun ganas. "Kanker" merupakan sebutan yang digunakan untuk tumor yang berbahaya / ganas (malignant). 7,8,9

Seringkali, sel-sel kanker menyebar ke berbagai bagian tubuh dimana mereka akan berkembang menggantikan jaringan yang normal. Proses ini disebut sebagai "metastasis". Tanpa memperhatikan ke organ atau jaringan tubuh mana kanker menyebar, kanker ini selalu diberi nama sesuai dengan dari mana sel kanker tersebut pertama kali muncul. 9

Pada tumor jinak, sel-sel tidak menyebar ke berbagai bagian dari tubuh dan juga tidak bersifat sebagai "kanker". Meskipun demikian, jika sel-sel ini terus-menerus berkembang di tempat semula maka akan menimbulkan masalah berupa penekanan ke organ-organ di sekitarnya. 8

Sel-sel kanker terbentuk karena terdapat kerusakan pada DNA (gambar 9). DNA terdapat pada setiap sel dan secara langsung mempengaruhi kerja dari sel tersebut. Pada umumnya, ketika DNA rusak maka tubuh akan mampu untuk memperbaikinya. Pada sel-sel kanker, kerusakan DNA tidak dapat diperbaiki. Seseorang dapat mewarisi DNA yang rusak tersebut, yang nantinya akan bermanifestasi sebagai inherited cancer. Seringkali, DNA seseorang menjadi rusak karena terpapar oleh sesuatu hal di lingkungan, seperti merokok. 9

Penting untuk diketahui, bahwa kanker bukan merupakan satu penyakit dengan satu tipe pengobatan. Terdapat lebih dari 200 tipe kanker yang masing-masing memiliki nama dan pengobatan tersendiri. 8

Gambar 9. Normal cells and cells forming a tumor

Insidens

Tumor primer muskulokeletal jarang terjadi. Insidens dari neoplasma berkaitan dengan usia, misalnya osteosarcoma terjadi kebanyakan pada anak dan remaja, dan osteoclastoma terjadi kebanyakan pada masa dewasa. Tipe histogenetik dari tumor tergantung darimana jaringan tumor tersebut berasal. Lagipula, beberapa lesi spesifik cenderung pada tulang-tulang khusus atau area tulang, biasanya pada area dimana terjadi pertumbuhan maksimal atau remodelling. 3

Giant cell tumor (osteoclastoma) terjadi di dekat growth plate, dimana di sini terjadi resorpsi utama sebagai bagian dari remodeling; osteosarcoma muncul pada metaphysis, dimana terjadi pertumbuhan maksimal tulang baru. Tumor kartilago meliputi metaphysis dekat daerah growth plate, sedangkan round cell tumor pada bagian metafisis / diafisis sumsum tulang. Proses neoplastik ini menggambarkan kekacauan terhadap pertumbuhan normal dan fungsi remodeling tulang, yang menjadi tidak terkontrol. 3

Etiology

Kebanyakan neoplasma tulang dan jaringan lunak tidak diketahui penyebabnya. Kebanyakan tumor tipe histogenetik memiliki derajat agresivitas bervariasi dan timbul dalam bentuk jinak (benign) ataupun ganas (malignant). (Tabel 2) mengilustrasikan berbagai insidens dan histogenesis dari neoplasma muskuloskeletal. Perilaku biologis tumor dapat bervariasi, digambarkan oleh grade patologis tumor. Walaupun system grading bervariasi untuk berbagai macam tumor yang berbeda-beda, pada umumnya sistem simpel yang diadopsi oleh Musculosceletal Tumor Society merefleksikan perbedaan perilaku tumor secara keseluruhan dalam bentuk jinak (benign), keganasan derajat rendah (low-grade malignant), dan keganasan derajat tinggi (high-grade malignant). 3

Causes of primary bone cancer

Etiologi yang pasti dari tumor primer tulang masih belum diketahui. Penelitian masih terus dilakukan untuk menemukan penyebab terjadinya tumor tulang primer. Insidens tumor tulang yang banyak pada remaja atau dewasa muda menunjukkan kemungkinan ada hubungannya dengan perubahan yang terjadi pada tulang ketika tulang mengalami pertumbuhan. 10

Orang yang mendapatkan radioterapi dosis tinggi dalam jangka lama pada area sekitar tulang, memiliki resiko yang lebih besar untuk mendapatkan tumor tulang. Orang yang menderita penyakit tulang kronis, dikenal sebagai Paget’s disease, juga memiliki resiko yang lebih tinggi untuk berkembang menjadi osteosarcoma. Jika seseorang memiliki tumor jinak tulang yang dikenal sebagai osteochondroma atau chondroma, akan memiliki resiko yang sedikit lebih tinggi untuk berkembang menjadi chondrosarcoma. 10

Beberapa orang yang memiliki kelainan genetik mengalami peningkatan resiko terhadap pertumbuhan kanker tulang. Orang yang memiliki kelainan yang didapat, misalnya sindrom Li-Fraumeni, memiliki resiko lebih besar terkena osteosarcoma dan beberapa tipe tumor tulang lainnya. Anak-anak penderita tumor mata yang dikenal sebagai retinoblastoma, yang disebabkan oleh kelainan genetik yang didapat, memiliki resiko tinggi untuk menderita osteosarkoma. Hereditary Multiple Exostoses (HME), kelainan genetik lainnya, juga memiliki resiko tinggi untuk berkembang menjadi chondrosarkoma. 10

Symptoms of primary bone cancer

Gejala yang ditimbulkan oleh kanker tulang bervariasi sesuai dengan partikel tulang yang terkena dan posisinya dalam tubuh. Gejala juga dapat bervariasi sesuai ukuran tumor itu sendiri. 11

Gejala awal yang ditimbulkan berupa nyeri pada daerah sekeliling tumor. Bermula dari perasaan nyeri yang persisten dan rasa nyeri bertambah pada malam hari ketika otot-otot berelaksasi. Pada anak, gejala ini dapat disalah-artikan sebagai “keseleo” atau “growing pains”. 11

Gejala lain yang mungkin timbul adalah pembengkakan daerah sekeliling tumor, terutama pada tumor yang sudah mulai membesar. 11

Penderita dengan tumor primer tulang umumnya datang karena pembengkakan, nyeri, atau patah tulang patologik. Sering pada diagnosis pertama disangka distorsi atau cedera olah raga karena sering didapat riwayat trauma lokal pada neoplasma muskuloskeletal. 12

Secara tipikal, pasien biasanya menunjukkan adanya riwayat nyeri yang seringkali memburuk pada malam hari dan biasanya tidak berhubungan dengan aktivitas. Mula-mula nyeri hanya sedang saja dan hilang timbul, tetapi akhirnya menjadi progresif, difus, dan terus-menerus. Nyeri umumnya karena periost dan endosteum yang sensitif. 12

Dapat juga timbul massa atau pembengkakan. Pembengkakan lokal biasanya dapat diketahui apabila kelainan telah menembus batas tulang. Pembengkakan dari kelainan jinak biasanya menetap dan tidak nyeri, kecuali pada osteoid osteoma. Gejala konstitusional (berat badan turun, demam, keringat malam, malaise) biasanya tidak ditemukan, kecuali pada kasus-kasus yang sudah mengalami penyebaran.

 Lesi yang berdekatan dengan persendian dapat menyebabkan efusi, kontraktur, dan nyeri pada pergerakan. Tumor jaringan lunak seringkali tidak terdapat nyeri, kecuali jika struktur neurovaskular ikut terlibat. Penekanan terhadap vena atau pembuluh limfe pada tungkai dapat menyebabkan edema pada bagian distal, dan massa yang lebih besar akan menunjukkan adanya gambaran distensi vena. 3

Massa ganas jaringan lunak dapat menjadi keras dan terpancang pada jaringan subkutan, otot, atau tulang, dan biasanya tidak lunak. Rasa hangat di daerah setempat dapat dirasakan dengan jelas karena lesi ganas ini menyebabkan local angiogenesis. Pasien mungkin juga datang dengan fraktur patologis sebagai manifestasi lesi intraosseus jinak atau ganas, dengan destruksi pada tulang dan diikuti oleh gangguan mekanisme. Nyeri ketika mengangkat beban berat merupakan gejala klinis yang seringkali mengindikasikan adanya impending fracture. Nyeri hebat dan tiba-tiba biasanya disebabkan oleh fraktur patologis. 3

Evaluasi sebaiknya meliputi riwayat dan pemeriksaan fisik pada regio yang terlibat, dengan perhatian khusus pada struktur sendi, otot, neurologis, dan vaskular. Pemeriksaan pembuluh limfe regional dan pembuluh limfe jauh merupakan hal penting, sebagaimana pemeriksaan paru-paru dan abdomen untuk menilai adanya kemungkinan penyakit yang bermetastasis. 12

Karakteristik

Foto rontgen dapat memberi keterangan penting:  12

  • Tumor jinak berbatas tegas dan korteks selalu utuh
  • Batas tumor ganas biasanya kurang jelas atau samar
  • Umumnya terlihat pembentukan tulang baru
  • Lokalisasi pada tulang vertebra:

          -    Jinak        : Osteoid osteoma, osteoblastoma, atau hemangioma

          -    Ganas      : Metastasis atau myeloma

  • Lokalisasi pada tulang pipih seperti pelvis atau scapula

          -    Metastasis, myeloma, atau chondrosarcoma

  • Lokalisasi pada tulang panjang

          -    Epifisis    :   Chondrosarcoma atau giant cell tumor

          -    Metafisis :   Osteosarcoma

          -    Diafisis   :   Metastasis atau Ewing’s tumor, Kista tulang aneurisma

Diagnosis Banding tumor primer berdasarkan foto rontgen adalah: 12

  • Metastasis Karsinoma
  • Osteomielitis
  • Kista Tulang Soliter (Solitary Bone Cyst)
  • Kalus bekas tulang patah
  • Kista tulang aneurisma (Aneurysmal Bone Cyst)
  • Tumor coklat pada hiperparatiroid
  • Displasia fibrosa (Fibrous Dysplasia)
  • Miositis osifikans

Sel neoplasma tidak selalu merusak tulang, tetapi keberadaanya menyebabkan resorpsi tulang atau osteoklastik lokal. Sebaliknya, sel neoplasma tertentu dapat bersifat osteoblastik lokal dan membentuk tulang normal yang disebut kelainan tulang reaktif. Sel neoplasma kelompok osteogenik adalah sel yang dapat menghasilkan osteoid dan tulang, sedangkan sel kelompok osteolitik adalah sel yang meresorpsi tulang yang tampak pada gambaran radiologik sebagai osteolisis atau osteosklerosis. 12

Neoplasma muskoloskeletal dicirikan sebagai pertumbuhan sentrifugal yang berasal dari satu fokus, pseudoencapsulation (pembentukan zona reactive tissue disekeliling lesi yang berkembang, dimana lesi keganasan dapat diinvasi secara lokal oleh tumor), dan memiliki kecenderungan untuk berada pada batas anatomi pada awal perkembangan tumor. Tumor-tumor ini memiliki kecenderungan untuk menyebar sepanjang bidang fascial dan cenderung mengandung sisa kompartemen anatomis, suatu karakteristik yang sangat penting untuk derajat dan pengobatan pembedahan pada lesi ini. Yang termasuk dalam kompartemen anatomis adalah tulang, kompartemen otot, persendian, jaringan subkutan dan kulit, dan pada beberapa kasus major neurovascular sheath. 12

Tulang yang lemah karena kerusakan lokal akibat resorpsi osteoklastik mudah mengalami patah tulang patologis. 12

Metastasis

Metastasis dari neoplasma ganas muskuloskeletal dihubungkan dengan prognosis yang buruk. Metastasis seringkali ke paru-paru, walaupun beberapa tumor cenderung melibatkan pembuluh limfe regional, dan juga kemungkinan metastasis ke tulang. Metastasis ke otak dan visceral tidak lazim, umumnya muncul hanya pada penyebaran penyakit tahap akhir (terminal end-stage disseminated disease). 3

Grading

Grading dapat mendeskripsikan penampilan dari sel-sel kanker di bawah mikroskop. Grading juga membantu menentukan seberapa cepat sel kanker tersebut melakukan pertumbuhan. Terdapat 3 grade, yaitu : grade 1(low grade), grade 2 (moderate grade), dan grade 3 (high grade). Low grade berarti sel kanker terlihat menyerupai sel-sel tulang yang normal. Sel-sel tersebut bertumbuh secara lambat dan melakukan penyebaran minimal. Pada tumor high grade, sel-sel kanker tampak sangat abnormal. Sel-sel tersebut melakukan pertumbuhan yang sangat cepat dan menyebar secara invasif. 13

  1. Grade I (atau “low grade”) tumor bersifat seperti kartilago normal, tetapi dikelilingi oleh daerah lamella tulang (tidak terdapat pada lesi jinak), atau menunjukkan sel-sel atipikal termasuk bentuk binucleate (sel dengan 2 inti yang menjadi satu). 25
  1. Grade II (atau “intermediate grade”) lebih banyak mengandung sel-sel atipikal, hiperkromatik, dan ukuran inti lebih besar. (Schiller, 1985). 25
  1. Grade III (atau “high grade”) tumor memiliki daerah pleomorphism, sel-sel lebih besar dan lebih hiperkromatik, sudah dapat dideteksi adanya mitosis. (Bjornsson et al., 1998). 25

Staging Bone Tumors

Pada tahun 1980 Musculoskeletal Tumor Society (MSTS) mengadopsi Surgical Staging System (SSS) untuk sarcoma tulang. Sistem ini berdasarkan pada fakta bahwa semua tipe sarkoma mesenkimal tulang memiliki sifat yang mirip. SSS di deskripsikan oleh Enneking, dkk yang berdasarkan pada klasifikasi GTM : grade (G), lokasi (T), dan keterlibatan limfe dan metastasis (M).

  • Stadium Surgical (G) merepresentasikan stadium histologi dari lesi dan data klinis lain yang digunakan untuk memberi batasan low grade (G1) dan high grade (G2).
  • Lokasi Surgical (T) merepresentasikan lokasi lesi, dapat intracompartmental  (T1) dan extracompartmental (T2). Pada T1 memiliki kemungkinan yang lebih besar untuk dilakukan pengangkatan tumor yang adekuat sehingga menjadi prosedur nonamputatif. Umumnya low grade sarcoma tulang biasanya intracompartment (T1) dan sarcoma high grade biasanya extracompartment (T2)
  • Keterlibatan limfe dan metastasis (M). Keterlibatan limfe biasanya berbanding lurus dengan metastasis jauh.

Sistem staging ini dapat menunjukkan taksiran yang baik dalam memprediksi kelangsungan hidup seseorang. 3

 

Pathology and Genetics of Tumours of Soft Tissue and Bone – World Health Organisation Classification of Tumours. Fletcher et al. Oxford University Press, 2002.

Stage

Characteristic

Metastases

Benign

1

2

3

 

Latent

Active

Aggressive

 

No

No

No

Malignant

IA

IB

IIA

IIB

III

 

Low grade: intracompartmental

Low grade: extracompartmental

High grade: intracompartmental

High grade: extracompartmental

Low or high grade:

intra or extracompartmental

 

No

No

No

No

Yes

Tabel 1. Surgical staging system for musculoskeletal tumor 13

Gambaran radiologi

Pemeriksaan foto polos merupakan satu-satunya pemeriksaan yang berguna untuk menentukan diagnosis banding dari lesi pada tulang. Hal yang digunakan sebagai pertimbangan.

Dengan menggunakan kriteria ini, diagnosis banding yang akurat dapat dirumuskan pada kebanyakan kasus.

Keadaan infeksi (osteomyelitis) dapat memberikan gambaran radiografik yang sangat bervariasi. Kondisi metabolik, inflamasi, displasia, trauma, kongenital dan degeneratif juga harus selalu dipertimbangkan. Lesi jaringan Iunak dapat dievaluasi Iehih baik dengan MRI dibandingkan pencitraan radiografi lainnya. 12

Diagnosis

Anamnesis. gambaran klinik, dan pemeriksaan radiologik adalah komponen penting untuk mendiagnosis suatu neoplasma. Selain itu, biopsi dan penemuan laboratorium biokimia juga penting. Bone scan dapat dipergunakan untuk menentukan lokasi neoplasma primer atau sekunder. 12

Tomografi dapat membuat visualisasi tiga dimensi neoplasma muskuloskeletal, umpamanya neoplasma di pelvis atau tulang belakang yang sulit ditentukan dengan pemeriksaan radiologik lain. 12

Pemeriksaan laboratorium rutin meliputi hitung darah lengkap dan hitung jenis; Erythrocyte Sedimentation Rate (ESR); serum fosfatase alkali, jumlah kalsium dan fosfat, fungsi ginjal dan hati, dan urinalisis. Jika multiple myeloma merupakan diagnosis banding, maka harus dilakukan pemeriksaan jumlah serum protein dan imunoelektroforesis. Pada kebanyakan tumor primer, kedua pemeriksaan utama ini dalam batas normal. Peninggian konsentrasi protein total serum memungkinkan adanya suatu mieloma multipel, yang ditunjukkan pula dengan pemeriksaan protein Bence Jones pada urine. 12

Fosfatase alkali mencerminkan aktivitas osteoblas, biasanya dapat meningkat pada keadaan osteosarcoma, dan hitung darah serta pemeriksaan ESR dapat membantu menyingkirkan adanya kemungkinan diagnosis ini. Langkah pemeriksaan lanjutan tergantung dari lokasi lesi, kemungkinan diagnosis, usia pasien, dan kemungkinan keganasan. 3

Bone scan hampir selalu digunakan untuk menilai aktivitas dan luas lesi primer dan juga untuk menyingkirkan adanya lesi di tempat lain. Soft-tissue tumor bone scan digunakan untuk menilai lesi yang berada di dekat tulang atau bila dicurigai terjadi suatu keganasan. Untuk berbagai lesi yang memiliki potensi keganasan, dianjurkan untuk dilakukan pemeriksaan pencitraan tiga dimensi (CT scan atau MRI) sebelum dilakukan biopsi untuk menilai luas lesi dan prosedur biopsi yang akan dipilih, meminimalisasi kontaminasi ke berbagai lokasi, selanjutnya dapat dipikirkan tindakan pembedahan. Pemeriksaan radiografi thorax (atau lebih baik dengan CT scan) dan CT scan abdomen digunakan untuk menyingkirkan kemungkinan adanya metasatasis dari penyakit lain. 12

How bone cancer is diagnosed

Ahli bedah tulang di rumah sakit akan melakukan anamnesa sejarah medis dari pasien sebelum melakukan beberapa pemeriksaan fisik. Pemeriksaan fisik ini meliputi pemeriksaan pada tulang yang bermasalah, apakah terdapat pembengkakan atau nyeri. Dokter juga akan menyarankan pasien untuk melakukan pemeriksaan darah di laboratorium untuk memeriksa kesehatan umum pasien. 14

Tes-tes di bawah ini dapat dilakukan untuk menegakkan diagnosis kanker tulang. 14

1. Rontgen tulang

Rontgen tulang merupakan pemeriksaan paling sederhana yang dapat dilakukan untuk menegakkan adanya kanker tulang, dan menentukan apakah kanker tersebut berasal dari tulang (primary bone cancer) atau metastasis ke tulang dari kanker pada organ lain di tubuh (secondary bone cancer). Terkadang, rontgen dapat memberikan gambaran karakteristik  yang dapat membantu dokter untuk mendiagnosis tipe dari kanker tulang. Hal ini sering terjadi pada osteosarcoma. Pada rontgen, kanker tulang dapat menunjukkan gambaran daerah yang rusak akibat pertumbuhan berlebihan sel-sel tulang yang mengelilingi sel kanker. 14

2. Bone scan

Pemeriksaan ini lebih sensitif dan lebih bermakna dibandingkan pemeriksaan rontgen tulang sederhana, dan dapat memberikan gambaran daerah abnormal secara sangat jelas. 14

Sejumlah kecil substansi radioaktif disuntikkan melalui intravena, biasanya di vena lengan. Tulang yang abnormal akan menyerap substansi tersebut lebih banyak dan bersifat lebih radioaktif dibandingkan dengan tulang yang normal, jadi daerah tulang abnormal akan menunjukkan gambaran “hot spot”. Tingkat keradioaktifan yang digunakan sangat rendah sehingga tidak berbahaya bagi tubuh. 14

Walaupun keabnormalan dapat dideteksi melalui “bone scan” ini, tapi tidak selalu dapat menentukan kelainan diakibatkan oleh kanker atau keadaan lain seperti arthritis. Kadang-kadang CT atau MRI scan dapat membantu dokter dalam menentukan kelainan tersebut. 14

3. Core needle biopsy

Biopsi terkadang dibutuhkan, apabila x-ray dan bone scan tidak dapat menunjukkan apakah tumor ini jinak (non-cancerous) atau ganas (cancerous). Ketika sel-sel dilihat dibawah mikroskop, barulah dapat ditentukan apakah tumor itu ganas atau tidak. Apabila ternyata merupakan suatu kanker, maka pemeriksaan lebih lanjut akan dibutuhkan untuk menentukan secara tepat tipe dari kanker tulang tersebut. 14

Sebelum dilakukan biopsi, sebaiknya dilakukan anestesi terlebih dahulu. Kemudian dilakukan penusukan dengan menggunakan jarum khusus pada tulang yang terkena untuk mendapatkan sampel sel. Apabila massa tumor teraba di permukaan tubuh dan mudah ditentukan letaknya, dokter dapat meraba untuk menentukan sampai dimana jarum telah masuk. Tetapi jika massa tumor tidak teraba di permukaan (seperti di abdomen) , dokter mungkin membutuhkan USG atau bahkan CT scan untuk memandu sampai jarum tepat masuk di lokasi tumor berada. Kadang-kadang, seperti pada anak-anak, biopsi dilakukan dibawah anestesi umum. 14

4. Open biopsy

Biopsi terbuka artinya, biopsy dilakukan dengan menggunakan scalpel (pisau bedah) untuk membuka area dan mengambil sampel jaringan. Jika massa tumornya kecil, dapat diambil secara utuh (excissional biopsy) untuk dijadikan sampel. Biopsi terbuka dapat dilakukan dibawah anestesi lokal maupun umum. Hal ini tergantung dari lokasi massa tumor tersebut berada. Sama seperti pada needle biopsy, sampel sel-sel yang telah diambil dikirim ke laboratorium untuk dilakukan pemeriksaan PA (patologi anatomi) terhadap sampel tersebut. Hasil terhadap sampel tersebut akan didapat setelah beberapa hari sampai 7 hari. 14

Tes-tes lanjutan pada Kanker Tulang Primer

Di bawah ini adalah tes-tes lanjutan pada kanker tulang primer : 15

  • Rontgen Thorax

Lokasi tersering yang menjadi tempat metastasis kanker tulang primer adalah paru-paru. Dan mungkin rontgen thorax dapat menunjukkan paru-paru terkena atau tidak. 15

  • CT (computerised tomography) scan

CT scan menggunakan serangkaian penyinaran dengan sinar-X, yang menghasilkan gambaran 3 dimensi dari tubuh. Pemeriksaan ini tidak menimbulkan rasa sakit, tetapi membutuhkan waktu cukup lama, sekitar 10-30 menit. CT scan menggunakan radiasi dalam jumlah kecil, sehingga tidak membahayakan pasien yang menjalani pemeriksaan maupun pemeriksa sendiri. Pasien yang menjalani pemeriksaan CT scan dianjurkan untuk puasa, minimal 4 jam sebelum melakukan pemeriksaan. 15

Pasien diberi suatu substansi berupa cairan yang dapat diminum atau disuntikkan untuk mewarnai daerah yang akan diberi sinar-X agar daerah tersebut dapat terlihat jelas dibandingkan dengan daerah lain. Cairan ini akan menimbulkan rasa panas dalam tubuh untuk beberapa menit. Untuk pasien yang memiliki alergi terhadap iodine atau mempunyai riwayat asthma, akan mengalami reaksi yang perlu diperhatikan setelah penyuntikan. Pasien dapat langsung pulang ke rumah setelah pemeriksaan CT scan selesai dilakukan. 15

 

Ilustrasi pemeriksaan CT scan

  • Bone marrow sample

Pemeriksaan ini hanya dilakukan dimana diagnosanya adalah kanker tulang tipe Ewing’s Sarcoma ataupun suspek Ewing’s Sarcoma, karena kanker tulang ini sangat jarang bermetastasis ke sumsum tulang. 15

Sumsum tulang merupakan material dalam tulang yang memiliki bentuk menyerupai sponge dimana sel-sel darah dibentuk. Sejumlah kecil sampel diambil dari tulang panggul (pelvis) dan kemudian diperiksa di bawah mikroskop untuk melihat komponen dari sel-sel tulang yang abnormal. 15

Sampel sumsum tulang dapat diambil dengan anestesi lokal, tetapi pada anak kecil bisanya dilakukan dengan anestesi umum. 15

 

Sampel sumsum tulang biasanya diambil dari tulang panggul (pelvis)

  • PET (positron emission tomography scan)

PET merupakan pemeriksaan terbaru yang dilakukan sebagai pemeriksaan penunjang untuk membantu menegakkan diagnosis kanker tulang primer. Pemeriksaan ini dilakukan oleh ahlinya pada pusat-pusat pemeriksaan khusus. Pemeriksaan ini tidak mutlak, tetapi pasien dapat mengkonsultasikannya dengan dokter spesialis apakah pemeriksaan ini perlu dilakukan pada kasusnya. 15

PET menggunakan substansi gula radioaktif dosis rendah untuk mengukur aktifitas sel-sel di beberapa tempat pada tubuh. Substansi gula radioaktif ringan tersebut disuntikkan dalam jumlah sangat kecil ke dalam vena, biasanya vena di lengan. Kemudian dilakukan scanning . Daerah letak kanker biasanya lebih radioaktif dibandingkan jaringan lain di sekitarnya, hal tersebut yang yang menjadi dasar pemeriksaan PET. 15

Mungkin akan membutuhkan waktu beberapa hari untuk mendapatkan hasil dari pemeriksaan ini, dan pada periode “menunggu” ini akan menjadi waktu yang sulit bagi pasien. 15

Apabila pemeriksaan menunjukkan hasil bahwa pasien menderita Ewing’s Sarcoma, pasien membutuhkan beberapa pemeriksaan lebih lanjut sebagai persiapan melakukan kemoterapi. 15

Kemoterapi pada Kanker Primer Tulang

Kemoterapi merupakan terapi yang penting pada beberapa tipe kanker primer tulang. Kemoterapi menggunakan obat-obat anti-kanker (sitotoksik) untuk menghancurkan sel-sel kanker. 16

 

How chemotherapy is given

Obat-obat kemoterapi dapat diberikan dalam bentuk tablet maupun disuntikkan ke dalam vena (intravena). Kadang-kadang, untuk lebih mudahnya dan untuk menghindari pasien mendapatkan suntikan terus-menerus, tabung plastik (disebut central line) ditanam pada vena di daerah dada. Penanaman tabung tersebut dilakukan di bawah anestesi lokal maupun umum. 16

Selain dapat melalui pemasangan secara central line, tabung dapat ditanam dalam vena pada lengan pasien; teknik ini disebut PICC (Peripherally Inserted Central Catheter). Kadang-kadang juga digunakan teknik dengan meletakkan tabung beserta injectable port yang ditanam dibawah kulit; dan teknik ini dikenal sebagai implantable port. 16

Kemoterapi akan dibagi menjadi beberapa sesi pertemuan yang membutuhkan waktu beberapa hari. Sesi ini diikuti oleh periode istirahat selama beberapa minggu, fungsi periode ini adalah untuk memulihkan keadaan tubuh dari segala efek samping yang didapat dari kemoterapi. Banyaknya sesi pertemuan tergantung dari tipe kanker tulang yang dimiliki dan seberapa baik sel kanker tersebut berespons terhadap obat-obat kemoterapi tersebut. 16

Kemoterapi biasaya akan membutuhkan waktu beberapa hari di Rumah Sakit. Tetapi dapat dilakukan juga secara berobat jalan, yaitu pada waktu yang ditentukan pasien datang ke Rumah Sakit untuk mendapatkan kemoterapi. Pada keadaan ini, kemoterapi diberikan secara kontinyu ke dalam vena melalui “central line” maupun “PICC line”. Dengan teknik tersebut, dosis dapat dikontrol melalui “small portable pump”. 16

Dokter biasanya akan merekomendasikan kemoterapi awal sebelum pasien menjalani operasi atau radioterapi, sesuai dengan tipe kanker tulang yang dimiliki oleh pasien. Pemberian kemoterapi ini bertujuan memperkecil ukuran tumor dan memudahkannya untuk diangkat. Juga dapat mengurangi gejala-gejala seperti nyeri dan dapat mengurangi kesempatan kanker untuk bermetastasis. Pemberian terapi yang dilakukan sebelum operasi disebut juga neo-adjuvant therapy. 16

Jika pasien menderita osteosarcoma atau Ewing’s Sarcoma, pasien akan membutuhkan lebih banyak kemoterapi setelah operasi atau radioterapi. Hal ini bertujuan menghancurkan sel kanker yang mungkin timbul lagi dan mencegah sarcoma bermetastasis jauh ke luar tulang. Terapi ini disebut adjuvant therapy dan terapi ini diberikan karena beberapa penelitian menunjukkan bahwa sejumlah kecil dari sel kanker akan timbul (khususnya di paru-paru), yang dapat dideteksi namun sangat minimal oleh scanning. 16

Sebelum mendapatkan kemoterapi, pasien membutuhkan beberapa tes untuk memeriksa keadaan jantung, hepar, dan ginjal pasien, apakah masih berfungsi dengan baik. Dan selanjutnya akan dilakukan pemeriksaan darah. Untuk memeriksa keadaan dan fungsi ginjal, disuntikkan sejumlah kecil cairan radioaktif ke dalam salah satu pembuluh darah vena. Cairan radioaktif tersebut akan ikut keluar melalui urin. Beberapa jam setelah penyuntikkan bahan radiokatif, baru dapat dilakukan pemeriksaan darah. EKG juga dilakukan untuk mendapatkan data mengenai jantung. 16

Setelah hasilnya diperoleh, dokter akan memberitahukan hasil dari semua pemeriksaan yang dilakukan, sebagai pertimbangan dilakukannya kemoterapi pada pasien. Hasil biasanya akan diperoleh dalam waktu beberapa hari. 16

Efek Samping Kemoterapi

Terkadang kemoterapi memberikan efek samping yang tidak menyenangkan. Beberapa efek samping akan timbul sementara dan dapat dikontrol dengan obat-obatan. Beberapa efek samping kemoterapi akan dijelaskan disini, disertai tips-tips untuk menghindari atau mengatasi efek samping tersebut. 16

1. Imunitas yang rendah terhadap infeksi.

Ketika obat bekerja pada sel-sel kanker dalam tubuh, obat-obat tersebut juga bekerja mengurangi sel-sel normal dalam darah. Saat sel-sel darah normal tersebut berkurang, pasien lebih mudah terserang infeksi dan lebih mudah lelah. Selama kemoterapi, sebaiknya dilakukan pemeriksaan darah secara reguler untuk memastikan tidak terdapat kelainan, dan jika memungkinkan, dapat diberikan antibiotik profilaksis untuk mencegah infeksi selama kemoterapi.

Obat-obatan yang berfungsi sebagai growth factors dapat diberikan untuk menstimulasi produksi dari sel darah putih oleh sumsum tulang dan mengurangi kemungkinan terkena infeksi.

Apabila suhu pasien meningkat sampai lebih dari 38ºC (100.5ºF), atau pasien tiba-tiba merasa tidak enak, walaupun dengan suhu yang normal, segera hubungi dokter atau Rumah Sakit terdekat. 

2.Anemia

Jika kadar sel darah merah (hemoglobin) dalam darah rendah, pasien akan merasa lemas dan letargi. Pasien kemudian akan merasa sulit bernapas. Ini merupakan gejala-gejala dari anemia – kadar hemoglobin yang rendah dalam darah. Anemia dapat diatasi dengan baik melalui transfusi darah. 

3. Bruising and bleeding

Platelet merupakan satu jenis sel yang berperan dalam pembekuan darah. Apabila jumlah dari platelet menurun dalam darah, maka akan mudah terjadi perdarahan kapiler, yang dapat membentuk bintik-bintik perdarahan (petechiae) maupun bercak-bercak perdarahan (purpura) yang tampak pada permukaan kulit, dan akan mudah mengalami perdarahan hebat hanya dengan goresan maupun irisan yang sangat kecil.

4. “Feeling sick” (Nausea-Vomitting)

Beberapa obat-obatan yang digunakan untuk kemoterapi pada kanker tulang primer akan menimbulkan perasaan mual, ingin muntah bahkan sampai muntah, seperti orang sakit. Namun saat ini, hal tersebut dapat diatasi dengan munculnya obat anti-sickness (anti-emesis) untuk mencegah dan juga mengurangi perasaan mual-muntah.

5. Mulut Kering

Beberapa kemoterapi dapat menyebabkan mulut pasien kering, dan hal tersebut memicu timbulnya tukak-tukak kecil dalam mulut. Hal ini dapat diatasi dengan obat kumur. Luka-luka di mulut dapat menyebabkan pasien sulit makan dan minum, dan ini dapat diatasi dengan cara menggantikan kebutuhan makan dengan minuman bernutrisi atau diet lunak.

6.  Rambut rontok

Beberapa obat kemoterapi juga menyebabkan kerontokan pada rambut. Namun rambut akan kembali tumbuh dalam waktu 3-6 bulan.

Walaupun hal ini sangat sulit untuk dihadapi, tetapi efek samping-efek samping tersebut akan menghilang saat kemoterapi dihentikan. Sangat penting untuk diingat bahwa kemoterapi menimbulkan pengaruh berbeda pada masing-masing pasien. Beberapa pasien tetap dapat hidup secara normal ketika menjalani kemoterapi, tetapi pada beberapa pasien lain mengalami efek samping yang tidak menyenangkan seperti yang telah disebutkan diatas. 16

  • Fertilitas

Kemampuan untuk hamil atau menjadi ayah dari seorang bayi akan terganggu karena efek dari obat-obatan kemoterapi yang digunakan pada treatment tumor tulang.

 

Beberapa pasien perempuan mengeluh setelah mendapatkan kemoterapi, ia akan segera mengalami menopause, dan juga mengalami tanda-tanda menopause seperti berkeringat dan hot flushes. Pada beberapa kasus, pemberian terapi berupa Hormones Replacement Therapy (HRT) dapat menggantikan hormon yang sudah tidak di produksi. 

  • Kontrasepsi

Tidak dianjurkan untuk hamil atau memiliki bayi selama menjalani kemoterapi, karena obat-obatan yang digunakan pada terapi tersebut dapat membahayakan perkembangan janin. Jadi, sebaiknya konsultasikan dengan dokter ahli mengenai kontrasepsi yang akan digunakan untuk mencegah kehamilan selama menjalani kemoterapi.

Terapi Kanker Tulang Primer dengan Radioterapi

Radioterapi mengatasi kanker dengan menggunakan sinar X energi tinggi, yang menghancurkan sel-sel kanker tetapi tidak membahayakan sel-sel yang normal. 17

Kapan Radioterapi diberikan ??

Lama pemberian terapi tergantung dari tipe dan ukuran kanker, rata-rata berlangsung selama beberapa minggu. Dokter sebelumnya akan mendiskusikan mengenai terapi ini kepada pasien untuk menjelaskan mengenai radioterapi lebih lanjut. 17

Radioterapi tidak biasa digunakan sebagai terapi pada osteosarcoma, karena tumor tipe ini tidak sensitif terhadap radiasi. Tetapi, jika tungkai mengalami fraktur dan resiko penyebaran ke organ lain meningkat, radioterapi mungkin harus diberikan setelah dilakukan operasi untuk menghancurkan sisa-sisa sel kanker, khususnya di sekitar jaringan yang terserang kanker. 17

Radioterapi yang diberikan setelah operasi biasanya sangat membantu untuk mengurangi kesempatan rekurensi sel-sel kanker, pada chondrosarcoma maupun pada “spindle cell sarcoma”. 17

Planning the treatment

Agar radioterapi efektif, terapi ini harus direncanakan secara tepat. Tahap awal, kulit tepat diatas tumor akan diberi tanda untuk membantu ahli radiografi menentukan dimana sinar X tepat diberikan. Tanda ini harus tetap terlihat selama terapi, dan dapat dibersihkan setelah terapi selesai dilakukan. Pasien sebelumnya akan diberikan instruksi untuk selalu memperhatikan perubahan pada kulit sekitar area yang terpajan oleh sinar X. 17

Sebelum setiap sesi radioterapi dilakukan, ahli radiografi akan mengatur posisi pasien agar terasa senyaman mungkin. Selama terapi, yang biasanya membutuhkan waktu selama beberapa menit, pasien akan ditinggal seorang diri dalam ruangan. Tetapi pasien diharapkan untuk tidak khawatir, karena ahli radiografi akan tetap memperhatikan pasien secara seksama dari ruangan lain. Radioterapi tidak menyebabkan rasa nyeri, namun pasien diharapkan tetap dalam posisi berbaring untuk beberapa menit selama terapi diberikan. 17

Efek Samping Radioterapi

Radioterapi dapat meyebabkan efek samping umum berupa mual (nausea) dan lemas. Efek samping yang timbul mulai dari ringan hingga berat dan dirasakan mengganggu, tergantung dari dosis radioterapi yang diberikan dan berapa lama terapi berlangsung. Ahli radioterapi akan menyampaikan terlebih dahulu apa yang kira-kira akan terjadi setelah terapi selesai. 17

  • Kelelahan

Radioterapi akan menimbulkan efek samping berupa perasaan lelah, maka pasien dianjurkan untuk beristirahat di sela waktu pemberian terapi, khususnya jika pasien akan menempuh perjalanan jauh yang melelahkan dalam melakukan terapi setiap hari.

  • Mual (Nausea)

Nausea biasanya dapat diatasi dengan obat-obatan anti-mual (anti-emesis), dan dokter akan menganjurkan kepada pasien untuk mengkonsumsinya agar efek samping mual dapat diatasi. Jika pasien mengalami anoreksia (tidak nafsu makan), kebutuhan nutrisi bisa digantikan dengan suplemen bernutrisi tinggi dan minuman berkalori tinggi.

  • Kerontokan Rambut

Radioterapi dapat menyebabkan kerontokan rambut pada tempat yang terpapar oleh sinar X.

Semua efek samping ini akan berangsur-angsur menghilang ketika terapi dihentikan, tetapi jika efek samping dirasakan menetap dan berkelanjutan, sebaiknya segera hubungi dokter. Radioterapi tidak membuat pasien menjadi radioaktif, juga aman bagi pasien untuk berada di tengah-tengah orang lain termasuk anak-anak, selama terapi berlangsung. 17

Jenis-jenis Kanker Tulang

Ketika seorang pasien dengan kanker mengeluhkan bahwa mereka memiliki kanker tulang, dokter mengatakan bahwa kanker tersebut merupakan penyebaran kanker primer yang berasal dari tempat lain. Ini disebut metastasis kanker dan dapat ditemui pada pasien dengan kanker payudara lanjut, juga pada kanker paru-paru. Ketika sel-sel kanker pada tulang diteliti di bawah mikroskop, sel-sel tersebut akan menunjukkan dari jaringan mana mereka berasal. Pada pasien dengan kanker paru-paru yang telah bermetastasis ke tulang, sel-sel kanker terlihat dan bersifat seperti sel-sel kanker paru-paru, bukan seperti sel-sel kanker tulang, bahkan setelah mereka bermetastasis dari paru-paru ke tulang. Sel-sel kanker yang telah bermetastasis ke tulang diterapi dengan obat-obatan yang sama dengan kanker paru. 18

Beberapa jenis kanker yang juga biasa disebut sebagi kanker tulang bermula dari sumsum tulang – pada sel-sel pembentuk darah. Yang paling sering adalah Multiple Myeloma. Leukemia lebih banyak digolongkan ke dalam “kanker darah” daripada “kanker tulang”, tetapi seperti Multiple Myeloma, sel-sel ganasnya berasal dari sumsum tulang. Terkadang, limfoma, yang seringnya berasal dari kelenjar limfe, dapat juga berasal dari sumsum tulang. Multiple Myeloma, leukemia, dan limfoma akan dijelaskan selanjutnya. 18

Tipe utama dari kanker tulang yang benar-benar berasal dari tulang disebut Sarcoma. Sarcoma adalah kanker tulang yang berasal pada tulang, otot, jaringan fibrous, pembuluh darah, jaringan lemak, juga jaringan lain. Sarcoma dapat berkembang pada bagian manapun dari tubuh. Pada bagian ini, akan dijelaskan macam-macam jaringan asal sel-sel kanker berkembang pada tulang. 18

Terapi pada Kanker Tulang Primer

Pasien dengan kanker tulang primer akan membutuhkan kombinasi beberapa terapi yang berbeda untuk menangani kanker yang dideritanya. Kombinasi terapi yang biasa diberikan adalah operasi, kemoterapi, dan radioterapi. 18

  • Operasi merupakan bagian terpenting dalam terapi pada kanker tulang, karena berfungsi membersihkan tumor pada tulang. Apabila operasi tidak memungkinkan untuk dilakukan, radioterapi sebagai pilihan terapi pada tipe tumor yang radiosensitive dapat dipertimbangkan, biasanya efektif pada Ewing’s sarcoma.
  • Kemoterapi juga merupakan terapiyang penting bagi penderita kanker tulang, terutama kanker tulang tipa osteosarcoma, Ewing’s sarcoma, dan Malignant Fibrous Histiocytoma. Kemoterapi biasanya diberikan sebelum dilakukan operasi, karena diduga dapat memperkecil ukuran tumor yang besar sehingga dapat menghindari dilakukannya amputasi. Beberapa kemoterapi diberikan setelah dilakukan operasi, tujuannya untuk menghancurkan sisa-sisa tumor yang mungkin masih ada.
  • Radioterapi, yang biasanya menjadi terapi pada kasus Ewing’s sarcoma, diberikan setelah dilakukan operasi. Walaupun radioterapi jarang digunakan sebagai treatment pada kasus-kasus osteosarcoma dan chondrosarcoma, tetapi kadang dibutuhkan pada keadaan tertentu.

Persiapan Terapi

Pada Rumah Sakit besar, dokter-dokter spesialis yang tergabung dalam tim dokter akan dengan pasien, terapi apa yang terbaik untuk diterapkan pada keadaan masing-masing pasien. Tim ini, yang biasa disebut “Multidisciplinary Team (MDT) termasuk didalamnya adalah ahli bedah tulang yang memiliki spesialisasi pada kanker tulang, ahli onkologi medis (spesialis kemoterapi), ahli onkologi klinis (spesialis radioterapi), dan juga beberapa tenaga paramedis professional, seperti: 18

  • perawat khusus
  • ahli gizi
  • ahli fisioterapi (fisiotherapist)
  • occupational therapist
  • ahli psikologi dan konseling

Tim dokter bersama-sama akan memberikan saran kepada pasien untuk mendapatkan pilihan terapi yang paling tepat, melihat dari beberapa faktor yang terlibat dan ikut mempengaruhi. Faktor-faktor ini meliputi usia pasien, keadaan kesehatan secara umum, tipe dan ukuran kanker, dan apakah kanker sudah mulai melakukan penyebaran. 18

Apabila kedua terapi dirasakan sama efektifnya untuk tipe dan stage dari kanker yang diderita, dokter akan menawarkan kepada pasien untuk memutuskan terapi apa yang akan dipilih. Kadang-kadang pasien sulit memutuskan dalam keadaan seperti ini, dan pasien membutuhkan informasi selengkap-lengkapnya tentang perbedaan kedua terapi, apa efek samping yang akan timbul pada terapi tersebut, dan juga kekurangan dan kelebihan masing-masing terapi, sebelum yakin untuk memutuskan terapi yang paling tepat bagi pasien tersebut. 18

Jangan ragu untuk selalu menanyakan tentang segala aspek yang ingin diketahui, kurang dimengerti, dan yang dikhawatirkan dari terapi. Mungkin dengan mengetahui informasi tentang kekurangan dan kelebihan dari masing-masing terapi, yang diperoleh dari dokter spesialis, perawat maupun pendukungnya, diharapkan dapat lebih membantu pasien. 18

Second opinion

Walaupun beberapa spesialis kanker bekerja bersama dalam satu tim dan menggunakan pedoman standar nasional untuk memutuskan terapi yang paling tepat pada kasus kanker tertentu, namun pasien tetap dianjurkan untuk mendapatkan opini medis dari spesialis lain, yang disebut sebagai second opinion, dengan tujuan agar pasien merasa yakin. Second opinion dapat menyebabkan penundaan dalam memulai suatu terapi, jadi sebaiknya dokter spesialis maupun pasien harus yakin akan mendapatkan opini lain dan informasi tambahan yang berguna. 18

Giving the consent

Sebelum pasien menjalani suatu terapi, dokter akan terlebih dahulu menjelaskan kepada pasien tujuan terapi ini bagi pasien. Dokter biasanya akan selalu meminta pasien untuk menandatangani suatu surat persetujuan, yang isinya menyatakan bahwa pasien setuju dan mengizinkan akan dilakukan suatu terapi atas pasien tersebut (consent) oleh staf Rumah Sakit. Tidak ada tindakan medis yang dilakukan tanpa surat persetujuan dari pasien, dan sebelum pasien diminta untuk menandatanganinya, pasien harus mendapatkan informasi lengkap terlebih dahulu mengenai : 18

  • terapi apa yang dianjurkan untuk pasien
  • keuntungan dan kerugian dari terapi
  • adakah terapi lain yang tersedia selain terapi yang didapat oleh pasien
  • adakah resiko yang signifikan maupun efek samping dari terapi

Pasien juga bebas memilih untuk tidak di terapi. Staf Rumah Sakit harus menjelaskan pada pasien apa yang akan terjadi jika pasien tidak mendapatkan terapi. Setelah pasien memutuskan untuk tidak di terapi, maka dokter atau perawat yang sedang bertugas akan mencatat keputusan itu pada catatan medis pasien (biasa disebut rekam medis). Pasien tidak diharuskan untuk menjelaskan alasan pasien menolak untuk dilakukan operasi, tetapi sebaiknya staf Rumah Sakit mengetahui alasan tersebut agar mereka dapat memberikan saran atau pilihan jalan keluar lain yang mungkin dapat ditempuh. 18

Keuntungan dan Kerugian

Kebanyakan pasien memiliki pikiran yang negatif tentang mendapatkan terapi kanker, terutama karena efek samping yang mungkin akan terjadi. Beberapa pasien juga akan bertanya apa yang akan terjadi apabila ia tidak mendapatkan terapi tersebut. Namun walaupun kebanyakan terapi kanker akan menimbulkan efek samping, ini biasanya akan segera dapat diatasi dengan pemberian obat-obatan. 18

Terapi dapat diberikan untuk alasan yang berbeda-beda, dan keuntungan yang akan didapat juga bervariasi bergantung kepada keadaan masing-masing pasien.

Pada pasien dengan kanker tulang stage awal, hanya dengan jalan operasi sudah bisa menyelesaikan masalah. Pada keadaan tertentu, terapi tambahan dibutuhkan untuk mengurangi resiko kanker timbul kembali dan mengalami rekurensi. 18

Jika kanker sudah berada pada stadium lebih lanjut, terapi mungkin hanya bisa dilakukan untuk mengontrol gejala-gejala yang timbul dan juga untuk meningkatkan kualitas hidup. Namun terkadang, untuk beberapa pasien, terapi tidak memiliki efek apapun terhadap kankernya, dan mereka hanya mendapatkan efek samping yang negatif tanpa mendapatkan manfaat dari terapi itu sendiri. 1

Pengambilan Keputusan Terapi

Ketika pasien sudah dijelaskan mengenai tujuan utama dari dilakukannya terapi yaitu untuk menyembuhkan kanker, memutuskan untuk menerima terapi adalah suatu hal yang mudah. Tetapi ketika dijelaskan bahwa terapi tidak dapat menyembuhkan, dan hanya berfungsi mengontrol perkembangan kanker untuk suatu waktu tertentu, keadaan tersebut mungkin akan lebih sulit bagi pasien untuk mengambil keputusan. Jika pasien pada akhirnya memilih untuk tidak melakukan terapi (operasi, kemoterapi, maupun terapi radiasi), pasien masih akan mendapatkan terapi suportif (paliatif) dengan medikasi untuk mengatasi gejala-gejala yang timbul. 18

Primary Bone Tumors

Terdapat bermacam-macam tipe tumor tulang. Tumor-tumor tulang tersebut diberi nama sesuai dengan lokasi tulang atau jaringan sekeliling yang terkena dan jenis sel-sel yang membentuknya. Beberapa tumor primer tulang merupakan tumor jinak (non-cancerous) dan yang lainnya ganas (cancerous). Kebanyakan tipe ganas dari tumor tulang disebut sarcoma. 8,9

Modified from Lichtenstein, Louis: Classification of Primary Tumors of Bone, Cancer 4:335, 1951

Histology

Benign

% Cases

Malignant

% Cases

Hemopoietic

(28%)

 

 

Myeloma

Lymphoma

24.7

3.1

Chondrogenic

(27%)

Osteochondroma

Enchondroma

Chondroblastoma

Chondromyxoid fibroma

12.0

4.3

0.7

0.6

Primary chondrosarcoma

8.7

Osteogenic (25%)

Osteoid osteoma

Osteoblastoma

2.5

0.7

Osteosarcoma

Chondroblastic osteosarcoma

Fibroblastic osteosarcoma

Parosteal osteosarcoma

9.9

6.0

 

4.6

0.9

Unknown

origin (12%)

Giant cell tumor

4.8

Ewing’s sarcoma

Giant cell tumor

Adamantinoma

6.3

0.5

0.2

Fibrogenic (4%)

Fibroma

1.5

Fibrosarcoma

2.5

Notochordal (3.5%)

 

 

Chordoma

3.5

Vascular (0.8%)

Hemangioma

Hemangiopericytoma

0.6

0.1

Hemangioendothelioma

0.1

 

Neurogenic (<0.1%)

Neurilemmoma

<0.1

 

 

Tabel 2. Incidence of bone tumor 3

Benign Bone Tumors

Tumor jinak tulang tidak bermetastasis ke jaringan maupun organ lain, dan terapinya tidak ada cara lain selain operasi. Beberapa tipe tumor jinak tulang meliputi osteoid osteoma, osteoblastoma, osteochondroma, enchondroma, dan chondromyxoid fibroma. 8,9

 

Malignant Bone Tumors

1. Osteosarcoma

Osteosarkoma (sarkoma osteogenik) adalah tumor tulang ganas, yang biasanya berhubungan dengan periode kecepatan pertumbuhan pada masa remaja. 7,8,9

Osteosarkoma merupakan tumor ganas yang paling sering ditemukan pada anak-anak. Rata-rata penyakit ini terdiagnosis pada umur 15 tahun. Angka kejadian pada anak laki-laki dan anak perempuan adalah sama, tetapi pada akhir masa remaja penyakit ini lebih banyak ditemukan pada anak laki-laki. 7,8,9

Penyebab yang pasti tidak diketahui. Bukti-bukti mendukung bahwa osteosarkoma merupakan penyakit yang diturunkan. 7,8,9

Osteosarkoma cenderung tumbuh di tulang paha (ujung bawah), tulang lengan atas (ujung atas), tulang pelvis, dan tulang kering (ujung atas). Ujung tulang-tulang tersebut merupakan daerah dimana terjadi perubahan dan kecepatan pertumbuhan yang terbesar. Meskipun demikian, osteosarkoma juga bisa tumbuh di tulang lainnya. 7,8,9

Gejala yang paling sering ditemukan adalah nyeri. Sejalan dengan pertumbuhan tumor, juga bisa terjadi pembengkakan dan pergerakan yang terbatas. Tumor di tungkai menyebabkan penderita berjalan timpang, sedangkan tumor di lengan menimbulkan nyeri ketika lengan dipakai untuk mengangkat sesuatu benda. Pembengkakan pada tumor mungkin teraba hangat dan agak memerah. 7,8,9

Tanda awal dari penyakit ini bisa merupakan patah tulang karena tumor bisa menyebabkan tulang menjadi lemah. Patah tulang di tempat tumbuhnya tumor disebut fraktur patologis dan seringkali terjadi setelah suatu gerakan rutin. 7,8,9

Pemeriksaan yang biasa dilakukan: 8,9

  • Rontgen tulang yang terkena
  • CT scan tulang yang terkena
  • Pemeriksaan darah (termasuk kimia serum)
  • CT scan dada untuk melihat adanya penyebaran ke paru-paru
  • Biopsi terbuka
  • Scanning tulang untuk melihat penyebaran tumor.

Sebelum dilakukan pembedahan, diberikan kemoterapi yang biasanya akan menyebabkan tumor mengecil. Kemoterapi juga penting karena akan membunuh setiap sel tumor yang sudah mulai menyebar. Kemoterapi yang biasa diberikan: 7,8,9

- metotreksat dosis tinggi dengan leukovorin

- doxorubicin (adriamisin)

- cisplatin

- cyclophosphamide (sitoksan)

- bleomycin.

Jika belum terjadi penyebaran ke paru-paru, maka angka harapan hidup mencapai 60%. Sekitar 75% penderita bertahan hidup sampai 5 tahun setelah penyakitnya terdiagnosis. 8,9

2. Chondrosarcoma

Kondrosarkoma adalah tumor yang terdiri dari sel-sel kartilago (tulang rawan) yang ganas dan merupakan primary bone cancer terbanyak kedua yang banyak dijumpai. Kanker ini tidak umum dijumpai pada orang berusia di bawah 20 tahun. Setelah berusia 20 tahun, resiko untuk timbulnya chondrosarcoma meningkat hingga mencapai usia sekitar 75 tahun. Insidens kanker ini sebanding antara laki-laki dan perempuan. Kebanyakan kondrosarkoma tumbuh lambat atau merupakan tumor derajat rendah, yang sering dapat disembuhkan dengan pembedahan. Tetapi, beberapa diantaranya adalah tumor derajat tinggi yang cenderung untuk menyebar. Untuk menegakkan diagnosis perlu dilakukan biopsi. Chondrosarcoma harus diangkat seluruhnya melalui pembedahan karena tidak bereaksi terhadap kemoterapi maupun terapi penyinaran. amputasi tungkai atau lengan jarang diperlukan. Jika tumor diangkat seluruhnya, lebih dari 75% penderita bertahan hidup. 8,9

3. Ewing’s tumor

Kanker tulang ini, dinamai sesuai dengan nama penemunya, dr. James Ewing, yang menjelaskan tentang kanker ini pertama kali pada tahun 1921. Ewing’s sarcoma biasanya berkembang di tulang, < 10% berkembang di jaringan/organ lain. Ewing’s tumor biasanya timbul pada tulang panjang di tungkai dan lengan, juga dapat berkembang pada tulang panggul (pelvis) dan tulang lainnya. Ewing’s tumor merupakan primary bone cancer terbanyak ketiga yang dijumpai. Tidak seperti osteosarcoma, Ewing’s tumor terbentuk di cavum tulang. Kanker ini biasanya diderita oleh anak-anak dan remaja, jarang pada dewasa usia > 30 tahun, Insidens Ewing’s sarcoma lebih banyak pada orang kulit putih, jarang pada ras Afro-Americans dan Asia-Americans. 8,9

Tumor Ewing (sarkoma ewing) muncul pada masa pubertas, dimana tulang tumbuh sangat cepat. Jarang ditemukan pada anak yang berumur kurang dari 10 tahun. Gejala yang paling sering dikeluhkan adalah nyeri dan kadang pembengkakan di bagian tulang yang terkena. penderita juga mungkin mengalami demam. Tumor mudah menyebar, seringkali menyebar ke paru-paru dan tulang lainnya.

 Pada saat terdiagnosis, penyebaran telah terjadi hampir pada 30% penderita. Jika diduga suatu tumor, maka biasanya dilakukan pemeriksaan untuk menentukan lokasi dan penyebaran tumor: 8,9

  • rontgen tulang kerangka tubuh
  • rontgen dada
  • CT scan dada
  • skening tulang
  • biopsi tumor

Pengobatan seringkali merupakan kombinasi dari: 8,9

  • kemoterapi (siklofosfamid, vinkristin, daktinomisin, doksorubisin, ifosfamid, etoposid)
  • terapi penyinaran tumor
  • terapi pembedahan untuk mengangkat tumor. 


Prognosis tergantung kepada lokasi dan penyebaran tumor. 8,9



4. Malignant fibrous histiocytoma

Jenis kanker tulang ini biasanya timbul pada “jaringan lunak” (jaringan ikat, seperti ligamen, tendon, lemak, dan otot), namun beberapa juga tumbuh pada tulang. Ketika tumor ini berkembang di tulang, biasanya bagian yang terkena adalah tungkai (pada daerah sekeliling lutut) dan lengan. Kanker ini biasanya diderita oleh orang lanjut usia dan dewasa usia pertengahan, jarang pada anak-anak. Malignant Fibrous Histiocytoma (MFH) berkembang sangat cepat. Biasanya menyebar ke organ lain dalam tubuh, seperti kelenjar limfe dan paru-paru. 8,9

5. Fibrosarcoma and malignant fibrous histiocytoma

Kanker ini biasanya berasal dari jaringan lunak (jaringan ikat selain tulang, yaitu ligamen, tendo, lemak dan otot) dan jarang berawal dari tulang. Kanker ini biasanya ditemukan pada usia lanjut dan usia pertengahan. Tulang yang paling sering terkena adalah tulang pada tungkai, lengan dan rahang. Fibrosarkoma dan histiositoma fibrosa maligna mirip dengan osteosarkoma dalam bentuk, lokasi dan gejala-gejalanya. pengobatannya juga sama. 8,9

6. Giant cell tumor of bone

Tipe tumor primer tulang ini memiliki bentuk jinak dan ganas. Tipe jinak (non-cancerous) lebih sering ditemui. Tumor ini mempunyai tempat predileksi di ekstremitas inferior (biasanya daerah sekitar lutut) atau daerah lengan pada usia dewasa muda maupun usia pertengahan. Lebih dari 10% dari Giant Cell Tumor didiagnosa sebagai keganasan dan menyebar ke organ lain, tetapi setelah dilakukan operasi  tumor ini biasanya akan mengalami rekurensi pada tempat asal tumor, dan biasanya ketika rekuren tumor akan menyebar ke organ lain. 8,9

7. Chordoma

Tumor primer tulang tipe ini biasanya terdapat pada basis cranii dan tulang belakang. Tumor ini berkembang pada dewasa usia diatas 30 tahun, dan dua kali lebih sering terdapat pada laki-laki dibanding perempuan. Chordoma berkembang secara lambat dan biasanya tidak menyebar ke organ lain pada tubuh, tetapi sering mengalami rekurensi pada tempat yang sama apabila tidak diangkat secara utuh. Tempat tersering yang menjadi lokasi metastasis tumor ini adalah kelenjar getah bening, paru-paru, dan hati. 8,9

8. Spindle cell sarcoma

Terdapat empat tipe dari spindle cell sarcoma, yaitu : malignant fibrous histiocytoma, fibrosarcoma, leiomyosarcoma, dan undifferentiated sarcoma of the bone. 8,9

    *  Malignant fibrous histiocytoma

Tipe ini sangat jarang terjadi, dan biasanya dialami pada masa usia dewasa pertengahan. Biasanya letaknya pada lengan atau kaki, khususnya pada persendian lutut.

    *  Fibrosarcoma

Tipe kanker tulang ini, yang juga sangat jarang, juga biasanya ditemukan pada usia dewasa, khususnya selama usia dewasa pertengahan. Lokasi tersering adalah pada femur.

    *  Leiomyosarcoma

Leiomyosarcoma tulang juga sangat jarang ditemukan. Dapat terjadi pada semua usia, tapi amat sangat jarang ditemukan pada usia di bawah 20 tahun. Laki-laki memiliki kemungkinan menderita leiomyosarcoma sedikit lebih tinggi dibanding dengan perempuan. Tempat predileksi biasanya pada tulang panjang, seperti tulang femur, tibia, dan humerus.

    *  Undifferentiated sarcoma of the bone

Tumor ini berasal dari sel-sel primitif, dan sulit untuk ditentukan tumor jenis ini berasal dari sel-sel normal tipe apa.

9. Angiosarcoma

Tipe tumor primer tulang ini jarang, lebih sering ditemukan pada laki-laki. Dapat terjadi pada semua usia, tapi sangat jarang pada usia di bawah 20 tahun. Angiosarcoma dapat mengenai semua tulang pada sistem skeleton. Angiosarcoma dapat mengenai lebih dari satu tulang pada waktu yang sama, atau berkembang pada lebih dari satu tempat dalam satu tulang. 8,9

Kanker Lain yang Berkembang dalam Tulang

1. Lymphoma

Limfoma Non-Hodgkin secara umum berkembang di kelenjar limfe, tetapi terkadang ditemukan pula pada tulang. Limfoma Non-Hodgkin tulang primer merupakan penyakit yang mengalami penyebaran luas karena lokasi tumor yang multipel dalam tubuh. Manifestasi klinis dan terapi Limfoma Non-Hodgkin pada tulang sama dengan pada Limfoma Non-Hodgkin subtipe dan stage lainnya. Terapinya sama dengan limfoma yang berasal dari kelenjar limfe, tapi berbeda dengan terapi pada sarcoma tulang primer. 8

Limfoma tulang maligna (sarkoma sel retikulum) biasanya timbul pada usia 40- 50 tahun. Bisa berasal dari tulang manapun atau berasal dari tempat lain di tubuh kemudian menyebar ke tulang. 
Biasanya tumor ini menimbulkan nyeri dan pembengkakan, dan tulang yang rusak lebih mudah patah. 

Pengobatan terdiri dari kombinasi kemoterapi dan terapi penyinaran, yang sama efektifnya dengan pengangkatan tumor. Amputasi jarang diperlukan. 8

2. Multiple myeloma

Mieloma multipel merupakan kanker tulang primer yang paling sering ditemukan, yang berasal dari sel sumsum tulang yang menghasilkan sel darah. Umumnya terjadi pada orang dewasa. 8

Tumor ini dapat mengenai satu atau lebih tulang sehingga nyeri dapat muncul pada satu tempat atau lebih. Pengobatannya rumit, yaitu meliputi kemoterapi, terapi penyinaran dan pembedahan. 8

What is osteosarcoma?

Neoplasma primer pada tulang biasanya jarang. Penelitian saat ini mengatakan angka kejadian osteosarcoma di Amerika Serikat adalah 2000 kasus baru setiap tahunnya. Angka ini hanya 0,2% dari jumlah total angka keganasan yang terjadi setiap tahun. Osteosarcoma adalah penyakit kanker tulang yang paling sering ditemukan pada rentang usia 10 – 25 tahun. Pada kebanyakan kasus kanker ini ditemukan pada tulang-tulang di sekitar lutut. Dan biasanya terletak pada growing ends of the bone (metaphysic). Kadang-kadang osteosarcoma ini juga disebut “osteogenic sarcoma’’ yang secara harafiah berarti tulang yang membentuk kanker.

 

Tabel 1-1 Demographic Features in

 Osteogenic Sarcoma

Variables

Features

Usia

60% terjadi pada dekade 2 dan 3

Jenis Kelamin

60% pria; 40% wanita

Lokasi

50% terletak di sekitar lutut

 

42% pada femur

 

18% pada tibia

 

10% pada humerus

 

8% pada pelvis

Faktor predisposisi

Radiasi tulang

 

Paget’s Disease

 

Retinoblastoma

 

Ollier’s Disease

Keluhan awal osteosarcoma biasanya adalah rasa nyeri, pada mulanya hanya nyeri samar, lalu menjadi kontinu dan secara bertahap bertambah hebat. Selanjutnya timbul pembengkakan setempat, yang membesar progresif. Nyeri dan bengkak ini dapat mempengaruhi gerakan sendi yang berdekatan. Riwayat penyakit umumnya 2-4 bulan, sebagian besar pasien telah menjalani fisioterapi, pemberian obat  luar, dan terapi yang tidak tepat lainnya. Sejalan dengan progresi penyakit dapat timbul pula demam, penurunan berat badan, dan anemia. Kausa kematian adalah metastasis      

Ukuran tumor dan atau derajat bengkak bervariasi menurut lingkup invasi tumor dan kedalaman lokasinya, berbatas tidak tegas. Membesarnya tumor membuat regangan kulit permukaannya bertambah, kulit mengkilap, suhu kulit dapat meningkat, vena superfisialis melebar.

 How to diagnose?

Diagnosis terutama berdasarkan tampilan klinis, pemeriksaan pencitraan, dan biopsy patologi. Pemeriksaan patologi merupakan tindakan diagnosa yang tidak boleh tidak ada. Terutama sebelum diberikan kemoterapi, radioterapi, dan amputasi serta terapi destruktif lain, harus terdapat diagnosis patologi yang jelas sebagai landasan. Dapat dengan biopsy pungsi atau eksisi untuk mendapatkan diagnosis patologi jelas. Insisi biopsy harus mempertimbangkan pengaruh bagi tindakan operasi berikutnya. 

Bila tumor tulang dicurigai telah terjadi kita harus melakukan pemeriksaan medis yang lengkap.

                                Tabel 1-2. Pemeriksaan Pasien Suspek Osteosarcoma

Prebiopsy

Postbiopsy

Anamnesa dan pemeriksaan fisik

CT-Scan & atau MRI

Pertanyaan spesifik

Arteriogram

     Riwayat trauma baru-baru ini

CT-Scan dada

     Infeksi baru-baru ini

 

    Gejala tambahan - anoreksia,    penurunan berat badan, demam

 

Foto Rontgen polos

 

    Posisi AP dan lateral pada tulang yang terkena

 

   Foto rontgen pada area yang dicurigai dan sekitarnya

 

Pemeriksaan Hematologi

 

   Pemeriksaan sedimentasi

 

   Alkaline fosfatase

 

Scanning radioisotop

 

Artrogram dan arthroscopy jarang digunakan

 

 Staging Osteosarcoma

 

Tabel 1-3. Surgical Staging

pada Osteosarcoma menurut Enneking

Stadium

Grade

Lokasi

IA

Low G1

Intracompartment (T1)

IB

Low G1

Extracompartment (T2)

IIA

High G2

Intracompartment (T1)

IIB

High G2

Extracompartment (T2)

III

Any G

Regional atau metastasis jauh (M1)

Any T

Pemeriksaan Penunjang

Pemeriksaan Laboratorium

1. sedimentasi darah

Sekitar separuh pasien, menunjukkan percepatan sedimentasi darah, umumnya pada kasus dengan tumor besar, diferensiasi buruk, progresi cepat. Laju sedimentasi darah dapat menjadi salah satu indicator progresi tumor atau pemantauan rekurensinya, tapi spesifitas dan sensitivitasnya kurang kuat.

2. alkali fosfatase.

Meningkat pada sekitar 50-70% pasien. Pada osteosarkoma stadium dini, osteosarkoma sklerotik, osteosarkoma well differentiated, osteosarkoma parosteal, nilai alkali fosfat dapat normal. Namun bila tumor berkembang cepat, bermetastasis, nilai alkali fosfatasenya dapat meninggi mencolok. Pasca eksisi tumor dan kemoterapi nilainya dapat menurun, namun jika timbul rekurensi atau metastasis dapat kembali meninggi. Karena itu, maka alkali fosfatase dapat menjadi salah satu indikator pemantau rekurensi dan metastasis serta untuk menilai prognosis.

Pemeriksaan pencitraan

1. Foto sinar X

Tampilan sinar X tipikal osteosarkoma adalah destruksi matriks tulang difus, infiltratif pada metafisis tulang panjang. Derajat destruksi berlainan, lingkupnya bervariasi, batas tidak tegas, lesi dominan osteolitik atau osteoblastik, atau campuran keduanya.

Dapat terlihat korteks tulang mengalami destruksi, defek, patah retak, dapat terjadi fraktur patologis, namun jarang dijumpai. Bila lesi mengenai jaringan lunak sekitar, tampak sebagai bayangan gelap jaringan lunak.

Reaksi periosteum berupa segitiga Codman atau seperti pancaran ’sinar matahari’. Segitiga Codman adalah periosteum yang terangkat pada tepi tumor di tempat berbatasan dengan korteks tulang, terbentuk tulang baru, tampak sebagai segitiga reaksi periosteum. Bayangan seperti pancaran ’sinar matahari’ merupakan gambaran tumor menginfiltrasi ke dalam jaringan lunak, membentuk tulang tumor yang tegak lurus terhadap diafisis.

Foto toraks dapat menemukan lesi metastatik paru.

2. CT

Tampak sebagai destruksi tak beraturan matriks tulang, pembentukan tulang tumor, reaksi periosteal, massa jaringan lunak dan tulang tumor didalamnya. Dapat menunjukkan lingkup invasi osteosarkoma dalam rongga sumsum tulang, korteks dan jaringan lunak. Membantu dalam estimasi stadium tumor. Sesuai untuk osteosarkoma yang terjadi pada vertebra, pelvis, dan lokasi relatif dalam lainnya.

Kebanyakan osteosarkoma ketika ditemukan sudah menginvasi jaringan di luar kompartmen, atau stadium IIB menurut kriteria bedah keganasan tulang. Karena perbedaan tingkat diferensiasi dan stadium tumor, maka lingkup invasi tumor berbeda derajatnya.

 

CT-scan thorax menunjukkan tumor osteoblatik pada sternum

3. Scanning  radioisotop seluruh tubuh

Dapat memaparkan lokasi dan lingkup osteosarkoma, lokasi dan jumlah lesi metastatik tulang. Sebagai salah satu kriteria dalam menilai stadium dan juga dapat menjadi materi pemeriksaan dalam tindak lanjut.

4. Angiografi

Dengan angiografi dapat diketahui kekhususan pasokan darah tumor, hubungan tumor dan pembuluh darah vital, menjadi rujukan dalam merancang teknik operasi.

5. MRI

Kegunaan MRI ini mirip dengan CT, terutama untuk menunjukkan lingkup lesi intramedular dan jaringan lunak hasilnya lebih jelas. Sesuai untuk tumor berlokasi agak dalam seperti vertebra, pelvis, dll. Pemeriksaan MRI praoperasi preservasi ekstremitas, untuk memahami luas invasi tumor dalam sumsum tulang dan lingkup invasi dalam jaringan lunak, berguna bagi penentuan bidang amputasi dan lingkup eksisi.

Patologi

1. Macroscopic

tumor menembus kortek tulang, menginvasi jaringan lunak sekitarnya. Tumor dapat menyebar dalam sumsum tulang. Jaringan tumor tampak berubah seperti ’daging ikan’, pada penampang tumor dapat terlihat kalsifikasi, jaringan kartilago, perdarahan, nekrosis, dan formasi kistik. Perubahan makroskopik tumor berkaitan dengan perbedaan densitas jaringan dan jenis komponen jaringan di dalam tumor.

2. Microscopic

sel sarkoma berbentuk spindel ataupun pleomorfik dan jaringan osteoid tumor yang dihasilkannya merupakan karakteristik patologi osteosarkoma. Yang terakhir merupakan kunci diagnosis osteosarkoma. Sel sarkoma memiliki heteromorfisme jelas, ukuran bervariasi, inti besar, bentuk aneh, hiperkromatik, banyak ditemukan mitosis, dapat pula ditemukan sel datia . tumor.

Terapi

Deteksi dini dan diagnosis tepat secepatnya sangat penting. Begitu terdiagnosis harus segera mulai diterapi. Dahulu terapi osteosarkoma terutama dengan amputasi tinggi. Dengan terapi operasi murni 5 years survival rate osteosarkoma hanya 5-20%. Sejak mulai dikombinasi dengan kemoterapi, survival rate osteosarkoma terus meningkat.

Kini terapi osteosarkoma bertumpu pada terapi kombinasi kemoterapi dan operatif. Terapi operatif mencakup pemastian stadium praoperatif. Metode operasi berkembang dari semata-mata amputasi menjadi teknik preservasi ekstremitas dengan dukungan efektif terapi adjuvan. Kemoterapi merupakan bagian penting dalam terapi osteosarkoma, dia bukan suatu terapi adjuvan yang boleh ada atau tidak ada. Kemoterapi mencakup dua tahap, pra operatif dan pasca operatif, mengkombinasikan kemoterapi intravena dan kemoembolisasi arterial.

Kemoterapi Osteosarkoma

Peranan Kempterapi dan Pemilihan Obat

Terapi operatif yang dikombinasikan dengan kemoterapi telah meningkatkan angka 5 years survival rates osteosarkoma dari 20% menjadi 50-70%. Peranan kemoterapi adalah membasmi sel tumor metastatik, menghambat atau menunda metastasis paru yang fatal, sambil mengontrol pertumbuhan tumor primer. Kemoterapi harus secepatnya dimulai setelah diagnosis dipastkan.

Dewasa ini yang banyak digunakan untuk kemoterapi osteosarkoma adalah terapi kombinasi bertumpu pada Metotreksat (MTX) dosis tinggi dan salvasi kalsium folinat. (HD-MTX-CF). Obat lain yang sering digunakan meliputi Adriamisin (ADR), Cisplatin (DDP), Siklofosfamid (CTX), dan Vinkristin (VCR).

Terapi MTX dosis tinggi + CF

Dosis tunggal MTX dikalkulasi berdasarkan berat badan atau luas permukaan tubuh pasien. Pada umumnya dosis tunggal di atas 5g, dosis total mencapai 10-15g atau lebih. Sebelum diberikan MTX dapat diberikan VCR 1-2mg/m2, kombinasi keduanya berguna untuk membasmi sel tumor.

Dosis tinggi MTX dapat menimbulkan reaksi sistemik pada tubuh pasien, karena itu sebelum dilakukan kemoterapi, harus dilakukan pemeriksaan menyeluruh, termasuk jantung, paru, hati, ginjal dan hematologi. Kontraindikasi penggunaan MTX dosis tinggi adalah: diagnosis belum jelas; fisik lemah; gangguan fungsi jantung, paru, hati, ginjal yang serius; leukosit darah kurang dari 4 x 109/L; Hb kurang dari 8g/dl, trombosit kurang dari 100 x 109/L. Selama terapi perkembangan penyakit harus diamati dengan ketat, dengan cara memeriksa ulang hematologi secara rutin, segera mendeteksi reaksi toksik dan menanganinya secara agresif.

Kemoembolisasi Arterial

Melalui kateter intra-arteri, dilakukan kateterisasi selektif ke arteri pemasok tumor, disuntikkan obat kemoterapi, dan dilakukan embolisasi. Melalui efek ganda obat kemoterapi dan embolisasi, pasokan darah ke tumor dikurangi, memacu kematian tumor hingga tumor mengecil, batas menjadi jelas. Hal ini sangat berguna bagi operasi. Jika tumor tidak dapat dieksisi, kemoterapi embolisasi dapat berefek menghambat progresi tumor.

Terapi Operasi

Amputasi

Tidak selalu mungkin untuk menggunakan “limb-sparing surgery”, dan terkadang amputasi seluruh ekstremitas merupakan satu-satunya pilihan yang harus dilakukan. Hal ini biasa dilakukan jika kanker sudah menyebar dari tulang ke pembuluh darah sekitar sel kanker. 46

Persiapan prosedur amputasi sama dengan pada “limb-sparing surgery”. Yang paling dibutuhkan disini adalah dukungan psikis kepada pasien. 46

1. Amputasi

Amputasi merupakan salah satu teknik operasi utama untuk terapi osteosarkoma. Sesuai untuk tumor berinvasi luas, mengenai neurovaskular, otot dan kulit di dekatnya terkena meluas, ekstremitas terkena tak lagi dapat dipreservasi. Bidang amputasi secara prinsip haruslah tepi amputasi radikal yaitu reseksi ekstrakompartmen.

2. Amputasi Modifikasi

Dengan prasyarat eksisi tuntas tumor, mempertahankan sebagian fungsi ekstremitas, hingga mengurangi kecacatan akibat amputasi.

 

Tabel 1-4. Landasan Batas Amputasi pada

Osteogenic Sarcoma Primer

Lokasi Tumor

Level Amputasi

Tungkai (tibia, fibula)

Above knee

Paha (femur)

 

    Distal – medial femur

High Above Knee

    Proximal – medial femur

Modified Hemipelvectomy

Pelvis (pubis, ischium, atau ilium)

Hemipelvectomy

Lengan Bawah (radius, ulna)

Transhumeral

Lengan Atas (humerus)

 

    Distal

Shoulder Disarticulation

    Proximal

Forequarter

After the operation

Lokasi bekas operasi ditutup dengan bandage khusus, sehingga tungkai artifisial tidak berubah letak selama penggunaannya. Tabung yang diletakkan di dalam luka operasi dialirkan ke luar agar sisa darah dapat dialirkan dengan baik dan tidak terjadi infeksi, biasanya dilakukan drainase ini selama 3-4 hari. 32,33

Pasien akan mengalami rasa nyeri dan tidak nyaman setelah operasi, hal ini dapat diatasi dengan penggunaan medikasi analgesik. Pada awalnya, pasien membutuhkan analgesik kuat seperti morfin. 32,33

Beberapa pasien mengalami nyeri yang menetap yang berasal dari tungkai yang telah diamputasi, hal ini dikenal sebagai “phantom pain” atau “phantom sensation”. Pasien terkadang merasa bahwa “phantom pain or sensation” itu sulit untuk dikontrol dan mereka membutuhkan analgesik secara permanen. 32,33

Follow-up

Setelah serangkaian terapi telah dilakukan dengan lengkap, pasien harus menjalani check-up kembali dan melakukan foto rontgen. Ini harus dilakukan secara kontinyu untuk beberapa tahun. Jika pada perjalanannya terdapat masalah kembali, atau timbul gejala baru, segera hubungi dokter untuk mengkonsultasikannya. 32,34

Prognosis

Prognosis osteosarkoma berkaitan dengan diferensiasi, lokasi, lingkup invasi tumor, stadium, usia, diagnosis dini, terapi tepat waktu dan rasional, efek kemoterapi, dan berbagai faktor lain. Osteosarkoma dengan lingkup invasi relatif terbatas, belum bermetastasis, didiagnosa segera, dilakukan kemoterapi praoperasi, dll angka 5 years survival ratenya dapat mencapai 50% lebih.

Kesimpulan

Osteosarcoma adalah penyakit kanker tulang yang paling sering ditemukan pada rentang usia 10 – 25 tahun. Pada kebanyakan kasus kanker ini ditemukan pada tulang-tulang di sekitar lutut. Dan biasanya terletak pada growing ends of the bone (metaphysic). Keluhan awal osteosarcoma biasanya adalah rasa nyeri. Riwayat penyakit umumnya 2-4 bulan. Kausa kematian adalah metastasis jauh.

Ukuran tumor dan atau derajat bengkak bervariasi menurut lingkup invasi tumor dan kedalaman lokasinya, berbatas tidak tegas. Diagnosis terutama berdasarkan tampilan klinis, pemeriksaan pencitraan, dan biopsy patologi. Deteksi dini dan diagnosis tepat secepatnya sangat penting. Begitu terdiagnosis harus segera mulai diterapi. Terapi osteosarkoma bertumpu pada terapi kombinasi kemoterapi dan operatif. Terapi operatif yang dikombinasikan dengan kemoterapi telah meningkatkan angka 5 years survival rates osteosarkoma dari 20% menjadi 50-70%. Prognosis osteosarkoma berkaitan dengan diferensiasi, lokasi, lingkup invasi tumor, stadium, usia, diagnosis dini, terapi tepat waktu dan rasional, efek kemoterapi, dan berbagai faktor lain. Penting juga bagi pasien untuk mengerti dengan jelas terhadap terapi dengan berkonsultasi pada pusat kanker (Sarcoma Centre).

DAFTAR  PUSTAKA

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