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TUTORIAL KLINIK OSTEOSARKOMA

DM BEDAH: DEVI NITA SASTIKA NIEKO RIO

DEFINISI
Osteosarkoma (osteogenik sarkoma)

neoplasma ganas yang berasal dari sel primitif (poorly differeatiated cells) di daerah metafise tulang panjang pada anak-anak. Disebut osteogenik karena perkembangannya berasal dari seri osteoblastik sel mesenkim primitif..

EPIDEMIOLOGI
Neoplasma primer dari tulang yang tersering

setelah myeloma multiple. Osteosarkoma biasanya terdapat pada metafisis tulang panjang dimana lempeng pertumbuhan (epiphyseal growth plate) yang sangat aktif, yaitu pada distal femur, proksimal tibia dan fibula, proksimal humerus dan pelvis. Tumor tulang dengan angka kematian 80% setelah 5 tahun di diagnosis.

Faktor Risiko
Pertumbuhan tulang yang cepat

Faktor Lingkungan
Predisposisi Genetik

Etiology
The exact cause of osteosarcoma is unknown. risk

factors are Rapid bone growth, Environmental factors: e.g. exposure to radiation and Genetic predisposition (Clark
2008)

Known causative agents are divided into chemicals,

viruses, radiation and miscellaneous

(Fuchs and Pritchard 2002)

Chemical factors e.g. Beryllium compounds and

methylcholanthrene act by leading to genetic alterations


FBJ (FBJ murine osteosarcoma viral oncogene homolog) is the only

viral agent isolated from a naturally occurring sarcoma and is known to be a potent inducer of osteosarcoma.
(Fuchs 2002)
5 Osteosarcoma

Role of radiation in osteosarcoma is best delineated by

its association with formation of secondary sarcomas occurring years after radiation treatment (Enzinger 1995)
Genetic alteration include mutation of Retinoblastoma

(RB) gene and p53 gene (Tumor suppressor). Loss of function of these gene allows cells to grow unregulated, leading to formation of certain cancers, including osteosarcoma. (Ladanyi 2003)
Human epidermal growth factor receptor (HER-2 or ERB-

2) is another molecular alteration associated with osteosarcoma. Its over expression is associated with a more clinically aggressive tumor, increased metastatic potential, shorter recurrence-free intervals and worse overall survival rates (Ferrari 2004)

Osteosarcoma

Skeletal distribution
Most common sites are the

distal FEMUR, the proximal TIBIA, and the proximal HUMERUS.

Osteosarcoma

Klasifikasi
75% dari osteosarkoma masuk ke dalam kategori

klasik atau konvensional, yang termasuk osteosarkoma osteoblastic, chondroblastic, dan fibroblastic. Sedangkan sisanya sebesar 25% diklasifikasikan sebagai varian berdasarkan:
(1) karakteristik klinik seperti pada kasus

osteosarkoma rahang, osteosarkoma postradiasi, atau osteosarkoma paget; (2) karakteristik morfologi, seperti pada osteosarkoma telangiectatic, osteosarkoma smallcell, atau osteosarkoma epithelioid; dan (3) lokasi, seperti pada osteosarkoma parosteal dan periosteal.

Klasifikasi

Staging

Gejala Klinik
Gejala biasanya telah ada selama beberapa minggu

atau bulan sebelum pasien didiagnosa. Gejala yang paling sering terdapat adalah:
nyeri, terutama nyeri pada saat aktifitas dan massa atau

pembengkakan. Fraktur patologis sangat jarang terjadi, terkecuali pada osteosarkoma telangiectatic yang lebih sering terjadi fraktur patologis. Nyeri pada ekstremitas dapat menyebabkan kekakuan. Riwayat pembengkakan dapat ada atau tidak, tergantung dari lokasi dan besar dari lesi. Gejala sistemik, seperti demam atau keringat malam sangat jarang. Penyebaran tumor pada paru-paru sangat jarang menyebabkan gejala respiratorik dan biasanya menandakan keterlibatan paru yang luas.

DDx.
Ewings Sarcoma
Osteomielitis
Osteoblastoma Giant Cell Tumor

Pemeriksaan Penunjang
Laboratorium

X ray
CT Scan MRI Bone Scan Angiografi Biopsi

Imagining studies

Plain x-rays Obtain plain films of the suspected lesions in 2 views. With joint above and joint below Lesions are usually permeative , associated with destruction of the cancellous and cortical elements of the bone, and show ossification within the soft tissue component

Osteosarcoma

15

Osteosarcoma lesions can be purely osteolytic (30%), purely osteoblastic (45%), or a mixture of both.

Lytic

Sclerotic

Mixed

Osteosarcoma

16

Elevation of the periosteum may appear as the characteristic Codman triangle. Extension of the tumor through the periosteum may result in a socalled sunburst appearance (approx 60% of cases).

Telangiectatic osteosarcomas are often very cystic and can be mistaken for an aneurysmal bone cyst, (biopsy is needed)

Codman triangle

Sun burst

Osteosarcoma

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CT scanning

CT scanning of the chest is more sensitive than is plain film radiography for assessing pulmonary metastases.
MRI

MRI of the primary lesion is the best method to assess the extent of intramedullary disease as well as associated soft-tissue masses and skip lesions.
(Estrada 1995)

Bone Scan

A bone scan should be obtained to look for skeletal metastases or multi focal disease.
18 Osteosarcoma

Thallium scan

Monitor effects of chemotherapy Detect local recurrence of tumor


Angiography

Determine vascularity of the tumor Detect vascular displacement and determine relationship of vessels to the tumor Identify vascular anomalies Estimate effects of chemotherapy.
Once all the initial imaging & lab exam has been done

biopsy is performed to conform the diagnosis.


19 Osteosarcoma

Biopsy
Principles of Biopsy:

A biopsy should be planned as carefully as the definitive procedure.


Biopsy should be done only after complete clinical, laboratory, and radiographic examinations. The biopsy track should be considered contaminated with tumor cells and should be excised en-bloc with the tumor. If a tourniquet is used, the limb may be elevated before Osteosarcoma inflation but should not be exsanguinated by compression.

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Transverse incisions should be avoided.

The deep incision should go through a single muscle compartment.


Major neurovascular structures should be avoided. Soft-tissue extension of a bone lesion should be sampled, if possible. If a hole must be made in the bone, it should be round or oval to minimize stress concentration and prevent a subsequent fracture.
21 Osteosarcoma

The hole should be plugged with methacrylate to limit hematoma formation. Biopsy should be taken from the periphery of a lesion as it usually contains the most viable tissue. A frozen section should be sent intraoperatively to ensure that diagnostic tissue has been obtained. Meticulous hemostasis should be ensured before closure. If a drain is used, it should exit in line with the incision.
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The wound should be closed tightly in layers. Osteosarcoma

Types of biopsy

Fine needle aspiration Core needle biopsy Open incisional biopsy

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Osteosarcoma

Staging
The staging system devised and introduced by

Enneking in 1980 is applies to all musculoskeletal tumors.


The key components to the staging system are the

histologic grade of the tumor (low grade vs high grade), the anatomic location of the tumor (intracompartmental vs extracompartmental), and the absence or presence of metastatic disease.
A compartment may be defined as any individual

bone, intra-articular space and clearly identified fascially enclosed space.


24 Osteosarcoma

The staging system is typically depicted as follows Stage I: Low grade tumors I-A intra compartmental I-B extra compartmental Stage II: High grade tumors II-A intra compartmental II-B extra compartmental Stage III: Any tumors with evidence of metastasis

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Osteosarcoma

American Joint Committee on Cancer System for Staging

Bone Sarcomas
Based on grade & size of tumor and presence of

metastasis Stage Grade Size Metastases I-A Low 8 cm None I-B Low >8 cm None II-A High 8 cm None II-B High >8 cm None III Any Any Skip metastasis IV-A Any Any Pulmonary metastases IV-B Any Any Nonpulmonary metastases
26 Osteosarcoma

Conventional osteosarcoma
These high-grade tumors begin in an intramedullary

location, but may break through the cortex and form a soft-tissue mass.
The histologic hallmark of osteosarcoma is the presence

malignant osteoblastic spindle cells producing osteoid. Currently WHO recognizes three distinct subtypes of conventional osteosarcoma: osteoblastic, chondroblastic and fibroblastic (Raymond 2002).
Mistaken diagnoses of chondrosarcoma or malignant

fibrous histiocytoma may occur. The presence of woven bone with malignant appearing stromal cells, regardless of associated chondroid or fibrous matrix, makes the diagnosis of osteosarcoma.
27 Osteosarcoma

Parosteal Osteosarcoma
Incidence

1% of primary malignant bone tumours Usually patient more than 20 years old Peak incidence 30 - 50 years Male : Female 2:3
Clinically

Present with a constant ache or lump Usually a long bone juxta metaphyseal Usually presents as a Stage 1A lesion (low grade) Commonest site = posterior aspect of distal femur
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X-Rays

Well circumscribed mass May be separated from cortex by a lucent line (30%)

Broad based tumour with mottled calcification


Cortex not eroded Does not invade medullary cavity (unlike chondrosarcoma) Tends to encircle bone Osteosarcoma
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Differential Diagnosis

Osteochondroma Myositis ossificans


Treatment

Chemotherapy or radiotherapy not effective wide surgical resection


Prognosis

Better than classical osteosarcoma 70-80% 5 year survival

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Osteosarcoma

Periosteal Osteosarcoma
Arises from surface of diaphysis

Characterized by bony spicule

formation perpendicular to shaft Sunburst Low grade Wide excision

Osteosarcoma

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Telangiectatic Osteosarcoma
Aggressive Presents with pathological fracture 5% of all osteosarcomas arises within the diaphysis
Radiology

Often entirely osteolytic Bone and cortex destruction Periosteal reaction Codman's triangles
Pathology

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Gross appearance is a multi-cystic similar to an aneurysmal bone cyst. Microscopically it has large blood filled spaces and thin septation. Within the septa there is scanty osteoid Osteosarcoma production by the pleomorphic malignant cells of this high grade tumor

Secondary Osteosarcoma
Secondary osteosarcomas occur at the site of another

disease process.
They constitute almost half of the osteosarcomas in patients

older than age 50 years.


The most common type of secondary osteosarcomas are

Paget disease and Previous radiation treatment.

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Osteosarcoma

Pagets Sarcoma
Incidence Age more than 45 years Male : Female 2:1 Occurs in advanced polyostotic disease 10% Affects 1% of all patients with Pagets
Pathology

50% or more are osteosarcomas 25% fibrosarcomas Remainder are chondrosarcomas or anaplastic tumours The pelvis is the most common location. Prognosis Osteosarcoma 34 Poor - less than 50% 1 year survival

Radiation sarcoma
Radiation-induced osteosarcoma occurs in

approximately 1% of patients who have been treated with greater than 2500 cGy.
occur in unusual locations, such as the skull, spine,

clavicle, ribs, scapula, and pelvis.


The time to onset of the secondary osteosarcoma

averages approximately 10 to 15 years after radiation exposure, but may occur 3 years to several decades after treatment.

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Osteosarcoma

Prognostic Factors
Extant of the disease Pts with pulmonary, non pulmonry (bone) or skip metastasis have poor prognosis Grade of the tumor High grade tumor have poor prognosis Size of the primary lesion Large size tumors have worse prognosis then small size tumors

Skeletal location proximal tumors do worse than distal tumors.


36 Osteosarcoma Secondary osteosarcoma:

Poor prognosis

Treatment
Current standard of care

1. Radiological staging 2. Biopsy to confirm diagnosis 3. Preoperative chemotherapy 4. Repeat radiological staging
(access chemo response, finalize surgical tx plan)

5. Surgical resection with wide margin 6. Reconstruction using one of many techniques 7. Post op chemo based on preop response

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Osteosarcoma

Chemotherapy
Before the era chemotherapy osteosarcoma was

usually treated with immediate wide or radical amputation on diagnosis.


This usually treated the local disease adequately.

However 80% of patients eventually died of micrometastatic disease.


With the use of modern chemotherapy protocols, the

current 5-year survival rate for osteosarcoma is approximately 70%.

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Osteosarcoma

Chemotherapy given preoperatively is known as

Neoadjuvant and that given postoperatively is known as Adjuvant chemotherapy


No study has proved a survival advantage with regard to

the timing of chemotherapy


Theoretical advantages of neoadjuvant chemotherapy

include. It causes regression of the primary tumor, making a successful limb salvage operation easier. It allows for histological evaluation of the effectiveness of treatment.
39 Osteosarcoma

It may decrease the spread of tumor cells at the time of surgery, It usually can be started immediately, effectively treating micrometastases at the earliest time possible. It avoid tumor progression, which may occur during any delay before surgery.

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Osteosarcoma

It allows time to plan the operation properly, including the possible manufacturing of a custom implant. It also allows time for the patient and the family to consider fully the options of limb salvage surgery versus amputation.
Neoadjuvant chemotherapy is given for about 3-4

weeks before definitive procedure

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Osteosarcoma

The drugs used most often to treat osteosarcoma are:

Methotrexate with leucovorin (folinic acid) Doxorubicin (Adriamycin) Cisplatin or carboplatin Etoposide Ifosfamide Cyclophosphamide Actinomycin D (dactinomycin) Bleomycin
(American Cancer Society www.cancer.org 2009)

Usually, several drugs are given together.


42 Osteosarcoma

Some common combinations of drugs include:

Cisplatin and Adriamycin (CA) Vincristine, Methotrexate, Leucovorin & Adriamycin High-dose methotrexate, Adriamycin, and cisplatin (sometimes with ifosfamide)

Dactinomycin, bleomycin and cyclophosphamide


Ifosfamide and Etoposide
43 Osteosarcoma

CA regimen

Cisplatin..... 90 mg/sqm IV over 6 h on day 1. Adriamycin..... 75 mg/sqm IV 48 h after cisplatin (day 3). FREQUENCY....... Repeat cycle every 21 days

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Osteosarcoma

VML-A regimen

Vincristine: 2.0 mg/sqm IV on day 1.


Methotrexate: 7,500 mg/sqm IV over 6 h beginning 30 min after vincristine.

Leucovorin: 15 mg IV every 3 h times 8, then 15 mg orally every 6 h times 8, beginning 2 h after methotrexate administration is completed.
Adriamycin: 75 mg/sqm IV every 3 weeks times 6, beginning with the fifth course of VML.
Goorin AM 1987
45 Osteosarcoma

FREQUENCY: 24 courses of VML + VML-A, cycled as follows, VML every week times 4, then VML-A every 3 weeks times 6, then VML every week times 4, then

VML every 3 weeks times 6, then


VML every week times 4.
Goorin AM. 1987
46 Osteosarcoma

Side effect
General side effects:

Nausea and vomiting, Loss of appetite, Hair loss, Mouth sores.


Chemotherapy can damage the blood-producing cells

resulting in: Increased chance of infection ( W B C) Bleeding or bruising ( Platelets) Fatigue or shortness of breath ( RBCs)
Most of these side effects are short-term and tend to go
47 Osteosarcoma away after treatment is finished.

Side effects of specific drugs.

Ifosfamide and cyclophosphamide : hemorrhagic cystitis. Cisplatin: neuropathy, nephropathy, ototoxicity. High-dose methotrexate: leukoencephalopathy and liver or kidney damage. Doxorubicin (Adriamycin): can cause heart damage over time.
Long-term side effects:

Infertility Heart damage Developing a second cancer


(American Cancer Society www.cancer.org 2009)
48 Osteosarcoma

Surgery
The main goal of surgery is to safely and completely

remove the tumor.


Historically, most patients had an amputation. Over

the past 30 years, limb-sparing procedures have become the standard, mainly due to advances in chemotherapy and sophisticated imaging techniques
(Scully 2002).

Limb salvage procedures now can provide rates of

local control and long-term survival equal to amputation.


49 Osteosarcoma

Surgery
Amputation versus Limb Salvage If the tumor can be removed safely while retaining a viable extremity, a limb sparing procedure may be appropriate. If major nerves or blood vessels are involved, or if complete tumor removal results in significant loss of function, amputation may be a better choice. patients age, desired level of function, cosmetic preference and long-term prognosis must also be considered. detailed dialogue between the patient, the patients family and the healthcare team is a necessity when deciding Osteosarcoma which surgical route to pursue.

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Effect of treatment choice on survival.

With Multimodal treatment including surgery and chemotherapy, long-term survival has improved from 20% to 70% in most series. For osteosarcoma of the distal femur, the rate of local recurrence after wide resection as well as transfemoral amputation is approximately 5% to 10%. Although hip disarticulation is associated with an extremely low rate of local recurrence, no study has shown a survival advantage for this technique.
51 Osteosarcoma

Attainment of a wide margin is the most important technical

aspect of the surgical procedure with regard to overall patient survival.


With regard to function, location of the tumor is the most

important issue. Resection of an upper extremity lesion with limb salvage, provides better function than amputation. Similarly, resection of a proximal femoral or pelvic lesion with local reconstruction provides better function than after a hip disarticulation or hemipelvectomy. Amputation followed by prosthetic fitting is favored for the lesions around the ankle and foot.
52 Osteosarcoma

Treatment for sarcomas around the knee must be

individualized. Wide resection & prosthetic knee replacement or Transfemoral amputation is common . Less commonly performed operations include osteoarticular allograft reconstruction, allograft arthrodesis, and rotationplasty.

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Osteosarcoma

Surgical Margins
In orthopaedic oncology, the surgical margin is described

by one of four termsintralesional, marginal, wide, or radical. Amputations and limb-sparing resections may be associated with any of the four types of margins.
Intralesional margin: is one in which the plane of

surgical dissection is within the tumor. Also known as debulking. It is appropriate for some symptomatic benign lesions or as a palliative procedure in metastatic disease.
Marginal Margin: is achieved when the closest plane of

dissection passes through the pseudocapsule. It is used for most benign lesions and some low-grade malignancies.
54 Osteosarcoma

Wide Margins: are achieved when the plane of

dissection is in normal tissue. Although no specific distance is defined, the entire tumor remains completely surrounded by a cuff of normal tissue. If the plane of dissection touches the pseudocapsule at any point, the margin should be defined as being marginal and not wide.
Radical Margins: are achieved when all the

compartments that contain tumor are removed en bloc. For bone tumors, this involves removing the entire bone and the compartments of any involved muscles. Radical operations were previously the procedures of choice for most high-grade neoplasms.
55 Osteosarcoma

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Osteosarcoma

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Osteosarcoma

Surgical options
Surgical procedures fall into three basic categories:

Amputation, Limb salvage and Rotationplasty. While differences between amputation and limb-sparing procedures do exist, long term outcomes with regards to patient function and satisfaction appear to be similar
(DiCaprio 2003, Refaat 2002, Nagarajan 2002).

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Osteosarcoma

Amputations
Amputation involves removal of the limb with a safe

margin between the end of the retained portion and the tumor
It should not be viewed as a failure of treatment, but

rather as the first step towards a patients return to a more comfortable and productive life. performed with the same care and skill used in any other reconstructive procedure

The operative procedure should be planned and

Previously osteosarcoma was usually treated with

immediate wide or radical amputation on diagnosis.


59 Osteosarcoma

Indication for amputation 1. Grossly displaced pathologic fracture 2. Encasement of neurovascular bundle 3. Tumor that enlarges during preop chemo and is adjacent to neurovascular bundle 4. Palliative measure in metastatic disease 5. If the tumor has caused massive necrosis, fungation, infection, or vascular compromise.

Although cure is not the goal, amputation dramatically improve the functional status and pain relief for the remaining months.
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Post operative care

Team approach is needed including the surgeon, physical medicine specialist, a physical therapist, an occupational therapist, a psychologist, and a social worker. Pain management includes the brief use of intravenous narcotics followed by oral pain medicine that is tapered as soon as tolerated.
Rigid dressings is preferable over conventional soft dressings.
Prevent edema at the surgical site, protect the wound from bed trauma, enhance wound healing and early maturation of the stump, decrease postoperative pain, allowing earlier mobilization from bed to chair prevent the formation of knee flexion contractures.

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Osteosarcoma

Drains usually are removed at 48 hours. The stump is elevated by raising the foot of the bed, which helps manage edema and postoperative pain. The patient is cautioned against leaving the stump in a dependent position. Patients should be mobilized from bed to chair on the first postoperative day. The rigid dressing should be removed and the wound inspected in 7 to 10 days. Any systemic symptoms of wound infection are indications for earlier cast removal. If the wound is healing well, a new rigid dressing is applied, the cast should be changed weekly until the wound has healed.
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Complications

Hematoma Infection Wound necrosis Contracture Pain


Phantom leg pain, Residual limb pain, Radiculopathy

Dermatological problems

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Osteosarcoma

Limb salvage
Limb salvage involves removing the tumor with a

normal cuff of tissue surrounding it while preserving vascular and nerve supply to the extremity.
Once the tumor is removed, the skeletal defect must

be reconstructed.(DiCaprio 2003). Options include use of metallic prostheses, allograft (cadaveric) bone, vascularized bone acquired from the patient, or replacement of the resected bone after sterilization in an autoclave.
Today, Endoprosthetic, Allograft or Allograft-prosthetic

composite reconstructions are most commonly performed.


64 Osteosarcoma

Endoprosthetic reconstruction has

gained wide popularity for limb-sparing surgery. This involves replacing the removed bone with a metal implant
Complications with this type of

reconstruction include component loosening and wound problems (Unwin


1996)

Even if catastrophic complications are

avoided, multiple revision/lengthening procedures may be needed (Tunn 2004).

Metallic Prosthesis

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Osteosarcoma

Cadaveric Allografts offer the benefit of biologic incorporation into

the host bone.


Chemotherapy has been shown to impair union of allograft to host

bone (Hazan 2001).


if the allograft survived beyond 3 years, it is associated with excellent

long-term graft survival (Mankin 1996).


The greatest barriers to overcome in the first 3 years were infection

(11% incidence), fracture (19%) and nonunion (17%).


Additional concerns with the use of bulk allografts are disease

transmission and immunogenic responses to the foreign material. While "rejection" does not occur, immune reaction may impair graft healing and delay incorporation.

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Osteosarcoma

Rotationplasty is a compromise between amputation

and limb salvage most commonly used for osteosarcomas of the distal femur.
It is a procedure where the neurovascular structures

and distal aspect of the limb (leg) are retained, and re-attached to the proximal portion after the tumor has been removed.
For functional purposes, the distal segment is turned

180 degrees so that the ankle joint functions as a knee joint, thus converting an above-knee to a belowknee amputation in order for prosthetic use to be maximized.
67 Osteosarcoma

Rotationplasty is best suited for skeletally immature patients

(less than 12 years old) with tumors about the knee. The main disadvantage to this form of reconstruction is the cosmetic appearance.
Winkelmann classified rotationplasty into 5 groups

A-I: lesion of distal femur A-II: lesion of proximal tibia B-I: lesion of proximal femur sparing the hip joint B-II: lesion of proximal femur involving the hip joint B-III: lesion of the mid femur

Osteosarcoma

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Radiotherapy
Radiation therapy has no major role in osteosarcoma Radiation therapy may be useful in some cases

where the tumor cannot be completely removed by surgery. E.g. in pelvic bones or in the bones of the face. In these situations, As much tumor as possible is removed, and then radiation is given to try to kill the remaining cancer cells. Chemotherapy may be used after radiation.
Radiation can also be helpful in controlling symptoms

like pain and swelling if the cancer has come back or surgery is not possible.
69 Osteosarcoma

Bone-seeking radioactive drugs, such as samarium-

153, are sometimes used to treat symptoms such as pain in people with advanced osteosarcoma. They are injected into a vein and collect in bones. The radiation they give off kills the cancer cells and relieves some of the pain caused by bone metastases.
These drugs are especially helpful in metastatic

disease
The major side effect of these drugs is a lowering of

blood cell counts, which could increase the risk for infections or bleeding, especially if the blood counts are already low.
70 Osteosarcoma

Skeletally immature patients


Special consideration must be given to skeletally immature patients

as continued growth of the uninvolved extremity may pose additional problem of limb length inequality and require multiple future operations. (Finn 1991).
Contralateral growth plate arrest or ipsilateral limb lengthening may

be required to equalize limb length differences.


Modular and expandable endoprostheses (repiphysis expandable

prosthesis) are being used more commonly to achieve limb length equality. (Neel 2004).
Attainment of skeletal maturity often necessitates revision to a more

"permanent" prosthesis with all of the associated risks.


Despite the potential need for multiple procedures, functional results
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and overall patient satisfaction appear to be acceptable (Neel 2003, Osteosarcoma


Pltz 2002).

Follow up
Once treatment has been completed, careful follow up is required to

monitor for signs of recurrence, metastasis and treatment related complications.


This involves careful physical examination, radiographs of the primary

site, serial chest imaging, bone scans and laboratory examinations.


Such evaluation is performed frequently in the immediate post-

treatment period and less frequently with time as long as the patient remains free of disease.
If recurrence is detected, additional surgery and chemotherapy may

be warranted. The same principles apply as for primary disease, though long-term survival rates are lower (Ferguson 2001).
Some data suggest that patients with early relapse (< 1 year after
72 Osteosarcoma treatment) have poorer outcomes than those who relapse later (Ferrari 1997).

Penatalaksanaan
Preoperatif kemoterapi (Induction/Neoadjuvant Chemotherapy) diikuti

dengan pembedahan limb-sparing (dapat dilakukan pada 80% pasien) dan diikuti dengan postoperatif kemoterapi (Adjuvant Chemotherapy) merupakan standar manajemen. Osteosarkoma merupakan tumor yang radioresisten, sehingga radioterapi tidak mempunyai peranan dalam manajemen rutin. Obat-obat kemoterapi yang mempunyai hasil cukup efektif untuk osteosarkoma adalah: doxorubicin (Adriamycin), cisplatin (Platinol), ifosfamide (Ifex), mesna (Mesnex), dan methotrexate dosis tinggi (Rheumatrex). Semua pasien dengan osteosarkoma harus menjalani pembedahan jika memungkinkan reseksi dari tumor primer. Tipe dari pembedahan yang diperlukan tergantung dari beberapa faktor yang harus dievaluasi dari pasien secara individual. Tipe pembedahan pada penatalaksanaan osteosarcoma antara lain:
Limb Salvage Rotation plasty Amputation

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