OSTEOSARCOMA

INTRODUCTION

• 20% OF ALL PRIMARY BONE TUMOR

• SECOND-MOST COMMON PRIMARY MALIGNANCY OF BONE

• INCIDENCE: 1 TO 3 PER MILLION PER YEAR

• MALE: FEMALE—1.6:1(EXCEPT PAROSTEAL VARIETY)

• AGE: CONVENTIONAL—2ND DECADE

SITE

AROUD THE KNEE JT.(ARISING MAINLY FROM METAPHYSIS;INTRAMEDULLARY REGION)

52% --LOWER END OF FEMUR

20%-- UPPER END OF TIBIA

9% -- UPPER END OF HUMERUS

PREDISPOSING FACTORS :

• RADIATION

• VIRAL INFECTION: PLYOMA VIRUS/HARVEY VIRUS

• CHEMICALS:BERYLLIUM 20-METHYL CHOLANTHRENE

CLINICAL FEATURES• PRESENTING FEATURES: - PAIN(NIGHT PAIN) -SOMETIMES ONLY TIREDNESS & LIMP -PALPABLE MASS -SKIN CONDITIONS TO BE EXAMINED CAREFULLY• H/O TRAUMA SOMETIMES DRAWS ATTENTION

ASSOCIATED FEATURES

• EFFUSION & SWELLING OF NEARBY JOINTS

• FEVER

• PALLOR & CACHEXIA

• REGIONAL LN

• FEATURES ASSOCIATED WITH PULMONARY METASTASIS

• PATHOLOGICAL #

OSTEOSARCOMA

CONTD….

DISTAL NEUROVASCULAR DEFICITS AND PRESSURE SYMPTOMS ….MAY BE ASSOCIATED WITH

CLASSIFICATION

• PRIMARY OSTEOSARCOMA

• SECONDARY OSTEOSARCOMA

CLASSIFICATION: WHO(PRIMARY OSTEOSARCOMA)

• CENTRAL(MEDULLARY)

• SURFACE(PERIPHERAL)

CENTRAL(MEDULLARY)

• CONVENTIONAL

• TELANGIECTATIC

• INTRAOSSEOUS/INTAMEDULLARY (WELL-DIFFERENTIATED/LOW-GRADE)

• SMALL CELL OSTEOSARCOMA

SURFACE(PERIPHERAL)

• PAROSTEAL(LOW-GRADE)

• PERIOSTEAL(LOW TO INTERMEDIATE GRADE)

• HIGH-GRADE SURFACE OSTEOSARCOMA

SECONDARY OSTEOSARCOMA

-PAGET’S DISEASE

-RADIATION

-BENIGN PRE-EXISTING CONDITIONS

[OSTEOCHONDROMA

SECONDARY OSTEOSARCOMA

• OLDER AGE GROUP

• PROGNOSIS POOR

• LONG H\O DULL ACHING PAIN&RECENT LYTIC DESTRUCTION

PATHOLOGY: MACROSCOPY

Typical osteosarcoma presents as a large ill-defined lesion in the metaphyseal region of the involved bone. It typically destroys cortex and frequently extends inwards marrow cavity and outwards into the adjacent soft tissue.

PATHOLOGY: MACROSCOPY

Tumour often elevates periosteum to produce codman’s triangle on radiograph. It also produces sunray appearance due to vessels which pass from the periosteum to the cortex & along which bone is laid down & some of the new bone may be reactionary

PATHOLOGY: MACROSCOPY• LARGE ILL-DEFINED LESION IN THE METAPHYSEAL

REGION OF LONG BONE

• LEG OF MUTTON’ APPEARANCE

• STONY-HARD TO SOFT AND GRITTY IN CONSISTENCY• AREAS OF HAEMORRHAGE & NECROSIS

• COLOUR: WHITE : FIBROBLASTIC YELLOW : OSTEOBLASTIC BLUISH WHITE: CARTILAGENOUS

CONTD…

• CODMAN’S TRIANGLE ---DUE TO SUBPERIOSTEAL NEW BONE FORMATION

• SUNRAY APPEARANCE ---DUE TO BONE DEPOSITION IN SUB-PERIOSTEAL SPACE ALONG THE VESSELS

SUNRAY APPEARENCE

PATHOLOGY:MICROSCOPY

LICHTENSTEN’S CRITERIA TO IDENTIFY OSTEOSARCOMA : 1)SARCOMATOUS STROMA 2)SPINDLE CELLS. 3) DIRECT FORMATION OF NEOPLASTIC

OSTEOID AND BONE.

PATHOLOGY:MICROSCOPY

Hallmark of osteosarcoma is the formation of osteoid by malignant mesenchymal cells . The neoplastic mesenchymal cells in between osteoid & cartilage elements may be spindle shaped and pleomorphic with bizarre hyperchromatic nuclei and frequent mitotic figures. Giant cells may be present.

RADIOLOGIC INVESTIGATIONS

• PLAIN RADIOGRAPH(X-RAY)

• CT SCAN

• MRI SCAN

• BONE SCAN

RADIOLOGY

• ARISES IN THE METAPHYSIAL REGION OF A LONG BONE

• OUTGROWS FROM THE MEDULLARY CANAL TO EXTRASKELETAL REGION

• DISPLAYS REPRESENTATIVE FEATURES OF A MALIGNANT LESION- PERMEATIVE GROWTH PATTERN/INDISTINCT MARGINS/CORTICAL EROSION

RADIOLOGY..

• PERIOSTEAL REACTION WITH FORMATION OF CODMAN’S TRIANGLE/SUNBURST APPEARANCE

• WIDE VARIETY OF RADIOGRAPHIC APPEARANCE LIKE BONE CYST

RADIOLOGY..

• CT SCAN AND MRI SCAN ARE NOT AS INSTRUMENTAL AS PLAIN RADIOGRAPH

• BONE SCAN IS USEFUL TO DETECT METASTASIS

RADIOLOGY..MRI SCAN

• EXCELLENT FOR DESCRIBING LESIONS IN THE MARROW CAVITY

• HELPFUL TO DETERMINE THE LEVEL OF RESECTION• USEFUL FOR SCREENING SKIP LESIONS• CAN DETECT MEDULLARY INVASION IN CASE OF

JUXTACORTICAL TUMORS• CAN DETECT EPIPHYSEAL INVOLVEMENT AND

PENETRATION OF PHYSEAL CARTILAGE

DIAGNOSIS

• HISTORY• CLINICAL EXAMINATION• HAEMATOLOGY• RADIOLOGICAL INVESTIGATIONS• HISTOPATHOLOGIC EXAMINATION

MANAGEMENT: MULTIDISCIPLINARY APPROACH

PRIMARY CARE PHYSICIAN ORTHOPAEDIC SURGEON RADIATION ONCOLOGIST PATHOLOGIST PHYSIOTHERAPIST REHABILITATION SPECIALIST SOCIAL WORKERS & OTHERS

TREATMENT OPTIONS

• CHEMOTHERAPY

• SURGERY

• RADIOTHERAPY

CHEMOTHERAPY

• Introduction of systemic chemotherapy has dramatically improved survival rates.

• Before the routine use of chemotherapy—treatment was immediate wide or radical amputation

• 80% patients died of metastasis eventually, though metastasis was not evident on presentation.

CHEMOTHERAPY

• NEO-ADJUVANT CHEMOTHERAPY: CT ADMINISTERED BEFORE THE SURGICAL

RESECTION OF PRIMARY TUMOUR

• ADJUVANT CHEMOTHERAPY: CT ADMINISTERED POSTOPERATIVELY TO TREAT PRESUMED MICRO-METASTASIS

NEO-ADJUVANT CHEMOTHERAPY

• IT SHRINKS THE TUMOUR MASS , MAKING IT EASIER FOR OPERATION

• IT DECREASES THE SPREAD OF TUMOUR CELLS DURING SURGERY,

• T/T AGAINST POTENTIAL MICRO-METASTASIS STARTED IMMEDIATELY,

(IT ALSO GIVES IDEA ABOUT RESPONSIVENESS & EFFECTIVENESS OF THE CHEMOTHERAPEUTIC AGENT TO THE TUMOUR)

NEO-ADJUVANT CHEMOTHERAPY DISADVANTAGES…

• IT MAY INCREASE PERI-OPERATIVE COMPLICATIONS(DELAYED WOUND HEALING, INFECTION)

• NAUSEA, VOMITING AND OTHER TOXICITIES MAY CAUSE DELAY IN SURGERY.

MANAGEMENT…

LOW GRADE OSTEOSARCOMA-- TREATED BY SURGERY ALONE.

HIGH GRADE OSTEOSARCOMA-- TREATED BY NEO-ADJUVANT CHEMOTHERAPY SURGERY ADJUVANT CHEMOTHERAPY,

MANAGEMENT…

AFTER INDUCTION OF CHEMOTHERAPY(LASTING ABOUT 2 MONTHS) SURGICAL RESECTION IS TO BE CARRIED OUT.

SURGERY IS CONTEMPLATED 3-4 WEEKS AFTER LAST DOSE OF CHEMOTHERAPEUTIC AGENT

ADJUVANT CHEMOTHERAPY AGAIN STARTED 2 WEEKS AFTER OPERATION

COMMON AGENTS USED

DOXORUBICIN – 60-75 MG/M² CARDIOTOXICITY, CISPLATIN -- 50-100 MG /M² NEPHROTOXICITY VINCRISTINE -- 1.5 MG /M²,WEEKLY PERIPHERAL NEUROPATHY METHOTREXATE – 500-1000 MG/M² IV MEGALOBLASTIC ANAEMIA, PANCYTOPENIA

CONTD…

CYCLOPHOSPHAMIDE & IFOSFAMIDE -- 1-1.5 G/M² B S A

HAEMORRHAGIC CYSTITIS

DACARBAZINE –250MG/M²BSA FLU LIKE SYNDROME DACTINOMYCIN – ERYTHEMA MYELOSUPPRESION

CONTD…

ROUTE OF ADMINISTRATION –• INTRAVENOUS –

• ORAL & INTRAMUSCULAR –

• INTRA ARTERIAL –

INTRA-ARTERIAL ADM OF CHEMOTHERAPY

• HIGHER CYTOTOXIC CONC. DIRECTED AGAINST TARGET TISSUE

• CISPLATIN – MOST SUCCESSFUL AGENT

• INFLUENCING FACTORS — PRETREATMENT ANGIOGRAPHY, CATHETER PLACEMENT,

RESPONSE TO PREOPERATIVE CHEMOTHERAPY ASSESSED BY

• CLINICAL

• RADIOGRAPHIC

• ANGIOGRAPHIC

• PATHOLOGICAL PARAMETERS

RADIATION THERAPY

• ROLE OF RADIOTHERAPY IS LIMITED IN THE TREATMENT OF OSTEO-SARCOMA --A RELATIVELY RADIO-RESISTANT TUMOR.

• RADIATION THERAPY CAN PALLIATE PAIN FROM LOCAL RECURRENCE AND PREVENT NEED FOR AMPUTATION IN PATIENTS WHO ARE PRESENTED WITH DISTANT METASTASIS

RADIATION THERAPY INDICATIONS

• POST-OPERATIVE -- WHERE SURGICAL MARGIN IS INVOLVED

• PALLIATION OF PAIN FROM PRIMARY TUMOUR IN THE PRESENCE OF METASTATIC DISEASE

• RADICAL TREATMENT OF INOPERABLE SITES (SKULL, VERTEBRA, ILIUM, SACRUM)

• BILATERAL LUNG IRRADIATION IN PULMONARY METASTASIS

RADIATION THERAPY

• EXTERNAL BEAM RADIATION — BY LINEAR ACCELERETER.

• BRACHYTHERAPY —LIMITED ROLE

• IORT – SINGLE DOSE,IN SPECIALLY PREPARED OT

RADIATION THERAPY

• AC. SIDE EFFECTS— SKIN REACTION MILD FATIGUE ANOREXIA ALTERED SLEEP & REST CYCLE• LATE EFFECTS — LYMPHATIC & VASCULAR OBST. OSTEO-NECROSIS JOINT STIFFNESS RADIATION INDUCED

SARCOMAS

SURGERY

SURGERY IS THE MAINSTAY OF THERAPY

• LIMB SACRIFICING SURGERY OR • LIMB SALVAGING SURGERY

?

PRINCIPLES OF SURGERY

CHOICE BETWEEN LIMB SALVAGE SURGERY AND AMPUTATION MUST BE MADE ON THE BASIS OF THE EXPECTATIONS AND DESIRES OF THE INDIVIDUAL PATIENT AND THE FAMILY.

PRINCIPLES OF SURGERY

POINTS TO BE STRESSED • SURVIVAL AFTER THE PROCEDURES• SHORT AND LONG TERM MORBIDITY • FUNCTION OF SALVAGED LIMB COMPARED TO

PROSTHETICS• PSYCHOSOCIAL CONSEQUENCES

PRINCIPLES OF SURGERYADVANCES IN DIAGNOSTIC IMAGING

CHEMOTHERAPY (NEO-ADJUVANT CHEMOTHERAPY)

SURGICAL TECHNIQUES …….HAVE MADE LIMB SALVAGE SURGERY…… A REASONABLE OPTION

LIMB SALVAGE SURGERY

“SURGICAL PROCEDURES DESIGNED TO ACCOMPLISH REMOVAL OF MALIGNANT TUMOURS & RECONSTRUCTION OF THE LIMB WITH AN ACCEPTABLE ONCOLOGIC, FUNCTIONAL & COSMETIC RESULTS.”

LIMB SALVAGE SURGERY

• NEW SURGICAL TECHNIQUES.

• PROGNOSIS IMPROVED GREATLY.

LIMB SALVAGE SURGERY

THREE IMPORTANT DEVELOPMENTS 1. Improvement in chemotherapy — In early

70s methotrexate and adriamycin was introduced.

2. Improvement in imaging techniques—

development of CT & MRI in late 70s.

3. Advances in micro- surgical techniques

GUIDELINES

• NO INVOLVEMENT OF MAJOR NEUROVASCULAR

STRUCTURES

• WIDE RESECTION OF AFFECTED BONE WITH A NORMAL

MUSCLE CUFF ALL AROUND

• EN-BLOCK REMOVAL OF ALL BIOPSY SITES &

CONTAMINATED TISSUE

GUIDELINES (contd.)

• RESECTION OF BONE 3-4 CM BEYOND ABNORMAL UPTAKE

• RESECTION OF ADJOINING JOINT & CAPSULE.

• ADEQUATE MOTOR RECONSTRUCTION • ADEQUATE SOFT TISSUE COVERAGE.

SURGICAL MARGINS IN ONCOLOGY

METHODS

• BONE GRAFTING AUTOLOGUS GRAFT : VASCULARISED

GRAFT ALLOGENIC GRAFT : BONE BANK• ROTATIONPLASTY • RESECTION/ARTHRODESIS• PROSTHESIS• COMPOSITE ALLOGRAFT PROSTHETIC COMPOSITES

CONTRAINDICATIONS

• DISPLACED PATHOLOGICAL FRACTURE

• INAPPROPRIATE BIOPSY SITE

• INFECTION

• SKELETAL IMMATURITY

• MAJOR NEUROVASCULAR INVOLVEMENT

• EXTENSIVE MUSCLE INVOLVEMENT

LIMB SALVAGE SURGERY…

• LIMB SALVAGE SURGERY HAS BECOME AN ACCEPTED STANDARD OF CARE FOR PATIENTS WITH SKELETAL MALIGNANCIES INCLUDING OSTEOSARCOMA

• MANY PATIENTS WHO ONCE WOULD HAVE HAD AN AMPUTATION ARE NOW HAVING THEIR LIMB SAVED

TREATMENT OF

• PULMONARY METASTASIS

• LOCAL RECURRENCE

• SECONDARY DISEASE

PRONOSTIC FACTORS

• EXTENT OF DISEASE AT THE TIME OF DIAGNOSIS• GRADE OF THE LESION• SIZE OF THE TUMOUR• LOCATION OF THE TUMOUR• PAGET’S SARCOMA• RADIATION INDUCED SARCOMA• RADIATION INDUCED NECROSIS

THANK YOU