Osteosarcoma: A Detailed Review
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Transcript of Osteosarcoma: A Detailed Review
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OSTEOSARCOMA
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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
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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
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PREDISPOSING FACTORS :
• RADIATION
• VIRAL INFECTION: PLYOMA VIRUS/HARVEY VIRUS
• CHEMICALS:BERYLLIUM 20-METHYL CHOLANTHRENE
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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
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ASSOCIATED FEATURES
• EFFUSION & SWELLING OF NEARBY JOINTS
• FEVER
• PALLOR & CACHEXIA
• REGIONAL LN
• FEATURES ASSOCIATED WITH PULMONARY METASTASIS
• PATHOLOGICAL #
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OSTEOSARCOMA
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CONTD….
DISTAL NEUROVASCULAR DEFICITS AND PRESSURE SYMPTOMS ….MAY BE ASSOCIATED WITH
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CLASSIFICATION
• PRIMARY OSTEOSARCOMA
• SECONDARY OSTEOSARCOMA
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CLASSIFICATION: WHO(PRIMARY OSTEOSARCOMA)
• CENTRAL(MEDULLARY)
• SURFACE(PERIPHERAL)
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CENTRAL(MEDULLARY)
• CONVENTIONAL
• TELANGIECTATIC
• INTRAOSSEOUS/INTAMEDULLARY (WELL-DIFFERENTIATED/LOW-GRADE)
• SMALL CELL OSTEOSARCOMA
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SURFACE(PERIPHERAL)
• PAROSTEAL(LOW-GRADE)
• PERIOSTEAL(LOW TO INTERMEDIATE GRADE)
• HIGH-GRADE SURFACE OSTEOSARCOMA
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SECONDARY OSTEOSARCOMA
-PAGET’S DISEASE
-RADIATION
-BENIGN PRE-EXISTING CONDITIONS
[OSTEOCHONDROMA
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SECONDARY OSTEOSARCOMA
• OLDER AGE GROUP
• PROGNOSIS POOR
• LONG H\O DULL ACHING PAIN&RECENT LYTIC DESTRUCTION
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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.
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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
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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
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CONTD…
• CODMAN’S TRIANGLE ---DUE TO SUBPERIOSTEAL NEW BONE FORMATION
• SUNRAY APPEARANCE ---DUE TO BONE DEPOSITION IN SUB-PERIOSTEAL SPACE ALONG THE VESSELS
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SUNRAY APPEARENCE
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PATHOLOGY:MICROSCOPY
LICHTENSTEN’S CRITERIA TO IDENTIFY OSTEOSARCOMA : 1)SARCOMATOUS STROMA 2)SPINDLE CELLS. 3) DIRECT FORMATION OF NEOPLASTIC
OSTEOID AND BONE.
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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.
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RADIOLOGIC INVESTIGATIONS
• PLAIN RADIOGRAPH(X-RAY)
• CT SCAN
• MRI SCAN
• BONE SCAN
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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
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RADIOLOGY..
• PERIOSTEAL REACTION WITH FORMATION OF CODMAN’S TRIANGLE/SUNBURST APPEARANCE
• WIDE VARIETY OF RADIOGRAPHIC APPEARANCE LIKE BONE CYST
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RADIOLOGY..
• CT SCAN AND MRI SCAN ARE NOT AS INSTRUMENTAL AS PLAIN RADIOGRAPH
• BONE SCAN IS USEFUL TO DETECT METASTASIS
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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
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DIAGNOSIS
• HISTORY• CLINICAL EXAMINATION• HAEMATOLOGY• RADIOLOGICAL INVESTIGATIONS• HISTOPATHOLOGIC EXAMINATION
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MANAGEMENT: MULTIDISCIPLINARY APPROACH
PRIMARY CARE PHYSICIAN ORTHOPAEDIC SURGEON RADIATION ONCOLOGIST PATHOLOGIST PHYSIOTHERAPIST REHABILITATION SPECIALIST SOCIAL WORKERS & OTHERS
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TREATMENT OPTIONS
• CHEMOTHERAPY
• SURGERY
• RADIOTHERAPY
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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.
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CHEMOTHERAPY
• NEO-ADJUVANT CHEMOTHERAPY: CT ADMINISTERED BEFORE THE SURGICAL
RESECTION OF PRIMARY TUMOUR
• ADJUVANT CHEMOTHERAPY: CT ADMINISTERED POSTOPERATIVELY TO TREAT PRESUMED MICRO-METASTASIS
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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)
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NEO-ADJUVANT CHEMOTHERAPY DISADVANTAGES…
• IT MAY INCREASE PERI-OPERATIVE COMPLICATIONS(DELAYED WOUND HEALING, INFECTION)
• NAUSEA, VOMITING AND OTHER TOXICITIES MAY CAUSE DELAY IN SURGERY.
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MANAGEMENT…
LOW GRADE OSTEOSARCOMA-- TREATED BY SURGERY ALONE.
HIGH GRADE OSTEOSARCOMA-- TREATED BY NEO-ADJUVANT CHEMOTHERAPY SURGERY ADJUVANT CHEMOTHERAPY,
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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
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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
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CONTD…
CYCLOPHOSPHAMIDE & IFOSFAMIDE -- 1-1.5 G/M² B S A
HAEMORRHAGIC CYSTITIS
DACARBAZINE –250MG/M²BSA FLU LIKE SYNDROME DACTINOMYCIN – ERYTHEMA MYELOSUPPRESION
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CONTD…
ROUTE OF ADMINISTRATION –• INTRAVENOUS –
• ORAL & INTRAMUSCULAR –
• INTRA ARTERIAL –
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INTRA-ARTERIAL ADM OF CHEMOTHERAPY
• HIGHER CYTOTOXIC CONC. DIRECTED AGAINST TARGET TISSUE
• CISPLATIN – MOST SUCCESSFUL AGENT
• INFLUENCING FACTORS — PRETREATMENT ANGIOGRAPHY, CATHETER PLACEMENT,
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RESPONSE TO PREOPERATIVE CHEMOTHERAPY ASSESSED BY
• CLINICAL
• RADIOGRAPHIC
• ANGIOGRAPHIC
• PATHOLOGICAL PARAMETERS
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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
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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
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RADIATION THERAPY
• EXTERNAL BEAM RADIATION — BY LINEAR ACCELERETER.
• BRACHYTHERAPY —LIMITED ROLE
• IORT – SINGLE DOSE,IN SPECIALLY PREPARED OT
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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
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SURGERY
SURGERY IS THE MAINSTAY OF THERAPY
• LIMB SACRIFICING SURGERY OR • LIMB SALVAGING SURGERY
?
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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.
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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
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PRINCIPLES OF SURGERYADVANCES IN DIAGNOSTIC IMAGING
CHEMOTHERAPY (NEO-ADJUVANT CHEMOTHERAPY)
SURGICAL TECHNIQUES …….HAVE MADE LIMB SALVAGE SURGERY…… A REASONABLE OPTION
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LIMB SALVAGE SURGERY
“SURGICAL PROCEDURES DESIGNED TO ACCOMPLISH REMOVAL OF MALIGNANT TUMOURS & RECONSTRUCTION OF THE LIMB WITH AN ACCEPTABLE ONCOLOGIC, FUNCTIONAL & COSMETIC RESULTS.”
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LIMB SALVAGE SURGERY
• NEW SURGICAL TECHNIQUES.
• PROGNOSIS IMPROVED GREATLY.
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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
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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
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GUIDELINES (contd.)
• RESECTION OF BONE 3-4 CM BEYOND ABNORMAL UPTAKE
• RESECTION OF ADJOINING JOINT & CAPSULE.
• ADEQUATE MOTOR RECONSTRUCTION • ADEQUATE SOFT TISSUE COVERAGE.
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SURGICAL MARGINS IN ONCOLOGY
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METHODS
• BONE GRAFTING AUTOLOGUS GRAFT : VASCULARISED
GRAFT ALLOGENIC GRAFT : BONE BANK• ROTATIONPLASTY • RESECTION/ARTHRODESIS• PROSTHESIS• COMPOSITE ALLOGRAFT PROSTHETIC COMPOSITES
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CONTRAINDICATIONS
• DISPLACED PATHOLOGICAL FRACTURE
• INAPPROPRIATE BIOPSY SITE
• INFECTION
• SKELETAL IMMATURITY
• MAJOR NEUROVASCULAR INVOLVEMENT
• EXTENSIVE MUSCLE INVOLVEMENT
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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
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TREATMENT OF
• PULMONARY METASTASIS
• LOCAL RECURRENCE
• SECONDARY DISEASE
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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
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THANK YOU