Principles

Approach to Primary Bone Tumour

Steps

 

1. Establish a differential

2. Stage locally and systemically

3. Biopsy

4. Definitive Treatment

 

1. Establish a Differential

 

Lytic Lesion Distal Femur0002

 

Lesion detected on X-ray

 

Questions

- what do you think it is?

- is it benign (latent, active, agressive)?

- is it malignant (primary or secondary)?

 

Enneking's four questions

 

1.  Where is the tumour?

 

Flat bone / long bone

Epiphysis / metaphysis / diaphysis

Medullary canal / cortex

Eccentric in bone

 

2.  What is it doing to the bone?

 

Expansion

Cortical erosion / breakthrough

Fracture

Permeative margins

 

Wide / narrow zone of transition

- narrow / can draw edge with a pen / good sign

- wide / infiltrative / bad sign

 

The best indication of the aggressiveness of a tumour is the transition zone or margin that surrounds the bone

 

3.  What is the bone doing to it?

 

Periosteal reaction

- Codman Triangle / Sunburst / Onion Skinning

 

Reactive rim

- Sclerotic = Slow growing

- Ill defined = Fast growing

 

Margin

1.  Moth eaten / permeative / ill defined / wide zone of transition / cortical or cancellous

2.  Well circumscribed / narrow zone of transition / sclerotic rim

 

4.  Are there any clues to its histological diagnosis?

 

Bone formation / Calcification

Soft tissue component

Radiolucent / ground glass

Matrix Osteoid / Chondroid / Myxoid / Collagen

 

DDx Lucent lesions

 

FOGMACHINES

 

Fibrous dysplasia

Osteoid Osteoma / Osteoblastoma / Osteosarcoma

Giant cell tumour

Metastasis / myeloma

ABC

Enchondroma / Chondroblastoma / Chondrosarcoma

Hemangioma / HPTH

Infection / Intraosseous ganglion or lipoma / Infarct

Non Ossifying Fibroma / Neurofibroma

EG

Simple bone cyst / Synovial Proliferation

 

Patient factors

 

Age

- consider primary bone tumour < age 40 

- consider metastasis > age 40

- consider EG < age 10

 

History

 

Malignant pain

- night time, severe, increasing

Trauma

 

Examination

 

Soft tissue mass = Aggressive lesion

 

Inflammation = Infection / Ewing's 

 

Pathology tests

 

Serum electrophoresis / Urine Bence Jones (Multiple Myeloma)

PSA - prostatic cancer

ESR - non specific (increased in infection / Ewing's / MM / lymphoma / metastasis)

ALP - increased in Osteosarcoma & Paget's

Calcium / PTH - think of hyperparathyroidism

 

Other Tests

 

Mammogram / Thyroid Ultrasound - metastasis

CT Chest / abdomen / pelvis - RCC, lung cancer, bowel cancer

 

Old X-rays

 

Consider observation if lesion unchanged from at least 2 years ago

 

2.  Stage Locally and Systemically

 

Purpose 

- accurately define the extent of the disease

- prior to proceeding with biopsy and definitive treatment

 

Local / Cross sectional imaging

 

CT

 

Best for assessing mineralisation & bony details

- benign bone tumours

- violation of cortex

- matrix mineralisation

- shows areas that plain X-ray visualise poorly i.e. Spine / Pelvis

 

MRI

 

Best for assessing soft tissue component

 

Assess

1.  ST tumours

2.  Cortical breakthrough / T2

3.  Soft tissue extension / T2

4.  Marrow involvement / intramedullary spread

- T1 with fat suppression

5.  Relationship to NV bundle / T2

6.  Joint & Epiphyseal involvement

7.  Infection - rim enhancement on gadolinium

 

Advantage

- guides extent of treatment

- > 5cm margin on MRI / wide excision

 

Disadvantage

- may be oversensitive

- oedema vs tumour

 

Distant

 

Bone scan

 

Determines if lesion polyostotic v monostotic

- this aids with differential diagnosis

- will identify metastasis

 

Bone Scan Metastasis

 

False negative / cold scan

- inactive benign tumours

- myeloma / EG / melanoma

 

CT Chest / Abdo / Pelvis

 

Purpose

- identify primary tumour that may have metastasised to bone

- identify liver and lung metastasis

 

Lung Metastasis CT Chest

 

Classify Lesion

 

Benign - no need for biopsy

Uncertain or malignant - need for biopsy

 

3. Biopsy

 

Aim

 

A.  To determine whether benign or malignant

 

B.  To determine specific cell type

 

C.  To determine grade

 

See Principles of Biopsy

 

4. Definitive Treatment

 

See specific tumour articles

Biopsy Anatomical Approach

Region specific approaches

 

Theory

- want to traverse one muscle / one compartment

- keep away from NV bundle

- as a rule perform open biopsy through compartment the tumour is in

- this is the compartment that will require surgical removal in wide excision

- direct approach without going through muscle if possible i.e. tibia, distal ulna

 

Lower Limb

 

Thigh

 

1.  Lateral compartment ST tumour

- lateral approach

- through ITB

- through vastus lateralis / anterior to lateral intermuscular septum

 

2.  Medial compartment ST tumour

- medial approach

- through gracilis

- keep away from NV bundle

 

3.  Posterior compartment ST tumour

- posterior approach / transmuscular

 

Femur

 

1.  Femoral head / neck

- depends if lesion benign or malignant

- tdranstrochanteric: for completely contained osseous tumour

- Watson-Jones: however if is malignant will consign patient to extra-articular resection

 

Proximal Femur Tumour

 

Proximal Femur Bony Tumour0001Proximal Femur Bony Tumour0002

 

2.  Subtrochanteric

- remember lesions here in elderly may be chondrosarcoma from enchondroma

- lateral approach

 

Tumour Subtrochanteric Femur

 

3.  Femoral Shaft

- lateral through vastus lateralis

- anterior cortical window

 

Femoral Shaft Bony Lesion

 

4.  Condyles

- medial or lateral approach

- incision through medial or lateral vastus

 

Bony Lesion Lateral Distal Femur

 

Popliteal fossa

 

Popliteal fossa / parosteal OS

- posterior approach

- go through hamstrings or gastrocnemius

- depending on whether lesion medial or lateral

 

Parosteal Osteosarcoma

 

Patella

 

Direct anterior

 

Patella Lytic Lesion

 

Tibial

 

1.  Medial plateau proximal tibial bony tumour

- direct medial approach directly onto bone

 

Proximal Tibial Lytic Epiphyseal Lesion XrayTibial Shaft Lesion

 

2.  Lateral plateau proximal tibial bony tumour

- through biceps femoris

- avoid CPN

 

3.  Tibial shaft

- through tibialis anterior

 

4.  Medial malleolus

- direct medial approach

 

5.  Posterior distal tibia

- posterolateral approach

 

Fibula

 

1.  Fibular head

- incision posterior fibular head

- expose and protect CPN

 

2.  Fibular shaft

A.  Direct lateral

- straight down to bone

- fibula / peroneals and nerve get taken in salvage

B.  Posterolateral approach

 

3.  Lateral malleolus

- direct lateral approach

 

Distal Fibular Lucent Lesion

 

Leg

 

1.  Proximal posterior compartment ST tumour

- medial to tibia

- preserve anterolateral compartment

 

2.  Proximal anterolateral compartment ST tumour

- direct approach through tibialis anterior

- will likely not be able to preserve CPN

 

Talus

 

1.  Head and neck

- medial approach between T anterior and T posterior

- may need medial malleolar osteotomy

 

2.  Body

- Ollier's approach

 

Calcaneum

 

Bony tumour

- direct lateral

- avoid medial NV bundles

 

Calcaneal Bony Lesion CTCalcaneal Bony Lesion MRI

 

Foot

 

1.  Navicular / Medial cuneiform

- direct medial

 

2.  Cuboid

- direct lateral

 

3.  Intermediate cuneiform

- between EHL and EDC but away from dorsalis pedis

 

4.  Lateral cuneiform

- lateral to EDC

 

5.  Metatarsals / phalangeals

- dorsal approach

 

Metatarsal tumour

 

6.  Soft tissue tumour

- medial or lateral as required

 

Soft tissue sarcoma medial foot

 

Pelvis

 

Iliac crest

- definitive surgery via ilioinguinal approach

- best to use iliac crest aspect of this approach

- can go medial or lateral to crest

 

Pelvis Soft Tissue Sarcoma

 

Anterior column

- Watson - Jones through G medius

- avoid femoral NV bundle

 

Posterior column

- Kocher - Lagenbeck through G maximus

 

Pubis

- Pfannenstiel approach

 

Ischium

- lithotomy position

- detach adductor and hamstrings

 

Sacrum

 

Direct posterior approach

 

Upper Limb

 

Humerus

 

1.  Proximal humeral bony tumour

- direct lateral

- through deltoid muscle

- never deltopectoral (condemns patient to forequarter amputation)

 

2.  Shaft

- modified Henry

 

3.  Distal humerus bony tumour

- lateral longitudinal to capitellum

- medial approach to trochlea

 

Radius

 

1.  Proximal bony tumour

- protect radial nerve at all times

 

A.   Radial head: Kocher approach / through anconeus

B.   Proximal third:  Henry approach / take off supinator

C.   Middle third: Henry approach / take off pronator teres

D.   Distal third: Henry approach / take off pronator quadratus

 

2.  Distal radius

- dorsal approach as salvage is always wrist fusion

- through second compartment / sacrificeable

 

Lesion distal radius

 

Wrist / Hand

 

1.  Carpus

- dorsal approach

 

2.  Metacarpal / phalanges

- dorsal approach

- avoid volar to preserve NV bundle

 

Sarcoma Finger

 

Ulna

 

1.  Proximal ulna bony tumour

- direct subcutaneous approach

- away from ulna nerve

 

2.  Coronoid

- posterior approach with window for biopsy

 

3.  Distal ulna bony tumour

- direct lateral approach between FCU and ECU

- down onto subcutaneous surface of ulna

 

Clavicle

 

Clavicle

- direct subcutaneous

 

Scapula

 

Acromion - deltoid split

Spine - transverse approach

Body - Judet posterior approach

Glenoid - posterior approach, through T major

Coracoid - deltopectoral approach

 

Spine

 

C1-2 bony tumour

- anterior retropharyngeal approach

- anterior to SCM

- resect submandibular gland and ligate duct

- CN XII superiorly

- between carotid sheath and larynx

- biopsy through longus colli

 

C3-T1

- Smith-Robinson approach

- vertical incision

- split longus colli

 

T2 - T12

- posterior approach and transpedicular

- open or CT guided

 

L1-L5

- anterior retroperitoneal approach

 

 

 

Chemotherapy

Sensitivity

 

High grade tumours often sensitive to intensive chemotherapy

- OS

- Ewings

- MFH

 

Low grade often insensitive 

- Chondrosarcoma

- Parosteal OS 

 

Role

 

1.  Eradication of overt & micrometastasis

- OS 80% have micrometastasis

 

2.  Reduce tumour locally 

- makes limb salvage easier

 

3.  Improve local control

- lesser role

- local control has no real impact on survival

 

Mode of Action

 

Interferes with synthesis of

- DNA

- RNA

- Protein

 

Action

 

Non-specific

- all cells

 

Cell Cycle-specific

- proliferating cells

 

Cell Phase-specific

- portion of proliferating cells

 

Types

 

1. Alkylating agents

- Cyclophosphomide

- Cisplatin

- Ifosfomide

 

2. Antitumoural Antibiotics

- Doxorubicin

- Bleomycin

 

3. Plant Alkaloids

- Vincristine

- Vinblastine

- VP-16 (Etoposide)

- Taxol

 

4. Antimetabolites

- Purine and Pyrimidine Antagonists

- Thioguanine & Mercaptopurine

- Cytarabine & 5-FU

- Methotrexate - Folate antagonist

 

Supportive therapy

 

Responsible for much of improvements in results

 

G-CSF 

- 175 amino acid glycopn 

- developed from E.coli recombinant DNA technology

- improves recovery by reducing neutropenic period

- neutropenia can be devastating in the more aggressive protocols

- G-CSF allows the dose to be increased further and achieve higher cell kill

 

Blood Products

- when needed 

- i.e. platelets

 

N 5-formyl-tetrahydrofolate

- MTX rescue

- following very high doses

 

Leucovarin 

- MTX rescue

 

Ondansetron 

- serotonin antagonist

 

Osteosarcoma Protocol

 

MACI pre op + G-CSF support

 

MTX

- high dose

- can see dramatic response

- blocks conversion folate ->tetrahydrofolate

- can cause renal failure

- alkylate urine and hydrate +++

- leucovorin rescue

- otherwise die very quickly

- doesn't suppress bone marrow to any great degree so use after an alkylating agent

- side effects related to levels

- mucositis and ulcers / pleuritis / conjunctivitis / hepatic and renal failure

 

Adriamycin

 

Cisplatin  

- standard drug for OS

- alkylating agent 

- direct DNA damage

- SE - emesis, renal and ototoxic

 

Ifosfamide

- new generation alkylating agent

- single most effective agent against sarcoma

- activated by hepatic P450 system

 

Timing

 

Adjuvant (Postoperative)

 

Neoadjuvant (Preoperative)

 

Standard strategy is neoadjuvant

- allows assessment of response early in disease

- restaging investigations after neoadjuvant chemotherapy

- imaging, histology

 

Advantage

- improves limb salvage

- allows planning of surgery

- re-stage after chemo

- prognostic

 

Efficacy 

 

Measured by extent of tumour necrosis

- good response is > 90% necrosis

- poor response is < 90% necrosis

- response is best prognostic factor

 

Rosen in vivo response dictates outcome

- Grade 1 = no cell death

- Grade 2 = partial <90%

- Grade 3 = necrosis >90%

- Grade 4 = complete necrosis

 

1 & 2 < 50% survival

3 & 4 > 75% long term survival in OS and MFH

 

Using Cisplatin, Doxorubicin, MTX

 

Resistance 

 

Tumour cells develop cell membrane pumps to expel chemotherapy

 

Side-Effects

 

A.  Proliferating tissues

 

Most commonly

- bone marrrow

- oral & GIT epithelium

 

Effects are

- myelosuppression

- stomatitis

- mucositis

- N & V

- anorexia

- infertility

- hair loss

 

All males store semen prior to chemotherapy

Females consider egg retrieval

 

B.  Non-Proliferating Tissues

 

Less predictable effects

 

1.  Pneumonitis & Pulmonary fibrosis 2° Bleomycin

(blasts the lungs)

 

2.  Cystitis 2° Cyclophosphamide

(cills the kidneys)

 

3.  Nephrotoxicity 2° MTX & Cisplatin

 

4.  Cardiotoxicity 2° Doxorubicin

(death to the heart)

 

5.  Neurotoxicity 2° Cisplatin & Vincristine

 

Adverse effects on Surgery

 

Systemic

- neutropenia

- thrombocytopenia

- coagulopathy

 

Local

- cytotoxicity to tissue

- wound complications

- delayed bone healing

 

Results

 

Osteosarcoma

 

Improved 5 year survival from 20 - 80%

- improved ability limb salvage OT

- multi-agent treatment

- Rosen T10 protocol (MAC CAB)

- Methotrexate / Adriamycin / Cyclophosphamide / Cis-Platin / Actinomycin-D / Bleomycin

 

Pre-operatively

- 2 / 12 months

- 3 cycles 2 weeks apart

 

Restage disease

- repeat MRI

- may repeat CT Chest / Abdo & bone scan

 

Surgery

 

Post-operatively

- regimen continued for further 6-12/12

 

Ewing's Sarcoma

 

Previous treatment was surgery or radiotherapy

- dismal outlook

- < 15% 5 year survival

 

Combination with chemotherapy gives much better results

- 50% 5 year disease-free survival

- 70% 5 year overall survival

- 30% 5 year if present with metastasis

 

Multiagent neoadjuvant chemotherapy

- 3/52

- Vincristine / Actinomycin D / Cyclophosphamide / Adriamycin

- alternating with 3/52 of Iphosphamide / VP-16

 

Surgery performed when estimated that maximal response achieved

- usually at 3-4 /12

 

Malignant Fibrous Histiocytoma

 

Mainstay of treatment is resection

- multiagent neoadjuvant chemotherapy improves 5 year survival from 50% - 75%

 

Chondrosarcoma

 

Primary treatment is surgery as tumour resistant to chemotherapy

- occasionally used for palliation but effects unclear

- hormonal agents may be effective

- i.e. HGH, somatomedin

 

Childhood Rhabdomyosarcoma

 

Improved survival from 20% to 60% 5 year

- much poorer for metastatic disease

 

Adult Soft Tissue Sarcomas

 

Treat as one disease

- controversial

- no clear evidence of long-term efficacy with chemotherapy

- exception is MFH and synovial sarcoma

 

 

 

 

Histopathology

Grading Neoplasia

 

Most important

 

Mitotic Figures

Necrosis

 

Next Important

 

Anaplasia

Pleomorphism

Atypia

  

Standard Microscopy

- specimen fixed in formalin

- decalcified if contains bone

- embedded in paraffin

- water replaced with wax

- fine sections cut

- stained with Haematoxylin & Eosin

- Haematoxylin stains Protein blue

- Eosin stains Cytoplasm & Collagen pink

 

Special Stains

 

Van Gieson's

- myogenic tumours

 

Reticulin

- vascular tumours, clear cell sarcoma

- alveolar soft part sarcoma

 

Periodic Acid Shift

- Ewing's/ PNET

- Rhabdomyosarc 

- Neuroblastoma

 

Melanin

- melanoma

 

Masson's Trichrome Stain

- presence of collagen = fibrosarcoma

 

Frozen Section

 

Specimen fresh

- specimen frozen with liquid nitrogen

- fine sections cut

- similarly stained

 

Immunohistochemical Stains

 

Rationale

 

Identifies certain proteins

 

Technique

 

Slide prepared as above

- particular antibody-containing solutions put on slide

- antibody binds with antigen if particular protein present

- then another antibody with attached colouring agent put on slide

- binds to antigen-antibody complex if present

- thus stains if protein of interest present

 

Types IHC Stains

 

Keratin + / Vimentin -

- carcinoma

 

Keratin - / vimentin +

- sarcoma

 

Keratin + / Vimentin +

- synovial / epitheloid sarcoma

- adamantinoma

- osteofibrous dysplasia

- chordoma

 

S100 

- Melanoma

- Schwann / Neural cells

- Ewings / PNET

 

Factor VIII

- vascular tumour

 

MIC2

- Ewing's, PNET

 

Actin

- muscle, myofibroblasts

 

Desmin

- muscle

 

Myoglobin

- skeletal muscle only

 

LCA (leucocyte common antigen)

- lymphoma

- haemopoietic lesions

 

Cytokeratin

- skin

- synovial sarcoma

- epithelioid sarcoma

 

Epithelial Membrane Antigen

- synovial sarcoma

- epithelioid sarcoma

 

NSE, GFAP, Neurofilament PR 

- round cell tumours

 

DNA Ploidy

 

Measure DNA content in each cell by flow cytometry

- quantify no cell with normal & abnormal amounts DNA

- N = 23 pairs (Diploid) or 46 total 

 

Little benefit as

1. Not used to grade neoplasia

2. Not useful for prognosis

3. Can't diagnose tumour type

 

Cytogenetics

 

Rationale

- certain tumours have identified genetic abnormalities

 

Technique

- cells cultured

- halted in metaphase

- karyotyping performed

- chromosomal banding patterns identified

 

Examples

 

Ewings / PNET

- t (11, 22)

- EWS - FLI

 

Clear Cell Sarcoma t (12, 22)

 

Synovial Sarcoma t(X, 18)

 

Liposarcoma

Rhabdomyosarcoma

Infantile Fibrosarcoma

Trisomy 11, 17, 20

 

Electron Microscopy

 

Rationale

 

Certain ultrastructural features differentiate tumour types

 

DDx PNET/ Ewing's / Neuroblastoma

 

Epithelial structures in carcinoma

 

Sarcomeres in Myosarcoma

 

Melanosomes in Melanoma

 

 

 

Principles of Biopsy

Aims

 

1.  Provide representative sample

- to determine whether benign or malignant

- to determine cell line

- to grade lesion

 

2.  Not compromise definitive treatment

 

Timing

 

Last step in evaluation / after staging

 

Don't perform definitive procedure immediately after biopsy unless

- pre-operative & Xray information characteristic

- fresh frozen section unquestionably confirms diagnosis

- i.e. ABC, GCT

 

Usually biopsy, then definitive OT later

 

Open vs Closed

 

Overall, open preferred

 

Open

 

Advantage

- more tissue

- lower sampling error

 

Disadvantage

- larger field to excise later

- higher local complications (i.e. infection, haematoma)

 

Needle Biopsy

 

Advantage

- less expensive / less risky

- smaller field to excise later

 

Disadvantage

- reduced accuracy 70-85% vs 95% with open

 

Indications

1.  Homogenous tissue expected - Myeloma

2.  Treatment unchanged by subtle differences - Soft Tissue Sarcoma

3.  Diagnosis relatively certain - Metastasis

4.  Access difficult - Spine, Pelvis

5.  Expert histologist available

6.  Patient not able to tolerate big surgery or GA

 

Complications biopsy tract

- wound contamination -> tumour recurrence

- wound dehiscence

- infection

- haematoma - always drain biopsies (haematoma spreads tumour)

 

Performed by treating surgeon at treatment centre

 

Results

 

Mankin 1982 JBJS 

- complication rate x 5~12  when performed by other surgeon / other hospital

- 60% major error in diagnosis

- 20% treatment compromised by biopsy

 

Mankin and Simon 1996

- musculoskeletal tumour society

- follow-up study from 1982

- results no different from previous study

- 597 patients 21 institutions

- rate of diagnostic error 17.8%

- problems with biopsy causing change in treatment to more difficult or complex procedure 19.3%

- change in outcome attributed to biopsy 10.1%

- 18 patients had unnecessary amputation

- errors, complications and changes in course and outcome

- 2 - 12x more common than if biopsy done in referring institute instead of treatment centre

- 19.3% of biopsies planned poorly

 

Most common errors

 

Transverse incisions in soft tissue tumours

Needle biopsies only 60% accurate compared to 76% with open biopsy 

 

Conclusion

 

Not always possible to perform biopsy in treatment centre

- do so after review of case and imaging with tumour surgeon

- discuss optimum biopsy approach

 

Biopsy Technique

 

Pre-operative

 

Tumour staging first / all imaging obtained

Images reviewed with experienced MSK radiologist

Treating surgeon does biopsy at treating hospital

- discussed with tumour centre if not possible

Ensure expert pathological facilities

- experienced MSK pathologist

- frozen section available

No pre-op antibiotics / infection always in DDx

Tourniquet

- no exsanguination

- release before closure and obtain hemostasis

 

Intra-operative

 

1.  Approach

- plan with future OT in mind

- all aspects of biopsy tract must be excised later

- incision must be incorporated in definitive surgery

- violate one compartment only / trans-muscular

- incision is longitudinal, no undermining skin edges

- don't expose NV structures

- meticulous haemostasis

 

2.  Biopsy

- round cortical windows / decreased stress-risers

- swab taken / tissue for M/C/S

- tissue for FFS / histology

- no closure until discussion with pathologist on phone

- ensure they have enough to make a definitive diagnosis / cell line / grade 

 

3.  Closure

- plug bone windows with PMMA / minimises tumour spread 

- achieve haemostasis

- closure in layers

- drain exit site in line with and through wound

- subcuticular suture to skin

- firm dressing

- immobilise 

 

Post operative

 

Very careful post op

- pathological fracture changes outcome

 

Team approach

- pathologist / radiologist / oncologists / radiation oncologist

- all results are reviewed to ensure correct diagnosis and management

 

Radiotherapy

Definition

 

Use of ionising radiation to damage DNA to prevent cell replication

 

Mechanism

 

Most rapidly replicating cells affected the most

 

Radiosensitive tissue

- high turnover tissue

- high blood supply

 

Give DXRT in incremental radiation

 

Produce free radical by breakup of H2O

- H2O -> H+ + OH-

- free radicals denature DNA

- damage DNA so that cell can't divide 

- cell then dies without dividing

 

Particles 

- bigger particle produces greater damage

- different particles have different RBE (Radiobiological effectiveness)

- each particle works the same way- free radical production

 

Both tumour & normal cells injured

- normal cells recover

- tumour dies

 

Need O2 for DXRT to work

- hyperbaric better

- unoperated bed better

 

Types

 

1.  Photons

 

2.  Gamma Rays 

 

Go through body / not absorbed as particles

- Cobolt 60 - Almost obsolete

- Iridium - Occasionally used in Brachytherapy

- Caesium - Used for Gynaecology tumours

- Radium - Now obsolete

 

3.  X-Rays 

- diagnostic 50-150 kv

- deep X-Ray Therapy - 300 kv

- linear accelerators - 4-24 mv

 

4. Particle beams

 

Electrons - Linear Accelerators

- particle beams via linear accelerator

- produce electron beams -> absorbed as particles

- depending on energy of beam can dial up depth of beam 

- 6MeV - 20MeV 

 

5.  Beta - Rays

- electrons given off by ionised substance

- injected locally

- Strontium, Yttrium & Samarium

 

6.  Neutron beams 

- very damaging

- experimentally are producing heavy particle beams via cyclotrons as neutron beams

 

Technique

 

Fractionation

- 1 large dose vs 60 small doses

- curative / fractionation

- palliative / minimal fractionation

 

100 Centigray = 100 Rad = 1 Gy

 

Metastasis

- 1000 Centigray in 10 doses

 

Bone Tumour

- 6000 Centigray in 30 doses

 

Curative

 

Maximum possible dose with acceptable damage to normal tissue

- 60 Gy in 30 fractions over 6/52

- equivalent to 18 Gy in one dose

- fractionation decreases late effects on normal tissue

- increased differential between tumour & tissue damage

- allows repair between treament

 

Usually given 3/52 postoperatively

- allows wound healing

- minimum delay as tumour interference activates cells in arrest phase

 

Careful planning

- multiple fields

- minimum normal tissue damage

 

Palliative

 

Short course with lower total dose

- 30 Gy in 10 fractions

- 3 CentiGy or 3 Rad or 0.03 mRad

 

Simple field set ups

- late morbidity less of an issue

- delays callus formation if pathogical fracture

- slows chondroid formation at fracture but not with osteogenesis 

- 96% local remission

 

Method of Delivery

 

External Beam

 

Brachytherapy

- old method

- place radioactive agent down tube 

- high risk to doctor giving treatment

- now use remote brachytherapy

 

Intrapoerative radiotherapy

- give dose to site at time of surgery

- give high dose with minimal local effects

 

Remote Afterloading

- pour radio-active agent down into tube

 

Timing 

 

6 Week Rule

- start radiotherapy < 6/52 after OT

 

Preoperative

- better blood supply 

- needs oxygen to effect cell kill

- shrinks tissue from neurovascular bundle

- may allow limb salvage

 

Disadvantage

- impairs healing

 

Postoperative

- usually preferred

- wait for wound to heal

- start within 6/52 otherwise repopulates with tumour cells

- also easier to identify site of tumour

 

Morbidity

 

100% side effects

 

Early 

 

Erythema / Dry desquamation / Ulceration skin

Lymphopaenia

Telangectasia

 

Myelosuppresion

 

GIT effects

 

Late

 

Skin Fibrosis

Joint Contracture

Muscle Atrophy

Lymphoedema

Hair loss

 

Chronic bone changes / fracture

 

Post Radiotherapy Changes With Stress Fracture

 

Osteoradionecrosis - eg AVN Femoral head

 

Transverse myelitis

 

Lung fibrosis

 

ST & bony hypoplasia in kids

- physeal arrest

 

Endocrine suppression

 

Infertility 

 

Skin cancers

 

Sarcomatous change

 

Specific tumours

 

Osteosarcoma

 

No indication for preoperative treatment

 

May be used for

- unresectable 

- palliation for metastasis

 

Ewing's Sarcoma

 

Very high radioresponsiveness 

- but low curability

- effective if combined with chemotherapy

- surgery & chemotherapy  have better results

 

Chondrosarcoma

 

Relatively radioresistant

 

May be used for

- recurrence

- inoperable disease

 

Myeloma

 

Effective for Plasmocytoma

Combined with chemotherapy for Multiple Myeloma

 

Soft Tissue Sarcomas

 

Indications

- doubt about surgical margins

- NV structures close to tumour

- 50 Gy DXRT  preoperatively

- 10 Gy Brachytherapy postoperatively

 

Useful to give radiotherapy preoperatively for sarcomas

- because it develops a rind around the tumour 

- makes it a lot easier to excise

- operate at about 6 weeks post radiotherapy

 

 

Staging

Musculoskeletal Tumour Society Staging System

 

Stage 1  Benign inactive

Stage 2 Benign active

Stage 3  Benign aggressive

 

Stage I Low grade malignant

Stage II  High grade malignant

Stage III  Metastases to any site

 

Purpose

- guide prognosis

- guide surgical management

- guide adjunctive therapies

 

Compartments

 

Definition

 

A compartment is an anatomically confining space

- will resist tumour spread beyond its boundaries 

 

Intra-compartmental (4)

- intra-osseous

- intra fascial compartments

- superficial to deep fascia 

- par-osseous

 

Extra-compartmental 

- extension beyond above

- pelvis

- popliteal fossa

- axilla

- cubital fossa

 

Benign

 

Latent / Inactive

 

Non-ossifying fibroma

- benign, intracapsular, no metastatic potential

- typical clinical course is unchanging or self-limiting

- tendency to self healing

 

Active

 

ABC

- characteristic is progressive growth

- benign, intracapsular, no metastatic

- X-ray and clinical appearance suggests active but contained growth

- without extracapsular penetration

 

5-10% local recurrence with curettage 

- respond well to wide excision

 

Aggressive 

 

GCT

- locally aggressive but no metastatic potential

- benign, extracapsular but intra-compartmental

- X-ray and clinically characterised by extracapsular penetration & destructive growth

 

10-20% recurrence after marginal excision 

- may even recur after wide excision

- best treatment by excision with cuff of tissue

 

Malignant

 

1A Low Grade Intra-compartmental

1B Low Grade Extra-compartmental

 

2A High Grade Intra-compartmental

2B High Grade Extra-compartmental

 

3 Metastasis

 

Low grade

- low metastatic potential

- parosteal OS

 

Treatment is surgery alone

- don't require systemic treatment

- tumour nodules in reactive zone but not beyond

- wide excision

 

High grade

- grow rapidly & metastasise early

- tumour nodules beyond reactive zone

- classis central OS

 

Treatment is surgery & systemic treatment

 

 

 

Tumour Surgery

Aim

 

Tumour removal to gain local control & minimize recurrence while maintaining functional limb 

 

Margins

 

1.  Intralesional

 

Within lesion

- macroscopic tumour remains

 

2.  Marginal

 

Within reactive zone

- microscopic tumour remains

 

3.  Wide 

 

Intra-compartment and outside of reactive zone

- tumour & cuff of normal tissue

 

Beyond reactive zone

- > 7cm level on Te99 scan

- > 5cm level on MRI

- may leave skip lesions behind

- hence MRI

- remove biopsy site

- may mean amputation

 

4.  Radical

 

Extra-compartmental 

- removal of all compartments that contain tumour

 

Amputation is not necessarily Radical

- radical resection possible with limb salvage 

 

Exceptions

 

Skin & subcutaneous tissue

- wide margin is < 5 cm

- radical margin is > 5 cm

 

Extracompartmental lesions

- can't have radical exision of extracompartmental lesions

- no longidudinal barriers to extracompartmental spaces

 

Two compartments

- both compartments must be removed to achieve radical resection

- sometimes only practical way to achieve this is amputation

 

Contamination

- when lesion entered, wound contaminated

- if exposed tissues not removed, margin is intracapsular

 

Surgery & Recurrence rate

 

  IA IB IIA IIB
Intralesional 90% 90% 100% 100%
Marginal 70% 70% 90% 90%
Wide 10% 30% 50% 70%
Radical 0% 0% 10% 20%

 

Limb Salvage

 

About 80 - 85% patients with OS, Ewing's, CS amenable to limb salvage

 

Principles

- must have same survival rates

- must not delay adjuvant treatment

- reconstruction should be enduring with minimal complications

- function should approach that achieved by amputation

 

Contraindications

 

PIN LEG

- pathological fracture

- infection

- NV bundle involvement

- LLD > 8 cm

- extensive muscle loss

- Good v poor biopsy

 

Absolute

 

1.  Can't obtain wide margins

2.   Major NV involvement

- vessel grafts are possible

- nerve remains at risk

3.  Infection

 

Relative

 

1.  Pathological  fracture

- hematoma spreads tumour beyond accurately defined limits

- may necessitate amputate

 

2.  Inappropriate previous biopsy

- contamination of other compartment

 

3.  Significant skeletal immaturity

- predicted LLD > 8cm

- adjustable / growing joint replacements availiable

 

4.  Extensive muscle involvement

- leave leg non functional

 

5.  Medically unfit

 

Technique

 

Radical or wide resection

- extra-articular resection is preferred if a tumour is adjacent to or involves a joint

- prophylactic antibiotics

- no tourniquet if possible

- no eschmarc

- biopsy site excised

- tumour &/or pseudocapsule not visualised during procedure.

- distant flaps should not be developed until the tumour has been removed

- all dead space should be eliminated, & haematoma formation should be prevented

- surgical wound marked with clips for later radiatherapy

- motor reconstruction by regional muscle transfer

- adequate soft tissue cover by flap to avoid skin necrosis

 

Reconstruction Options

 

Arthrodesis

Autograft (remove and irradiate)

Allograft arthrodesis

Allograft arthroplasty

Modular Endoprosthesis

 

Modular Endoprosthesis 

 

Proximal Femoral Replacement

 

Advantage

- early weight bear and rehabilitation

- lower infection rates than allograft

- no risk of non union like allograft

 

Types

- rotating hinge

- expandable if final LLD > 2cm

- modular

 

Contraindications

- < 8 years old

 

Complications

 

Early complications

- wound infection

- skin necrosis

- DVT

- neuropraxia

- instability

 

Late complications

- prosthesis breakage

- LLD 

- lysis

- instability

- late infection

 

Expandable Prostheses

 

Lengthen 2cm every 18 months

- surgical procedure

- excise fibrous tissue to prevent joint stiffness and protect NV bundle

 

Average lengthening 9 cm

 

50% complication rate

 

Massive Allograft 

 

Massive Femoral Allograft0001Massive Femoral Allograft0002

 

Advantage

- biological reconstruction

 

Disadvantage

- incorporation is a slow and incomplete process

- 20% will fail within 5 years

 

Indications

- patient < 20 years old

 

Complications

- infection 11% (sometimes only salvageable by amputation)

- fracture 16% (up to 3 years later)

- joint instability

- non union (increased by chemo/DXRT)

- OA (15% at 10 years with osteochondral allograft)

 

Results

 

Intercalary > osteochondral

 

Intercalary

- 80% good results

- 30% non union at one osteosynthesis site requiring intervention

 

Osteochondral

- 73% good results

 

Allograft - prosthetic

- 77% good results

 

Rotationplasty

 

Concept

- creates a functional BKA

- superior to AKA

 

Advantage

- low complication rate

- very functional

 

Disadvantage

- high rate cosmetic dissatisfaction

- patients should meet others with same procedure

 

Indication

- young child in whom endoprosthesis has high rate failure

- wide resection about knee

- sciatic nerve preserved

 

Technique

- tibia rotated 180o

- fused to femur

 

Complications

- post operative vascular occlusion

- tibio-femoral pseudoarthrosis

 

Results

- patients can play sports

 

Limb lengthening

 

Usually very large osseous defects

- difficult

- associated with significant complications

- better suited as adjuvant to other procedures or for smaller defects

 

Vascularised fibula graft

 

Advantage over allografts

- more rapid incorporation

- stronger initial construct secondary to graft hypertrophy

 

Disadvantage

- increased surgical time

- surgical site morbidity

- size limitations

- stress fractures

 

Amputation v Limb Salvage

 

Limb Sparing

Amputation

Local Recurrence

5 - 10%

5%

Survival

70%

70%

Functional Outcome

Good

Good

Initial Cost

High

Low

Long term cost

 

 

 

Outcome

- limb salvage often functionally better

- complication rate and incidence multiple surgery higher