Bony metastases profoma Flashcards
Epidemiology of bony metastases
More common than primary bone cancers.
Bone is the 3rd most common site for metastasis.
The big five cancers that metastasise to bone are: breast, lung, thyroid, prostate and kidney. Plus myeloma
Why do these 5 particularly lodge in bone?
- Have the ability to cause angiogenesis - grow new blood vessels.
- Can induce osteoclasts to create space
- Osteoblastic response is variable depending on tumour.
Pathophysiology of bony metastases
Disruption to normal OPG-RANK-RANKL pathway → increased osteoclast formation → increased bone resorption → more bone loss → osteolysis → release of bone derived growth factors → interaction w/ tumour cells → increased osteoclastogenesis & osteolytic activity + aggressive growth & behaviour of the tumour cells.
3 types of metastasis:
1. Osteolytic
2. Osteoblastic
3. Mixed: both osteolytic & osteoblastic lesions
3 ways of spreading:
1. haematogenous
2. lymphatic system
3. direct contact.
Process of bone formation & reabsorption can release/activate survival & growth promoting factors that may contribute to bone metastases development.
Development of bone pain can either be inflammatory or mechanical origin.
Inflammatory pain is related to:
- Release of cytokines & chemical mediators by the tumour cells.
- Periosteal irritation
- Stimulation of intraosseus nerves
Mechanical pain is related to:
- Pressure of tumour tissue w/in bone
- Loss of bone strength thus activity related pain
Presentation of bony metastases
- Severe bone pain- worse at night, doesn’t relieve when resting, NSAIDS don’t work.
- Pathological fractures (common in long bones, especially femur)
- Spinal cord compression
- Systemically unwell - weight loss & anorexia.
- Impaired mobility - difficulty weight-bearing.
- Bone marrow aplasia
- Hypercalcaemia- if left untreated will present w/ constipation, polyuria (excess urine), polydipsia (excessive thirst) & fatigue
Investigations for bony metastases: Blood tests
FBC - for anaemia or myelosuppression
High alkaline phosphatase - together w/ high Ca, makes malginancy more likely. If ALP is high on its own, Paget’s disease is more likely.
High serum Ca- hypercalcaemia of malignancy.
PTH levels - to look for bone turnover.
Phosphorus
25 (OH) D
Creatinine
Thyroid stimulating hormone
Myeloma screen
Investigations for bony metastases: Imaging
X rays- osteolytic & sclerotic lesions but metastatic lesions may not appear at initial stages of disease.
MRI is good for detecting vertebral metastases, useful in telling whether tumour has invaded bone marrow (required to diagnose spinal cord compression).
CT scan - bone destruction, sclerotic areas, will show if it has metastasised to soft tissue.
Isotope bone scan - identifies areas of high metabolic activity.
Biopsy - can help discover where the primary tumour is. You wouldn’t do this for a primary tumour due to risk of seeding.
Management for bony metastases: pharmacological
Treatments are not curative, they only slow growth of bone metastases & help w/ symptoms.
Inhibition of osteoclastic bone reabsorption reduces bone pain, so osteoclast inhibitors e.g. bisphosphonates & Denosumab, reduce bone pain.
- If both these drugs are used via IV on a monthly basis for control of metastases, osteonecrosis of the jaw may occur)
Bisphosphonates e.g. zolendronic acid
- Used w/ vitamin D & Ca!
- Can cause osteoclast apoptosis
- Standard treatment for tumour induced hypercalcaemia
- Contraindication → renal impairment
- Works by interrupting osteolysis cycle, delay bone lesion progression, & inhibit activity of GTPases, which down regulate proapoptotic genes in malignant cells.
- Side effects: flu-like symptoms, anaemia, nausea, peripheral oedema, dyspnea.
Denosumab
- Used in renal failure due to bisphosphonate contraindication.
- Inhibits RANKL activity, preventing development of osteoclasts.
- Can help prevent or delay fractures.
- Greater suppression of bone turnover markers than bisphosphonates.
- However will cause increased infection rate in patients w/ osteoporosis & breast cancer.
- Injected subcutaneously.
- Effects will reverse if treatment is discontinued (this sounds like a bad thing but actually its a good thing)
- Side effects: nausea, diarrhoea, weakness, increased infection rate in those w/ osteoporosis or breast cancer & osteonecrosis of jaw.
If patient has spinal cord compression, high dose corticosteroids treatment, rapid assessment & urgent referral for both decompression & spinal stabilisation.
Management for bony metastases: Radiotherapy
Used for localised bone pain, but bisphosphonates preferred if pain is recurring at previously irradiated sites
External radiotherapy really good for localised metastatic bone pain.
Indications for radiotherapy: pain, risk of fracture, neurological complications
Types of radiotherapy:
1. local-field radiation therapy
- Conventional treatment for bony metastases
- Treats the involved bone
- Pain relief rate 80-90%
- wide-field radiation therapy
- Used for widespread symptomatic bone metastases
- Or can be used as an adjuvant to local-field to reduce later metastases & re-treatment
- Pain relief rate 64-100% - radionuclide therapy
- Uses radioisotopes
- Reduced bone pain
- Taken up at sites of bone formation so most useful for osteoblastic metastases
- Examples: strontium-89, rhenium-186, samarium-153
- Side effects: myelosuppresion & pain flare
Management for bony metastases: Surgical
Ablation
- Procedure where a needle or probe is introduced into a tumour, & destroyed using heat, cold or chemicals
- Used if 1-2 bone tumours are causing symptoms
- Most common types include:
- Radio frequency ablation - where an electric current is delivered through needle to heat the tumour & destroy it.
- Cyroablation - where a cold probe is used to freeze the tumour cells.
Surgery - only for fractures, spinal cord involvement & peripheral nerve compression.
Screws, cement, joint replacement, plates.
Prognosis for bony metastases
Major cause of morbidity
Median survival time more than 20 months in bone metastatic breast cancer, prostate cancer & thyroid cancer.
Once cancer has spread to the bones it can rarely be cured, but often can still be treated to slow its growth.
If patient has spinal cord compression, diagnosis needs to be fast, if the compression is not relieved w/in 24-48 hours, neurologic recovery is unlikely.
