Download Skeletal Metastasis

Seminar in Palliative Care
September 26 – October 02, 2010
Salzburg, Austria
in Collaboration with
Skeletal
Complications
Eugenie A.M.T. Obbens, MD PhD
Pain & Palliative Care Service
Memorial Sloan-Kettering Cancer Service
Objectives
• Discuss the physiology of bone
metastasis
• Know skeletal related events and
complications
• Review the treatment options for
skeletal metastasis
Take Home Message:
Poorly managed skeletal metastasis
can lead to diminished quality of life
and increased suffering.
Pathophysiology
of Bone
Metastasis
Mechanism of Bone Metastasis
1. Ca cells detach from primary
tumor
2. Travel via blood and attaches to
target tissue (bone)
3. Adhere to endosteal surface and
colonize bone
Mechanism of Bone Metastasis
• Bone Microenvironment
– Highly favorable for tumor invasion
– Hypoxic
– Acidic pH
– Extracellular Calcium
– Growth factors
Kingsley LA. Molecular biology of bone metastasis. Mol Cancer
Ther. 2007;6(10):2609-2617.
Mechanism of Bone Metastasis
• Vicious Cycle
– Promoted by crosstalk between tumor
cells and microenvironment
– Results in tumor growth and bone
destruction
Kingsley LA. Molecular biology of bone metastasis. Mol Cancer
Ther. 2007;6(10):2609-2617.
Types of Bone Metastasis
• Osteolytic
• Osetosclerotic
• Mixed type
Osteolytic
• Result of stimulation of bone resorbing
cells
• Radiolucent on X-ray
Skull, long bones
• Increased fracture risk
• Breast Ca, M. Myeloma
Clezardin P, Teti A. Bone metastasis: pathogenesis and therapeutic
implications. Clin Exp Metastasis 2007(24):599-608.
Osteosclerotic
• Stimulation of bone forming cells
• Appear as dense areas on X-ray
Axial skeleton, vertebral bodies, pelvis
• Poorly organized bone structure
• Increased fracture risk
• Prostate Ca
Clezardin P, Teti A. Bone metastasis: pathogenesis and therapeutic
implications. Clin Exp Metastasis 2007(24):599-608.
Cancers That Metastasize to Bone
1. Breast
2. Prostate
3. Lung
6. Bladder
4. Colon
5. Stomach
9. Thyroid
10. Kidney
7. Uterus
8. Rectum
Wilfred CG. http://www.emedicine.com/radio/byname/bone-metastases.htm
Diagnosis and
Risks of Bone
Metastasis
Case:
Diane G.
Diane G.
47 yr old F with L leg pain, L arm pain
• 8/10 in Leg, 4/10 in Arm
• Dull, ache
• Worse with movement, ok at rest most of time
• Motrin of no help
• Xray: lytic lesions in L femur, L humerus
• Biopsy: metastatic Breast Cancer
Diagnosis
•
•
•
•
•
•
Plain radiographs
Radionuclide bone scan
CT
MRI
Positron emission tomography (PET)
Biopsy if no diagnosis yet
Guise TA. Molecular mechanisms and treatment of bone metastasis.
Expert Reviews in Molecular Medicine. Vol 10; e7; March 2008.
Skeletal Related Events
(SRE)
• Pain
• Fracture
• Hypercalcemia
Addressed in PC Emergencies
• Spinal Cord Compression
Addressed in PC Emergencies
Pain
• Most frequent type of cancer pain
– Direct invasion with microfractures
– Increased pressure on endosteum
– Distortion of periosteum
– Nerve root compression
– Chemical mediators of pain
Mercadante S, Fulfaro F. Management of painful bone metastasis.
Curr Opin Oncol 2007; 19:308-314.
Fracture
• Causes pain
• May require surgical repair
• Reduces quality of life
– Decreases mobility
– Increases care giving needs
Hypercalcemia of Malignancy
• Lung/Breast Ca accounts for > 50%
• Symptoms
– N/V, renal dysfunction, delirium, abd pain, coma,
cardiac arrhythmias
• Treatment
– Hydration, Bisphosphonates, Calcitonin
Ernst DS, Wolch G. Textbook of Palliative Medicine. Great Britain:
Hodder Arnold, 2006.
Spinal Cord Compression
• Palliative Care Emergency
– Paralysis
– Dysreflexia
– Incontinence of Bowel/Bladder
• Suspect with worsening back pain
• Paraplegia >24-48 hrs may be
irreversible
Ferris FD, et al. The palliative uses of radiation therapy in surgical
oncology patients. Surg Oncol Clin N Am. 2001 Jan;10(1):185-201.
Treatment
Options
Analgesics
• WHO Stepladder
• NSAIDS
– Prostaglandin inhibitor
• Pain mediator within bone
• Opioids
• Co-analgesics
Corticosteroids
• Decreases peritumoral edema
– Alleviates symptoms
• Response may indicate favorable
response to radiation
• Dexamethasone is preferred
– Minimal mineralocorticoid effect
Ferris FD, et al. The palliative uses of radiation therapy in surgical
oncology patients. Surg Oncol Clin N Am. 2001 Jan;10(1):185-201.
Bisphosphonates
•
•
•
•
•
Hypercalcemia of malignancy
Prevention of SRE’s
Relieve pain
Improve pt functioning and QOL
Does not prolong life in advanced Ca
Body JJ. Bisphosphonates for malignancy-related bone disease: current
status, future developments. Support Care Cancer. 2006(14):408-418.
Bisphosphonates
• Mechanism of action
– Pyrophosphate analogue
– Bind to active sites of remodeling
– Inhibit osteoclast mediated bone
resorption
– Causes osteoclast apoptosis
Body JJ. Bisphosphonates for malignancy-related bone disease: current
status, future developments. Support Care Cancer. 2006(14):408-418.
Bisphosphonates
• Zoledronic Acid
– Proven efficacy across solid tumors
• Pamidronate
– Breast, Prostate, M. Myeloma
• Clodronate
– Breast, Prostate, M. Myeloma
• Ibandronate
– Breast
Coleman RE. Risks and benefits of bisphosphonates. British Journal of
Cancer. 2008(98):1736-1740.
Bisphosphonates: Treatment Risks
• Transient fever, Muscle/Joint aches
– 15 - 30% with first dose
• Renal dysfunction
– IV agents at high dose or rapid
infusion
Bisphosphonates: Treatment Risks
• Osteonecrosis of the Jaw
– Nonhealing area of exposed bone in
maxillofacial region after 8 weeks in pt who
was receiving Bisphosphonates and no XRT
– Conservative management
• Oral rinses and antibiotics
Coleman RE. Risks and benefits of bisphosphonates. British Journal of
Cancer. 2008(98):1736-1740.
Bisphosphonates
• American Society of Clinical Oncology,
2007
– M. Myeloma, Met Breast Ca to bone
• Bisphosphonate from time of diagnosis
• Development of SRE does not mean
failure
– Can delay onset of subsequent SRE
Coleman RE. Risks and benefits of bisphosphonates. British Journal of
Cancer. 2008(98):1736-1740.
Radiation Therapy
Considerations
• Pathology
• Location
• Size of tumor
• Performance
status
• Goals of Care
• Potential benefit
• Risk if not
radiated
• Adverse events of
treatment
• Life expectancy
Ferris FD, et al. The palliative uses of radiation therapy in surgical
oncology patients. Surg Oncol Clin N Am. 2001 Jan;10(1):185-201.
Radiation Therapy
• Radiosensitivity
– Cell type
– Degree of differentiation
– Volume of tumor
Ferris FD, et al. The palliative uses of radiation therapy in surgical
oncology patients. Surg Oncol Clin N Am. 2001 Jan;10(1):185-201.
Radiation Therapy
• Indications for Palliative XRT of
Bone Metastasis
– Relieve pain
– Prevent pathologic fracture
– Prevent neurologic dysfunction
– Prevent/delay progression of metastatic
disease at surgically repaired pathologic
fracture sites
Ferris FD, et al. The palliative uses of radiation therapy in surgical
oncology patients. Surg Oncol Clin N Am. 2001 Jan;10(1):185-201.
Radioisotopes
• Indicated for widespread bone metastasis
• Strontium-89
– Emits high energy ß-particle
• Samarium-135
– Shorter t1/2 so can give larger doses over shorter time
– Lower energy particle therefore reduced marrow
toxicity
Guise TA. Molecular mechanisms and treatment of bone metastasis.
Expert Reviews in Molecular Medicine. Vol 10; e7; March 2008.
Chemotherapy
• Effect depends on chemosensitivity
of the cancer
• Lymphoma, myeloma, testicular ca >
renal or hepatocellular
Mercadante S, Fulfaro F. Management of painful bone metastasis.
Curr Opin Oncol 2007; 19:308-314.
Hormonal Therapy
• Hormone sensitive tumors
• Breast Ca
– Selective Estrogen Receptor Modulators
– Aromatase Inhibitors
• Prostate Ca
– Gonadotropin releasing hormone agonists
– Antiandrogens
Guise TA. Molecular mechanisms and treatment of bone metastasis. Expert
Reviews in Molecular Medicine. Vol 10; e7; March 2008.
Surgery
• Fracture Prevention
– Plate Osteosynthesis
– Nailing
– Prosthetic Inserts
• Fracture Repair
– Vertebroplasty
– Kyphoplasty
Let’s not forget Diane G.
• Pain control
Morphine PCA
Dexamethasone
NSAID
Bisphosphonate
XRT
• Fractured L humerus (pathologic)
Surgical repair of L humerus, prophylactic
strengthening of L femur
Summary
• Skeletal metastasis can lead to
diminished quality of life
• Treat SREs aggressively to prevent
morbidity
• Select the most appropriate treatment for
each patient