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Seminar in Palliative Care

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

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Seminar in Palliative Care

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  1. Seminar in Palliative Care September 26 – October 02, 2010Salzburg, Austria in Collaboration with

  2. Skeletal Complications Eugenie A.M.T. Obbens, MD PhDPain & Palliative Care ServiceMemorial Sloan-Kettering Cancer Service

  3. Objectives • Discuss the physiology of bone metastasis • Know skeletal related events and complications • Review the treatment options for skeletal metastasis

  4. Take Home Message: Poorly managed skeletal metastasis can lead to diminished quality of life and increased suffering.

  5. Pathophysiology of Bone Metastasis

  6. Mechanism of Bone Metastasis • Ca cells detach from primary tumor • Travel via blood and attaches to target tissue (bone) • Adhere to endosteal surface and colonize bone

  7. 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.

  8. 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.

  9. Types of Bone Metastasis • Osteolytic • Osetosclerotic • Mixed type

  10. 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.

  11. 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.

  12. Breast Prostate Lung Colon Stomach 6. Bladder 7. Uterus 8. Rectum Thyroid Kidney Cancers That Metastasize to Bone Wilfred CG. http://www.emedicine.com/radio/byname/bone-metastases.htm

  13. Diagnosis and Risks of Bone Metastasis

  14. Case:Diane G.

  15. 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

  16. 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.

  17. Skeletal Related Events (SRE) • Pain • Fracture • Hypercalcemia • Addressed in PC Emergencies • Spinal Cord Compression • Addressed in PC Emergencies

  18. 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.

  19. Fracture • Causes pain • May require surgical repair • Reduces quality of life • Decreases mobility • Increases care giving needs

  20. 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.

  21. 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.

  22. TreatmentOptions

  23. Analgesics • WHO Stepladder • NSAIDS • Prostaglandin inhibitor • Pain mediator within bone • Opioids • Co-analgesics

  24. 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.

  25. 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.

  26. 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.

  27. 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.

  28. Bisphosphonates: Treatment Risks • Transient fever, Muscle/Joint aches • 15 - 30% with first dose • Renal dysfunction • IV agents at high dose or rapid infusion

  29. 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.

  30. 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.

  31. Pathology Location Size of tumor Performance status Goals of Care Potential benefit Risk if not radiated Adverse events of treatment Life expectancy Radiation Therapy Considerations 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.

  32. 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.

  33. 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.

  34. 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.

  35. 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.

  36. 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.

  37. Surgery • Fracture Prevention • Plate Osteosynthesis • Nailing • Prosthetic Inserts • Fracture Repair • Vertebroplasty • Kyphoplasty

  38. 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

  39. Summary • Skeletal metastasis can lead to diminished quality of life • Treat SREs aggressively to prevent morbidity • Select the most appropriate treatment for each patient

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