Program Objectives

2. Program Objectives 1. Discuss vertebral compression fracture and how it relates to breast cancer and multiple myeloma. 2. Summarize best practices for managing pain related to vertebral compression fracture. 3. Explain differences between vertebroplasty and balloon kyphoplasty. 4. Develop a plan of care that increases patient compliance and quality of life.

3. Metastatic Disease—It is a Problem! • Patients with metastatic breast cancer and multiple myeloma are living longer than ever…why? • Heightened awareness and screening • Better treatment options • Therefore, skeletal-related events impact negatively on quality of life and overall survival.

4. Breast Cancer—Epidemiology Most common cancer among women (26%) In 2008, about 184,450 new cases were diagnosed. Cause of 40,930 deaths Is the second leading cause of cancer deaths in women (15%) after lung and bronchus (26%). Jemal et al., 2008

5. Pattern of Spread Within the breast Regional spread via lymph system Axillary nodes Internal mammary nodes Clavicular nodes Systemic spread via blood stream

6. Breast Cancer Sites of Recurrence

7. Bone Metastasis First site of metastasis in more than 45% of patients with breast cancer. Bone involvement is found in more than 70% of patients with metastatic breast cancer. Janjan, 2001

8. Bone Metastasis About two-thirds of patients with bone metastases suffer severe pain and disability. Creates high risk for vertebral compression fractures —About 50% of patients with metastatic breast cancer to bone experience a new vertebral fracture each year Body, 2003; Solomayer et al., 2000

9. Complications from Spinal Metastasis Severe pain Pathologic vertebral fractures Hypercalcemia of malignancies Spinal cord compression Neurologic symptoms (i.e., loss of bowel or bladder control) Alberico, 2007; Roodman, 2004

10. Bone Metastasis Goals for Care Improve overall survival Maintain quality of life Manage spinal metastasis complications Reduce/eliminate pain Improve mobility Reduce/eliminate use of narcotics and their related side effects

11. Treatments Hormone therapy Chemotherapy (trastuzumab if HER2 positive) Bisphosphonates with bone disease Palliative radiation Balloon kyphoplasty or vertebroplasty Hartsell et al., 2005; Hortobagyi et al., 1996; Taylor et al., 2007

12. Multiple Myeloma—What is it? • Plasma cell malignancy • Multiple organs and body systems may be affected. • Bone marrow—anemia • Kidney dysfunction—protein deposition • Hypercalcemia and bone destruction • Immune system—immunoglobulin defect

13. Epidemiology • Prevalence • Over 55,000 people in the United States have myeloma • Demographics • Age • Gender • Race • Risk with environmental exposures, Agent Orange • Five-year survival is 33%. Jemal et al., 2006; Kumar, 2008

14. Pathophysiology: What Happens? • Abnormal, overproduction of immunoglobulin • Usually IgG or IgA (68%) • Light chain MM—kappa or lambda (30%) • Referred to as the “M” protein (monoclonal), or “M spike” • Normal plasma cell turns malignant; makes a clone of itself • M protein is present in 80%–90% of patients. • Excess amounts of abnormal immunoglobulin proteins interfere with humoral immunity.

15. Patient Evaluation/Diagnosis • Blood tests: • CBC, differential • BUN/creatinine, electrolytes • Calcium, albumin • Quantitative immunoglobulins • Serum protein electrophoresis and immunofixation • B2M, C-reactive protein, LDH • Serum free light chain assay (Freelite™) NCCN, 2006.

16. Patient Evaluation/Diagnosis • Urine tests: • 24-hour urine protein electrophoresis • Immunofixation • Imaging: • Plain X-rays, skeletal survey • CT, MRI, PET scan as indicated • Pathology: • BM aspirate and biopsy with cytogenetics as indicated NCCN, 2006

17. Incidence of Skeletal Complications in Myeloma • Bone Involvement = Pain! • Most patients with myeloma will have pain. • Skeletal survey to identify specific lesions • Bone scan for breast, prostate • Plasmacytoma with significant bone destruction could be elicited clinically and radiologically (MRI).

18. Metastatic Bone Disease Faiman, 2007

19. Pathogenesis of Metastases in Patients With Cancer • Normal bone: • Osteoblasts “build” bone • Osteoclasts “nibble” away bone • Cancerous cells secrete a multitude of growth factors • Bone remodeling is altered locally by a two-way interaction between tumors and bone marrow microenvironment. Abeloff, 2004

20. Pathogenesis of Metastases Patients With in Cancer • Tumor cells secrete growth factors, peptides, proteins and “cytokines.” • These act directly on osteoclast • Osteoclast activity liberates growth factors • Leads to tumor growth • This leads to bone loss • This can further lead to weak bone structure, high blood calcium levels Abeloff, 2004

21. Osteolytic Metastatic Lesions • Decreased bone density • Numerous, circular areas of eroded bone, ‘punched-out’ • Weaken bone and increase risk of fracture • Common in patients with metastatic breast cancer, MM • 70% of MM patients present with osteolytic involvement of the spine. Lieberman, et al. , 2003 Patel, B. ,DeGroot, H. 2001

22. Spine Architecture .

23. Spine Architecture

24. Spine Architecture

25. Signs of Vertebral Compression Fractures (VCFs) • Acute event: • Sudden onset of back pain with little or no trauma • The majority of cancer-related VCFs are acute but some occur slowly over time. • Chronic manifestation(s): • Loss of height • Spinal deformity • Protuberant abdomen Gold et al., 1996, 2001

26. VCFs in Patients With Breast Cancer and Multiple Myeloma • Bone fractures can cause pain and inactivity. • Increased risk of infection • Increased blood clot risk • Systemic de-conditioning from inactivity and lack of weight bearing • Pain • VCFs classically cause incident pain (pain with movement) • Medication high enough to relieve pain with movement, may over sedate at rest • Therefore, treat the fracture to relieve the pain

27. VCFs in Patients With Breast Cancer and Multiple Myeloma • Pain • Tumor in bone • Inflammatory mediators • Increased intraosseous pressure • Functional (incident) pain • Inadequate control • “Good relief” 45% • Ineffective 23% Janjan, 1998

28. Pain Assessment for Vertebral Compression Fractures • Location • Radiation • Quality (description) • Severity • Associated symptoms • Time course • Provoking/relieving factors

29. Severity • Numerical rating scales (NRS) most common in clinical practice • On a scale of 0-10 with 0 = no pain and 10 = worst imaginable, how would you rate your pain? • VAS (visual analog scales) more common in research • Line of a certain length with anchor statements • Patient marks the line, then measured • Faces, thermometers, etc. • Categorical scale—mild, moderate, severe

30. Time Course • Often neglected in history taking • Constant, intermittent or both • Constant pain should = constant medication • Simplest way to give constant medication is sustained release products

31. WHO 3-step Ladder 3 SEVERE (8-10) Morphine Hydromorphone Methadone Levorphanol Fentanyl Oxycodone ± Adjuvants 2 MODERATE (5-7) 1 MILD (1-4) A/Codeine A/Hydrocodone A/Oxycodone A/Dihydrocodeine Tramadol ± Adjuvants ASA Acetaminophen NSAID’s ± Adjuvants WHO, 2008

32. Intermittent Pain • Breakthrough • Baseline pain that unpredictably worsens • Incident • Pain that is provoked • Voluntary movement-classic pain of VCF • Also called “functional” pain • Can be involuntary (i.e., cough, sneeze, etc.) • End-of-dose failure • Pain recurs before next dose of medication is due

33. Incident Pain • The most difficult to control—common with VCFs • Doses required may be significantly more than the breakthrough/sustained release dose • May require PCA (patient controlled analgesia) • Often needs an intervention • Disease specific therapy (radiation or chemotherapy) • Surgical stabilization

34. Identifying Fractures and Complications • Physical examination • Percuss the spine to identify location • Assess for neurologic impairment • Deep knee bends, heel-toe walking, sensory changes and deep tendon reflexes (DTRs). • Pathologic fracture • Spinal cord compression • Hypercalcemia (high calcium) • Marrow suppression from radiation or disease

35. Imaging of Spinal Fractures: Plain Film Radiography • Inexpensive and easily obtained • Not sensitive but … • Identify structural integrity • Follow-up after intervention • MRI must be done to confirm

36. Imaging of Spinal Fractures:Scintigraphy and Skeletal Survey • Bone scan • Sensitive but not specific • Detects occult disease • Plain film confirmation • Bone survey • Plain film radiography assessing skull, spine, long bones, pelvis and femurs to rule out lytic lesions, particularly among patients with MM

37. Imaging of Spinal Fractures: CT Scans • Not useful for primary detection • Pre-operative evaluation/biopsy • Superior to plain films • Cortical destruction • Soft tissue component

38. Imaging of Spinal Fractures: Magnetic Resonance Imaging (MRI) • Highly sensitive • Not specific • Infection versus inflammation versus tumor • Preferred test for spinal cord compression

39. Treatment Options: VCFs (Medical Management) • Prevention • Exercise (physical or aquatic therapy) • Bisphosphonates • Diet high in calcium? • Treatment • Chemotherapy/radiotherapy for disease progression • Analgesics (also bisphosphonates for HCM) • Bed rest • Braces should not be encouraged, use only when spine stability is compromised.

40. Prevention: Bisphosphonates in Skeletal Metastases • Potent inhibitors of resorption • Indicated for patients with metastatic bone disease and myeloma • Osteoporosis • Optimal duration of therapy is unknown • ONJ risk should be considered • Baseline and biannual dental examination Berenson et al., 2002

41. Radiation Therapy Treatment in Metastatic Disease • Local therapy that damages DNA • Cancer cells less able to repair • Pain relief up to 80% identified lesions • Daily treatment (fraction) to achieve a total cumulative dose • Total dose determined by pathology, location, goal of treatment Kachnick, 2006

42. Surgical Treatment of Metastatic Disease • Oldest treatment • Local therapy to control the primary site • Palliative in metastatic breast and myeloma to relieve a symptom (pain usually) Foote, 2005

43. Surgical Treatment Options • Treatment – Aim is to improve quality of life, enhance functioning. • Minimize damage • Restoration of function • Are they a candidate for: • Open surgical repair (less favorable) • Vertebroplasty • Balloon kyphoplasty

44. Therapy: Recap • Analgesics • Systemic tumor therapy • Bisphosphonates • Radiation • External beam • Radiopharmaceuticals • Surgery

45. Vertebroplasty and Balloon Kyphoplasty Indications Uncontrolled severe back pain from micro-motion and inflammation Tumor infiltrated vertebrae at risk for instability, collapse, and fracture Poor quality of life related to limited physical mobility Stabilization of vertebral integrity (to some extent you reduce the fracture) Alberico, 2007; Fourney, 2003

46. Vertebroplasty • Augmentation of vertebral compression fractures with polymethylmethacrylate • Uses pressure to introduce the material • Used successfully to treat pain • This technique does not attempt to restore the height of the collapsed vertebral body • Higher leakage rate than kyphoplasty, but the symptomatic leakage rates are the same. • Dudeney, 2002

47. Procedure Animations

48. Vertebroplasty

49. Balloon Kyphoplasty

50. Vertebroplasty and Balloon Kyphoplasty Contraindications Coagulation disorders Unstable fractures or complete vertebral collapse (vertebra plana) Cord compression Severe canal stenosis without cord compression Active infection requiring IV antibiotics Fourney et al., 2003; Masala et al., 2005