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J KMA Special Issue Chung Soo Han, MD Department of Orthopaedic Surgery, Kyung Hee University College of Medicine E mail : cshan1129@yahoo.co.kr J Korean Med Assoc 2006; 49(12): 1097-1109J Korean Med Assoc 2006; 49(10): 773-80 Abstract M etastatic bone tumor is a clinical challenge to most orthopaedic surgeons, and physicians. The bone lesions present pain, can progress to pathologic fractures, and cause neurologic deficits. The adequate treatment for the lesions can mean the difference between good and poor quality of life during their remaining time. The goals of the treatment are relief of pain, preservation of function, and maintenance of independence. In orthopaedic field, the goals include prophylactic fixation of metastatic deposits when there is a risk of fracture, stabilization or reconstruction after pathological fracture, and decompression the spinal cord and nerve roots and/or stabilization the spine. To achieve the goals, we should understand the evaluation methods, a pathogenesis of metastasis and the characters of the specific metastatic site. Finally we should have a knowledge about the treatment strategy and understand what the indications of operative treatment are and which conservative managements is correct for the metastatic bone lesions. It is important to consider the type of primary cancer, location of metastasis, extent of disease, expected patient life span, comorbidities, and level of pain when making treatment recommendations. New discoveries and modifications of existing treatments such as percutaneous stabilization of spinal compression fractures and the use of bisphosphonates may decrease the need for invasive surgical management of metastatic bone lesions in the future. Metastatic bone disease should be approached systematically by multidisciplinary team that has various treatment options, and then quality of life of the patients can be improved during their remaining life span. All the doctors participating in the treatment should try to do their best to get an optimal goal, even though the patients should be informed clearly that the treatments may not be curative. Keywords : Metastatic bone tumor; Treatment options 1097

Han CS Location of primary neoplasm producing metastatic bone lesions Primary site No. of lesions(%) Breast 2,020 (40) Lung 2,646 (13) Prostate 2,296 (6) Kidney 2,284 (6) Gastrointestinal tract 2,255 (5) Bladder 2,160 (3) Thyroid 2,110 (2) Total 5,006 Rothman Simone The Spine, 5th ed. Elsevier, 2006: 1248 1098

Radiologic features of metastatic bone lesion Feature Primary lesion Osteolytic Lung, Thyroid, Kidney, Colon Osteoblastic Prostate, Bladder, Stomach Mixed Breast 1099

Han CS Predicting the risk of pathologic fracture Points 1 2 3 Image Blastic Mixed Lytic Size <1 / 3 1 / 3 to 2 / 3 >2 / 3 Site Upper extremity Lower extremity Peritrochanteric Pain Mild Moderate Mechanical Clin Orthop 1989; 249: 256-64 1100

A (A) Osteolytic lesion associated with pathologic fracture was found in femoral neck of 48 year old female patient who had chemotherapy for breast cancer. It was proved as being a bone metastasis from breast cancer. (B) Acetabulum was intact and hemiarthroplasty was performed. B 1101

Han CS A B C (A) A 50 year old female patient who had hepatoma showed osteolytic lesion associated with pathologic fracture in left subtrochanteric area. Then reconstruction intramedullary device was applied. (B) Refracture occurred associated with metal failure of reconstruction intramedullary device at postoperative 23 months. (C) Proximal femoral replacement was performed via tumor prosthesis. 1102

A (A) A pathologic fracture occurred in osteolytic lesion of left femoral shaft of 53 year old male patient who had renal cell cancer (B) An intramedullary device was inserted in the femur B 1103

Han CS A B C (A) 76 year old female patient complaint severe back pain and progressive dysuria and weakness of lower extremities. Her third thoracic vertebra showed compression fracture in X ray(black arrow) (B) In MRI, the third thoracic vertebral lesion that had homogenous low signal intensity and disrupted end plates compressed spinal cord and it was found through various work-up that she had lung cancer (C) Her spinal cord was decompressed via en bloc spondylectomy of third thoracic vertebra and her vertebra was stabilized via posterior instrumentation and mesh cage 1104

Tokuhashi's scoring system for spinal metastasis Characteristic Score General condition (performance status) Poor (PS 10 40%) 0 Moderate (PS 50 70%) 1 Good (PS 80 100%) 2 No. of extraspinal bone metastases foci 3 0 1 2 1 0 2 No. of metastases in the vertebral body 3 0 2 1 1 2 Metastases to the major internal organs Unremovable 0 Removable 1 No metastases 2 Primary site of the cancer Lung, osteosarcoma, stomach, bladder, esophagus, pancreas 0 Liver, gallbladder, unidentified 1 Others 2 Kidney, uterus 3 Rectum 4 Thyroid, breast, prostate, carcinoid tumor 5 Palsy Complete (Frankel A, B) 0 Incomplete (Frankel C, D) 1 None (Frankel E) 2 Criteria of predicted prognosis: Total Score (TS)0 8=>6 mo; TS 9 11= 6 mo; TS 12 15= 1yr Spine 2005; 30(19): 2186-91 1105

Han CS Eur Rev Med Pharmacol Sci 2004; 8(6): 265-74 1106

Cancer Institute Hospital, Japan bone Joint Surg Am 1993; 75; 1276-81 5. Paget S. The distribution of secondary growths in cancer of the breast. Lancet 1889; 1: 571-73 6. Ewing J, ed. Metastasis, in Neoplastic Diseases: A Treatise on Tumor, 3rd ed. Philadelphia: WB Saunders, 1928: 77-89 1. Dahlin DC. Bone Tumors: General Aspects and Data on 6,221 Cases, 3rd ed. Springfield, IL, Charles C Thomas, 1978 2. Jemal A, Thomas A, Murray T, Thun M. Cancer statistics, 2002. CA cancer J Clin 2002; 52: 23-47 3. Frassica FJ, Gitelis S, Sim FH. Metastatic bone disease: General principles, pathophysiology, evaluation, and biopsy. Instr Course Lect 1992; 41: 293-300 4. Rougraff BT, Kneisl JS, Simon MA. Skeletal metastases of unknown origin: A prospective study of a diagnotic strategy. J 7. ST Canale. Campbell's operative orthopaedics, 10th ed. Mosby, 2003: 848 8. Clohisy DR, Palkert D, Ramnaraine ML, Pekurovsky I, Oursler MJ. Human breast cancer induces osteoclast activation and increases the number of osteoclast at sites of tumor osteolysis. J Orthop Res 1996; 14: 396-402 9. Beals RK, Lawton GD, Snell WE. Prophylactic internal fixation of the femur in metastatic breast cancer. Cancer 1971; 28: 1350-54 1107

Han CS 10. Mirels H. Metastatic disease in long bones: A proposed scoring system for diagnosing impending pathologic fractures. Clin Orthop 1989; 249: 256-64 11. Katzer A, Meenen NM, Grabbe F, Reuger JM. Surgery of skeletal metastases. Arch Orthop Trauma Surg 2002; 122: 251-8 12. Redmond BJ, Biermann JS, Blasier RB. Interlocking intramedullary nailing of pathological fractures of the shaft of the humerus. J Bone Joint Surg Am 1996; 78: 891-6 13. Damron TA, Sim FH, Shives TC, An KN, Rock MG, Pritchard DJ. Intercalary spacers in the treatment of segmentally destructive diaphyseal humeral lesions in disseminated malignancies. Clin Othop 1996; 324: 233-43 14. Dijkstra S, Stapert J, Boxma H, Wiggers T. Treatment of pathological fractures of the humeral shaft due to bone metastases: A comparison of intramedullay locking nail and plate osteosynthesis with adjunctive bone cement. Eur J Surg Oncol 1996; 22: 621-6 15. Harrington KD. The management of acetabular insufficiency secondary to metastatic malignant disease. J Bone Joint Surg Am 1981; 63: 653-64 16. Marco RA, Sheth DS, Boland PJ, et al. Functional and oncological outcome of acetabular reconstruction for the treatment of metastatic disease. J Bone Joint Surg Am 2000; 82: 642-51 17. Vena VE, Hsu J, Rosier RN, O'Keefe RJ. Pelvic reconstruction for severe periacetabular metastatic disease. Clin Orthop 1999; 362: 171-80 18. Yazawa Y, Frassica FJ, Chao EY, Pritchard DJ, Sim FH, Shives TC. Metastatic bone disease: A study of the surgical treatment of 166 pathologic humeral and femoral fractures. Clin Orthop 1990; 251: 213-9 19. Lane JM, Sculco TP, Zolan S. Treatment of pathological fractures of the hip by endoprosthetic replacement. J Bone Joint Surg Am 1980; 62: 954-9 20. Papagelopoulos PJ, Galanis EC, Greipp PR, Sim FH. Prosthetic hip replacement for pathologic or impending pathologic fractures in myeloma. Clin Orthop 1997; 341: 192-205 21. Behr JT, Dobozi WR, Badrinath K. The treatment of pathologic and impending pathologic fractures of the proximal femur in the elderly. Clin Orthop 1985; 198: 173-8 22. Ward WG, Spang J, Howe D, Gordan S. Femoral recon nails for metastatic disease: Indications, technique, and results, Am J Orthop 2000; 29(S9): 34-42 23. Weikert DR, Schwartz HS. Intramedullary nailing for impending pathological subtrochanteric fractures. J Bone Joint Surg Br 1991; 73: 668-70 24. Favorito PJ, McGrath BE. Impending or completed pathologic femur fracruters treated with intramedullary hip screws. Orthopedics 2001; 24: 359-63 25. Sim FH, Chao EY. Hip salvage by proximal femoral replacement. J Bone Joint Surg Am 1981; 63: 1228-39 26. Healey JH, Lane JM. Treatment of pathologic fractures of the distal femur with the Zickel supracondylar nail. Clin Orthop 1990; 250: 216-20 27. De Geeter K, Reynders P. Samson I, Broos PL. Metastatic fractures of the tibia. Acta Orthop Belg 2001; 67: 54-9 28. Hattrup SJ, Amadio PC, Sim FH, Lombardi RM. Metastatic tumors of the foot and ankle. Foot Ankle 1988; 8: 243-7 29. Boland PJ, Lane JM, Sundaresan N. Metastatic disease of the spine. Clin Orthop 1982; 169: 95-102 30. Suen KC, Lau LL, Yermakov V. Cancer and old age. An autopsy study of 3,535 patients over 65 years old. Cancer 1974; 33: 1108

1164-8 31. Galasko CS, Sylvester BS. Back pain in patients treated for malignant tumours. Clin Oncol 1978; 4: 273-83 32. Gilbert RW, Kim JH, Posner JB. Epidural spinal cord compression from metastatic tumor: Diagnosis and treatment. Ann Neurol 1978; 3: 40-51 33. Weill A, Chiras J, Simon JM, Rose M, Sola Martinez T, Enkaoua E. Spinal metastases: Indications for and results of percutaneous injection of acrylic surgical cement. Radiology 1996; 199: 241-7 34. Harrington KD. Metastatic disease of the spine. J Bone Joint Surg Am 1986; 68: 1110-5 35. Arcangeli G, Micheli A, Arcangeli F, et al. The responsiveness of bone metastases to radiotherapy: The effect of site, histology and radiation dose on pain relief. Radiolther Oncol 1989; 14: 95-101 36. Coleman RE. Management of bone metastases. Oncologist 2000; 5: 463-70 37. Crawford ED, Eisenberger MA, McLeod DG, et al. A controlled trial of leuprolide with and without flutamide in prostatic carcinoma. N Engl J Med 1989; 321: 419-24 38. Tomita K, Kawahara N, Kobayashi T, Yoshida A, Murakami H, Akamaru T. Surgical strategy for spinal metastases. Spine 2001 1; 26: 298-306 Peer Reviewer Commentary 1109