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Protocol of surgical treatment of long bone pathological fractures
Injury, Int. J. Care Injured 41 (2010) 1161–1167
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Protocol of surgical treatment of long bone pathological fractures Pietro Ruggieri *, Andreas F. Mavrogenis, Roberto Casadei, Costantino Errani, Andrea Angelini, Teresa Calabro`, Elisa Pala, Mario Mercuri Department of Orthopaedics, Istituto Ortopedico Rizzoli, University of Bologna, Bologna, Italy
A R T I C L E I N F O
A B S T R A C T
Keywords: Bone tumours Metastatic bone disease Pathological fractures Chemotherapy Limb salvage surgery Radiation therapy Amputation
Long bone pathological fractures in patients with primary and metastatic bone tumours are difficult to treat and their management may alter the prognosis of the disease and jeopardize survival. The aim of this article was to review the relevant studies reporting on the management of tumour patients with pathological fractures of the long bones, to discuss the most suitable approach in these patients, to highlight specific treatment recommendations, and finally based on this analysis and our clinical practice, to propose a treatment algorithm for decision making and treatment. ß 2010 Elsevier Ltd. All rights reserved.
Introduction Pathological long bones fractures in patients with primary and metastatic bone tumours posses many difficulties to the most experienced surgeons. Their management may alter prognosis, affecting both the quality of life and survival of the patients.3 Cortical bone destruction and loss of bone matrix,25 mechanical weakness of bone caused by biopsy, and post-chemotherapy tumour necrosis contribute to the occurrence of pathological fractures.15,25,39 Formation of haematoma may contaminate the adjacent joint, soft tissue, nerves and vessels. Damage to the microcirculation may favour distant haematogenous dissemination of the tumour.27,29,60,79 The most common site for long bone pathological fractures is the femur, followed by the humerus and the tibia.19,31,77,78,83 Aggressive benign bone tumours and tumour-like conditions including fibrous dysplasia, simple bone cysts, aneurysmal bone cyst and giant cell tumour have a high risk of pathological fracture, especially in the proximal femur.31,42,43,67,68 The incidence of pathological fractures in these patients at the time of diagnosis is approximately 12%.21,54 The incidence of long bone pathological fracture in patients with primary bone sarcomas ranges between 5% and 10%.18,44,78 In children and young adults, osteosarcoma and Ewing’s sarcoma are
* Corresponding author at: Department of Orthopaedics, University of Bologna, Orthopaedic Oncology Service, Istituto Ortopedico Rizzoli, Via Di Barbiano 1/10, 40136 Bologna, Italia. Tel.: +39 051 6366460/3333266234; fax: +39 051 6366540. E-mail address: [email protected] (P. Ruggieri). 0020–1383/$ – see front matter ß 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.injury.2010.09.018
the common primary bone tumours that may present with a pathological fracture.44 In osteosarcoma, the diaphyseal location, the large dimensions, the osteolytic radiographic pattern, and the telangiectatic and fibroblastic types are the most important risk factors for pathological fractures.1,3,34,40,65 In Ewing’s sarcoma, pathological fractures have been associated with the effect of radiation therapy that further weakens the bone.18,29,51,79 In the elderly, local recurrence of a primary bone tumour and secondary sarcomas including pagetic and post-irradiation sarcomas are the most common sarcomas that may present with a pathological fracture, occurring as late as 20 years after the initial diagnosis.18,24,27,35,49,79 The incidence of a long bone pathological fracture in skeletal metastases has been reported to be between 10% and 29%.10,16,19,83,84 The overall union rate for these fractures can be as low as 35% of the cases whereas in lung cancer patients, fracture healing rarely occurs.30 Even when healing is possible, it is often delayed, placing the load-bearing implant at high risk for failure. Therefore, prediction of impending pathological fractures in patients with metastatic bone disease and rigid fixation or reconstruction of sustained fractures is important.20,36,45,55,80 In the past, the occurrence of a pathological fracture through bone sarcomas or skeletal metastases was an absolute contraindication for limb salvage; in this setting, treatment traditionally consisted of amputation proximal to the most superior aspect of the fracture haematoma.26,44,48 Currently, the decision for limb salvage surgery should be reconsidered.13,23,44,48,57,64,66 Multiagent chemotherapy, advanced surgical approaches and radiation therapy have resulted in improved local control and survival in patients with bone tumours complicated by pathological
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fractures.1,29,32,35,53,65,79,82 In this article, we present our experience and current practice in bone tumour patients with long bone pathological fractures and provide an algorithm for their management. Staging The evaluation of a patient with a pathological fracture through a bone lesion should begin with standard anteroposterior and lateral radiographs of the affected limb. A technetium bone scan should be used to screen for additional bony lesions. A skeletal survey may be helpful if myeloma is suspected. The imaging workup should be completed with computed tomography scan of the chest, abdomen and pelvis. Screening laboratory studies should include complete blood cell count, erythrocyte sedimentation rate, biochemistry values including liver function, creatinine, calcium, phosphorus, lactate dehydrogenase, alkaline phosphatase and prostate-specific antigen (if male), serum and urine immunoelectrophoresis, and coagulation studies.61,72 Oncological staging should be accomplished with biopsy. Biopsy should constantly be performed for both primary and secondary bone tumours. The diagnosis should always be confirmed in patients with a history of cancer and an isolated metastasis, and in contrary, patients with a destructive long bone lesion but no history of cancer should not have fixation without a biopsy assuming that a metastasis is present. Although this assumption may be correct in more than 98% of the cases, in the remaining patients a sarcoma will be present, and amputation will be necessitated because of extensive tumour contamination after inappropriate treatment.28 Trocar or open biopsy can be performed according to the principles of musculoskeletal tumour biopsy. The biopsy tract should be placed in a location that will allow wide resection with a surrounding cuff of tumour-free tissue, and will not compromise limb salvage surgery. Open biopsy incision should be in a direct approach in line with the projected incision if a resection is to be performed following the diagnosis of malignancy, [()TD$FIG]
should be vertical, muscle splitting, and good hemostasis should be achieved before wound closure. The role of the treating surgeon, radiologist and pathologist is paramount in biopsy evaluation. The biopsy tract should be carefully planned in adequate imaging studies of the lesion by an experienced radiologist, and should be performed by the orthopaedic oncologist who will also perform the definitive surgical procedure. The biopsy specimen should be evaluated by an experienced pathologist; fracture haematoma and callus may have similar histology to osteosarcoma. Interpretation of frozen sections can only be done safely by an experienced bone tumour pathologist with good communication between the surgeon, the radiologist, and the pathologist. When frozen pathology findings are unusual or not diagnostic, surgery should be delayed until final pathology is available. Treatment Following biopsy, stabilization of the fracture and oncologically oriented surgical treatment should be performed. Attention should be given to the initial displacement, stability and location of the pathological fracture.27 Brace or cast, or external fixation have been employed to stabilize the fracture whilst further therapy is undertaken.1,29,65,66,79 Although it has been reported that operative stabilization of pathological fractures in osteosarcoma patients did not influence local tumour control or overall survival from tumour-cell dissemination,65,66 we recommend brace or cast immobilization as the standard management in patients with pathological fractures in bone tumours. In patients with pathological fractures in primary bone sarcomas, chemotherapy should be given as primary treatment, followed by limb-salvage surgery if possible. Preoperative chemotherapy is important for local tumour control and can make limb-salvage surgery feasible in most patients.3,44,65,74 Occasionally, response to preoperative chemotherapy, tumour necrosis, decrease or regression of the soft-tissue mass and
Fig. 1. (A) Anteroposterior and (B) lateral radiograph, and (C) coronal T2-weighted magnetic resonance imaging of a 25-year-old woman with a distal femoral pathological fracture in telangiectatic osteosarcoma. (D) Anteroposterior and (E) lateral radiograph after wide resection and reconstruction with a modular rotating hinge knee megaprosthesis. Three cycles of preoperative chemotherapy and 13 cycles of postoperative chemotherapy using cisplatinum, adriamycin, ifosfamide and methotrexate were administered. At 5 years after diagnosis and treatment, the patient is alive without any evidence of local recurrence. A lung nodule is present without evidence of progression. Early knee stiffness required arthrolysis.
[()TD$FIG]
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Fig. 1. (Continued).
periosteal bone formation may induce fracture healing.29,44,65,74,85 A non-healing fracture during chemotherapy is probably associated with a chemotherapy-resistant tumour, and aggressive resection or amputation may be necessary to achieve adequate tumour control.29,79 Following preoperative chemotherapy, the lesion should be re-staged. The stability and displacement of the fracture should be evaluated in standard radiographs and magnetic resonance imaging. In patients with pathological fractures in skeletal metastases, determining prognosis and expected survival is important to establish further treatment. Patients with longer expected survival require a more aggressive treatment with wide resection,
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megaprosthetic reconstruction and postoperative radiation therapy. In contrary, patients with shorter expected survival may benefit from a less aggressive, less morbid treatment with rigid internal fixation and adjuvant radiation therapy.2,5,10,22,47,64,81 Since most of these patients have limited life expectancy, the goals of surgical treatment should be fracture stabilization and pain relief, early mobilization and restoration of limb function and weight-bearing, minimal surgical morbidity and perioperative complications, and ease of nursing care.4,6,16,38,45,62,80,83,84 In patients with pathological fractures in primary benign bone tumours, although wide resection is debatable in the context of benign tumour, it can be considered for some aggressive, stage 3 tumours.77 In addition, wide en bloc resection is known to provide the lowest local recurrence rate for aggressive giant cell tumours and aneurysmal bone cysts in expendable bones.8,11,12,17,33,52,59,77 However, most benign tumours presenting with pathological fractures are typically managed by intralesional surgery after fracture healing in cast immobilization. In patients with pathological fractures in primary bone sarcomas, if the tumour and the fracture haematoma can be resected with wide margins, limb-salvage surgery including en bloc, wide excision of the tumour and the fracture haematoma with preservation of the major nerves and vessels and the adjacent joint, and reconstruction may be possible.13,18,23,29,48,57 The type of reconstruction depends on age, expectations and daily activities of the patients, tumour location, and anticipated prognosis. Current options for reconstruction include arthrodesis, megaprostheses, and intercalary allografts or allograft composite prostheses.1,13,23,29,48,57,65,66,79 The indications for amputation must be individualized; in general, improper or infected biopsy sites, pathological fractures with large haematomas, poor response to preoperative chemotherapy, neurovascular or joint involvement by the tumour or fracture haematoma, excision of a great muscle unit that diminishes adequate function of the limb, and subcutaneous location of the bone such as the distal tibia should be considered indications for amputation.1 In patients with pathological fractures in skeletal metastases, wide resection is justified for solitary metastasis, ‘‘favorable’’ tumour histotype, good general condition and long free interval from treatment of primary cancer. In addition, metastatic disease in the proximal or distal femur or the proximal humerus, especially those involving the joint surface, are often best treated with wide resection and arthroplasty.38,56 However, in many cases, surgical treatment is intended for palliation. In this setting, minimizing the morbidity associated with an orthopaedic procedure is important. In the upper limb, conservative therapy may be an alternative, although nonoperative treatment of pathological fractures rarely leads to pain relief or return of function.28,38 Percutaneous osteoplasty46 and embolization9 have also been reported as a minimally invasive techniques for pathological fractures of long bones. Closed intramedullary fixation, supports the concept of minimal surgical morbidity over open reduction and internal fixation or megaprosthetic reconstruction, since the surgical technique is less aggressive, produces less morbidity, and facilitates rehabilitation.38,56 Closed intramedullary nailing is feasible in the presence of minimal bone destruction and intact segments of the long bone proximal and distal to the fracture. Open intramedullary nailing or plate and screws fixation with or without acrylic bone cement augmentation may be necessary for fractures with large areas of bone destruction.28,38,41,83 The disadvantages of open nailing include extensive dissection, bleeding from the tumour, and potential for delayed wound healing; plate fixation requires adequate cortical bone proximal and distal to the fracture.28 Reconstruction nails should be preferred in all cases to prophylactically stabilize the neck of femue and intertrochanteric proximal femoral region. We
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do not recommend retrograde femoral nails.28,38,41 In all cases, fixation should be rigid to allow for postoperative function. When rigid fixation cannot be achieved with internal fixation or the articular surfaces have been destroyed, resection of the diseased bone and reconstruction using acrylic cement,37,41,50 standard arthroplasty, megaprosthesis, intercalary spacer, allograft composite, or total joint replacement can be considered as alternative options.14,19,28,70,75,83 Megaprosthetic reconstruction is an effective method of achieving rigid fixation for patients with extensive bone disease or failed fixation devices.64,75,83 Although it requires more dissection and has more early complications such as infection, hematomas, and subluxation or dislocation, the risk of failure is small.14,19,28,64,70,83 Radiation therapy has shown variable results in patients with pathological fractures in primary bone sarcomas.29,32,79,82 External beam radiation therapy in patients with Ewing’s sarcoma who sustain a pathological fracture at presentation or during preoperative chemotherapy, is associated with a lower risk for local recurrence or distant metastases, because the Ewing’s sarcoma cells in the fracture haematoma are very radiosensitive, allowing the tumour bed around the fracture to be sterilized by the radiation.29,32,79,82 However, radiation therapy has not been successful in preventing local recurrence or distant metastases in patients with osteosarcoma.39 In patients with pathological fractures in skeletal metastases, external beam radiation therapy is necessary to prevent progressive bone destruction and loss of fixation following surgical treatment. Radiation therapy is used for radiosensitive tumours, mostly breast cancer, followed by multiple myeloma, lung, prostate and kidney cancer. Most radiation therapists administer fractionated doses of 20–40 Gy for 1–4 weeks.7,30,76 However, although local progression may be inhibited by radiation therapy in radiosensitive tumours, the risk of radiation-induced skeletal complications such as stress fractures and non-unions increases.7,30,83
[()TD$FIG]
Outcome The factors associated with improved outcome for patients with primary bone sarcomas complicated by pathological fractures are the response to chemotherapy, fracture union, wide resection, and response to radiation therapy.1,3,23,29,32,44,57,65,66,69,71,73,74,79,82 The factors associated with a worse prognosis are poor response to chemotherapy and local tumour recurrence. Fracture displacement and type of stabilization including open reduction and internal fixation versus closed treatment do not significantly affect the outcome.65 The local response to chemotherapy is indicative of a similar response of the subclinical disseminated disease.23 Fracture union during preoperative chemotherapy has been related to a favourable prognosis including increased overall and disease-free survival and decreased local recurrence rate.44,65,74 If wide resection is obtained, the rates of local recurrence are similar to those for limb-salvage surgery in general.1,3,29,57,65,73,79 Although amputation may be related to better eradication of the local tumour than limb-salvage, it does not influence the overall survival.1,29,57,79 Wide resection can still be achieved in the majority of patients without compromising survival, and the occurrence of a pathological fracture should no longer favour for amputation if adequate local resection can be performed after preoperative chemotherapy.57,65 In patients with pathological fractures in skeletal metastases, the presence of non-osseous metastases considerably deteriorates the prognosis.16,58,62 In addition, a better prognosis has been reported in patients with pathological fractures of the upper limb compared to those with fractures of the lower limb. Moreover, a longer median postoperative survival has been shown in patients with pathological fractures secondary to breast cancer compared to other types of primary tumours.62,63 The long survival after surgery is the most important risk factor for failure of the reconstruction or osteosynthesis of the pathological fracture
Fig. 2. (A) Anteroposterior radiograph of the right arm of a 75-year-old man with a pathological fracture of the humeral diaphysis in lung metastasis. (B) Indirect reduction and intramedullary nailing was done, followed by postoperative radiation therapy (30 Gy) and 5 cycles of chemotherapy. At 2 years postoperatively, the patient is alive with disease.
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secondary to disease progression, implant failure, or loss of fixation.28,86 This highlights the importance to identify the patients with a long expected survival and a good prognosis, for wide resection and megaprosthetic reconstruction, or rigid internal fracture fixation and augmentation of bone defects with acrylic cement.83 Authors’ recommendation After decades of treating tumour patients with different methods and approaches, the questions raised by this manuscript are still challenging. Surgeons should follow oncological principles in treating tumour patients. Referral to a specialized orthopaedic oncology centre is generally recommended. From a series of patients with primary benign and malignant bone tumours and skeletal metastases, we analysed the medical files of 122 patients with a pathological fracture of the upper and lower limb treated with internal fixation or resection and megaprosthetic reconstruction (unpublished data). In 55 patients, the pathological fracture occurred in primary bone tumours including osteosarcoma (16 patients), chondrosarcoma (6 patients), Ewing’s sarcoma (4 patients) fibrosarcoma, multiple myeloma and lymphoma (11 patients) and aggressive giant cell tumour of bone and aneurysmal bone cyst secondary to fibrous dysplasia (18 patients). In 74 patients the pathological fracture occurred in skeletal metastases. The mean age of the patients with pathological fractures in primary bone tumours was 65 years
[()TD$FIG]
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(range 33–81 years), and the mean age of the patients with pathological fractures in skeletal metastases was 68 years (range 49–93 years). In all patients, initial fracture stability was obtained with a brace or cast and preoperative staging and trocar biopsy was performed. Preoperative chemotherapy was administered in all patients with pathological fractures in primary bone sarcomas and in eight patients with pathological fractures in skeletal metastases with multiple metastatic bone lesions from breast cancer and adenocarcinoma grade 4. Preoperative radiation therapy was administered in six patients with pathological fractures in primary bone sarcomas. Wide resection and megaprosthetic reconstruction was carried out in all patients with pathological fractures in primary bone tumours, in 18 patients with proximal femoral pathological fractures in skeletal metastases and in 7 patients with humeral pathological fractures in skeletal metastases; intramedullary nailing using reconstruction nails was performed in 25 patients with humeral pathological fractures and 24 patients with femoral pathological fractures in skeletal metastases. Postoperative chemotherapy was administered in 14 patients with pathological fractures in primary bone sarcomas and in 7 patients with pathological fractures in skeletal metastases. Postoperative radiation therapy was administered in five patients with pathological fractures in primary bone sarcomas and in 63 patients with pathological fractures in skeletal metastases. Adjuvant selective embolization was done in 5 patients with skeletal metastases.
Fig. 3. Treatment algorithm for patients with pathological fractures in primary bone tumours and skeletal metastases. *When limb salvage is not feasible due to extent of lesion, neurovascular involvement, and/or massive contamination. **Radiation therapy rarely given; only if margins are not wide, or contaminated. ***Wide resection if fixation is not feasible. ****Wide resection only if fixation is not feasible due to extent of the lesion or meta-epiphyseal involvement. yChemotherapy in patients with skeletal metastases only if feasible depending on age, general condition and expected survival.
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At a mean follow-up of 80 months (range 1–275 months), 27% of the patients with primary bone tumours and 74% of the patients with skeletal metastases died of the disease. Although a discussion of the final results of our patients is outside the scope of this article, two patients with pathological fracture in primary bone sarcoma had local recurrence and required amputation (2/37 patients, distal femoral prostheses; 5.4%), and two patients had infection (2/ 55 patients, proximal and distal femoral prostheses; 3.6%). Amputation was necessary for local tumour progression in one patient with a femoral and one patient with a humeral pathological fracture in skeletal metastases (2/74 patients; 2.7%); both of these patients had intramedullary nail fixation. Failure of the osteosynthesis was not observed in any of the patients; one patient (1/ 18 patients; 5.5%) with a proximal femoral megaprosthetic reconstruction for a pathological fracture in skeletal metastases had aseptic loosening at 46 months, three patients (3/18 patients; 16%) had infection at 23 months, and one patient (1/18 patients; 5.5%) had dislocation of the prosthesis at 20 months after surgical treatment (Figs. 1 and 2). Based on the results of a large institutional study with great experience for the management of tumour patients, we propose a treatment algorithm that would be helpful for decision making and treatment of patients with long bone pathological fractures from primary and metastatic bone tumours (Fig. 3). Based on this analysis we apply these management guidelines to our patients. Treatment decision in these patients require complete staging and oncological principles. Initial fracture management should include cast immobilization or external fixation avoiding tumour-cell dissemination. Pathological fractures of the long bones in tumour patients should not be considered an absolute indication for amputation, since limb salvage surgery of patients with pathological fractures, particularly these that unite following chemotherapy, does not appear to increase the risk of local recurrence or death. Patients should be treated by preoperative chemotherapy followed by limb salvage surgery with wide margins, with or without radiation therapy. Tumours that are not sensitive to chemotherapy should not be amenable to limb-salvage surgery if pathological fractures have occurred. Tumour response to chemotherapy and radiation therapy, fracture union, and wide resection are the most significant predictive factors for overall survival and local disease control. Fracture displacement and type of stabilization do not significantly affect the outcome. Conflict of interest statement None of the authors have any financial and personal relationships with other people or organizations that could inappropriately influence (bias) their work. Role of the funding source There are no study sponsor for this paper and no sources of funding to acknowledge. References 1. Abudu A, Sferopoulos NK, Tillman RM, et al. The surgical treatment and outcome of pathological fractures in localised osteosarcoma. J Bone Joint Surg Br 1996;78:694–8. 2. Althausen P, Althausen A, Jennings LC, Mankin HJ. Prognostic factors and surgical treatment of osseous metastases secondary to renal cell carcinoma. Cancer 1997;80:1103–9. 3. Bacci G, Ferrari S, Longhi A, et al. Nonmetastatic osteosarcoma of the extremity with pathologic fracture at presentation: local and systemic control by amputation or limb salvage after preoperative chemotherapy. Acta Orthop Scand 2003;74(4):449–54. 4. Barwood SA, Wilson JL, Molnar PR, Choong PF. The incidence of cardiorespiratory and vascular dysfunction following intramedullary nail fixation of femoral metastasis. Acta Orthop Scand 2000;71:147–52.
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64. Scotti C, Camnasio F, Peretti GM, Fonatana F, Fraschini G. Modular prostheses in the treatment of proximal humerus metastases: review of 40 cases. J Orthop Traumatol 2008;9(1):5–10. 65. Scully SP, Ghert MA, Zurakowski D, et al. Pathologic fracture in osteosarcoma: prognostic importance and treatment implications. J Bone Joint Surg Am 2002;84A(1):49–57. 66. Scully SP, Temple HT, O’Keefe RJ, et al. The surgical treatment of patients with osteosarcoma who sustain a pathologic fracture. Clin Orthop Relat Res 1996;324:227–32. 67. Shih HN, Chen YJ, Huang TJ, Hsu KY, Hsu RWW. Treatment of fibrous dysplasia involving the proximal femur. Orthopedics 1998;21:1263–6. 68. Shih HN, Cheng CY, Chen YJ, Huang TJ, Hsu RWW. Treatment of the femoral neck and trochanteric benign lesions. Clin Orthop Relat Res 1996;328:220–6. 69. Shin KH, Rougraff BT, Simon MA. Oncologic outcome of primary bone sarcoma of the pelvis. Clin Orthop Relat Res 1994;304:207–17. 70. Sim FH, Frassica FJ, Chao EY. Orthopaedic management using new devices and prostheses. Clin Orthop Relat Res 1995;312:160–72. 71. Simon MA, Aschiliman MA, Thomas N, Mankin HJ. Limb-salvage treatment versus amputation for osteosarcoma of the distal end of the femur. J Bone Joint Surg Am 1986;68A:1331–7. 72. Simon MA, Nachman J. The clinical utility of pre-operative therapy for sarcomas. J Bone Joint Surg Am 1986;68:1458–63. 73. Springfield DS, Pagliarulo C. Fractures of long bones previously treated for Ewing’s sarcoma. J Bone Joint Surg Am 1985;67:477–81. 74. Thompson RC JJr, Pritchard DJ, Nelson TE. Pathologic fractures in osteosarcoma. J Bone Joint Surg Br 1992;74B(SIII):277. 75. Tong D, Gillick L, Hendrickson FR. The palliation of symptomatic osseous metastases: final results of the Study by the Radiation Therapy Oncology Group. Cancer 1982;50(5):893–9. 76. Townsend PW, Rosenthal HG, Smalley SR, et al. Impact of postoperative radiation therapy and other perioperative factors on outcome after orthopedic stabilization of impending or pathologic fractures due to metastatic disease. J Clin Oncol 1994;12:2345–50. 77. Turcotte RE. Giant cell tumor of bone. Orthop Clin North Am 2006;37:35–51. 78. Vlasak R, Sim FH. Ewing’s sarcoma. Orthop Clin North Am 1996;27:591–603. 79. Wagner LM, Neel MD, Pappo AS, et al. Fractures in pediatric Ewing sarcoma. J Pediatric Hematol Oncol 2001;23(9):568–71. 80. Ward WG, Holsenbeck S, Dorey FJ, et al. Metastatic disease of the femur: surgical treatment. Clin Orthop Relat Res 2003;415:230–44. 81. Weber KL, Lewis VO, Randall RL, et al. An approach to the management of the patient with metastatic bone disease. Instr Course Lect 2004;53:663–76. 82. Weber KL, Sim FH. Ewing’s sarcoma: presentation and management. J Orthop Sci 2001;6:366–71. 83. Wedin R, Bauer HC, Wersa¨ll P. Failures after operation for skeletal metastatic lesions of long bones. Clin Orthop Relat Res 1999;358:128–39. 84. Wedin R, Bauer HC. Surgical treatment of skeletal metastatic lesions of the proximal femur. Endoprosthesis or reconstruction nail? J Bone Joint Surg 2005;87B:1653–7. 85. Wunder JS, Paulian G, Huvos AG, et al. The histological response to chemotherapy as a predictor of the oncological outcome of operative treatment of Ewing sarcoma. J Bone Joint Surg Am 1998;80(7):1020–33. 86. Yazawa Y, Frassica FJ, Chao EY, et al. Metastatic bone disease: a study of the surgical treatment of 166 pathologic humeral and femoral fractures. Clin Orthop Relat Res 1990;251:213–9.
Contents lists available at ScienceDirect
Injury journal homepage: www.elsevier.com/locate/injury
Protocol of surgical treatment of long bone pathological fractures Pietro Ruggieri *, Andreas F. Mavrogenis, Roberto Casadei, Costantino Errani, Andrea Angelini, Teresa Calabro`, Elisa Pala, Mario Mercuri Department of Orthopaedics, Istituto Ortopedico Rizzoli, University of Bologna, Bologna, Italy
A R T I C L E I N F O
A B S T R A C T
Keywords: Bone tumours Metastatic bone disease Pathological fractures Chemotherapy Limb salvage surgery Radiation therapy Amputation
Long bone pathological fractures in patients with primary and metastatic bone tumours are difficult to treat and their management may alter the prognosis of the disease and jeopardize survival. The aim of this article was to review the relevant studies reporting on the management of tumour patients with pathological fractures of the long bones, to discuss the most suitable approach in these patients, to highlight specific treatment recommendations, and finally based on this analysis and our clinical practice, to propose a treatment algorithm for decision making and treatment. ß 2010 Elsevier Ltd. All rights reserved.
Introduction Pathological long bones fractures in patients with primary and metastatic bone tumours posses many difficulties to the most experienced surgeons. Their management may alter prognosis, affecting both the quality of life and survival of the patients.3 Cortical bone destruction and loss of bone matrix,25 mechanical weakness of bone caused by biopsy, and post-chemotherapy tumour necrosis contribute to the occurrence of pathological fractures.15,25,39 Formation of haematoma may contaminate the adjacent joint, soft tissue, nerves and vessels. Damage to the microcirculation may favour distant haematogenous dissemination of the tumour.27,29,60,79 The most common site for long bone pathological fractures is the femur, followed by the humerus and the tibia.19,31,77,78,83 Aggressive benign bone tumours and tumour-like conditions including fibrous dysplasia, simple bone cysts, aneurysmal bone cyst and giant cell tumour have a high risk of pathological fracture, especially in the proximal femur.31,42,43,67,68 The incidence of pathological fractures in these patients at the time of diagnosis is approximately 12%.21,54 The incidence of long bone pathological fracture in patients with primary bone sarcomas ranges between 5% and 10%.18,44,78 In children and young adults, osteosarcoma and Ewing’s sarcoma are
* Corresponding author at: Department of Orthopaedics, University of Bologna, Orthopaedic Oncology Service, Istituto Ortopedico Rizzoli, Via Di Barbiano 1/10, 40136 Bologna, Italia. Tel.: +39 051 6366460/3333266234; fax: +39 051 6366540. E-mail address: [email protected] (P. Ruggieri). 0020–1383/$ – see front matter ß 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.injury.2010.09.018
the common primary bone tumours that may present with a pathological fracture.44 In osteosarcoma, the diaphyseal location, the large dimensions, the osteolytic radiographic pattern, and the telangiectatic and fibroblastic types are the most important risk factors for pathological fractures.1,3,34,40,65 In Ewing’s sarcoma, pathological fractures have been associated with the effect of radiation therapy that further weakens the bone.18,29,51,79 In the elderly, local recurrence of a primary bone tumour and secondary sarcomas including pagetic and post-irradiation sarcomas are the most common sarcomas that may present with a pathological fracture, occurring as late as 20 years after the initial diagnosis.18,24,27,35,49,79 The incidence of a long bone pathological fracture in skeletal metastases has been reported to be between 10% and 29%.10,16,19,83,84 The overall union rate for these fractures can be as low as 35% of the cases whereas in lung cancer patients, fracture healing rarely occurs.30 Even when healing is possible, it is often delayed, placing the load-bearing implant at high risk for failure. Therefore, prediction of impending pathological fractures in patients with metastatic bone disease and rigid fixation or reconstruction of sustained fractures is important.20,36,45,55,80 In the past, the occurrence of a pathological fracture through bone sarcomas or skeletal metastases was an absolute contraindication for limb salvage; in this setting, treatment traditionally consisted of amputation proximal to the most superior aspect of the fracture haematoma.26,44,48 Currently, the decision for limb salvage surgery should be reconsidered.13,23,44,48,57,64,66 Multiagent chemotherapy, advanced surgical approaches and radiation therapy have resulted in improved local control and survival in patients with bone tumours complicated by pathological
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fractures.1,29,32,35,53,65,79,82 In this article, we present our experience and current practice in bone tumour patients with long bone pathological fractures and provide an algorithm for their management. Staging The evaluation of a patient with a pathological fracture through a bone lesion should begin with standard anteroposterior and lateral radiographs of the affected limb. A technetium bone scan should be used to screen for additional bony lesions. A skeletal survey may be helpful if myeloma is suspected. The imaging workup should be completed with computed tomography scan of the chest, abdomen and pelvis. Screening laboratory studies should include complete blood cell count, erythrocyte sedimentation rate, biochemistry values including liver function, creatinine, calcium, phosphorus, lactate dehydrogenase, alkaline phosphatase and prostate-specific antigen (if male), serum and urine immunoelectrophoresis, and coagulation studies.61,72 Oncological staging should be accomplished with biopsy. Biopsy should constantly be performed for both primary and secondary bone tumours. The diagnosis should always be confirmed in patients with a history of cancer and an isolated metastasis, and in contrary, patients with a destructive long bone lesion but no history of cancer should not have fixation without a biopsy assuming that a metastasis is present. Although this assumption may be correct in more than 98% of the cases, in the remaining patients a sarcoma will be present, and amputation will be necessitated because of extensive tumour contamination after inappropriate treatment.28 Trocar or open biopsy can be performed according to the principles of musculoskeletal tumour biopsy. The biopsy tract should be placed in a location that will allow wide resection with a surrounding cuff of tumour-free tissue, and will not compromise limb salvage surgery. Open biopsy incision should be in a direct approach in line with the projected incision if a resection is to be performed following the diagnosis of malignancy, [()TD$FIG]
should be vertical, muscle splitting, and good hemostasis should be achieved before wound closure. The role of the treating surgeon, radiologist and pathologist is paramount in biopsy evaluation. The biopsy tract should be carefully planned in adequate imaging studies of the lesion by an experienced radiologist, and should be performed by the orthopaedic oncologist who will also perform the definitive surgical procedure. The biopsy specimen should be evaluated by an experienced pathologist; fracture haematoma and callus may have similar histology to osteosarcoma. Interpretation of frozen sections can only be done safely by an experienced bone tumour pathologist with good communication between the surgeon, the radiologist, and the pathologist. When frozen pathology findings are unusual or not diagnostic, surgery should be delayed until final pathology is available. Treatment Following biopsy, stabilization of the fracture and oncologically oriented surgical treatment should be performed. Attention should be given to the initial displacement, stability and location of the pathological fracture.27 Brace or cast, or external fixation have been employed to stabilize the fracture whilst further therapy is undertaken.1,29,65,66,79 Although it has been reported that operative stabilization of pathological fractures in osteosarcoma patients did not influence local tumour control or overall survival from tumour-cell dissemination,65,66 we recommend brace or cast immobilization as the standard management in patients with pathological fractures in bone tumours. In patients with pathological fractures in primary bone sarcomas, chemotherapy should be given as primary treatment, followed by limb-salvage surgery if possible. Preoperative chemotherapy is important for local tumour control and can make limb-salvage surgery feasible in most patients.3,44,65,74 Occasionally, response to preoperative chemotherapy, tumour necrosis, decrease or regression of the soft-tissue mass and
Fig. 1. (A) Anteroposterior and (B) lateral radiograph, and (C) coronal T2-weighted magnetic resonance imaging of a 25-year-old woman with a distal femoral pathological fracture in telangiectatic osteosarcoma. (D) Anteroposterior and (E) lateral radiograph after wide resection and reconstruction with a modular rotating hinge knee megaprosthesis. Three cycles of preoperative chemotherapy and 13 cycles of postoperative chemotherapy using cisplatinum, adriamycin, ifosfamide and methotrexate were administered. At 5 years after diagnosis and treatment, the patient is alive without any evidence of local recurrence. A lung nodule is present without evidence of progression. Early knee stiffness required arthrolysis.
[()TD$FIG]
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Fig. 1. (Continued).
periosteal bone formation may induce fracture healing.29,44,65,74,85 A non-healing fracture during chemotherapy is probably associated with a chemotherapy-resistant tumour, and aggressive resection or amputation may be necessary to achieve adequate tumour control.29,79 Following preoperative chemotherapy, the lesion should be re-staged. The stability and displacement of the fracture should be evaluated in standard radiographs and magnetic resonance imaging. In patients with pathological fractures in skeletal metastases, determining prognosis and expected survival is important to establish further treatment. Patients with longer expected survival require a more aggressive treatment with wide resection,
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megaprosthetic reconstruction and postoperative radiation therapy. In contrary, patients with shorter expected survival may benefit from a less aggressive, less morbid treatment with rigid internal fixation and adjuvant radiation therapy.2,5,10,22,47,64,81 Since most of these patients have limited life expectancy, the goals of surgical treatment should be fracture stabilization and pain relief, early mobilization and restoration of limb function and weight-bearing, minimal surgical morbidity and perioperative complications, and ease of nursing care.4,6,16,38,45,62,80,83,84 In patients with pathological fractures in primary benign bone tumours, although wide resection is debatable in the context of benign tumour, it can be considered for some aggressive, stage 3 tumours.77 In addition, wide en bloc resection is known to provide the lowest local recurrence rate for aggressive giant cell tumours and aneurysmal bone cysts in expendable bones.8,11,12,17,33,52,59,77 However, most benign tumours presenting with pathological fractures are typically managed by intralesional surgery after fracture healing in cast immobilization. In patients with pathological fractures in primary bone sarcomas, if the tumour and the fracture haematoma can be resected with wide margins, limb-salvage surgery including en bloc, wide excision of the tumour and the fracture haematoma with preservation of the major nerves and vessels and the adjacent joint, and reconstruction may be possible.13,18,23,29,48,57 The type of reconstruction depends on age, expectations and daily activities of the patients, tumour location, and anticipated prognosis. Current options for reconstruction include arthrodesis, megaprostheses, and intercalary allografts or allograft composite prostheses.1,13,23,29,48,57,65,66,79 The indications for amputation must be individualized; in general, improper or infected biopsy sites, pathological fractures with large haematomas, poor response to preoperative chemotherapy, neurovascular or joint involvement by the tumour or fracture haematoma, excision of a great muscle unit that diminishes adequate function of the limb, and subcutaneous location of the bone such as the distal tibia should be considered indications for amputation.1 In patients with pathological fractures in skeletal metastases, wide resection is justified for solitary metastasis, ‘‘favorable’’ tumour histotype, good general condition and long free interval from treatment of primary cancer. In addition, metastatic disease in the proximal or distal femur or the proximal humerus, especially those involving the joint surface, are often best treated with wide resection and arthroplasty.38,56 However, in many cases, surgical treatment is intended for palliation. In this setting, minimizing the morbidity associated with an orthopaedic procedure is important. In the upper limb, conservative therapy may be an alternative, although nonoperative treatment of pathological fractures rarely leads to pain relief or return of function.28,38 Percutaneous osteoplasty46 and embolization9 have also been reported as a minimally invasive techniques for pathological fractures of long bones. Closed intramedullary fixation, supports the concept of minimal surgical morbidity over open reduction and internal fixation or megaprosthetic reconstruction, since the surgical technique is less aggressive, produces less morbidity, and facilitates rehabilitation.38,56 Closed intramedullary nailing is feasible in the presence of minimal bone destruction and intact segments of the long bone proximal and distal to the fracture. Open intramedullary nailing or plate and screws fixation with or without acrylic bone cement augmentation may be necessary for fractures with large areas of bone destruction.28,38,41,83 The disadvantages of open nailing include extensive dissection, bleeding from the tumour, and potential for delayed wound healing; plate fixation requires adequate cortical bone proximal and distal to the fracture.28 Reconstruction nails should be preferred in all cases to prophylactically stabilize the neck of femue and intertrochanteric proximal femoral region. We
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do not recommend retrograde femoral nails.28,38,41 In all cases, fixation should be rigid to allow for postoperative function. When rigid fixation cannot be achieved with internal fixation or the articular surfaces have been destroyed, resection of the diseased bone and reconstruction using acrylic cement,37,41,50 standard arthroplasty, megaprosthesis, intercalary spacer, allograft composite, or total joint replacement can be considered as alternative options.14,19,28,70,75,83 Megaprosthetic reconstruction is an effective method of achieving rigid fixation for patients with extensive bone disease or failed fixation devices.64,75,83 Although it requires more dissection and has more early complications such as infection, hematomas, and subluxation or dislocation, the risk of failure is small.14,19,28,64,70,83 Radiation therapy has shown variable results in patients with pathological fractures in primary bone sarcomas.29,32,79,82 External beam radiation therapy in patients with Ewing’s sarcoma who sustain a pathological fracture at presentation or during preoperative chemotherapy, is associated with a lower risk for local recurrence or distant metastases, because the Ewing’s sarcoma cells in the fracture haematoma are very radiosensitive, allowing the tumour bed around the fracture to be sterilized by the radiation.29,32,79,82 However, radiation therapy has not been successful in preventing local recurrence or distant metastases in patients with osteosarcoma.39 In patients with pathological fractures in skeletal metastases, external beam radiation therapy is necessary to prevent progressive bone destruction and loss of fixation following surgical treatment. Radiation therapy is used for radiosensitive tumours, mostly breast cancer, followed by multiple myeloma, lung, prostate and kidney cancer. Most radiation therapists administer fractionated doses of 20–40 Gy for 1–4 weeks.7,30,76 However, although local progression may be inhibited by radiation therapy in radiosensitive tumours, the risk of radiation-induced skeletal complications such as stress fractures and non-unions increases.7,30,83
[()TD$FIG]
Outcome The factors associated with improved outcome for patients with primary bone sarcomas complicated by pathological fractures are the response to chemotherapy, fracture union, wide resection, and response to radiation therapy.1,3,23,29,32,44,57,65,66,69,71,73,74,79,82 The factors associated with a worse prognosis are poor response to chemotherapy and local tumour recurrence. Fracture displacement and type of stabilization including open reduction and internal fixation versus closed treatment do not significantly affect the outcome.65 The local response to chemotherapy is indicative of a similar response of the subclinical disseminated disease.23 Fracture union during preoperative chemotherapy has been related to a favourable prognosis including increased overall and disease-free survival and decreased local recurrence rate.44,65,74 If wide resection is obtained, the rates of local recurrence are similar to those for limb-salvage surgery in general.1,3,29,57,65,73,79 Although amputation may be related to better eradication of the local tumour than limb-salvage, it does not influence the overall survival.1,29,57,79 Wide resection can still be achieved in the majority of patients without compromising survival, and the occurrence of a pathological fracture should no longer favour for amputation if adequate local resection can be performed after preoperative chemotherapy.57,65 In patients with pathological fractures in skeletal metastases, the presence of non-osseous metastases considerably deteriorates the prognosis.16,58,62 In addition, a better prognosis has been reported in patients with pathological fractures of the upper limb compared to those with fractures of the lower limb. Moreover, a longer median postoperative survival has been shown in patients with pathological fractures secondary to breast cancer compared to other types of primary tumours.62,63 The long survival after surgery is the most important risk factor for failure of the reconstruction or osteosynthesis of the pathological fracture
Fig. 2. (A) Anteroposterior radiograph of the right arm of a 75-year-old man with a pathological fracture of the humeral diaphysis in lung metastasis. (B) Indirect reduction and intramedullary nailing was done, followed by postoperative radiation therapy (30 Gy) and 5 cycles of chemotherapy. At 2 years postoperatively, the patient is alive with disease.
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secondary to disease progression, implant failure, or loss of fixation.28,86 This highlights the importance to identify the patients with a long expected survival and a good prognosis, for wide resection and megaprosthetic reconstruction, or rigid internal fracture fixation and augmentation of bone defects with acrylic cement.83 Authors’ recommendation After decades of treating tumour patients with different methods and approaches, the questions raised by this manuscript are still challenging. Surgeons should follow oncological principles in treating tumour patients. Referral to a specialized orthopaedic oncology centre is generally recommended. From a series of patients with primary benign and malignant bone tumours and skeletal metastases, we analysed the medical files of 122 patients with a pathological fracture of the upper and lower limb treated with internal fixation or resection and megaprosthetic reconstruction (unpublished data). In 55 patients, the pathological fracture occurred in primary bone tumours including osteosarcoma (16 patients), chondrosarcoma (6 patients), Ewing’s sarcoma (4 patients) fibrosarcoma, multiple myeloma and lymphoma (11 patients) and aggressive giant cell tumour of bone and aneurysmal bone cyst secondary to fibrous dysplasia (18 patients). In 74 patients the pathological fracture occurred in skeletal metastases. The mean age of the patients with pathological fractures in primary bone tumours was 65 years
[()TD$FIG]
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(range 33–81 years), and the mean age of the patients with pathological fractures in skeletal metastases was 68 years (range 49–93 years). In all patients, initial fracture stability was obtained with a brace or cast and preoperative staging and trocar biopsy was performed. Preoperative chemotherapy was administered in all patients with pathological fractures in primary bone sarcomas and in eight patients with pathological fractures in skeletal metastases with multiple metastatic bone lesions from breast cancer and adenocarcinoma grade 4. Preoperative radiation therapy was administered in six patients with pathological fractures in primary bone sarcomas. Wide resection and megaprosthetic reconstruction was carried out in all patients with pathological fractures in primary bone tumours, in 18 patients with proximal femoral pathological fractures in skeletal metastases and in 7 patients with humeral pathological fractures in skeletal metastases; intramedullary nailing using reconstruction nails was performed in 25 patients with humeral pathological fractures and 24 patients with femoral pathological fractures in skeletal metastases. Postoperative chemotherapy was administered in 14 patients with pathological fractures in primary bone sarcomas and in 7 patients with pathological fractures in skeletal metastases. Postoperative radiation therapy was administered in five patients with pathological fractures in primary bone sarcomas and in 63 patients with pathological fractures in skeletal metastases. Adjuvant selective embolization was done in 5 patients with skeletal metastases.
Fig. 3. Treatment algorithm for patients with pathological fractures in primary bone tumours and skeletal metastases. *When limb salvage is not feasible due to extent of lesion, neurovascular involvement, and/or massive contamination. **Radiation therapy rarely given; only if margins are not wide, or contaminated. ***Wide resection if fixation is not feasible. ****Wide resection only if fixation is not feasible due to extent of the lesion or meta-epiphyseal involvement. yChemotherapy in patients with skeletal metastases only if feasible depending on age, general condition and expected survival.
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At a mean follow-up of 80 months (range 1–275 months), 27% of the patients with primary bone tumours and 74% of the patients with skeletal metastases died of the disease. Although a discussion of the final results of our patients is outside the scope of this article, two patients with pathological fracture in primary bone sarcoma had local recurrence and required amputation (2/37 patients, distal femoral prostheses; 5.4%), and two patients had infection (2/ 55 patients, proximal and distal femoral prostheses; 3.6%). Amputation was necessary for local tumour progression in one patient with a femoral and one patient with a humeral pathological fracture in skeletal metastases (2/74 patients; 2.7%); both of these patients had intramedullary nail fixation. Failure of the osteosynthesis was not observed in any of the patients; one patient (1/ 18 patients; 5.5%) with a proximal femoral megaprosthetic reconstruction for a pathological fracture in skeletal metastases had aseptic loosening at 46 months, three patients (3/18 patients; 16%) had infection at 23 months, and one patient (1/18 patients; 5.5%) had dislocation of the prosthesis at 20 months after surgical treatment (Figs. 1 and 2). Based on the results of a large institutional study with great experience for the management of tumour patients, we propose a treatment algorithm that would be helpful for decision making and treatment of patients with long bone pathological fractures from primary and metastatic bone tumours (Fig. 3). Based on this analysis we apply these management guidelines to our patients. Treatment decision in these patients require complete staging and oncological principles. Initial fracture management should include cast immobilization or external fixation avoiding tumour-cell dissemination. Pathological fractures of the long bones in tumour patients should not be considered an absolute indication for amputation, since limb salvage surgery of patients with pathological fractures, particularly these that unite following chemotherapy, does not appear to increase the risk of local recurrence or death. Patients should be treated by preoperative chemotherapy followed by limb salvage surgery with wide margins, with or without radiation therapy. Tumours that are not sensitive to chemotherapy should not be amenable to limb-salvage surgery if pathological fractures have occurred. Tumour response to chemotherapy and radiation therapy, fracture union, and wide resection are the most significant predictive factors for overall survival and local disease control. Fracture displacement and type of stabilization do not significantly affect the outcome. Conflict of interest statement None of the authors have any financial and personal relationships with other people or organizations that could inappropriately influence (bias) their work. Role of the funding source There are no study sponsor for this paper and no sources of funding to acknowledge. References 1. Abudu A, Sferopoulos NK, Tillman RM, et al. The surgical treatment and outcome of pathological fractures in localised osteosarcoma. J Bone Joint Surg Br 1996;78:694–8. 2. Althausen P, Althausen A, Jennings LC, Mankin HJ. Prognostic factors and surgical treatment of osseous metastases secondary to renal cell carcinoma. Cancer 1997;80:1103–9. 3. Bacci G, Ferrari S, Longhi A, et al. Nonmetastatic osteosarcoma of the extremity with pathologic fracture at presentation: local and systemic control by amputation or limb salvage after preoperative chemotherapy. Acta Orthop Scand 2003;74(4):449–54. 4. Barwood SA, Wilson JL, Molnar PR, Choong PF. The incidence of cardiorespiratory and vascular dysfunction following intramedullary nail fixation of femoral metastasis. Acta Orthop Scand 2000;71:147–52.
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