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Proximal Femoral Allograft: Prognostic Indicators
The Journal of Arthroplasty Vol. 25 No. 7 2010
Proximal Femoral Allograft: Prognostic Indicators Pedro J. Roque, BS,* Henry J. Mankin, MD,y and Henrik Malchau, MDz
Abstract: Between 1972 and 1999, the Orthopedic Oncology Service treated 150 patients with resection and allograft transplantation of the proximal femur. Of the group, 121 patients had malignant tumors of the proximal femur and 29 had benign disorders. Four types of allografts were used: osteoarticular (46 patients), allograft-prosthesis (73), intercalary (20), and allograft-arthrodesis (5). Only 16% of the patients died of disease and 3% required amputation. The overall success rate for the series was 77% with the best results for the allograft prosthetic (82%) and intercalary procedures (87%). Graft infection (15 patients), allograft fracture (26 patients), and local recurrence (11 patients) most markedly affected outcome. With the exception of deaths of disease, no significant outcome difference occurred between the patients with malignant and benign disorders. In conclusion, allograft implantation especially for aggressive or malignant tumors of the proximal femur appears to be a competent system for therapy. Keywords: proximal femur, allograft, tumors, outcome. © 2010 Elsevier Inc. All rights reserved.
In the earlier days, patients with high-grade connective tissue tumors were routinely treated with surgical excision [1-3], most often amputation, because limbsalvage surgery was usually considered too complex and difficult [2,3]. Allografts were introduced in the 1920s by Lexer [4], but the reports of Frank Parrish [5,6] and Carlos Ottolenghi [7] in the sixties suggested that the procedure could be successful in the management of sarcomas. In 1986, Michael Simon and coworkers [8] conducted a retrospective study comparing 227 patients with highgrade osteosarcomas of the distal end of the femur who had either a limb-sparing procedure or an amputation and reported that for most patients, limb-salvage surgery was as safe as amputation. In addition, because of the use of adjuvant chemotherapy, radiation, or both, patients now live longer, sometimes outliving not only their sarcomatous disease but also, in some cases, the devices that were inserted as limb-sparing replacements [9-14]. Currently, the 3 preferred reconstructive options in adults after resection of bone lesion of the proximal femur include implantation of a megaprosthesis, an osteoarticu-
From the *Oliver Wendell Holmes Society Mentee Program, Harvard Medical School, Boston, Massachusetts; yOrthopedic Oncology Service, Massachusetts General Hospital, Boston, Massachusetts; and zOrthopedic Hip and Implant Service, Massachusetts General Hospital, Boston, Massachusetts. Submitted February 13, 2009; accepted July 21, 2009. No funds or contributions for this study were received by the authors or their families. Reprint requests: Henry J. Mankin, MD, Orthopedic Service, 1122A Jackson Building, Massachusetts General Hospital, Boston, MA 02114. © 2010 Elsevier Inc. All rights reserved. 0883-5403/2507-0004$36.00/0 doi:10.1016/j.arth.2009.07.018
lar allograft, or an allograft-prosthesis composite reconstruction [15-23]. A cadaveric allograft with or without a metallic prosthesis offers some degree of biologic restoration of the defect but in addition includes improved soft tissue attachment about the hip, resulting in improved stability [10,12,13]. The problems that arise with time include osteoarthritis (which occurs with osteoarticular grafts) [9,10,24-26], allograft fracture (often necessitating revision) [24,25,27-29], nonunion of the allograft-host junction (often successfully treated by revision) [24,3032], possible transmission of infectious disease (such as hepatitis C or human immunodeficiency virus [24,33,34]), and a risk of graft infection [24,32,35-37]. As an alternative to allograft systems, surgical implantation of proximal femoral megaprosthesis is not as technically demanding, requires a shorter recovery period, and most important, eliminates the concern regarding infectious disease transmission associated with cadaveric biologic tissue [16,18-22,38]. However, metallic devices are not without limitations, notable dislocation, or abnormal gait secondary to poor abductor attachments; loosening of the stem-host interface; or prosthesis failure [15,18,19,21,23,38,39]. It is clear that each reconstruction method has its own advantages and disadvantages, and particularly for tumors of the proximal femur, neither method appears to be statistically superior in longevity, function, or need for revision. Although health-related quality of life has become of great interest among cancer patients and their treating physicians, there have been few investigations directly dealing with the long-term survival of proximal femoral allograft reconstructions for patients who are principally
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Fig. 1. A 25-year-old male presented with a chondrosarcoma of the proximal femur in 1982. An x-ray (A) showed a lytic area below the trochanter, and when the tissue was removed, it seemed to be entirely within the bone. (B) An intercalary allograft was inserted, and the patient has done well with no complications and is free of disease 24 years later.
treated for connective tissue neoplasms [9,10,13,17]. The purpose of the current study is to analyze the long-term survival, complications, and function of proximal femoral allografts in 121 patients with aggressive or malignant tumors treated in one institution for a 27-year period and in addition comparing the results with those for 29 patients with benign conditions.
Materials and Methods Between 1972 and 1999, the Massachusetts General Hospital Orthopedic Oncology Service (Boston, Mass) performed 150 proximal femoral allograft implantations as treatment of 121 aggressive or malignant tumors
of bone and for 29 patients with benign conditions. A study was performed to analyze the results of these procedures. Patient information was gathered retrospectively from charts and from a computer database [40]. The data were recorded in a computer system and then analyzed using Kaplan-Meier graphic studies [41], Cox regression technique [42], and χ2 analyses [43]. The study was approved by the hospital institutional review board, and patient confidentiality was not violated. All patients were studied before surgery by available techniques that most often included radiographic images, computerized tomography, technetium bone scan, and more recently, an magnetic resonance imaging of the local
Fig. 2. (A) A 44-year-old woman presented in 1987 with a malignant fibrous histiocytoma of the proximal thigh that had invaded and partially destroyed the bone. (B) A resection was performed, and an allograft prosthesis was inserted. The patient did well, and although she has a mild Trendelenburg gait, she has no pain and has excellent function 20 years later.
1030 The Journal of Arthroplasty Vol. 25 No. 7 October 2010 site. All patients were observed for an average of 8 ± 6 years (range, 1 month to 27 years). There were 87 males and 63 females in the series with an average age of 45 years at the time of surgery (range, 5-79 years). The diagnoses for the 121 procedures for malignant or aggressive tumors included chondrosarcoma (48 patients); osteosarcoma (29); metastatic carcinoma (13); Ewing's sarcoma (9); malignant fibrous histiocytoma (9); giant cell tumor (2); lymphoma (2); and one each for patients with myeloma, fibrosarcoma, osteoblastoma, angiosarcoma, basal cell carcinoma, rhabdomyosarcoma, clear cell sarcoma, alveolar soft part sarcoma, and rhabdomyosarcoma. The diagnoses for the 29 benign disorders included failed femoral allograft (10); failed femoral total hip arthroplasty (6); fibrous dysplasia (5); Gaucher disease (4); and one each with enchondroma, ostecartilaginous exostosis, osteonecrosis, and pigmented villonodular synovitis. In 46 of the patients, the implanted devices were osteoarticular, and in 73 patients, the bone grafts were augmented by a total joint arthroplasty (usually a bipolar device) [9,10,15-17,23,44]. Twentythree of the patients had intercalary allografts [36] and 8 had allograft-arthrodeses [25,45]. Fresh-frozen allografts were obtained from the authors' institutional bone bank [34]. All allografts were sized preoperatively using special radiographs of the graft taken with rulers in place and compared with similar imaging of the host bone [13]. After tumor resection, surgical fixation was achieved either by plating (osteoarticular, intercalary, and alloarthrodesis grafts) or a long stem hip prosthesis often with cementation (allograft-prosthesis composites). Postoperatively, the limbs were placed in braces, and the patients maintained nonweightbearing or partial weightbearing for as many as 8 weeks. At that time if the patients had no complications, they were allowed to progressively increase their activity. The braces were removed when host-allograft union was observed radiographically [24,25]. Functional physical status was evaluated by data recorded in our registry and by review of the data from the patient's medical records. A grading system based on functional status established in 1983, was utilized [28]. A score of excellent meant the patient had no tumor recurrence, was pain-free, and had normal function; a score of good meant no tumor recurrence, pain-free status, but moderate activity restrictions; a score of fair meant no tumor recurrence, mild to moderate pain, and marked functional limitation; a failure score meant a complication necessitating amputation or graft removal. A successful graft was defined as either having either excellent or good results, and an allograft failure was defined as either having a score of fair or failure [28]. A complication was defined as a condition leading to additional treatment after the primary reconstruction procedure, being either allograft or tumor related. Complications included allograft fracture, infection, nonunion, dislocation, or local tumor recurrence. None of the patients in this series had a
dislocation or significant loosening of the prosthetic stem within the graft. Examples of the clinical presentations of osteoarticular, intercalary, alloprosthesis, and alloarthrodesis are shown in Figs. 1-3.
Results The patient's outcome data for the entire series are displayed in Table 1. One hundred fifty patients in the series with a mean follow-up of 8 ± 6 years (range, 1 month to 27 years) were evaluated for outcome and complications. For the total series of 150 patients, 115 were classified as having good or excellent results (77%) (Fig. 4), and 35 patients (23%) were considered to be failures. Twenty-four (16%) of the patients described as
Fig. 3. (A) A 39-year-old male presented in 1988 with a very destructive osteosarcoma of the proximal femur with an enormous soft tissue mass and a pathologic fracture. (B) The lesion was resected, and an allograft arthrodesis was performed. The patient did well in function but died of pulmonary metastases 3 years later.
Proximal Femoral Allograft Roque et al
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Table 1. Results for 150 Allograft Transplants of the Proximal Femur Overall success rate Patients died of disease Amputations
115/150 24/150
77% 16%
4/150
3%
Successful
Failure (%)
Age, average, 45 y (range, 5-9) b25 y (38) 30 8 25-45 y (45) 32 13 N45 y (67) 51 16 Sex Males (87) 68 19 Females (63) 46 17 Types of grafts Osteoarticular (46) 30 16 Alloprosthesis (73) 60 13 Intercalary (23) 20 3 Alloarthrodesis (8) 5 3 Complications Infection (15) 1 14 Allograft fracture (26) 10 16 Nonunion (20) 17 3 Local recurrence (11) 5 6 Diagnosis for primary malignant tumors Chondrosarcoma (48) 36 12 Osteosarcoma (29) 20 9 Metastatic 9 4 carcinoma (13) Ewing's sarcoma (9) 7 2 MFH (9) 7 2 Therapeutic effects Chemotherapy (43) 30 13 Radiation (13) 12 1
Success
P
79% 71% 76%
NS
78% 73%
NS
65% 82% 87% 63%
b .03 b .04
7% 38% 85% 55%
b .00001 b .004 NS b .0001
75% 69% 69% 77% 77%
NS
70% 92%
NS
NS indicates not significant; MFH, malignant fibrous histiocytoma. *P values were determined by Fisher exact test (45).
failure died of disease, 4 of whom required amputation for local recurrence or infection. For allograft complications, 15 patients (10%) had an infection, and of these patients, only one (7%) achieved a successful result (Table 1) (Fig. 5). Twenty-six (17%) of the 150 patients had an allograft fracture, and the graft success rate after surgical repair for these patients was 38%. Seventeen of the patients had a nonunion (11%), which generally responded well to realigning hardware and for some, autograft implantation (Table 1). Eighteen of the patients with osteoarticular allografts required a total hip arthroplasty at approximately 8 years after the surgery, and all but 3 of these are currently good or excellent. Eighty-five of the patients had no allograft complications, and these patients had a 98% success rate. Dislocation did not occur in this series. Graft survival varied with the type of reconstruction used (Table 1). The patients with osteoarticular allografts had the poorest results with a mean success rate of 30 (65%) of 46. The 8 patients with allograft-arthrodesis had approximately the same result, with only 5 (63%) of 8 patients having a good or excellent result. The 73 patients with allograft-prosthesis and 25 with intercalary
Fig. 4. Kaplan-Meier curve demonstrating the statistics for the entire series. The overall survival figure was 77%.
grafts did better with a success rate of 82% and 87%, respectively (P b .05 by χ2 analysis). Age, sex, type of tumor, and use of chemotherapy or radiation did not materially alter the success rate (Table 1). Of the 150 patients, 43 received chemotherapy, and the percentage of successful outcome was 70%, whereas 13 received radiation and had a success of 92% (Table 1). Of considerable importance, diagnosis as malignant or benign did not have any statistical effect on outcome with the exception of death of disease (Table 2). This seeming unusual set of results is probably based on some special issues. First, the number of cases with benign disease was small as compared with the malignant group. Of greater importance, the “benign”
Fig. 5. The effect of infection on outcome is shown in this graphic display. It is evident that infection has a serious affect on outcome (P b .00001).
1032 The Journal of Arthroplasty Vol. 25 No. 7 October 2010 Table 2. Comparison Between 121 Patients With Malignant Tumors and 29 With Benign Disease Graft failure Infection Fracture Nonunion Local recurrence Reoperations Amputation Deaths
Malignant
Benign
30 (25%) 13 (11%) 22 (18%) 14 (12%) 10 (8%) 71 (59%) 4 (3%) 41 (34%)
5 (17%) 2 (7%) 4 (14%) 6 (21%) 0 (0%) 16 (55%) 0 (0%) 1 (3%)
Significance NS NS NS NS NS NS NS P b .0008
*P values were determined by Fisher exact test (45).
disorders for which an allograft was performed were aggressive and bone destructive with sometimes soft tissue extension. Such lesions as osteoblastoma, giant cell tumor, enchondroma, and chondroblastoma are sometimes so destructive as to require resective surgery rather than local treatment. Thus, the results for the patients with benign disorders were essentially the same as for the malignant tumors except for the number of amputations and deaths. Local recurrence resulted in a poor outcome for 6 of 11 patients (45% success rate P b .0001). The 14 patients with nonunions did well with an 85% success rate after reoperation. Assessment of patient outcome with advancing time was evaluated assuming all patients started with ratings of excellent or good results. Most complications occurred within 2 to 4 years and dramatically decreased the functional rating then and thereafter.
Discussion The study provides evidence that proximal femoral allograft prostheses, especially intercalary and alloprosthetic devices, have a high success rate even with the patients with high-grade tumors followed for a mean time of 8 ± 6 years (range, 1 month to 27 years). If the patients survive and have no difficulties with infection, fracture, or local recurrence, the success rate is well more than 95%. These data are highly competitive to metallic implants, which in patients with tumors, have additional problems including fracture, loosening of the device, and dislocation of the prosthesis [15,18,19,22,23,38]. The issues that make these procedures less acceptable include complexity of the operative procedure, concern regarding infection, the duration of limited activities, and the frequency of subsequent surgery for osteoarthritis, nonunion, or fracture [9,24,27,30]. There is also a concern about the effect of chemotherapy on the allograft and the possibility that infection is more likely and that union at the host-donor junction sites may be delayed or markedly limited [32,33,36]. Clearly, these are important issues, which must be addressed. The proximal femur is a frequent site for both tumorous and nontumorous lesions, and reconstructions are complex and sometimes very concerning to the patient and physician. The use of alloimplants may be an
important approach and the results of this study support that suggestion.
References 1. Jaffe HL. Tumors and tumorous conditions of bones and joints. Philadelphia: Lea and Febiger; 1958. 2. Mankin HJ. History of treatment of musculoskeletal tumours. In: Klenerman L, editor. The evolution of orthopaedic surgery. London: Royal Society of Medicine Press Ltd; 2002. p. 191. 3. Dahlin DC, Coventry MB. Osteogenic sarcoma: a study of six hundred cases. J Bone Joint Surg 1967;49A:101. 4. Lexer E. Joint transplantation and arthroplasty. Surg Gynec Obstet 1925;40:782. 5. Parrish FF. Treatment of bone tumors by total excision and replacement with massive autologous and homologous grafts. J Bone Joint Surg 1966;48A:968. 6. Parrish FF. Allograft replacement of part of the end of a long bone following excision of a tumor: report of twenty-one cases. J Bone Joint Surg 1973;55A:1. 7. Ottolenghi CE. Massive osteoarticular bone grafts. J Bone Joint Surg 1966;48B:646. 8. Simon MA, Aschliman MA, Thomas N, et al. Limb-salvage treatment versus amputation for osteosarcoma of the distal end of the femur. J Bone Joint Surg 1986;68A:1331. 9. Fox EJ, Hau MA, Gehbhardt MC, et al. Long-term followup of proximal femoral allografts. Clin Orthop 2002;397:106. 10. Jofe MH, Gebhardt MC, Tomford WW, et al. Reconstruction for defects of the proximal part of the femur using allograft arthroplasty. J Bone Joint Surg 1988;70A:507. 11. Gitelis S, Piasecki P. Allograft prosthetic composite arthroplasty for osteosarcoma and other aggressive bone tumors. Clin Orthop 1991;270:197. 12. Harris A, Poddar S, Gitelis S, et al. Arthroplasty with composite of an allograft and a prosthesis for knees with severe deficiency of bone. J Bone Joint Surg 1995;75A: 373. 13. Jofe MH, Gebhardt MC, Mankin HJ. The use of proximal femoral allografts in the treatment of bone tumors. In: Yamamuro T, editor. New developments for limb salvage in musculoskeletal tumors Kyocera orthopaedic symposium. Tokyo: Springer-Verlag; 1989. p. 387. 14. Zeegen EN, Aponte-Tinao LA, Hornicek FJ, et al. Survivorship analysis of 141 modular metallic endoprostheses at early followup. Clin Orthop Relat Res 2004;420:239. 15. Farid Y, Linn PP, Lewis VO, et al. Endoprosthetic and allograft prosthetic composite reconstruction of the proximal femur for bone neoplasms. Clin Orthop 2006;442:223. 16. Anract P, Coste J, Vastel L. Proximal femoral reconstruction with megaprosthesis versus allograft prosthesis composite: a comparative study of functional results, complications and longevity in 41 cases. Rev Chir Orthop Reparatrice Appar Mot 2000;86:278. 17. Zehr RJ, Enneking WF, Scarborough MT. Allograft-prosthesis composite versus megaprosthesis in proximal femoral reconstruction. Clin Orthop 1996;322:207. 18. Dobbs HS, Scales JT, Wilson JN, et al. Endoprosthetic replacement of the proximal femur and acetabulum. J Bone Joint Surg 1981;63B:219. 19. Horowitz SM, Glasser DB, Lane JM, et al. Prosthetic and extremity survivorship after limb salvage for sarcoma: how long do the reconstructions last? Clin Orthop 1993;293:280.
Proximal Femoral Allograft Roque et al 20. Scales JT. Massive bone and joint replacement involving the upper femur, acetabulum and iliac bone. The hip: proceedings of the open third scientific meeting of the hip society. St. Louis: CV. Mosby; 1975. p. 245. 21. Sim FH, Chao EY. Bone and joint reconstruction for primary bone tumors of the proximal femur. In: Enneking WF, editor. Limb salvage in muscoskeletal oncology. New York: Churchill Livingstone; 1987. p. 227. 22. Lavoie G, Healey JH, Lane JM, et al. Prosthetic total femur replacement following massive resection for sarcoma. In: Brown KL, editor. Complications of limb salvage: prevention, management and outcome. Montreal, Canada: Montreal ISOLS; 1991. p. 129. 23. Zeegen EK, Aponte L, Hornicek FJ, et al. Survivorship analysis of 141 modular metallic endoprostheses. Clin Orthop 2004;420:239. 24. Mankin HJ, Gebhardt MC, Jennings L, et al. Long-term results of allograft replacement in the management of bone tumors. Clin Orthop 1996;324:86. 25. Mankin HJ, Doppelt SH, Sullivan TR, et al. Osteoarticular and intercalary allograft transplantation in the management of malignant tumors of bone. Cancer 1992; 50:613. 26. Mankin HJ, Springfield DS, Gebhardt MC, et al. Allograft bones and soft tissues: current status of allografting for bone tumors. Orthopedics 1992;15:1147. 27. Berrey BH, Lord CF, Gebhardt MC, et al. Fractures of allografts. J Bone Joint Surg 1990;72A:825. 28. Mankin HJ, Doppelt SH, Tomford WW. Clinical experience with allograft implantation. Clin Orthop 1983;74:69. 29. Sorger JI, Hornicek FJ, Zavatta M, et al. Allograft fractures revisited. Clin Orthop 2001;382:66. 30. Hornicek FJ, Gebhardt MC, Tomford WW, et al. Factors affecting nonunion of the allograft-host junction. Clin Orthop 2001;382:87. 31. Vander Griend RA. The effect of internal fixation on the healing of large allografts. J Bone Joint Surg 1994;76A: 657. 32. Friedlaender GE, Strong DM, Tomford WW, et al. Long term followup of patients with osteochondral allografts. A
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correlation between immunologic responses and clinical outcome. Orthopedic Clin North Am 1991;30:583. Lord FC, Gebhardt MC, Tomford WW, et al. Infection in bone allografts. J Bone Joint Surg 1988;70A:369. Tomford WW, Mankin HJ. Bone banking: update on methods and materials. Orthopedic Clin North Am 1999; 30:553. Dick HM, Malinin TI, Mnaymneh WA. Massive allograft implantation following radical resection of high-grade tumors requiring adjuvant chemotherapy treatment. Clin Orthop 1985;197:88. Hazan EJ, Hornicek FJ, Tomford WW, et al. The effect of adjuvant chemotherapy on osteoarticular allografts. Clin Orthop 2001;385:176. Tomford WW, Thongphasuk J, Mankin HJ, et al. Frozen musculoskeletal allografts. A study of the clinical incidence and causes of infection associated with their use. J Bone Joint Surg 1990;172A:1137. Mittermayer F, Krepler P, Dominkus M, et al. Long-term followup of uncemented tumor endoprostheses for the lower extremity. Clin Orthop 2001;388:167. Unwin PS, Cobb JP, Walker PS. Loosening in cemented femoral prostheses: a study of 668 tumour cases. In: Brown KL, editor. Complications of limb salvage: prevention, management and outcome. Montreal ISOLS; 1991. p. 133. Mankin HJ. A computerized system for orthopaedic oncology. Clin Orthop 2002;399:252. Kaplan E, Meier P. Non-parametric estimation for incomplete observations. J Am Stat Assoc 1958;53:457. Cox DR. Regression models and life tables. J R Stat Soc 1972;34:187. Lang TA, Secic M. How to report statistics in medicine. Philadelphia: ACP; 1997. McGoveran B, Davis AM, Gross AE, et al. Evaluation of the allograft-prosthesis composite technique for proximal femoral reconstructive after resection of a primary bone tumor. Can J Surg 1999;42:37. Donati D, Giacomini S, Gozzi E, et al. Allograft arthrodesis treatment of bone tumors: a two center study. Clin Orthop 2002;400:217.
Proximal Femoral Allograft: Prognostic Indicators Pedro J. Roque, BS,* Henry J. Mankin, MD,y and Henrik Malchau, MDz
Abstract: Between 1972 and 1999, the Orthopedic Oncology Service treated 150 patients with resection and allograft transplantation of the proximal femur. Of the group, 121 patients had malignant tumors of the proximal femur and 29 had benign disorders. Four types of allografts were used: osteoarticular (46 patients), allograft-prosthesis (73), intercalary (20), and allograft-arthrodesis (5). Only 16% of the patients died of disease and 3% required amputation. The overall success rate for the series was 77% with the best results for the allograft prosthetic (82%) and intercalary procedures (87%). Graft infection (15 patients), allograft fracture (26 patients), and local recurrence (11 patients) most markedly affected outcome. With the exception of deaths of disease, no significant outcome difference occurred between the patients with malignant and benign disorders. In conclusion, allograft implantation especially for aggressive or malignant tumors of the proximal femur appears to be a competent system for therapy. Keywords: proximal femur, allograft, tumors, outcome. © 2010 Elsevier Inc. All rights reserved.
In the earlier days, patients with high-grade connective tissue tumors were routinely treated with surgical excision [1-3], most often amputation, because limbsalvage surgery was usually considered too complex and difficult [2,3]. Allografts were introduced in the 1920s by Lexer [4], but the reports of Frank Parrish [5,6] and Carlos Ottolenghi [7] in the sixties suggested that the procedure could be successful in the management of sarcomas. In 1986, Michael Simon and coworkers [8] conducted a retrospective study comparing 227 patients with highgrade osteosarcomas of the distal end of the femur who had either a limb-sparing procedure or an amputation and reported that for most patients, limb-salvage surgery was as safe as amputation. In addition, because of the use of adjuvant chemotherapy, radiation, or both, patients now live longer, sometimes outliving not only their sarcomatous disease but also, in some cases, the devices that were inserted as limb-sparing replacements [9-14]. Currently, the 3 preferred reconstructive options in adults after resection of bone lesion of the proximal femur include implantation of a megaprosthesis, an osteoarticu-
From the *Oliver Wendell Holmes Society Mentee Program, Harvard Medical School, Boston, Massachusetts; yOrthopedic Oncology Service, Massachusetts General Hospital, Boston, Massachusetts; and zOrthopedic Hip and Implant Service, Massachusetts General Hospital, Boston, Massachusetts. Submitted February 13, 2009; accepted July 21, 2009. No funds or contributions for this study were received by the authors or their families. Reprint requests: Henry J. Mankin, MD, Orthopedic Service, 1122A Jackson Building, Massachusetts General Hospital, Boston, MA 02114. © 2010 Elsevier Inc. All rights reserved. 0883-5403/2507-0004$36.00/0 doi:10.1016/j.arth.2009.07.018
lar allograft, or an allograft-prosthesis composite reconstruction [15-23]. A cadaveric allograft with or without a metallic prosthesis offers some degree of biologic restoration of the defect but in addition includes improved soft tissue attachment about the hip, resulting in improved stability [10,12,13]. The problems that arise with time include osteoarthritis (which occurs with osteoarticular grafts) [9,10,24-26], allograft fracture (often necessitating revision) [24,25,27-29], nonunion of the allograft-host junction (often successfully treated by revision) [24,3032], possible transmission of infectious disease (such as hepatitis C or human immunodeficiency virus [24,33,34]), and a risk of graft infection [24,32,35-37]. As an alternative to allograft systems, surgical implantation of proximal femoral megaprosthesis is not as technically demanding, requires a shorter recovery period, and most important, eliminates the concern regarding infectious disease transmission associated with cadaveric biologic tissue [16,18-22,38]. However, metallic devices are not without limitations, notable dislocation, or abnormal gait secondary to poor abductor attachments; loosening of the stem-host interface; or prosthesis failure [15,18,19,21,23,38,39]. It is clear that each reconstruction method has its own advantages and disadvantages, and particularly for tumors of the proximal femur, neither method appears to be statistically superior in longevity, function, or need for revision. Although health-related quality of life has become of great interest among cancer patients and their treating physicians, there have been few investigations directly dealing with the long-term survival of proximal femoral allograft reconstructions for patients who are principally
1028
Proximal Femoral Allograft Roque et al
1029
Fig. 1. A 25-year-old male presented with a chondrosarcoma of the proximal femur in 1982. An x-ray (A) showed a lytic area below the trochanter, and when the tissue was removed, it seemed to be entirely within the bone. (B) An intercalary allograft was inserted, and the patient has done well with no complications and is free of disease 24 years later.
treated for connective tissue neoplasms [9,10,13,17]. The purpose of the current study is to analyze the long-term survival, complications, and function of proximal femoral allografts in 121 patients with aggressive or malignant tumors treated in one institution for a 27-year period and in addition comparing the results with those for 29 patients with benign conditions.
Materials and Methods Between 1972 and 1999, the Massachusetts General Hospital Orthopedic Oncology Service (Boston, Mass) performed 150 proximal femoral allograft implantations as treatment of 121 aggressive or malignant tumors
of bone and for 29 patients with benign conditions. A study was performed to analyze the results of these procedures. Patient information was gathered retrospectively from charts and from a computer database [40]. The data were recorded in a computer system and then analyzed using Kaplan-Meier graphic studies [41], Cox regression technique [42], and χ2 analyses [43]. The study was approved by the hospital institutional review board, and patient confidentiality was not violated. All patients were studied before surgery by available techniques that most often included radiographic images, computerized tomography, technetium bone scan, and more recently, an magnetic resonance imaging of the local
Fig. 2. (A) A 44-year-old woman presented in 1987 with a malignant fibrous histiocytoma of the proximal thigh that had invaded and partially destroyed the bone. (B) A resection was performed, and an allograft prosthesis was inserted. The patient did well, and although she has a mild Trendelenburg gait, she has no pain and has excellent function 20 years later.
1030 The Journal of Arthroplasty Vol. 25 No. 7 October 2010 site. All patients were observed for an average of 8 ± 6 years (range, 1 month to 27 years). There were 87 males and 63 females in the series with an average age of 45 years at the time of surgery (range, 5-79 years). The diagnoses for the 121 procedures for malignant or aggressive tumors included chondrosarcoma (48 patients); osteosarcoma (29); metastatic carcinoma (13); Ewing's sarcoma (9); malignant fibrous histiocytoma (9); giant cell tumor (2); lymphoma (2); and one each for patients with myeloma, fibrosarcoma, osteoblastoma, angiosarcoma, basal cell carcinoma, rhabdomyosarcoma, clear cell sarcoma, alveolar soft part sarcoma, and rhabdomyosarcoma. The diagnoses for the 29 benign disorders included failed femoral allograft (10); failed femoral total hip arthroplasty (6); fibrous dysplasia (5); Gaucher disease (4); and one each with enchondroma, ostecartilaginous exostosis, osteonecrosis, and pigmented villonodular synovitis. In 46 of the patients, the implanted devices were osteoarticular, and in 73 patients, the bone grafts were augmented by a total joint arthroplasty (usually a bipolar device) [9,10,15-17,23,44]. Twentythree of the patients had intercalary allografts [36] and 8 had allograft-arthrodeses [25,45]. Fresh-frozen allografts were obtained from the authors' institutional bone bank [34]. All allografts were sized preoperatively using special radiographs of the graft taken with rulers in place and compared with similar imaging of the host bone [13]. After tumor resection, surgical fixation was achieved either by plating (osteoarticular, intercalary, and alloarthrodesis grafts) or a long stem hip prosthesis often with cementation (allograft-prosthesis composites). Postoperatively, the limbs were placed in braces, and the patients maintained nonweightbearing or partial weightbearing for as many as 8 weeks. At that time if the patients had no complications, they were allowed to progressively increase their activity. The braces were removed when host-allograft union was observed radiographically [24,25]. Functional physical status was evaluated by data recorded in our registry and by review of the data from the patient's medical records. A grading system based on functional status established in 1983, was utilized [28]. A score of excellent meant the patient had no tumor recurrence, was pain-free, and had normal function; a score of good meant no tumor recurrence, pain-free status, but moderate activity restrictions; a score of fair meant no tumor recurrence, mild to moderate pain, and marked functional limitation; a failure score meant a complication necessitating amputation or graft removal. A successful graft was defined as either having either excellent or good results, and an allograft failure was defined as either having a score of fair or failure [28]. A complication was defined as a condition leading to additional treatment after the primary reconstruction procedure, being either allograft or tumor related. Complications included allograft fracture, infection, nonunion, dislocation, or local tumor recurrence. None of the patients in this series had a
dislocation or significant loosening of the prosthetic stem within the graft. Examples of the clinical presentations of osteoarticular, intercalary, alloprosthesis, and alloarthrodesis are shown in Figs. 1-3.
Results The patient's outcome data for the entire series are displayed in Table 1. One hundred fifty patients in the series with a mean follow-up of 8 ± 6 years (range, 1 month to 27 years) were evaluated for outcome and complications. For the total series of 150 patients, 115 were classified as having good or excellent results (77%) (Fig. 4), and 35 patients (23%) were considered to be failures. Twenty-four (16%) of the patients described as
Fig. 3. (A) A 39-year-old male presented in 1988 with a very destructive osteosarcoma of the proximal femur with an enormous soft tissue mass and a pathologic fracture. (B) The lesion was resected, and an allograft arthrodesis was performed. The patient did well in function but died of pulmonary metastases 3 years later.
Proximal Femoral Allograft Roque et al
1031
Table 1. Results for 150 Allograft Transplants of the Proximal Femur Overall success rate Patients died of disease Amputations
115/150 24/150
77% 16%
4/150
3%
Successful
Failure (%)
Age, average, 45 y (range, 5-9) b25 y (38) 30 8 25-45 y (45) 32 13 N45 y (67) 51 16 Sex Males (87) 68 19 Females (63) 46 17 Types of grafts Osteoarticular (46) 30 16 Alloprosthesis (73) 60 13 Intercalary (23) 20 3 Alloarthrodesis (8) 5 3 Complications Infection (15) 1 14 Allograft fracture (26) 10 16 Nonunion (20) 17 3 Local recurrence (11) 5 6 Diagnosis for primary malignant tumors Chondrosarcoma (48) 36 12 Osteosarcoma (29) 20 9 Metastatic 9 4 carcinoma (13) Ewing's sarcoma (9) 7 2 MFH (9) 7 2 Therapeutic effects Chemotherapy (43) 30 13 Radiation (13) 12 1
Success
P
79% 71% 76%
NS
78% 73%
NS
65% 82% 87% 63%
b .03 b .04
7% 38% 85% 55%
b .00001 b .004 NS b .0001
75% 69% 69% 77% 77%
NS
70% 92%
NS
NS indicates not significant; MFH, malignant fibrous histiocytoma. *P values were determined by Fisher exact test (45).
failure died of disease, 4 of whom required amputation for local recurrence or infection. For allograft complications, 15 patients (10%) had an infection, and of these patients, only one (7%) achieved a successful result (Table 1) (Fig. 5). Twenty-six (17%) of the 150 patients had an allograft fracture, and the graft success rate after surgical repair for these patients was 38%. Seventeen of the patients had a nonunion (11%), which generally responded well to realigning hardware and for some, autograft implantation (Table 1). Eighteen of the patients with osteoarticular allografts required a total hip arthroplasty at approximately 8 years after the surgery, and all but 3 of these are currently good or excellent. Eighty-five of the patients had no allograft complications, and these patients had a 98% success rate. Dislocation did not occur in this series. Graft survival varied with the type of reconstruction used (Table 1). The patients with osteoarticular allografts had the poorest results with a mean success rate of 30 (65%) of 46. The 8 patients with allograft-arthrodesis had approximately the same result, with only 5 (63%) of 8 patients having a good or excellent result. The 73 patients with allograft-prosthesis and 25 with intercalary
Fig. 4. Kaplan-Meier curve demonstrating the statistics for the entire series. The overall survival figure was 77%.
grafts did better with a success rate of 82% and 87%, respectively (P b .05 by χ2 analysis). Age, sex, type of tumor, and use of chemotherapy or radiation did not materially alter the success rate (Table 1). Of the 150 patients, 43 received chemotherapy, and the percentage of successful outcome was 70%, whereas 13 received radiation and had a success of 92% (Table 1). Of considerable importance, diagnosis as malignant or benign did not have any statistical effect on outcome with the exception of death of disease (Table 2). This seeming unusual set of results is probably based on some special issues. First, the number of cases with benign disease was small as compared with the malignant group. Of greater importance, the “benign”
Fig. 5. The effect of infection on outcome is shown in this graphic display. It is evident that infection has a serious affect on outcome (P b .00001).
1032 The Journal of Arthroplasty Vol. 25 No. 7 October 2010 Table 2. Comparison Between 121 Patients With Malignant Tumors and 29 With Benign Disease Graft failure Infection Fracture Nonunion Local recurrence Reoperations Amputation Deaths
Malignant
Benign
30 (25%) 13 (11%) 22 (18%) 14 (12%) 10 (8%) 71 (59%) 4 (3%) 41 (34%)
5 (17%) 2 (7%) 4 (14%) 6 (21%) 0 (0%) 16 (55%) 0 (0%) 1 (3%)
Significance NS NS NS NS NS NS NS P b .0008
*P values were determined by Fisher exact test (45).
disorders for which an allograft was performed were aggressive and bone destructive with sometimes soft tissue extension. Such lesions as osteoblastoma, giant cell tumor, enchondroma, and chondroblastoma are sometimes so destructive as to require resective surgery rather than local treatment. Thus, the results for the patients with benign disorders were essentially the same as for the malignant tumors except for the number of amputations and deaths. Local recurrence resulted in a poor outcome for 6 of 11 patients (45% success rate P b .0001). The 14 patients with nonunions did well with an 85% success rate after reoperation. Assessment of patient outcome with advancing time was evaluated assuming all patients started with ratings of excellent or good results. Most complications occurred within 2 to 4 years and dramatically decreased the functional rating then and thereafter.
Discussion The study provides evidence that proximal femoral allograft prostheses, especially intercalary and alloprosthetic devices, have a high success rate even with the patients with high-grade tumors followed for a mean time of 8 ± 6 years (range, 1 month to 27 years). If the patients survive and have no difficulties with infection, fracture, or local recurrence, the success rate is well more than 95%. These data are highly competitive to metallic implants, which in patients with tumors, have additional problems including fracture, loosening of the device, and dislocation of the prosthesis [15,18,19,22,23,38]. The issues that make these procedures less acceptable include complexity of the operative procedure, concern regarding infection, the duration of limited activities, and the frequency of subsequent surgery for osteoarthritis, nonunion, or fracture [9,24,27,30]. There is also a concern about the effect of chemotherapy on the allograft and the possibility that infection is more likely and that union at the host-donor junction sites may be delayed or markedly limited [32,33,36]. Clearly, these are important issues, which must be addressed. The proximal femur is a frequent site for both tumorous and nontumorous lesions, and reconstructions are complex and sometimes very concerning to the patient and physician. The use of alloimplants may be an
important approach and the results of this study support that suggestion.
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