Long-Term Follow-up After Limb Salvage in Skeletally Immature Children with a Primary Malignant Tumor of the Distal End of the Femur

Futani, Hiroyuki MD; Minamizaki, Takeshi MD; Nishimoto, Yutaka MD; Abe, Satoshi MD; Yabe, Hiroo MD; Ueda, Takafumi MD

Journal of Bone & Joint Surgery - American Volume:
doi: 10.2106/JBJS.C.01686
Scientific Articles
Abstract

Background: Skeletally immature children with a primary malignant tumor in the distal end of the femur are candidates for limb-salvage surgery; however, functional impairment due to subsequent limb-length discrepancy must be considered. Our aim was to evaluate the long-term clinical outcome of limb salvage in patients with a sarcoma of the distal end of the femur who were eleven years old or less, focusing on limb-length discrepancy and complications.

Methods: The cases of forty children were retrospectively reviewed in a multicenter study based on the responses to a questionnaire. Twenty-eight patients had had endoprosthetic reconstruction, and twelve had had biological reconstruction. Functional evaluation was based on the Musculoskeletal Tumor Society scoring system, with numerical values from 0 to 5 points assigned for each of the following six categories: pain, function, emotional acceptance, use of supports, walking ability, and gait. These values were added, and the functional score was presented as a percentage of the maximum possible score. Limb-length discrepancy was measured with orthoroentgenograms. Complications and their treatment were analyzed. Patient survival and the survival of the reconstructions were analyzed with use of the Kaplan-Meier method.

Results: Seven patients died and thirty-three remained alive, for a survival rate of 82% at ten years postoperatively. For the surviving patients, the mean follow-up periods (and standard deviations) were similar for the twenty-two who had endoprosthetic reconstruction (13.2 ± 3.9 years) and the eleven who had biological reconstruction (10.4 ± 4.4 years). All patients had reached skeletal maturity. The mean final functional score was 74% ± 18% in the endoprosthetic reconstruction group and 68% ± 17% in the biological reconstruction group (p = 0.37). For the nineteen patients who underwent limb-lengthening, the mean functional score increased significantly from 65% ± 21% before the procedure to 81% ± 11% after the lengthening (p = 0.0016). There were five early and twenty-eight late complications. In the endoprosthetic reconstruction group, the most frequent complications were deep infection and aseptic loosening. In the biological reconstruction group, the most frequent complications were implant breakage and nonunion. Revision surgeries were required in seventeen patients, including five who had an amputation. The rate of survival of the endoprosthetic reconstructions was 77% at five years and 51% at ten years postoperatively, whereas the rate of survival of the biological reconstructions was 46% at both five and ten years postoperatively.

Conclusions: Endoprosthetic or biological reconstructions as limb salvage provided good functional outcome in skeletally immature children with a malignant bone tumor of the distal aspect of the femur despite a high rate of revisions and limb-lengthening procedures.

Level of Evidence: Therapeutic Level III. See Instructions to Authors for a complete description of levels of evidence.

Author Information

1 Department of Orthopaedic Surgery, Hyogo College of Medicine, 1-1 Mukogawa Nishinomiya, Hyogo 663-8501, Japan. E-mail address: h-futani@hyo-med.ac.jp

2 Department of Orthopedic Surgery, Tottori University, 36-1 Nishimachi Yonago, Tottori 683-8504, Japan

3 Department of Orthopaedic Surgery, Gifu University, 40 Tsukasa-machi, Gifu, Gifu 500-8705, Japan

4 Department of Orthopaedic Surgery, Teikyo University School of Medicine, 2-11-2 Kaga, Itabashi-ku, Tokyo 173-8605, Japan

5 Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582, Japan

6 Department of Orthopaedic Surgery, Osaka University, 2-2 Yasuda-oka, Suita, Osaka 565-0871, Japan

Article Outline

Limb-salvage surgery is a widely accepted alternative to amputation in patients with a sarcoma affecting the distal aspect of the femur1,2. The success of limb salvage is the result of advances in the understanding of the biology and staging of tumors, improvement in the reconstructive techniques, and the development of effective adjuvant chemotherapy for the primary tumors. The patients can be expected to have long-term survival, which is due, in particular, to the advances in chemotherapy3-6.

The distal end of the femur is the most common site for a primary malignant bone tumor in children6-8. The distal femoral physis presumably contributes approximately 10 mm of growth per year until skeletal maturity at approximately sixteen years of age in boys and fourteen years of age in girls9,10. In skeletally immature patients, the eventual functional impairment that is due to the subsequent growth inhibition and the discrepancy in the length of the lower extremities must be considered in conjunction with limb-salvage surgery of the distal end of the femur. Several techniques, such as extendable endoprostheses8,11,12 or distraction osteogenesis13,14, have been applied to address this problem.

We performed a multi-institutional retrospective analysis based on responses to a questionnaire. Our aim was to assess the long-term clinical outcome of limb-salvage techniques for the treatment of sarcomas in the distal end of the femur in children who were eleven years old or less. In particular, we focused on problems related to limb-length discrepancy and complications.

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Materials and Methods

Questionnaires

In 1998, questionnaires were sent to 101 institutions belonging to the Japanese Musculoskeletal Oncology Group. The group consists of institutions with a department of orthopaedic oncology. The questionnaires were completed by orthopaedic surgeons on the basis of the data in the patients' charts. Questionnaires were received from forty-one (41%) of the 101 institutions.

The questionnaires included the following basic parameters: the age and sex of the patient, date of hospitalization, primary site of the lesion, histological diagnosis, and surgical stage according to the system of Enneking et al.15. Stage I indicates a low-grade lesion; stage II, a high-grade lesion; and stage III, a lesion with either regional or distant metastases. Also, questions were asked with regard to treatment, including neoadjuvant and/or adjuvant chemotherapy, radiation therapy, the date of surgery, the surgical margin15, and the type of surgery (endoprosthetic or biological reconstruction). Furthermore, the recipients were asked to grade the functional assessment, using the scoring system of the Musculoskeletal Tumor Society16, and to describe the limb-length discrepancy and limb-lengthening procedures, complications, and the management of complications. The scoring system of the Musculoskeletal Tumor Society is based on six categories: pain, function, emotional acceptance, use of supports, ability to walk, and gait. Each category was assigned a numerical value from 0 to 5 points, with 5 points indicating the best function. The values for each category were added, and the functional score was presented as a percentage of the maximum possible score (30 points).

Finally, the status of the patient with regard to the disease at the time of final follow-up was recorded as continuously disease-free, no evidence of disease at present but recurrence or metastasis in the past, or died of disease.

In order to extend the follow-up data, subsequent questionnaires were sent in September 2001 and April 2004 to the institutions that had responded in 1998. Responses were received from thirty-four (83%) of the forty-one institutions in 2001 and from all forty-one in 2004.

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Selection of the Patients

Patients were eligible for this study if they met the following criteria: (1) they were eleven years of age or less at the time of diagnosis, (2) they had a primary malignant bone tumor in the metaphysis and/or the epiphysis of the distal end of the femur, and (3) they had been selected to have limb-salvage surgery. Patients who had amputation or rotationplasty were excluded. Also, patients with a primary malignant bone tumor in the proximal end or shaft of the femur were excluded. Thus, forty patients from twenty-three institutions who were treated during the period from 1981 to 1997 met the eligibility criteria. The patients were divided into two groups according to the primary operative procedure: endoprosthetic reconstruction (twenty-eight patients) and biological reconstruction (twelve patients).

Since this was a multicenter retrospective study, no randomization protocol for implementation of the surgical procedures was followed. The final decision was made by the treating orthopaedic surgeons at each of the participating institutions.

Complete informed consent was obtained from each patient and his or her parents. Institutional review board approval was obtained from the institutions of the primary investigators.

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Characteristics of the Patients

Demographic data on the patients are provided in the Appendix. Thirty-nine patients had osteosarcoma, and one had Ewing sarcoma. The surgical stage according to the system of Enneking et al.15 was stage II-B in thirty-five patients and stage II-A in five patients. The surgical margin was wide in all patients except for two who had radical margins and three who had marginal margins. The twenty-eight patients who had endoprosthetic reconstruction were managed with custom-made endoprostheses (eighteen patients), extendable endoprostheses (seven patients), and modular resection systems (three patients). Of the twelve patients who had biological reconstruction, eight were managed with knee arthrodesis after resection and interposition with autogenous bone grafts (four patients), allograft (two patients), or a vascularized fibular graft (two patients), and four underwent en bloc tumor resection with preservation of the epiphysis, followed by reconstruction with distraction osteogenesis (three patients) or a vascularized fibular graft (one patient).

All patients received neoadjuvant and adjuvant chemotherapy except one (Case 17) with a parosteal osteosarcoma. In the one patient with a Ewing sarcoma (Case 4), preoperative and postoperative radiation therapy was also performed. One other patient (Case 40) received preoperative radiation therapy to obtain adequate surgical margins since there was a pathological fracture and the extraosseous tumor was adjacent to a neurovascular bundle.

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Clinical Outcome

Postoperative function was assessed with the scoring system of the Musculoskeletal Tumor Society16. The limb-length discrepancy was evaluated with use of orthoroentgenograms. A discrepancy of ≥2 cm was considered substantial enough to require correction surgery17. Two major procedures, either distraction osteogenesis or endoprosthetic expansion, were used. In addition, the use of a shoe lift was noted. The limb-length discrepancy at the time of the last follow-up was measured.

Complications related to surgery, such as infection, implant breakage, aseptic loosening, dislocation, skin necrosis, fractures, and nonunion, were evaluated. Local recurrences were also recorded. A complication was defined as early when it occurred within six months after the primary surgery and as late when it occurred more than six months after the primary surgery. The management of the complications, such as revision surgery (removal of the endoprosthesis, arthrodesis, or amputation), was also recorded. Furthermore, complications related to the disease itself, such as metastases, and any treatment of such complications, were recorded.

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Survival of the Reconstructions

The procedure was considered to be a failure when revision surgery had to be performed for any reason or when the patient needed an amputation. The survival of the reconstructions was calculated, with use of the Kaplan-Meier method, from the time of the initial surgery until the date when revision or amputation had to be performed or until the time of the latest follow-up. Furthermore, the limb salvage was considered successful whenever the patient had a preserved limb at the time of final follow-up despite any complications or revisions.

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Survival of the Patients

At the time of final follow-up, the patients were categorized according to their prognosis into one of three groups: those who were continuously disease-free, those with no evidence of disease, and those who had dvied of disease. We calculated the survival rates for all patients and for the subgroups according to the reconstruction procedure.

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Statistical Analyses

For comparisons among groups, analysis of variance and analysis of variance factorial tests were used, except for categorical data for which chi-square tests were applied. Simple and multiple regression analyses were performed. The survival rate of the patients was estimated with the method of Kaplan and Meier18. This method was also used to estimate complicationfree rates and survival of the reconstruction procedures. The Mantel-Cox log-rank test was used to compare the survivorship curves. All analyses were performed with use of the StatView software package for Macintosh (Abacus Concepts, Berkeley, California). A p value of <0.05 for a type-I error was considered to be significant.

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Results

Oncological Results

Seven patients died from metastases (six had lung metastases, and one had brain metastases) at a mean duration of follow-up (and standard deviation) of 2.8 ± 2.3 years (range, 0.8 to 6.3 years). Three patients had no evidence of disease, and thirty were continuously disease-free. No local recurrence was found in the total series of forty patients. The cumulative rates of survival in the total series of patients were 85% (95% confidence interval, 74% to 96%) at five years postoperatively and 82% (95% confidence interval, 71% to 94%) at ten years postoperatively. Furthermore, we calculated the cumulative rates of survival for each of the surgical subgroups. The survival rates at five and ten years were 82% (95% confidence interval, 68% to 96%) and 78% (95% confidence interval, 63% to 94%), respectively, in the endoprosthetic reconstruction group and 92% (95% confidence interval, 76% to 100%) at both five and ten years in the biological reconstruction group (Fig. 1). There was no significant difference between the groups (p = 0.3160).

For the subsequent analyses, the patients who had died of the disease were excluded; thus, only the thirty-three surviving patients (twenty-two who had endoprosthetic reconstruction and eleven who had biological reconstruction) were included. The mean age of the patients was 10 ± 1 years (range, six to eleven years) at the time of diagnosis and 22 ± 4 years (range, fourteen to thirty years) at the time of the latest follow-up. All patients were skeletally mature. There were thirteen male and twenty female patients (ratio, 0.65). The mean duration of follow-up for the endoprosthetic reconstruction group (13.2 ± 3.9 years; range, 5.9 to twenty years) was similar to that of the biological reconstruction group (10.4 ± 4.4 years; range, six to 19.8 years) (p = 0.0760).

Metastases to the lungs occurred in two patients who were successfully treated with resection of the metastases. Skip metastasis to the tibia occurred in one patient, who then underwent an amputation.

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Functional Assessment

The Musculoskeletal Tumor Society functional scores at the time of final follow-up were available for all patients. The mean final functional score was 74% ± 18% in the endoprosthetic reconstruction group and 68% ± 17% in the biological reconstruction group (p = 0.3672). Furthermore, with the numbers available, no differences in functional scores were detected with regard to sex, surgical staging, or margins. The mean values for the six functional categories in the endoprosthetic reconstruction group and the biological reconstruction group were 4.7 ± 0.9 and 4.8 ± 0.4, respectively, for pain; 3.3 ± 1.0 and 3.5 ± 1.4 for function; 3.2 ± 1.3 and 2.7 ± 1.7 for emotional acceptance; 4.0 ± 1.4 and 3.5 ± 1.5 for the use of supports; 3.8 ± 1.2 and 3.5 ± 1.3 for gait; and 3.3 ± 1.3 and 2.3 ± 1.5 for the ability to walk.

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Limb-Length Discrepancy

Nineteen (58%) of the thirty-three living patients had a limb-lengthening procedure. Of the remaining fourteen patients, eight preferred not to undergo limb-lengthening, five needed an amputation, and one had a limb-length discrepancy of <2 cm. Twelve patients who had a lengthening procedure were in the endoprosthetic reconstruction group (Fig. 2), and seven were in the biological reconstruction group. Lengthening was performed with distraction osteogenesis in thirteen patients, including one who received a vascularized fibular graft, and endoprosthetic expansion was used in the remaining six patients. One of the patients who had distraction osteogenesis also had an endoprosthetic expansion. A total of sixteen procedures were performed in the thirteen patients undergoing distraction osteogenesis, with a mean lengthening of 9.3 ± 7.8 cm for each procedure. A total of eighteen procedures were performed in the six patients who had endoprosthetic expansion, with a mean lengthening of 1.5 ± 0.4 cm for each procedure. The mean interval from the time of the initial surgery to the first lengthening procedure was 43 ± 41 months in the distraction osteogenesis group and 37 ± 32 months in the endoprosthetic expansion group (p = 0.7265). At the time of the final follow-up, a limb-length discrepancy of ≥2 cm was present in fifteen of the patients who had lengthening and in eight others who had not had lengthening. These twenty-three patients had a mean discrepancy of 5.5 ± 3.3 cm (range, 2 to 15 cm). When limb-length discrepancy was assessed on the basis of the type of lengthening procedure (distraction osteogenesis, endoprosthetic expansion, or none), no significant differences were noted, with the numbers available (Fig. 3).

Nine of the nineteen patients who had a lengthening procedure and six of those who did not were treated with a shoe lift. The Musculoskeletal Tumor Society functional scores were available for sixteen patients before the limb-lengthening procedure. Importantly, the mean functional score increased significantly to 81% ± 11% (range, 60% to 100%) after limb-lengthening from 65% ± 21% (range, 23% to 100%) before the lengthening (p = 0.0016). Regression analysis showed a significant negative correlation between functional score and a limb-length discrepancy of ≥2 cm (r = 0.53 and p = 0.0091) (Fig. 4).

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Complications

Five early complications occurred in four patients, and twenty-eight late complications occurred in twenty-two patients. In summary, one patient had three complications, seven patients had two complications, and sixteen patients had one complication each, while the remaining nine patients had no complications. Early complications included skin necrosis, infection, vessel occlusion, and peroneal nerve palsy, and late complications included superficial and deep infection, implant breakage, aseptic loosening, fracture, nonunion, and dislocation. Details of the complications are shown in Table I. In the endoprosthetic reconstruction group, the most frequent complication was deep infection (six patients) followed by aseptic loosening (five patients), and implant breakage and dislocation (two patients each). In the biological reconstruction group, the most frequent complications were implant breakage and nonunion (three patients each), followed by superficial infection, deep infection, and fracture (two patients each).

A tendency toward higher functional scores was noted in the patients who did not have complications (mean score, 77% ± 27%) compared with those who did (mean score, 70% ± 13%); however, the difference did not reach significance (p = 0.3596).

The cumulative event-free rate with regard to complications related to surgery was calculated for the total series of patients. Complications had occurred in 55% (95% confidence interval, 38% to 71%) of the patients at five years, and the rate increased to 74% (95% confidence interval, 57% to 90%) at ten years. Furthermore, the cumulative event-free rate in the two surgical groups was determined (Fig. 5). At five years, complications had occurred in 45% (95% confidence interval, 25% to 66%) of the patients in the endoprosthetic reconstruction group and in 73% (95% confidence interval, 46% to 99%) of those who had biological reconstruction (p = 0.0472). At ten years, the complication rate had increased to 69% (95% confidence interval, 47% to 91%) of the patients in the endoprosthetic reconstruction group and to 86% (95% confidence interval, 63% to 109%) of those in the biological reconstruction group (p = 0.0836).

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Survival of Reconstruction Modes

With regard to the management of the complications, revision operations were necessary in thirteen patients, and one of them eventually underwent amputation. In addition, four other amputations were performed. The details of the revisions and amputations for these patients are shown in the Appendix and are summarized in relation to complications in Table I. A total of seventeen patients (52%) needed additional surgery because of complications of the initial surgery.

The survival rate of the reconstructions in the two surgical groups was estimated (Fig. 6). The survival rate was 77% (95% confidence interval, 60% to 95%) at five years and 51% (95% confidence interval, 29% to 73%) at ten years for the endoprosthetic reconstructions and 46% (95% confidence interval, 16% to 75%) at both five and ten years for the biological reconstructions. Interestingly, during the first six years, a tendency toward better survival was noted for the endoprosthetic reconstructions, but it did not reach significance (p = 0.0646) and did not persist during longer follow-up. The total success rate for limb salvage was 85%, with a success rate of 91% for the endoprosthetic reconstructions and 73% for the biological reconstructions.

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Discussion

Chemotherapy has dramatically changed the cure rate of malignant bone tumors5,19. Since the introduction of effective neoadjuvant chemotherapy in the 1980s, >80% of patients with osteosarcoma of the extremity have been considered candidates for limb-salvage surgery20. Previous studies have found no difference in the long-term survival rate between patients treated with amputation and those treated with limb-salvage of the distal end of the femur1,2. In the present study, the ten-year cumulative survival rate was 82%. This finding is comparable with that in the study by Schindler et al.8, who reported an overall survival rate of 78% in children after limb-salvage surgery of the femur. Local recurrence was not observed in any patient in our series. This finding was similar to that in the study by Schiller et al.19, who performed limb salvage of the distal end of the femur in five children who were less than fourteen years old, and to that described by Wilkins and Miller21 in a study of thirty-one patients who were less than nineteen years old.

We studied forty children who were eleven years of age or less at the time of diagnosis. The purpose of selecting patients of this age was to evaluate the effect of growth for at least two years, as skeletal maturity is expected by the age of sixteen years in boys and fourteen years in girls9,10. The children were selected to undergo limb salvage with one of two major procedures, either endoprosthetic or biological reconstruction. Furthermore, they had a relatively long duration of follow-up of six to twenty years. All patients had reached skeletal maturity at the time of the last follow-up. To our knowledge, this is the largest report of the long-term results of limb salvage for the treatment of sarcomas of the distal end of the femur in skeletally immature children.

Kenan and Lewis reported that limb-lengthening was necessary in twenty-one patients who were twelve years old or less at the time of limb-salvage surgery11. A limb-length discrepancy of ≥2 cm has been considered substantial enough to require corrective surgery17. Therapeutic options range widely from no treatment or the use of a shoe lift to contralateral surgical shortening or a limb-lengthening procedure14,22,23. In the present study, limb-lengthening procedures were performed in nineteen (58%) of the thirty-three surviving patients. Only one patient had a discrepancy of <2 cm, five patients needed amputation, and the eight other patients refused to undergo any lengthening procedure (six of them used a shoe lift). Lengthening was achieved mainly with two procedures, distraction osteogenesis and endoprosthetic expansion. In nearly half of these patients (nine of the nineteen patients), an additional shoe lift was necessary, as a considerable discrepancy remained. Importantly, we found that the functional score was significantly higher following limb-lengthening. In addition, at the time of the final follow-up, we found that, as the limb-length discrepancy decreased, the functional score increased (see Fig. 4). Even if this relationship were significant, the functional score is clearly not only dependent on limb-length discrepancy, as other factors that have not been explored further in this study may contribute. However, we believe that limb-length discrepancy is a rather important factor relating to a poor functional outcome, and our findings support the concept that lengthening procedures are required to obtain better function in these young patients.

The final functional scores in the endoprosthetic and biological reconstructions were 74% and 68%, respectively, despite the frequent necessity for additional operations, such as limb-lengthening procedures and revisions. Function in the endoprosthetic group was comparable with that described in the study by Schindler et al., in which the mean Musculoskeletal Tumor Society functional score was 77% in twelve children with Stanmore custom-made extendable distal femoral prostheses8. Wilkins and Miller21 found mean functional scores of 73% in twenty-six patients with primary limb-preservation surgery with reoperations and 79% in ten patients without reoperations. With regard to the different categories of the Musculoskeletal Tumor Society functional scoring system, pain received the highest score, which indicated that the patients experienced little pain, whereas emotional acceptance and the ability to walk received the lowest scores.

Deep infection was the most common complication, occurring in eight (24%) of the thirty-three patients in our study. In the previous literature, the rate of deep infection in the femur has ranged from 4% (one of twenty-four patients) in the study by Cool et al.24 to two of five patients in the study by Schiller et al.19. Comparable results have been reported by other investigators8,25,26. Among the patients who had endoprosthetic reconstruction in our study, six had a deep infection. Débridement and irrigation without removal of the endoprosthesis was performed in two patients; staged reimplantation, in two patients27; removal of the endoprosthesis followed by arthrodesis28, in one patient; and amputation8, in one patient. Two of the patients in the biological reconstruction group had a deep infection. One was treated with débridement alone, and the other required amputation.

In the present study, five (23%) of twenty-two patients with endoprosthetic replacement experienced aseptic loosening. Aseptic loosening has been reported as a major problem, accounting for a complication rate of 13% (three of twenty-four patients) in the series by Cool et al.24 and up to six of twelve patients in the study by Schindler et al.8. Our results are comparable with those in several other reports19,24,29. Unwin and Walker30 found that sixteen (15%) of 105 patients managed with a Stanmore custom-made extendable endoprosthesis of the distal end of the femur had to have a revision because of aseptic loosening. This rate is similar to that in our study, in which revision surgery was required in three (14%) of twenty-two patients.

Implant breakage was found in 15% (five) of our thirty-three patients. In the endoprosthetic reconstruction group, two patients fell accidentally; one had breakage of the femoral stem and the other had breakage of the femoral ceramic component. Those types of prostheses are no longer used. In the biological reconstruction group, three of four patients who had reconstruction with a Küntscher nail had breakage. Breakage of the nail after arthrodesis occurred in twenty (24%) of eighty-four patients in the series by Donati et al.31 and in four of thirty-nine patients in the series by Weiner et al.32.

In the present study, revision surgery other than limb-lengthening was necessary in seventeen (52%) of thirty-three patients; five of them eventually needed amputation. In previous studies, revision rates have ranged from a minimum of 21% (five of twenty-four patients in the series by Cool et al.24) to 100% (all twelve patients in the study by Schindler et al.8). Comparable results have been reported by other investigators19,24,26,30,33. After long-term follow-up in our series of patients, the survival rates for endoprosthetic and biological reconstructions were similar. The survival rate for endoprosthetic reconstruction was 77% at five years and 51% at ten years, whereas the survival rate for biological reconstruction was 46% at both five and ten years. Unwin and Walker reported that 105 patients with distal femoral extendable prostheses had a probability of survival of 80% at four years30. However, long-term results were not reported in that study. Our long-term results are comparable with those reported in studies that included all age-groups, such as that by Kawai et al., who found a survival rate for endoprosthetic reconstruction of 67% at five years and 48% at ten years in thirty-two patients33.

There are few studies on the survival rate of biological reconstructions. In a report on eighty-four patients who had knee arthrodesis with use of a temporary spacer, Donati et al.31 found that the overall rate of implant survival was only 5% at twelve years, which was low compared with our findings. It should be noted that the rate of mechanical complications, such as implant breakage, bending, and migration, in that study was very high (39%; thirty-three patients). Those complications occurred soon after the initial surgery. Also, wound complications occurred in twenty-six patients. Alman et al.26 reported on eight young patients with a tumor of the femur who were managed with knee arthrodesis or an intercalary reconstruction of the femur; all except one had failure of the reconstruction and needed a revision.

The use of arthrodesis has decreased after the introduction of expandable endoprostheses26. However, an arthrodesis may still be considered in patients with a large tumor when an extensive resection of bone or soft tissue, such as complete resection of the quadriceps muscle, is expected; when there is a lack of bone source; or when there is a poor prognosis for the patient31. Furthermore, tumor resection with preservation of the epiphysis followed by reconstruction with distraction osteogenesis is the only current technique that has the advantage of preserving the natural joint, and thus it might be considered for patients with a tumor of <15 cm in length and with at least 0.5 cm of the epiphysis remaining after removal of the tumor14.

The rate of amputation in our study (five patients; 15%) is comparable with that in previous reports8,26. In our series, the causes leading to the amputations varied. In the previous literature, the major causes of amputation were infection or local recurrence8,30,31. In order to improve the success rate of limb-salvage surgery, every effort should be made to avoid these two complications.

One limitation of this study is the relatively small number of patients in each of the surgical reconstruction groups, and therefore any firm conclusion about differences across the groups should be made with caution. The study design represents another limitation, since this was a multicenter retrospective study and no randomization protocol for the implementation of surgical procedures was followed. Thus, tumor-related factors; the preferences of the institution, the surgeon, or the patient; or other unexplored factors might have biased the decision with regard to the type of surgery performed.

We concluded that, even if additional revision and limb-lengthening procedures are required, endoprosthetic or biological reconstructions provide good functional outcome in skeletally immature children with a malignant bone tumor of the distal end of the femur. However, the patients and their families must be carefully selected with an emphasis on motivation and acceptance, since rather frequent and substantial treatment during follow-up is inevitably required. In the future, improvements in the surgical techniques and equipment are needed to diminish the number of complications related to the initial limb-salvage surgery.

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Appendix

A table presenting demographic data on the patients in the study is available with the electronic versions of this article, on our web site at jbjs.org (go to the article citation and click on “Supplementary Material”) and on our quarterly CD-ROM (call our subscription department, at 781-449-9780, to order the CD-ROM). ▪

A commentary is available with the electronic versions of this article, on our web site () and on our quarterly CD-ROM (call our subscription department, at 781-449-9780, to order the CD-ROM).

NOTE: The authors thank their colleagues in the Japanese Musculoskeletal Oncology Group for their participation in the present study: H. Yoshida, MD, Nihon University; K. Yonemura, MD, Kumamoto University; K. Isu, MD, National Sapporo Hospital; K. Yokoyama, MD, National Kokura Hospital; N. Araki, MD, Osaka University; T. Goto, MD, The University of Tokyo; A. Kawai, MD, National Cancer Center Hospital; T. Ozaki, MD, Okayama University; S. Tatezaki, MD, Chiba Cancer Center Hospital; T. Hotta, MD, Niigata University; T. Tajino, MD, Fukushima Medical University; S. Nasuno, MD, Kitasato University; E. Chousa, MD, Miyazaki Medical College; H. Kakizaki, MD, National Hirosaki Hospital; K. Shinjo, MD, Nagoya National Hospital; N. Ueda, MD, Osaka Medical College; Y.H. Lee, MD, Tokai University; H. Watanabe, MD, Gunma University; H. Murata, MD, Kyoto Prefectural University of Medicine; K. Ihara, MD, Yamaguchi University; T. Nakagawa, MD, Kansai Medical University; H. Isaki, MD, National Defense Medical College; T. Nishikori, MD, Shimane Medical University; T. Takagi, MD, Juntendo University; A. Imakiire, MD, Tokyo Medical University; H. Tsuchiya, MD, Kanazawa University; Y. Aoki, MD, Osaka National Hospital; T. Nagai, MD, Saitama Medical School; H. Kuroda, MD, Tokyo Medical and Dental University; and M. Hatori, MD, Tohoku University.

In support of their research for or preparation of this manuscript, one of the authors (H.F.) received grants or outside funding from the Fund for Cancer Research from Hyogo Prefecture Health Promotion Association. None of the authors received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.

Investigation performed at the Department of Orthopaedic Surgery, Hyogo College of Medicine, Hyogo, Japan

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