Does the Addition of a Vascularized Fibula Improve the Results of a Massive Bone Allograft Alone for Intercalary Femur Reconstruction of Malignant Bone Tumors in Children?

Abstract

Background

Massive bone allograft with or without a vascularized fibula is a potentially useful approach for femoral intercalary reconstruction after resection of bone sarcomas in children. However, inadequate data exist regarding whether it is preferable to use a massive bone allograft alone or a massive bone allograft combined with a vascularized free fibula for intercalary reconstructions of the femur after intercalary femur resections in children. Because the addition of a vascularized fibula adds to the time and complexity of the procedure, understanding more about whether it reduces complications and improves the function of patients who undergo these resections and reconstructions would be valuable for patients and treating physicians.

Questions/purposes

In an analysis of children with bone sarcomas of the femur who underwent an intercalary resection and reconstruction with massive bone allograft with or without a vascularized free fibula, we asked: (1) What was the difference in the surgical time of these two different surgical techniques? (2) What are the complications and number of reoperations associated with each procedure? (3) What were the Musculoskeletal Tumor Society scores after these reconstructions? (4) What was the survival rate of these two different reconstructions?

Methods

Between 1994 and 2016, we treated 285 patients younger than 16 years with a diagnosis of osteosarcoma or Ewing sarcoma of the femur. In all, 179 underwent resection and reconstruction of the distal femur and 36 patients underwent resection and reconstruction of the proximal femur. Additionally, in 70 patients with diaphyseal tumors, we performed total femur reconstruction in four patients, amputation in five, and a rotationplasty in one. The remaining 60 patients with diaphyseal tumors underwent intercalary resection and reconstruction with massive bone allograft with or without vascularized free fibula. The decision to use a massive bone allograft with or without a vascularized free fibula was probably influenced by tumor size, with the indication to use the vascularized free fibula in longer reconstructions. Twenty-seven patients underwent a femur reconstruction with massive bone allograft and vascularized free fibula, and 33 patients received massive bone allograft alone. In the group with massive bone allograft and vascularized fibula, two patients were excluded because they did not have the minimum data for the analysis. In the group with massive bone allograft alone, 12 patients were excluded: one patient was lost to follow-up before 2 years, five patients died before 2 years of follow-up, and six patients did not have the minimum data for the analysis. We analyzed the remaining 46 children with sarcoma of the femur treated with intercalary resection and biological reconstruction. Twenty-five patients underwent femur reconstruction with a massive bone allograft and vascularized free fibula, and 21 patients had reconstruction with a massive bone allograft alone. In the group of children treated with massive bone allograft and vascularized free fibula, there were 17 boys and eight girls, with a mean ± SD age of 11 ± 3 years. The diagnosis was osteosarcoma in 14 patients and Ewing sarcoma in 11. The mean length of resection was 18 ± 5 cm. The mean follow-up was 117 ± 61 months. In the group of children treated with massive bone allograft alone, there were 13 boys and eight girls, with a mean ± SD age of 12 ± 2 years. The diagnosis was osteosarcoma in 17 patients and Ewing sarcoma in four. The mean length of resection was 15 ± 4 cm. The mean follow-up was 130 ± 56 months. Some patients finished clinical and radiological checks as the follow-up exceeded 10 years. In the group with massive bone allograft and vascularized free fibula, four patients had a follow-up of 10, 12, 13, and 18 years, respectively, while in the group with massive bone allograft alone, five patients had a follow-up of 10 years, one patient had a follow-up of 11 years, and another had 13 years of follow-up. In general, there were no important differences between the groups in terms of age (mean difference 0.88 [95% CI -0.6 to 2.3]; p = 0.26), gender (p = 0.66), diagnosis (p = 0.11), and follow up (mean difference 12.9 [95% CI-22.7 to 48.62]; p = 0.46). There was a difference between groups regarding the length of the resection, which was greater in patients treated with a massive bone allograft and vascularized free fibula (18 ± 5 cm) than in those treated with a massive bone allograft alone (15 ± 4 cm) (mean difference -3.09 [95% CI -5.7 to -0.4]; p = 0.02). Complications related to the procedure like infection, neurovascular compromise, and graft-related complication, such as fracture and nonunion of massive bone allograft or vascularized free fibula and implant breakage, were analyzed by chart review of these patients by an orthopaedic surgeon with experience in musculoskeletal oncology. Survival of the reconstructions that had no graft or implant replacement was the endpoint. The Kaplan-Meier test was performed for a survival analysis of the reconstruction. A p value less than 0.05 was considered significant.

Results

The surgery was longer in patients treated with a massive bone allograft and vascularized free fibula than in patients treated with a massive bone allograft alone (10 ± 0.09 and 4 ± 0.77 hours, respectively; mean difference -6.8 [95% CI -7.1 to -6.4]; p = 0.001). Twelve of 25 patients treated with massive bone allograft and vascularized free fibula had one or more complication: allograft fracture (seven), nonunion (four), and infection (four). Twelve of 21 patients treated with massive bone allograft alone had the following complications: allograft fracture (five), nonunion (six), and infection (one). The mean functional results were 26 ± 4 in patients with a massive bone allograft and vascularized free fibula and 27 ± 2 in patients with a massive bone allograft alone (mean difference 0.75 [95% CI -10.6 to 2.57]; p = 0.39). With the numbers we had, we could not detect a difference in survival of the reconstruction between patients with a massive bone allograft and free vascularized fibula and those with a massive bone allograft alone (84% [95% CI 75% to 93%] and 87% [95% CI 80% to 94%], respectively; p = 0.89).

Conclusion

We found no difference in the survival of reconstructions between patients treated with a massive bone allograft and vascularized free fibula and patients who underwent reconstruction with a massive bone allograft alone. Based on this experience, our belief is that we should reconstruct these femoral intercalary defects with an allograft alone and use a vascularized fibula to salvage the allograft only if a fracture or nonunion occurs. This approach would have resulted in about half of the patients we treated not undergoing the more invasive, difficult, and risky vascularized procedure.

Level of Evidence Level III, therapeutic study.

Introduction

Limb salvage surgery is currently the most commonly used method of achieving local control in pediatric patients with bone sarcomas [15, 20, 22]. If tumor extension allows for the preservation of adjacent joints, an intercalary resection can be performed [24]. However, reconstruction of the femoral diaphysis after the resection of a bone tumor is surgically demanding [1, 3, 12]. Options for femoral reconstruction after intercalary tumor resection include biologic or prosthetic reconstructions [1, 2, 12, 16]. Compared with modular intercalary prostheses, the benefits of intercalary biologic reconstructions include preserving bone stock, and many surgeons prefer allografts or autografts in children with bone sarcomas [1, 2]. Traditionally, the biologic reconstruction of diaphyseal femur defects after the resection of bone tumors includes a massive bone allograft with or without a vascularized free fibula [3, 15, 16]. Massive bone allograft alone has been associated with a high proportion of complications such as host-allograft nonunion, allograft fracture, and infection, presumably because of the avascular nature of the allograft [3, 16, 22]. Despite these complications, allograft survival has been reported to be in the range of 76% to 80% in long-term outcome studies [1, 3, 5]. Typically, these reconstructions are used in adults, and there is a paucity of data on their use in pediatric patients [15]. To reduce the risk of complications related to the avascular nature of massive bone allograft, the use of a vascularized free fibula has been reported [8, 12, 15, 16]. However, the combination of massive bone allograft and vascularized free fibula is associated with a longer surgical time, a risk of donor site morbidity, and possible graft stress fracture [7, 22]. A massive bone allograft seems to increase the initial strength of the reconstruction, whereas a vascularized free fibula is thought to increase the biologic potential, providing a potentially lifelong durable reconstruction [26].

A massive bone allograft with or without a vascularized free fibula has advantages and disadvantages, but only a few studies have examined the outcomes of these two surgical techniques [7, 12, 16]. To our knowledge, only one study has compared the outcomes of massive bone allograft with or without vascularized free fibula in children undergoing intercalary reconstruction for bone sarcomas, including both femoral and tibial reconstructions, without differentiating the results of the reconstruction in these two different anatomical sites [15]. There is general agreement regarding the combination of massive bone allograft with a vascularized fibula in the tibia with the advantages of pedicled vascularized fibula over free fibula grafts to supplement allografts [15, 22]. There is no clear evidence to support the use of a massive bone allograft in association with a vascularized free fibula in the intercalary reconstruction of the femur in children [3, 7]. Therefore, we sought to compare these two surgical techniques in children undergoing intercalary resection of bone sarcomas in the femur after reconstruction using a massive bone allograft with or without a vascularized free fibula.

Specifically, we asked: (1) What was the difference in the surgical time of these two different surgical techniques? (2) What are the complications and number of reoperations associated with each procedure? (3) What were the Musculoskeletal Tumor Society scores after these reconstructions? (4) What was the survival rate of these two different reconstructions?

Patients and Methods

Study Design and Setting

For this retrospective, comparative study, we retrieved patient data from the medical record system of our institution. Between 1994 and 2016, we treated 285 patients younger than 16 years with a diagnosis of osteosarcoma or Ewing sarcoma of the femur; 179 patients underwent resection and reconstruction of the distal femur, and 36 patients underwent resection and reconstruction of the proximal femur. In the remaining 70 patients with diaphyseal tumors, we performed a total femur reconstruction in four patients, an amputation in five, and a rotationplasty in one. Sixty patients underwent intercalary resection and reconstruction with massive bone allograft with or without vascularized free fibula (Fig. 1).

Fig. 1.

Flow diagram of children with Ewing sarcoma or osteosarcoma of the femur treated at our institution during the time period of the study.

Indications

The indication for intercalary resection and reconstruction with massive bone allograft with or without vascularized free fibula was bone sarcoma growing in the metadiaphyseal area of the femur with no epiphyseal compromise and without any evidence of disease progression during preoperative chemotherapy. The choice of the type of reconstruction was probably influenced by the length of the tumor resection, with the indication to use the vascularized free fibula in the longer reconstructions.

Patients

We treated 60 patients younger than 16 years with intercalary resection of the femur and reconstruction with a massive bone allograft and vascularized free fibula (27 patients) or with massive bone allograft alone (33 patients). The diagnosis was osteosarcoma in 40 patients and Ewing sarcoma in 20 patients. We excluded patients with a follow-up duration of less than 2 years and those without sufficient clinical or imaging data for a retrospective analysis. In the group with massive bone allograft and vascularized free fibula, we excluded two patients because they did not have the minimum data for the analysis. In the group with massive bone allograft alone, we excluded 12 patients: one patient was lost to follow-up before 2 years, five patients died before 2 years of follow-up, and six patients did not have the minimum data for the analysis. Our study included 46 children with a sarcoma of the femur treated in a single institution. Of those, 25 patients underwent femur reconstruction with a massive bone allograft and a vascularized free fibula, and 21 patients underwent reconstruction with a massive bone allograft alone (Table 1). Some patients finished clinical and radiological checks as the follow-up exceeded 10 years. In the group with massive bone allograft and vascularized free fibula, four patients had a follow-up of 10, 12, 13, and 18 years, respectively, whereas in the group with massive bone allograft alone, five patients had a follow-up of 10 years, one patient had a follow-up of 11 years, and another had 13 years of follow-up. In the group who underwent reconstruction with massive bone allograft and vascularized free fibula, there were 17 boys and eight girls, with a mean age of 11 ± 3 years. The diagnosis was osteosarcoma in 14 patients and Ewing sarcoma in 11. The proximal metadiaphysis was involved in four patients, diaphysis in six, and distal metadiaphysis in 15. In the group who underwent reconstruction with massive bone allograft alone, there were 13 boys and 8 girls, with a mean age of 12 ± 2 years. The diagnosis was osteosarcoma in 17 patients and Ewing sarcoma in four. The proximal metadiaphysis was involved in three patients, diaphysis in five, and distal metadiaphysis in 13. In general, there were no important differences between the groups in terms of age (mean difference 0.88 [95% CI -0.6 to 2.3]; p = 0.26), gender (p = 0.66), diagnosis (p = 0.11), and follow-up (mean difference 12.9 [95% CI -22.7 to 48.6]; p = 0.46). There was a difference between the groups regarding the length of the resection, which was greater in patients treated with a massive bone allograft and vascularized free fibula (18 ± 5 cm) than in those treated with a massive bone allograft alone (15 ± 4 cm) (mean difference -3.0 [95% CI -5.7 to -0.4]; p = 0.02).

Table 1.

Patient demographics

Variable	MBA without VFF (n = 21)	MBA with VFF (n = 25)	p value
Age in years	12 ± 2	11 ± 3	0.26a
Gender			0.66b
Male	62 (13)	68 (17)
Female	38 (8)	32 (8)
Diagnosis			0.11c
Osteosarcoma	81 (17)	56 (14)
Ewing sarcoma	19 (4)	44 (11)
Length resection in cm	15 ± 4	18 ± 5	0.02a
Follow-up in months	130 ± 56	117 ± 61	0.46a

Data presented as mean ± SD or % (n).

^aMann-Whitney U test.

^bChi-square.

^cFisher exact test; MBA = massive bone allograft; VFF = vascularized free fibula.

Treatment Approaches

All patients were provided neoadjuvant chemotherapy according to protocols used at the time of treatment. No patient was treated with radiotherapy. A chest CT scan and PET or bone scan were performed for disease staging. None of our study patients had detectable metastases at diagnosis. MRI of the affected femur was performed in all patients to plan the surgical treatment. A CT angiography study of the lower limbs was performed routinely in patients in whom the surgical plan was to harvest the vascularized free fibula to highlight any vascular compromise, which would therefore be a possible contraindication to the use of the vascularized free fibula.

The surgery began with lesion resection, including a biopsy scar, with the appropriate bone and soft tissue margins. After resection, reconstruction was performed with a massive bone allograft, with or without a vascularized free fibula. The massive bone allograft was selected from the musculoskeletal tissue bank of our institution, and the most suitable structural allograft was chosen according to size and shape based on a radiograph of the affected femur of the patient and the femur of the donor. After being thawed in a warm solution, the donor bone was cut to match the proper defect length. We inserted the massive bone allograft, which was size-matched to fit the bone defect, and we used a plate and screws for internal fixation (Fig. 2).

Fig. 2.

A-C (A) A preoperative radiograph shows an osteosarcoma of the right distal femur in a 12-year-old boy. (B) An immediate postoperative radiograph shows reconstruction with massive bone allograft. (C) A radiograph taken 15 years postoperatively shows consolidation of the graft.

In patients in whom the surgical plan was reconstruction with a massive bone allograft and vascularized free fibula, the fibula was harvested in the standard fashion through a lateral approach, with preservation of the peroneal artery and its feeding vessels. In most patients, the ipsilateral fibula was harvested to allow for easier postoperative mobilization. The amount of harvested fibula depended on the defect size; we kept the fibular grafts at least 2 to 4 cm longer than the defect to allow for any overlap of the recipient bone osteotomy site. The fibula was then passed into the medullary canal of the massive bone allograft (concentric assembly) or beside the massive bone allograft (parallel assembly). The massive bone allograft was prepared with a hole in the AP aspect to allow passage of the peroneal pedicle. The vascularized free fibula was inserted into the massive bone allograft, and the whole system was slotted into both ends of the autologous bone and secured using a plate and screws with a diameter of 4.5 mm and different lengths. Initially, we always used the concentric bone assembly, but we later switched to parallel bone assembly after we reported that the concentric assembly could be associated with an overall negative balance of bone remodeling in the reconstruction. We now believe that the parallel assembly could promote mechanical stimulus and avoid bone resorption [25]. The composite massive bone allograft and vascularized free fibula was fixed at the host bone by internal fixation using a plate and screws. At least one plate (up to two) was used for surgical stabilization in all patients. Microvascular anastomoses were performed after bony fixation. The anastomosis was done between the donor’s peroneal artery and the deep femoral artery (Fig. 3). The mean ± SD length of resection was 16 ± 5 cm. The mean resection length for the group treated with massive bone allograft alone was 15 ± 4 cm, which differed from that of the group treated with massive bone allograft supplemented by a vascularized free fibula (18 ± 5 cm; mean difference -3.09 [95% CI -5.7 to -0.4]; p = 0.02). The mean length of the harvested vascularized fibula was 19 ± 3.7 cm. We observed only one patient who had a transient nerve palsy from the donor site. Surgical margins were negative in all patients. The two groups of children who were analyzed were homogeneous with regard to the characteristics of the patients and those of the tumor (Table 1).

Fig. 3.

A-C (A) A preoperative radiograph shows a Ewing sarcoma of the right femur in a 11-year old-boy. (B) Immediate postoperative radiograph shows reconstruction with a massive bone allograft and vascularized free fibula. (C) A 5-year postoperative radiograph shows graft consolidation.

Aftercare

Postoperatively, in patients treated with massive bone allograft and vascularized free fibula, the leg was immobilized in a short-leg cast or splint for 4 to 6 weeks. Patients treated with massive bone allograft alone could start joint rehabilitation immediately postoperatively. Patients were allowed to begin partial weightbearing at a mean of 2 months to 4 months postoperatively, and full weight-bearing was delayed until a mean of 8 months to 10 months. Surveillance for local and systemic recurrence consisted of clinical and radiologic assessments (radiograph of the femur and CT of the lung) every 3 months for the first 2 years, then every 6 months up to 5 years, and annually thereafter.

Follow-up

The median (range) follow-up duration was 123 months (28 to 261 months). The median time of follow-up for the group treated with massive bone allograft alone was 130 ± 56 months and for the group treated with massive bone allograft supplemented by a vascularized free fibula was 117 ± 61 months (mean difference 13 months [95% CI-22.7 to 48.6]; p = 0.46).

Primary and Secondary Study Outcomes

Our main objective of the study was to understand whether the addition of a vascularized free fibula could improve the results of a massive bone allograft for reconstruction of the intercalary femur of malignant bone tumors in children. Therefore, we analyzed the survival of reconstructions of two groups of children with femoral sarcoma treated with intercalary resection and reconstruction with massive bone allograft alone or massive bone allograft and vascularized free fibula. A successful reconstruction was identified as the survival free from allograft or implant removal.

Our secondary study goals were to analyze the difference in the surgical time of these two different surgical techniques, the complications and number of reoperations associated with each procedure, and the Musculoskeletal Tumor Society scores after these two different reconstructions. Therefore, three of the study authors (CE, PAA, VP) analyzed the patients’ medical records, looking for the surgical time of each operation. Then, they analyzed the radiographic images, searching for complications such as fracture or nonunion of the graft, implant breakage, or infection. Finally, they analyzed functional outcomes and possible deformities, such as genu valgu, as a consequence of surgery. The patients were functionally evaluated at the last follow-up using the Musculoskeletal Tumor Society score for the lower limbs [11]. Some patients finished clinical and radiological checks as the follow-up exceeded 10 years: In the group with massive bone allograft and vascularized free fibula alone, four patients had a follow-up of 10, 12, 13 and 18 years, respectively, whereas in the group with massive bone allograft alone, five patients had a follow-up of 10 years, as well as 11 and 13 years for two other patients, respectively. Local recurrence occurred in three patients: one in the massive bone allograft alone group and two in the massive bone allograft with vascularized free fibula group. Two of these patients died because of disease progression to the lung. The mean (range) time between surgery and local recurrence was 86 months (25 to 136 months).

Lung metastases occurred in eight patients; two occurred in the massive bone allograft alone group and six in the massive bone allograft with vascularized free fibula group. Four of these patients died because of disease progression to the lung. The mean (range) time between surgery and lung metastases was 64 months (17 to 195 months). Five patients died because of disease, one in the massive bone allograft alone group, and four in the massive bone allograft with vascularized free fibula group.

Radiologic union was assessed using plain AP and lateral-view radiographs or CT of the surgically treated bone, which was also evaluated at the follow-up examination for graft incorporation and changes in the vascularized fibula (resorption, hypertrophy, or fracture). Signs of progressive loss of the osteotomy line or haziness between the allograft and host femur, cortical continuity, and haziness at the fibula-host bone junction were parameters to assess radiographic union. We considered the allograft-host junction to be radiologically healed when the junction line was no longer visible or the junction was bridged with periosteal bone on three of the four cortices.

Complications related to the procedure (neurovascular compromise, soft tissue failure, infection) and graft-related complications (fracture or nonunion of the graft or implant breakage) with subsequent revision surgery were assessed. Regular CT of the surgically treated leg was performed every 6 months for the first 2 years and once a year thereafter to evaluate morphologic changes and incorporation of the massive bone allograft with or without vascularized free fibula.

Ethical Approval

Ethical approval for this study was obtained from the institutional review board of Istituto Ortopedico Rizzoli (REGI-SARC-PED).

Statistical Analysis

Statistical analyses were performed using SPSS software, version 25.0 (SPSS Inc). Chi-square or Fisher exact test was used to evaluate any difference between the two groups. The Mann-Whitney U test was performed to compare means between the two groups. The Kaplan-Meier test was performed for a survival analysis of the reconstruction free from graft or implant removal at a minimum follow-up of 10 years. A p value less than 0.05 was considered significant.

Results

Surgical Time

The duration of surgery was longer in patients treated with a massive bone allograft and vascularized free fibula than in patients treated with a massive bone allograft alone: 10 versus 4 hours (mean difference -6.8 [95% CI -7.1 to -6.4]; p = 0.001).

Complications and Reoperations

With the numbers we had, we found no difference between the two groups in terms of complications, such as nonunion or allograft fracture and infection. Twelve of 25 patients treated with a massive bone allograft and vascularized free fibula had one or more complication: allograft fracture (7 of 25 patients), nonunion (4 of 25 patients), and infection (4 of 25 patients). Twelve of 21 patients treated with a massive bone allograft alone had the following complications: nonunion (6 of 21 patients), allograft fracture (5 of 21 patients), and infection (1 of 21 patients). With the numbers we had, we could not detect a difference in the use of an additional iliac crest bone graft to treat nonunion between patients with massive bone allograft alone (6 of 21 patients) and patients with a massive bone allograft and vascularized free fibula (4 of 25 patients) (odds ratio 2.1 [95% CI 0.5 to 8.7]; p = 0.47). In addition, we did not detect a difference in the proportion of allograft fractures between patients with a massive bone allograft alone (5 of 21 patients) and patients with a massive bone allograft and vascularized free fibula (7 of 25 patients) (OR 0.8 [95% CI 0.2 to 3.0]; p > 0.99). Reoperation related to a complication of the massive bone allograft alone occurred in 12 of 21 patients at a mean (range) of 27 months (6 to 82 months) postoperatively. One patient had an early infection and was treated with surgical debridement. The most common complication was nonunion of the host-allograft junction (6 of 21 patients). The indications for reconstruction revision included a graft fracture (2 of 21 patients) and nonunion with implant breakage (1 of 21 patients); in the two patients with graft fracture, the reconstruction was revised using a new massive bone allograft and vascularized free fibula, while in the patient with a graft nonunion and implant breakage, the reconstruction was revised using vascularized free fibula and new internal fixation (Fig. 4).

Fig. 4.

A-E (A) A preoperative radiograph shows an osteosarcoma of the left distal femur in an 8-year-old boy. (B) An immediate postoperative radiograph shows reconstruction with a massive bone allograft. (C) A radiograph 6 months later shows nonunion with implant breakage. (D) The patient underwent a revision procedure using a vascularized free fibula and new osteosynthesis. (E) A radiograph 9 years after the last surgery shows graft consolidation.

Reoperation related to a complication of the massive bone allograft with vascularized free fibula occurred in 12 of 25 patients at a mean (range) of 11 months (1 to 21 months) postoperatively. Nine of 25 patients underwent multiple surgical procedures. The indications to perform autogenous bone grafting were nonunion of the host-allograft junction (despite repeated surgery) in three patients. Additional surgical procedures included revision of internal fixation for the allograft fracture (5 of 25 patients) (two additional patients had allograft fractures, which were successfully treated with a cast) and irrigation and debridement of a deep infection (3 of 25 patients). Of these reoperations, the graft was saved with open reduction and internal fixation in five patients. The allograft was revised in three patients at a mean (range) of 20 months (16 to 21 months) postoperatively. The indications for allograft removal included graft fracture (1 of 25 patients), nonunion (1 of 25 patients), and infection (1 of 25 patients); in two patients, the implant was revised using a modular prosthesis, and in one patient, it was revised using a massive bone allograft (Table 2). With the numbers we had, we could not demonstrate a difference in limb length discrepancy between patients treated with massive bone allograft alone and patients treated with a massive bone allograft and vascularized free fibula (mean difference -1.16 [95% CI -3.02 to 0.69]; p = 0.20) (Table 3). Six of 46 patients underwent surgery to correct a genu valgus deformity of the resected limb; 4 of 21 patients were in the massive bone allograft alone group and 2 of 25 were in the massive bone allograft with vascularized free fibula group, with no difference between the two groups (OR 2.7 [95% CI 0.4 to 16.5]; p = 0.38).

Table 2.

Complications related with MBA alone or MBA with VFF

Complication	MBA alone (n = 21)	MBA with VFF (n = 25)	Odds ratio (95% CI)	p valuea
Nonunion			2.1 (0.5-8.7)	0.47
Yes	29 (6)	16 (4)
No	71 (15)	84 (21)
Allograft fracture			0.8 (0.2-3.0)	> 0.99
Yes	24 (5)	28 (7)
No	76 (16)	72 (18)
Infection (superficial or deep)			0.2 (0.02-2.5)	0.35
Yes	5 (1)	16 (4)
No	95 (20)	84 (21)
Genu valgu			2.7 (0.4-16.5)	0.38
Yes	19 (4)	8 (2)
No	81 (17)	92 (23)
Revision of the reconstruction			1.2 (0.2-6.8)	> 0.99
Yes	14 (3)	12 (3)
No	86 (18)	88 (22)

Data presented as % (n).

^aFisher exact test; MBA = massive bone allograft; VFF = vascularized free fibula.

Table 3.

Outcome of MBA alone or MBA with VFF

Variable	MBA alone (n = 21)	MBA with VFF (n = 25)	p valuea
Final dysmetria in cm	0.8 ± 1.3	2.0 ± 2.4	0.2
Functional results (MSTS)	26.7 ± 2.3	25.9 ± 3.5	0.39

^aMann-Whitney U test; MBA = massive bone allograft; VFF = vascularized free fibula; MSTS = Musculoskeletal Tumor Society score.

MSTS Scores

The functional evaluation of the patients was done at the end of follow-up using the modified 30-point MSTS score for the lower limb [10]. With the numbers available, we found no difference between the two groups regarding functional results. The functional results were 25.9 ± 3.5 in patients with a massive bone allograft and vascularized free fibula and 26.7 ± 2.3 in those with a massive bone allograft alone (p = 0.39). Patients were generally able to have a lifestyle that allowed them the normal activities of daily living.

Survivorship

With the numbers available, we found no difference between the groups in terms of survivorship of reconstruction free from removal of the graft or implant. The overall survivorship at 10 years free from removal of the reconstruction was 84% (95% CI 75% to 93%) and 87% (95% CI 80% to 94%) in patients with massive bone allograft and vascularized free fibula and in those with massive bone allograft alone, respectively (p = 0.89) (Fig. 5).

Fig. 5.

This graph shows a Kaplan-Meier curve for survival of reconstructions free from removal of the graft or implant: massive bone allograft with and without vascularized free fibula. A color image accompanies the online version of this article.

Discussion

The options for reconstruction of diaphyseal femur defects after resection of bone sarcomas include biologic or prosthetic implants [1, 2, 12, 21]. Various types of reconstructions have been reported, including intercalary modular prostheses, distraction osteogenesis, extracorporeal autogenous grafts, and massive bone allograft with or without a vascularized free fibula [1, 3, 14, 16-18, 21]. However, there is a general consensus that biologic reconstructions with massive bone allograft with or without a vascularized free fibula are predominantly useful in children treated with intercalary femur resection for bone sarcomas [2, 3, 12]. In fact, this biological reconstruction allows surgeons to preserve bone stock after intercalary resection, which is a potential advantage, particularly in young patients [1]. One previous report suggested that massive bone allograft combined with a vascularized fibula is beneficial in the tibia with the advantages of pedicled vascularized fibula over free fibula grafts to supplement allografts [22], but reports vary about whether massive bone allograft should be associated with vascularized free fibula in the femur because this combination is associated with a longer surgical time to harvest the graft, as well as donor site morbidity and possible stress fracture of the vascularized free fibula [2, 7, 12, 22]. A longer surgical time could increase the infection risk. In addition, donor site complications, such as valgus ankle deformity or flexion deformity of the big toe, may occur in up to 17% of patients [7, 24]. The purpose of our study was to analyze reconstruction with massive bone allograft with or without vascularized free fibula following intercalary femur resection for children with bone sarcomas. Because the addition of the vascularized free fibula adds to the time and complexity of the procedure, the indication for the association of the massive bone allograft with the vascularized fibula has always been a topic of debate [3, 5, 7, 12, 16, 24, 26]. We found that vascularized free fibula did not appear to improve healing or reduce complications of the grafts, but a vascularized free fibula can be used to save a reconstruction with massive bone allograft alone in the event of a subsequent fracture or nonunion of the graft.

Limitations

Our study has several limitations. First, its retrospective nature is a major limitation. It has been difficult to establish how the criteria were established for the indication of the use of the massive bone allograft with or without the vascularized fibula. Patients with a sarcoma of the femur who received a massive bone allograft with or without a vascularized free fibula were not randomized; therefore, the two groups may not be directly comparable. Although the two groups did not differ with the numbers available regarding patient characteristics (age and gender), diagnosis, and tumor location, the two groups were not homogeneous regarding the resection length, which was greater in the patients in whom a vascularized free fibula was used. Therefore, the decision to use the massive bone allograft with vascularized free fibula may have been the consequence of longer reconstructions. However, based on the results of our study, we can at least suggest the use of allograft alone in intercalary femur resections of less than 15 cm. Second, although this study was performed in a single institution and biological reconstruction has traditionally been the treatment of choice in our institute, patients were probably treated differently over the years, and the surgical procedure was performed by multiple surgeons. In our hospital, the choice of using one type of reconstruction over than another has always depended on a multidisciplinary meeting, and so the surgeon’s preference is usually secondary to multidisciplinary discussion. Therefore, the surgical indication is the result of a discussion between different surgeons with the result of a shared and homogeneous surgical approach over the years. Third, we had a relatively small series of patients because of the rarity of femur sarcomas treated with intercalary resection and biologic reconstructions; the outcome of the study could change with a larger patient population. We did not do a power analysis to document whether we had sufficient numbers to have a truly “no difference” study. In general, small studies miss or underestimate the occurrence of less common complications. However, the population of the study was homogenous by patient characteristics, diagnosis and location of the tumor, and length of follow-up. Fourth, it is possible that some of the vascularized free fibula did not keep their blood supply, but if so, this could reinforce our study’s message that allograft alone may be the treatment of choice in intercalary femur reconstruction of children with sarcoma. Finally, although the mean follow-up duration was 10 years, with a longer follow-up duration, late complications may occur. In addition, there are patients who we have not seen any more after 10 years. However, when we finish the checkups of our patients we always tell patients to come back if they need to. In addition, complications after intercalary biological reconstruction usually appear in the first few years; therefore, we believe that if the patient has not returned after 10 years of follow-up in our clinic, they probably have no complications.

Surgical Time

The duration of surgery was longer in children treated with a massive bone allograft and vascularized free fibula than in children treated with massive bone allograft alone (10.4 ± 0.09 hours versus 3.6 ± 0.77 hours). We were not able to compare cost differences between the two procedures but we can speculate that the reduction in surgery time may also have reduced hospitalization costs. In fact, without considering hospitalization times, which in major surgery are probably longer, the cost of time in the operating room is estimated to be USD 37 per minute, with a possible difference between the two procedures of approximately USD 15,540 [9].

Complications and Reoperations

The proportions of nonunion, fracture, and infection were not different in children who underwent reconstruction with massive bone allograft alone from those of children treated with massive bone allograft and vascularized free fibula. A possible explanation for the lower nonunion rate in patients with massive bone allograft alone reported in the study by Houdek et al. [15] and our study compared with that in previous studies [1, 3, 5] is that we and Houdek et al. [15] only analyzed children with bone sarcomas and not adult patients, so we may speculate that the risk of nonunion of massive bone allograft alone in children is lower than in the adult population. Previous reports concluded that the proportion of patients with nonunion was greater in patients treated with massive bone allograft alone than in patients treated with massive bone allograft and vascularized free fibula [3, 12, 16]. The union of massive bone allograft alone is a slow, osteogenic, creeping substitution process, whereas vascularized free fibula union is secondary to the intrinsic blood supply [12]. Vascularized free fibula can facilitate bone healing and union, promoting a remodeling process following hypertrophy of the fibular graft [25]. However, Houdek et al. [15] reported no difference in the nonunion rate between children treated with massive bone allograft alone and those treated with massive bone allograft and vascularized free fibula: 36% and 33%, respectively. We confirmed the data of Houdek et al. [15], reporting no difference of nonunion in children treated with intercalary resection and reconstruction using massive bone allograft with or without vascularized free fibula.

Fractures of a biologic autograft or allograft reconstruction occur in up to 20% of patients after resection of bone sarcomas [3, 7, 12]. Prior reports showed no difference regarding the rate of graft fracture between patients treated with a massive bone allograft and patients treated with massive bone allograft and vascularized free fibula [7, 12, 15, 16]. However, the blood supply of a vascularized free fibula may provide increased healing compared with massive bone allograft alone. The incidence of massive bone allograft fractures seems to be related with the patient’s age (> 18 years) and length of resection (> 17 cm) [13]. In patients treated with massive bone allograft and vascularized free fibula, the biologic properties of a vascularized free fibula could promote massive bone allograft fracture healing and decrease the risk of reconstruction removal [1, 6]. By contrast, in the series of patients treated with massive bone allograft alone reported by Aponte-Tinao et al. [3], no fracture healing was seen, and except for one patient, all of the fractured allografts were removed. In the series of patients reported by Houdek et al. [15], there was a similar fracture proportion in a series of 29 children with bone sarcomas treated with massive bone allograft with or without a vascularized free fibula: 44% and 45%, respectively [15]. Our study had similar findings: There was a similar risk of fracture between patients treated with massive bone allograft and vascularized free fibula and patients treated with a massive bone allograft alone. However, similar to the study by Houdek et al. [15], in our study, the vascularized free fibula could save biologic reconstruction in most patients treated with massive bone allograft and vascularized free fibula who had a fracture (6 of 7 patients). In contrast, among patients with massive bone allograft alone, the reconstruction needed to be revised in 3 of 5 patients who had graft fracture or implant breakage.

Infection occurs in up to 18% of patients with massive bone allograft alone [3, 5, 23]. The long surgical time because of fibula harvesting and vascular anastomosis may increase the infection risk in patients treated with massive bone allograft and vascularized free fibula [24]. However, others have reported a similar rate of infection between patients treated with massive bone allograft and vascularized free fibula and patients treated with massive bone allograft alone [12, 19, 24, 26]. Houdek et al. [15] reported no infection in patients treated with massive bone allograft and vascularized free fibula and only a 7% infection proportion in patients treated with massive bone allograft alone. In our series, the proportion of infection was higher in patients treated with massive bone allograft and vascularized free fibula than in those treated with massive bone allograft alone, perhaps because of the longer surgical duration. However, the vascularized free fibula could survive infection, avoiding possible implant removal in 3 of 4 patients who had an infection.

Possible complications related to limb salvage surgery in children are limb length discrepancies, even after intercalary resection and reconstruction using a massive bone allograft with or without a vascularized free fibula. In addition, donor site morbidity, such as valgus deformity of the ankle or flexor halluces contracture, can be expected as a complication of using a vascularized free fibula in growing children [7, 15]. Houdek et al. [15] reported on a series of pediatric patients treated with a massive bone allograft with or without vascularized free fibula; the mean (range) limb length inequality was 3.5 cm (1.8 to 6.9 cm), and one patient had a flexor hallucis contracture [15]. We confirmed these data, reporting no difference regarding length inequality between children treated with massive bone allograft alone and those treated with massive bone allograft and vascularized free fibula.

MSTS Scores

We found no differences in MSTS scores between our study groups. This generally supports the findings of others who found no difference in outcomes scores between children treated with a massive bone allograft alone and those treated with massive bone allograft and vascularized free fibula [3, 7, 12]. In fact, the possibility of saving the joint in both types of intercalary reconstructions allows the patient to obtain similar functional results and allows the patient to pursue normal activities of daily life [12, 25]. When biologic reconstruction is successful, the outcomes are similar and almost always good, with knee motion greater than 90° in all patients. Biologic reconstructions are associated with a long period of nonweightbearing to allow for union and graft hypertrophy [1]. The mean consolidation time for diaphyseal biologic reconstructions ranges between 9 and 17 months [5, 10, 15]. Once union of osteotomies is achieved, the results are usually good because the proximal and distal joints are preserved [1].

Survivorship

With the numbers available, we found no difference in the survival of the reconstruction between children treated with massive bone allograft and vascularized free fibula and children who underwent reconstruction with massive bone allograft alone, although larger studies with more control over selecting patients for each approach may show differences in the future. The use of massive bone allograft in diaphyseal skeletal reconstruction for bone tumors replaces the bone stock to some extent and provides initial mechanical strength [24]. After healing, the massive bone allograft may be incorporated by the host and can survive for decades, probably because the outer surface of massive bone allograft becomes populated with living cells and thus is revascularized [3, 10, 15, 23]. However, especially during the first 2 years postoperatively, and before incorporation by the host, massive bone allograft has a high rate of complications because of the avascular nature of the graft, including nonunion, fracture, and infection [3, 12, 16]. Previous studies have shown that massive bone allograft is acellular and lacks blood supply, so when complications such as a fracture or nonunion occur, the massive bone allograft is unable to heal the injury [25]. According to the reports of others, a femoral intercalary allograft seems to have a higher risk of fracture or nonunion than grafts of other long bones [1, 5, 13]. However, most studies reported the outcomes of massive bone allograft in adult patients, and there are few reports on their use in pediatric patients [8, 13, 16, 19, 23]. One of the most adverse factors for long-term graft survival seems to be age older than 18 years at the time of surgery [13]. To reduce the number of complications, some authors recommended reconsidering the use of massive bone allograft alone to reconstruct defects that are ≥ 15 cm, especially in older patients [5, 10, 13]. Our data support the contention that in resections of less than 15 cm, a massive bone allograft alone can be a reasonable reconstruction option. A vascularized free fibula may help improve the surgeon’s ability to achieve union in much longer resections or to rescue biological reconstructions with massive bone allograft alone that had fracture or nonunion [1, 3, 6, 7, 21], although we could not definitively show that in this study. In our study, we could salvage the reconstructions of patients treated with massive bone allograft alone who had a fracture of the graft or nonunion with implant breakage using a vascularized free fibula.

Conclusion

We found that biologic reconstruction with massive bone allograft with or without vascularized free fibula after intercalary femur resection for bone tumors was a reasonable reconstruction option for children with malignant tumors of the femoral shaft. Because adding the vascularized free fibula adds time and probably cost, and did not appear to improve healing or reduce complications of the grafts, we believe that a vascularized free fibula might be best reserved for salvaging a femoral allograft if it fractures or does not unite. The one caveat is that these patients were not randomly selected for the use of vascularized free fibula, and the vascularized free fibula was used more frequently in longer resections. We cannot answer the question of whether a surgeon should use vascularized free fibulas for longer resections, but that could be the focus of another study. Our preference is to start with massive bone allograft alone and use vascularized free fibulas only in patients in whom grafts do not unite or in those in whom the graft is fractured.