Does Augmenting Irradiated Autografts With Free Vascularized Fibula Graft in Patients With Bone Loss From a Malignant...

Extracorporeally irradiated autografting is a recognized technique in reconstruction after intercalary resections, but it has drawbacks such as nonunion and graft fracture. Because sterilized autografts lose some of their mechanical properties due to involvement of the cortex with tumor, the curettage, and the adverse effects of irradiation or other sterilization techniques, some have proposed adding vascularized fibula to augment the autograft. Because this potentially adds morbidity, we sought to address the value of adding vascular fibular grafts to reconstruction with irradiated autografts.

Comparing patients who received an extracorporeally radiated autograft alone with those who received such a graft augmented by a free vascularized fibular autograft: (1) Was the proportion of patients who did not achieve union by 12 months higher in the group that received the augmented (vascularized) graft? (2) Did the augmented-graft group demonstrate greater survivorship free from graft loss at 72 months than did the group receiving an irradiated graft alone? (3) Were there between-group differences in functional results? (4) Were there between-group differences in complications, defined as those substantial enough to result in further surgery?

In our single-center study, conducted in a tertiary academic referral center, we performed a retrospective chart audit of patients undergoing intercalary resections for primary sarcomas of the femur and tibia. Between January 2002 and April 2023, three surgeons (HK, BK, DS) treated 345 patients for bone sarcoma of the femur or tibia. Of those, we considered 25% (85) treated with intercalary resection for primary bone sarcomas as potentially eligible. A further 7% (23 of 345) of patients were excluded because their reconstruction was performed using a technique other than irradiated autografts. Another 2% (6) had died prior to the minimum follow-up period of 24 months, another 1% (3) did not finish the 24-month follow-up, and 1% (3) were lost to follow-up for > 5 years, leaving 14% (50 of 345) for analysis here. Among these, 26% (13 of 50) of patients underwent reconstruction involving an extracorporeally irradiated autograft and augmentation with a vascularized fibula autograft. In the remaining 37 patients, reconstruction was performed using extracorporeally irradiated bone alone. During this period, intercalary resection was typically indicated for patients with primary bone sarcomas located in the metaphyseal or diaphyseal regions without articular involvement, provided that they demonstrated a favorable response to neoadjuvant therapy. In this predominantly young patient cohort, extracorporeally irradiated autografts were our preferred reconstruction method after sarcoma resection. Isolated extracorporeally irradiated autografts were selected for patients with radiologic evidence of adequate bone quality and preserved cortical integrity. In patients who have a tumor with extensive cortical destruction-yet still considered suitable for reconstruction after irradiation-vascularized fibular grafts were added to the irradiated autografts. In the group reconstructed with irradiated autograft alone, 54% (20 of 37) of patients were male and 46% (17) were female, with a median (range) age of 15 years (4 to 60). The diagnoses included osteosarcoma in 51% (19 of 37) of patients and Ewing sarcoma in 32% (12). The tumor was located in the tibia in 59% (22) of patients and in the femur in 41% (15). In the group receiving irradiated autograft augmented with vascularized fibula, 6 of the 13 patients were male and 7 were female, with a median (range) age of 13 years (6 to 40). Diagnoses included osteosarcoma in eight of 13 patients, Ewing sarcoma in four, and malignant mesenchymal tumor in one patient. Tumor originated from the femur in 11 patients and from the tibia in two. The two groups were similar in terms of histopathologic diagnosis, age, gender, follow-up duration, and tumor location within bone while the proportion of tumors originating from the femur was higher in the group treated with vascularized fibula augmentation (85% versus 41%; p < 0.05). Fixation technique and the ratio of the resected bone length to the entire bone were noted using the first postoperative radiograph. Bony union, defined as bony bridging in at least three cortices, was assessed using two-plane radiographs. Patients who achieved bony union within the first 12 months without undergoing any additional surgical intervention were classified as having union. Patients whose autograft incorporation exceeded 12 months but ultimately achieved union before 15 months without the need for additional intervention were classified as having delayed union. Nonunion was defined as when patients demonstrated incomplete integration at the 15-month follow-up or when patients needed additional intervention before healing. The survival of extracorporeally irradiated autografts, free from any degree of loss (partial or complete graft loss attributed to graft fracture resorption or graft removal after infection or recurrence), was assessed using competing risk analysis, with death as a competing event at 72 months postoperatively. Functional outcomes were measured using the 1993 version of the Musculoskeletal Tumor Society (MSTS) scoring system with its six subheadings. Complications were defined as events that were substantial enough to result in surgery. Problems related to fibular donor site were also recorded.

In patients who received reconstruction with irradiated autografts alone, graft loss occurred in five patients before union was achieved, and one patient died before 12 months; thus, these patients were excluded from analysis on union within 12 months. Among the remaining 31 patients, union was achieved within 12 months in 71% (22) of patients, delayed union in 16% (5) of patients, and nonunion in 13% (4) of patients. In the group in which vascularized fibula was used to augment the irradiated autograft, union occurred within 12 months in 9 of 13 patients, while delayed union and nonunion were observed in two patients each. There was no difference between the groups (p > 0.99). At 72 months, the cumulative incidence of graft loss was 32% (95% confidence interval [CI] 19.1% to 47.6%) in the irradiated autograft-alone group and 13% (95% CI 2.3% to 40.3%) in the fibula-augmented group. The cumulative incidence of death at 72 months was 25% (95% CI 13.9% to 40.3%) in the irradiated autograft-alone group and 20% (95% CI 5.0% to 48.6%) in the fibula-augmented group. Competing risk regression for graft loss, treating death as a competing event, showed no difference between the groups (subdistribution HR 0.42 [95% CI 0.10 to 1.84]; p = 0.25). The median (range) MSTS score in patients reconstructed with irradiated autograft alone was 27 (18 to 30), while the median (range) MSTS score in those reconstructed with irradiated autograft augmented with vascularized fibula was 24 (20 to 30), and there were no differences between the groups in terms of total MSTS scores or any of the MSTS subdomains. In patients reconstructed with irradiated autograft alone, a total of 28 complications were observed in 20 patients. For those patients, the median (range) time from surgery to complication was 15 months (2 to 72). In patients reconstructed with irradiated autograft augmented with vascularized fibula, a total of nine complications were observed in seven patients. For those patients, the median (range) time from surgery to occurrence of complication was 18 months (1 to 23). There was no difference between the two groups in terms of the proportion of patients who faced complication or the median time to occurrence of complications. A total of four patients experienced donor site-related problems, none of which resulted in further surgery.

Despite being applied in tougher lesions with less favorable bone quality, the addition of a vascularized fibula into extracorporeally irradiated autograft for reconstruction of intercalary resections yielded comparable outcomes in terms of bony union, graft survival, functional scores, and complications when compared with patients with more favorable host bone who received reconstruction with irradiated graft alone. Although our numbers were small, given the complexity and additional morbidity associated with vascularized fibular graft, its use might be reserved for selected patients in whom biological reconstruction is desired, but the host bone is deemed weakened and unlikely to be successful compared with those patients with more intact bone. Larger studies comparing this technique with other reconstruction options such as structural allografts, intercalary endoprostheses, or cement-rod constructs are needed to better define its role. We recommend reserving the use of vascularized fibula augmentation as a reinforcement strategy in reconstructions with irradiated autografts after intercalary resections of the femur and tibia, opting for it only when additional benefit is anticipated, given that it prolongs operative time, necessitates the involvement of a reconstructive surgery team, and introduces additional donor-site considerations.

Level III, therapeutic study.