Intraoperative Extracorporeal Irradiation and Frozen Treatment on Tumor-bearing Autografts Show Equivalent Outcomes for Biologic Reconstruction
Authors: Wu Po-Kuei , Chen Cheng-Fong , Chen Chao-Ming , Cheng Yu-Chi , Tsai Shang-Wen , Chen Tain-Hsiung , Chen Wei-Ming 
Published: April 2018

Abstract

Background
Immediately recycling the resected bone segment in a biologic limb salvage reconstruction is an option after wide resection of bone. Intraoperative extracorporeal irradiation and freezing are the two major tumor-killing techniques applied on the fresh tumor-bearing autografts. However, graft-derived tumor recurrence and complications are concerns affecting graft survival.

Questions/Purposes
We therefore asked: (1) Is there a difference in the proportion of patients achieving union by 18 months after surgery between the groups with extracorporeal-irradiated autografts and frozen-treated autografts? (2) Is there any difference in the frequency of graft-related complications for patients receiving either an extracorporeal-irradiated or a frozen-treated autograft? (3) Is there a difference between the techniques in terms of graft-derived recurrence? (4) Are there differences in failure-free grafts, and limb and overall survivorship between autografts treated by extracorporeal irradiation or by freezing?

Methods
During the study period we treated a total of 333 patients with high-grade osteosarcoma. One hundred sixty-nine patients were excluded. Overall, 79 of the enrolled 164 patients received recycled autografts treated with extracorporeal irradiation whereas the other 85 received frozen-treated autografts. The mean followup was 82 ± 54 months for the extracorporeal irradiation group and 70 ± 25 months for the frozen autograft group, and one patient was lost to followup. Complications and graft failure (revision required for primary graft removal) were characterized by adapting the International Society of Limb Society (ISOLS) system modified for inclusion of biologic and expandable reconstruction. The primary study endpoints were the proportion of patients in each group who achieved radiographic union, and had an ISOLS grade of fair or good host graft fusion at 6, 9, 12, and 18 months after surgery. Five-year survival data for graft failure and limb amputation were analyzed by a cumulative incidence function regression model whereas the Kaplan-Meier function was used to test the 5-year overall survival rate between the two techniques.

Results
With the numbers available, no differences were found in the accumulated proportion of patients achieving union between the groups at 6, 9, 12, and 18 months. Radiographic evaluation did not show differences in the average scores of compared criteria. However in the subchondral bone subcriterion, more patients receiving frozen-treated autografts had higher scores (p = 0.03). Complications leading to a second surgery were not different between extracorporeal irradiation and frozen autografts in aspects of soft tissue failure (Type 1B), nonunion (Type 2B), structural failure (Type 3A and Type 3B), or infection (Type 4A and Type 4B). No graft-originating tumor recurrence was found and there was no difference in Type 5A tumor progression originating from soft tissue in the groups (odds ratio, 0.8; 95% CI, 0.3-2.1; p = 0.7). Neither group showed a difference in the cumulative incidence for graft failure and limb amputation. Five-year overall survival rates were 83% and 84% (p = 0.69) for extracorporeal-irradiated and frozen autografts respectively. A decrease in survivorship was seen at 50 to 100 months after surgery for the extracorporeal irradiation group.

Conclusion
We segregated the ISOLS criteria evaluating the graft-mediated tumor progression into host- or graft-derived complications (Types 5B and 5C) in this study. With the available data, there was no difference in the incidence of tumor recurrence derived from irradiation- or frozen-treated autografts. Ongoing evaluations comparing 10-year survivorship for both groups will be helpful to elucidate the possible difference found after 100 months.

Level of Evidence Level
III, therapeutic study