Background
Osteosarcoma is the most common primary bone tumor, and approximately 70% of osteosarcomas occur around the knee joint [
1,
2]. Though in the past bone sarcomas were primarily treated with amputation, advances in surgical techniques and chemotherapy have greatly improved the prognosis, and currently long-term disease free survival rates for patients with osteosarcomas with no metastases at presentation range from 60 to 80% [
3]. Limb salvage surgery has replaced amputation as the primary surgical treatment with the goal of surgery to achieve a normal margin of tissue around the pseudo capsule of the tumor and in general, the larger the margin the less chance of recurrence [
1,
4]. However, reconstruction becomes more complicated when a greater amount of bone is removed. While all methods of reconstruction have their own unique benefits and drawbacks, the use of an endoprosthesis is associated with earlier weight-bearing and improved functional outcomes [
5‐
8]. The biggest problem with allograft-prosthetic composites is healing at the allogeneic-autologous bone interface [
1‐
6]. In addition, proper fitting of the prosthesis is important for good long-term functional outcomes.
Technological advances have led to the use of computer-assisted surgery and computer-aided design (CAD) in many medical fields including oncology and orthopedics [
9‐
19]. Reports by Wong et al. [
10,
13] and Khan et al. [
11] have indicated that computer-assisted methods can improve the accuracy of resection of malignant bone tumors. Similarly, other authors have reported the utility of CAD for custom endoprosthesis construction [
4,
18,
19].
We have uniquely used preoperative CAD to plan the surgical resection and develop a custom endoprosthesis for patients with malignant bone tumors. The technique allows precise planning of the surgical resection and development of an allograft-prosthetic composite that precisely fits the area of resection. The purpose of this study is to describe the technique and to report the results in 12 patients with malignant bone tumors of the distal femur or proximal tibia.
Methods
Patients
This study was been approved by the Institutional Review Board (IRB) of School of Materials Science and Engineering, South China University of Technology, Guangzhou, Guangdong, China. All patients provided written informed consent for the procedures performed.
Patients were recruited between November 2006 and January 2012. Inclusion criteria were distal femur and proximal tibia malignant bone tumor around the knee. Exclusion criteria were: (1) distant metastasis; (2) benign tumor; (3) metastatic tumor around the knee.
This study included 9 males and 3 females with a mean age of 25.3 years (range, 13 to 40 years) with malignant bone tumors. There were 9 cases of tumors in the distal femur and 3 cases of tumors in the proximal tibia. Patient data are summarized in Table
1. In all cases, pathological examination of a tumor specimen was performed before surgery for definite diagnosis. Patients received 2 courses of chemotherapy. One week prior to surgery, computed tomography (CT) and magnetic resonance imaging (MRI) examinations were carried out to obtain two-dimensional (2D) CT and MRI data of the lesion, and preoperative simulation processes including CAD design template assisted tumor resection, allogeneic bone trimming templates, and computer simulation surgical procedure were performed.
Table 1
The demographic characteristics of 12 subjects
1
| M | 19 | Left distal femur osteosarcoma | Y | Radical resection, allogeneic bone + full knee reconstruction | 74/Alive |
2
| M | 39 | Right tibia chondrosarcoma | N | Radical resection, allogeneic bone + plate fixation reconstruction | 47/Alive |
3
| F | 32 | Left femur osteosarcoma | Y | Radical resection, allogeneic bone + personalized full knee reconstruction | 33/Alive |
4
| M | 40 | Left femur osteosarcoma and fractures | Y | Radical resection allogeneic bone + personalized full knee reconstruction | Died of lung metastases at 18 months |
5
| F | 13 | Left tibia osteosarcoma | Y | Radical resection, allogeneic bone + personalized full knee reconstruction | 26/Alive |
6
| M | 26 | Left distal femur chondrosarcoma | N | Radical resection, allogeneic bone + personalized full knee reconstruction | 17/Alive |
7
| M | 26 | Left distal femur osteosarcoma | Y | Radical resection allogeneic bone + personalized knee reconstruction | 29/Alive, lung metastases |
8
| M | 13 | Left distal femur osteosarcoma | Y | Radical resection, allogeneic bone + personalized full knee reconstruction | Died of lung metastases at 1 year |
9
| M | 16 | Left distal femur osteosarcoma | Y | Radical resection, allogeneic bone + personalized full knee reconstruction | 15/Alive |
10
| M | 26 | Right femur myofibroblastic sarcoma | N | Radical resection, allogeneic bone + femoral nail fixation | 12/Alive |
11
| F | 31 | Giant cell tumor of the left tibia | N | Margin resection, bone cement + plate fixation reconstruction | 5/Alive |
12
| M | 23 | Giant cell tumor of the left tibia | N | Extended resection, allogeneic bone + plate fixation reconstruction | 5/Alive |
Computer aided design
Computer simulation of individualized bone tumor resection and reconstruction included three-dimensional (3D) reconstruction of the disease area, identification of tumor resection range, computer-aided design (CAD) surgical template, CAD individualized prosthesis, and computer-simulated bone tumor resection and reconstruction. The 2D CT image data were imported into Mimics 14.0 software (Belgium) to reconstruct a 3D anatomical model of the bone and joint at the site of the lesion. Thin-section 2D MRI image data were imported into Mimics software to reconstruct a 3D model of the region invaded by the tumor, and accurately identify the range of the lesion. Image registration and alignment of the bone and joint anatomical model and the tumor invasion model were performed. Imageware 12.0 (UGS Corporation, USA) was used for the 3D reconstruction of lower limb mechanical parameters, tumor range boundary measurements, design-assisted surgery template, and computer-aided simulation surgery.
The boundary of surgical resection was decided according to the nature of the tumor. Generally, normal bone tissue 3–5 cm distal to the tumor boundary was removed together with the tumor. The distance from the tumor to the articular surface was used to decide whether or not to remove the joint. If the distance was more than 5 cm, the joint was not removed and bone grafting was performed using a large allogeneic bone matching the normal anatomical structure. If the distance was less than 5 cm, the joint was removed and bone grafting using a large allogeneic bone together with an individualized artificial joint was performed.
Surgical procedure
After induction of general anesthesia, the surgical area was prepared and draped, and the tumor was sufficiently exposed. An auxiliary template was installed to guide accurate tumor resection. The surgical area was soaked by distilled water for 10 min to promote necrosis of free tumor cells due to the low osmolality. Using an allogeneic trimming template, a large allogeneic bone obtained before surgery was trimmed into a 3D shape matching the bone defect after tumor resection. If needed, it was fixed to an individualized metal prosthesis with screws or bone cement to form an individualized prosthesis for repair of the bone defect. The individualized prosthesis for bone defect repair was then implanted into the bone defect area. Bone cement, bone ingrowth, or screw fixation were used to fix the prosthesis to the autogenic bone.
Postoperative care
In general at 10 days after surgery patients were fitted with a brace and allowed to walk with crutches. Patients were discharged at 14 days after surgery after removal of sutures and there was no evidence of infection. Weight bearing was begun 12 weeks after surgery.
During follow-up, patients were evaluated with International Society of Limb Salvage (ISOLS) scores. The ISOLS system scores 6 categories (pain, overall function, acceptance, supporting tools, walking, and gait). Each category is rated 0–5 with 0 being the worst score and 5 the best (e.g., for the pain category 0 = serious pain and 5 = no pain), for a total score of 30. A score of 24 to 30 is considered excellent, 18 to 23 good, 12 to 17 fair, and < 12 points poor.
Discussion
In this report we have shown the utility of computer-aided analysis, design, and surgical simulation in the management of osteosarcomas in 12 patients. The techniques allowed precise resection of the lesion and the sacrifice of a minimal amount of normal bone and the construction and placement of an accurate fitting endoprosthesis. One week after surgery, computed tomography and magnetic resonance imaging (MRI) examinations were applied to patients’ lower extremity to obtain two-dimensional (2D) CT and MRI data. Postoperative radiographs confirmed limb length, resection boundaries, and other anatomical parameters consistent with the preoperative planning. Additionally, re-applied with CAD design, three-dimensional reconstructions of lower limb joints, allogeneic bone implants and total knee prosthesis were established. To compare the post-operative CAD design with the preoperative CAD design, the whole appearances, the length of the limb, the line of force of limbs are consistent with preoperative planning. In all cases, complete resection of the lesion with clear surgical margins was achieved. The technique, however, requires specialized equipment and expertise.
Surgical resection of the lesion is a critical part in the treatment of malignant bone tumors. The purpose of surgery is to remove the tumor sufficiently to reduce the rate of local recurrence and distant metastasis [
1‐
4]. Although a greater range of excision will decrease the likelihood of recurrence, extensive resection may increase the difficulty of bone and joint reconstruction. Selection of an appropriate range of surgical resection or an accurate surgical boundary can remove the tumor lesion completely and maximally preserve the normal bone structure.
In the past, tumors were removed based on visual identification of the margins, ruler measurement, or palpation, and the actual resection range varied from the preoperative design. Surgical navigation systems were introduced to resolve this problem; however, they are complicated, time-consuming, and associated with a high initial cost [
20]. The use of computer-assisted imaging can accurately provide a 3D image of the extent of a tumor to provide for complete resection while salvaging the maximal amount of normal bone [
10,
11]. Wong et al. [
13] used computer-aided bone resection in 20 patients with 21 malignant bone tumors and clear surgical margins were achieved in all cases and the achieved bone resection was within 2 mm of the planned resection in all cases. In another study of 8 patients, Wong et al. [
21] reported that computer-assisted surgery was useful for the planning and execution of joint-preserving tumor resection. We applied CAD to create an auxiliary tumor resection template to guide intraoperative tumor resection and achieved excellent outcomes. Postoperative evaluation proved that the template-guided tumor resection is very precise.
Prior studies have reported the production of a solid model with rapid prototyping technology based on CT scans, and then use of the model for prosthesis design and simulated surgery [
10,
15,
16,
19]. In this study, we also used CAD to prepare an allogenic bone graft and accurately design a custom endoprosthesis. A 3D model of the allogenic bone was prepared from CT scan data, and bone defect reconstruction and the outcome of bone defect repair were simulated before surgery. The allogeneic bone was trimmed to a 3D shape matching the bone defect according to the CAD auxiliary trimming template. The trimmed allogeneic bone and the individualized metal prosthesis were combined to form a custom prosthesis, which had the strength of a metal prosthesis for early weight-bearing. The 3D modeling allowed the allogenic bone to fit the bone defect area precisely. This not only enhances the early recovery of local mechanical support, but also accelerates the healing speed of the interface and reduces operative time. By designing an individualized prosthesis it was assured that it would match the residual bone, the mechanical strength of the integrated prosthesis was known, and by simulating the installation before surgery any potential problems could be identified, thus reducing operative time and complications.
There are a number of theoretical advantages to the use of computer simulation of bone tumor resection and subsequent reconstruction. 1) By simulating the surgery, potential problems can be identified and remedial methods and preventive measures can be considered. 2) Advantages and disadvantages of various methods can be compared to determine the best one and constantly improve the surgical procedure. 3) The surgical team can exchange opinions with respect to the surgical procedure and all members can become familiar with the technique. 4) The simulation can be shown to the patient and family members to provide them a better understanding of the surgery and reduce their anxiety. We utilized a completely digital simulation such that the surgical procedure and the prosthesis design could be freely adjusted during simulation to decide the best treatment method and produce an individualized prosthesis according to the design.
There are few reports of the combined use of an endoprosthesis and allogeneic bone [
22,
23]. In the current study, the prosthesis surface was covered with allogeneic bone to increase the strength of the bone and joint structure, and improved the attachment of peripheral soft tissue to convert the previous hinged total knee arthroplasty into a procedure close to a conventional prosthetic replacement. The semiconstrained knee design with collateral ligament reconstruction that was used, rather than a rotating hinge knee design that is common in bone tumor reconstruction around the knee, provides a large segment of allogeneic bone around the prosthesis, and ligament reconstruction at the same time provides lateral stability of the prosthesis. Allogeneic bone combined with a non-hinged prosthesis provides reduced stress and less occurrence of loosening and also allows earlier physical activity and better recovery of knee function. The use of a CAD template for the trimming allogeneic bone to exactly match the bone defect allowed for improved contact between the autologous bone and the allogeneic bone to enhance bone union.
There are limitations of this report that should be considered. The primary limitations of this study are the small number of cases and the relatively short follow-up time. In addition, no control group or comparison group was included.
Acknowledgments
This study was supported by grants from Natural Science Foundation of China (No. 30571897), Key Programs of Science and Technology of Guangzhou (No. 2008Z1-D131), and Project on the Integration of Industry, Education and Research, Guangdong Province and Ministry of Education (2009B090300454), Province Science and Technology of Guangdong (No. 2012A030400024).
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
HWD: guarantor of integrity of the entire study; study concepts; study design; manuscript preparation; manuscript editing; manuscript review. GWY: data acquisition; data analysis; manuscript editing; manuscript review. QT: definition of intellectual content; clinical studies; manuscript preparation. BL: literature research; data acquisition; data analysis; statistical analysis; manuscript editing. JJS: clinical studies; manuscript preparation. HW: statistical analysis. YJW: experimental studies. All authors read and approved the final manuscript.