Primary malignant bone tumors (PMBT) account for 0.2% of all malignancies in adults and 3-6% in pediatric patients.‌^[1–6] Osteosarcoma and Ewing’s sarcoma are the most common entities in children and teenagers, while chondrosarcoma is the most common bone tumor in adult patients.‌^[6] The treatment of PMBT is challenging and requires a multidisciplinary approach. Surgery is the method of choice for local control of the disease and is usually done after neoadjuvant chemo- and radiotherapy. The main goal of the surgeon is to achieve a wide resection of the tumor, which is done by ablative procedures or limb sparing surgery.

In the present day, more than 85% of patients with PMBT can undergo some form of limb salvage surgery.‌^[7] Bone defects after resection are large and range from 15 to 20 cm.^[7] In pediatric patients, the resection specimen usually contains a growth plate, which leads to limb length discrepancy at skeletal maturity. Modular tumor endoprostheses have become one of the most used methods of reconstruction in limb salvage surgery because of the excellent intraoperative flexibility and the ability for early rehabilitation and weight bearing. The problem with the developing limb length discrepancy after limb sparing surgeries in pediatric patients can be solved with the implementation of expandable tumor endoprostheses, which offer a non-invasive regular elongation of the affected limb. In Bulgaria, very little research has been conducted on the functional outcomes of patients who have undergone this type of reconstruction.

The aim of our study was to analyze the functional outcome in a Bulgarian group of patients with PMBT who underwent limb salvage surgery and reconstruction with modular tumor endoprostheses.

this study was conducted at Prof. Boycho Boychev University Orthopedic Hospital, in the Department of Orthopedics and Traumatology of the Medical University of Sofia. Our series consists of 14 patients with PMBT who underwent limb salvage surgery and reconstruction with modular tumor endoprostheses in the mentioned institution between February 2012 and January 2021. The diagnosis was Ewing’s sarcoma in 7 patients, osteosarcoma in 4 patients, malignant giant cell tumor of the bone in 1 patient, mesenchymal chondrosarcoma in 1 patient, and malignant chondroblastoma in 1 patient. Our series consists of 10 males and 4 females, with a mean age of 20.5 years (range 13 to 71 years). Localizations of the primary tumor include the humerus, tibia, and femur, the most common being the distal femur.‌^[1] MRT, CT, and/or PET/CT were conducted in all cases for the diagnosis, staging, preoperative planning, and follow up.

For staging, we used the AJCC staging system for bone sarcoma, which is based on 4 key aspects of the tumor: T – size of the tumor, N – lymph node involvement, M – distant metastases, and G – histological grade of the tumor.^[8] There are 4 different stages with additional substages. All 14 patients underwent neoadjuvant chemotherapy after which they were restaged and evaluated for surgical treatment. The patients diagnosed with Ewing’s sarcoma were treated with the EURO EWING 2012 protocol.^[9] As for the patients with osteosarcoma, depending on the stage of the tumor, a combination of methotrexate, cisplatin, doxorubicin, and ifosfamide were used.^[6] For the reconstruction, we used modular tumor endoprostheses type MUTARS and MUTARS Xpand (WITTENSTEIN intens GmbH, Igersheim, Germany). A total of 8 distal femur reconstructions were conducted, making it the most common localization. One of our patients received a total humeral mega-endoprosthesis, after resection (Fig. 1). In 2 of our cases, the reconstruction was done with a femoral mega-endoprosthesis after a total femur resection (Fig. 2C). Expandable tumor endoprostheses were implemented in 5 of our patients. Adjuvant chemotherapy was done in all patients after surgery.

For functional assessment of the patients after surgery we used the MSTS score system for upper and lower extremity.^[10] MSTS score is composed of 6 criteria, the first three being pain, emotional acceptance, and functionality. Walking ability, the need for walking aid, and gait are the 3 additional criteria for lower extremity. For the upper extremity hand positioning, manual dexterity, and lifting capability are assessed. Each of these criteria is rated on a scale of 0 to 5 with a maximum score of 30 points. The higher score indicates a better functional outcome. A follow-up was done every 6 months for 2 years, after which yearly for at least 5 years.

The mean follow-up time was 38.5 months (range 8 to 96). A total of 17 operative procedures were conducted, 3 of which were secondary revisional surgeries.

The main advantage of modular tumor endoprostheses comes from their modular design, which allows the surgical team to adjust the length of bone resection intraoperatively and gives them the freedom to achieve a wide resection of the tumor especially in cases in which tumor infiltration is more severe than that seen on the preoperative imaging studies. Unlike biological reconstruction methods, modular tumor endoprostheses offer lower risk of deep infections and completely avoid any risk of non-union, disease transmission, and immune response. Patients with this type of reconstruction can start rehabilitation and weight bearing as early as the next day after the procedure. Expandable tumor endoprostheses are also modular and were designed to prevent limb length discrepancy in pediatric patients who underwent limb salvage surgery for malignant bone tumors. The expandable endoprosthesis that we used in our series is MUTARS® Xpand, the lengthening of which is based on a “growing” intramedullary nail or “FITBONE^®”.^[11] The lengthening itself is non-invasive, daily and could be done by the parents after proper training. A downside of these expanding endoprostheses is the need for a conversion to a conventional modular endoprosthesis after skeletal maturity.

Early complications after reconstruction with a modular tumor endoprosthesis include wound necrosis, peripheral nerve damage, infection, and thromboembolic incidents.‌^[‌7,11-14] The late complications associated with this method are severe and usually require surgical management. Aseptic loosening is the most common late complication with an incidence of 5-27%. It is the most common reason for failure of the reconstruction.^[1,11,14-19] The aseptic loosening of endoprosthesis usually occurs in reconstructions of the distal femur and proximal tibia. Unwin et al. reported that 32.8% of all revision surgeries done in their series were due to aseptic loosening.^[19] Fracture of the endoprosthesis is another late complication with an incidence ranging from 1% to 22%, which depends on the site of reconstruction and the length of the stem.^[7,17,18,20] Joint instability and dislocation of the modular endoprosthesis usually occur in reconstruction of the hip and shoulder joint. The incidence of dislocation after shoulder joint reconstruction is 56%, and between 10% and 15% after hip reconstruction.^[7,15,21,22] The infection rate after reconstruction with a modular tumor endoprosthesis is 1%–13%.^{[17,18,20,23,24]} This is a serious complication that could potentially lead to amputation after limb sparing surgery. Gosheger at al. reports a 13% infection rate from their series of 250 patients treated with resection and endoprosthetic reconstruction for malignant bone tumors.^[20] Mechanical failure of the expanding mechanism is a specific complication for the expandable modular endoprosthesis, which requires a revision surgery for its management. Gilg et al. reported a failure in the lengthening mechanism in 5 prostheses (9.8%).^[25]

Endoprosthesis survival rates and overall reconstruction longevity vary by anatomic site. Pala et al. reported an overall prosthesis survival rate of 70% at 4 years and 58% at 10 years.^[26] Grimer et al. reported a 18% endoprosthesis survival rate after a mean follow-up of 29.4 years.^[27] In the Horowitz et al. series of 93 reconstructions, prosthesis survival at 5 years was 88% for the proximal femur. Distal femur and proximal tibia reconstructions had 59% and 54%, respectively. Overall endoprosthesis survival for the same series was 63% at 5 years and 36% at 10 years.^[28]

The functional results after reconstruction with modular tumor endoprostheses are generally positive. According to most literature sources, the mean MSTS score value is between 60 and 90.^{[12,15,16,20,24,25,27-30]} Gosheger at al. report a MSTS score of 70% in their series of 250 patients.^[20] Rougraff et al. also report an MSTS score of 77% after reconstruction of the distal femur.^[17] Upper extremity functional results are also positive as Wang et al. report a mean MSTS score of 66.7% after reconstruction of the proximal humerus.^[22] Tang et al. achieved even better results with the usage of a synthetic mesh for soft tissue reinsertion, as that patient group had an MSTS score of 79% in comparison to 66% for the patient group with no synthetic mesh.^[21] Balke et al. report excellent functional results and an MSTS score of 80% and 83% after reconstruction of the distal femur and proximal tibia, respectively.^[31] An expandable modular endoprosthesis also offers good functional results as the mean MSTS score for reconstructions around the knee is between 75-90%, between 50-75% in patients with a hip endoprosthesis, and 50% in those with a shoulder expandable endoprosthesis.^[7,16,18,25] Torner et al. report a mean MSTS score of 86% in their series of 7 pediatric patients with expandable endoprostheses.^[30] Gilg et al. also reported a MSTS score of 86% in their patient group.^[25]

Atalay et al. compare the functional levels of patients with a conventional total hip endoprosthesis and those with a tumor hip endoprosthesis.^[32] Interestingly, patients with conventional total hip endoprostheses have no significant difference in functionality from the patients with a tumor endoprosthesis.

The mean MSTS score and overall functional results in our patient group were very good and comparable to those of other authors (Table 1).

As for the complications until now, we have encountered only 2 severe ones that required surgical management. The misuse of the impulse transmitter for the expanding endoprosthesis was probably the reason for the mechanical failure of the expanding mechanism, which required replacement in one of our patients. The aseptic loosening of the femoral component that we encountered was caused by a shorter femoral stem that was used in the initial reconstruction. To lower the risk of these complications, a proper diameter and length of the femoral stem should always be used.

The limitations of the study are the short follow-up period and the small patient group, which did not allow for a more in-depth analysis of the late complications, the secondary surgeries needed for their management and for the conversion from an expandable to a conventional modular endoprosthesis at skeletal maturity in some patients. All the mentioned conditions cause a significant impact on the end functional results. The strict follow-up of the patients will continue, as some of them will soon need conversion surgery.

Reconstruction with modular tumor endoprostheses offers superb functionality and improved life quality in patients with primary malignant bone tumors.

This study is part of the National Scientific Program “Young Scientists and Postdoctoral researchers”, The ‘Young Scientists’ Module, Medical University of Sofia, Medical Faculty, No. D – 39/ 01.03.2021

The authors have declared that no competing interests exist.

The authors have no support to report.