Risks and benefits of combining denosumab and surgery in giant cell tumor of bone-a case series

BACKGROUND The RANK ligand inhibitor denosumab is being investigated for treatment of giant cell tumor of bone, but the available data in the literature remains sparse and controversial. This study analyzes the results of combining denosumab with surgical treatment and highlights possible changes for the oncologic surgeon in daily practice. METHODS A total of 91 patients were treated surgically for giant cell tumor of bone between 2010 and 2014 in an institution, whereas 25 patients of the total additionally received denosumab and were part of this study. The average age of the patients was 35 years. Eleven patients received denosumab pre- and postoperatively, whereas with 14 patients, the denosumab treatment was applied either before (7 patients) or after (7 patients) the surgery. The average preoperative therapy duration was 3.9 months and the postoperative therapy 6 months by default. RESULTS Sixteen patients presented a large tumor extension necessitating a resection of the involved bone or joint. In 10 of these patients, the indication for a resection procedure was abandoned due to the preoperative denosumab treatment and a curettage was performed. In the remaining six cases, the surgical indication was not changed despite the denosumab treatment, and two of them needed a joint replacement after the tumor resection. Also with patients treated with curettage, denosumab seems to facilitate the procedure as a new peripheral bone rim around the tumor was built, though a histologic analysis reveals viable tumor cells persisting in the denosumab-induced bone formation. After an average follow-up of 23 months, one histologically proven local recurrence occurred, necessitating a second curettage. A second patient showed a lesion in the postoperative imaging highly suspicious for local relapse which remained stable under further denosumab treatment. No adverse effect of the denosumab medication was observed in this study. CONCLUSIONS Denosumab can be a help to the oncologic surgeon by reconstituting a peripheral rim and switching the stage from aggressive to active or latent disease. But as tumor cells remain in the new-formed bone, the surgical technique of curettage has to be changed from gentle to more aggressive to avoid higher local recurrence rates

Allograft Reconstruction of the Extensor Mechanism after Resection of Soft Tissue Sarcoma

Soft tissue tumors around the knee joint still pose problems for the excision and subsequent reconstruction. Methods. In the 6 included patients the soft tissue sarcoma has its base on the anterior surface of the extensor mechanism and expands towards the skin. The entire extensor apparatus (quadriceps tendon, patella, and patellar tendon) was resected and replaced by a fresh-frozen allograft. Results. The mean follow-up was 6.7 years (range: 2-12.4 years). In two patients a local recurrence occurred, resulting in a 5-year local recurrence-free rale of 66.7% (95% CI: 19.5%-90.4%). Distant metastases were found in 4 patients resulting in a 5-year metastasis-free rate of 33.3% (95% CI: 4.6%-67.5%). Two patients underwent at least one revision surgery, including one patient in whom the allograft had to be removed. According to the ISOLS function score 24.7 points (range: 19-28 points) were achieved at the last follow-up. The mean active flexion of the knee joint was 82.5 degrees (range: 25-120 degrees) and a mean extension lag of 10 degrees (range: 0-30 degrees) was observed. Conclusions. Ihe replacement of the extensor mechanism by an allograft is a reasonable option, allowing wide margins and restoration of active extension in most patients. Trial Registration. The presented study is listed on the ISRCTN registry with trial number ISRCTN63060594

What was the survival of megaprostheses in lower limb reconstructions after tumor resections?

Analisi retrospettiva delle ricostruzioni dell'arto inferiore con protesi modulariBackground: Prosthetic replacement is the most commonly used option for reconstruction of osteoarticular bone loss resulting from bone neoplasm resection or prosthetic failure. Starting in late 2001, we began exclusively using a single system for large-segment osteoarticular reconstruction after tumor resection; to our knowledge, there are no published series from one center evaluating the use of this implant. Questions/purposes: We investigated the following issues: (1) What is the overall survival, excluding local tumor recurrence, for these endoprostheses used for tumor reconstructions of the lower extremities (knee and hip)? (2) What types of failure were observed in these reconstructions? (3) Do the survival and complications vary according to site of implant? Methods: Between September 2001 and March 2012, we exclusively used this implant for tumor reconstructions. During that time, 278 patients underwent tumor reconstructions of the hip or knee, of whom 200 (72%) were available at a minimum 2 years followup. Seventy-eight patients were excluded from the study for insufficient followup as a result of early death (42) or loss at followup (36). The reconstruction types were the following: proximal femur (69 cases), distal femur (87), proximal tibia (32), and total knee (12). Failures were classified according to the Henderson classification. Nine patients among those with followup shorter than 2 years had presented one or more failures and they were included in our analysis but separately evaluated. Results: Overall survival (no further surgical procedures of any type after primary surgery), excluding Type 5 failure (tumor recurrence), was 75.9% at 5 years and 66.2% at 10 years. Seventy-one failures occurred in 58 implants (29%). Mechanical failures accounted for 59.2% and nonmechanical failures for 40.8%. The first causes of failure of the implants were the result of soft tissue failure in 6%, aseptic loosening in 3%, structural failure in 7%, infection in 8.5%, and tumor recurrence in 4.5% of the whole series. Nine implants sustained two or more failures. Overall incidence of infection was 9.5%. No statistically significant differences were observed according to anatomical site. Conclusions: Like in the case with many such complex oncologic reconstructions, the failure rate at short- to midterm in this group was over 20%. Comparative trials are called for to ascertain whether one implant is superior to another. Infection and structural failure were the most frequent modes of failure in our experience. Level of Evidence: Level IV, therapeutic study. See Instructions for Authors for a complete description of levels of evidence

Denosumab in patients with aneurysmal bone systs: A case series with preliminary results

Abstract PURPOSE:: Aneurysmal bone cyst (ABC) is a rare skeletal tumor usually treated with surgery/embolization. We hypothesized that owing to similarities with giant cell tumor of bone (GCTB), denosumab was active also in ABC. METHODS:: In this observational study, a retrospective analysis of ABC patients treated with denosumab was performed. Patients underwent radiologic disease assessment every 3 months. Symptoms and adverse events were noted. RESULTS:: Nine patients were identified (6 male, 3 female), with a median age of 17 years (range 14-42 years). Primary sites were 6 spine-pelvis, 1 ulna, 1 tibia, and 1 humerus. Patients were followed for a median time of 23 months (range 3-55 months). Patients received a median of 8 denosumab administrations (range 3-61). All symptomatic patients had pain relief and 1 had paresthesia improvement. Signs of denosumab activity were observed after 3 to 6 months of administration: bone formation by computed tomography scan was demonstrated in all patients and magnetic resonance imaging gadolinium contrast media decrease was observed in 7/9 patients. Adverse events were negligible. At last follow-up, all patients were progression-free: 5 still on denosumab treatment, 2 off denosumab were disease-free 11 and 17 months after surgery, and the last 2 patients reported no progression 12 and 24 months after denosumab interruption and no surgery. CONCLUSIONS:: Denosumab has substantial activity in ABCs, with favorable toxicity profile. We strongly support the use of surgery and/or embolization for the treatment of ABC, but denosumab could have a role as a therapeutic option in patients with uncontrollable, locally destructive, or recurrent disease

Ankle arthrodesis with bone graft after distal tibia resection for bone tumors

Background: Treatment of distal tibial tumors is challenging due to the scarce soft tissue coverage of this area. Ankle arthrodesis has proven to be an effective treatment in primary and post-traumatic joint arthritis, but few papers have addressed the feasibility and techniques of ankle arthrodesis in tumor surgery after long bone resections. Materials and Methods: Resection of the distal tibia and reconstruction by ankle fusion using non-vascularized structural bone grafts was performed in 8 patients affected by malignant (5 patients) or aggressive benign (3 patients) tumors. Resection length of the tibia ranged from 5 to 21 cm. Bone defects were reconstructed with cortical structural autografts (from contralateral tibia) or allografts or both, plus autologous bone chips. Fixation was accomplished by antegrade nailing (6 cases) or plating (2 cases). Results: All the arthrodesis successfully healed. At followup ranging from 23 to 113 months (average 53.5), all patients were alive. One local recurrence was observed with concomitant deep infection (a below-knee amputation was performed). Mean functional MSTS score of the seven available patients was 80.4% (range, 53 to 93). Conclusion: Resection of the distal tibia and arthrodesis of the ankle with non-vascularized structural bone grafts, combined with autologous bone chips, can be an effective procedure in bone tumor surgery with durable and satisfactory functional results. In shorter resections, autologous cortical structural grafts can be used; in longer resections, allograft structural bone grafts are needed

Allograft-prosthetic composite versus megaprosthesis in the proximal tibia-What works best?

Modular megaprosthesis (MP) and allograft-prosthetic composite (APC) are the most commonly used reconstructions for large bone defects of the proximal tibia. The primary objective of this study was to compare the two different techniques in terms of failures and functional results. A total of 42 consecutive patients with a mean age of 39.6 years (range 15-81 years) who underwent a reconstruction of the proximal tibia between 2001 and 2012 were included. Twenty-three patients were given an MP, and 19 patients received an APC. There were nine reconstruction failures after an average follow-up of 62 months: five in the MP group and four in the APC group (p=0.957). The 10-year implant survival rate was 78.8% for the MP and 93.7% for the APC (p=0.224). There were no relevant differences between the two groups in functional results. Both MP and APC are valid and satisfactory reconstructive options for massive bone defects in the proximal tibia. In high-demanding patients with no further risk factors, an APC should be considered to provide the best possible functional result for the extensor mechanism

Levels of silver ions in body fluids and clinical results in silver-coated megaprostheses after tumour, trauma or failed arthroplasty

Introduction: Infection in megaprostheses remains an unsolved problem, with a rate of occurrence ranging from 5% to 12%. Silver coating of medical devices has recently been proposed to reduce infection rate because of the antibacterial effect of silver. This innovation could be particularly interesting for megaprostheses, but few data have been reported in the literature. Materials and methods: From June 2010 to August 2014 a modified MegaC System megaprosthesis with an innovative peripheral silver-added layer of titanium alloy ('Porag') was implanted in 33 patients after previous infection (21 patients) or at high risk for infection because of local or general conditions (12 patients). Previous infection followed megaprosthesis or standard arthroplasty procedures in 14 patients and trauma surgery in seven patients. A proximal femur replacement was performed in 13 patients, distal femur replacement in 13, total femur in one, and knee arthrodesis in six. Clinical results and levels of silver in blood, urine and wound drains were examined. Results: Minimum follow-up of the patients was one year (average 25.9 months).There was no infection during the first two years after surgery in the 12 patients who received a silver-coated megaprosthesis and had no previous history of infection. An infection developed in one patient at 25 months after surgery following two further surgical procedures.Infection recurred at seven months and 24 months in two out of the 21 patients (9.5%) who had received the implant because of previous septic complications.There was no clinical evidence of argyria, and no local or systemic side effects related to silver were detected.Mean levels of silver ranging from 0.41 to 5.33. μg/L in blood and from 0.28 to 0.86. μg/L in urine were detected at 24. h to 36 months after surgery. Conclusions: Silver-coated megaprostheses showed promising results in this series in terms of prevention of infection in a high-risk group of patients, many of whom had a history of infection. No side-effects were detected. The circulating silver levels confirm both the persistence of silver-coating activity after three years and the safety of silver-coated implants. Longer follow-up and larger series are needed