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. 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? 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. 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. 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 IV, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.

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. 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. 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. 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.

Background Diagnosis and treatment of low-grade chondrosarcoma remain controversial. We performed a review of a single-center series with the aims of assessing the oncologic outcome of these patients, verifying if intralesional curettage can be adequate treatment, and defining clinical criteria to support the surgeon and the oncologist in decision-making for surgery and subsequent follow-up. Materials and methods A retrospective review of 85 patients was performed (61 females and 24 males, age range 20–76 years). The site of the lesion was the femur in 35 cases, humerus in 33, tibia in 15, and fibula in 2. Sixty-four patients were treated by intralesional curettage. Twenty-one patients with aggressive radiological patterns were treated with wide resection. Results Mean follow-up was 67 months (range 24–206 months). Two patients developed local recurrence, both after intralesional curettage. The difference in incidence of recurrence was not statistically significant between the two groups. No distant metastases were observed. Postsurgical complications were significantly higher in the resection group. Conclusions Low-grade chondrosarcoma of the appendicular skeleton without aggressive radiological patterns can be treated with intralesional surgery with good oncological outcome and very low rate of postsurgical complications. Wide resection, following surgical principles of malignant bone tumors, should be considered only when aggressive biologic behavior is evident on imaging.

We recently developed a clinical decision support tool, capable of estimating the likelihood of survival at 3 and 12 months following surgery for patients with operable skeletal metastases. After making it publicly available on www.PATHFx.org , we attempted to externally validate it using independent, international data. We collected data from patients treated at 13 Italian orthopaedic oncology referral centers between 2010 and 2013, then applied to PATHFx, which generated a probability of survival at three and 12-months for each patient. We assessed accuracy using the area under the receiver-operating characteristic curve (AUC), clinical utility using Decision Curve Analysis (DCA), and compared the Italian patient data to the training set (United States) and first external validation set (Scandinavia). The Italian dataset contained 287 records with at least 12 months follow-up information. The AUCs for the three-month and 12-month estimates was 0.80 and 0.77, respectively. There were missing data, including the surgeon’s estimate of survival that was missing in the majority of records. Physiologically, Italian patients were similar to patients in the training and first validation sets. However notable differences were observed in the proportion of those surviving three and 12-months, suggesting differences in referral patterns and perhaps indications for surgery. PATHFx was successfully validated in an Italian dataset containing missing data. This study demonstrates its broad applicability to European patients, even in centers with differing treatment philosophies from those previously studied.

Soft tissue sarcomas (STSs) are a heterogeneous group of rare tumors. Although constituting only 1% of all human malignancies, STSs represent the second most common type of solid tumors in children and adolescents and comprise an important group of secondary malignancies. Over 100 histologic subtypes have been characterized to date (occurring predominantly in the trunk, extremity, and retroperitoneum), and many more are being discovered due to molecular profiling. STS mortality remains high, despite adjuvant chemotherapy. New prognostic stratification markers are needed to help identify patients at risk of recurrence and possibly apply more intensive or novel treatments. Recent scientific advancements have enabled a more precise molecular characterization of sarcoma subtypes and revealed novel therapeutic targets and prognostic/predictive biomarkers. This review aims at providing a comprehensive overview of the most relevant cellular, molecular and metabolic biomarkers for STS, and highlight advances in STS-related biomarker research.