Ewing sarcoma, a highly aggressive bone and soft-tissue cancer, is considered a prime example of the paradigms of a translocation-positive sarcoma: a genetically rather simple disease with a specific and neomorphic-potential therapeutic target, whose oncogenic role was irrefutably defined decades ago. This is a disease that by definition has micrometastatic disease at diagnosis and a dismal prognosis for patients with macrometastatic or recurrent disease. International collaborations have defined the current standard of care in prospective studies, delivering multiple cycles of systemic therapy combined with local treatment; both are associated with significant morbidity that may result in strong psychological and physical burden for survivors. Nevertheless, the combination of non-directed chemotherapeutics and ever-evolving local modalities nowadays achieve a realistic chance of cure for the majority of patients with Ewing sarcoma. In this review, we focus on the current standard of diagnosis and treatment while attempting to answer some of the most pressing questions in clinical practice. In addition, this review provides scientific answers to clinical phenomena and occasionally defines the resulting translational studies needed to overcome the hurdle of treatment-associated morbidities and, most importantly, non-survival.

Custom-made, three-dimensionally-printed (3D) bone prostheses gain increasing importance in the reconstruction of bone defects after musculoskeletal tumor resections. They may allow preservation of little remaining bone stock and ensure joint or limb salvage. However, we believe that by constructing anatomy-imitating implants with highly cancellous titanium alloy (TiAl₆V₄) surfaces using 3D printing technology, further benefits such as functional enhancement and reduction of complications may be achieved. We present a case series of four patients reconstructed using custom-made, 3D-printed intercalary monobloc tibia prostheses treated between 2016 and 2020. The mean patient age at operation was 30 years. Tumor resections were performed for Ewing sarcoma (n = 2), high-grade undifferentiated pleomorphic bone sarcoma (n = 1) and adamantinoma (n = 1). Mean resection length was 17.5 cm and mean operation time 147 min. All patients achieved full weight-bearing and limb salvage at a mean follow-up of 21.25 months. One patient developed a non-union at the proximal bone-implant interface. Alteration of implant design prevented non-union in later patients. Mean MSTS and TESS scores were 23.5 and 88. 3D-printed, custom-made intercalary tibia prostheses achieved joint and limb salvage in this case series despite high, published complication rates for biological and endoprosthetic reconstructions of the diaphyseal and distal tibia. Ingrowth of soft tissues into the highly cancellous implant surface structure reduces dead space, enhances function, and appears promising in reducing complication rates.

Despite very good prosthesis retention times, the growing numbers of primary implantations of hip endoprostheses are leading to increasing numbers of revision operations. Periprosthetic infection, particularly in revision implants, often leads to a massive loss of bone stock, so that in a two-stage exchange the only option left is implantation of a megaendoprosthesis. This retrospective study investigated the clinical and functional outcome for patients who received megaendoprostheses in the proximal femur in two-stage exchange procedures. Forty-nine patients were treated between 1996 and 2014 (mean age 71 years, mean follow-up period 52 months). Microorganisms were isolated intraoperatively in 44 patients (89.9%). The reinfection rate was documented in patients who did not undergo any further revision surgery due to mechanical failure (primary) and in patients who had subsequent revisions after reimplantation and subsequent reinfection (secondary). The mean C-reactive protein level at the time of reimplantation was 1.25 mg/dL (range 0.5–3.4). The primary success rate with curative treatment for prosthetic joint infection was 92% (four of 49 patients). The secondary success rate with infection revision cases was 82% (three of 17 revision cases). The mean Harris hip score was 69 (range 36–94). The majority of patients needed different types of walking aid or even wheelchairs, and only 50% of the patients were able to walk outside. Reinfections occurred in only 8% of patients who underwent two-stage exchanges with a proximal femur replacement. When revision surgery for the proximal femur replacement was required for mechanical reasons, however, the associated reinfections increased the reinfection rate to 18%. Proximal femur replacement achieves a clear reduction in pain, maintenance of leg length, and restoration of limited mobility, and the procedure thus represents a clear alternative to the extensive Girdlestone procedure, which is even more immobilising, or mutilating amputation.

Background: Fluorescence-guided surgery (FGS) with 5-aminolevulinic acid (5-ALA) and other contrast agents has shown its efficacy in improving resection margins, local recurrence and survival rates in several medical disciplines. It is the objective of this study to analyze the engraftment rate of musculoskeletal tumor specimens on the chick chorio-allantoic membrane (CAM), the rate of tumor fluorescence (PDD), and the effects of photodynamic therapy (PDT) after exposure of tumors to 5-ALA in an in vivo environment. Methods: A total of 486 CAMs were inoculated with macroscopic tumor grafts (n = 26; n = 478 eggs) and primary cell culture suspensions (n = 2; n = 8 eggs) from 26 patients on day 10 of egg development. On day 16, 2 mg/200 µl 5-ALA were topically applied per egg. After 4 h of incubation, Protoporphyrin IX was excited using blue light (420 ± 10 nm). Tumor fluorescence (PDD) was photo-documented. A subgroup of specimens was additionally exposed to red light (635 nm ± 10 nm; PDT). After the termination of the experiment, CAM-grown tumors were histopathologically analyzed. Results: Benign and borderline tumors (chondroblastoma, giant cell tumor of bone and atypical chondrogenic tumor) presented with high rates of detectable fluorescence. Comparable results were found for chondrosarcoma, osteosarcoma and Ewing’s sarcoma among bone and dedifferentiated liposarcoma, myxofibrosarcoma and undifferentiated pleomorphic sarcoma among soft tissue sarcomas. Overall, tumor fluorescence was negative for 20.2%, single-positive (+) for 46.9% and double-positive (++) for 32.9% of macroscopic xenografts, and negative in 20% and (+) in 80% of primary cell culture tumors. Macroscopic tumor xenografts (n = 478) were identified as viable in 14.8%, partially viable in 2.9% and partially to completely regressive in 45.2%. All (n = 8) tumors grown from primary cell culture were viable. After PDT, tumor samples were found viable in 5.5%, partially viable in 5.5% and partially to completely regressive in 68%. Egg survival increased with decreasing PDT doses. Conclusions: The CAM model proves to be a suitable in vivo model for the investigation of short-term observation questions in musculoskeletal tumors. The findings of this study warrant further investigation of PDT effects on musculoskeletal tumors and a possible incorporation of 5-ALA FGS in clinical Orthopedic Oncology care.

Intra-articular sarcoma of the knee joint is a very rare condition. Extra-articular resection and reconstruction with a tumor prosthesis is usually performed. This report describes the results with this rare surgical procedure. This retrospective study evaluated the clinical and functional results after extra-articular resection of the knee joint in eight patients with soft-tissue sarcomas of the knee that were reconstructed using a tumor endoprosthesis. Five of the eight patients (62.5%) ultimately had to undergo amputation, mainly due to periprosthetic infection. In addition, two patients experienced periprosthetic fractures. The mean Musculoskeletal Tumor Society score was 18 (range 10-22), as function was impaired due to a weak extensor mechanism. These results suggest that in patients with intraarticular soft-tissue sarcomas, limb salvage procedures with tumor prostheses after extra-articular resection are associated with very high complication rates. In most cases, long-term limb salvage was not possible. When limb salvage is successful, function is also poor due to a weak extensor mechanism in the knee joint. The indication for this procedure should therefore be considered critically.