Jendrik Hardes

Endoprosthetic reconstruction in 250 patients with sarcoma

We assessed the clinical results and complications associated with a new endoprosthetic replacement system (Mutars®) used in 250 patients with a malignant bone or soft tissue tumor. The key features of the system are its cementless, hexagonal-shaped stem (titanium alloy), the possibility of torsion adjustments in 5°-increments, and the Trevira® tube for soft tissue attachment. The mean age of the patients was 30.7 years, and the mean followup was 45 months. Prosthetic survival at 5 years was 89.7% for the upper extremity and 68.5% for the lower extremity. Prosthetic survival without any reoperation was 73.4% at 3 years postoperatively and 60.4% at 5 years postoperatively. Prosthetic failure was caused by deep infection in 12% (30 patients) of patients and aseptic loosening in 8% (20 patients) of patients. Stem fracture occurred in only 1.6% (four patients) of patients. Dislocation rates were reduced by using the Trevira® tube. Limb survival was achieved in 82.6% to 93.1% of patients depending on the endoprosthetic replacement site, and functional results ranged between 63% to 83% according to the Tumor Society score. Our results suggest limb salvage with the Mutars® endoprosthesis is successful with good functional results.Level of Evidence: Therapeutic study, Level IV (case series). See the Guidelines for Authors for a complete description of levels of evidence.

Reduction of periprosthetic infection with silver-coated megaprostheses in patients with bone sarcoma.

The placement of megaprostheses in patients with bone sarcoma is associated with high rates of infection, despite prophylactic antibiotic administration. In individual cases, secondary amputation is unavoidable in the effort to cure infection.

Bone Tumors in Adolescents and Young Adults

Opinion statementBone tumors, particularly osteosarcomas and members of the Ewing Sarcoma Family of Tumors (ESFT), are typical malignancies of adolescents and young adults. Current diagnostic and therapeutic guidelines for patients of all ages were developed in this specific age group. The aim of bone sarcoma therapy should be to cure the patient from both the primary tumor and all (micro-)metastatic deposits while maintaining as much (extremity) function and causing as few treatment-specific late effects as possible. Bone sarcoma therapy requires close multidisciplinary cooperation. Usually, it consists of induction chemotherapy, followed by local therapy of the primary tumor (and, if present, primary metastases) and further, adjuvant chemotherapy. Local treatment for osteosarcoma should be surgery whenever feasible. Surgery is also gaining importance in ESFT, which was long considered a domain of radiotherapy. Modern reconstructive techniques continue to expand the indications for limb salvage, particularly for patients who have not yet reached skeletal maturity. Treatment within the framework of prospective, multi-institutional trials should be considered standard of care not only for children, but also for affected adolescents and (young) adults. Such trials are essential in guaranteeing that all patients have access to appropriate care and that progress from biological studies can be translated into prognostic improvements without undue delay. The rarity of bone sarcomas increasingly requires trials to be multinational.

Risk of recurrence and survival after relapse in patients with Ewing sarcoma.

The prognosis in patients with relapsed Ewing sarcoma is unfavorable. Our investigation identifies factors predicting for the outcome following relapse.

Level of activity in children undergoing cancer treatment

The diagnosis of cancer bears severe implications for pediatric patients. One immense restriction consists in a reduced level of activity due to different factors. Physical activity affects various aspects of development and can be regarded as an essential part of a childs life. In the present study physical activity in patients undergoing cancer therapy was quantified in order to determine the extent of the restriction and to provide baseline information for the assessment of possible interventions.

Expression of β-catenin and p53 are prognostic factors in deep aggressive fibromatosis

Aims:  To determine the prognostic significance of β‐catenin in aggressive fibromatosis and to identify potential molecular markers for new targeted therapies.

Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial

Summary Background We designed the EURAMOS-1 trial to investigate whether intensified postoperative chemotherapy for patients whose tumour showed a poor response to preoperative chemotherapy (≥10% viable tumour) improved event-free survival in patients with high-grade osteosarcoma. Methods EURAMOS-1 was an open-label, international, phase 3 randomised, controlled trial. Consenting patients with newly diagnosed, resectable, high-grade osteosarcoma aged 40 years or younger were eligible for randomisation. Patients were randomly assigned (1:1) to receive either postoperative cisplatin, doxorubicin, and methotrexate (MAP) or MAP plus ifosfamide and etoposide (MAPIE) using concealed permuted blocks with three stratification factors: trial group; location of tumour (proximal femur or proximal humerus vs other limb vs axial skeleton); and presence of metastases (no vs yes or possible). The MAP regimen consisted of cisplatin 120 mg/m2, doxorubicin 37·5 mg/m2 per day on days 1 and 2 (on weeks 1 and 6) followed 3 weeks later by high-dose methotrexate 12 g/m2 over 4 h. The MAPIE regimen consisted of MAP as a base regimen, with the addition of high-dose ifosfamide (14 g/m2) at 2·8 g/m2 per day with equidose mesna uroprotection, followed by etoposide 100 mg/m2 per day over 1 h on days 1–5. The primary outcome measure was event-free survival measured in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00134030. Findings Between April 14, 2005, and June 30, 2011, 2260 patients were registered from 325 sites in 17 countries. 618 patients with poor response were randomly assigned; 310 to receive MAP and 308 to receive MAPIE. Median follow-up was 62·1 months (IQR 46·6–76·6); 62·3 months (IQR 46·9–77·1) for the MAP group and 61·1 months (IQR 46·5–75·3) for the MAPIE group. 307 event-free survival events were reported (153 in the MAP group vs 154 in the MAPIE group). 193 deaths were reported (101 in the MAP group vs 92 in the MAPIE group). Event-free survival did not differ between treatment groups (hazard ratio [HR] 0·98 [95% CI 0·78–1·23]); hazards were non-proportional (p=0·0003). The most common grade 3–4 adverse events were neutropenia (268 [89%] patients in MAP vs 268 [90%] in MAPIE), thrombocytopenia (231 [78% in MAP vs 248 [83%] in MAPIE), and febrile neutropenia without documented infection (149 [50%] in MAP vs 217 [73%] in MAPIE). MAPIE was associated with more frequent grade 4 non-haematological toxicity than MAP (35 [12%] of 301 in the MAP group vs 71 [24%] of 298 in the MAPIE group). Two patients died during postoperative therapy, one from infection (although their absolute neutrophil count was normal), which was definitely related to their MAP treatment (specifically doxorubicin and cisplatin), and one from left ventricular systolic dysfunction, which was probably related to MAPIE treatment (specifically doxorubicin). One suspected unexpected serious adverse reaction was reported in the MAP group: bone marrow infarction due to methotrexate. Interpretation EURAMOS-1 results do not support the addition of ifosfamide and etoposide to postoperative chemotherapy in patients with poorly responding osteosarcoma because its administration was associated with increased toxicity without improving event-free survival. The results define standard of care for this population. New strategies are required to improve outcomes in this setting. Funding UK Medical Research Council, National Cancer Institute, European Science Foundation, St Anna Kinderkrebsforschung, Fonds National de la Recherche Scientifique, Fonds voor Wetenschappelijk Onderzoek-Vlaanderen, Parents Organization, Danish Medical Research Council, Academy of Finland, Deutsche Forschungsgemeinschaft, Deutsche Krebshilfe, Federal Ministry of Education and Research, Semmelweis Foundation, ZonMw (Council for Medical Research), Research Council of Norway, Scandinavian Sarcoma Group, Swiss Paediatric Oncology Group, Cancer Research UK, National Institute for Health Research, University College London Hospitals, and Biomedical Research Centre.

The Influence of the Alloy of Megaprostheses on Infection Rate

We retrospectively reviewed 197 patients who underwent reconstruction with a megaprosthesis of the lower extremity. A cobalt-chrome alloy system was used in 77 patients and a titanium alloy system in 120 patients. The overall infection rate was 20.8% (n = 41). Separated into the 2 prosthesis systems used, an infection rate of 31.2% was found in the patients with a cobalt-chrome-alloy prosthesis and 14.2% in the titanium alloy group of patients (P < .01). Early infection occurred in 5.1% (n = 10) and late infection in 15.7% (n = 31). Selecting 2 identical subgroups for further analysis, the cobalt-chrome alloy prostheses were associated with a significantly higher infection rate, with 5 infections of 26 megaprostheses vs 1 infection of 36 titanium megaprostheses (P < .05).

Hip transposition as a limb salvage procedure following the resection of periacetabular tumors

One of the most difficult problems in tumor surgery is the treatment of pelvic tumors, particularly those in the periacetabular region. This retrospective study serves to analyze clinical and functional outcome of the new surgical technique of hip transposition.

The influence of elementary silver versus titanium on osteoblasts behaviour in vitro using human osteosarcoma cell lines.

Purpose. The antimicrobial effect of a silver-coated tumor endoprosthesis has been proven in clinical and experimental trials. However, in the literature there are no reports concerning the effect of elementary silver on osteoblast behaviour. Therefore, the prosthetic stem was not silver-coated because of concerns regarding a possible inhibition of the osseointegration. The aim of the present study was to investigate the effect of 5–25 mg of elementary silver in comparison to Ti-6Al-4V on human osteosarcoma cell lines (HOS-58, SAOS). Methods. Cell viability was determined by measuring the MTT proliferation rate. Cell function was studied by measuring alkaline phosphatase (AP) activity and osteocalcine production. Results. In the HOS-58 cells, the AP activity was statistically significant (P < 0.05) higher at a supplement of 5–10 mg of silver than of Ti-6 Al-4V at the same doses. For both cell lines, a supplement above 10 mg of silver resulted in a reduced AP activity in comparision to the Ti-6 Al-4V group, but a statistically significant difference (P < 0.05) was observed at a dose of 25 mg for the SAOS cells only. At doses of 20–25 mg in the HOS-58 cells and 10–25 mg in the SAOS cells, the reduction of the proliferation rate by silver was statistically significant (P < 0.05) compared to the Ti-6 Al-4V supplement. Discussion. In conclusion, elementary silver exhibits no cytotoxicity at low concentrations. In contrast, it seems to be superior to Ti-6 Al-4V concerning the stimulation of osteogenic maturation at these concentrations, whereas at higher doses it causes the known cytotoxic properties.