H. W. Bart Schreuder

Function and complications after ablative and limb-salvage therapy in lower extremity sarcoma of bone.

The functional results and the complications after several limb‐saving and ablative treatments because of lower extremity bone sarcoma were evaluated.

Pathological fracture prediction in patients with metastatic lesions can be improved with quantitative computed tomography based computer models.

PURPOSE In clinical practice, there is an urgent need to improve the prediction of fracture risk for cancer patients with bone metastases. The methods that are currently used to estimate fracture risk are dissatisfying, hence affecting the quality of life of patients with a limited life expectancy. The purpose of this study was to assess if non-linear finite element (FE) computer models, which are based on Quantitative Computer Tomography (QCT), are better than clinical experts in predicting bone strength. MATERIALS AND METHODS Ten human cadaver femurs were scanned using QCT. In one femur of each pair a hole (size 22, 40, or 45 mm diameter) was drilled at the anterior or medial side to simulate a metastatic lesion. All femurs were mechanically tested to failure under single-limb stance-type loading. The failure force was calculated using non-linear FE-models, and six clinical experts were asked to rank the femurs from weak to strong based on X-rays, gender, age, and the loading protocol. Kendall Tau correlation coefficients were calculated to compare the predictions of the FE-model with the predictions of the clinicians. RESULTS The FE-failure predictions correlated strongly with the experimental failure force (r(2)=0.92, p<0.001). For the clinical experts, the Kendall Tau coefficient between the experimental ranking and predicted ranking ranged between tau=0.39 and tau=0.72, whereas this coefficient was considerably higher (tau=0.78) for the FE-model. CONCLUSION This study showed that the use of a non-linear FE-model can improve the prediction of bone strength compared to the prediction by clinical experts.

Functional ability and physical activity in children and young adults after limb-salvage or ablative surgery for lower extremity bone tumors

Aim of our study was to compare functional ability and physical activity in children and young adults who underwent surgery for a malignant bone tumor that was located around the knee.

Quality of life in young patients after bone tumor surgery around the knee joint and comparison with healthy controls.

This study aimed to compare the health related quality of life (HRQoL) of children and adolescents after malignant bone tumor surgery of the leg with healthy controls.

Long-term follow-up results of primary and recurrent pigmented villonodular synovitis

OBJECTIVE Adequate documentation of the outcome of treatment of pigmented villonodular synovitis (PVNS) is sparse. Available case series show relatively short follow-up times and often combine locations or subtypes to increase patient numbers. This article describes the long-term follow-up of a single institutions large consecutive series of PVNS. METHODS Retrospectively, 107 PVNS patients were identified between 1985 and 2011 by searching pathology and radiology records. Treatment complications, recurrences and quality of life were evaluated. Most patients (85.2%) were primarily or secondarily treated at our institution. RESULTS Both subtypes, localized PVNS [29 (27%)] and diffuse PVNS [75 (70%)] were represented. The knee was affected in 88% of patients. Treatments received were surgery, external beam radiotherapy, radiosynovectomy, targeted therapy, immunotherapy or combinations of these. Forty-nine (46%) patients had prior treatment elsewhere. The mean follow-up from diagnosis until last contact was 7.0 years (range 0.3-27.4) for localized PVNS and 14.5 years (range 1.1-48.7) for diffuse PVNS. The 1- and 5-year recurrence-free survival rates for diffuse PVNS were 69% and 32%, respectively. Quality of life, estimated by 36-item Short Form Health Survey (SF-36) scores, were not significantly different between localized and diffuse PVNS. However, both patient groups scored lower than the general population norms on the general health component (59.2 and 56.3, respectively, P < 0.05). CONCLUSION Recurrence rates of PVNS increase with time. Long-term follow-up shows, particularly in diffuse PVNS, it is a continually recurring problem, and over time it becomes increasingly difficult to cure. The quality of life is decreased in patients with PVNS compared with the general population.

Pigmented villonodular synovitis: current concepts about diagnosis and management

At present, the treatment strategies in patients with localized and diffuse forms of pigmented villonodular synovitis have more or less been standardized. However, these strategies are not optimal because high recurrence rates persist and studies with a sufficient level of evidence are lacking. This systematic review article describes all known treatment options for intra-articular pigmented villonodular synovitis and their clinical results. Based on this research, we provide guidelines to support physicians in making the optimal treatment decisions. Given the rarity of the disease, randomized studies are not to be expected, but an international registry through existing networks would offer the benefit of getting a better insight into the outcome of this disease. Therefore, we propose a basic set of data to be investigated and ideally to be reported on in such a registry.

The presence of periosteum is essential for the healing of large diaphyseal segmental bone defects reconstructed with trabecular metal: A study in the femur of goats

Large segmental diaphyseal bone defects can be reconstructed with massive structural allografts, but this technique is associated with high complication rates. Tantalum tabecular metal implants have been successfully used to restore bone defects associated with revision total knee or hip arthroplasties. The aim of this study was to investigate if tantalum cylinders could be used to reconstruct large load bearing segmental diaphyseal bone defects in the presence or absence of a periosteum coverage. Segmental bone defects were reconstructed with tantalum cylinders with or without preservation of the periosteum and stabilized by an intramedullary nail. Radiological analysis was performed postop and at 26 weeks follow-up. New bone was labeled with fluorochromes at 13 and 26 weeks follow-up. Reconstructions were tested mechanically and subsequently investigated histologically. Contra-lateral femurs were used as controls. Clinically all goats returned to normal functional loading after 2 weeks allowing unlimited weight bearing. Radiologically, all tantalum cylinders with periosteum coverage united with the host bone. Reconstructions with cylinders without periosteum coverage lead to radiological nonunion in five out of six cases. The strengths of the reconstruction with and without periosteum preservation were respectively 102.1% and 24.5% compared to controls. In the periosteum covered implants, bone contact was found at all levels of the tantalum cylinder and more and deeper bone ingrowth was found in this group. Tantalum cylinders seem a safe and reliable alternative for a massive cortical graft to reconstruct large diaphyseal bone defects in a goat model if healthy periosteum is present.

Eosinophilic granuloma of bone: results of treatment with curettage, cryosurgery, and bone grafting.

Intralesional instillation of steroids is currently the first choice of treatment for eosinophilic granuloma of bone. However, some lesions fail to respond or are unsuitable for injection therapy due location, pending pathologic fracture, and soft tissue intrusion. The authors treated six patients with these lesion characteristics using curettage, cryosurgery, and bone grafting. After a mean follow-up of 34.3 months, all lesions healed completely, although one femoral fracture occurred 8 months after the operation. In selected cases of eosinophilic granuloma of bone, a primary surgical treatment seems feasible. The use of cryosurgery as adjuvant treatment extends the surgical margin and is of value in averting local recurrence.

Age as prognostic factor in patients with osteosarcoma

Age at diagnosis is a well known prognostic factor in many different malignancies; its significance for patients with osteosarcoma is however controversial. To gain more insight in the prognostic role of age, we performed a retrospective study at our institute. We included 102 patients with de-novo osteosarcoma and formed three age groups to evaluate age specific survival rates: ≤ 14 years, 15-19 years and 20-40 years. Differences in outcome between patients aged 15-19 years treated at either the pediatric department or the adult department of oncology were evaluated. The 5-year overall survival rate (OSR) of the whole population was 53.5%±1.5%. OSR of 70.6%±0.8% was seen in patients ≤ 14 years old, 52.5%±1.1% in patients 15-19 years old and 33.3%±0.9% in the patients aged 20-40 years (p=0.01). Significant differences were observed with regard to stage at presentation (higher in older age groups), size of the tumor (larger in younger age groups) and histological response (more good responders in younger age groups). No significant difference was seen between outcomes of patients aged 15-19 years treated at the pediatric or adult oncology department. In conclusion, younger patients have a significantly better outcome than older patients.

A First Step toward Personalized Medicine in Osteosarcoma: Pharmacogenetics as Predictive Marker of Outcome after Chemotherapy-Based Treatment.

Purpose: Overall survival in patients with osteosarcoma is only 60%. Poor response to chemotherapy is the dominant risk factor for poor survival. Pharmacogenetic research can offer possibilities to optimize treatment and improve outcome. We applied a pathway-based approach to evaluate the cumulative effect of genes involved in the metabolism of cisplatin and doxorubicin in relationship to clinical outcome. Experimental Design: We included 126 patients with osteosarcoma. To comprehensively assess common genetic variation in the 54 genes selected, linkage disequilibrium (LD; r2 = 0.8)–based tag-single nucleotide polymorphisms (SNP) strategy was used. A final set of 384 SNPs was typed using Illumina Beadarray platform. SNPs significantly associated with 5-year progression-free survival (PFS) were replicated in another 64 patients with osteosarcoma. Results: We identified five variants in FasL, MSH2, ABCC5, CASP3, and CYP3A4 that were associated with 5-year PFS. Risk stratification based on the combined effects of the risk alleles showed a significant improvement of 5-year PFS. Patients that carried no or only one risk allele had a 5-year PFS of 100% compared with a 5-year PFS of 84.4% for carriers of two or three risk alleles, 66.7% PFS if a patient carried four to five alleles, and a 5-year PFS of 41.8% for patients with >5 risk alleles (P < 0.001). Conclusions: We identified several genes that showed association with PFS in patients with osteosarcoma. These pharmacogenetic risk factors might be useful to predict treatment outcome and to stratify patients immediately after diagnosis and offer the possibility to improve treatment and outcome. Clin Cancer Res; 21(15); 3436–41. ©2015 AACR.