[Is there a magic bullet for sarcomas? : Personalised treatment for maligant tumours of bone and soft tissue]. / Gibt es eine Magic Bullet für Sarkome? : Personalisierte Therapie von malignen Tumoren des Stütz- und Bewegungsapparates.

BACKGROUND: Personalised tumour therapies aim to selectively target pathways and structures to which a tumour shows an oncogenic addiction. OBJECTIVE AND METHOD: This article aims to provide an overview of relevant genetic alterations in bone and soft-tissue tumours, which might serve as potential therapeutic targets for personalised medicines in the future. Recent approaches towards a personalised treatment of various tumours of bone and soft tissues are reviewed. RESULTS: Molecular diagnosis has become an essential tool for the characterisation of bone and soft-tissue tumours. Currently, no targeted therapies are routinely available for bone sarcomas. Denosumab is merely a symptomatic treatment for giant cell tumours of the bone. Imatinib has become the paradigm of a targeted treatment for subgroups of malignant gastrointestinal stromal tumours (GISTs) and dermatofibrosarcoma protuberans. Antiangiogenic multikinase inhibitors, various other tyrosine kinase inhibitors (TKIs) and monoclonal antibodies are currently being evaluated in several (sub-)types of soft-tissue sarcomas. Sorafenib showed promising results in the treatment of aggressive desmoid-type fibromatosis. Histology-tailored chemotherapies did not yield superior results in a prospective randomised multicentre trial. CONCLUSION: More in-depth knowledge is required for many sarcomas to link their genetic alterations to tumorigenesis in order to develop efficient personalised treatment strategies. Clinical trial designs need to be adapted to evaluate new therapeutic strategies in these ultra-rare tumours and their various sub-types more efficaciously.

Langerhans cell sarcoma: a case report and review of the literature.

We present the case of a 62-year-old male patient with a three-month history of pain in the left shoulder. Magnetic resonance imaging of the left scapula showed an osteo-destructive lesion. H and E stained sections revealed a Langerhans cell sarcoma, and immunohistochemistry was performed additionally; CD68, CD163, CD14, fascin, HLA-DR, lysozyme, S100 CD1a and langerin showed a positive reaction, while CD20, CD30, CD34, CD31, pan-cytokeratin, AE/1AE3, SMA, desmin, EMA, ERG, INI-1, CD21, CD4, PLAP, MPO and CD117c were negative. We suggested palliative treatment with chemotherapy and radiation. The patient refused any treatment and died 2 weeks later.

The width of resection margins influences local recurrence in soft tissue sarcoma patients.

BACKGROUND: Patients with soft tissue sarcoma (STS) being treated following the standardized guidelines can still not be guaranteed to remain free from local recurrence (LR). A complete tumour resection has been accepted as a major prognostic factor for LR. This retrospective study was designed to analyse the influence of two different classifications of resection margins (R-classification and UICC-classification) on LR in STS patients. MATERIALS AND METHODS: Of 411 patients treated at our institution for STS, 265 were eligible for statistical analysis. Kaplan-Meier curves and Cox regression models were used to assess the impact of an R0 resection according to the R-classification (resection margin clear but allowing <1 mm) and according to the UICC-classification (minimal resection margin ≥1 mm) on LR. RESULTS: Survival curves showed a lower LR rate for R0 resections in the UICC-classification, namely 1.3%, 12% and 12% as compared to 2.1%, 9.5% and 16.5% for the R-classification. In multivariate analysis calculated separately for each classification, R1 resection as defined by the R-classification (HR: 11.214; 95%CI: 2.394-52.517; p = 0.002) as well as by UICC-classification (HR: 15.634; 95%CI: 2.493-98.029; p = 0.003) remained significant. CONCLUSION: In our study, margin status according to both classifications represents an independent prognostic factor for LR in patients with STS following curative surgery. Local control rates were superior after a minimal resection margin of 1 mm (R0 by UICC-classification) compared to R0 resections after the R-classification.

Validation of the prognostic relevance of plasma C-reactive protein levels in soft-tissue sarcoma patients.

BACKGROUND: The concept of the involvement of systemic inflammation in cancer progression and metastases has gained attraction within the past decade. C-reactive protein (CRP), a non-specific blood-based marker of the systemic inflammatory response, has been associated with decreased survival in several cancer types. The aim of the present study was to validate the prognostic value of pre-operative plasma CRP levels on clinical outcome in a large cohort of soft-tissue sarcoma (STS) patients. METHODS: Three hundred and four STS patients, operated between 1998 and 2010, were retrospectively evaluated. CRP levels and the impact on cancer-specific survival (CSS), disease-free survival (DFS) and overall survival (OS) were assessed using Kaplan-Meier curves and univariate as well as multivariate Cox proportional models. Additionally, we developed a nomogram by supplementing the plasma CRP level to the well-established Kattan nomogram and evaluated the improvement of predictive accuracy of this novel nomogram by applying calibration and Harrell's concordance index (c-index). RESULTS: An elevated plasma CRP level was significantly associated with established prognostic factors, including age, tumour grade, size and depth (P<0.05). In multivariate analysis, increased CRP levels were significantly associated with a poor outcome for CSS (HR=2.05; 95% CI=1.13-3.74; P=0.019) and DFS (HR=1.88; 95% CI=1.07-3.34; P=0.029). The estimated c-index was 0.74 using the original Kattan nomogram and 0.77 when the plasma CRP level was added. CONCLUSION: An elevated pre-operative CRP level represents an independent prognostic factor that predicts poor prognosis and improves the predictive ability of the Kattan nomogram in STS patients. Our data suggest to further prospectively validate its potential utility for individual risk stratification and clinical management of STS patients.

Elevated preoperative neutrophil/lymphocyte ratio is associated with poor prognosis in soft-tissue sarcoma patients.

BACKGROUND: Recent data indicate that tumour microenvironment, which is influenced by inflammatory cells, has a crucial role in cancer progression and clinical outcome of patients. In the present study, we investigated the prognostic relevance of preoperative neutrophil/lymphocyte (N/L) ratio on time to tumour recurrence (TTR) and overall survival (OS) in soft-tissue sarcoma (STS) patients who underwent curative surgical resection. METHODS: In all, 260 STS patients were included in this retrospective study. Kaplan-Meier curves and multivariate Cox proportional models were calculated for TTR and OS. RESULTS: In univariate analysis, elevated N/L ratio was significantly associated with decreased TTR (hazard ratio (HR), 2.32; 95% confidence interval (CI), 1.30-4.14; P=0.005) and remained significant in the multivariate analysis (HR, 1.98; 95%CI, 1.05-3.71; P=0.035). Patients with elevated N/L ratio showed a median TTR of 77.9 months. In contrast, patients with low N/L ratio had a median TTR of 99.1 months. Regarding OS, elevated N/L ratio was also significantly associated with decreased survival in univariate analysis (HR, 2.90; 95%CI, 1.82-4.61; P=0.001) and remained significant in multivariate analysis (HR, 1.88; 95%CI, 1.14-3.12; P=0.014). CONCLUSION: In conclusion, our findings suggest that an elevated preoperative N/L ratio predicts poor clinical outcome in STS patients and may serve as a cost-effective and broadly available independent prognostic biomarker.

[The use of frozen sections in the handling of soft tissue tumors]. / Der intraoperative Schnellschnitt im Umgang mit Weichteiltumoren.

Due to the multiplicity of localizations and entities, handling of soft tissue tumors is a very challenging subject requiring intensive interdisciplinary collaboration. With respect to the use of intraoperative frozen sections, the following facts are of special relevance: 1) the usual criteria for malignancy, such as infiltrative growth and high mitotic rate are only restrictedly applicable to soft tissue tumors. 2) Correct diagnosis of the tumor entity often requires not only the use of immunohistochemistry but also the identification of genetic alterations by the polymerase chain reaction and/or fluorescence in situ hybridization. In many centres, 14G core biopsies taken from different tumor areas represent the preferred method for a diagnostic biopsy. Apart from cryocollection additional frozen section investigations are used especially in case of open biopsies for quality control of the submitted material or in cases of excision biopsies to ascertain a highly probable radiological diagnosis. The use of intraoperative frozen sections to clarify the resection margins is generally undisputed but should definitely be restricted to centres specialized and experienced in the handling of soft tissue tumors.