Publications by authors named "Dimosthenis Andreou"

43 Publications

Treatment of Angiosarcoma with Pazopanib and Paclitaxel: Results of the EVA (Evaluation of Votrient in Angiosarcoma) Phase II Trial of the German Interdisciplinary Sarcoma Group (GISG-06).

Cancers (Basel) 2021 Mar 11;13(6). Epub 2021 Mar 11.

Division of Surgical Oncology and Thoracic Surgery, University Medical Center Mannheim, University of Heidelberg, 68167 Mannheim, Germany.

We aimed to evaluate the efficacy and toxicity of paclitaxel combined with pazopanib in advanced angiosarcoma (AS). The primary end point was progression-free survival (PFS) rate at six months (PFSR6). Planned accrual was 44 patients in order to detect a PFSR6 of >55%, with an interim futility analysis of the first 14 patients. The study did not meet its predetermined interim target of 6/14 patients progression-free at 6 months. At the time of this finding, 26 patients had been enrolled between July 2014 and April 2016, resulting in an overrunning of 12 patients. After a median follow-up of 9.5 (IQR 7.7-15.4) months, PFSR6 amounted to 46%. Two patients had a complete and seven patients a partial response. Patients with superficial AS had a significantly higher PFSR6 (61% vs. 13%, = 0.0247) and PFS (11.3 vs. 2.7 months, < 0.0001) compared to patients with visceral AS. The median overall survival in the entire cohort was 21.6 months. A total of 10 drug-related serious adverse effects were reported in 5 patients, including a fatal hepatic failure. Although our study did not meet its primary endpoint, the median PFS of 11.6 months in patients with superficial AS appears to be promising. Taking recent reports into consideration, future studies should evaluate the safety and efficacy of VEGFR and immune checkpoint inhibitors with or without paclitaxel in a randomized, multiarm setting.
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http://dx.doi.org/10.3390/cancers13061223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000466PMC
March 2021

What Is the Implant Survivorship and Functional Outcome After Total Humeral Replacement in Patients with Primary Bone Tumors?

Clin Orthop Relat Res 2021 Feb 16. Epub 2021 Feb 16.

K. N. Schneider, J. N. Bröking, G. Gosheger, T. Lübben, J. Hardes, D. Schorn, C. Theil, D. Andreou, Department of Orthopaedics and Tumor Orthopaedics, Muenster University Hospital, Muenster, Germany.

Background: Total humeral replacement is an option to reconstruct massive bone defects after resection of locally advanced bone tumors of the humerus. However, implant survivorship, potential risk factors for implant revision surgery, and functional results of total humeral replacement are poorly elucidated because of the rarity of the procedure.

Questions/purposes: We asked: (1) What is the revision-free implant and overall limb survivorship after total humerus replacement? (2) What factors are associated with implant revision surgery? (3) What is the functional outcome of the procedure as determined by the Musculoskeletal Tumor Society (MSTS) score and the American Shoulder and Elbow Surgeons (ASES) score?

Methods: Between August 1999 and December 2018, 666 patients underwent megaprosthetic reconstruction after resection of a primary malignant or locally aggressive/rarely metastasizing tumor of the long bones at our department. In all, 23% (154) of these patients had a primary tumor located in the humerus. During the study, we performed total humeral replacement in all patients with a locally advanced sarcoma, in patients with pathological fractures, in patients with skip metastases, or in patients with previous intralesional contaminating surgery, who would have no sufficient bone stock for a stable implant fixation for a single joint megaprosthetic replacement of the proximal or distal humerus. We performed no biological reconstructions or reconstructions with allograft-prosthetic composites. As a result, 5% (33 of 666) of patients underwent total humerus replacement. Six percent (2 of 33) of patients were excluded because they received a custom-made, three-dimensionally (3-D) printed hemiprosthesis, leaving 5% (31) of the initial 666 patients for inclusion in our retrospective analysis. Of these, 6% (2 of 31) had surgery more than 5 years ago, but they had not been seen in the last 5 years. Median (interquartile range) age at the time of surgery was 15 years (14 to 25 years), and indications for total humeral replacement were primary malignant bone tumors (n = 30) and a recurring, rarely metastasizing bone tumor (n = 1). All megaprosthetic reconstructions were performed with a single modular system. The implanted prostheses were silver-coated beginning in 2006, and beginning in 2010, a reverse proximal humerus component was used when appropriate. We analyzed endoprosthetic complications descriptively and assessed the functional outcome of all surviving patients who did not undergo secondary amputation using the 1993 MSTS score and the ASES score. The median (IQR) follow-up in all survivors was 75 months (50 to 122 months), with a minimum follow-up period of 25 months. We evaluated the following factors for possible association with implant revision surgery: age, BMI, reconstruction length, duration of surgery, extraarticular resection, pathological fracture, previous intralesional surgery, (neo-)adjuvant radio- and chemotherapy, and metastatic disease.

Results: The revision-free implant survivorship at 1 year was 77% (95% confidence interval 58% to 89%) and 74% (95% CI 55% to 86%) at 5 years. The overall limb survivorship was 93% (95% CI 75% to 98%) after 1 and after 5 years. We found revision-free survivorship to be lower in patients with extraarticular shoulder resection compared with intraarticular resections (50% [95% CI 21% to 74%] versus 89% [95% CI 64% to 97%]) after 5 years (subhazard ratios for extraarticular resections 4.4 [95% CI 1.2 to 16.5]; p = 0.03). With the number of patients available for our analysis, we could not detect a difference in revision-free survivorship at 5 years between patients who underwent postoperative radiotherapy (40% [95% CI 5% to 75%]) and patients who did not (81% [95% CI 60% to 92%]; p = 0.09). The median (IQR) MSTS score in 9 of 13 surviving patients after a median follow-up of 75 months (51 to 148 months) was 87% (67% to 92%), and the median ASES score was 83 (63 to 89) of 100 points, with higher scores representing better function.

Conclusion: Total humeral replacement after resection of locally advanced bone tumors appears to be associated with a good functional outcome in patients who do not die of their tumors, which in our study was approximately one- third of those who were treated with a resection and total humerus prosthesis. However, the probability of early prosthetic revision surgery is high, especially in patients undergoing extraarticular resections, who should be counseled accordingly. Still, our results suggest that if the prosthesis survives the first year, further risk for revision appears to be low. Future studies should reexamine the effect of postoperative radiotherapy on implant survival in a larger cohort and evaluate whether the use of soft tissue coverage with plastic reconstructive surgery might decrease the risk of early revisions, especially in patients undergoing extraarticular resections.

Level Of Evidence: Level III, therapeutic study.
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http://dx.doi.org/10.1097/CORR.0000000000001677DOI Listing
February 2021

Invasive diagnostic and therapeutic measures are unnecessary in patients with symptomatic van Neck-Odelberg disease (ischiopubic synchondrosis): a retrospective single-center study of 21 patients with median follow-up of 5 years.

Acta Orthop 2021 Feb 4:1-5. Epub 2021 Feb 4.

Department of Orthopedics and Tumor Orthopedics; University Hospital of Münster, Münster.

Background and purpose - Van Neck-Odelberg disease (VND) is a self-limiting skeletal phenomenon characterized by a symptomatic or asymptomatic uni- or bilateral overgrowth of the pre-pubescent ischiopubic synchondrosis. It is frequently misinterpreted as a neoplastic, traumatic, or infectious process, often resulting in excessive diagnostic and therapeutic measures. This study assessed the demographic, clinical, and radiographic features of the condition and analyzed diagnostic and therapeutic pathways in a large single-center cohort. Patients and methods - We retrospectively analyzed 21 consecutive patients (13 male) with a median age of 10 years (IQR 8-13) and a median follow-up of 5 years (IQR 42-94 months), who were diagnosed at our department between 1995 and 2019. Results - VND was unilateral in 17 cases and bilateral in 4 cases. Initial referral diagnoses included suspected primary bone tumor (n = 9), fracture (n = 3), osteomyelitis (n = 2), and metastasis (n = 1). The referral diagnosis was more likely to be VND in asymptomatic than symptomatic patients (4/6 vs. 2/15). More MRI scans were performed in unilateral than bilateral VND (median 2 vs. 0). All 15 symptomatic patients underwent nonoperative treatment and reported a resolution of symptoms and return to physical activity after a median time of 5 months (IQR 0-6). Interpretation - By understanding the physiological course of VND during skeletal maturation, unnecessary diagnostic and therapeutic measures can be avoided and uncertainty and anxiety amongst affected patients, their families, and treating physicians can be minimized.
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http://dx.doi.org/10.1080/17453674.2021.1882237DOI Listing
February 2021

Medical Care and Survival of Soft-Tissue and Bone Sarcoma Patients: Results and Methodological Aspects of a German Subnational Cohort Study Based on Administrative Healthcare Data.

Oncol Res Treat 2021 30;44(3):103-110. Epub 2020 Dec 30.

Zentrum für evidenzbasierte Gesundheitsversorgung (ZEGV), Universitätsklinikum und Medizinische Fakultät Carl Gustav Carus an der TU Dresden, Dresden, Germany.

Introduction: Medical care of soft-tissue sarcoma (STS) and bone sarcoma (BS) patients in Germany has rarely been investigated. The objectives of this article were (1) to investigate medical care and survival in STS and BS patients, and (2) to examine methodological aspects of corresponding analyses based on administrative healthcare data.

Methods: We analyzed data from a statutory health insurance located in Saxony, Germany, covering approximately 2 million individuals. We identified incident STS and BS patients in the period 2012-2016 using 4 different case definitions. We examined treatment rates and visits to medical oncologists and medical practices descriptively, and then compared results between case definitions. We investigated survival prospects using a relative survival analysis and estimated hazard ratios (HRs) for risk factors for mortality using Cox regression.

Results: Across case definitions, the number of included sarcoma patients (STS: n = 871-1,757; BS: n = 216-689) and applied treatments (STS: 42.2-83.1%; BS: 28.3-77.8%) varied substantially. Irrespective of the case definition, the minority of patients visited medical oncologists (STS: 9.8-10.8% BS: 4.4-7.9%) and "experienced" medical practices (STS: 27.7-38.4%; BS: 18.3-23.6%). Survival prospects were better for patients who visited "experienced" medical practices (STS: HR = 0.55; BS: HR = 0.42).

Conclusion: Treatment rates clearly <100% and evidence from survival analyses indicate the potential for improvements in the care of sarcoma patients in Germany, e.g., by physicians in "experienced" medical practices.
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http://dx.doi.org/10.1159/000513178DOI Listing
December 2020

Treatment options in unresectable soft tissue and bone sarcoma of the extremities and pelvis - a systematic literature review.

EFORT Open Rev 2020 Nov 13;5(11):799-814. Epub 2020 Nov 13.

Department of Orthopaedics and Trauma, Medical University of Graz, Graz, Austria.

In patients with metastatic or unresectable soft tissue and bone sarcoma of extremities and pelvis, survival is generally poor. The aim of the current systematic review was to analyse recent publications on treatment approaches in patients with inoperable and/or metastatic sarcoma.Original articles published between 1st January 2011 and 2nd May 2020, using the search terms 'unresectable sarcoma', 'inoperability AND sarcoma', 'inoperab* AND sarcoma', and 'treatment AND unresectable AND sarcoma' in PubMed, were potentially eligible. Out of the 839 initial articles (containing 274 duplicates) obtained and 23 further articles identified by cross-reference checking, 588 were screened, of which 447 articles were removed not meeting the inclusion criteria. A further 54 articles were excluded following full-text assessment, resulting in 87 articles finally being analysed.Of the 87 articles, 38 were retrospective (43.7%), two prospective (2.3%), six phase I or I/II trials (6.9%), 22 phase II non-randomized trials (27.6%), nine phase II randomized trials (10.3%) and eight phase III randomized trials (9.2%). Besides radio/particle therapy, isolated limb perfusion and conventional chemotherapy, novel therapeutic approaches, including immune checkpoint inhibitors and tyrosine kinase inhibitors were also identified, with partially very promising effects in advanced sarcomas.Management of inoperable, advanced or metastatic sarcomas of the pelvis and extremities remains challenging, with the optimal treatment to be defined individually. Besides conventional chemotherapy, some novel therapeutic approaches have promising effects in both bone and soft tissue subtypes. Considering that only a small proportion of studies were randomized, the clinical evidence currently remains moderate and thus calls for further large, randomized clinical trials. Cite this article: 2020;5:799-814. DOI: 10.1302/2058-5241.5.200069.
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http://dx.doi.org/10.1302/2058-5241.5.200069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722943PMC
November 2020

The Health-Related Quality of Life of Sarcoma Patients and Survivors in Germany-Cross-Sectional Results of a Nationwide Observational Study (PROSa).

Cancers (Basel) 2020 Nov 30;12(12). Epub 2020 Nov 30.

Clinic and Polyclinic for Internal Medicine I, University Hospital Carl Gustav Carus, TU Dresden, 01307 Dresden, Germany.

Sarcomas are rare cancers with high heterogeneity in terms of type, location, and treatment. The health-related quality of life (HRQoL) of sarcoma patients has rarely been investigated and is the subject of this analysis. Adult sarcoma patients and survivors were assessed between September 2017 and February 2019 in 39 study centers in Germany using standardized, validated questionnaires (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)). Associated factors were analyzed exploratively using multivariable linear regressions. Among 1113 patients, clinically important limitations and symptoms were most pronounced in emotional (63%, 95% CI 60-66%), physical (60%, 95% CI 57-62%), role functioning (51%, 95% CI 48-54%), and pain (56%, 95% CI 53-59%) and fatigue (51%, 95% CI 48-54%). HRQoL differed between tumor locations with lower extremities performing the worst and sarcoma types with bone sarcoma types being most affected. Additionally, female gender, higher age, lower socioeconomic status, recurrent disease, not being in retirement, comorbidities, and being in treatment were associated with lower HRQoL. Sarcoma patients are severely restricted in their HRQoL, especially in functioning scales. The heterogeneity of sarcomas with regard to type and location is reflected in HRQoL outcomes. During treatment and follow-up, close attention has to be paid to the reintegration of the patients into daily life as well as to their physical abilities and emotional distress.
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http://dx.doi.org/10.3390/cancers12123590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759994PMC
November 2020

Long-term outcome of arthroscopic debridement of massive irreparable rotator cuff tears.

PLoS One 2020 12;15(11):e0241277. Epub 2020 Nov 12.

Department of General Orthopedics and Tumor Orthopedics, Münster University Hospital, Münster, Germany.

Objectives: To evaluate the clinical and radiographic outcome of low-demand patients with massive rotator cuff tears undergoing arthroscopic debridement in mid- and long-term follow-up, as well as the rate of conversion to reverse shoulder arthroplasty.

Methods: We performed a retrospective analysis of 19 patients with a mean age at surgery of 68 years (range, 55-80 years) from a previously described consecutive cohort and after a mean follow up of 47 month (FU1) and 145 month (FU2). The functional outcome was evaluated with the VAS score, the American Shoulder and Elbow Surgeons (ASES) score, and the age- and gender-adjusted Constant (aCS) score. The radiographic outcome was classified according to the Hamada classification. Non-parametric analyses were carried out with the Mann-Whitney U for independent samples and the Wilcoxon signed-rank test for related samples.

Results: Five patients (26%) developed symptomatic cuff tear arthropathy and underwent reverse shoulder arthroplasty after a mean time of 63 months (range, 45-97 months). These patients were excluded from further analyses. The mean VAS score of the remaining 14 patients at FU1 was significantly lower compared to preoperatively (P = .041), while there were no significant differences between the VAS score at FU1 and FU2 (P = 1.0). The ASES score of the affected shoulder at FU1 was significantly higher compared to prior to surgery (P = .028), while there were no significant differences between the scores of the affected shoulder between FU1 and FU2 (P = .878). While the ASES score of the contralateral shoulder at FU1 was significantly higher than the score of the affected shoulder (P = .038), there were no significant differences in the ASES scores of the affected and the healthy shoulder at FU2 (P = .575). The evaluation of the aCS produced similar results. A progression of the Hamada grade was documented in 6 patients.

Conclusions: Arthroscopic debridement is a safe and valid option for low-demand middle-age or elderly patients with symptomatic massive rotator cuff tears, leading to a significant pain relief and significantly improved functional outcome at mid- and long-term follow up. However, about a quarter of the patients in our cohort had to undergo reverse shoulder arthroplasty due to symptomatic cuff tear arthropathy. Furthermore, some of the remaining patients continued to undergo radiographic progression. This might be due to the natural history of their disease and/or the surgical procedure, and the clinical relevance of this finding should be evaluated in further studies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241277PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660551PMC
December 2020

Reconstruction of Total Bone Defects following Resection of Malignant Tumors of the Upper Extremity with 3D Printed Prostheses: Presentation of Two Patients with a Follow-Up of Three Years.

Case Rep Orthop 2020 2;2020:8822466. Epub 2020 Oct 2.

Department of General Orthopedics and Tumor Orthopedics, Muenster University Hospital, Muenster, Germany.

Wide tumor resection is the local treatment of choice for patients with primary malignant bone tumors and a prerequisite for long-term survival. We present two patients that underwent total bone resection in the upper limb because of primary malignant bone tumors. The defects were then reconstructed by a 3D printed prosthesis, a procedure that, to our knowledge, has not been reported for bone defects of the upper extremity so far. Complete resection of the affected bone was required in a five-year-old girl with a high-grade osteoblastic osteosarcoma of the humerus and a 53-year-old man with a dedifferentiated leiomyosarcoma of the radius, due to the tumor's extent. Following neoadjuvant chemotherapy, resection of the entire affected humerus including the axillary nerve took place in the first case and the entire affected radius including parts of the radial nerve in the second case. Approximately three years after surgery, both patients are alive and pain-free. Despite a postoperative drop hand that affected the now 56-year-old man, he is able to carry out everyday activities such as brushing his teeth, writing, and eating. The now eight-year-old girl is also able to engage in normal activities with her left arm such as eating and carrying lightweight objects. Both patients are tumor-free to date.
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http://dx.doi.org/10.1155/2020/8822466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559838PMC
October 2020

[Systemic Therapy Options for Locally Advanced and Metastatic Myxoid, Dedifferentiated and Pleomorphic Liposarcoma].

Zentralbl Chir 2020 Apr 8;145(2):160-167. Epub 2020 Apr 8.

Abteilung für Tumororthopädie und Sarkomchirurgie, Klinik für Traumatologie und Orthopädie - Sarkomzentrum Berlin-Brandenburg, HELIOS Klinikum Bad Saarow, Deutschland.

Just a few years ago, all patients with metastatic soft tissue sarcoma received the same chemotherapy drugs. However, it is now recognised that the various sarcoma subtypes are different tumours with distinct genetic alterations and different biological behaviour, so that histology-specific treatment protocols have been increasingly implemented in recent years. This is also the case for the different subtypes of liposarcoma - the myxoid/round cell variant, as well as dedifferentiated and pleomorphic liposarcoma. This article will present published data and the authors' experience with the various systemic treatment options. both in first line and in subsequent lines of treatment, as well as a brief overview of experimental treatment approaches.
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http://dx.doi.org/10.1055/a-1117-4143DOI Listing
April 2020

Incidence, treatment and outcome of abdominal metastases in extremity soft tissue sarcoma: Results from a multi-centre study.

J Surg Oncol 2020 Mar 31;121(4):605-611. Epub 2020 Jan 31.

Tumour Orthopaedics and Sarcoma Surgery, HELIOS Klinikum Bad Saarow, Bad Saarow, Germany.

Background And Objectives: Abdominal metastases (AM) from soft tissue sarcoma (STS) are rare and prognosis is poor. The aims of the study were to (a) identify risk factors for the development of AM and to (b) investigate the outcome of AM-patients.

Methods: Seven-hundred-sixty-nine STS-patients with localised disease at diagnosis treated at three tumour centres (2000-2016) were retrospectively included (409 males; mean age, 55.6 years [range, 8-96 years]; median follow-up, 4.1 years [interquartile-range, 2.5-6.6 years]).

Results: Two-hundred-two patients (26.3%) developed secondary metastases, and 24 of them AM (3.1%). Ten patients developed first AM (FAM) after a mean of 2.4 years and 14 patients late AM (LAM, after being diagnosed with metastases to other sites) after a mean of 2.0 years. Patients with liposarcoma had a significantly higher risk of developing AM (P = .007), irrespective of grading. There was no difference in post-metastasis-survival (PMS) between patients with AM at any time point and those with metastases to other sites (P = .585). Patients with LAM or FAM showed no difference in post-abdominal-metastasis-survival (P = .884).

Conclusions: Survival in patients with AM is poor, irrespective of whether they develop secondarily to other metastases or not. Patients at high-risk of AM (ie, liposarcoma) may be followed-up regularly by abdominal-ultrasound/CT.
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http://dx.doi.org/10.1002/jso.25856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065201PMC
March 2020

Gorham-Stout disease: good results of bisphosphonate treatment in 6 of 7 patients.

Acta Orthop 2020 04 13;91(2):209-214. Epub 2020 Jan 13.

Department of Orthopaedics and Tumor Orthopaedics, University Hospital of Münster, Germany.

Background and purpose - Gorham-Stout disease (GSD) is a rare mono- or polyostotic condition characterized by idiopathic intraosseous proliferation of angiomatous structures resulting in progressive destruction and resorption of bone. Little is known about the course of disease and no previous study has evaluated patients' quality of life (QoL).Patients and methods - This is a retrospective analysis of 7 consecutive patients (5 males) with a median age at diagnosis of 14 years and a median follow-up of 7 years who were diagnosed with GSD in our department between 1995 and 2018. Data regarding clinical, radiographic, and histopathological features, and treatment, as well as sequelae and their subsequent therapy, were obtained. QoL was assessed by Musculoskeletal Tumor Society Score (MSTS), Toronto Extremity Salvage Score (TESS), and Reintegration to Normal Living (RNL) Index.Results - 3 patients had a monoostotic and 4 patients a polyostotic disease. Besides a diagnostic biopsy, 4 of the 7 patients had to undergo 8 surgeries to treat evolving sequelae. Using an off-label therapy with bisphosphonates in 6 patients, a stable disease state was achieved in 5 patients after a median of 20 months. The median MSTS, TESS, and RNL Index at last follow-up was between 87% and 79%.Interpretation - Due to its rare occurrence, diagnosis and treatment of GSD remain challenging. Off-label treatment with bisphosphonates appears to lead to a stable disease state in the majority of patients. QoL varies depending on the individual manifestations but good to excellent results can be achieved even in complex polyostotic cases with a history of possibly life-threatening sequelae.
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http://dx.doi.org/10.1080/17453674.2019.1709716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144312PMC
April 2020

Individualizing Follow-Up Strategies in High-Grade Soft Tissue Sarcoma with Flexible Parametric Competing Risk Regression Models.

Cancers (Basel) 2019 Dec 21;12(1). Epub 2019 Dec 21.

Division of Clinical Oncology, Department of Medicine, Medical University of Graz, 8036 Graz, Austria.

Currently, patients with extremity soft tissue sarcoma (eSTS) who have undergone curative resection are followed up by a heuristic approach, not covering individual patient risks. The aim of this study was to develop two flexible parametric competing risk regression models (FPCRRMs) for local recurrence (LR) and distant metastasis (DM), aiming at providing guidance on how to individually follow-up patients. Three thousand sixteen patients (1931 test, 1085 validation cohort) with high-grade eSTS were included in this retrospective, multicenter study. Histology (9 categories), grading (time-varying covariate), gender, age, tumor size, margins, (neo)adjuvant radiotherapy (RTX), and neoadjuvant chemotherapy (CTX) were used in the FPCRRMs and performance tested with Harrell-C-index. Median follow-up was 50 months (interquartile range: 23.3-95 months). Two hundred forty-two (12.5%) and 603 (31.2%) of test cohort patients developed LR and DM. Factors significantly associated with LR were gender, size, histology, neo- and adjuvant RTX, and margins. Parameters associated with DM were margins, grading, gender, size, histology, and neoadjuvant RTX. C-statistics was computed for internal (C-index for LR: 0.705, for DM: 0.723) and external cohort (C-index for LR: 0.683, for DM: 0.772). Depending on clinical, pathological, and patient-related parameters, LR- and DM-risks vary. With the present model, implemented in the updated Personalised Sarcoma Care (PERSARC)-app, more individualized prediction of LR/DM-risks is made possible.
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http://dx.doi.org/10.3390/cancers12010047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017264PMC
December 2019

Which Factors Are Associated with Local Control and Survival of Patients with Localized Pelvic Ewing's Sarcoma? A Retrospective Analysis of Data from the Euro-EWING99 Trial.

Clin Orthop Relat Res 2020 02;478(2):290-302

D. Andreou, G. Gosheger, Department of General Orthopedics and Tumor Orthopedics, University Hospital Münster, Westfälische Wilhelms-University, Münster, Germany.

Background: Local treatment of pelvic Ewing's sarcoma may be challenging, and intergroup studies have focused on improving systemic treatments rather than prospectively evaluating aspects of local tumor control. The Euro-EWING99 trial provided a substantial number of patients with localized pelvic tumors treated with the same chemotherapy protocol. Because local control included surgical resection, radiation therapy, or a combination of both, we wanted to investigate local control and survival with respect to the local modality in this study cohort.

Questions/purposes: (1) Do patients with localized sacral tumors have a lower risk of local recurrence and higher survival compared with patients with localized tumors of the innominate bones? (2) Is the local treatment modality associated with local control and survival in patients with sacral and nonsacral tumors? (3) Which local tumor- and treatment-related factors, such as response to neoadjuvant chemotherapy, institution where the biopsy was performed, and surgical complications, are associated with local recurrence and patient survival in nonsacral tumors? (4) Which factors, such as persistent extraosseous tumor growth after chemotherapy or extent of bony resection, are independently associated with overall survival in patients with bone tumors undergoing surgical treatment?

Methods: Between 1998 and 2009, 1411 patients with previously untreated, histologically confirmed Ewing's sarcoma were registered in the German Society for Pediatric Oncology and Hematology Ewing's sarcoma database and treated in the Euro-EWING99 trial. In all, 24% (339 of 1411) of these patients presented with a pelvic primary sarcoma, 47% (159 of 339) of which had macroscopic metastases at diagnosis and were excluded from this analysis. The data from the remaining 180 patients were reviewed retrospectively, based on follow-up data as of July 2016. The median (range) follow-up was 54 months (5 to 191) for all patients and 84 months (11 to 191) for surviving patients. The study endpoints were overall survival, local recurrence and event-free survival probability, which were calculated with the Kaplan-Meier method and compared using the log-rank test. Hazard ratios (HRs) with their respective 95% CIs were estimated in a multivariate Cox regression model.

Results: Sacral tumors were associated with a reduced probability of local recurrence (12% [95% CI 1 to 22] versus 28% [95% CI 20 to 36] at 5 years, p = 0.032), a higher event-free survival probability (66% [95% CI 51 to 81] versus 50% [95% CI 41 to 58] at 5 years, p = 0.026) and a higher overall survival probability (72% [95% CI 57 to 87] versus 56% [95% CI 47 to 64] at 5 years, p = 0.025) compared with nonsacral tumors. With the numbers available, we found no differences between patients with sacral tumors who underwent definitive radiotherapy and those who underwent combined surgery and radiotherapy in terms of local recurrence (17% [95% CI 0 to 34] versus 0% [95% CI 0 to 20] at 5 years, p = 0.125) and overall survival probability (73% [95% CI 52 to 94] versus 78% [95% CI 56 to 99] at 5 years, p = 0.764). In nonsacral tumors, combined local treatment was associated with a lower local recurrence probability (14% [95% CI 5 to 23] versus 33% [95% CI 19 to 47] at 5 years, p = 0.015) and a higher overall survival probability (72% [95% CI 61 to 83] versus 47% [95% CI 33 to 62] at 5 years, p = 0.024) compared with surgery alone. Even in a subgroup of patients with wide surgical margins and a good histologic response to induction treatment, the combined local treatment was associated with a higher overall survival probability (87% [95% CI 74 to 100] versus 51% [95% CI 33 to 69] at 5 years, p = 0.009), compared with surgery alone.A poor histologic response to induction chemotherapy in nonsacral tumors (39% [95% CI 19 to 59] versus 64% [95% CI 52 to 76] at 5 years, p = 0.014) and the development of surgical complications after tumor resection (35% [95% CI 11 to 59] versus 68% [95% CI 58 to 78] at 5 years, p = 0.004) were associated with a lower overall survival probability in nonsacral tumors, while a tumor biopsy performed at the same institution where the tumor resection was performed was associated with lower local recurrence probability (14% [95% CI 4 to 24] versus 32% [95% CI 16 to 48] at 5 years, p = 0.035), respectively.In patients with bone tumors who underwent surgical treatment, we found that after controlling for tumor localization in the pelvis, tumor volume, and surgical margin status, patients who did not undergo complete (defined as a Type I/II resection for iliac bone tumors, a Type II/III resection for pubic bone and ischium tumors and a Type I/II/III resection for tumors involving the acetabulum, according to the Enneking classification) removal of the affected bone (HR 5.04 [95% CI 2.07 to 12.24]; p < 0.001), patients with a poor histologic response to induction chemotherapy (HR 3.72 [95% CI 1.51 to 9.21]; p = 0.004), and patients who did not receive additional radiotherapy (HR 4.34 [95% CI 1.71 to 11.05]; p = 0.002) had a higher risk of death. The analysis suggested that the same might be the case in patients with a persistent extraosseous tumor extension after induction chemotherapy (HR 4.61 [95% CI 1.03 to 20.67]; p = 0.046), although the wide CIs pointing at a possible sparse-data bias precluded any definitive conclusions.

Conclusion: Patients with sacral Ewing's sarcoma appear to have a lower probability for local recurrence and a higher overall survival probability compared with patients with tumors of the innominate bones. Our results seem to support a recent recommendation of the Scandinavian Sarcoma Group to locally treat most sacral Ewing's sarcomas with definitive radiotherapy. Combined surgical resection and radiotherapy appear to be associated with a higher overall survival probability in nonsacral tumors compared with surgery alone, even in patients with a wide resection and a good histologic response to neoadjuvant chemotherapy. Complete removal of the involved bone, as defined above, in patients with nonsacral tumors may be associated with a decreased likelihood of local recurrence and improved overall survival. Persistent extraosseous tumor growth after induction treatment in patients with nonsacral bone tumors undergoing surgical treatment might be an important indicator of poorer overall survival probability, but the possibility of sparse-data bias in our cohort means that this factor should first be validated in future studies.

Level Of Evidence: Level III, therapeutic study.
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http://dx.doi.org/10.1097/CORR.0000000000000962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438129PMC
February 2020

Current State of Sarcoma Care in Germany: Results of an Online Survey of Physicians.

Oncol Res Treat 2019 11;42(11):589-598. Epub 2019 Sep 11.

Department of Internal Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany.

Background: Sarcoma treatment is a complex and multidisciplinary process. Little is known about the actual status of sarcoma care in Germany.

Objectives: We evaluated: (1) on an institutional level, which physician diagnosed and treated sarcomas; (2) whether guidelines and tumor board recommendations were routinely implemented; and (c) access to which diagnosis and treatment options was regarded as problematic. We also examined factors that were associated with access problems.

Methods: A cross-sectional online survey was employed among German sarcoma physicians between June 2017 and February 2018 with convenience sampling.

Results: Two hundred fourteen physicians participated; 46% were oncologists and 27% surgeons, 38% worked in hospitals of maximum care, 34% were office based and 27% worked in other hospitals, 68% of all of the physicians consulted established guidelines, and 93% presented their patients in multidisciplinary tumor boards. The most common access problems were: isolated limb perfusion (39%), deep-wave hyperthermia (33%), and FDG-PET (27%), and 42% reported no access problems at all. Those physicians who treat more than 100 patients per year reported "no access problems" more frequently compared to centers with lower patient numbers (vs. 0-10 patients, OR 0.14; 95% CI 0.03-0.61; vs. 11-100 patients, OR 0.21; 95% CI 0.06-0.73).

Conclusions: Access to multidisciplinary tumor boards seems to be largely guaranteed in the participants of our survey. The use of guidelines could be further implemented and expanded. The number of treated patients appears to be a significant factor to avoid access problems to treatment options.
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http://dx.doi.org/10.1159/000502758DOI Listing
April 2020

Advances in tumour endoprostheses: a systematic review.

EFORT Open Rev 2019 Jul 2;4(7):445-459. Epub 2019 Jul 2.

Department of Orthopaedics and Trauma, Medical University of Graz, Austria.

Tumour endoprostheses have facilitated limb-salvage procedures in primary bone and soft tissue sarcomas, and are increasingly being used in symptomatic metastases of the long bones.The objective of the present review was to analyse articles published over the last three years on tumour endoprostheses and to summarize current knowledge on this topic. The NCBI PubMed webpage was used to identify original articles published between January 2015 and April 2018 in journals with an impact factor in the top 25.9% of the respective category (orthopaedics, multidisciplinary sciences).The following search-terms were used: tumour endoprosthesis, advances tumour endoprosthesis, tumour megaprosthesis, prosthetic reconstruction AND tumour. We identified 347 original articles, of which 53 complied with the abovementioned criteria.Articles were categorized into (1) tumour endoprostheses in the shoulder girdle, (2) tumour endoprostheses in the proximal femur, (3) tumour endoprostheses of the knee region, (4) tumour endoprostheses in the pelvis, (5) (expandable) prostheses in children and (6) long-term results of tumour endoprostheses.The topics of interest covered by the selected studies largely matched with the main research questions stated at a consensus meeting, with survival outcome of orthopaedic implants being the most commonly raised research question.As many studies reported on the risk of deep infections, research in the future should also focus on potential preventive methods in endoprosthetic tumour reconstruction. Cite this article: 2019;4:445-459. DOI: 10.1302/2058-5241.4.180081.
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http://dx.doi.org/10.1302/2058-5241.4.180081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667979PMC
July 2019

Acetabular Erosion After Bipolar Hemiarthroplasty in Proximal Femoral Replacement for Malignant Bone Tumors.

J Arthroplasty 2019 Nov 13;34(11):2692-2697. Epub 2019 Jun 13.

Department of Orthopedics and Tumor Orthopedics, Münster University Hospital, Münster, Germany.

Background: Hemiarthroplasty megaprosthetic proximal femur reconstruction after tumor resection is a widespread procedure in orthopedic oncology. One potential complication is acetabular wear requiring secondary acetabular revision. The study's purpose is to investigate prevalence of acetabular erosion, secondary revisions, and potential risk factors.

Methods: We retrospectively identified 112 patients who underwent proximal femur replacement after resection of a malignant bone tumor and had radiological follow-up longer than 12 months. Patient demographic, surgical, and oncologic factors were recorded, acetabular wear was measured using the classification proposed by Baker, and prosthetic failure was classified using the International Society on Limb Salvage classification. Functional assessment was performed using the Musculoskeletal Tumor Society Score and Harris Hip Score.

Results: Prevalence of acetabular wear was 28.6%. Secondary conversion to total hip arthroplasty was required in 5 patients (4.6%), all treated for primary bone tumors. No patient treated for metastatic tumor had higher grade acetabular wear or required revision. Significant risk factors for the development of acetabular wear were age under 40 (P = .035) and longer follow-up (63 vs 43 months, P = .004). Other patient, surgical, or adjuvant treatment-related factors were not associated with acetabular revision or acetabular wear. The dislocation rate in the patient cohort was 0.9%.

Conclusion: Bipolar hemiarthroplasty proximal femoral replacement represents a durable reconstruction after tumor resection. Hip instability is rare. Acetabular erosion is rare and can be successfully treated with conversion to total hip arthroplasty. Young patients with long-term survival over 10 years are at risk. In reconstruction for metastases, instability and acetabular wear are rare.
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http://dx.doi.org/10.1016/j.arth.2019.06.014DOI Listing
November 2019

Adaptive Changes on the Dominant Shoulder of Collegiate Handball Players-A Comparative Study.

J Strength Cond Res 2019 Mar;33(3):701-707

Department of General Orthopedics and Tumor Orthopedics, Muenster University Hospital, Muenster, Germany.

Vogler, T, Schorn, D, Gosheger, G, Kurpiers, N, Schneider, K, Rickert, C, Andreou, D, and Liem, D. Adaptive changes on the dominant shoulder of collegiate handball players-A comparative study. J Strength Cond Res 33(3): 701-707, 2019-Handball players are susceptible to adaptive bony and soft-tissue changes of the dominant shoulder. Our goal was to compare the glenohumeral range of motion and posterior capsule thickness between the dominant and nondominant arm of throwing athletes and between the dominant arm of nonthrowers and throwing athletes. Twenty-three collegiate handball players and 23 nonthrowing athletes underwent an examination of the dominant and the nondominant shoulder. Humeral retroversion and posterior capsule thickness were assessed with an ultrasound examination, whereas external rotation and internal rotation were determined with a digital inclinometer. The dominant shoulder of handball players had a significantly higher external rotation compared with their nondominant shoulder and the dominant shoulder of nonthrowing athletes. Furthermore, the dominant shoulder of handball players had a significantly lower internal rotation compared with their nondominant shoulder, with no differences compared with the dominant shoulder of the nonthrowing athletes. There was a trend for an increased posterior capsule thickness and an increased humeral retroversion between the dominant and the contralateral shoulder of handball players. Moreover, we found a significant increase in the capsule thickness of the dominant shoulder of throwing athletes compared with the dominant shoulder of nonthrowers. However, there were no differences in humeral retroversion. Our analysis suggests that a comparison of the dominant shoulder of overhead throwing athletes with the dominant shoulder of nonthrowing athletes might be more appropriate than the comparison of the dominant and the nondominant shoulder to evaluate the adaptive changes on the dominant side.
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http://dx.doi.org/10.1519/JSC.0000000000003014DOI Listing
March 2019

Dislocation rates with combinations of anti-protrusio cages and dual mobility cups in revision cases: Are we safe?

PLoS One 2019 7;14(2):e0212072. Epub 2019 Feb 7.

Department of Orthopaedics and Tumor Orthopaedics, University of Muenster, Muenster, Germany.

Background: Due to the increasing numbers of revision total hip arthroplasty (THA) procedures being carried out, the frequency of major acetabular defects is also rising. A combination of an anti-protrusio cage and a dual mobility cup has been used in our department since 2007 in order to reduce the dislocation rate associated with complex defects. Although both implants have an important place in endoprosthetics, there are as yet limited data on the dislocation and complication rates with this combination.

Methods: This retrospective study included all patients in whom a Burch-Schneider cage and a dual mobility cup were implanted in our department between 2007 and 2014 and who had a minimum follow-up period of 24 months.

Results: The study included 79 patients with a mean follow-up period of 5.3 years. The implant survival rate was 85% at 65 months. Postoperative dislocation occurred in two cases (2.1%), with the first dislocation taking place within the first 3 weeks in both of these patients.

Conclusions: The present study shows a promising dislocation rate with a combination of an anti-protrusio cage and a dual mobility cup. Particularly in the medium-term follow-up, no further dislocations occurred in the study. A maximum cup inclination of 45° in revision cases was associated with a lower dislocation rate in this group of patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0212072PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366705PMC
November 2019

Megaprosthetic replacement of the distal humerus: still a challenge in limb salvage.

J Shoulder Elbow Surg 2019 May 1;28(5):908-914. Epub 2019 Feb 1.

Department of Orthopedics and Tumor Orthopedics, Muenster University Hospital, Münster, Germany; Department of Musculoskeletal Surgical Oncology, Essen University Hospital, Essen, Germany.

Background: The distal humerus is a rare location of bone tumors. Because of the complexity of the elbow joint, poor soft-tissue coverage, and proximity of nerves and vessels, resection and endoprosthetic reconstruction are demanding.

Methods: This retrospective study evaluated the clinical results after distal humeral resection and megaprosthetic reconstruction in 12 patients with an average age of 46 years. All patient files were reviewed for clinical information, and postoperative function and patients' contentment were assessed using the Musculoskeletal Tumor Society score.

Results: The predominant diagnoses were bone and soft-tissue sarcoma (n = 6), giant cell tumor (n = 2), and renal cell carcinoma metastasis (n = 2). Local recurrence was the reason for secondary amputation in all cases (n = 3). The prosthetic survival rate after surgery was 82% at 2 years and 64% at 5 years. Reconstruction failure was mainly caused by aseptic loosening of the humeral stem, occurring in 27% (n = 3), followed by aseptic loosening of the ulnar stem in 9% (n = 1) and periprosthetic infection in 9% (n = 1). The mean Musculoskeletal Tumor Society score was 24 points (range, 20-30 points). An extension lag of more than 10° was noted in 6 patients (55%).

Conclusion: Our results suggest that limb salvage with a distal humeral replacement can achieve good functional results in most patients, although the complication rate with special emphasis on the loosening rate of the humeral stem is high. However, limb salvage was not achieved in 27% of patients because of local recurrence.
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http://dx.doi.org/10.1016/j.jse.2018.11.050DOI Listing
May 2019

Aminopeptidase N (CD13): Expression, Prognostic Impact, and Use as Therapeutic Target for Tissue Factor Induced Tumor Vascular Infarction in Soft Tissue Sarcoma.

Transl Oncol 2018 Dec 17;11(6):1271-1282. Epub 2018 Aug 17.

Department of Medicine A, Hematology, Oncology, University Hospital Muenster, Muenster, Germany.

Aminopeptidase N (CD13) is expressed on tumor vasculature and tumor cells. It represents a candidate for targeted therapy, e.g., by truncated tissue factor (tTF)-NGR, binding to CD13, and causing tumor vascular thrombosis. We analyzed CD13 expression by immunohistochemistry in 97 patients with STS who were treated by wide resection and uniform chemo-radio-chemotherapy. Using a semiquantitative score with four intensity levels, CD13 was expressed by tumor vasculature, or tumor cells, or both (composite value, intensity scores 1-3) in 93.9% of the STS. In 49.5% tumor cells, in 48.5% vascular/perivascular cells, and in 58.8%, composite value showed strong intensity score 3 staining. Leiomyosarcoma and synovial sarcoma showed low expression; fibrosarcoma and undifferentiated pleomorphic sarcoma showed high expression. We found a significant prognostic impact of CD13, as high expression in tumor cells or vascular/perivascular cells correlated with better relapse-free survival and overall survival. CD13 retained prognostic significance in multivariable analyses. Systemic tTF-NGR resulted in significant growth reduction of CD13-positive human HT1080 sarcoma cell line xenografts. Our results recommend further investigation of tTF-NGR in STS patients. CD13 might be a suitable predictive biomarker for patient selection.
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http://dx.doi.org/10.1016/j.tranon.2018.08.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113655PMC
December 2018

Risk factors for acute injuries and overuse syndromes of the shoulder in amateur triathletes - A retrospective analysis.

PLoS One 2018 1;13(6):e0198168. Epub 2018 Jun 1.

Department of General Orthopedics and Tumor Orthopedics, Münster University Hospital, Münster, Germany.

Objectives: To investigate the prevalence of shoulder-related acute and overuse injuries in triathletes and examine the role of possible risk factors, in order to identify potential preventive measures.

Methods: We performed a retrospective epidemiologic study of 193 amateur triathletes between June and August 2013 and evaluated their competition and training habits, as well as the presence of acute and overuse injuries of the shoulder sustained during the past 12 months. Contingency tables were analyzed using Pearson's chi-squared test. Normally distributed data were compared with the independent samples t-test, while non-parametric analyses were performed with the Mann-Whitney U test. Binary logistic regression was used to identify important predictors of injuries.

Results: 12 participants (6%) sustained acute injuries and 36 athletes experienced an overuse injury. The acute injury rate amounted to 0.11 per 1000 hours of training and the overuse injury rate to 0.33 per 1000 hours of training. There was no association between athletes' age, height, weight, BMI, a history of shoulder complaints or triathlon experience in years and acute or overuse injuries. Male athletes had a trend for sustaining more acute injuries then female athletes (8% vs. 2%, p = 0.079). Athletes with acute injuries spent a significantly higher amount of time per week doing weight training (p = 0.007) and had a trend for a higher weekly duration of cycling training (p = 0.088). Athletes with overuse injuries participated in a significantly higher number of races compared to athletes without overuse injuries (p = 0.005). The regular use of paddles was associated with a significantly higher rate of overuse injuries (24% vs. 10%, p = 0.014).

Conclusion: The regular use of paddles during swimming training appears to be a risk factor for the development of overuse injuries, while an increased duration of weight and cycling training seems to be associated with a higher rate of acute injuries.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0198168PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983428PMC
December 2018

Adjuvant chemotherapy-Radiotherapy-Chemotherapy sandwich protocol in resectable soft tissue sarcoma: An updated single-center analysis of 104 cases.

PLoS One 2018 22;13(5):e0197315. Epub 2018 May 22.

University Hospital Muenster, Department of Medicine A, Muenster, Germany.

Adjuvant therapy of local soft tissue sarcomas (STS) after wide surgical excision still is a topic under controversial scientific debate. In this single center report we have offered an adjuvant "sandwich" therapy protocol consisting of 4 cycles of doxorubicin (75 mg/m2 i.v. over 1 h on day 1) followed by ifosfamide (5 g/m2 i.v. over 24 h starting on day 1) and local radiotherapy scheduled between chemotherapy cycles 2 and 3 to 104 consecutive patients after wide surgical excision (R0) of histologically proven high-grade STS. After a mean follow-up of 39 months (range 5-194 months) relapse free survival (RFS) at 2 and 5 years was 68.1% (95% CI, 58.5-77.7%) and 61.2% (95% CI, 50.4-71.6%). When analyzing the 82 STS cases of the extremities only 2- and 5-year RFS was 74.0% (95% CI, 64.0-84.0%) and 65.3% (95% CI, 53.7-76.9%). By intent-to-treat analysis, the overall survival (OS) at 2 years was 87.3% (95% CI, 80.5-94.1%) and 75.6% (95% CI, 65.2-86.0%) at 5 years, while OS for STS of the extremities only cohort was 90.5% (95% CI, 83.7-97.3%) and 79.0% (95% CI, 68.4-89.6%), respectively. Tolerability of the treatment was good. This analysis demonstrates the feasibility of adjuvant chemoradiotherapy and reflects the results of the long lasting intensive multidisciplinary team approach at our "high-volume" sarcoma center. The long-term survival in our patients is among the highest reported and the low local and distant recurrence rate in high-risk STS is at least comparable to the published data.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0197315PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5963910PMC
December 2018

Tumour endoprosthesis replacement in the proximal tibia after intra-articular knee resection in patients with sarcoma and recurrent giant cell tumour.

Int Orthop 2018 10 22;42(10):2475-2481. Epub 2018 Mar 22.

Department of Orthopaedics and Tumor Orthopaedics, University Clinics of Münster, Münster, Germany.

Purpose: Proximal tibia replacements are commonly associated with post-operative complications and poor functional results due to an insufficiency of the extensor mechanism.

Methods: This study evaluated the clinical results with a special emphasis of the extensor mechanism reconstruction with a reattachment tube and complications after intra-articular resection of the proximal tibia and reconstruction with a tumour endoprosthesis (MUTARS®) in 98 patients (median age 18 years) with malignant bone tumours or giant cell tumours.

Results: Kaplan-Meier analysis showed that the limb survival rates were 94.9, 90.5 and 74.5% at one, two and ten years, respectively. Periprosthetic infection was the most common reason for secondary amputation (eight patients). The cumulative incidence rates of prosthetic failure (Henderson II-IV) were 18% at two years and 29% at five years post-operatively. An active extension deficit of more than 10° was noted in six patients only.

Conclusions: These results suggest that limb salvage with tumour prostheses after intra-articular resection can achieve good functional results with an active extension of the knee in the majority of patients. While mechanical complications can be treated successfully with revision surgery, periprosthetic infection continues to be the main reason for secondary amputation.
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http://dx.doi.org/10.1007/s00264-018-3893-zDOI Listing
October 2018

Diagnosis and treatment of soft-tissue sarcomas of the extremities and trunk.

EFORT Open Rev 2017 Oct 17;2(10):421-431. Epub 2017 Oct 17.

Medical University of Graz, Austria.

The relatively low incidence and often atypical clinical presentation of soft-tissue sarcomas (STS) impedes early and adequate diagnosis. Patients may report on recently enlarged soft-tissue swellings, infrequently complain of painful lesions, or even have no symptoms at all.A thorough diagnostic work-up is essential in order to distinguish between benign soft-tissue tumours and STSs. Patient history, clinical features and radiological findings all help in assessing the underlying pathology. 'Worrying' features such as recent increase in size, deep location relative to the fascia, a tumour exceeding 4 cm in size, and invasive growth patterns seen on imaging should prompt verification by biopsy.Even though acquisition of biopsy material may be incomplete, one should bear in mind some essential rules. Regardless of the biopsy technique applied, the most direct route to the lump in question should be identified, contamination of adjacent structures should be avoided and a sufficient amount of tissue acquired.Treatment of STS is best planned by a multidisciplinary team, involving experts from various medical specialities. The benchmark therapy consists of resection of the tumour, covered by a safety margin of healthy tissue. Depending on tumour histology, grade, local extent and anatomical stage, radiotherapy, chemotherapy and isolated hyperthermic limb perfusion may be employed.Due to the complexity of treatment, any soft-tissue swelling suspected of malignancy is best referred directly to a sarcoma centre, where therapeutic management is carefully planned by an experienced multidisciplinary team. Cite this article: 2017;2:421-431. DOI: 10.1302/2058-5241.2.170005.
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http://dx.doi.org/10.1302/2058-5241.2.170005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702952PMC
October 2017

Long-term outcomes after combined arthroscopic medial reefing and lateral release in patients with recurrent patellar instability - a retrospective analysis.

BMC Musculoskelet Disord 2017 Jun 24;18(1):277. Epub 2017 Jun 24.

Department of General Orthopedics and Tumor Orthopedics, Münster University Hospital, Albert-Schweitzer-Campus 1, 48149, Münster, Germany.

Background: There is currently no consensus regarding the optimal surgical treatment method for patients with recurrent patella instability. Our goal was to evaluate the long-term results of combined arthroscopic medial reefing and lateral release, to identify possible risk factors for recurrent dislocations and residual complaints after surgical treatment and to assess functional outcome.

Methods: We performed a retrospective study of 38 patients (43 knees) treated with all-inside technique between 2001 and 2010. The functional outcome was evaluated with the Kujala score, while pain intensity was scored on a visual analogue scale (VAS). Contingency tables were analysed with Fisher's exact test. Non-parametric analyses were carried out with the Mann-Whitney U and the Wilcoxon signed-rank test. Survival curves were calculated with the Kaplan-Meier method and compared with the log-rank test.

Results: The median age at surgery was 16 years (range, 9-44 years) and the median follow-up amounted to 9.7 years (range, 4.7-14.7 years). Residual complaints were present in 34 cases (79%). Patients with residual complaints had a trend for a higher body mass index (BMI) at surgery (25.7 vs. 21.6, P = .086). Twenty-two cases had recurrent dislocation after a median interval of 30 months. The probability of recurrent dislocations amounted to 16% after 1 year and 52% after 10 years. There were no significant differences in the presence of residual complaints (P = .721) and median VAS score (P = .313) between patients with or without recurrent dislocation. Patients with recurrent dislocations had a trend towards younger age at surgery (15 vs. 18 years, P = .076). The median Kujala score of the affected knee was 81. Patients with recurrent dislocations had a significantly lower score compared to patients without recurrent dislocations (67 vs. 91, P < .001).

Conclusions: The combined arthroscopic lateral release with medial reefing does not appear to be an adequate treatment for patients with chronic patellar instability in long-term follow-up. Younger patients might be at a higher risk for recurrent dislocations, while a higher BMI at surgery might be associated with residual complaints.
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http://dx.doi.org/10.1186/s12891-017-1636-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5483275PMC
June 2017

Silver-coated megaprostheses: review of the literature.

Eur J Orthop Surg Traumatol 2017 May 6;27(4):483-489. Epub 2017 Mar 6.

Department of Orthopedics and Tumor Orthopedics, Muenster University Hospital, Muenster, Germany.

Periprosthetic infection remains one of the most serious complications following megaendoprostheses. Despite a large number of preventive measures that have been introduced in recent years, it has not been possible to further reduce the rate of periprosthetic infection. With regard to metallic modification of implants, silver in particular has been regarded as highly promising, since silver particles combine a high degree of antimicrobial activity with a low level of human toxicity. This review provides an overview of the history of the use of silver as an antimicrobial agent, its mechanism of action, and its clinical application in the field of megaendoprosthetics. The benefits of silver-coated prostheses could not be confirmed until now. However, a large number of retrospective studies suggest that the rate of periprosthetic infections could be reduced by using silver-coated megaprostheses.
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http://dx.doi.org/10.1007/s00590-017-1933-9DOI Listing
May 2017

Is superior tibiofibular joint resection necessary in extraarticular knee resection for sarcomas? A systematic review.

World J Surg Oncol 2016 Feb 3;14(1):28. Epub 2016 Feb 3.

Department of Orthopedics and Orthopedic Surgery, Medical University of Graz, Auenbruggerplatz 5, 8036, Graz, Austria.

Background: Sarcomas infiltrating the knee joint require extraarticular resection to achieve wide margins. Opinions differ as to whether the superior tibiofibular joint (STFJ) is part of the knee joint and should be removed in the course of extraarticular resection. Thus, we investigated the frequency of communication between the tibiofemoral joint (TFJ) and the STFJ, and the reported local recurrence rates (LRR) following extraarticular knee resection.

Methods: A systematic literature review on STFJ and TFJ communication and local recurrence rates following extraarticular knee resections was undertaken.

Results: Cadaver studies detected communication between the TFJ and STFJ in 10-64% of the cases. Direct arthrography with physical loading verified a 100% communication rate. Regarding the extent of extraarticular knee resection, two institutions where the STFJ was resected had a LRR of 4-8%, while studies from another three where the STFJ was not routinely resected reported a LRR of 0-21%.

Conclusions: Since the literature reports about a 100% communication rate between the TFJ and the STFJ, resection of the STFJ in patients with sarcomas involving the knee joint would seem to be indicated, although it is not clear whether resection of the STFJ reduces local recurrence rates.
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http://dx.doi.org/10.1186/s12957-016-0783-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4738782PMC
February 2016

Histological response assessment following neoadjuvant isolated limb perfusion in patients with primary, localised, high-grade soft tissue sarcoma.

Int J Hyperthermia 2016 15;32(2):159-64. Epub 2015 Dec 15.

b Department of Orthopaedic Oncology , Sarcoma Centre Berlin-Brandenburg, HELIOS Klinikum Berlin-Buch , Berlin , Germany .

Purpose: Histological response assessment following neoadjuvant treatment can help identify patients at a higher risk for systemic disease progression. Our goal was to evaluate whether mitotic count and the amount of viable tumour following neoadjuvant isolated limb perfusion (ILP) for primary, locally advanced, non-metastatic, high-grade extremity soft tissue sarcoma correlate with prognosis.

Patients And Methods: This study is a retrospective analysis of 61 patients who underwent neoadjuvant ILP followed by surgical resection with curative intent between 2001 and 2011. Non-parametric analyses were carried out with the Mann-Whitney U and the Wilcoxon signed-rank test. Survival curves were calculated with the Kaplan-Meier method and compared with the log-rank test.

Results: The median follow-up was 44 months for all patients and 55 months for survivors. The amount of viable tumour after ILP had no correlation with overall (OS) (P = 0.227) or event-free (EFS) (P = 0.238) survival probability. Patients with a low mitotic count after ILP had a significantly higher OS (P < 0.001), EFS (P = 0.002) and post-relapse survival probability (P = 0.030) compared to patients with an intermediate or high mitotic count.

Conclusions: The mitotic count following ILP for primary, high-grade, locally advanced, non-metastatic soft tissue sarcoma appears to significantly correlate with prognosis. If these results are validated in a prospective setting, they could provide a rationale for the design of adjuvant systemic chemotherapy trials with the goal of improving the prognosis of patients with an intermediate or high mitotic count after ILP.
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http://dx.doi.org/10.3109/02656736.2015.1109146DOI Listing
January 2017