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Background: Improved patient and limb survival rates have led to an increased interest in the functional outcome and return to sports of patients undergoing megaprosthetic reconstruction in musculoskeletal oncology. This study evaluates the functional outcome and postoperatively performed level of sports in patients undergoing proximal humeral replacement (PHR) following resection of a primary bone sarcoma and identifies potential beneficial and limiting factors., Patients and Methods: Between 2007 and 2020, a total of 606 patients underwent resection of a primary bone sarcoma and reconstruction with a single-design modular implant. For 112 (18%) patients, the location of the tumour was the proximal humerus. Exclusion criteria were death (n = 65), patients living overseas (n = 8), and subsequent amputation (n = 1), leaving 38 patients for evaluation, of whom 32 were available for the study (13 women, median age 42 years). Clinical data regarding oncological and surgical treatment as well as subsequent complications were obtained from the patients' electronic medical records. Functional outcome was determined using the Musculoskeletal Tumor Society Score (MSTS) and Toronto Extremity Salvage Score (TESS) as well as the Subjective Shoulder Value (SSV). Return to sports was assessed using the Tegner Activity Score (TS) and the modified Weighted Activity Score (WAS)., Results: At the last follow-up after a median of 30 months (IQR 22-58), median MSTS was 18 (IQR 12-24), median TESS was 80% (IQR 69-87), median SSV was 35% (IQR 10-58), median TS was 5 (IQR 4-6) and median WAS was 5 (IQR 0-10). Preservation of the axillary nerve, a reverse shoulder reconstruction and a WAS of > 10 prior to surgery were associated with better functional outcome and return to sports activity scores., Conclusion: Following PHR, good to excellent functional outcomes are possible, and patients regularly return to participate in sports activities-most commonly in low-impact types of sports, but some individuals are even able to participate in high-impact sports activities., Level of Evidence: IV., (© 2022. The Author(s).)

Aneurysmal bone cyst (ABC) is a benign locally aggressive tumor that occurs in childhood and early adulthood. Most relevant differential diagnoses are the telangiectatic osteosarcoma and the giant cell tumor. In the present case series chemotherapy following the EURAMOS or the Euro-Ewing 99 protocol was externally applied in three patients with the misdiagnosis of ABC as malignant bone tumor. In all three cases, a significant reduction of the volume of the ABC was achieved. This is the first report about the use of neoadjuvant chemotherapy in ABC. Chemotherapy reduces the size of an ABC and leads to progressive sclerosis., (© 2020 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Purpose: The objective of this study was to investigate potential correlations between pathologic fractures (PFs) and prognosis of patients with primary central high-grade osteosarcoma of the extremities., Methods: We retrospectively analyzed 2,847 patients registered in the Consecutive Cooperative Osteosarcoma Study Group database with primary central high-grade osteosarcoma of the extremities, treated between 1980 and 2010. Intended treatment included pre- and postoperative chemotherapy and surgery. Univariable and multivariable survival analyses were performed for all patients and then differentiated for adult and pediatric (≤ 18 years at time of diagnosis) patients., Results: A total of 2,193 patients were ≤ 18 years of age; 11.3% of all patients had PFs. In the overall cohort, presence of PF correlated significantly with tumor site, histologic subtype, relative tumor size, and primary metastases, but not with body mass index or local surgical remission. In univariable analysis, 5-year overall survival (OAS) of patients with and without PF was 63% versus 71%, respectively ( P = .007), and 5-year event-free survival (EFS) was 51% versus 58% ( P = .026). In pediatric patients, OAS and EFS did not differ significantly between patients with and without PF. In adults, 5-year OAS in patients with and without PF was 46% versus 69% ( P < .001), and 5-year EFS was 36% versus 56% ( P < .001). In multivariable analysis, PF was not a statistically significant factor for OAS or EFS in the total cohort or in pediatric patients. In adult patients, PF remained an independent prognostic factor for OAS ( P = .013; hazard ratio [HR], 1.893). It was not a significant prognostic factor for EFS ( P = .263; HR, 1.312)., Conclusion: In this largest study to date with extremity osteosarcomas, we observed the occurrence of PF to correlate with inferior OAS expectancies in adult but not in pediatric patients.

Purpose: Active shoulder function after segmental tumour resection of the proximal humerus and endoprosthetic reconstruction is regularly compromised, while the overall arm function allows a satisfying use in daily activities. The main functional problem remains the loss of huge parts of the shoulder girdle musculature and its bony attachment. In revision arthroplasty inverse shoulder implants can improve the active range of motion significantly in comparison to anatomical shaped prostheses. The aim of this study was to investigate if these promising experiences are transferable to reconstructions after tumour resection of the proximal humerus by using a modular inverse tumour prosthesis., Methods: In this study we observed the functional and oncological results of 18 inverse proximal humerus endoprosthetic replacements (IPHP) with the MUTARS system (Implantcast®) after resection of benign (1x giant cell) and malignant (11x primary bone sarcoma, 5x bone metastasis of carcinoma) bone tumours. Mean age at operation was 42 years. The mean postoperative follow-up was 33 months (range ten to 120)., Results: Resection margins were wide in 13 and marginal in five patients. Mean reconstruction length was 15.1 cm (range 6-25 cm). Mean operation time was 191 minutes. The axillary nerve was mostly preserved in 78 % (n = 14). At latest follow-up the patients presented a medium MSTS-score of 24.6/30. The mean active arm abduction in the shoulder joint was 78° and 88° active arm elevation for patients with intact axillary nerve function, but significantly reduced for the four patients with compromised deltoid function. One patient needed a surgical revision due to a deep implant infection., Conclusions: The IPHP offers a significant improvement of active shoulder function in patients in whom the axillary nerve can be preserved in comparison to anatomically-shaped implants. However, for patients without any deltoid function there is no benefit regarding an improved active range of motion using an IPHP.

Background: Tumors of the distal femur and diaphysis with proximal metaphyseal extension into the femur present a challenge for limb salvage. The conventional treatment consists of limb salvage with total femur replacement. This case study aims to present preliminary results and experience with short-stem reconstruction, focusing on the mechanical stability of the procedure., Methods: Sixteen short stems were implanted in 15 patients. The patients' mean age was 33,3 years (range 11-73). In 10 patients, the stem was used for distal femur reconstruction, in one patient for diaphyseal reconstruction, and in four for a stump lengthening procedure. All of the patients had a primary sarcoma in their history. The mean follow-up period was 37 months (range 5-95 months). The clinical and functional follow-up data were analyzed., Results: Ten patients (67%) were still alive at the time of evaluation. Three complications associated with the stem were noted. In one case, there was aseptic loosening after 58 months; in another, aseptic loosening occurred because the diameter of the stem had initially been too small; and in one case, there was breakage of the fixation screw, without any clinical symptoms. The average Musculoskeletal Tumor Society score for all patients was 23 (range 9-28). The mean result for the distal femur replacement was 24 (range 22-28). None of the surviving patients with distal femur replacements needed any crutches or had a Trendelenburg limp. Both living patients who underwent a stump lengthening procedure were able to walk with an exoprosthesis., Conclusions: The short stem is a good solution that can prevent or delay proximal femur resection in patients with tumors extending into the proximal metaphyseal femur. Additional risks of proximal femur resection, such as dislocation, opening of another oncological compartment, Trendelenburg limp, and chondrolysis can be avoided.

Background: While research on exercise interventions during anticancer treatment is well-established in adults, only very few studies exist in children. However, pediatric patients experience great limitations to being physically active, and appropriate interventions are desired., Procedure: The present study aimed at investigating the effects of individualized exercise interventions during inpatient stays on pediatric patients with a malignant bone tumor. The parameter of interest was physical activity (PA). Patients' PA during home stays was assessed 6 weeks as well as 3, 6, 12, and 18 months post-surgery. Patients were distinguished into an intervention group and a control group. All patients received endoprosthetic replacement of the affected bone in the same institution., Results: A constant increase in all PA parameters was observed during follow-up. Exercise interventions were possible and appeared worthwhile. The intervention group showed better PA results at all measurements; however, no significant differences between groups were found. Furthermore, differences decreased especially after the cessation of the intervention. General problems in reaching appropriate power and compliance were observed., Conclusions: Individualized exercise interventions in pediatric bone tumor patients are possible and appear to be beneficial. Such interventions should be implemented in adjuvant care; however, future research is needed to understand more about the effects of different interventions.

Background: Bone mineral density (BMD) accrual during childhood and adolescence is important for attaining peak bone mass. BMD decrements have been reported in survivors of childhood bone sarcomas. However, little is known about the onset and development of bone loss during cancer treatment. The objective of this cross-sectional study was to evaluate BMD in newly diagnosed Ewing's and osteosarcoma patients by means of dual-energy x-ray absorptiometry (DXA) after completion of neoadjuvant chemotherapy., Methods: DXA measurements of the lumbar spine (L2-4), both femora and calcanei were performed perioperatively in 46 children and adolescents (mean age: 14.3 years, range: 8.6-21.5 years). Mean Z-scores, areal BMD (g/cm2), calculated volumetric BMD (g/cm3) and bone mineral content (BMC, g) were determined., Results: Lumbar spine mean Z-score was -0.14 (95% CI: -0.46 to 0.18), areal BMD was 1.016 g/cm2 (95% CI: 0.950 to 1.082) and volumetric BMD was 0.330 g/cm3 (95% CI: 0.314 to 0.347) which is comparable to healthy peers. For patients with a lower extremity tumor (n = 36), the difference between the affected and non-affected femoral neck was 12.1% (95% CI: -16.3 to -7.9) in areal BMD. The reduction of BMD was more pronounced in the calcaneus with a difference between the affected and contralateral side of 21.7% (95% CI: -29.3 to -14.0) for areal BMD. Furthermore, significant correlations for femoral and calcaneal DXA measurements were found with Spearman-rho coefficients ranging from ρ = 0.55 to ρ = 0.80., Conclusions: The tumor disease located in the lower extremity in combination with offloading recommendations induced diminished BMD values, indicating local osteopenia conditions. However, the results revealed no significant decrements of lumbar spine BMD in pediatric sarcoma patients after completion of neoadjuvant chemotherapy. Nevertheless, it has to be taken into account that bone tumor patients may experience BMD decrements or secondary osteoporosis in later life. Furthermore, the peripheral assessment of BMD in the calcaneus via DXA is a feasible approach to quantify bone loss in the lower extremity in bone sarcoma patients and may serve as an alternative procedure, when the established assessment of femoral BMD is not practicable due to endoprosthetic replacements.

Expression of EGFR in high grade osteosarcomas has been observed to be correlated with an improved prognosis. Yet, the underlying mechanism remained unclear since amplifications of EGFR have rarely been described. Recently, the length of a polymorphic CA repeat located at a 5'-regulatory sequence in the intron 1 of the EGFR gene (SSR I) has been shown to be associated with its basal transcriptional activity. We therefore determined the allelic length of CA SSR-I in 219 cases of high grade osteosarcoma and correlated the results with EGFR expression in 34 cases, the presence of amplifications within the CA SSR-I repeat in 59 cases, and clinical follow-up. Our results confirm that in osteosarcoma patients short alleles are more frequent than longer ones, 16 CA repeats being the most frequent. The allele composition differed significantly from the one recently described in a healthy control population (P < 0.01). Short alleles tended to be associated with increased expression of EGFR. Amplifications of the EGFR gene were seen in 13.5% of cases. Significant correlations between allele length composition and neoadjuvant chemotherapy response or long term clinical outcome could not be established. While we were able to show that high frequency of EGFR expression in osteosarcomas is associated with predominantly short alleles of EGFR-CA SSR I, persisting shortcomings in the correspondence with clinical data point toward the existence of additional, putatively more important transcription control mechanisms for EGFR in osteosarcomas which might account for the good prognostic value of EGFR expression., ((c) 2008 Wiley-Liss, Inc.)

En bloc spondylectomy is a technique that enables wide or marginal resection of malignant lesions of the spine. Both all posterior techniques as well as combined approaches are reported. Aim of the present study was to analyse the results of 21 patients with malignant lesions of the spine, all treated with en bloc excision in a combined posteroanterior (n = 19) or all posterior approach (n = 2). Twenty-one consecutive patients, operated between 1997 and 2005, were included into this retrospective study. Thirteen patients had primary malignant lesions, eight patients had solitary metastases, all located in the thoracolumbar spine. There were 16 single level, three two-level, one three-level and one four-level spondylectomy. The patients were followed clinically and radiographically (including CT studies) with an average follow-up of 4 years. Out of 11 patients with primary Ewing or osteosarcoma seven patients are alive without any evidence of disease. One patient died after 5 years from other causes and three are alive with evidence of disease. Latter had either a poor histologic response to the preoperative chemotherapy (n = 2) or an intralesional resection (n = 1). All three patients with solitary spinal metastases of Ewing or osteosarcoma died of the disease. Five patients with solitary metastases of mainly hypernephroma are alive. In total, six resections were intralesional, mainly due to large intraspinal tumor masses, with two patients having had previous surgery. In the remaining cases, wide (n = 10) or marginal (n = 5) resection was accomplished. There were one pseudarthrosis requiring extension of the fusion and two cases with local recurrences and repeated excisional surgery. At follow-up CT studies, all cages were fused. Health related quality of life analysis (SF-36) revealed only slightly decreased physical component and normal mental component scores compared to normals in those patients with no evidence of disease. En bloc spondylectomy enables wide or marginal resection of malignant lesions of the spine in most cases with acceptable morbidity. Intralesional resection, poor histologic response, and solitary spinal metastases of Ewing and osteosarcoma are associated with a poor prognosis.

Purpose: The expression of the epidermal growth factor receptor (EGFR) in osteosarcomas has repeatedly been described. With the introduction of anti-EGFR-targeted therapies in clinical practice, these findings regain increased attention. Experience with anti-EGFR-targeted therapies in other cancers has made clear that besides the expression status of EGFR, a detailed knowledge about gene mutations is of major predictive power. We therefore aimed to explore the EGFR expression and gene mutation status in high-grade osteosarcomas., Experimental Design: We investigated tumor samples of osteosarcoma patients of all age groups by means of immunohistochemistry (n=111) and egfr fluorescence in situ hybridization (n=39). Sixty-three patients were treated according to the Cooperative Osteosarcoma Study Group protocols and complete clinical follow-up was available in these cases., Results: Ninety-one of 111 (81%) of osteosarcomas revealed an expression of EGFR. EGFR expression showed a dose-response relation with improved event-free and overall survival. This was independent of the degree of tumor regression due to neoadjuvant chemotherapy. Nine of 39 (23%) osteosarcomas showed egfr amplifications by means of fluorescence in situ hybridization. All these cases expressed EGFR. When comparing EGFR expression between primary biopsy and resection specimen (n=19), viable residual tumor cells in resection specimens revealed a lower EGFR expression and a tendency toward membranous staining compared with the initial biopsy., Conclusions: In conclusion, expression and amplification of EGFR are frequently observed in high-grade osteosarcomas and are associated with improved prognosis in a dose-responsive way. This implies that low EGFR expression possibly predicts lack of response to conventional treatment in high-grade osteosarcomas and may warrant a more intensive therapeutic approach, although not based on EGFR targeting.

Background: The prognostic relevance of dose intensity in the treatment of osteosarcoma is still under discussion. The aim of this study was to investigate whether higher dose intensities of chemotherapy correlated with better outcomes., Procedure: This study contains 917 consecutive Cooperative Osteosarcoma Study Group (COSS) patients <40 years with primary, high-grade central, nonmetastatic osteosarcoma of the extremities, who were in complete remission at least until day 200 after the start of chemotherapy. All COSS-protocols were based on a uniform treatment concept of aggressive polychemotherapy and definitive surgery. Chemotherapy dose intensity in the first 200 days of treatment (DI200) and possible correlations to overall and event-free survival were investigated. The study focused on methotrexate, doxorubicin, cisplatin, and ifosfamide, which are considered to be the most active drugs against osteosarcoma. Multivariate analyses including well-known prognostic factors were added to complete this investigation., Results: Until day 200, patients received 80.7 +/- 26.1 g/m2 methotrexate (MTX); 242 +/- 69 mg/m2 doxorubicin (DOX); 324 +/- 133 mg/m2 cisplatin (DDP); and 13.9 +/- 9.8 g/m2 ifosfamide (IFO) (mean +/- SD). Median follow-up from day 200 was 6.6 (0.02-22.1) years. There was no correlation between a higher DI200 of any one drug and better outcomes in uni- or multi-variate analyses. Total treatment intensity did not show such correlations either., Conclusions: In an overall setting of intensive multidrug treatment of osteosarcoma, we could not prove that higher dose intensities correlate with better outcomes., (Copyright 2006 Wiley-Liss, Inc.)

Matrix-producing bone lesions consist of a wide variety of benign and malignant conditions. With respect to morphology, an overlap exists between benign and malignant bone tumors that causes difficulties in the final determination of the tumor. This study was conducted to show the potential of comparative genomic hybridization as a tool in the differential diagnosis of matrix-producing bone lesions. Thirty benign bone tumors were evaluated by conventional comparative genomic hybridization. To test its diagnostic reliability, 5 additional cases were analyzed, all with differential diagnostic difficulties related to morphology and radiology. All were ultimately diagnosed as malignant sarcomas, and unbalanced alterations were detected. In contrast benign tumors or tumor-like lesions did not reveal any chromosomal alterations. Comparative genomic hybridization is a useful adjunct in the complicated differential diagnostic algorithms of matrix-producing bone tumors.

Periosteal osteosarcoma is a rare primary malignant bone tumour. Treatment is by surgical excision, but controversy remains about the value of chemotherapy. The members of the European Musculo Skeletal Oncology Society (EMSOS) collaborated to produce a dataset of 119 patients. The predominant site for the tumour was the femur, followed by the tibia. All but 2 patients underwent surgery, with 9 requiring amputation and the others having limb salvage. A total of 81 patients had chemotherapy, of whom 50 had neoadjuvant chemotherapy. There was no standard chemotherapy regime, but all patients receiving chemotherapy were given doxorubicin combined with at least one other agent. The overall survival was 89% at 5 years and 83% at 10 years. Eight patients developed local recurrence, of whom 5 died. Survival was related to appearance of local recurrence (P < 0.0001) but no other single factor. The use of chemotherapy was not shown to be a prognostic factor, but was used in two-thirds of the patients in this study.

Purpose: The aims of this analysis were to investigate the clinical features of extraskeletal osteosarcoma (ESOS) and examine the outcome after multi-modal therapy., Methods: The co-operative osteosarcoma study-group database was searched for patients with extraskeletal osteosarcoma. Eligible patients were included in a retrospective analysis of patient, tumour and treatment related variables and outcome. As for conventional osteosarcoma, scheduled treatment included surgery and multi-agent chemotherapy., Results: Seventeen eligible patients were identified with a median age of 44 years (range, 3-65 years). The thigh was the commonest tumour site. Two patients had a history of previous malignancies and two had primary metastases. Median follow-up was 3.2 years (range: 0.6-7.4 years) and at last follow-up, 11 patients were alive in complete remission, 3 patients were alive with disease and 3 patients had died of their disease. Three-year overall actuarial and event-free survival rates were 77% and 56%, respectively. Patients with macroscopically complete surgical remission had an improved overall survival (P = 0.0004)., Conclusions: The patients in this retrospective study had a surprisingly good survival rate. This may be due to the combination of multi-agent chemotherapy with surgery, and we recommend this approach in the treatment of ESOS.

Purpose: The purpose of this work was to evaluate the prognostic relevance of microvessel density (MVD) for response to chemotherapy and long-term outcome in osteosarcoma., Experimental Design: Pretherapeutic tumor biopsies of 60 patients with high-grade central osteosarcoma, who were treated according to multimodal neoadjuvant protocols of the German-Austrian-Swiss Cooperative Osteosarcoma Study Group, were evaluated for intratumoral MVD. MVD was correlated with demographic and tumor-related variables, response, and survival., Results: The median intratumoral MVD was 52 microvessels per 0.26-mm2 field area (interquartile range, 31-77 microvessels per 0.26-mm2 field area). At a median follow-up period of 3.5 years, patients with a high (>median) MVD had significantly higher 5- and 10-year overall survival rates (84%) than patients with low (< or =median) MVD (49%; P = 0.0029). Furthermore, increased relapse-free survival for patients with high MVD (P = 0.0064) was observed. In a subgroup analysis of 44 patients with primary high-grade central osteosarcoma of the extremities without primary metastases and good surgical remission, high MVD was associated with 5- and 10-year overall survival rates of 91% compared with 58% for low MVD (P = 0.034). Cox regression analysis revealed that MVD was an independent prognostic factor for survival. A good response to chemotherapy (histologic grading scale of Salzer-Kuntschik) correlated significantly with a high MVD (P = 0.006)., Conclusions: Increased angiogenesis is a prognostic indicator for higher survival and response rates to chemotherapy in patients with osteosarcoma. Thus, measurement of MVD might be useful in decisions selecting patients for future neoadjuvant treatment.

Four patients were treated with limb lengthening to correct a leg-length discrepancy that developed after a hip transposition after pelvic resection for sacroma of the pelvis. Three patients had Ewing's sacroma and one patient had osteosarcoma. All patients received chemotherapy; radiotherapy also was administered to the three patients with Ewing's sacroma. Femur lengthening was started at an average of 5.7 years (range, 4.4-6.8 years) after tumor surgery. At the start of elongation, the average age of the patients was 17.3 years (range, 10.3-20.8 years). The average leg-length discrepancy was 10.3 cm (range, 6-12 cm). The average of achieved lengthening was 6.4 cm (range 6-7.5 cm). The average healing index was 32 days (range, 27-40 days) per 1-cm elongation. According to the classification of Paley, two problems and two minor complications were treated by additional interventions. At the final followup, the average functional score was 22 (73%) according to the system of the Musculoskeletal Tumor Society. Leg-length discrepancy after hip transposition can be corrected with distraction osteogenesis. All patients who wore a stiff ankle-foot orthosis before lengthening wore an ordinary shoe lift after lengthening. The problems of the lengthening procedure are similar to the general complication rate of bone lengthening. Because the 5-year survival after resection of a pelvic sarcoma is only 20% to 30%, leg lengthening after hip transposition should be offered only to long-term survivors with at least 5 years event-free survival.

The incidence and characteristics of sacral infiltration in pelvic sarcomas were analyzed. Fifty-one patients with a pelvic sarcoma (chondrosarcoma, 15 patients; Ewing's sarcoma, 23 patients; and osteosarcoma, 13 patients) abutting the sacroiliac joint had surgical treatment. Tumor infiltration into the sacrum was suspected based on preoperative images in 18 patients; 15 of 18 patients had histologic tumor invasion. There was a significant difference of median volume of sarcomas with and without infiltration. One of 23 Ewing's sarcomas, seven of 15 chondrosarcomas, and seven of 13 osteosarcomas penetrated the sacroiliac joint into the sacrum. Logistic regression test showed that diagnosis was the most important factor influencing sacral infiltration. Twelve tumors infiltrated through the posterior part of the joint, two tumors infiltrated through the anterior part, and one large tumor infiltrated through an unknown route. To obtain wide surgical margins, patients at risk (elderly, large tumor, or diagnosis of osteosarcoma or chondrosarcoma) for sacral involvement may require extended internal hemipelvectomy with the medial margin extending into the sacrum. High quality imaging studies should be used to assess the need for transarticular resection.

Simple Summary: Postoperative infection is one of the gravest complications in patients following megaprosthetic replacement due to primary malignant bone tumors. On the other hand, several studies have also suggested that patients with a variety of different cancers may have a better chance of survival following the development of an infection, possibly as a result of the immune and inflammatory host responses to infection. Our retrospective analysis of 437 extremity osteosarcoma patients found that patients with a poor response to neoadjuvant chemotherapy and an infection in the first 12 months after primary tumor surgery had a better chance of survival compared to patients without infections. If this finding can be validated in a different patient cohort, it would suggest that the efficacy of novel immunomodulatory treatments in osteosarcoma patients should be evaluated and reported separately for patients with a good and a poor response to preoperative chemotherapy, as the latter might benefit more from such treatments. Recent retrospective studies suggested that early postoperative infections might be associated with a survival benefit for extremity osteosarcoma patients, but the reported results have been conflicting. The files of 437 patients with a newly diagnosed, high-grade osteosarcoma of the extremities treated at 5 referral centers in Germany and Austria between 1989 and 2016 were retrospectively evaluated. All patients underwent multi-agent chemotherapy and limb-sparing tumor excision, followed by endoprothetic replacement. We used the Kaplan–Meier method to calculate survival curves, which we compared with the log-rank test. With a median follow-up of 100 months (interquartile range, 49–155 months), local recurrence (LR) probability, event-free survival (EFS), and disease-specific survival (DSS) after 5 years in this selected patient cohort amounted to 5%, 67%, and 79%, respectively, and 46 patients (10.5%) developed an early postoperative infection. We found no significant differences in LR, EFS, or DSS between patients with and without early infections, and there were no differences in known prognostic factors between the two groups. However, in subgroup analyses patients with a poor response to neoadjuvant chemotherapy and an early infection had a better DSS compared to patients without early infections (93% vs. 62% after 5 years, p = 0.044). Provided that our findings can be validated in separate patient cohorts, we believe that patient outcome after adjuvant immunomodulatory treatments in osteosarcoma patients should be evaluated and reported separately for good and poor responders to neoadjuvant chemotherapy in future studies. [ABSTRACT FROM AUTHOR]

• Hemipelvectomy (PI-II) after rotationplasty on the same leg resulted in a good functional result in a 16 year old male patient with osteosarcoma. • For hemipelvectomy, the musculus gluteus maximus is essential for soft tissue coverage, therefore supplying structures must be preserved. • The triradiate cartilage of the acetabulum closes around a bone age of 12 years in boys and then is no sufficient barrier for an osteosarcoma. The hip transposition is a limb salvage procedure for periacetabular malignancies. Here we present the case of a patient that already had a preexisting ipsilateral rotationplasty. A 16 year old male patient with an Osteosarcoma of the left distal femur was treated with wide surgical resection of the tumor and rotationplasty (Salzer/Winkelmann type A1). Despite adjuvant chemotherapy (EURAMOS protocol) he was diagnosed with metachronous metastases in the lung and in the left ilium affecting the acetabulum. As a limb salvage procedure the patient received an internal hemipelvectomy Enneking PI-II and an attachment of the femoral head with a Trevira tube to the sacrum using suture anchors. After six weeks a prosthesis was fitted and gradually full weight bearing was allowed. The patient achieved a good functional result as he was able to walk freely for three more years before he passed away. The hip transposition procedure does not require the implantation of a large tumor prosthesis and thus avoids the problem of an increased risk of infection. Even with preexisting ipsilateral rotationplasty a good functional outcome that allowed the patient full weight bearing could be achieved. If there are already existing deformities, such as rotationplasty on the same leg, the hip transposition procedure can be considered for periacetabular malignancies, as it can achieve satisfactory results. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Forequarter amputation (FQA) is a surgical treatment of tumors in the upper extremity and shoulder girdle that infiltrate the neurovascular bundles. In both curative and palliative settings, FQA can serve as an effective oncological treatment. Methods: This study presents the FQA-related data of 30 patients (mean age 50 years) treated between 2000 and 2012. Their medical condition was high-grade bone or soft tissue sarcoma in 26 and high-grade carcinoma in four cases. Results: Mean operation time was 119 min. One major and five minor complications occurred in the postoperative period. Resection margins were wide in 91% of patients. Local recurrence was observed in four patients after 19 months on average. Patients treated with curative intention had a 5-year survival chance of 39%. Average survival after palliative amputation was 11 months. Conclusions: FQA provides an opportunity for adequate oncological margins in large tumors, while offering relief from tumor-induced distress in palliative situations. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• Limb-preserving treatment in young children suffering malignant bone tumors remains challenging. • MUTARS® Humero pro Femur replacement represents a salvage procedure. • Distal humerus component serves as a hinged knee joint after 180° rotation. • Satisfactory complication rates and functional results. • Subsequent conversion to conventional tumor endoprosthesis. Limb-preserving surgery in young children suffering malignant bone tumor of the femur is challenging due to the specific anatomical conditions. Extendable tumor endoprostheses are often oversized, while custom-made endoprostheses do not provide the intraoperatively required variability regarding reconstruction length. Allo- and autograft replacements, on the other hand, show high complication and revision rates. We report a novel reconstructive procedure after resection of malignant bone tumors of the femur in young children, and present our preliminary results of this technique. [ABSTRACT FROM AUTHOR]

Background: The chick chorio-allantoic membrane (CAM) assay is a commonly used method for studying angiogenic or anti-angiogenic activities in vivo. The ease of access allows direct monitoring of tumour growth by biomicroscopy and the possibility to screen many samples in an inexpensive way. The CAM model provides a powerful tool to study effects of molecules, which interfere with physiological angiogenesis, or experimental tumours derived from cancer cell lines. We therefore screened eight osteosarcoma cell lines for their ability to form vascularized tumours on the CAM. Findings: We implanted 3-5 million cells of human osteosarcoma lines (HOS, MG63, MNNG-HOS, OST, SAOS, SJSA1, U2OS, ZK58) on the CAM at day 10 of embryonic development. Tumour growth was monitored by in vivo biomicroscopy at different time points and tumours were fixed in paraformaldehyde seven days after cell grafting. The tissue was observed, photographed and selected cases were further analyzed using standard histology. From the eight cell lines the MNNG-HOS, U2OS and SAOS were able to form solid tumours when grafted on the CAM. The MNNG-HOS tumours showed the most reliable and consistent growth and were able to penetrate the chorionic epithelium, grow in the CAM stroma and induce a strong angiogenic response. Conclusions: Our results show that the CAM assay is a useful tool for studying osteosarcoma growth. The model provides an excellent alternative to current rodent models and could serve as a preclinical screening assay for anticancer molecules. It might increase the speed and efficacy of the development of new drugs for the treatment of osteosarcoma. [ABSTRACT FROM AUTHOR]

Although the recurrence rate of giant cell tumors of bone (GCTB) is relatively high exact data on treatment options for the recurrent cases is lacking. The possible surgical procedures range from repeated intralesional curettage to wide resection. Two hundred and fourteen patients with histologically certified GCTB have been treated at the authors department from 1980 to 2007. Sixty-seven patients with at least one local recurrence were included in this study. The mean follow-up was 77.3 months. The data was evaluated according the re-recurrence rate with regard to the surgical procedure for the recurrence. The mean time until the first local recurrence was 22.0 months; the mean number of recurrences per patient was 1.4. The recurrence occurred in 69.7% (46 out of 66 patients) within the first 2 years. If after intralesional procedures (curettage or intralesional resection) no adjunct was used the re-recurrence rate was 58.8% (10 out of 17 patients) and decreased to 21.7% (5 out of 23 patients) if a combination of all adjuncts (PMMA + burring) was used. The likelihood of re-recurrence was reduced by the factor 5.508 which was clearly significant ( P = 0.016). In case of wide resection no re-recurrence occurred. Seven patients (10.5%) developed pulmonary metastases. Fourteen patients (20.9%) finally received an endoprosthesis; 12 due to tumor recurrence, 2 due to secondary arthritis. Recurrent GCTB can be treated by further curettage with additional burring and cementing with an acceptable re-recurrence rate of 21.7%. The rate of patients finally needing an endoprosthesis is 20.9%. Due to the high rate of pulmonary metastases recurrent GCTB may be considered as a severe disease. [ABSTRACT FROM AUTHOR]

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 5–25mg 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. [ABSTRACT FROM AUTHOR]

The article presents a case report of total tibial endoprosthesis including ankle joint and knee joint replacement in a 32-year-old patient with Ewing sacroma. Total endoprosthetic replacement of the complete tibia including a rotating-hinge knee prosthetis and a trans-talar and trans-calcanear stem was performed for the first time on the patient.