Surgical Outcome and Oncological Survival of Osteofibrous Dysplasia-Like and Classic Adamantinomas: An International Multicenter Study of 318 Cases.

BACKGROUND: Osteofibrous dysplasia-like adamantinoma (OFD-AD) and classic adamantinoma (AD) are rare, neoplastic diseases with only limited data supporting current treatment protocols. We believe that our retrospective multicenter cohort study is the largest analysis of patients with adamantinoma to date. The primary purpose of this study was to describe the disease characteristics and evaluate the oncological outcomes. The secondary purpose was to identify risk factors for local recurrence after surgical treatment and propose treatment guidelines. METHODS: Three hundred and eighteen confirmed cases of OFD-AD and AD for which primary treatment was carried out between 1985 and 2015 were submitted by 22 tertiary bone tumor centers. Proposed clinical risk factors for local recurrence such as size, type, and margins were analyzed using univariable and multivariate Cox regression analysis. RESULTS: Of the 318 cases, 128 were OFD-AD and 190 were AD. The mean age at diagnosis was 17 years (median, 14.5 years) for OFD-AD and 32 years (median, 28 years) for AD; 53% of the patients were female. The mean tumor size in the OFD-AD and AD groups combined was 7.8 cm, measured histologically. Sixteen percent of the patients sustained a pathological fracture prior to treatment. Local recurrence was recorded in 22% of the OFD-AD cases and 24% of the AD cases. None of the recurrences in the OFD-AD group progressed to AD. Metastatic disease was found in 18% of the AD cases and fatal disease, in 11% of the AD cases. No metastatic or fatal disease was reported in the OFD-AD group. Multivariate Cox regression analysis demonstrated that uncontaminated resection margins (hazard ratio [HR] = 0.164, 95% confidence interval [CI] = 0.092 to 0.290, p < 0.001), pathological fracture (HR = 1.968, 95% CI = 1.076 to 3.600, p = 0.028), and sex (female versus male: HR = 0.535, 95% CI = 0.300 to 0.952, p = 0.033) impacted the risk of local recurrence. CONCLUSIONS: OFD-AD and AD are parts of a disease spectrum but should be regarded as different entities. Our results support reclassification of OFD-AD into the intermediate locally aggressive category, based on the local recurrence rate of 22% and absence of metastases. In our study, metastatic disease was restricted to the AD group (an 18% rate). We advocate wide resection with uncontaminated margins including bone and involved periosteum for both OFD-AD and AD. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

[Osteosarcomatous dedifferentiated chondrosarcoma]. / Osteosarkomatös dedifferenziertes Chondrosarkom.

A secondary peripheral chondrosarcoma (SPC) evolving from an osteochondroma is rare, but it has been described several times. The development of an osteosarcomatous dedifferentiated chondrosarcoma in a locally recurrent SPC is extremely rare. The following case report of a 46-year-old man demonstrates and discusses this phenomenon.

Prognostic relevance of the mitotic count and the amount of viable tumour after neoadjuvant chemotherapy for primary, localised, high-grade soft tissue sarcoma.

BACKGROUND: We sought to examine whether mitotic count (MC) and the amount of viable tumour (VT) following neoadjuvant systemic chemotherapy (SC) for primary, localised, high-grade soft tissue sarcoma (STS) correlate with prognosis. METHODS: Retrospective analysis of 57 patients who underwent SC involving a combination of an anthracycline and an alkylating agent, followed by surgical resection between 2001 and 2011. RESULTS: The amount of VT after chemotherapy was significantly associated with disease-specific survival (DSS) and event-free survival (EFS). Patients with <10% VT had a DSS of 94% at 5 years, compared with 61% for patients with ⩾10% VT (P=0.033); EFS was 75%, compared with 48% (P=0.030). Patients with an MC of ⩾20/10 high power fields (HPF) after chemotherapy had a significantly lower DSS (33% vs 84% at 5 years, P<0.001) and EFS (40% vs 63% at 5 years, P=0.019) than patients with an MC of <20/10 HPF. CONCLUSIONS: The MC and the amount of VT after neoadjuvant therapy for primary, localised, high-grade STS appear to correlate with prognosis. If these results are validated prospectively, then they could provide a rational for the design of neoadjuvant treatment modification/escalation studies, analogue to the EURAMOS-1 trial for bone sarcomas.

[Resection margins in bone tumors: what is adequate?]. / Tumorresektion: Wie weit ist weit genug?

BACKGROUND: In multimodal therapy concepts for bone sarcomas, tumor resection is a deciding factor. Modern imaging techniques have made preoperative resection planning much easier and precisely allow tumor boundaries to be defined. OBJECTIVES: There is recent data clearly showing that compartmental resections have no significant advantages compared to wide resections in terms of local recurrence or overall survival. But it remains unclear, how "wide" a "wide resection" should be done. MATERIALS AND METHODS: A literature review of the last 15 years, discussion of review articles and multidisciplinary expert opinions as published in major multinational studies. RESULTS: Intralesional resection (R1) is feasible in highly differentiated (G1) chondrosarcoma (atypical cartilaginous tumor) of the extremity. In both osteosarcoma and Ewing's sarcoma, R0 resection is mandatory. If these fails, there is evidence that in selected cases of osteosarcoma, adjuvant radiotherapy is justified if a second resection is not possible. Expecting contaminated (R1) margins in patients with Ewing's sarcoma (e.g., in critical locations such as the pelvis), radiotherapy only is better than hoping for the "cure" of insufficient resections margins with a combination of both methods. With regard to the necessary safety distances for a R0 resection, recommendations from the literature are heterogeneous. In addition to the distance measurement, the quality of the anatomic resection margins (e.g., fascia) is of great importance. A distinct recommendation of at least x millimeters or centimeters cannot be given based on the currently available data. CONCLUSION: The aim of the resection of a bone sarcoma should be a wide margin with the exception of chondrosarcoma (G1). Ultraradical resections which sacrifice vital structures in order to extend an already wide (R0) resection margin showed no significant benefits. In patients with osteosarcoma, adjuvant radiotherapy should be considered if resection or re-resection is not in sound tissue (R1). Patients with Ewing's sarcoma should not undergo resection if a contaminated margin is expected. In patients with chondrosarcoma, the available data as for example from pelvic tumors are contradictory and do not allow a clear recommendation.

[Surveillance in patients with bone sarcomas. When, how, and for how long?]. / Nachsorge von Patienten mit Knochensarkomen. Wann, wie und wie lange?

BACKGROUND: The overall survival in patients with typical bone sarcomas such as Ewing-sarcoma, osteosarcoma, or chondrosarcoma exceeds 60% in localized disease after 5 years. Local or systemic recurrence detected by surveillance may not only improve or solve the local problem but also significantly improves the prognosis of the patient. Thus, surveillance seems to be justified. OBJECTIVES: As a consequence, the questions of how and how long surveillance should be performed must be answered. METHODS: A literature review of the last 15 years, discussion of review articles, and multidisciplinary expert opinions as published in major multinational studies. RESULTS: The decision which surveillance scheme outside of clinical studies might be appropriate largely depends on the prognostic benefit of early detection of local or systemic recurrence. The detection rate of local recurrence by the patient himself is high in extremities. A systematic technical examination for the detection of pulmonary metastases is controversial because the chance of cure in systemic progression is generally unfavorable. Whether the earlier detection of both types of recurrence due to reduced examination intervals and/or the use of a CT or MRI is significantly advantageous, remains unproven. The duration of surveillance is even less clear. Both local and systemic recurrences may be seen more than 10 years after treatment of the primary tumor. CONCLUSION: Surveillance makes sense in any case, since the detection of a local recurrence is possible already with methods easy to apply. Whether and to what extent local imaging is used is left to the individual case. Under the current conditions in Germany, local (e.g., MRI) imaging at least every 6 months during the first 2-3 years, then possibly on an annual basis is recommended. There is no evidence-based support for the decision whether and when an X-ray of the chest is indicated and whether and when a CT scan should be performed. Striking is the lack of prospective studies on surveillance concerning both patient- and economically relevant aspects of tumor therapy.

Differentiation of myxoid liposarcoma by magnetic resonance imaging: a histopathologic correlation.

BACKGROUND: Myxoid liposarcomas represent a heterogeneous group of soft tissue tumors in which prognosis is dependent on differentiation. PURPOSE: To identify magnetic resonance imaging (MRI) criteria to distinguish low-grade from high-grade myxoid liposarcomas. MATERIAL AND METHODS: MR images of 30 histologically proven myxoid liposarcomas were retrospectively reviewed. Tumors were evaluated according to size, localization, tumor border, and structure as well as tumor composition. These imaging criteria were correlated with histopathological findings. RESULTS: Nineteen myxoid liposarcomas were histologically classified as low-grade myxoid liposarcomas, whereas 11 were considered high-grade myxoid liposarcomas. Mean tumor volume of low-grade myxoid liposarcomas (710.1 ± 960.1 ccm) was significantly smaller as compared to high-grade myxoid liposarcomas (2737.0 ± 3423.7 ccm; P = 0.04). In addition to necrotic areas, three tumor components - fatty, myxoid, as well as contrast-enhancing non-fatty, non-myxoid - could be identified. The mean fraction of fatty tumor areas in low-grade myxoid liposarcomas was 10 ± 11% as compared to 6 ± 4% for high-grade myxoid liposarcomas (P = 0.66). Myxoid components accounted for 88 ± 16% in low-grade myxoid liposarcomas, but only for 45 ± 25% in high-grade myxoid liposarcomas (P < 0.0001). The non-fatty, non-myxoid tumor fraction was significantly higher in high-grade myxoid liposarcomas (50 ± 25%) as compared to low-grade myxoid liposarcomas (2 ± 9%; P < 0.0001). A proportion of > 5% of this tumor fraction was found to be a precise unique predictor for high-grade myxoid liposarcomas with a sensitivity of 100% and a specificity of 95%. CONCLUSION: Tumor components with contrast-enhancing non-fatty, non-myxoid imaging features were predominantly found in high-grade myxoid liposarcomas, which may histologically resemble round cell clusters.

Radiofrequency ablation of osteoid osteomas: analgesia and patient satisfaction in long-term follow-up.

PURPOSE: To review the long term clinical outcomes in the treatment of osteoid osteoma (OO) using radiofrequency ablation (RFA). MATERIALS AND METHODS: Our retrospective study included 59 patients who were treated in the period from April 2001 to December 2012 due to a symptomatic OO using RFA. Here, the occurrence of complications and postoperative recurrence, as well as postoperative patient satisfaction were examined. Patients satisfaction was assessed by means of a telephone interview with the visual analogue scale (VAS). RESULTS: Mean follow-up was 50 months (2 - 116 months). The average size of the nidus was 6 mm (range 2 - 14 mm). After initial radiofrequency ablation 11.8 % (7/59) of patient showed a recurrence of symptoms. Symptoms could successfully be treated by a second ablation in 5 patients. Assisted success rate was therefore 96.6 % (57/59). The complication rate was 5.1 % (2 major and one minor complication). Furthermore we report a very high patient satisfaction and acceptance of therapy. CONCLUSION: RFA is a very successful therapy of symptomatic OOs with a high patient satisfaction. KEY POINTS: ▶ Osteoid osteomas (OO) are rare benign bone tumors of the childhood and adolescence. ▶ Treatment of OOs with minimal-invasive radiofrequency ablation (RFA) shows a high patient satisfaction. ▶ RFA is by now the standard therapy of symptomatic OOs.

Argyria following the use of silver-coated megaprostheses: no association between the development of local argyria and elevated silver levels.

The aims of this study were to evaluate the incidence of local argyria in patients with silver-coated megaprostheses and to identify a possible association between argyria and elevated levels of silver both locally and in the blood. Between 2004 and 2011, 32 megaprostheses with silver coatings were implanted in 20 female and 12 male patients following revision arthroplasty for infection or resection of a malignant tumour, and the levels of silver locally in drains and seromas and in the blood were determined. The mean age of the patients was 46 years (10 to 81); one patient died in the immediate post-operative period and was excluded. Seven patients (23%) developed local argyria after a median of 25.7 months (interquartile range 2 to 44.5). Patients with and without local argyria had comparable levels of silver in the blood and aspiration fluids. The length of the implant did not influence the development of local argyria. Patients with clinical evidence of local argyria had no neurological symptoms and no evidence of renal or hepatic failure. Thus, we conclude that the short-term surveillance of blood silver levels in these patients is not required.

Sentinel node biopsy in soft tissue sarcoma subtypes with a high propensity for regional lymphatic spread--results of a large prospective trial.

BACKGROUND: The role of sentinel lymph node biopsy (SLNB) in soft tissue sarcoma patients has yet to be determined. We sought to evaluate the role of SLNB in the treatment of patients with clear cell sarcoma (CCS), synovial sarcoma (SS), epithelioid sarcoma (ES) and rhabdomyosarcoma (RMS). PATIENTS AND METHODS: Sixty-two consecutive patients without history of regional lymphatic spread or evidence of distant metastases underwent SLNB. RESULTS: Positive sentinel nodes were identified in 2 out of 42 patients with SS and in 6 out of 12 patients with CCS. Only two CCS patients had further metastatic nodes in regional dissection. Both of these patients, along with another CCS patient, developed distant metastases and ultimately died of disease. The remaining three CCS patients are disease-free in follow-up. One patient with SS and another with ES developed regional lymph node metastases following a negative SLNB, while a further patient with RMS developed distant metastases followed by a local recurrence with regional metastases shortly after. CONCLUSIONS: SLNB is an important diagnostic tool for patients with CCS, who appear to have a high rate of clinically occult regional lymph node metastases at diagnosis. For SS patients, SLNB appears to be of very little relevance.

Radiofrequency ablation of osteoid osteomas: analgesia and patient satisfaction in long-term follow-up.

PURPOSE: To review the long term clinical outcomes in the treatment of osteoid osteoma (OO) using radiofrequency ablation (RFA). MATERIALS AND METHODS: Our retrospective study included 59 patients who were treated in the period from April 2001 to December 2012 due to a symptomatic OO using RFA. Here, the occurrence of complications and postoperative recurrence, as well as postoperative patient satisfaction were examined. Patients satisfaction was assessed by means of a telephone interview with the visual analogue scale (VAS). RESULTS: Mean follow-up was 50 months (2 ­116 months). The average size of the nidus was 6mm (range 2 ­ 14 mm). After initial radiofrequency ablation 11.8 % (7/59) of patient showed a recurrence of symptoms. Symptoms could successfully be treated by a second ablation in 5 patients. Assisted success rate was therefore 96.6 % (57/59). The complication rate was 5.1 % (2 major and one minor complication). Furthermore we report a very high patient satisfaction and acceptance of therapy. CONCLUSION: RFA is a very successful therapy of symptomatic OOs with a high patient satisfaction. KEY POINTS: Osteoid osteomas (OO) are rare benign bone tumors of the childhood and adolescence. Treatment of OOs with minimal-invasive radiofrequency ablation (RFA) shows a high patient satisfaction. RFA is by now the standard therapy of symptomatic OOs.

[Bone metastases treatment strategies]. / Behandlungsstrategien bei Skelettmetastasen.

The primary goals of multimodal, interdisciplinary treatment of bone metastases are to achieve mobility, pain relief, and improve quality of life. In cooperation with radiotherapists and oncologists, an individual therapy plan has to be designed. As bone metastases are a sign of a systemic spread of the disease, cure is not possible in nearly all cases. A singular bone metastasis of a renal cell carcinoma may be regarded as an exemption, where wide resection might cure the patient. The extent of the operation should be based on the 3S principle "save, short & simple". The prognosis of survival should influence the treatment regime. If it is unclear whether a bone metastasis or a primary bone tumor is present, a biopsy is required.

Identification of the primary tumour with the help of diffusion-weighted MRI in a patient with autosomal dominant polycystic kidney disease and metastatic renal cell carcinoma.

We report the case of a 47-year-old patient with autosomal dominant polycystic kidney disease, who became symptomatic owing to a painful metastasis of a renal cell carcinoma. Abdominal sonography, multiphase CT and MRI were performed in order to localise and resect the primary tumour, but its identification was severely hampered owing to multiple renal cysts. In addition to standard MRI protocol, a spin-echo, single-shot echo planar diffusion-weighted imaging sequence was performed. The mean apparent diffusion coefficient (ADC) of renal cysts was 2.66±0.12 × 10(-3) mm(2) s(-1), 1.76±0.19 × 10(-3) mm(2) s(-1) of renal parenchyma in and 1.26±0.18 × 10(-3) mm(2) s(-1) of a suspicious soft-tissue mass at the midsection of the right kidney, indicating an area of higher cellularity. This value was significant lower than the ADC obtained for renal parenchyma (p<0.0001). Right-sided nephrectomy was performed and the pathological diagnosis of the suspicious lesion was clear cell renal carcinoma.

Computed tomographic criteria for the discrimination of subcentimeter lung nodules in patients with soft-tissue sarcomas.

The aim of this study was to identify criteria for nodule characterization on chest computed tomography in patients with soft tissue sarcomas. In 195 patients, a total of 194 benign and 117 malignant subcentimeter lung nodules were retrospectively analyzed according to lesion size, shape, margins, density, and localization. Benign lesions more frequently displayed complex shape and were of ground-glass density (P<.0001, respectively). In contrast, round shape and solid density were more frequently found in malignant lesions (P<.0001, respectively).

The influence of tumor- and treatment-related factors on the development of local recurrence in osteosarcoma after adequate surgery. An analysis of 1355 patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols.

BACKGROUND: Local recurrence (LR) in osteosarcoma is associated with very poor prognosis. We sought to evaluate which factors correlate with LR in patients who achieved complete surgical remission with adequate margins. PATIENTS AND METHODS: We analyzed 1355 patients with previously untreated high-grade central osteosarcoma of the extremities, the shoulder and the pelvis registered in neoadjuvant Cooperative Osteosarcoma Study Group trials between 1986 and 2005. Seventy-six patients developed LR. RESULTS: Median follow-up was 5.56 years. No participation in a study, pelvic tumor site, limb-sparing surgery, soft tissue infiltration beyond the periosteum, poor response to neoadjuvant chemotherapy, failure to complete the planned chemotherapy protocol and biopsy at a center other than the one performing the tumor resection were significantly associated with a higher LR rate. No differences were found for varying surgical margin widths. Surgical treatment at centers with small patient volume and additional surgery in the primary tumor area, other than biopsy and tumor resection, were significantly associated with a higher rate of ablative surgery. CONCLUSIONS: Patient enrollment in clinical trials and performing the biopsy at experienced institutions capable of undertaking the tumor resection without compromising the oncological and functional outcome should be pursued in the future.

Limb-salvage reconstruction with MUTARS hemipelvic endoprosthesis: a prospective multicenter study.

BACKGROUND: Limb-sparing surgery with hemipelvic megaprosthetic replacement is often limited by the high rate of associated complications. The aim of this evaluation was to assess clinical and oncological findings with respect to type, treatment and outcome of post-operative complications. METHODS: First results of 40 patients treated with individual MUTARS hemipelvic endoprostheses were evaluated in a prospective multicenter study. RESULTS: The mean follow-up period of the 27 male and 13 female patients was 24 months (range 1-61). The diagnosis was, in 29 cases, a primary bone or soft tissue sarcoma, in 11 patients, a metastasis. Clinical evaluation showed a mean Enneking score of 50% (range 10-70%). The oncological outcome revealed 25 patients (62.5%) alive with no evidence of disease. Seventeen of them had a primary tumour, eight a metastatic malignancy. Seven patients (17.5%) had died of their disease and eight (20%) were still alive but had developed a metastases and/or had had a recurrence of the primary tumour. The one- and two-year overall survival rate of the patients was 89% (+/- 0.10) and 81% (+/- 0.19), respectively. Post-operative complications occurred in 75% of the patients, predominantly wound-related disorders. The rate of implant revision was 22.5% with three septic and six aseptic cases of implant loosening. The estimated three-year-survival rate of the implant was 61.4% [CI95%: 0.36;0.87]. CONCLUSIONS: Periacetabular endoprosthetic replacement showed an acceptable functional and oncological outcome but had a high complication rate owing, predominantly, to infection. The indication for hemipelvic prosthesis in patients with a metastatic disease must be considered seriously.

Functional outcome after endoprosthetic limb-salvage therapy of primary bone tumours--a comparative analysis using the MSTS score, the TESS and the RNL index.

Limb-saving therapy for primary bone tumours is the treatment of choice. We aimed at analysing the quality of life of this group of patients by combining three different tools. Eighty-seven patients (46 females, 41 males) with a primary bone tumour of the extremity who had undergone endoprosthetic reconstruction between 1982 and 2000 were included in this retrospective study. The median age at the time of evaluation was 30 (12-73) years. The Toronto Extremity Salvage Score (TESS) and the Reintegration to Normal Living index (RNL) were recorded an average of 5.8 years after reconstruction and the Musculoskeletal Tumour Society Score (MSTS) after an average of 6.5 years. The mean MSTS score was 77% (13-93%). The mean TESS was 82% (22-99%), and the mean RNL index was 87% (32-98%). The subjective satisfaction and acceptance of physical impairment were significantly higher than the objective score (p < 0.001). The TESS was 88% in patients aged 12-25 years, 81% in those aged 26-40 years and 57% in those aged 41-73 years. Parallel recording of the MSTS score, TESS and RNL index provides a better measure reflecting the complex situation of the patients by combining objective and subjective parameters.

Sentinel node biopsy in synovial sarcoma.

AIMS: To examine the relevance of sentinel node biopsy in patients with synovial sarcoma. METHODS: Between July 2004 and February 2007 11 consecutive patients with synovial sarcoma treated in our clinic underwent sentinel node biopsy after a preoperative lymphoscintigraphy. A handheld gamma-probe was used during the procedure to identify the sentinel nodes, which were then resected and submitted for histopathologic evaluation. RESULTS: At least one sentinel node was identified in every patient. Of a total of 15 sentinels, one was positive and 14 negative. The patient with the positive sentinel underwent a regional lymph node dissection and remains disease-free 17 months later. One patient developed regional nodal metastases despite negative sentinel node biopsy and died 12 months after the procedure. No biopsy-associated complications were observed. CONCLUSIONS: Sentinel node biopsy can be successfully and safely applied to patients with synovial sarcoma. Further prospective studies are required to determine the optimal treatment approach, the false negative rate and the prognostic significance of a positive sentinel node biopsy.