The Effect of chemo- and radiotherapy on tumor necrosis in soft tissue sarcoma- does it influence prognosis?

BACKGROUND: Soft tissue sarcomas (STSs) are a heterogeneous group of tumors. Wide surgical resection is standard, often combined with neoadjuvant chemotherapy, radiotherapy, or both. Studies have shown the predictive value of tumor necrosis in bone sarcoma (BS); however, the role of necrosis in STS after neoadjuvant therapies is still unclear. This study aimed to investigate the role of chemo- and radiotherapy in the formation of tumor necrosis and to evaluate the influence of tumor necrosis on overall survival and local recurrence-free survival. Data from BS patients and patients who did not receive neoadjuvant therapy were compared. METHODS: A total of 779 patients with STS or BS were treated surgically. In all patients, tumor-specific factors such as type, size, or grading and the type of adjuvant therapy were documented. Local recurrence (LR), the diagnosis of metastatic disease, and survival during follow-up were evaluated. RESULTS: A total of 565 patients with STS and 214 with BS were investigated. In STS, 24.1% G1 lesions, 34.1% G2 lesions, and 41.8% G3 lesions were observed. Two hundred twenty-four of the patients with STS and neoadjuvant therapy had either radiotherapy (RTx) (n = 80), chemotherapy (CTx) (n = 93), or both (n = 51). Three hundred forty-one had no neoadjuvant therapy at all. In STS, tumor necrosis after neoadjuvant treatment was significantly higher (53.5%) than in patients without neoadjuvant therapy (15.7%) (p < 0.001). Patients with combined neoadjuvant chemo-/radiotherapy had substantially higher tumor necrosis than those with radiotherapy alone (p = 0.032). There was no difference in tumor necrosis in patients with combined chemo-/radiotherapy and chemotherapy alone (p = 0.4). The mean overall survival for patients with STS was 34.7 months. Tumor necrosis did not influence survival in a subgroup of G2/3 patients. In STS with no neoadjuvant therapy and grading of G2/3, the correlation between necrosis and overall survival was significant (p = 0.0248). There was no significant correlation between local recurrence (LR) and necrosis. CONCLUSION: STS shows a broad spectrum of necrosis even without neoadjuvant chemo- or radiotherapy. After CTx or/and RTx necrosis is enhanced and is significantly pronounced with a combination of both. There is a trend toward higher necrosis with CTx than with RTx. Grading substantially influences the necrosis rate, but necrosis in soft-tissue sarcoma following neoadjuvant therapy does not correlate with better survival or a lower local recurrence rate, as in bone sarcomas.

Ten recommendations for sarcoma surgery: consensus of the surgical societies based on the German S3 guideline "Adult Soft Tissue Sarcomas".

PURPOSE: The evidence-based (S3) guideline "Adult Soft Tissue Sarcomas" (AWMF Registry No. 032/044OL) published by the German Guideline Program in Oncology (GGPO) covers all aspects of sarcoma treatment with 229 recommendations. Representatives of all medical specialties involved in sarcoma treatment contributed to the guideline. This paper compiles the most important recommendations for surgeons selected by delegates from the surgical societies. METHODS: A Delphi process was used. Delegates from the surgical societies involved in guideline process selected the 15 recommendations that were most important to them. Votes for similar recommendations were tallied. From the resulting ranked list, the 10 most frequently voted recommendations were selected and confirmed by consensus in the next step. RESULTS: The statement "Resection of primary soft tissue sarcomas of the extremities should be performed as a wide resection. The goal is an R0 resection" was selected as the most important term. The next highest ranked recommendations were the need for a preoperative biopsy, performing preoperative MRI imaging with contrast, and discussing all cases before surgery in a multidisciplinary sarcoma committee. CONCLUSION: The evidence-based guideline "Adult Soft Tissue Sarcomas" is a milestone to improve the care of sarcoma patients in Germany. The selection of the top ten recommendations by surgeons for surgeons has the potential to improve the dissemination and acceptance of the guideline and thus improve the overall outcome of sarcoma patients.

Impact of postoperative baseline MRI on diagnostic confidence and performance in detecting local recurrence of soft-tissue sarcoma of the limb.

OBJECTIVE: To evaluate the impact of a postoperative baseline (PB) MRI on diagnostic confidence and performance in detecting local recurrence (LR) of soft-tissue sarcoma (STS) of the limb. MATERIALS AND METHODS: A total of 72 patients (8 with LR, 64 without LR) with primary STS of the limb were included. Routine follow-up MRI (1.5 T) at 6 and approximately 36 months (meanLR: 39.7 months; meanno LR: 34.9 months) after multimodal therapy or at time of LR were assessed by three independent readers using a 5-point Likert scale. Furthermore, the following imaging parameters were evaluated: presence of a mass, signal characteristics at T2- and T1-weighted imaging, contrast enhancement (CE), and in some of the cases signal intensity on the apparent diffusion coefficient (ADC). U-test, McNemar test, and ROC-analysis were applied. Interobserver reliability was calculated using Fleiss kappa statistics. A p value of 0.05 was considered statistically significant. RESULTS: The presence of a PB MRI significantly improved diagnostic confidence in detecting LR of STS (p < 0.001) and slightly increased specificity (mean specificity without PE 74.1% and with presence of PB MRI 81.2%); however, not to a significant level. The presence of a mass showed highest diagnostic performance and highest interreader agreement (AUC [%]; κ: 73.1-83.6; 0.34) followed by T2-hyperintensity (50.8-66.7; 0.08), CE (52.4-62.5; 0.13), and T1-hypointensity (54.7-77.3; 0.23). ADC showed an AUC of 65.6-96.6% and a κ of 0.55. CONCLUSION: The presence of a PB MRI increases diagnostic confidence in detecting LR of STS of the limb.

Sarcomas of the extremities and the pelvis: comparing local recurrence after incisional and after core-needle biopsy.

BACKGROUND: The degree of contamination of healthy tissue with tumor cells during a biopsy in bone or soft tissue sarcomas is clearly dependant on the type of biopsy. Some studies have confirmed a clinically relevant contamination of the biopsy tract after incisional biopsies, as opposed to core-needle biopsies. The aim of our prospective study was to evaluate the risk of local recurrence depending on the biopsy type in extremity and pelvis sarcomas. METHODS: We included 162 patients with a minimum follow-up of 6 months after wide resection of extremity sarcomas. All diagnostic and therapeutic procedures were performed at a single, dedicated sarcoma center. The excision of the biopsy tract after an incisional biopsy was performed as a standard with all tumor resections. All patients received their follow-up after the conclusion of therapy at our center by means of regional MRI studies and, at a minimum, CT of the thorax to rule out pulmonary metastatic disease. The aim of the study was the evaluation of the influence of the biopsy type and of several other clinical factors on the rate of local recurrence and on the time of local recurrence-free survival. RESULTS: One hundred sixty-two patients with bone or soft tissue tumors of the extremities and the pelvis underwent either an incisional or a core-needle biopsy of their tumor, with 70 sarcomas (43.2%) being located in the bone. 84.6% of all biopsies were performed as core-needle biopsies. The median follow-up time was 55.6 months, and 22 patients (13.6%) developed a local recurrence after a median time of 22.4 months. There were no significant differences between incisional and core-needle biopsy regarding the risk of local recurrence in our subgroup analysis with differentiation by kind of tissue, grading of the sarcoma, and perioperative multimodal therapy. CONCLUSIONS: In a large and homogenous cohort of extremity and pelvic sarcomas, we did not find significant differences between the groups of incisional and core-needle biopsy regarding the risk of local recurrence. The excision of the biopsy tract after incisional biopsy in the context of the definitive tumor resection seems to be the decisive factor for this result.

Hematopoietic islands mimicking osteoblastic metastases within the axial skeleton.

BACKGROUND: Hyperplasia of the hematopoietic bone marrow in the appendicular skeleton is common. In contrast, focal hematopoietic islands within the axial skeleton are a rare entity and can confuse with osteoblastic metastases. This study aimed to characterize typical MRI and CT findings of hematopoietic islands in distinction from osteoblastic metastases to help both radiologists and clinicians, on the one hand, not to overdiagnose this entity and, on the other hand, to decide on a reasonable work-up. METHODS: We retrospectively analyzed the imaging findings of 14 hematopoietic islands of the axial skeleton in ten patients (nine females, median age = 65.5 years [range, 49-74]) who received both MRI and CT at initial diagnosis between 2006 and 2020. CT-guided biopsy was performed in five cases to confirm the diagnosis, while the other five patients received long-term MRI follow-up (median follow-up = 28 months [range, 6-96 months]). Diffusion-weighted imaging was available in three, chemical shift imaging respectively 18F- fluorodeoxyglucose PET/CT in two, and Technetium 99 m skeletal scintigraphy in one of the patients. RESULTS: All lesions were small (mean size = 1.72 cm2) and showed moderate hypointense signals on T1- and T2-weighted MRI sequences. They appeared isointense to slightly hyperintense on STIR images and slightly enhanced after gadolinium administration. To differentiate this entity from osteoblastic metastases, CT provides important additional information, as hematopoietic islands do not show sclerosis. CONCLUSIONS: Hematopoietic islands within the axial skeleton can occur and mimic osteoblastic metastases. However, the combination of MRI and CT allows for making the correct diagnosis in most cases.

Functional results after oncological scapula resections.

INTRODUCTION: Tumors of the scapula are rare representing only 1.6%-2.8% of all skeletal tumor localizations. Wide resection of these tumors is often necessary, and their anatomic location is the most decisive factor for the extent of the resection. Because of the importance of the shoulder girdle for all daily activities, such resections can have major functional consequences. However, only few reports with small numbers of cases are found in the literature. PATIENTS AND METHODS: We retrospectively evaluated 31 consecutive patients with scapular tumors treated surgically for aggressive benign or malignant tumors of the scapula. Patients who had received curettage only were excluded. Four of these 31 patients were lost to follow-up. In 7 of the remaining 27 patients, a total scapulectomy had to be performed, whereas all others received a partial resection. In 1 case, a partial resection and replantation after irradiation was performed. Musculoskeletal Tumor Society Scoring System (MSTS) and Toronto Extremity Salvage Score (TESS) scores were evaluated postoperatively at the time of their follow-up. RESULTS: In 16 men and 11 women, the median age was 46.2 years and the tumor entities were heterogeneous. The median follow-up time was 71 months. Three patients died during follow-up due to their tumor and 1 due to cardiac disease. We found significantly better functional results in the group with incomplete scapula resections as opposed to the scapulectomy group. We did not see a significant functional difference between the patients with benign and those with malignant lesions. Both the MSTS score with median 83.3% (range between 23% and 100%) and the TESS score with 81.6% (ranging from 20.4% to 100%) were at a satisfactory level. The preservation of the supraspinatus muscle was shown to be advantageous for better shoulder function, and younger patients also tended to have better postoperative results. CONCLUSION: The resection of scapular tumors may lead to a significant functional disability of the shoulder girdle and the affected arm in many cases. However, this is represented neither in the MSTS or TESS score nor in the overall acceptance of the patients. Only 1 patient, an artisan, had to change his job. In total, the clinical results are quite good in short- and long-term follow-up. The score results were comparable to other studies.

Technique and results after immediate orthotopic replantation of extracorporeally irradiated tumor bone autografts with and without fibular augmentation in extremity tumors.

BACKGROUND: Reconstruction of the skeletal defects resulting from the resection of bone tumors remains a considerable challenge and one of the possibilities is the orthotopic replantation of the irradiated bone autograft. One technical option with this technique is the addition of a vital autologous fibular graft, with or without microvascular anastomosis. The aim of our study was to evaluate the clinical results of the treatment of our patient cohort with a specific view to the role of fibular augmentation. METHODS: Twenty-one patients with 22 reconstructions were included. In all cases, the bone tumor was resected with wide margins and in 21 of them irradiated with 300 Gy. In the first case, thermal sterilization in an autoclave was used. The autograft was orthotopically replanted and stabilized with plates and screws. Fifteen patients underwent an additional fibular augmentation, 8 of which received microvascular anastomoses or, alternatively, a locally pedicled fibular interposition. RESULTS: the most common diagnosis was a Ewing sarcoma (8 cases) and the most common location was the femur (12 cases). The mean follow-up time was 70 months (16-154 months). For our statistical analysis, the one case with autoclave sterilization and 3 patients with tumors in small bones were excluded. During follow-up of 18 cases, 55.6% of patients underwent an average of 1.56 revision surgeries. Complete bony integration of the irradiated autografts was achieved in 88.9% of cases after 13.6 months on average. In those cases with successful reintegration, the autograft was shorter (n.s.). Microvascular anastomosis in vascularized fibular strut grafts did not significantly influence the rate of pseudarthrosis. CONCLUSIONS: the replantation of extracorporeally irradiated bone autografts is an established method for the reconstruction of bone defects after tumor resection. Our rate of complications is comparable to those of other studies and with other methods of bone reconstruction (e.g. prosthesis). In our opinion, this method is especially well suited for younger patients with extraarticular bone tumors that allow for joint preservation. However, these patients should be ready to accept longer treatment periods.

Hydroxyapatite deposition disease of the wrist with intraosseous migration to the lunate bone.

Hydroxyapatite deposition disease (HADD) is a mostly uniarticular, self-limiting condition caused by deposition of hydroxyapatite (HA) crystals in tendons or in the peritendinous soft tissues. Commonly, the glenohumeral joint is affected. More rarely, the HA depot can be cause of a carpal tunnel syndrome due to an acute inflammatory reaction and space-occupying soft tissue oedema. We report a case of acute HA depot located at the volar site of the right wrist with affection of the deep flexor tendons and intraosseous migration into the lunate bone in a 50-year-old female. There are two main goals of this case report: First, to remind the diagnosis of HADD as a cause of wrist pain and also of carpal tunnel syndrome, as this entity being often misdiagnosed clinically, and second, to report a rare case of intraosseous migration of HA crystals into the lunate bone.

Tumor load in patients with multiple myeloma: ß2-microglobulin levels versus low-dose whole-body CT.

OBJECTIVE: Beta-2-microglobulin is a serum marker of tumor burden in multiple myeloma (MM). Our aim was to correlate serum ß2-microglobulin levels in patients with MM to tumor burden determined by low-dose whole-body CT (LDWBCT). MATERIALS AND METHODS: A total of 52 patients with newly diagnosed, untreated MM who underwent LDWBCT were included. LDWBCT scans were assessed by two musculoskeletal radiologists in consensus for focal lesions. The Durie and Salmon PLUS staging system was used for staging patients in stages I-III. ß2-microglobulin was also subdivided into stages I-III on the basis of the multiple myeloma International Staging System (ISS). RESULTS: Using the Durie and Salmon PLUS staging system criteria for image evaluation, we were able to identify stage I MM in 17 patients, stage II MM in nine patients, and stage III MM in 26 patients. Eight of nine patients with stage II MM and 16 of 26 patients with stage III MM had normal ß2-microglobulin levels. Thus, 24 of 35 patients (68.6%) had 5 or more focal lesions and false-negative ß2-microglobulin levels. CONCLUSION: Serum ß2-microglobulin levels alone may not indicate the full extent of tumor burden in a significant subset of myeloma patients.

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.

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.

[Resection of soft tissue tumours : Pitfalls, typical complications and prevention strategies]. / Weichteiltumorresektionen : Fallstricke, typische Komplikationen und Vermeidungsstrategien.

Benign soft tissue lesions are 300 times as common as soft tissue sarcomas; hence, the likelihood of confusion is high. Lesions that are larger than 5 cm, deep, show infiltrative growth, or recur despite benign histology are suspicious for soft tissue sarcoma. The biopsy incision must be carefully chosen; in large lipomas, atypical lipomatous tumor should be considered in the differential diagnosis. Lymphomas can be misdiagnosed and treated as undifferentiated soft tissue sarcoma. Vascular tumors and epithelioid lesions require more attention in histopathologic diagnostics and staging. Inflammatory lesions and aggressive fibromatosis (desmoid tumor) should also be borne in mind. In general, staging should be adapted to the underlying tumor biology. Neoadjuvant and adjuvant multimodal therapy must be discussed with the patient and used in a targeted manner. Superficial infiltrating sarcomas are prone to intralesional resection and may require intraoperative frozen section histology. If plastic reconstruction is necessary, a two-step procedure after proven tumor-free margins can be beneficial. Cavities and seromas, tight sutures, and closing the wound with clips are particularly critical. Wound drains at the thigh, pelvis, and groin should be left longer. Early revision in cases of hematoma or critical wound healing have proven beneficial. Adjuvant therapies are best planned before discharge from hospital. Overall, tumor-specific follow-up can significantly reduce the disadvantages of a recurrence resection.

Survival and prognostic factors in conventional G1 chondrosarcoma.

BACKGROUND: Chondrosarcoma is the second most frequent malignant bone tumor. Grade I chondrosarcoma (syn.: atypical cartilaginous tumor) is classified as an intermediately and locally aggressive neoplasm and typically is treated less aggressively (i.e., by intralesional curettage). Does the data regarding local recurrence (LR) and metastatic disease justify this? METHODS: From 1982 to 2014, 37 consecutive patients with G1 chondrosarcoma had been resected or curetted. The margin was defined as R0 (wide resection) or R1 (marginal resection). All patients were followed for evidence of local recurrence or metastatic disease. Overall and recurrence-free survival were calculated, and various potentially prognostic factors were evaluated. RESULTS: In 23 patients (62%), the tumor was widely (R0) resected, whereas in 14 patients, (38%) the resection was marginal (R1). Overall survival was 97% after 5 years, 92% after 10 years, and 67% after 20 years. Five-year local recurrence-free survival was 96%. Ten-year local recurrence-free survival was 83%. Local recurrence-free survival showed a significant correlation to margin status but no correlation to location or age. None of the patients with local recurrence died during the follow-up. One patient had metastatic disease at initial presentation, and a further five patients developed metastatic disease during follow-up. Metastatic disease proofed to be a highly significant factor for survival but was not correlated to local recurrence. CONCLUSIONS: There was no significant correlation between the outcome and the primary tumor location. Marginal resection was a risk factor for LR, but there was no significant difference in the overall survival in patients with or without LR. Metastatic disease (16%) was more common than expected from the literature and a significant predictor for poor overall survival.

Aneurysmal bone cyst: results of an off label treatment with Denosumab.

BACKGROUND: The treatment of aneurysmal bone cysts (ABCs) has evolved and less invasive methods have been tried. Denosumab is a monoclonal antibody which inhibits osteoclasts. It has been shown to be effective in giant cell tumour of bone (GCT) of bone and hence promises some effect also in ABC. We report on 6 patients treated with Denosumab and compare our results to the cases already published. METHODS: Data of 6 patients with ABCs and patients whose treatment included Denosumab were retrospectively analyzed. Denosumab was used at a dose of 120 mg on days 1, 8, 15 and 29, and every 4 weeks thereafter. In some of these patients the dose was reduced at the end of the treatment. Clinical and radiological responses were evaluated. RESULTS: In 4 female and 2 male patients with a mean age of 17 years (range: 6-30 years) the lesions were located in the sacrum (2), in distal radius, distal femur, talus and pelvis. One of the sacral lesions healed after 12 months and has stayed stable for 3 years since. The second patient received 2 years of therapy with recalcification, but recurred 1 year later and is under renewed therapy. The pelvic lesion improved but recurred. This patient has a 13-years history of intermittent therapy including surgery, two pregnancies and remains in a stable situation. The lesion of the talus did not improve with Denosumab after surgery and was complicated by destruction of the ankle joint with osteoarthritis. Recurrent lesions of the distal femur and the distal radius, previously treated by curettage and bone grafting healed under Denosumab and have remained stable for 2 and 3 years, respectively. One case of severe hypercalcemia was observed in a 7-year old child 6 months after discontinuation of Denosumab. CONCLUSION: Denosumab provides a treatment option for ABCs in anatomically critical locations. Adjuvant application might reduce the rate of local recurrence. In young patients, severe rebound hypercalcemia months after discontinuation of Denosumab may occur.

The effects of radiosynoviorthesis in pigmented villonodular synovitis of the knee.

INTRODUCTION: Tenosynovial giant-cell tumor also known as pigmented villonodular synovitis (PVS) is a benign but aggressive synovial proliferative disease most often affecting the knee joint. The mainstay of therapy is surgical resection. Due to a high rate of local recurrence, radiosynoviorthesis (RSO) is used as an adjuvant method in many cases. The aim of this study was to compare local recurrence (LR) rates after surgical synovectomy with and without adjuvant RSO. MATERIALS AND METHODS: From 1996 to 2014, 37 surgical interventions were performed in 32 patients with diffuse pigmented villonodular synovitis of the knee. All patients underwent open synovectomy. Adjuvant radiosynoviorthesis (RSO) was applied in 26 cases, the control group consists of 11 cases without RSO. RESULTS: 9 (24%) lesions recurred within a median of 19 months after surgery. Of those 9 recurrences, 3 (17%) were seen in primary disease, 6 (32%) in already recurring cases (n.s.). In 26 RSO treated patients 6 (23%) recurred, in 11 patients of the control group, 3 (27%) recurred (n.s.). CONCLUSIONS: RSO is effective in PVS as also shown in some smaller reports in the literature. But surgery is still the mainstay of therapy. RSO is not a method of compensating for an insufficient surgical approach, but it may reduce the high rate of LR in patients with large and even recurrent diffuse forms of the disease.

Lowering the recurrence rate in pigmented villonodular synovitis: A series of 120 resections.

OBJECTIVES: Tenosynovial giant-cell tumour or pigmented villonodular synovitis is an aggressive synovial proliferative disease, with the knee joint being the most commonly affected joint. The mainstay of therapy is surgical resection. The aim of this study was to evaluate the main patient characteristics, treatment and outcomes in a large single-centre retrospective study, focusing on meticulous aggressive open surgical procedures. METHODS: From 1996 through 2014, 122 surgical interventions were performed in 105 patients. All patients underwent open synovectomy and when the knee joint was affected, combined anterior and posterior synovectomy. Radiotherapy was applied in 2 patients, radiosynoviorthesis in 27 patients. RESULTS: In histopathology, the diffuse type was seen in 66 (54%) lesions. Two patients were lost during follow-up. At a median follow-up time of 71 months (range: 13-238), 22 (18%) lesions recurred within a median of 18 months, >90% in the first 3 years. Out of those 22 recurrences, 9 (11%) were seen in primary disease and 13 (34%) were a second recurrence. After renewed resection, 6 (5%) out of the 120 resections had persistent tumour at the end of follow-up. Based on the number of patients with complete follow-up (n = 103), this represents 5.8%. CONCLUSION: In diffuse-type pigmented villonodular synovitis, total synovectomy might be difficult to achieve. As shown in our results and also in the literature, meticulous open resection, especially in difficult to approach areas such as the popliteal space, reduces local recurrence rates. External beam radiation is an option in prevention of otherwise non-operable local recurrences or in non-operable disease.

Myxoid liposarcoma: local relapse and metastatic pattern in 43 patients.

BACKGROUND: Liposarcomas are the second most common type of soft tissue sarcomas, 30-50% of these are of myxoid subtype. The aim of this retrospective study was to analyze the local control rate, the metastatic pattern and survival of patients in a consecutive single-institution series. METHODS: From 1983 to 2015, 43 patients with myxoid liposarcoma of the extremities and trunk wall underwent resections. The margin was defined as R0 (wide) or R1 (marginal). Patients were followed for evidence of local recurrence or distant metastasis. Overall and recurrence-free survival was calculated. RESULTS: The mean age was 48.6 years. The lower extremity was involved in 40 cases, the mean tumour size was 12 cm. In 31 cases a wide and in 12 cases a marginal resection was performed. Grading was G1 in 14, G2 in 25 and G3 in 4 cases. Nine patient died in follow-up, 4 of them with metastatic disease, all nonpulmonary. 5-year local recurrence (LR) free survival was 82%. 4 (9.3%) patients developed LR (all R1). Overall survival (OS) was 81% after 5 and 72% after 10 years. In multivariate analysis age and Grading proved to be significant on OS. According to univariate analysis, only age over 48 years and distant metastasis had a significant impact on overall survival. CONCLUSIONS: Patients with myxoid liposarcomas have a good prognosis. Myxoid liposarcoma has a distinct pattern of nonpulmonary metastatic disease. Therefore, patients with high-risk extremity myxoid liposarcoma should undergo imaging studies of the chest, abdomen, spine and pelvis as part of their staging and follow-up examinations preferably with whole body MRI, or CT scans and MRI of the spine and pelvic region for detection of suspected metastatic disease.

Survival and prognostic factors in conventional central chondrosarcoma.

BACKGROUND: Chondrosarcoma is the second most frequent primary malignant bone tumor. Treatment is mainly based on surgery. In general, wide resection is advocated at least in G2 and G3 tumors. But which margins should be achieved? Does localization as for example in the pelvis have a higher impact on survival than surgical margins themselves? METHODS: From 1982 to 2014, 87 consecutive patients were treated by resection. The margin was defined as R0 (wide resection), R1 (marginal resection) or, R2 if the tumor was left intentionally. All patients were followed for evidence of local recurrence or distant metastasis. Overall and recurrence-free survival were calculated, significance analysis was performed. RESULTS: In 54 (62%) cases a R0 resection, in 31 (36%) a R1 and in 2 (2%) patients a R2-resection was achieved. Histology proved to be G1 in 37 patients (43%), G2 in 41 (47%) and G3 in 9 cases (10%). 5-year local recurrence-free survival (LRFS) was 75%. Local recurrence-free survival showed a significant association with the margin status and the localization of the tumor with pelvic lesions doing worst. Metastatic disease was initially seen in 4 patients (4.6%), 19 others developed metastatic disease during follow-up. Overall survival of the entire group at 5 and 10 years were 79 and 75%, respectively. The quality of surgical margins and the presence of local recurrence did not influence overall survival in a multivariate analysis. Pelvic lesions had a worse prognosis as did higher grades of the tumor, metastatic disease and age. CONCLUSIONS: The mainstay of therapy in Chondrosarcoma remains surgery. Risk factors as grading, metastatic disease, age and location significantly influence overall survival. Margin status (R0 vs. R1) did influence local recurrence-free survival but not overall survival. Chondrosarcomas of the pelvis have a higher risk of local recurrence and should be treated more aggressively.

Desmoid Tumours of the extremity and trunk. A retrospective study of 44 patients.

BACKGROUND: Desmoid-type fibromatosis (DF) is a aggressive (myo)fibroblastic neoplasm with an infiltrative growth and a tendency to local recurrence. Resection of the tumour and/or radiation were proposed as principal treatment. The aim of this retrospective study was to analyze the local control rates focusing on the effect of surgical margins and radiotherapy. METHODS: From 1981 to 2014, 44 patients had been treated. Fifty four therapies had been applied, in 50 cases surgery +/- radiation therapy, NSAIDs or chemotherapy. In 4 cases a conservative approach was chosen. Thirty seven patients had primary, 17 recurrent disease. Endpoint was either local recurrence (LR), progression of residual disease or rare non-metastatic secondary lesions at the same extremity. RESULTS: The mean age was 39,4 years. In 17 cases a R0, in 27 a R1 and in 6 cases a R2 resection was achieved. Four patients were treated conservatively. All together in 21 cases radiotherapy, in 5 NSAIDs, in 3 imatinib and in 2 cases each tamoxifen or chemotherapy had been applied. The median follow-up was 119 months. 5-year recurrence free survival after resection was 78%. 10 (20.4%) patients developed LR between 5 and 42 months after therapy. Recurrent disease was a negative factor on LR. Margins, radiotherapy, sex, or size of the tumour had no significant impact on LR. Patients younger than 40 years had a significant higher risk of LR. CONCLUSIONS: Surgical margins are less important than keeping function. Radiotherapy might be an option in unresectable lesions, the role of adjuvant radiotherapy is controversially discussed.

The role of surgical margins in atypical Lipomatous Tumours of the extremities.

BACKGROUND: Atypical lipomatous tumours (ALT) are common adipocytic tumours. Due to their large size and deep-seated location, wide resection might result in severe functional deficits. The question which margins should be aimed is hence discussed controversially. METHODS: Forty consecutive patients underwent limb-sparing resections. Margins were defined as R0 (wide resection), R1 (marginal resection) or R2 if tumour was left. All patients were followed for evidence of local recurrence or remote metastases. Overall and recurrence-free survival was calculated. RESULTS: The mean age at the time of surgery was 61.9 years. The mean tumour diameter was 17 cm with no patient having metastatic disease. In 8 cases a wide (R0) resection, in 31 cases a marginal (R1) and in one patient a R2-resection was performed. The median follow-up time was 40 months. Four patients died due to causes that were not tumour-related. 3 (7.5%) patients (all R1) developed local recurrences. Two of our 3 recurrences in this series occurred in 6 already recurring cases. We observed no dedifferentiation of tumours and no metastatic disease. CONCLUSIONS: ALT represents a comparatively common diagnosis in large deep-seated lesions of the extremities, especially in patients over 60 years. Marginal resection shows an acceptable rate of local recurrence. The risk of dedifferentiation as proven also in a metaanalysis of the English literature of the last 30 years is close to 1%, metastatic disease is exceedingly rare.