IDH mutations in G2-3 conventional central bone chondrosarcoma: a mono institutional experience.

BACKGROUND: Heterozygous isocitrate dehydrogenase (IDH) mutations occur in about half of conventional central bone chondrosarcomas (CCBC). Aim of this study was to assess the frequency and prognostic impact of IDH mutations in high grade CCBC patients. METHODS: 64 patients with G2 and G3 CCBC were included. DNA extraction, PCR amplification of IDH1/2 exon 4s, and sequencing analysis with Sanger were performed. RESULTS: IDH mutations were detected in 24/54 patients (44%): IDH1 in 18, IDH2 in 4, and both IDH1/2 in 2 patients. The frequency of mutations was 37% in G2 vs. 69% in G3 (p = 0.039), and 100% in three Ollier disease associated chondrosarcoma. 5-year overall survival (OS) at 124 months (range 1-166) was 51%, with no significant difference based on the IDH mutational status: 61% in IDHmut vs. 44% in IDH wild type (IDHwt). The 5-year relapse free survival (RFS) was 33% (95% CI:10-57) for IDHmut vs. 57% (95%CI: 30-77) for IDHwt. Progression free survival (PFS) was 25% (95%CI:1-65) IDHmut vs. 16% (95%CI: 0.7-52) IDHwt. 55% (5/9) of IDHmut G2 became higher grade at the recurrence, as compared with 25% (3/12) of G2 IDHwt. CONCLUSIONS: This study shows a higher frequency of IDH mutations in G3 CCBC as compared with G2. No significant differences in OS, RFS, and PFS by mutational status were detected. After relapse, a higher rate of G3 for IDH mutated CCBC was observed.

SELNET clinical practice guidelines for bone sarcoma.

Bone sarcoma are infrequent diseases, representing < 0.2% of all adult neoplasms. A multidisciplinary management within reference centers for sarcoma, with discussion of the diagnostic and therapeutic strategies within an expert multidisciplinary tumour board, is essential for these patients, given its heterogeneity and low frequency. This approach leads to an improvement in patient's outcome, as demonstrated in several studies. The Sarcoma European Latin-American Network (SELNET), aims to improve clinical outcome in sarcoma care, with a special focus in Latin-American countries. These Clinical Practice Guidelines (CPG) have been developed and agreed by a multidisciplinary expert group (including medical and radiation oncologist, surgical oncologist, orthopaedic surgeons, radiologist, pathologist, molecular biologist and representatives of patients advocacy groups) of the SELNET consortium, and are conceived to provide the standard approach to diagnosis, treatment and follow-up of bone sarcoma patients in the Latin-American context.

Reconstruction of the pelvic ring in iliac or iliosacral resections: allograft or autograft?

BACKGROUND: The necessity to reconstruct the pelvic ring after an iliac or iliosacral resection is still debated. Different reconstructive techniques are available, including autologous and homologous graft and custom-made prosthesis. The aim of this study was to evaluate the functional outcome and complications of patients who underwent resection of iliac bone and part of the sacrum for primary bone tumour and reconstruction with an allograft or autograft. METHODS: We retrospectively evaluated 18 patients (10 males and 8 female) with a mean age of 28 years (range 9-56) who were operated between 1992 and 2015. Six patients were reconstructed with an autograft (Group A) and 12 patients with an allograft (Group B). All complications were recorded. At final follow-up, patients with the original reconstruction still in site were functionally evaluated with MSTS Score. RESULTS: Mean follow-up time was 107 months (range 4-221). Two patients (11.1%) had an external hemipelvectomy for local recurrence, and 3 patients died of the disease. Mean MSTS Score was comparable between the two groups 21.7 (range 20-25) in Group A and 19.9 (range 4-28) in Group B. Patients with partial sacral resection had an increased risk of local recurrence and lower MSTS Score [15.5 (range 7-20) vs. 22.2 (range 4-28)]. CONCLUSIONS: Biological reconstruction of pelvic ring with autologous or homologous bone graft gives acceptable functional results. However, the decision on how to reconstruct the pelvic ring after iliac resection should be taken on a patient-by-patient basis.

The sacral chordoma margin.

OBJECTIVE: Aim of the manuscript is to discuss how to improve margins in sacral chordoma. BACKGROUND: Chordoma is a rare neoplasm, arising in half cases from the sacrum, with reported local failure in >50% after surgery. METHODS: A multidisciplinary meeting of the "Chordoma Global Consensus Group" was held in Milan in 2017, focusing on challenges in defining and achieving optimal margins in chordoma with respect to surgery, definitive particle radiation therapy (RT) and medical therapies. This review aims to report on the outcome of the consensus meeting and to provide a summary of the most recent evidence in this field. Possible new ways forward, including on-going international clinical studies, are discussed. RESULTS: En-bloc tumor-sacrum resection is the cornerstone of treatment of primary sacral chordoma, aiming to achieve negative microscopic margins. Radical definitive particle therapy seems to offer a similar outcome compared to surgery, although confirmation in comparative trials is lacking; besides there is still a certain degree of technical variability across institutions, corresponding to different fields of treatment and different tumor coverage. To address some of these questions, a prospective, randomized international study comparing surgery versus definitive high-dose RT is ongoing. Available data do not support the routine use of any medical therapy as (neo)adjuvant/cytoreductive treatment. CONCLUSION: Given the significant influence of margins status on local control in patients with primary localized sacral chordoma, the clear definition of adequate margins and a standard local approach across institutions for both surgery and particle RT is vital for improving the management of these patients.

Angiosarcoma around total hip arthroplasty: case series and review of the literature.

BACKGROUND: Angiosarcoma (AS) is a rare and malignant tumor which mainly arises in the skin and superficial soft tissue and less frequently in deep soft tissue and bones. Some cases of AS are described in association with vascular and orthopedic devices. Nonetheless, only a few cases of AS around THA are reported in the literature. MATERIALS AND METHODS: We describe five cases of AS arising around total hip arthroplasty who received surgery at our institution (Istituto Ortopedico Rizzoli, Bologna, Italy), and we report the cases described in literature. RESULTS: Foreign bodies such as polyethylene were demonstrated to have a carcinogenic role in animals, but reports of similar cases in humans are rare. Nevertheless, osteolysis induced by wear particles of polyethylene is a frequent event and could induce to desist form considering other more rare causes of osteolysis such as AS. This could be the reason why the diagnosis in several cases was significantly delayed. Common features of these cases could be helpful for doing a prompt diagnosis. The initial presentation is suggestive for septic or aseptic loosening with a massive osteolysis around the cup and/or the stem associated with peculiar aspects as bleeding and loss of weight. Frequently, needle biopsy is negative because foreign-body reaction might have "covered" the most relevant condition of epithelioid AS. CONCLUSIONS: In conclusion in a patient who presents with uncontrollable bleeding, loss of weight and massive osteolysis, AS must be actually considered as possible diagnosis.

Extraskeletal osteosarcoma: A European Musculoskeletal Oncology Society study on 266 patients.

PURPOSE: Prognosis of extraskeletal osteosarcoma (ESOS) is reported to be poorer than that of skeletal osteosarcoma. This multicenter retrospective study aimed to evaluate factors influencing ESOS prognosis. PATIENTS AND METHODS: Members of the European Musculoskeletal Oncology Society (EMSOS) submitted institutional data on patients with ESOS. RESULTS: Data from 274 patients treated from 1981 to 2014 were collected from 16 EMSOS centres; 266 patients were eligible. Fifty (18.7%) had metastases at diagnosis. Of 216 patients with localised disease, 211 (98%) underwent surgery (R0 = 70.6%, R1 = 27%). Five-year overall survival (OS) for all 266 patients was 47% (95% CI 40-54%). Five-year OS for metastatic patients was 27% (95% CI 13-41%). In the analysis restricted to the 211 localised patients who achieved complete remission after surgery 5-year OS was 51.4% (95% CI 44-59%) and 5-year disease-free survival (DFS) was 43% (95% CI 35-51%). One hundred twenty-one patients (57.3%) received adjuvant or neoadjuvant chemotherapy and 80 patients (37.9%) received radiotherapy. A favourable trend was seen for osteosarcoma-type chemotherapy versus soft tissue sarcoma-type (doxorubicin ± ifosfamide) regimens. For the 211 patients in complete remission after surgery, patient age, tumour size, margins and chemotherapy were positive prognostic factors for DFS and OS by univariate analysis. At multivariate analysis, patient age (≤40 years versus >40 years) (P = 0.05), tumour size (P = 0.0001) and receipt of chemotherapy (P = 0.006) were statistically significant prognostic factors for survival. CONCLUSION: Patient age and tumour size are factors influencing ESOS prognosis. Higher survival was observed in patients who received perioperative chemotherapy with a trend in favour of multiagent osteosarcoma-type regimen which included doxorubicin, ifosfamide and cisplatin.

Short, full-dose adjuvant chemotherapy (CT) in high-risk adult soft tissue sarcomas (STS): long-term follow-up of a randomized clinical trial from the Italian Sarcoma Group and the Spanish Sarcoma Group.

BACKGROUND: To report on long-term results of a phase 3 trial comparing three versus five cycles of adjuvant chemotherapy (CT) with full-dose epirubicin+ifosfamide in high-risk soft tissue sarcomas (STS). METHODS: Patients (pts) were randomized to receive three preoperative cycles of epirubicin 120 mg/m2 and ifosfamide 9 g/m2 (Arm A) or to receive the same three preoperative cycles plus two postoperative cycles (Arm B). Radiotherapy could be either delivered in the preoperative or in the postoperative setting. Non-inferiority of the primary end point, OS, was assessed by the confidence interval of the hazard ratio (HR; Arm A/Arm B) derived from Cox model. RESULTS: Between January 2002 and April 2007, 164 pts were assigned to arm A and 164 to arm B. At a median follow-up (FU) of 117 months (IQ range 103-135 months), 123 deaths were recorded: 58 in Arm A and 65 in Arm B. Ten-year OS was 61% for the entire group of patients: 64% in Arm A and 59% in Arm B. The intention-to-treat analysis confirmed that three cycles were not inferior to five cycles (one-sided 95% upper confidence limit was 1.24). A per protocol analysis was consistent with these results. Pts with leiomyosarcoma and undifferentiated pleomorphic sarcoma (UPS) had the lowest, and the highest response rates, respectively. Consistently, Leiomyosarcoma and UPS had the worse and the best prognosis, respectively. CONCLUSIONS: At a longer FU, the non-inferiority of three cycles of a full-dose conventional CT in comparison to five is confirmed. Response to therapy is also confirmed to be associated with better survival. This regimen is currently tested within an ongoing international trial against three cycles of a neoadjuvant histology-tailored CT (ClinicalTrials.gov Identifier: NCT01710176).

Clear cell sarcoma of soft tissue: a retrospective review and analysis of 31 cases treated at Istituto Ortopedico Rizzoli.

INTRODUCTION: Clear cell sarcoma (CCS) of soft tissue is a rare melanocytic soft tissue sarcoma with different cytogenetic and natural history than that of melanoma. Objective of this study was to determine outcome predictors in patients treated in our Institute. This objective included the effectiveness of surgical intervention and disease progression after surgery. MATERIALS AND METHODS: Thirty-one patients were diagnosed at our institute with clear cell sarcoma through tissue pathology and immunohistochemistry. Patients received multimodality treatment (surgery, radiotherapy and chemotherapy). Five-year survival rates and prognostic predictors were determined. RESULTS: Sixteen patients were males and 15 females with a median age of 37 years (8-72-years). Twenty-eight tumors were located in extremities and 3 in the trunk area. Eight patients had metastases at their first presentation (6 local lymph nodes and 2 pulmonary metastases). Five and ten-year disease-specific survival rates were 56% and 41%. Two-year disease-specific survival rates for lymph node and pulmonary metastasis groups were 40% and 0%. All metastatic patients died within 5 years follow-up. Five and ten-year disease-specific survival rates for localized tumor cases were 72% and 53%. Male gender, less than 30-years of age, trunk tumor location and size greater than 5 cm were poor prognostic factors according to univariate analysis. Tumor location in the trunk was the only negative prognostic determinant in multivariate model. CONCLUSIONS: Although surgical treatment may be beneficial for tumors without systemic involvement, new chemotherapeutic agents and molecular targeted therapy should be implemented to improve the oncologic outcome in both early and late stage disease.

Factors affecting outcome of massive intercalary bone allografts in the treatment of tumours of the femur.

We retrospectively reviewed 101 consecutive patients with 114 femoral tumours treated by massive bone allograft at our institution between 1986 and 2005. There were 49 females and 52 males with a mean age of 20 years (4 to 74). At a median follow-up of 9.3 years (2 to 19.8), 36 reconstructions (31.5%) had failed. The allograft itself failed in 27 reconstructions (24%). Mechanical complications such as delayed union, fracture and failure of fixation were studied. The most adverse factor on the outcome was the use of intramedullary nails, followed by post-operative chemotherapy, resection length > 17 cm and age > 18 years at the time of intervention. The simultaneous use of a vascularised fibular graft to protect the allograft from mechanical complications improved the outcome, but the use of intramedullary cementing was not as successful. In order to improve the strength of the reconstruction and to advance the biology of host-graft integration, we suggest avoiding the use of intramedullary nails and titanium plates, but instead using stainless steel plates, as these gave better results. The use of a supplementary vascularised fibular graft should be strongly considered in adult patients with resection > 17 cm and in those who require post-operative chemotherapy.