Aims. The aim of this study is to determine the predictors of overall survival (OS) and predictive factors of poor prognosis of conventional high-grade osteosarcoma of the limbs in a single-centre in South Africa. Methods. We performed a retrospective cross-sectional analysis to identify the prognostic factors that predict the OS of patients with histologically confirmed high-grade conventional osteosarcoma of the limbs over ten years. We employed the Cox proportional regression model and the Kaplan-Meier method for statistical analysis. Results. This study comprised 77 patients at a three-year minimum follow-up. The predictors of poor OS were: the median age of ≤ 19 years (hazard ratio (HR) 0.96; 95% confidence interval (CI) 0.92 to 0.99; p = 0.021); median duration of symptoms ≥ five months (HR 0.91; 95% CI 0.83 to 0.99; p < 0.037); metastasis at diagnosis (i.e. Enneking stage III) (HR 3.33; 95% CI 1.81 to 6.00; p < 0.001); increased alkaline phosphatase (HR 3.28; 95% CI 1.33 to 8.11; p < 0.010); palliative treatment (HR 7.27; 95% CI 2.69 to 19.70); p < 0.001); and amputation (HR 3.71; 95% CI 1.12 to 12.25; p < 0.032). In contrast, definitive surgery (HR 0.11; 95% CI 0.03 to 0.38; p < 0.001) and curative treatment (HR 0.18; 95% CI 0.10 to 0.33; p < 0.001) were a protective factor. The Kaplan-Meier median survival time was 24 months, with OS of 57.1% at the three years. The projected five-year event-free survival was 10.3% and OS of 29.8% (HR 0.76; 95% CI 0.52 to 1.12; p = 0.128). Conclusion. In this series of high-grade conventional osteosarcoma of the appendicular skeleton from South Africa, 58.4% (n = 45) had detectable metastases at presentation; hence, an impoverished OS of five years was 29.8%. Large-scale future research is needed to validate our results. Cite this article: Bone Jt Open 2024;5(3):210–217

Purpose: Compared to paediatric cancer patients adolescents and young adults may have disadvantaged access to care. Therefore we investigated the correlation of patient, tumour and institutional characteristics with the outcome of osteosarcoma in this age group. Method: Analysis of consecutive patients aged 15–24 years with newly diagnosed high-grade osteosarcoma entered into the Cooperative Osteosarcoma Study Group(COSS) registry 1980–2004 and treated in pediatric (PO) or medical oncology institutions (MO). Standardised multimodal therapy according to a COSS-protocol. Event-free survival rates (EFS) evaluated in relation to patient demographics and registering institution (MO vs PO and treatment volume as: < 1, 1–3 or > 3 osteosarcoma/year). Results: 944 patients identified (median age: 17.35 years; range: 15.01–24.99; 79% aged < 20 years). Patients > 20 years were more likely than younger patients to be treated in centers with low treatment volume (p< .0001) and MO (p< .0001) but otherwise comparable. After a median follow-up of 5.59 years (range: 0.12 – 27.92) for all patients and 8.08 years (range: 0.19 – 27.92) for 617 survivors, actuarial 5/10 year event-free survival probability (EFS) was 58%/54%. Upon univariate analysis of the total cohort neither of the institutional variables correlated significantly with EFS. There was a correlation between treatment in PO and improved EFS for patients > 20 years (p=.001) and for those with primary metastases (p=.009). Upon multivariate testing type of center (odds ratio: 1.26; p=.022) but not treatment volume were significant. Conclusion: Within a framework of standardised regimens and consultation supportby our group’s infrastructure, similar EFS-probabilites were obtained regardless of institutional treatment volumes. Observed variations in outcome between PO and MO may be partly due to different distributions of presenting factors but deserve further investigation

Only few patients with osteosarcoma relapse with solitary skeletal lesions as only sign of recurrence. We used the COSS database to learn more about these rare occurrences. This report covers all patients with high-grade osteosarcoma of the limbs or axial skeleton registered into the COSS database between 1980 and 2003 who developed 1st recurrences as solitary osseous lesions distant from the primary tumour before 01/2005. Patient-, tumour-, and treatment-related variables and outcomes were evaluated. 38 patients (27 male, 11 female) developed solitary osseous recurrences a median of 2.1 years (range:.5 – 14.3) from primary diagnosis. Primary sites had been limbs in 36 and axial in 2, relapses involved axial sites (24), limbs (10), or craniofacial bones (4). Treatment for osseous recurrence included surgery in 28 patients, radiotherapy in 10, and chemotherapy in 27. After a median follow-up of 1.9 years (range:.1–21.2) from 1st recurrence for all 38 patients and 5.5 years (.3–21.2) for 16 survivors (10 of these in continuous 2nd surgical remission), 2- & 5-year overall and event-free survival probabilities were 55% & 34% and 34% & 27%, respectively. A long interval to recurrence (> 1.5 years) predicted for better outcomes (p< .01). For those 21 patients achieving a 2nd complete surgical remission, 2- & 5-year overall and event-free survival probabilities were 81% & 61% and 52% & 49%, respectively, while only 1/17 patients failing to achieve a 2nd complete surgical remission survived beyond 5 years (p< .001) after additional radiotherapy. 14/16 survivors had also received 2nd-line chemotherapy. 1st solitary skeletal recurrences of osteosarcoma seem to have a favourable outcome provided treatment includes complete surgery as part of multimodal therapy. Some presumed bone metastases may rather represent second primary osteosarcomas. The COSS studies that form the basis of this report were supported by Deutsche Krebshilfe

Paediatric bone sarcomas around the knee are often amenable to either endoprosthetic reconstruction or rotationplasty. Cosmesis and durability dramatically distinguish these two options, although patient-reported functional satisfaction has been similar among survivors. However, the impact on oncological and surgical outcomes for these approaches has not been directly compared. We retrospectively reviewed all wide resections for bone sarcoma of the distal femur or proximal tibia that were reconstructed either with an endoprosthesis or by rotationplasty at our institution between June 2004 and December 2014 with a minimum two year follow-up. Pertinent demographic information, surgical and oncological outcomes were reviewed. Survival analysis was performed using the Kaplan-Meier method with statistical significance set at p<0.05. Thirty eight patients with primary sarcomas around the knee underwent wide resection and either endoprosthetic reconstruction (n=19) or rotationplasty (n=19). Groups were comparable in terms of demographic parameters and systemic tumour burden at presentation. We found that selection of endoprosthetic reconstruction versus rotationplasty did not impact overall survival for the entire patient cohort but was significant in subgroup analysis. Two-year overall survival was 86.7% and 85.6% in the endoprosthesis and rotationplasty groups, respectively (p=0.33). When only patients with greater than 90% chemotherapy-induced necrosis were considered, overall survival was significantly better in the rotationplasty versus endoprosthesis groups (100% vs. 72.9% at two years, p=0.013). Similarly, while event-free survival was not affected by reconstruction method (60.2% vs. 73.3% at two years for endoprosthesis vs rotationplasty, p=0.27), there was a trend towards lower local recurrence in rotationplasty patients (p=0.07). When surgical outcomes were considered, a higher complication rate was seen in patients that received an endoprosthesis compared to those who underwent rotationplasty. Including all reasons for re-operation, 78.9% (n=15) of the endoprosthesis patients required a minimum of one additional surgery compared with only 26.3% (n=5) among rotationplasty patients (p=0.003). The most common reasons for re-operation in endoprosthesis patients were wound breakdown/infection (n=6), limb length discrepancy (n=6) and periprosthetic fracture (n=2). Excluding limb length equalisation procedures, the average time to re-operation in this patient population was 5.6 months (range 1 week to 23 months). Similarly, the most common reason for a secondary procedure in rotationplasty patients was wound breakdown/infection, although only two patients experienced this complication. Average time to re-operation in this group was 23.8 months (range 5 to 49 months). Endoprosthetic reconstruction and rotationplasty are both viable limb-salvage options following wide resection of high-grade bony sarcomas located around the knee in the paediatric population. Endoprosthetic reconstruction is associated with a higher complication rate and may negatively impact local recurrence. Study of a larger number of patients is needed to determine whether the reconstructive choice affects survival

High grade sarcoma present a systemic metastatic progression in approximaly 50% of cases. The effectiveness of palliative chemotherapy as a treatment of systemic metastases is still controversed. The main objectif of this study is to assess disease progression and survival of patients diagnosed with metastatic soft tissue sarcomas treated with palliative chemotherapy, analyse chemotherapy treatment patterns and response to different lines of treatment. Retrospective chart review of 75 patients treated with palliative chemotherapy for metastatic soft tissue sarcomas between 2003 and 2013 at Maisonneuve-Rosemont Hospital. Data for control group of 40 patients with metastatic soft tissue sarcomas not treated with chemotherapy was collected retrospectively. Collected data include demographic data, overall survival, time free survival, type of chemotherapy treatment, surgical treatment and adverse reaction to palliative chemotherapy. Overall survival was analysed with Kaplan-Meier test. Categorial variable were compared with Log-Rank test. Seventy-five patients (37% female; mean age 50.4 years) received minimally one line of chemotherapy for their metastatic sarcomas. The regimens most commonly used in first-line were doxorubicin (48%) and doxorubicin combined with ifosfamide (21.3%). Favorable response was achieved by 38.7% in first-line and 27.9% in second-line therapy. Median overall survival with chemotherapy treatments was more than two times overall survival without treatments. Median overall survival was 19 months with chemotherapy treatments and 7 months without chemotherapy (p<0.0001). There was no statistically significant difference between survivals for treated and untreated patients with chemotherapy when analysed in term of the histological subtype, age and monotherapy versus combined treatment. Event-free survival was statistically longer during the first year for the group of patients treated with combined chemotherapy (p=0.0125). Results have shown a significantly improved overall survival in all histological groups, resulting in an OS of 19 vs 7 months for the chemotherpy and non chemotherapy group respectively. Nevertheless, patients with favorable response to chemotherapy have poor outcomes. Additional treatment options are needed

We analyzed the results of the intensive multimodality therapy of children with localized Ewing’s family tumors of the ribs (EFTR). 22 patients with localized EFTR were treated in our institute between 1996 and 2006. The age is ranged from 4 to 15 years. 10 patients were male, 12 – female. Eight patients had a classic Ewing sarcoma(ES), 14 – PNET. The high risk criterion was tumor volume over 100 ml. The treatment plan included intensive induction chemotherapy (adapted to risk group) consist of 5 courses (1, 3, 5 courses – vincristine, adriamicin, cyclophosphamide, 2, 4 courses – ifosfamide and etoposide) and local control (surgery and radiotherapy), and consolidation with or 5 courses standard therapy or high-dose chemotherapy with stem-cell rescue. 4 patients underwent high-dose chemotherapy, 18 – consolidation with standard arm. Two patients died from complications of chemotherapy, 20 patients completed the treatment. 5-year overall survival (OAL) of patients was 70±10,4%, 5-year event-free survival (EFS) was 58,9±11,4%. We conclude that Ewing’s family tumors are the most common tumors of ribs in childhood. Improved EFS requires more aggressive systemic chemotherapy and surgery (removing of entire affected ribs). Long-term survival is possible, even for high risk patients

Introduction: The role of surgery for local control in the multimodal management of Ewing’s sarcoma has substantially increased during the past 20 years. However, selection bias due to location (extremities vs axial skeleton) and relatively non-homogeneous treatment received by patients in multi-institutional trials may limit objective evaluation and comparison of the relative role of surgery and radiation therapy in this setting. Purpose of this study was to review a large series of patients homogeneously treated at a single institution. Methods: 268 patients with non-metastatic Ewing’s sarcoma of the extremities treated by contemporary multimodal management were reviewed. Chemotherapy was administered according to 4 sequential protocols of adjuvant (1) and neoadjuvant (3) treatment. Local control consisted of surgery in 136 patients, surgery and radiation therapy in 70 patients, and radiation therapy in 60 patients. Two patients underwent only chemotherapy. Results: The 5-year event-free survival (EFS) and overall survival (OS) were 62 and 69 per cent respectively. The rates of 5-year EFS and local control were significantly lower in patients treated with radiation therapy compared to patients treated by surgery or surgery and radiation therapy (48 vs 66 per cent, p=0.002; 80 vs 94 per cent, p= 0,0001). In group 3 (Radiation Therapy only) there were also 6 secondary malignancies. Conclusion: Surgery was associated with better survival and local control in this series. In our opinion, surgery should always be considered in the local treatment of Ewing’s sarcoma of the extremities. Postoperative Radiation Therapy must be added in cases of inadequate surgical margins

While STS as a group represent a significant portion of all solid tumors in childhood, individual histologic entities are rare due to their extreme heterogeneity. This represents the principal obstacle to clinical trials. A compromise between clinical vs. statistical precision has been necessary in the majority of clinical trials on STS resulting in contradictory conclusions. Clinical trials have to reduce uncertainty but trials, which overlook clinical heterogeneity can even contribute to it. An example is many clinical trials, which have been carried out in the recent decades to answer the question of the role of adjuvant chemotherapy in “Non-RMS-STS”. Majority of these trials have overlooked clinically relevant subgroups. The result is that we still do not have certainty whether and which adjuvant chemotherapy is beneficial. In addition, most clinical trials of treatments for STS rely on the endpoints of survival or event-free survival, so results have taken years to accrue and even longer to report. However, in STS with well defined genetic abnormalities and strong preclinical rationale for activity of a molecular targeted therapy the demonstration of clinical activity in only a few cases might be sufficient. In dermatofibrosarcoma protuberans, a very rare entity, the demonstration of clinical activity of the molecular targeted therapy was very convincing and led to approval of the drug, although the number of cases was very low. International collaboration is necessary to obtain a sufficient number of patients but participation of many different centers with different expertise for a given rare tumor may compromise the quality of patient’s care. It is also difficult for many pediatric departments to open and maintain large numbers of trials with low accrual rates. In conclusion, new methods for clinical research in the field of STS especially surrogate outcome variables and novel technique for early assessment of response are urgently needed

Tumor size and metastases are known risk factors in Ewing tumors. Adequate staging is essential to stratify treatment intensity, but TNM staging is not established. The validity of TNM staging was tested based on tumor volume (T1 ≤200 ml; T2 > 200 ml ≤500 ml; T3, > 500 ml), the presence or absence of lymph node metastases (N0, N1), and distant metastases (M0, no metastases; M1 lung/pleura metastases; M1a ≤5 nodules; M1b > 5 lesions; M2 bone metastases; M2a, 1 lesion; M2b > 1 lesion and/or microscopic bone marrow contamination; M3, multi-system metastases). 1799 Ewing sarcoma patients of the (EI)CESS/EE99 studies entered into the Muenster database from 1981–2008 were analyzed. Ten-year event-free survival (EFS) was 0.46. EFS in patients without metastases (T1-3N0M0) was 0.56 compared to 0.22 in metastatic patients (T1-3N0,1M1-3), p< .0001. In non-metastatic patients, tumor volume discriminated EFS: T1:0.62; T2:0.43; T3:0.40, p< .0001. The rare event of lymph node metastases correlated with unfavorable prognosis (N0:0.47, N1:0.12, p< .0001). The difference in EFS between pulmonary, skeletal and multi-system dissemination was significant: M1:0.29, M2:0.23; M3:0.12, p< .0001. The discrimination of M1 subgroups (M1a/M1b) was of prognostic relevance (p=.0050); M2 subgroups (M2a/M2b) discriminated outcome less clearly (p=.0457). TNM staging is appropriate in Ewing tumors and should be incorporated in future trials

The Euro-E.W.I.N.G. 99 trial aimed to improve the dismal prognosis of patients with primary disseminated multifocal Ewing tumors (PDM-ET) with a dose-intense treatment concept. From 1999 to 2005, 281 patients with PDM-ET were enrolled onto the EURO-E.W.I.N.G. 99 trial. Median age was 16.2 years (0.4–49). Recommended treatment consisted of 6 VIDE, one VAI cycle, local treatment (surgery and/or radiotherapy), and high-dose busulfan-melphalan followed by autologuous stem cell transplantation (HDT/SCT). After a median follow up of 3.8 years, event-free survival (EFS) and overall survival (OS) at 3 years for all 281 patients were 27%±3% and 34%±4%. Six VIDE cycles were completed by 250 patients (89%); 169 (60%) received HDT/SCT. Forty-six children less than 14 years and HDT/SCT achieved a 3-year EFS of 45%. Cox regression analyses demonstrated increased risk at diagnosis for patients over 14 years (HR 1.6), a primary tumor volume > 200ml (HR 1.8), more than one bone metastatic site (hazard ratio: HR 2.0, bone marrow metastases (HR 1.6) and additional lung metastases (HR 1.5). An “up front” risk score based on these HR factors identified three groups with EFS rates of 50% for score ≤3 (82 patients), 25% for score > 3 to < 5 (102 patients), and 10% for score ≥5 (70 patients), p< 0.0001. PDM-ET patients may survive with intensive multimodal therapy. Age, tumor volume, and extent of meta-static spread are relevant risk factors. A score based on these factors identifies PDM-ET patients may facilitate risk adapted treatment approaches

Desmoid tumours are a rare fibroblastic proliferation of monoclonal origin, arising in deep soft-tissues. Histologically, they are characterized by locally aggressive behaviour and an inability to metastasize, and clinically by a heterogeneous and unpredictable course. Desmoid tumours can occur in any anatomical site, but commonly arise in the limbs. Despite their benign nature, they can be extremely disabling and sometimes life-threatening, causing severe pain and functional limitations. Their surgical management is complex and challenging, due to uncertainties surrounding the biological and clinical behaviour, rarity, and limited available literature. Resection has been the first-line approach for patients with a desmoid tumour but, during the last few decades, a shift towards a more conservative approach has occurred, with an initial ‘wait and see’ policy. Many medical and regional forms of treatment are also available for the management of this condition, and others have recently emerged with promising results. However, many areas of controversy remain, and further studies and global collaboration are needed to obtain prospective and randomized data, in order to develop an appropriate shared stepwise approach.

Cite this article: Bone Joint J 2023;105-B(7):729–734.

Aims

To determine the major risk factors for unplanned reoperations (UROs) following corrective surgery for adult spinal deformity (ASD) and their interactions, using machine learning-based prediction algorithms and game theory.

The June 2012 Oncology Roundup³⁶⁰ looks at: avoiding pelvic hemipelvectomy; proximal femoral metastasis; extendible prostheses; rotationplasty; soft-tissue sarcomas; osteosarcoma of the pelvis; recurrent chondrosarcoma ; MRI and the differentiation between benign and malignant lesions; and malignant fibrous histiocytoma.

The April 2014 Oncology Roundup³⁶⁰ looks at: Eyeball as good as microscope for tumour margins; when is best to stabilise femoral metastases?; fluorine does not cause bone tumours; whether giant cell tumour of the proximal femur ever successfully managed; extraskeletal osteosarcoma; modular lower limb tumour reconstruction; and observational studies the basis for most bone tumour treatment.