Primary bone tumors are rare, complex and highly heterogeneous. Its diagnostic and treatment are a challenge for the multidisciplinary team. Developments on tumor biomarkers, immunohistochemistry, histology, molecular, bioinformatics, and genetics are fundamental for an early diagnosis and identification of prognostic factors. The personalized medicine allows an effective patient tailored treatment. The bone biopsy is essential for diagnosis. Treatment may include systemic therapy and local therapy. Frequently, a limb salvage surgery includes wide resection and reconstruction with endoprosthesis, biological or composites. The risk for local recurrence and distant metastases depends on the primary tumor and treatment response.

Cancer patients are living longer and bone metastases are increasing. Bone is the third most frequently location for distant lesions. Bone metastases are associated to pain, pathological fractures, functional impairment, and neurological deficits. It impacts survival and patient quality of life. The treatment of metastatic disease is a challenge due to its complexity and heterogeneity, vascularization, reduced size and limited access. It requires a multidisciplinary treatment and depending on different factors it is palliative or curative-like treatment. For multiple bone metastases it is important to relief pain and increases function in order to provide the best quality of life and expect to prolong survival. Advances in nanotechnology, bioinformatics, and genomics, will increase biomarkers for early detection, prognosis, and targeted treatment effectiveness. We are taking the leap forward in precision medicine and personalized care.

Primary malignant bone tumours are a scarce entity with limited population-based data from developing countries. The aim of the study is to investigate the frequency and anatomical distribution of primary malignant bone tumours in a local South African population.

This will be an epidemiological retrospective study. Data will be used of patients that were diagnosed with primary malignant bone tumours over a period of nine years spanning from 1 January 2014 to 31 December 2022. This data will be received from private and government laboratories. Data to be considered are type of primary malignant bone tumours diagnosed, incidence of primary malignant bone tumours over a period of nine years and the most common anatomical sites of primary malignant bone tumours. The rationale behind our study is to assess the frequency of different primary malignant bone tumours in another geographic area of South Africa and to compare these findings to local and international literature. With a projected increase in diagnosis of primary malignant bone tumours in developing countries it is important to have more available data about primary malignant bone tumours from these areas to have a better understanding of these conditions and to understand the impact of the burden they impose on healthcare systems so that management of these conditions can also be improved. Preliminary results show that 23.83% of primary malignant bone tumours occurred in the age group 0–24 years of age, 49.22% in the 25–59 age group and 26.95% in the 60+ age group. The most common tumour that occurred was chondrosarcoma (49.21%) followed by osteosarcoma (41.80%) then Ewing's sarcoma (4,69%) and lastly chordoma (4.30%). From the 256 samples that met the inclusion criteria the five most common anatomical sites were distal femur (63), proximal tibia (41), proximal humerus (38), pelvis (34) and proximal femur (20).

Residual tumor cells left in the bone defect after malignant bone tumor resection can result in local tumor recurrence and high mortality. Therefore, ideal bone filling materials should not only aid bone reconstruction or regeneration, but also exert local chemotherapeutic efficacy. However, common bone substitutes used in clinics are barely studied in research for local delivery of chemotherapeutic drugs. Here, we aimed to use facile manufacturing methods to render polymethylmethacrylate (PMMA) cement and ceramic granules suitable for local delivery of cisplatin to limit bone tumor recurrence.

Porosity was introduced into PMMA cement by adding 1-4% carboxymethylcellulose (CMC) containing cisplatin, and chemotherapeutic activity was rendered to two types of granules via adsorption. Then, mechanical properties, porosity, morphology, drug release kinetics, ex vivo reconstructive properties of porous PMMA and in vitro anti-cancer efficacy against osteosarcoma cells were assessed. Morphologies, molecular structures, drug release profiles and in vitro cytostatic effects of two different drug-loaded granules on the proliferation of metastatic bone tumor cells were investigated.

The mechanical strengths of PMMA-based cements were sufficient for tibia reconstruction at CMC contents lower than 4% (≤3%). The concentrations of released cisplatin (12.1% and 16.6% from PMMA with 3% and 4% CMC, respectively) were sufficient for killing of osteosarcoma cells, and the fraction of dead cells increased to 91.3% within 7 days. Functionalized xenogeneic granules released 29.5% of cisplatin, but synthetic CaP granules only released 1.4% of cisplatin over 28 days. The immobilized and released cisplatin retained its anti-cancer efficacy and showed dose-dependent cytostatic effects on the viability of metastatic bone tumor cells.

Bone substitutes can be rendered therapeutically active for anticancer efficacy by functionalization with cisplatin. As such, our data suggest that multi-functional PMMA-based cements and cisplatin-loaded granules represent viable treatment options for filling bone defects after bone tumor resection.

En bloc resection for primary bone tumours and isolated metastasis are complex surgeries associated with a high rate of adverse events (AEs). The primary objective of this study was to explore the relationship between frailty/sarcopenia and major perioperative AEs following en bloc resection for primary bone tumours or isolated metastases of the spine. Secondary objectives were to report the prevalence and distribution of frailty and sarcopenia, and determine the relationship between these factors and length of stay (LOS), unplanned reoperation, and 1-year postoperative mortality in this population.

This is a retrospective study of prospectively collected data from a single quaternary care referral center consisting of patients undergoing an elective en bloc resection for a primary bone tumour or an isolated spinal metastasis between January 1st, 2009 and February 28th, 2020. Frailty was calculated with the modified frailty index (mFI) and spine tumour frailty index (STFI). Sarcopenia, determined by the total psoas area (TPA) vertebral body (VB) ratio (TPA/VB), was measured at L3 and L4. Regression analysis produced ORs, IRRs, and HRs that quantified the association between frailty/sarcopenia and major perioperative AEs, LOS, unplanned reoperation and 1-year postoperative mortality.

One hundred twelve patients met the inclusion criteria. Using the mFI, five patients (5%) were frail (mFI ³ 0.21), while the STFI identified 21 patients (19%) as frail (STFI ³ 2). The mean CT ratios were 1.45 (SD 0.05) and 1.81 (SD 0.06) at L3 and L4 respectively. Unadjusted analysis demonstrated that sarcopenia and frailty were not significant predictors of major perioperative AEs, LOS or unplanned reoperation. Sarcopenia defined by the CT L3 TPA/VB and CT L4 TPA/VB ratios significantly predicted 1-year mortality (HR of 0.32 per one unit increase, 95% CI 0.11-0.93, p=0.04 vs. HR of 0.28 per one unit increase, 95% CI 0.11-0.69, p=0.01) following unadjusted analysis. Frailty defined by an STFI score ≥ 2 predicted 1-year postoperative mortality (OR of 2.10, 95% CI 1.02-4.30, p=0.04).

The mFI was not predictive of any clinical outcome in patients undergoing en bloc resection for primary bone tumours or isolated metastases of the spine. Sarcopenia defined by the CT L3 TPA/VB and L4 TPA/VB and frailty assessed with the STFI predicted 1-year postoperative mortality on univariate analysis but not major perioperative AEs, LOS or reoperation. Further investigation with a larger cohort is needed to identify the optimal measure for assessing frailty and sarcopenia in this spine population.

Introduction

“Bioexpandable” prostheses after resection of malignant bone tumors in children to lengthen the bone using the method of callus distraction may offer new perspectives and better long-term results.

In the past decades, a huge amount of effort has been devoted to translate evidence based on standard preclinical models of bone tumours to effective tools for clinical applications. Although cancer is a genetic disease, hence the emphasis on -omics approaches, the complexity of cancer tissue, a mix of competing clones of transformed elements that react differently to microenvironmental stimuli, may hardly be reproduced by standard approaches. Cost, biological differences and ethical concerns are increasingly recognized as weaknessess of animal models. To overcome these limitations and provide reliable, reproducible, and affordable tools for predicting the effectiveness of treatments, environmental-controlled 3D cultures and co-cultures (spheroids, organoids) coupled with microfluidics and advanced imaging have recently being considered as effective instrument to increase knowledge on the pathophysiology of bone tumours and define effective therapeutic solutions.

The management of primary malignant bone tumors with metastatic disease at presentation remains a challenge. While surgical resection has been shown to improve overall survival among patients with non-metastatic malignant bone tumors, current evidence regarding the utility of surgery in improving overall survival in metastatic patients remains limited.

The 2004–2016 National Cancer Database (NCDB) was queried using International Classification of Diseases 3rd Edition (ICD-O-3) topographical codes to identify patients with primary malignant bone tumors of the extremities (C40.0-C40.3, C40.8 and C40.9) and/or pelvis (C41.4). Patients with malignant bone tumors of the axial skeleton (head/skull, trunk and spinal column) were excluded, as these cases are not routinely encountered and/or managed by orthopaedic oncologists. Histological codes were used to categorize the tumors into the following groups - osteosarcomas, chondrosarcomas, and Ewing sarcomas. Patients who were classified as stage I, II or III, based on American Joint Commission of Cancer (AJCC) guidelines, were excluded. Only patients with metastatic disease at presentation were included in the final study sample. The study sample was divided into two distinct groups – those who underwent surgical resection of the primary tumors vs. those who did not receive any surgery of the primary tumor. Kaplan-Meier survival analysis was used to report unadjusted 5-year overall survival rates between patients who underwent surgical resection of the primary tumor, compared to those who did not. Multi-variate Cox regression analyses were used to assess whether undergoing surgical resection of the primary tumor was associated with improved overall survival, after controlling for differences in baseline demographics, tumor characteristics (grade, location, histological type and tumor size), and treatment patterns (underwent metastatectomy of distal and/or regional sites, positive vs. negative surgical margins, use of radiation therapy and/or chemotherapy). Additional sensitivity analyses, stratified by histologic type for osteosarcomas, chondrosarcomas and Ewing sarcomas, were used to assess prognostic factors for overall survival.

A total of 2,288 primary malignant bone tumors (1,121 osteosarcomas, 345 chondrosarcomas, and 822 Ewing sarcomas) with metastatic disease at presentation were included – out of which 1,066 (46.0%) underwent a surgical resection of the primary site. Overall 5-year survival rates, on unadjusted Kaplan-Meier log-rank analysis, were significantly better for individuals who underwent surgical resection vs. those who did not receive any surgery (31.7% vs. 17.3%; p<0.001). After controlling for differences in baseline demographics, tumor characteristics and treatment patterns, undergoing surgical resection of primary site was associated with a reduced overall mortality (HR 0.42 [95% CI 0.36–0.49]; p<0.001). Undergoing metastectomy (HR 0.92 [95% CI 0.81–1.05]; p=0.235) was not associated with a significant improvement in overall survival. On stratified analysis, radiation therapy was associated with improved overall survival for Ewing Sarcoma (HR 0.71 [95% CI 0.57–0.88]; p=0.002), but not for osteosarcoma (HR 1.14 [95% CI 0.91–1.43]; p=0.643) or chondrosarcoma (HR 1.08 [95 % CI 0.78–1.50]; p=0.643). Chemotherapy was associated with improved overall survival for osteosarcoma (HR 0.50 [95% CI 0.39–0.64]; p<0.001) and chondrosarcoma (HR 0.62 [95% CI 0.45–0.85]; p=0.003), but not Ewing sarcoma (HR 0.79 [95% CI 0.46–1.35]; p=0.385).

Surgical resection of the primary site significantly improves overall survival for primary malignant bone tumors with metastatic disease at presentation. Physicians should strongly consider surgical resection of the primary tumor, with adjunct systemic and/or radiation therapy (dependent on tumor histology), in patients presenting with metastatic disease at presentation.

Introduction

Bone tumours of the foot are rare, representing 3–6% of all bone tumours. Of these 15–25% are thought to be malignant. Obtaining clear surgical margins remains an important factor in improving outcome from tumours. However, the anatomical complexity of the foot can lead to an inadequate resection, particularly if the operating surgeon is attempting to preserve function. The aim of this paper is to identify the clinical course of patients suffering from malignant bone tumours of the foot.

The aim of this study was to evaluate the functional and oncological outcome of extracorporeally irradiated autografts used to reconstruct the pelvis after a P1/2 internal hemipelvectomy.

The study included 18 patients with a primary malignant bone tumour of the pelvis. There were 13 males and five females with a mean age of 24.8 years (8 to 62). Of these, seven had an osteogenic sarcoma, six a Ewing’s sarcoma, and five a chondrosarcoma. At a mean follow-up of 51.6 months (4 to 185), nine patients had died with metastatic disease while nine were free from disease. Local recurrence occurred in three patients all of whom eventually died of their disease. Deep infection occurred in three patients and required removal of their graft in two while the third underwent a hindquarter amputation for extensive flap necrosis.

The mean Musculoskeletal Tumor Society functional score of the 16 patients who could be followed-up for at least 12 months was 77% (50 to 90). Those 15 patients who completed the Toronto Extremity Salvage Score questionnaire had a mean score of 71% (53 to 85).

Extracorporeal irradiation and re-implantation of bone is a valid method of reconstruction after an internal hemipelvectomy. It has an acceptable morbidity and a functional outcome that compares favourably with other available reconstructive techniques.

Cite this article: Bone Joint J 2014;96-B:1404–10

Purpose of the study

To review the primary bone tumours of the spine treated at our unit.

Summary Statement

Treatment of non-union is a highly demanding field with respect to bone healing. BMP 7 is a useful, wide-ranged tool in treating non-union of the foot and benign bone tumors. It represents a low-risk procedure with a high level of reliability.

In this case study, we describe the clinical presentation and treatment of 36 patients with periosteal chondrosarcoma collected over a 59-year period by the archive of the Netherlands Committee on Bone Tumours. The demographics, clinical presentation, radiological features, treatment and follow-up are presented with the size, location, the histological grading of the tumour and the survival. We found a slight predominance of men (61%), and a predilection for the distal femur (33%) and proximal humerus (33%). The metaphysis was the most common site (47%) and the most common presentation was with pain (44%). Half the tumours were classified histologically as grade 1. Pulmonary metastases were reported in one patient after an intra-lesional resection. A second patient died from local recurrence and possible pulmonary and skin metastases after an incomplete resection. It is clearly important to make the diagnosis appropriately because an incomplete resection may result in local recurrence and metastatic spread. Staging for metastatic disease is recommended in grade II or III lesions. . These patients should be managed with a contrast-enhanced MRI of the tumour and histological confirmation by biopsy, followed by en-bloc excision. Cite this article: Bone Joint J 2014;96-B:823–8

Primary bone tumours of the clavicle are rare. Currently the existing literature is limited to a single case series and case reports or cases. Information regarding the patient's demographics and tumour types is therefore limited.

The aim of this study was to investigate the and also suggest a management protocol for suspected primary bone tumours of the clavicle. We retrospectively reviewed the Scottish Bone Tumour Register from January 1971 to January 2012 and included all primary bone tumours of the clavicle.

We identified only sixteen primary bone tumours over forty one year's highlighting the rarity of these tumours. There were ten benign and six malignant tumours with a mean age of 32 years (Range 4 to 66). The average presentation to orthopaedics after onset of symptoms was two months with five patients presenting following a pathological fracture. Malignant tumour types identified were consistent with previous literature with two cases of Ewing's sarcoma and osteosarcoma and a single case of osteosarcoma post radiotherapy and a single case of chondrosarcoma. Benign tumours were treated effectively with intralesional procedures. Malignant tumours were treated with wide local excision and subtotal or total clavicle excision.

We suggest an investigatory and treatment protocol for patients with a suspected primary bone tumour of the clavicle. This is the largest series of primary bone tumours of the clavicle in the literature.

Introduction

To look at the effect of width and tissue at surgical margins, together with the use of adjuvant therapy on locally recurrent disease and disease free survival.

Aim

To identify patterns in referral and the management pathway of patients with primary bone tumours of the spine referred to the Orthopaedic Spine Unit in order to recommend ways to improve the service.

Primary bone tumours of the talus are rare. Currently the existing literature is limited to a single case series and case reports or cases described in series of foot tumours. Information regarding the patient's demographics and tumour types is therefore limited.

The aim of this study was to investigate these questions and also suggest a management protocol for suspected primary bone tumours of the talus. We retrospectively reviewed the Scottish Bone Tumour Register from January 1954 to May 2010 and included all primary bone tumours of the talus. We identified only twenty three bone tumours over fifty six years highlighting the rarity of these tumours. There were twenty benign and three malignant tumours with a mean age of twenty eight years. A delay in presentation was common with a mean time from onset of symptoms to diagnosis of ten months. Tumour types identified were consistent with previous literature. We identified cases of desmoplastic fibroma and intraosseous lipodystrophy described for the first time.

We suggest an investigatory and treatment protocol for patients with a suspected primary bone tumour of the talus. This is the largest series of primary bone tumours of the talus in the literature.

Background

Treatment of aggressive benign bone lesions with curettage, burring, cementation and plate augmentation is a widely accepted treatment. We have used the above method using a locked plate (rather than conventional), facilitating stability and early mobilisation. We hypothesise that this is an alternative to megaprosthetic joint replacement, and provides acceptable functional outcomes at follow-up.

The management of pathological fractures due to Metastatic Bone Disease (MBD) and Primary Bone Tumours (PBTs) has implications for the Trauma service due to the extra pressures on staff, service delivery and budgets. We undertook an analysis of a cohort of patients presenting with MBD and PBTs. A retrospective chart review of all cases with MBD and PBTs admitted to a 40-bed Trauma Unit between 2005 and 2009 was conducted. The study looked at frequency, primary pathology, and site of pathology/fracture, time from primary diagnosis to referral, subsequent interventions and others. The results identified 34 patients, 21 females (62%) and 13 males (38%) (mean age: 64.6 years) with MBD or PBTs. Metastases secondary to breast cancer (n=13, 38%) and Myeloma (n=5, 15%) were the most common with the majority being found in the femur (n=22, 65%) and the Humerus (n=6, 18%). The mean time from primary tumour diagnosis to fracture referral was 29.6 months with 27 (79%) patients undergoing definitive surgical management within the unit. The conclusions of the study demonstrate that a wide variety of pathology presented to the unit over a 5 year period. Considerable variation was noted in the time from primary tumour diagnosis to presentation with a fracture. This could be due to improvements in treatments of specific cancers or a lack of understanding of what an Orthopaedic surgeon can offer the cancer patient. No definitive increase in pathological fractures was seen. The consensus opinion is that prompt and appropriate management of pathological fractures in cancer patients is cost effective. Management of these injuries, in a Trauma Unit, represents a small, but significant part of the annual work-load. While no significant trend has been seen, with respect to an increased incidence, it is noted that a proportion of these patients were a number of years from their initial diagnosis. With improvements in the survivorship of cancer patients, close scrutiny will be required to determine whether this ultimately translates into an increased fracture burden

Since 1970, 2200 primary endoprosthetic replacements have been carried out at our Unit for bone tumours. 3% were carried out in the 1970s, 21% in the 1980s, 33% in the 1990s and 43% since 2000.

The most common diagnosis was osteosarcoma (839)(38%) followed by metastatic disease (18%) and chondrosarcoma (13%). The most common site was the distal femur (35%) followed by the proximal femur and proximal tibia. The least common sites were the scapula and distal radius. The mean age at operation was 35 but varied widely, being 19 in patients with osteosarcoma and 58 for those with metastases. 239 extendable prostheses were inserted in children. 50% of the patients were alive at 10yrs and 42% at 20yrs. 7% required an amputation either for local recurrence or infection.

The failure rate of the prostheses varied by age and site, with pelvic and proximal tibial replacements having the highest risk of infection and proximal humeral replacements the lowest risk of any complication. The failure rates of the most common prostheses (distal femur and proximal tibia) have improved over time and are now ~ 1.5% per year. Hydroxyapatite collars have largely resolved the problem of aseptic loosening. Silver coated prostheses have been used in 48 complex cases with encouraging results in controlling infection. Functional scores averaged 80% and were the same for revision as for primary implants.

Patients with peripheral primary bone tumours are often identified and referred at an early stage to a regional tumour service according to established guidelines. In patients with primary bone tumours of the spine, however, the definitive management or outcome of such patients is being prejudiced by preliminary intervention from non-specialist services prior to their referral.

Objective: To audit the standards of management of patients with primary bone tumours of the spine referred to a regional tumour service.

Retrospective review of case notes and radiology.

Subjects: Patients with primary bone tumour of the spine managed at the Orthopaedic Spine Unit with the Regional Bone Tumour Service in Newcastle Upon Tyne Hospitals NHS Trust.

Referral to tumour service, prior intervention, operative treatment, survival, factors affecting definitive management

31 of 39 (16 benign, 23 malignant) patients were initially referred from primary care to services other than the regional tumour service, most commonly neurosurgery (11/39) and paediatric oncology (4/39). Seven of 39 of these patients had undergone interventions prior to their referral to the tumour service, which may have negatively impacted their definitive management or curative surgery.

These tumours present complex issues regarding their definitive management to optimise outcome. Closer links between departments are required to enable the multidisciplinary management of primary bone tumours of the spine. Prior surgical intervention may compromise cure. Those involved in their management should be encouraged to liaise with their regional bone tumour service to improve outcome.