Bone Tumours Research Articles

UK guidelines for the management of bone sarcomas.

This document is an update of the British Sarcoma Group guidelines (2016) and provides a reference standard for the clinical care of UK patients with primary malignant bone tumours (PMBT) and giant cell tumours (GCTB) of bone. The guidelines recommend treatments that are effective and should be available in the UK, and support decisions about management and service delivery. The document represents a consensus amongst British Sarcoma Group members in 2024. Key recommendations are that bone pain, or a palpable mass should always lead to further investigation and that patients with clinical or radiological findings suggestive of a primary bone tumour at any anatomic site should be referred to a specialist centre and managed by an accredited bone sarcoma multidisciplinary team. Treatment recommendations are provided for the major tumour types and for localised, metastatic and recurrent disease. Follow-up schedules are suggested.

Reconstruction of large post-traumatic segmental femoral defects using vascularised bone flaps: a retrospective case series.

Large femoral defects after trauma, femoral non-unions, fractures complicated by osteomyelitis or defects after bone tumour resection present high burden and increased morbidity for patient and are challenging for reconstructive surgeons. Defects larger than 6 cm and smaller defects after failed spongioplasty are suitable for reconstruction using a free, eventually a pedicled vascularised bone flap. The free fibular flap is preferred but an iliac crest free flap or a pedicled medial femoral condyle flap can be also used. These vascularised flaps are ideal for bridging defects of long bones and can be also used as osteocutaneous or osteomuscular flaps for coverage of soft tissue defect if present. The patients and their families were informed that data will be submitted for publication and they gave their written informed consent prior to the submission. The study was approved by the institutional ethic committee. We analysed a group of eight patients with large diaphyseal or distal metaphyseal femoral defects. A free fibular flap was used in six patients, a pedicled medial ipsilateral femoral condyle flap was used in two patients and a defect in one patient was reconstructed using an iliac crest free flap. All flaps healed completely in all patients and no fracture of the flap was detected during the study period. In one patient, a locking plate broke and was replaced by a compression plate. At the last check-up all patients were able to step on the reconstructed limb with full weight. Although our study comprises a heterogeneous group of cases, they all have been successfully treated by a similar technique, adapted in each case specifically to the needs of the patient. A major limitation parameter of reconstruction by a free vascularised flap is the size of bone defect needed to be reconstructed. In case of a bone defect longer than 6cm and a concomitant soft tissue disruption, a vascularised double-barrel fibula is the preferred. Large femoral defects can be successfully reconstructed with good long-term results using suitable free or pedicled vascularised bone flaps, especially preferring the free fibular flap.

Aggressive bone tumours: What a radiologist can offer to the surgeon?

The complexity of aggressive bone tumours necessitates a comprehensive approach that combines radiological assessments with clinical and pathological findings. Radiologists offer valuable insights to surgeons throughout the diagnostic and therapeutic journey, enhancing the precision and efficacy of surgical interventions. Radiologists contribute to definitive diagnosis in the majority of benign and certain aggressive tumours, although the complexity of aggressive bone tumours often requires histopathological confirmation. They assist in characterizing tumours and evaluating their extension, providing critical information for treatment planning. Radiologists guide biopsy procedures, ensuring representative tissue samples while minimizing morbidity and the risk of tumour spread. In preoperative planning, radiologists construct detailed 3D reconstructions of tumours, aiding surgeons in strategizing surgical approaches and anticipating challenges. During surgery, radiologists offer intraoperative guidance through techniques like image fusion and intraoperative MRI, enhancing surgical precision. Post-surgical surveillance for tumour recurrence heavily relies on radiological imaging, with functional MR sequences providing valuable insights. Radiologists also play a significant role in image-guided therapeutic interventions for aggressive bone tumours, offering procedures like osteoplasty and ablation techniques for pain relief and tumour control. In conclusion, radiologists are indispensable members of the multidisciplinary team and offer expertise in diagnosis, biopsy guidance, preoperative planning, intraoperative guidance, post-surgical surveillance, and interventional therapy. Their collaborative efforts significantly optimize patient's outcome and quality of life.

Shared decision making in primary malignant bone tumour surgery around the knee in children and young adults: protocol for a prospective study

BackgroundChildren and young adults needing surgery for a primary malignant bone tumour around the knee face a difficult, life-changing decision. A previous study showed that this population wants to be involved more in the decision-making process and that more involvement leads to less decisional stress and regret. Therefore, a well-designed and standardized decision-making process based on the principles of shared decision-making needs to be designed, implemented, and evaluated.MethodsWe developed a shared decision-making (SDM) model for this patient population, including an online decision aid (DA). This model has been implemented in the standard care of patients with a primary malignant bone tumour around the knee. Following implementation, we will analyse its effect on the decision-making process and the impact on patient experiences using questionnaires and interviews. Moreover, potential areas for improvement will be identified.DiscussionGiven the importance of involving patients and parents in surgical decision-making, particularly in life-changing surgery such as malignant bone tumour surgery, and given the lack of SDM models applicable for this purpose, we want to share our model with the international community, including our study protocol for evaluating and optimising the model. This study will generate valuable knowledge to facilitate the optimisation of current patient care for local treatment. The sharing of our implementation and study protocol can serve as an example for other centres interested in implementing SDM methods in an era characterized by more empowered patients and parents who desire autonomy and reliable and realistic information.

Subchondral curettage cement packing in the distal radius causes wrist joint degeneration: long-term evaluation of distal radius giant-cell bone tumour.

This study investigated wrist joint degeneration after curettage and PMMA treatment for giant cell bone tumours (GCBT) at the distal radius. We performed a retrospective single-centre study, which included 23 patients with GCBT at distal radius treated with curettage and PMMA between 2001 and 2021. The progression of wrist joint degeneration was assessed through radiographic evidence, comparing the postoperative grade with both the preoperative grade and the grade of the contralateral wrist at the latest follow-up. We also analyzed the influence of age, sex, tumour distance of the joint, subchondral bone involvement, tumour size and body mass index. The study included 23 patients with a mean age of 32.1 ± 13.3 years. The average duration of follow-up was 96.4 ± 69 months (range, 24-265 months). The mean tumour-cartilage distance was 1.79 ± 2.4 mm (range, 0-10 mm) and the mean BMI was 23.5 ± 3.8 kg/m2. Degeneration of the wrist joint was evident in 16 patients (69.6%) at the final assessment, however, 10 patients (43.4%) were identified as having a progression of joint degeneration secondary to the surgical procedure among the 16 patients with wrist joint degeneration at the final control view. Age, gender, dominance, tumour-cartilage distance, subchondral bone involvement, tumour size, patient height, weight, and BMI were not associated with secondary joint degeneration. Ten of 23 patients developed wrist joint degeneration over an average follow-up period of 8 years, and no particular factors associated with the degeneration were identified.

Accuracy of clinical diagnosis, imaging methods, and biopsy in tumours and pseudo-tumours of the hand.

The appropriate use of imaging methods in bone and soft tissue tumours of the hand is well established in the radiological literature. However, since most of the tumoral conditions of the hand are benign, the use of imaging methods may be based on clinician preferences and technical availability. The aim of this work is to present the experience in our institution in the management of tumours and pseudo-tumours of the hand and to review the utility of different imaging methods in their diagnosis. We present a retrospective and consecutive case series of patients referred to Hospital Universitario Virgen de las Nieves due to clinical suspicion of hand tumour in the last 10 years. We assessed the accuracy of clinical and imaging diagnoses, matching the final pathological or surgical results, considering a diagnosis as "correct" if it was included in the differential diagnosis suggested in the clinical (including all provided diagnoses) or radiological report (only the first 2 diagnoses), respectively. Biopsy accuracy was contrasted with surgical findings. We included 175 patients with a pathological or microbiological diagnosis of hand tumors, obtained through surgery (n=124) and/or core needle biopsy (n=62), or puncture-drainage (n=30). Among these, 21 cases were identified as infectious, metabolic, or inflammatory processes, while 154 were classified as hand tumours or pseudotumours (101 in soft tissues and 53 in bone). The overall diagnostic accuracy (95% confidence interval) for each approach was as follows: clinical diagnosis, 26.3% (19.8-32.8%); ultrasound, 72.6% (64.3-80.8%); magnetic resonance imaging (MRI), 80.6% (73.8-87.4%); computed tomography (CT), 84.6% (74.8-94.4%); and radiography, 46.8% (38.6-55.0%). The overall accuracy of imaging was 81.1% (75.3-86.9%). For soft tissue masses, the diagnostic accuracy was: clinical, 30.7% (25.5-42.1%); ultrasound, 69.8% (62.9-80.1%); MRI, 73.9% (65.5-83.4%); CT, 75.0% (30-92%); and radiography, 20.3% (14-33%), with an overall imaging accuracy of 75.2% (69.2-84.1%). For bone tumours, the accuracy was: clinical, 10.9% (5.2-21.8%); ultrasound, 75.0% (46.8-91.1%); MRI, 90.7% (78.4-96.3%); CT, 92.3% (79.7-97.3%); and radiography, 83.3% (71.3-91%), with an overall imaging accuracy of 89.1% (78.2-94.9%). Biopsy accuracy was 90.7% (83-98.5%) overall, 86.4% (74-98%) for soft tissue masses, and 100% (81.5-100%) for bone tumours. Imaging outperforms clinical diagnosis in terms of accuracy and should be mandatory before any interventional procedure. Imaging-guided biopsy is an efficient complementary technique when doubts persist about the nature or potential malignancy of a hand tumour.

Measurable Progression of Giant Cell Tumour of Bone Associated with Pregnancy - A Tertiary Sarcoma Centre Analysis

Measurable Progression of Giant Cell Tumour of Bone Associated with Pregnancy - A Tertiary Sarcoma Centre Analysis

Reconstruction after proximal ulnar resection.

Reconstruction after osteoarticular resection of the proximal ulna for tumours is technically difficult and little has been written about the options that are available. We report a series of four patients who underwent radial neck to humeral trochlea transposition arthroplasty following proximal ulnar osteoarticular resection. Between July 2020 and July 2022, four patients with primary bone tumours of the ulna underwent radial neck to humeral trochlea transposition arthroplasty. Their mean age was 28 years (12 to 41). The functional outcome was assessed using the range of motion (ROM) of the elbow, rotation of the forearm and stability of the elbow, the Musculoskeletal Tumor Society score (MSTS), and the nine-item abbreviated version of the Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH-9) score. All patients were available for follow-up at a mean of 33 months (25 to 43) and were disease-free. The mean flexion arc was 0° to 105°. Three patients had complications. One had neuropraxia of the ulnar nerve. The symptoms resolved after three months. In one patient, the screw used for fixation of the triceps tendon became exposed and was removed, six months postoperatively. One patient with wound dehiscence required a local flap for soft-tissue cover, four months postoperatively. At a mean follow-up of 33 months (25 to 43), the mean flexion arc was 0° to 105°. All patients had full supination (85°) but none had any pronation. The mean MSTS score was 23.5 (23 to 24) and mean QuickDASH-9 score was 26.13 (16.5 to 35.75). Three patients had varus-valgus instability on examination, although only one had a sense of instability while working. Radial neck to humeral trochlea transposition offers a satisfactory and cost-effective biological reconstructive option after osteoarticular resection of the proximal ulna, in the short term. It provides good elbow function and, being a biological reconstruction option using native bone, is likely to provide long-term stability and durability.

Chondromyxoid Fibroma of Phalanges

Chondromyxoid fibroma (CMF) is a rare, benign metaphyseal bone tumour characterised by a combination of chondroid, myxoid, and fibrous elements, which can affect any bone at any age, without a gender predilection. We report the case of CMF in a 47-year-old lady who presented with swelling of the left little finger to a tertiary care hospital at Kolkata, India, in May 2024. Imaging showed presence of a lobulated lesion arising from the middle phalanx of the left little finger, extending to involve the base of the distal phalanx. Fine needle aspiration cytology of the lesion was indicative of a moderately cellular myxoid lesion. Histopathology remains crucial for diagnosis, which revealed a lobulated tumour with zones of spindle to stellate cells, associated with abundant myxoid and chondroid matrix in the intercellular areas. Treatment involves complete local excision with tumor free margins, as recurrence can occur with local curettage.

A rare case of trapezium osteochondroma: unveiling a unique tumour with clinical implications

Osteochondroma is a benign bone tumour commonly found on the metaphysis of long bones. The presentation of osteochondroma on the trapezoid bone, a carpal bone in the wrist, is exceptionally rare. To our knowledge, no such cases have been reported in India. This report details a rare case of osteochondroma located on the trapezoid bone and its successful surgical management. A 55-year-old female presented with pain and swelling in the wrist. Radiological imaging, including X-rays and MRI, revealed a well-defined, pedunculated mass arising from the trapezoid bone. The patient underwent surgical resection of the tumour. Histopathological examination confirmed the diagnosis of osteochondroma. Postoperatively, the patient experienced significant relief from symptoms and showed no evidence of tumour recurrence during follow-up. This case contributes to the limited body of literature on osteochondromas in rare locations, particularly on the trapezoid bone. It illustrates the successful outcome of surgical treatment for rare bone tumours and emphasizes the need for heightened awareness and comprehensive diagnostic approaches in similar cases.

Impact of metadata in multimodal classification of bone tumours

The accurate classification of bone tumours is crucial for guiding clinical decisions regarding treatment and follow-up. However, differentiating between various tumour types is challenging due to the rarity of certain entities, high intra-class variability, and limited training data in clinical practice. This study proposes a multimodal deep learning model that integrates clinical metadata and X-ray imaging to improve the classification of primary bone tumours. The dataset comprises 1,785 radiographs from 804 patients collected between 2000 and 2020, including metadata such as age, affected bone site, tumour position, and gender. Ten tumour types were selected, with histopathology or tumour board decisions serving as the reference standard.MethodsOur model is based on the NesT image classification model and a multilayer perceptron with a joint fusion architecture. Descriptive statistics included incidence and percentage ratios for discrete parameters, and mean, standard deviation, median, and interquartile range for continuous parameters.ResultsThe mean age of the patients was 33.62 ± 18.60 years, with 54.73% being male. Our multimodal deep learning model achieved 69.7% accuracy in classifying primary bone tumours, outperforming the Vision Transformer model by five percentage points. SHAP values indicated that age had the most substantial influence among the considered metadata.ConclusionThe joint fusion approach developed in this study, integrating clinical metadata and imaging data, outperformed state-of-the-art models in classifying primary bone tumours. The use of SHAP values provided insights into the impact of different metadata on the model’s performance, highlighting the significant role of age. This approach has potential implications for improving diagnostic accuracy and understanding the influence of clinical factors in tumour classification.

Abstract B005: Denosumab Enhances Cytotoxic T Cell Infiltration by supressing SPP1 Expression in Giant Cell Tumour of Bone

Abstract Denosumab, a RANKL inhibitor, is primarily used to prevent osteoclastogenesis for the treatment of conditions like osteoporosis, bone metastasis, and giant cell tumor of bone (GCTB). RANKL is also key in immunity, activating NFκB and its target genes, including the osteopontin-coding gene SPP1, which is linked with CXCL9:SPP1 macrophage polarization and prognosis. Retrospective studies of bone metastasis have demonstrated improved clinical outcomes when immune checkpoint inhibitors (ICIs) are combined with denosumab. We undertook a study to explore denosumab's direct role in anti-tumor immunity. Single-cell RNA sequencing was performed on nine primary human GCTB samples, including three untreated and six treated solely with denosumab, to exclude confounding treatment factors linked with bone metastasis samples. Furthermore, we utilized immunohistochemistry staining from paired pre- and post-denosumab treated samples from a cohort of nine GCTB patients and conducted pan-cancer analysis on primary tumors, spanning 31 distinct types of cancers, sourced from the Genomic Data Commons Data Portal. Our single-cell analysis of GCTB resulted in a comprehensive cell atlas of this rare disease, revealing denosumab's role in inhibiting SPP1 expression and augmenting cytotoxic T cell infiltration. This was confirmed in nine pairs of pre- and post-denosumab treated GCTB samples using immunohistochemistry staining. The pan-cancer analysis indicated a negative correlation between SPP1 expression and CD8A levels across most tumor types, with the CD8A/SPP1 ratio correlating with clinical outcomes in 14 cancer types. Our research provides robust clinical evidence that denosumab improves anti-tumor immunity by inhibiting SPP1 expression, presenting a significant step towards patient selection for combined ICI and denosumab therapy. Citation Format: Zezhuo Su, Maximus Chun Fai Yeung, Jason Pui Yin CHEUNG, Kelvin Sin Chi Cheung. Denosumab Enhances Cytotoxic T Cell Infiltration by supressing SPP1 Expression in Giant Cell Tumour of Bone [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr B005.

Follow-up analysis of lesion characteristics of enchondromas and atypical cartilaginous tumours of the knee and shoulder region on MRI.

Enchondromas (ECs) and atypical cartilaginous tumours (ACTs), respectively, represent benign and intermediate cartilaginous bone tumours. Differentiation between these tumour entities bears difficulties, as histology and MRI cannot always provide exact diagnoses. Observation of the natural course of ECs/ACTs via follow-up MRIs might support tumour distinction without needing biopsy harbouring sampling error. Reports of patients that had undergone MRI exams of the knee (n = 44.762) or shoulder (n = 21.550) at a single radiology institute between 01.01.2007 and 01.03.2020 were searched for ECs/ACTs with at least one follow-up MRI. Scans of 176 patients (with 182 cartilage lesions) fulfilling these criteria were subsequently re-examined together with corresponding MRI reports to evaluate morphological tumour development over time, focusing on potential alterations of lesion size, tumour-related oedema, and scalloping. Median follow-up time was 27 ± 53 months for knee tumours and 26 ± 32 months for shoulder lesions. Presence of tumour growth was significantly higher in ACTs than in ECs both at the knee (p = 0.04) and shoulder (p = 0.03). While ACTs were associated with median tumour growth rates of 0.039 mm/month (knee) and 0.083 mm/month (shoulder), ECs of the knee and shoulder showed lower median growth rates equivalent to 0.0 mm/month (p < 0.01, p < 0.01). ECs and ACTs both presented stable regarding tumour-related oedema and scalloping during follow-up. ACTs and ECs show different tumour growth rates. Growth rates are slow for both, ECs and ACTs, supporting the current concept of watchful waiting. ECs may decrease in size. Follow-up MRIs may support the radiological differentiation of cartilage lesions. Question Both singular MRI and histological examination have limitations regarding differentiation of enchondromas (EC) and atypical cartilaginous tumours (ACTs). Findings Median ACT growth rates were 0.039 mm/month (knee) and 0.083 mm/month (shoulder), while median growth rates of EC in the knee and shoulder were 0.0 mm/month. Clinical relevance Active surveillance is a safe strategy when dealing with ECs and ACTs of the long bones; follow-up MRIs may support tumour distinction of cartilage lesions, as ECs and ACTs show different growth behaviour.

Targeting Bone Tumours with 45S5 Bioactive Glass.

Despite advances in treatment modalities, bone tumour therapies still face significant challenges. Severe side effects of conventional approaches, such as chemo- and radiation therapy, result in poor survival rates and high tumour recurrence rates, which are the most common issues that need to be improved upon. The aim of this study was to evaluate the therapeutic properties of 45S5 bioactive glass (BG) for targeting bone tumours. The viability of the cells derived from osteosarcoma, chondrosarcoma, and giant cell tumours was significantly reduced in the presence of 45S5-BG. In contrast, the viability of non-malignant osteoblast-like cells, chondrocytes, and bone marrow-derived stromal cells was not or only slightly affected. While alterations to the particle surface induced by heat treatment, acid etching, or incubation in a simulated body fluid had only minor effects on cytotoxicity, reducing the particle size or sintering the material significantly improved the cytotoxic effect of 45S5-BG. Further, using a chicken chorioallantoic membrane assay, the co-transplantation of 45S5-BG resulted in a significant reduction in tumour formation in vivo. Given the known positive effects of BGs on bone regeneration, our findings suggest that 45S5-BG holds great potential for the development of new and effective bone tumour therapies, with minimal side effects on non-malignant cells and simultaneous contribution to bone healing.

Shikonin induces ferroptosis in osteosarcomas through the mitochondrial ROS-regulated HIF-1α/HO-1 axis

BackgroundThe most common malignant bone tumour is osteosarcoma, which has an unsatisfactory prognosis and unsatisfactory treatment. Ferroptosis shows promise as an effective OS therapy. A substance extracted from the Lithospermum erythrorhizon, Shikonin (SHK), inhibits a number of tumours, including ovarian, gastric, and lung cancers. However, whether SHK induces OS ferroptosis and its mechanisms are not clear. PurposeOur study is aimed at investigating whether SHK causes ferroptosis and elucidating its molecular mechanism. MethodsCell counting Kit-8, cell cycle and cell apoptosis assay were utilised to assess therapeutic effect of SHK against OS. Normal cells, including H9C2, AML-12 and HK-2, haematoxylin and eosin staining and mice serum biomarker tests were used to assess SHK biosafety. Malondialdehyde (MDA) levels, the glutathione (GSH)/oxidized glutathione (GSSG) ratio, reactive oxygen species (ROS), lipid peroxide (LPO), and intracellular Fe2+ detection, quantitative reverse transcription PCR (qRT-PCR), Western blotting (WB) and rescue experiments were employed to confirm whether SHK induced ferroptosis in OS cells. Molecular docking, cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS) assay were used to evaluate the direct binding between SHK and hypoxia-inducible factor-1α (HIF-1α). Protein stability and degradation analysis, small RNA interference, flow cytometry, qRT-PCR, and WB were used to investigate the molecular mechanism of ferroptosis. In vivo xenografts of nude mouse was used to study the anti-OS effect of SHK. ResultsSHK significantly reduced OS cell viability and induced apoptosis and G2/M arrest. SHK increased intracellular levels of MDA, ROS, LPO, and Fe2+ while simultaneously reducing the GSH/GSSG ratio and GPX4 and SLC7A11 expression. CETSA and DARTS results demonstrated that SHK did not bind targetly to HIF-1α. Instead, mitochondrial ROS (MitoROS) promoted HIF-1α expression, resulting in HO-1 overexpression, excess Fe2+ production, ROS accumulation and GPX depletion, and ferroptosis. Furthermore, inhibition of MitoROS using Mito-TEMPO downregulated HIF-1α/HO-1 axis and mitigated the SHK-induced ferroptosis. In vivo, SHK effectively suppressed OS growth with favourable biosafety, confirming the molecular mechanism underlying SHK-induced ferroptosis in OS. ConclusionWe observe that HIF-1α/HO-1 axis is the crucial factor in SHK-induced OS ferroptosis. Importantly, we demonstrate that HIF-1α is indirectly regulated by MitoROS rather than SHK bound directly to HIF-1α. Our research suggest that SHK is a potential drug candidate for OS treatment and may help in identifying novel therapeutic targets for OS.

OTHR-16 UNVEILING THE GAMUT OF SKULL TUMORS: A CALL FOR COLLABORATIVE ONCOLOGICAL CARE IN SUB-SAHARAN AFRICA

Abstract INTRODUCTION Primary and metastatic tumours of the skull are relatively rare and have variable histological characteristics. They have been reported to represent 0.8 to 1% of all bone tumours and majority were malignant with attendant morbidity and mortality. With the current advances in neurosurgical techniques, neuroimaging and improvement in histopathological diagnosis more cases are expected to be diagnosed and treated successfully. Only few studies in literature focused on the profile and outcome of skull tumours especially in sub-Saharan Africa. This study aims to unravel the spectrum of skull tumors and describe the profile and outcome of management of skull tumours in our centre. METHODOLOGY We retrospectively reviewed cases of skull tumours managed in our centre between July 2015 to March 2024. Clinical parameters and histological diagnoses were noted. Data analysed using spss version 25.0 IBM. RESULTS We found 69 cases of skull tumours, 21 (30.4%) were benign and 48 (69.6%) were malignant. Majority (54/69, 78.2%) were males, the mean age of presentation was 28 and 50 years for benign and malignant tumours respectively. 95.6% of cases were adults. All benign tumours were osteoma, the commonest primary malignant tumour was osteosarcoma (9/48) followed by fibrosarcoma (6/48), while the most common histological subtype of metastatic tumours was adenocarcinoma. There were 4 cases of malignant sino-nasal tumours invading the frontal skull. Tumours were mostly located in the vault (66/69). All benign tumour had good post-operative recovery and malignant were managed in conjunction with plastic surgeons and radio-oncologist. No post-operative mortality recorded. CONCLUSION Majority of skull tumours were malignant and were seen in adult males, cranial vault was more affected compared to skull base. Synergy in oncological care will improve outcomes of care of malignant skull tumors.

Enzymatic TET-1 inhibition highlights different epigenetic behaviours of IL-1β and TNFα in tumour progression of OS cell lines

Osteosarcoma (OS) is the most frequent primary malignant bone tumour, whose heterogeneity represents a major challenge for common antitumour therapies. Inflammatory cytokines are known to be necessary for OS progression. Therefore, to optimise therapy, it is important to discover reliable biomarkers by identifying the mechanism generating OS and investigating the inflammatory pathways that support the undifferentiated state. In this work, we highlight the differences of epigenetic activities of IL-1β and TNFα, and the susceptibility of TET-1 enzymatic inhibition, in tumour progression of three different OS cell lines. Investigating DNA methylation of IL-6 promoter and determining its expression, we found that TET enzymatic inhibition influences proliferation induced by inflammatory cytokines in OS cell lines. Moreover, Bobcat 339 treatment blocks IL-1β epigenetic action on IL-6 promoter, while only partially those of TNFα as well as inhibits IL-1β-dependent epithelial–mesenchymal transition (EMT) process, but only partially those of TNFα. In conclusion, this work highlights that IL-1β and TNFα have different effects on DNA demethylation in OS cell lines, making DNA methylation a potential biomarker of disease. Specifically, in IL-1β treatment, TET-1 inhibition completely blocks tumour progression, while in TNFα actions, it is only partially effective. Given that these two inflammatory pathways can be therapeutic targets for treating these tumours, knowledge of their distinct epigenetic behaviours can be useful for developing precise and specific therapeutic strategies for this disease.

Metronomic chemotherapy for paediatric extracranial solid tumours: a systematic review and meta-analysis of randomised clinical trials

BackgroundMetronomic chemotherapy (‘less is more, regularly’) could be an alternative to the maximum tolerated dose (‘the more, the better’) in the chemotherapeutic cancer treatment of high-risk malignant solid extracranial tumours...

Pelvic Stress Fractures Following Resection and Reconstruction of Pelvis Tumours—An Observational Study

Background and Aims: Pelvic bone tumours are rare, with a guarded prognosis despite advances in radiological imaging and surgical techniques. Despite this, limb salvage surgery has become the mainstay treatment for patients presenting with primary bone sarcomas, especially those with low histological grade variants. However, the rate of peri-operative-associated complications remains high in the form of local recurrence and surgical site infections (SSI). Objective: We highlight our experience from a tertiary referral oncology centre of incidence and clinical and radiological features, as well as discuss the risk factors for developing pelvic stress fractures (PSFs) in patients treated with hemipelvis resection. Materials and Methods: We performed a retrospective search from our radiology and oncology database at our tertiary orthopaedic oncology referral centre for patients referred, diagnosed and managed for stress fractures following an internal hemipelvectomy for pelvic tumours/Sarcoma through the service between 2007 and 2019. Patient demographics, clinical characteristics, complementary imaging, clinical management outcome and peri-operative complications were documented. A focussed evaluation of patients diagnosed and managed for PSFs in patients treated with hemipelvis resection. Results: We identified a total of six patients with stress fractures following internal hemipelvectomy. The sacrum was the most common anatomical region ( n = 3). Other areas identified with insufficiency stress fractures included the ischium and femoral neck. Conclusion: Stress fractures post pelvis resection and reconstruction is a rare complication. Radiologists and orthopaedic oncology surgeons need to be aware of this complication to aid with an early diagnosis and initiate appropriate management.

Wrist fusion with ulnar translocation for aggressive giant cell tumour of distal end radius: Short-term functional and clinico-radiological outcomes

BackgroundThe distal end radius (DER) is the third most common site of a giant cell tumour (GCT) in bone. GCT is a locally aggressive benign tumour with metastatic potential. The main goals in the management of GCT of DER are the complete removal of the tumours, the prevention of recurrence, and the restoration of the functional wrist. PurposeThis case series reports the clinical and functional outcome of en bloc tumour resection, ulnar translocation and wrist arthrodesis in patients with high-grade GCT of DER. MethodsSixteen patients with Campanacci grade II & III GCT of distal end radius who underwent the procedure between 2009 and 2018 and had a follow-up of 2 years were included. Patients with distant metastasis, chronic severe systemic illness, operated previously, and follow-up dropouts were excluded from the study. The patient's demographic profile and tumour characteristics were collected at the initial visit. Grip strength, modified MAYO wrist score, and VAS score for wrist pain were collected preoperatively and at 1-year and 2-year follow-ups. ResultsThe study included predominantly females (13 vs 3). The mean age was 31.5 ± 8 years with a symptom duration of 6.5 ± 3.1 months (range 3–14). The mean resection length was 8.31 ± 1.5 cm (range 6–12). The mean Ulnoradial and ulnocarpal union time was 22.7 ± 8.0 and 17.5 ± 2.3 weeks, respectively. The mean modified Mayo Wrist score was 20.63 ± 9.4, 48.7 ± 5.6 and 60.6 ± 4.0 at preop, 1 year and 2 years follow-up. The mean MSTS score was 22.68 ± 1.8 (range 19–26). Two patients had ulnoradial nonunion. ConclusionWrist arthrodesis by ulnar translocation and plate fixation is a viable option in the management of GCT of distal end radius. The short-term clinical and functional outcomes are favourable for restoring adequate wrist function.