Controversies in orthopaedic oncology.

Chondrosarcoma is the second most common surgically treated primary bone sarcoma. Despite a large number of scientific papers in the literature, there is still significant controversy about diagnostics, treatment of the primary tumour, subtypes, and complications. Therefore, consensus on its day-to-day treatment decisions is needed. In January 2024, the Birmingham Orthopaedic Oncology Meeting (BOOM) attempted to gain global consensus from 300 delegates from over 50 countries. The meeting focused on these critical areas and aimed to generate consensus statements based on evidence amalgamation and expert opinion from diverse geographical regions. In parallel, periprosthetic joint infection (PJI) in oncological reconstructions poses unique challenges due to factors such as adjuvant treatments, large exposures, and the complexity of surgery. The meeting debated two-stage revisions, antibiotic prophylaxis, managing acute PJI in patients undergoing chemotherapy, and defining the best strategies for wound management and allograft reconstruction. The objectives of the meeting extended beyond resolving immediate controversies. It sought to foster global collaboration among specialists attending the meeting, and to encourage future research projects to address unsolved dilemmas. By highlighting areas of disagreement and promoting collaborative research endeavours, this initiative aims to enhance treatment standards and potentially improve outcomes for patients globally. This paper sets out some of the controversies and questions that were debated in the meeting.

High accuracy of positioning custom triflange acetabular components in tumour and total hip arthroplasty revision surgery.

Aims: Custom triflange acetabular components (CTACs) play an important role in reconstructive orthopaedic surgery, particularly in revision total hip arthroplasty (rTHA) and pelvic tumour resection procedures. Accurate CTAC positioning is essential to successful surgical outcomes. While prior studies have explored CTAC positioning in rTHA, research focusing on tumour cases and implant flange positioning precision remains limited. Additionally, the impact of intraoperative navigation on positioning accuracy warrants further investigation. This study assesses CTAC positioning accuracy in tumour resection and rTHA cases, focusing on the differences between preoperative planning and postoperative implant positions. Methods: A multicentre observational cohort study in Australia between February 2017 and March 2021 included consecutive patients undergoing acetabular reconstruction with CTACs in rTHA (Paprosky 3A/3B defects) or tumour resection (including Enneking P2 peri-acetabular area). Of 103 eligible patients (104 hips), 34 patients (35 hips) were analyzed. Results: CTAC positioning was generally accurate, with minor deviations in cup inclination (mean 2.7°; SD 2.84°), anteversion (mean 3.6°; SD 5.04°), and rotation (mean 2.1°; SD 2.47°). Deviation of the hip centre of rotation (COR) showed a mean vector length of 5.9 mm (SD 7.24). Flange positions showed small deviations, with the ischial flange exhibiting the largest deviation (mean vector length of 7.0 mm; SD 8.65). Overall, 83% of the implants were accurately positioned, with 17% exceeding malpositioning thresholds. CTACs used in tumour resections exhibited higher positioning accuracy than rTHA cases, with significant differences in inclination (1.5° for tumour vs 3.4° for rTHA) and rotation (1.3° for tumour vs 2.4° for rTHA). The use of intraoperative navigation appeared to enhance positioning accuracy, but this did not reach statistical significance. Conclusion: This study demonstrates favourable CTAC positioning accuracy, with potential for improved accuracy through intraoperative navigation. Further research is needed to understand the implications of positioning accuracy on implant performance and long-term survival.

A complicated Chiari type 1 malformation and holocord syrinx as a likely cause for heel pain.

BACKGROUND: Chiari malformations are a rare group of rhomboencephalic abnormalities involving the brain, craniocervical junction and spine. They may manifest in a variety of clinical presentations which relate to the variable involvement of the cerebellum, brainstem, lower cranial nerves, spinal cord and altered CSF flow dynamics. METHOD: We report an unusual case of incidental diagnosis of a type I Chiari malformation with secondary cystic cerebellar tonsillar encephalomalacia and holocord syrinx following investigation of a 5YO girl presenting with heel swelling related to progressive neuropathic osteoarthropathy of the posterior calcaneal body and apophysis. RESULT: The child was treated with decompressive suboccipital craniectomy and C1 laminectomy and tonsillar resection. Cerebellar tonsillar gliosis and cystic degeneration were confirmed on histopathology. Referral for ongoing engagement with occupational and physical therapy. CONCLUSION: Most type I Chiari malformations in the paediatric population are incidental and asymptomatic. Neurological symptoms are typically mild and relate to altered CSF flow dynamics; however, we present a complex case of type I Chiari malformation with an unusual constellation of associated complications.

Managing patients with advanced soft tissue sarcoma: Evolving landscape from an Australian perspective.

AIM: Despite lack of advances in the first-line systemic therapy, the overall survival (OS) has continued to improve in patients with advanced soft tissue sarcoma (STS) with the recent estimation of median OS at 20 months. Several systemic therapy options are available now for the second-line and beyond, with more treatment tailored to histology and molecular subtype. The aim of this retrospective study was to characterize current patterns of care in managing patients with advanced STS (aSTS) in Australia. METHODS: Sarcoma databases from 7 Australian sarcoma services were accessed to identify patients diagnosed with locally advanced inoperable and/or metastatic STS between January 1, 2010 and December 31, 2015. Baseline clinicopathological factors and initial treatment patterns were descriptively analyzed. For the Victorian cohort where treatment of aSTS and follow-up details were available, further exploratory analysis was conducted to determine the impact of patient and tumor characteristics and the use of palliative-intent treatment OS. RESULTS: Of 2261 cases of STS, 671 were deemed as aSTS. Two thirds were relapsed disease with a mean 1.9 years from initial diagnosis. Median age at diagnosis of aSTS was 59 years (18-95 years) and 56.3% was male. Histology classification revealed four main subtypes: undifferentiated pleomorphic sarcoma (UPS) (23.1%), leiomyosarcoma (18.2%), liposarcoma (12.8%), synovial sarcoma (8.2%), and other comprising 14 STS subtypes. For the Victorian cohort (N = 361), approximately 80% of patients accessed palliative-intent treatment of various modalities. Nearly 40% of patients underwent tumor-debulking surgery or metastasectomy, of which lung wedge resection was the most common (N = 83, 47.7%). A total of 438 palliative-intent radiotherapy treatments were delivered to 259 patients (71.7%), with the majority in the form of external beam radiotherapy. Palliative-intent systemic therapy was delivered to 51.5% of patients (N = 186), mostly (73%). Anthracycline-based therapy was the most commonly delivered therapy (N = 135, 72.6%). Approximately half of the patients in each line of therapy failed to proceed to the subsequent line of systemic therapy with 29.4% receiving three or more lines of therapy (N = 55). A total of 18.3% of patient (N = 34) participated in clinical trials or accessed off-label drugs. The median OS for the Victoria cohort was 15.4 months (95% confidence interval: 12.1, 18.2). The UPS histology subtype was associated with poorer OS, whereas receiving any modality of palliative-intent treatment conferred survival benefit. CONCLUSION: In Australia, aSTS is managed with diverse treatment approaches comprising various therapy modalities. Further work is planned in describing healthcare resource utilization and estimating costs by this patient cohort.

"We're on a Merry-Go-Round": Reflections of Patients and Carers after Completing Treatment for Sarcoma.

Sarcoma is a rare cancer that has a significant impact on patients' and carers' quality of life. Despite this, there has been a paucity of research exploring the diverse experiences of patients and carers following sarcoma treatment. The aim of this study was to explore patients' and carers' reflections on life after treatment for sarcoma. A qualitative research design with a social constructionist epistemology was used. Participants included patients previously treated for sarcoma (n = 21) and family carers of patients treated for sarcoma (n = 16). Participants completed semi-structured interviews which were analysed using thematic analysis. Three primary themes were identified: "This journey is never going to be over", "But what happens when I am better?", and finding a silver lining. Participants represented sarcoma as having a long-term, and sometimes indefinite, threat on their life that they had limited control over. Conclusions: This study highlight the heterogeneous and ongoing needs of sarcoma survivors and their families. Patients and carers strove to translate their experiences in a meaningful way, such as by improving outcomes for other people affected by sarcoma. Parental carers in particular attempted to protect the patient from the ongoing stress of managing the disease.

Additive manufacturing of porous titanium metaphyseal components: Early osseointegration and implant stability in revision knee arthroplasty.

AIMS: Metaphyseal cones and sleeves are components used in revision knee arthroplasty to ensure load transfer, encourage bone on-growth and prevent stress shielding. Additive manufacturing of titanium alloy implants is a novel technique with limited clinical outcome reports in the literature. The aim of this study was to determine radiographic evidence of osseointegration and early results of a single manufacturer porous titanium metaphyseal components in the proximal tibia. METHODS: We retrospectively reviewed the prospectively collected database of two institutions. Patients who underwent revision knee arthroplasty using porous titanium components by a single manufacturer were identified. Immediate post-operative and latest follow-up radiographs were independently analysed by 2 reviewers to determine metaphyseal bone contact and level of osseointegration in relevant Knee Society Radiographic Evaluation and Scoring System zones. RESULTS: 22 patients (15 males; 7 females) with a mean age of 71 (49-92) years were included. The mean follow-up period was 14 months (2-44 months). Cones were used in 16 patients and sleeves in 6. Interobserver reliability assessment showed substantial agreement (weighted Kappa 0.71, (95% CI: 0.60, 0.81). There was significant correlation between the bone contact in the immediate postop radiograph and osseointegration at final follow-up (kendall's tau-b: 0.698, p < 0.001). Infection free prosthetic joint survival was 20/22 at final follow-up. CONCLUSION: Porous titanium metaphyseal components produced with additive manufacturing provided excellent osseointegration and no early clinical failures. Partial or complete contact of the cone with native bone in the immediate postoperative radiograph resulted in osseointegration in all cases.

The unmet needs of carers of patients diagnosed with sarcoma: A qualitative study.

OBJECTIVE: Sarcoma is a rare cancer that may result in reduced mobility, social isolation, poorer mental health, and ongoing medical issues for patients. Family carers play a crucial role in supporting patients throughout their sarcoma journey. Despite the aggressive and debilitating nature of the disease, the unmet needs of these carers are yet to be explored. The aim of this study was to explore the unmet needs of carers of patients diagnosed with sarcoma. METHODS: An exploratory qualitative research design with a social constructionist epistemology was used. Participants were carers of patients diagnosed with a sarcoma (n = 33). Semi-structured interviews were conducted with carers of patients who completed treatment for sarcoma and also bereaved carers (BC). Interviews were transcribed verbatim and analysed using thematic analysis. FINDINGS: Four overarching themes were identified: support with medical aspects of caregiving, support for self, needing information about the patient, and financial support. Participants recognised that they needed psychosocial support, however, many were reluctant to access support as they perceived this to be prioritising their own needs instead of the patients'. They also needed more information about the patients' disease and how to navigate the health system. CONCLUSIONS: Family carers for patients with sarcoma have onerous responsibilities that affect their ability to access care for themselves and their family. Providing more holistic patient care and carer-specific information and training could reduce carer burden. Establishing support groups specific to carers and BC of patients diagnosed with sarcoma could provide opportunities for social interaction and psychosocial support.

Treatment and outcomes for synovial sarcoma patients in Western Australia: the role of neoadjuvant chemoradiotherapy.

BACKGROUND: This is a retrospective review of synovial sarcoma (SS) patients treated over the last 12 years in Western Australia (WA). SS is both chemo and radiotherapy sensitive. Results of trials in adjuvant chemotherapy are conflicting and there is limited support for neoadjuvant chemotherapy. The use of combined chemoradiotherapy is based on institutional preferences. AIM: We reviewed the outcomes for SS patients treated in WA over a 12 year period focusing on patients who received neoadjuvant chemoradiotherapy (NACRT). METHODS: Patient details including demographics, histopathology, treatment details, were obtained from the WA sarcoma database (2006-2018). Progression free survival (PFS) and overall survival (OS) were derived for whole cohort. RESULTS: Twenty seven patients were identified with SS with equal gender incidence. Median age of the cohort was 36 (14-76) years. The most common primary site of disease was extremity (81.5%). 22/27 patients presented with only localized disease and 59.2% of these received neo-adjuvant treatment. Of those who received neoadjuvant treatment, 56.2% had NACRT, while 25.0% and 18.7% of patients had chemotherapy and radiotherapy respectively. Mesna, doxorubicin, ifosfamide, dacarbazine (MAID) was the most commonly used chemotherapy regimen as neoadjuvant or adjuvant treatment while ifosfamide (93.7%) was the most commonly used chemotherapy drug in any setting. There was no reported case of disease progression in group of patients who received NACRT apart from one patient who had oligometastatic disease at diagnosis. Median OS of the whole cohort was 38 months while median PFS was 24 months. Bone marrow toxicity was the most commonly reported high grade toxicity in NACRT group (55.5%) but there were no treatment related deaths. CONCLUSION: NACRT is not widely adopted and treatment is based on institutional preferences, however our data shows that NACRT is a feasible therapy option. NACRT should be evaluated prospectively in a randomized trial.

The complexity of diagnosing sarcoma in a timely manner: perspectives of health professionals, patients, and carers in Australia.

BACKGROUND: Prolonged diagnosis intervals occur more often in rare cancers, such as sarcoma. Patients with a delayed diagnosis may require more radical surgery and have a reduced chance of survival. Previous research has focused on quantifying the time taken to achieve a diagnosis without exploring the reasons for potential delays. The aim of this study was to explore patients', carers', and health professionals' perceived barriers to timely diagnosis and referral for treatment for sarcoma. METHODS: Semi-structured interviews were conducted with: health professionals working with sarcoma (n = 21); patients who have been diagnosed with sarcoma (n = 22); and carers of patients diagnosed with sarcoma (n = 17). Interview transcripts were analysed using thematic analysis. RESULTS: Four overarching themes were identified: patient perception of symptoms, difficulties of diagnosis, lack of experience, and availability of health services. Diagnosis was prolonged by the limited availability of health services, lack of prompt referrals to a sarcoma specialist centre, and diagnostic challenges. Intervals also occurred when patients underestimated the severity of their symptoms and did not seek prompt medical consultation. CONCLUSIONS: Patients with a potential sarcoma need to be promptly referred to a sarcoma specialist centre and additional diagnosis pathways need to be developed to reduce the rate of patients being referred to wrong specialists. Sarcoma education must be embedded in medical courses and professional development curricula. A public health approach should be taken to improve sarcoma knowledge and health seeking behaviours in the community.

Sarcoma epidemiology and cancer-related hospitalisation in Western Australia from 1982 to 2016: a descriptive study using linked administrative data.

BACKGROUND: Sarcomas are a heterogeneous group of malignancies arising from mesenchymal cells. Epidemiological studies on sarcoma from Australia are lacking, as previous studies have focused on a sarcoma type (e.g. soft tissue) or anatomical sites. METHODS: Linked cancer registry, hospital morbidity and death registration data were available for Western Australia (WA) from 1982 to 2016. All new sarcoma cases among WA residents were included to estimate incidence, prevalence, relative survival and cancer-related hospitalisation, using the Information Network on Rare Cancers (RARECARENet) definitions. To provide a reference point, comparisons were made with female breast, colorectal, prostate and lung cancers. RESULTS: For 2012-16, the combined sarcoma crude annual incidence was 7.3 per 100,000, with the majority of these soft tissue sarcoma (STS, incidence of 5.9 per 100,000). The age-standardised incidence and prevalence of STS increased over time, while bone sarcoma remained more stable. Five-year relative survival for the period 2012-16 for STS was 65% for STS (higher than lung cancer, but lower than prostate, female breast and colorectal cancers), while five-year relative survival was 71% for bone sarcoma. Cancer-related hospitalisations cost an estimated $(Australian) 29.1 million over the study period. CONCLUSIONS: STS incidence has increased over time in WA, with an increasing proportion of people diagnosed aged ≥65 years. The analysis of health service use showed sarcoma had a lower mean episode of cancer-related hospitalisation compared to the reference cancers in 2016, but the mean cost per prevalent person was higher for sarcoma than for female breast, colorectal and prostate cancers.

The unmet needs of patients with sarcoma.

OBJECTIVE: Sarcoma is a rare cancer that imposes a significant burden on the lives of patients. Many survivors have long-term disability as a result of treatment and the disease. Patients often experience functional issues, poorer mental health, reduced quality of life, and interpersonal issues. There is a need to explore the unmet needs of sarcoma patients as it is unclear how these issues are being addressed. The aim of this study was to explore the unmet needs of patients who have been diagnosed with sarcoma. METHODS: The participants were individuals previously diagnosed with a sarcoma (n = 22). Participants completed a semi-structured interview about their unmet needs relating to sarcoma. The transcripts were analyzed using thematic analysis. RESULTS: Five overarching themes were identified: daily living, financial needs, lack of information, need for a community, and navigating the healthcare system. Participants reported a range of practical needs, including transport, limited understanding of their treatments, and financial issues. Participants also described a need to connect with people who had gone through similar experiences. CONCLUSIONS: Sarcoma patients have fundamental needs that affect their capacity to live their life in the best possible way. Health services need to better facilitate sarcoma patients at each stage of their experience by providing individualized referrals, support, and coordination. Support interventions are needed to help patients adjust to sarcoma and to improve their quality of life as an outpatient. Connecting patients with sarcoma support groups may provide them with more relevant and intimate support.

Horizontal fissuring at the osteochondral interface: a novel and unique pathological feature in patients with obesity-related osteoarthritis.

OBJECTIVES: Obesity is a well-recognised risk factor for osteoarthritis (OA). Our aim is to characterise body mass index (BMI)-associated pathological changes in the osteochondral unit and determine if obesity is the major causal antecedent of early joint replacement in patients with OA. METHODS: We analysed the correlation between BMI and the age at which patients undergo total knee replacement (TKR) in 41 023 patients from the Australian Orthopaedic Association National Joint Replacement Registry. We then investigated the effect of BMI on pathological changes of the tibia plateau of knee joint in a representative subset of the registry. RESULTS: 57.58% of patients in Australia who had TKR were obese. Patients with overweight, obese class I & II or obese class III received a TKR 1.89, 4.48 and 8.08 years earlier than patients with normal weight, respectively. Microscopic examination revealed that horizontal fissuring at the osteochondral interface was the major pathological feature of obesity-related OA. The frequency of horizontal fissure was strongly associated with increased BMI in the predominant compartment. An increase in one unit of BMI (1 kg/m2) increased the odds of horizontal fissures by 14.7%. 84.4% of the horizontal fissures were attributable to obesity. Reduced cartilage degradation and alteration of subchondral bone microstructure were also associated with increased BMI. CONCLUSIONS: The key pathological feature in OA patients with obesity is horizontal fissuring at the osteochondral unit interface. Obesity is strongly associated with a younger age of first TKR, which may be a result of horizontal fissures.

A novel scoring system to guide prognosis in patients with pathological fractures.

BACKGROUND: The most appropriate treatment of pathological fractures from metastatic disease depends on several factors, one of the most important being predicted life expectancy. The aim of this study was to identify the variables that influence prognosis and utilise these to develop a novel scoring system to better predict life expectancy post-pathological fracture. METHODS: The records of all patients that presented with metastatic pathological fractures over a 10-year period from the only tertiary orthopaedic departments in Western Australia were retrospectively examined. Variables assessed were primary cancer type, fracture site, fixation method, cement augmentation, pre-morbid level of physical functioning, complication rate, treatment with chemotherapy or radiotherapy and appendicular, spinal and visceral metastatic load. RESULTS: A total of 233 patients were included. Median survival from fracture to death was 4.1 months. Median time from cancer diagnosis to pathological fracture was 14.2 months. There was a statistically significant association between patient survival and primary cancer type, physical functional score, spinal metastatic burden and use of chemotherapy or radiotherapy. CONCLUSION: A novel scoring system has been developed that offers a survival probability based on patient's individual circumstances. This can guide specialist management and offer patients a more accurate expectation of functional outcome and survival time.

The use of whole exome sequencing and murine patient derived xenografts as a method of chemosensitivity testing in sarcoma.

BACKGROUND: Soft tissue and bone sarcoma represent a broad spectrum of different pathology and genetic variance. Current chemotherapy regimens are derived from randomised trials and represent empirical treatment. Chemosensitivity testing and whole exome sequencing (WES) may offer personalized chemotherapy treatment based on genetic mutations. METHODS: A pilot, prospective, non-randomised control experimental study was conducted. Twelve patients with metastatic bone or soft tissue sarcoma that had failed first line chemotherapy treatment were enrolled for this study. Human tissue taken at surgical biopsy under general anaesthetic was divided between two arms of the trial. Subsections of the tumour were used for WES and the remainder was implanted subcutaneously in immunodeficient mice (PDX). Results of WES were analysed using a bioinformatics pipeline to identify mutations conferring susceptibility to kinase inhibitors and common chemotherapeutic agents. PDX models exhibiting successful growth underwent WES of the tumour and subsequent chemosensitivity testing. RESULTS: WES was successful in all 12 patients, with successful establishment PDX tumours models in seven patients. WES identified potential actionable therapeutics in all patients. Significant variation in predicted therapeutics was demonstrated between three PDX samples and their matched tumour samples. CONCLUSION: Analysis of WES of fresh tumour specimens via a bioinformatics pipeline may identify potential actionable chemotherapy agents. Further research into this field may lead to the development of personalized cancer therapy for sarcoma.

Strength and functional symmetry is associated with post-operative rehabilitation in patients following anterior cruciate ligament reconstruction.

PURPOSE: To investigate strength and functional symmetry during common tests in patients after anterior cruciate ligament reconstruction (ACLR), and its association with post-operative rehabilitation. METHODS: At a median 11.0 months post-surgery (range 10-14), 111 ACLR patients were assessed. A rehabilitation grading tool was employed to evaluate the duration and supervision of rehabilitation, as well as whether structured jumping, landing and agility exercises were undertaken. Patients completed the Noyes Activity Score (NSARS), maximal isokinetic knee extensor and flexor strength assessment, and a 4-hop test battery. Limb Symmetry Indices (LSIs) were calculated, presented for the entire group and also stratified by activity level. ANOVA evaluated differences between the operated and unaffected limbs across all tests. Correlations were undertaken to assess the relationship between post-operative rehabilitation and objective test LSIs. RESULTS: The unaffected limb was significantly better (p < 0.0001) than the operated limb for all tests. Only 52-61 patients (47-55%) demonstrated LSIs ≥ 90% for each of the hop tests. Only 34 (30.6%) and 61 (55.0%) patients were ≥ 90% LSI for peak quadriceps and hamstring strength, respectively. Specifically in patients actively participating in jumping, pivoting, cutting, twisting and/or turning sports, 21 patients (36.8%) still demonstrated an LSI < 90% for the single hop for distance, with 37 patients (65.0%) at < 90% for peak knee extension strength. Rehabilitation was significantly associated with the LSIs for all tests. CONCLUSION: Rehabilitation was significantly correlated with limb symmetry, and lower limb symmetry was below recommended criterion for many community-level ACLR patients, including those already engaging in riskier activities. It is clear that many patients are not undertaking the rehabilitation required to address post-operative strength and functional deficits, and are being cleared to return to sport (or are returning on their own accord) without appropriate evaluation and further guidance. LEVEL OF EVIDENCE: IV.

Plexiform neurofibroma causing an ossifying subperiosteal haematoma: a rare case in the tibia of an 11-year-old girl.

Ossifying subperiosteal haematoma is an exceedingly rare manifestation of Neurofibromatosis type 1 (NF-1). We report an interesting case of plexiform neurofibroma causing a rapidly growing tibial mass as a result of subperiosteal haemorrhage, in an 11-year-old girl with previously undiagnosed NF-1. This reflects a precursor of the more mature periosteal ossification seen in cases traditionally termed "subperiosteal cysts". A previously well young girl was referred by her general practitioner with an increasingly large, mildly tender, soft lump on the anterior aspect of her right tibia. Plain radiographs demonstrated soft tissue thickening overlying the anterior tibia, without appreciable periosteal ossification. Magnetic resonance imaging (MRI) illustrated a single central fluid-fluid level and periosteal elevation with saucerisation of the anterior tibial cortex and mild surrounding oedema. Histopathology revealed a large plexiform neurofibroma. Interestingly, this was associated with haemorrhagic change and a peripheral rim of florid reactive new bone formation. This unusual presentation was discussed at a multidisciplinary bone and soft tissue tumour meeting, where in combination with the clinical history of café au lait spots and positive family history, a consensus diagnosis of NF-1 was made. To date, there have only been limited case reports of this rare pathological process. In summary, this case report accounts an acute presentation of this rare osseous manifestation of NF-1, being the first to clearly demonstrate a timeline of subperiosteal haematoma with subsequent subperiosteal bone proliferation. The clinical reasoning and radiological features for such a presentation are also described.

Patterns of care for patients with advanced soft tissue sarcoma: experience from Australian sarcoma services.

BACKGROUND: There is a paucity of data on the current management of patients with advanced soft tissue sarcoma (STS) in the Australian health care setting. This study utilised the Australian sarcoma database to evaluate the patterns of care delivered to patients with advanced STS at Australian sarcoma services. METHODS: Prospectively collected data from six sarcoma centres in Australia were sourced to identify patients diagnosed with advanced STS between 1 January 2010 and 31 December 2012. Descriptive statistics were analysed for patient demographics, clinicopathological characteristics and treatment patterns. Overall survival was estimated using the Kaplan-Meier product limit method. RESULTS: Of 253 patients with advanced STS, four major STS subtypes were identified: undifferentiated pleomorphic sarcoma (23 %), leiomyosarcoma (17 %), liposarcoma (14 %), and synovial sarcoma (8 %); with the rest grouped as "other STS" (38 %). Approximately one-third of patients received palliative systemic therapy with the most common first-line therapy being doxorubicin alone (50 %). A small percentage of patients participated in clinical trials (20 %). Palliative radiotherapy was utilised mostly for treatment of symptomatic distant metastases and one-third of patients underwent metastasectomy, most commonly for pulmonary metastases. The median overall survival (OS) in this series was 18 months and no significant difference in OS was observed across different STS histological subtypes. CONCLUSIONS: This is the first detailed study outlining patterns of care for Australian patients with advanced STS managed at sarcoma services. These data highlight a particular area of weakness in the lack of clinical trials for sarcoma patients and also serve as an important reference point for understanding how practice may change over time as treatment options evolve.

Treatment of Articular Cartilage Defects With Microfracture and Autologous Matrix-Induced Chondrogenesis Leads to Extensive Subchondral Bone Cyst Formation in a Sheep Model.

BACKGROUND: Microfracture and the autologous matrix-induced chondrogenesis (AMIC) technique are popular for the treatment of articular cartilage defects. However, breaching of the subchondral bone plate could compromise the subchondral bone structure. HYPOTHESIS: Microfracture and AMIC will cause deleterious effects on the subchondral bone structure. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 36 sheep received an 8-mm-diameter cartilage defect in the left medial femoral condyle. Control animals (n = 12) received no further treatment, and the rest received 5 microfracture holes either with a type I/III collagen scaffold implanted (n = 12; AMIC group) or without the collagen scaffold (n = 12; microfracture group). Macroscopic infill of defects, histology, and histomorphometry of the subchondral bone were performed at 13 and 26 weeks postoperatively, and micro-computed tomography (CT) was also performed at 26 weeks postoperatively. RESULTS: Microfracture and AMIC resulted in subchondral bone cyst formation in 5 of 12 (42%) and 11 of 12 (92%) specimens at 13 and 26 weeks, respectively. Subchondral bone changes induced by microfracture and AMIC were characterized by an increased percentage of bone volume, increased trabecular thickness, and a decreased trabecular separation, and extended beyond the area below the defect. High numbers of osteoclasts were observed at the cyst periphery, and all cysts communicated with the microfracture holes. Cartilage repair tissue was of poor quality and quantity at both time points and rarely reached the tidemark at 13 weeks. CONCLUSION: Microfracture technique caused bone cyst formation and induced severe pathology of the subchondral bone in a sheep model. CLINICAL RELEVANCE: The potential of microfracture technique to induce subchondral bone pathology should be considered.

MDM2/CDK4 gene amplification in large/deep-seated 'lipomas': incidence, predictors and clinical significance.

This study of 140 cases assessed the incidence of MDM2/CDK4 gene amplification in lipomatous neoplasms with histological features of a lipoma but which were of clinical concern due to large size (≥50 mm) and/or deep-seated (subfascial) location. Univariate and multivariate statistical analyses were used to identify clinical, radiological and pathological predictors of gene amplification. Differences in local recurrence rates between amplified and non-amplified cases were assessed using survival analysis. The findings indicate that the incidence of MDM2/CDK4 amplification in this setting is low at 5% (95%CI 1.4-8.6%). Variables associated with amplification on univariate analysis were tumour site (thigh, p = 0.004), size (>100 mm, p = 0.033) and presence of equivocal atypia (p = 0.001). Independent predictors on multivariate analysis were size (OR 3.9, 95%CI 1.4-11.3, p = 0.012) and presence of equivocal atypia (OR 12.5, 95%CI 1.9-80.3, p = 0.008). There was no significant difference in local recurrence rates between amplified and non-amplified cases (p = 0.461) based on a median follow-up time of 31 months. Assessment for MDM2/CDK4 amplification, therefore, should be considered in 'lipomas' which are >100 mm in size, show equivocal atypia and arise in the thigh. However, the clinical significance of gene amplification in this setting is unclear and requires confirmation in larger studies.