The Sarcoma Assessment Measure (SAM): Preliminary Psychometric Validation of a Novel Patient-Reported Outcome Measure.

The Sarcoma Assessment Measure (SAM) was developed as a sarcoma-specific patient-reported outcome measure to be used in clinical practice. We have reported in detail how SAM has been developed in collaboration with patients and healthcare professionals. The aim of this paper is to report the preliminary validation of SAM. The 22-item SAM was administered alongside a validated quality of life questionnaire and measure of activities of daily living. Linear modelling was used to build a measure, which had predictive validity in comparison to more established outcome measures. Of the 762 patients who participated in the study, 44.1% identified as male, and participant age ranged from 13 to 82 years. Clinically, participants presented with a range of soft tissue (82.2%) and bone (21.8%) sarcomas. Our preliminary analysis indicates that SAM accounts for 35% of the global quality of life scale and 18% of the Toronto Extremity Salvage Scale (TESS); so psychometrically, it overlaps with quality of life and activities of daily living, but also measures distinct concerns. This demonstrates that this measure picks up issues that are important to patients with sarcoma that are not reflected in other measures. We have established the preliminary validity of SAM and believe it has utility as a patient-reported outcome measure both as a research tool and for assessing the impact of symptoms and dysfunction related to sarcoma as part of clinical care. Further validation using a larger and more clinically diverse sample is now needed.

Feasibility of using low-cost markerless motion capture for assessing functional outcomes after lower extremity musculoskeletal cancer surgery.

BACKGROUND: Physical limitations are frequent and debilitating after sarcoma treatment. Markerless motion capture (MMC) could measure these limitations. Historically expensive cumbersome systems have posed barriers to clinical translation. RESEARCH QUESTION: Can inexpensive MMC [using Microsoft KinectTM] assess functional outcomes after sarcoma surgery, discriminate between tumour sub-groups and agree with existing assessments? METHODS: Walking, unilateral stance and kneeling were measured in a cross-sectional study of patients with lower extremity sarcomas using MMC and standard video. Summary measures of temporal, balance, gait and movement velocity were derived. Feasibility and early indicators of validity of MMC were explored by comparing MMC measures i) between tumour sub-groups; ii) against video and iii) with established sarcoma tools [Toronto Extremity Salvage Score (TESS)), Musculoskeletal Tumour Rating System (MSTS), Quality of life-cancer survivors (QoL-CS)]. Statistical analysis was conducted using SPSS v19. Tumour sub-groups were compared using Mann-Whitney U tests, MMC was compared to existing sarcoma measures using correlations and with video using Intraclass correlation coefficient agreement. RESULTS: Thirty-four adults of mean age 43 (minimum value-maximum value 19-89) years with musculoskeletal tumours in the femur (19), pelvis/hip (3), tibia (9), or ankle/foot (3) participated; 27 had limb sparing surgery and 7 amputation. MMC was well-tolerated and feasible to deliver. MMC discriminated between surgery groups for balance (p<0.05*), agreed with video for kneeling times [ICC = 0.742; p = 0.001*] and showed moderate relationships between MSTS and gait (p = 0.022*, r = -0.416); TESS and temporal outcomes (p = 0.016* and r = -0.0557*), movement velocity (p = 0.021*, r = -0.541); QoL-CS and balance (p = 0.027*, r = 0.441) [* = statistical significance]. As MMC uncovered important relationships between outcomes, it gave an insight into how functional impairments, balance, gait, disabilities and quality of life (QoL) are associated with each other. This gives an insight into mechanisms of poor outcomes, producing clinically useful data i.e. data which can inform clinical practice and guide the delivery of targeted rehabilitation. For example, patients presenting with poor balance in various activities can be prescribed with balance rehabilitation and those with difficulty in movements or activity transitions can be managed with exercises and training to improve the quality and efficiency of the movement. SIGNIFICANCE: In this first study world-wide, investigating the use of MMC after sarcoma surgery, MMC was found to be acceptable and feasible to assess functional outcomes in this cancer population. MMC demonstrated early indicators of validity and also provided new knowledge that functional impairments are related to balance during unilateral stance and kneeling, gait and movement velocity during kneeling and these outcomes in turn are related to disabilities and QoL. This highlighted important relationships between different functional outcomes and QoL, providing valuable information for delivering personalised rehabilitation. After completing future validation work in a larger study, this approach can offer promise in clinical settings. Low-cost MMC shows promise in assessing patient's impairments in the hospitals or their homes and guiding clinical management and targeted rehabilitation based on novel MMC outcomes affected, therefore providing an opportunity for delivering personalised exercise programmes and physiotherapy care delivery for this rare cancer.

A feasibility study into the use of the tilt table in the early postoperative rehabilitation of patients undergoing sacrectomy surgery with plastic reconstruction within the Orthopaedic Oncology Service.

PURPOSE: Standard post-operative care following sacrectomy requiring plastic surgical reconstruction limits hip flexion and avoids wound pressure. Extended bed rest adversely affects patient function, strength and range of movement. This feasibility study assessed whether early postoperative use of the tilt table was possible and promoted faster mobilisation. METHODS: Data from 10 patients were collected; five from a "standard tilt table group" and five from an "early tilt table group". Number of days post-operatively patients stood, walked, and were discharged was recorded. RESULTS: Patients had undergone partial or sub-total sacrectomy with wound closure using a variety of plastic surgical techniques. The "early tilt table" group started on the tilt table at 4.8 ± 2.8 days whereas the "standard tilt table" group started at 13 ± 5.1 days (p = 0.01*). Patients in the "early tilt table group" walked significantly earlier [10.6 ± 2.7*] than the standard group (28 ± 13) (p = 0.02*). LOS in the "early" group was 37.11 ± 11.9 days compared to 58.2 ± 21.8 days in the standard group (p = 0.10). No difference in complications between the groups. CONCLUSIONS: Early tilt table use after sacrectomy was safe and enabled a faster achievement of functional goals, thereby reducing LOS. This highlights the need for further evaluation of rehabilitation practice for this group of patients.IMPLICATIONS FOR REHABILITATIONMultidisciplinary discussion between the plastic surgeon, the tissue viability nurse and the physiotherapist about post-operative precautions and their impact on rehabilitation is essential and may enable earlier use of the tilt table.Early use of the tilt table can enable quicker mobilisation leading to the faster achievement of functional milestones and potentially a reduced length of stay (LOS) without detriment to patient outcomes/complications.The early use of the tilt table can support the central goal of surgery of enabling independence, especially as with such extensive surgery there is a big risk of institutionalisation and prolonged disability.There are potential mental health benefits to earlier mobilisation; however, this needs further investigation.

Antimicrobial prophylaxis with teicoplanin plus gentamicin in primary total joint arthroplasty.

Objectives: To compare prosthetic joint infection (PJI) and acute kidney injury (AKI) rates among cohorts before and after changing our hospital's antimicrobial prophylactic regimen from cefuroxime to teicoplanin plus gentamicin. Methods: We retrospectively studied all patients undergoing primary total joint arthroplasty at our hospital 18 months pre- and post-implementation of the change in practice. All deep infections identified during follow-up were assessed against the European Bone and Joint Infection Society (EBJIS) definitions for PJI. Survival analysis using Cox regression was employed to adjust for differences in baseline characteristics and compare the risk of PJI between the groups. AKIs were identified using pathology records and categorized according to the KDIGO (Kidney Disease - Improving Global Outcomes) criteria. AKI rates were calculated for the pre- and post-intervention periods. Results: Of 1994 evaluable patients, 1114 (55.9 %) received cefuroxime only (pre-intervention group) and 880 (44.1 %) patients received teicoplanin plus gentamicin (post-intervention group). The overall rate of PJI in our study was 1.50 % (30 of 1994), with a lower PJI rate in the post-intervention group (0.57 %; 5 of 880) compared with the pre-intervention group (2.24 %; 25 of 1114). A corresponding risk reduction for PJI of 75.2 % (95 % CI of 35.2-90.5; p=0.004) was seen in the post-intervention group, which was most pronounced for early-onset and delayed infections due to coagulase-negative staphylococci (CoNS) and cefuroxime-resistant Enterobacteriaceae. Significantly higher AKI rates were seen in the post-intervention group; however, 84 % of cases (32 of 38) were stage 1, and there were no differences in the rate of stage-2 or -3 AKI. Conclusions: Teicoplanin plus gentamicin was associated with a significant reduction in PJI rates compared with cefuroxime. Increases in stage-1 AKI were seen with teicoplanin plus gentamicin.

Patients' Experiences of a Sarcoma Diagnosis: A Process Mapping Exercise of Diagnostic Pathways.

Patients with sarcoma often report prolonged time to diagnosis, which is attributed to the rarity of sarcoma and the low awareness of pre-diagnostic signs and symptoms. AIMS: To describe patients' experiences of pre-diagnostic signs/symptoms and pathways to diagnosis, including where help was sought, and the processes involved. METHODS: Mixed methods involving quantitative, qualitative and inductive thematic analyses using novel process mapping of patient journey data, as reported by the patients. We examined the time from symptom onset to first professional presentation (patient interval, PI), first consultation to diagnostic biopsy, first consultation to diagnosis (diagnostic interval) and first presentation to diagnosis (total interval). RESULTS: A total of 87 interviews were conducted over 5 months in 2017. Of these, 78 (40 males/38 females) were included. The sarcoma subtypes were bone (n = 21), soft tissue (n = 41), head and neck (n = 9) and gastro-intestinal (GIST; n = 7). Age at diagnosis was 13-24 (n = 7), 25-39 (n = 23), 40-64 (n = 34) and 65+ (n = 14) years. The median PI was 13 days (1-4971) and similar between sarcoma subtypes, with the exception of GIST (mPI = 2 days, (1-60). The longest mPI (31 days, range 4-762) was for those aged 13-24 years. The median diagnostic interval was 87.5 (range 0-5474 days). A total of 21 patients were misdiagnosed prior to diagnosis and symptoms were commonly attributed to lifestyle factors. CONCLUSIONS: Prolonged times to diagnosis were experienced by the majority of patients in our sample. Further research into the evolution of pre-diagnostic sarcoma symptoms is required to inform awareness interventions.

Prophylactic antibiotics for massive endoprostheses in orthopaedic oncology.

The recently published Prophylactic Antibiotic Regimens In Tumor Surgery (PARITY) trial found no benefit in extending antibiotic prophylaxis from 24 hours to five days after endoprosthetic reconstruction for lower limb bone tumours. PARITY is the first randomized controlled trial in orthopaedic oncology and is a huge step forward in understanding antibiotic prophylaxis. However, significant gaps remain, including questions around antibiotic choice, particularly in the UK, where cephalosporins are avoided due to concerns of Clostridioides difficile infection. We present a review of the evidence for antibiotic choice, dosing, and timing, and a brief description of PARITY, its implication for practice, and the remaining gaps in our understanding.

Return to sports following lower limb musculoskeletal tumor surgery-A systematic review.

BACKGROUND: Survivors of primary malignant musculoskeletal tumors often face long-term disability. Clinicians at present are unable to provide evidence-based advice about returning to sports, which is important for active patients. PURPOSES: Identify patients returning to sports. Describe the sporting activities in which patients participate. Identify the outcome measures used to assess return to sport. Identify barriers preventing return to sports. STUDY DESIGN: Systematic review. METHODS: A comprehensive search strategy was used to identify relevant studies combining the following concepts: (1) Bone/Soft tissue tumor, (2) Lower limb, (3) Surgical interventions, and (4) Sports. Studies were selected according to eligibility criteria with the consensus of three authors (MTB, FS, and CG). RESULTS: Twenty-two studies were selected, published between 1985 and 2020, including 1005 patients. Fifteen of the 22 studies had valid data on return to sports, with 705 participants, of which 412 (58.4%) returned to some form of sport such as swimming and cycling, at a mean follow-up period of 7.6 years. Four studies directly compared limb sparing surgery and amputation; none of these were able to identify a difference in sports participation or ability. CONCLUSION: There is insufficient published research to provide guidance for patients with respect to return to sports following musculoskeletal tumors. Future prospective studies are needed to collect better pre- and post-treatment data at multiple time intervals. Validated clinical and patient sports participation outcomes such as type of sports, level, frequency, and validated sports-specific outcome scores should be recorded. In particular, more comparison between limb sparing surgery and amputation would be welcome.

Fear of Cancer Recurrence in Patients with Sarcoma in the United Kingdom.

Fear of cancer recurrence (FCR) is a persistent concern among those living with cancer and is associated with a variety of negative psychosocial outcomes. However, people with sarcoma have been underrepresented within this area of research. We aimed to determine the prevalence of FCR experienced by people with sarcoma in the United Kingdom and explore factors that may predict FCR, such as the perceived impact of cancer and psychological flexibility. Participants (n = 229) with soft tissue (n = 167), bone (n = 25), and gastrointestinal stromal tumours (n = 33) completed an online survey including the self-reported measures of FCR, the perceived physical and psychological impact of cancer and psychological flexibility, and demographic information. Data were analysed using ANOVA and multiple regression modelling. Mean FCR scores (M = 91.4; SD = 26.5) were higher than those reported in meta-analytic data inclusive of all cancer types (M = 65.2; SD = 28.2). Interest in receiving support for FCR was also high (70%). Significant factors associated with FCR included cognitive and emotional distress and psychological flexibility, but not perceptions of the physical impact of cancer (R2 = 0.56). The negative association between psychological flexibility and FCR suggests the potential benefit of intervention approaches which foster psychological flexibility, such as acceptance and commitment therapy.

Risk factors for recurrent infection in the surgical treatment of infected massive endoprostheses implanted for musculoskeletal tumours.

BACKGROUND: Infection is a devastating complication of endoprosthetic replacement (EPR) in orthopaedic oncology. Surgical treatments include debridement and/or one- or two-stage exchange. This study aims to determine the infection-free survival after surgical treatment for first and recurrent EPR infections and identify the risk factors associated with infection recurrence. METHODS: This single-centre cohort study included all patients with primary bone sarcomas or metastatic bone disease treated for infected EPR between 2010 and 2020. Variables included soft tissue status using McPherson classification, tumour type, silver coating, chemotherapy, previous surgery and microorganisms identified. Data for all previous infections were collected. Survival analysis, with time to recurrent infection following surgical treatment, was calculated at 1, 2 and 4 years. Cox regression analysis was used to assess the influence of different variables on recurrent infection. RESULTS: The cohort included 99 patients with a median age of 44 years (29-58 IQR) at the time of surgical treatment. The most common diagnoses were osteosarcoma and chondrosarcoma. One hundred and thirty-three surgical treatments for first or subsequent infections were performed. At 2 years of follow-up, overall success rates were as follows: two-stage exchange 55.3%, one-stage exchange 45.5%, DAIR with an exchange of modular components 44.6% and DAIR without exchange of modular components 24.7%. Fifty-one (52%) patients were infection-free at the most recent follow-up. Of the remaining 48 patients, 27 (27%) were on antibiotic suppression and 21 (21%) had undergone amputation. Significant risk factors for recurrent infection were the type of surgical treatment, with debridement alone as the highest risk (HR 4.75: 95%CI 2.43-9.30; P < 0.001); significantly compromised soft tissue status (HR 4.41: 95%CI 2.18-8.92; P = 0.001); and infections due to Enterococcus spp.. (HR 7.31: 95%CI 2.73-19.52); P = 0.01). CONCLUSIONS: Two-stage exchange with complete removal of all components where feasible is associated with the lowest risk of recurrent infection. Poor soft tissues and enterococcal infections are associated with higher risks of recurrent infection. Treatment demands an appropriate multidisciplinary approach. Patients should be counselled appropriately about the risk of recurrent infection before embarking on complex treatment.

Do frailty scores predict outcome after proximal femoral replacement for musculoskeletal tumours: a case series?

PURPOSE: Frailty has a negative independent relationship with morbidity and mortality. A frail individual has low resilience and adaptive capacity to stressors with unfavourable consequences. The relationship between musculoskeletal tumour patients undergoing surgery and frailty is underrepresented in literature. This study's questions are; what is the prevalence of frailty in patients undergoing surgery for musculoskeletal tumours; what is the correlation between frailty and survival plus secondary outcome measures including length of hospital stay (LOS); can clinicians use frailty scoring to support preoperative decision-making? METHODS: Patients over 60 years of age undergoing proximal femoral replacement for musculoskeletal tumours were included and classified as fit, vulnerable or frail using the modified frailty index (mFI), Rockwood and American Society of Anaesthesiologist's physical status classification (ASA) grading systems. Correlation with outcomes including survival and (LOS) was determined. RESULTS: 85 patients were identified of mean age 72.6 years. Median follow-up was 18.9 months. The prevalence of frailty ranged between 55 to 76% and the overall median survival in frail groups were 19.8 months with all scoring systems used. Frail patients classified by the Rockwood score had a greater LOS and a trend to reduced survival. CONCLUSIONS: There is a high prevalence of frailty in this cohort and frailty scores should be considered when planning surgery as part of holistic care. Moreover, a median survival greater than 18 months in frail patients supports the decision to offer surgery which may positively impact quality of life. Further research to identify the relationship between frailty and outcomes in musculoskeletal tumour patients is needed. LEVEL OF EVIDENCE: IV, Retrospective Case Series.

Free-living monitoring of ambulatory activity after treatments for lower extremity musculoskeletal cancers using an accelerometer-based wearable - a new paradigm to outcome assessment in musculoskeletal oncology?

PURPOSE: Ambulatory activity (walking) is affected after sarcoma surgery yet is not routinely assessed. Small inexpensive accelerometers could bridge the gap. Study objectives investigated, whether in patients with lower extremity musculoskeletal tumours: (A) it was feasible to conduct ambulatory activity assessments in patient's homes using an accelerometer-based wearable (AX3, Axivity). (B) AX3 assessments produced clinically useful data, distinguished tumour sub-groups and related to existing measures. METHODS: In a prospective cross-sectional pilot, 34 patients with musculoskeletal tumours in the femur/thigh (19), pelvis/hip (3), tibia/leg (9), or ankle/foot (3) participated. Twenty-seven had limb-sparing surgery and seven amputation. Patients were assessed using a thigh-worn monitor. Summary measures of volume (total steps/day, total ambulatory bouts/day, mean bout length), pattern (alpha), and variability (S2) of ambulatory activity were derived. RESULTS: AX3 was well-tolerated and feasible to use. Outcomes compared to literature but did not distinguish tumour sub-groups. Alpha negatively correlated with disability (walking outside (r=-418, p = 0.042*), social life (r=-0.512, p = 0.010*)). Disability negatively predicted alpha (unstandardised co-efficient= -0.001, R2=0.186, p = 0.039*). CONCLUSIONS: A wearable can assess novel attributes of walking; volume, pattern, and variability after sarcoma surgery. Such outcomes provide valuable information about people's physical performance in their homes, which can guide rehabilitation. Implications for rehabilitationRoutine capture of ambulatory activity by sarcoma services in peoples' homes can provide important information about individuals "actual" physical activity levels and limitations after sarcoma surgery to inform personalised rehabilitation and care needs, including timely referral for support.Routine remote ambulatory monitoring about out of hospital activity can support personalised care for patients, including identifying high risk patients who need rapid intervention and care closer to home.Use of routine remote ambulatory monitoring could enhance delivery of evidence-based care closer to peoples' homes without disrupting their daily routine and therefore reducing patient and carer burden.Collection of data close to home using questionnaires and objective community assessment could be more cost effective and comprehensive than in-hospital assessment and could reduce the need for hospital attendance, which is of importance to vulnerable patients, particularly during the Covid-19 pandemic.

Stable Cortical Body Maps Before and After Arm Amputation.

Neuroscientists have long debated the adult brain's capacity to reorganize itself in response to injury. A driving model for studying plasticity has been limb amputation. For decades, it was believed that amputation triggers large-scale reorganization of cortical body resources. However, these studies have relied on cross-sectional observations post-amputation, without directly tracking neural changes. Here, we longitudinally followed adult patients with planned arm amputations and measured hand and face representations, before and after amputation. By interrogating the representational structure elicited from movements of the hand (pre-amputation) and phantom hand (post-amputation), we demonstrate that hand representation is unaltered. Further, we observed no evidence for lower face (lip) reorganization into the deprived hand region. Collectively, our findings provide direct and decisive evidence that amputation does not trigger large-scale cortical reorganization.

A Qualitative Study of the Factors Influencing Patients' Experience of Soft Tissue Sarcoma in the United Kingdom.

BACKGROUND: Treatment of soft tissue sarcoma frequently involves extensive surgery, loss of mobility, and complex rehabilitation programs. Poorer patient-reported outcomes are reported in comparison to those from patients with other cancer types. Understanding patient experience is therefore important to support patients and improve care. OBJECTIVE: The aim of this study was an in-depth exploration of patients' experience of being diagnosed with soft tissue sarcoma. METHODS: Semistructured interviews and focus groups were conducted with 68 patients with soft tissue sarcoma (59% female; aged 23-82 years). These were analyzed using adapted framework analysis. RESULTS: Two overarching themes explained the factors influencing patients' experiences: individual and social factors to manage the impact of soft tissue sarcoma; and context and processes of care. Access to professionals with sarcoma expertise and services in specialist hospitals had an impact on patients' well-being. Lack of access to specialist services and coordinated care were associated with worse experiences. These were influenced by age and support from family/friends/other patients and were crucial in patients' adaptation to living with and beyond a sarcoma diagnosis. CONCLUSION: We describe factors that both negatively and positively influenced the experience of patients with soft tissue sarcoma. Access to specialist soft tissue sarcoma and rehabilitation services and support tailored to patients' age and disease trajectory are needed to improve these experiences. IMPLICATION FOR PRACTICE: Nurses are important for helping patients manage the long-term effects and directing them to supportive care services. Rehabilitation services need to be available and easily accessible.

Endoprosthetic replacement of the proximal tibia for oncological conditions.

AIMS: The proximal tibia (PT) is the anatomical site most frequently affected by primary bone tumours after the distal femur. Reconstruction of the PT remains challenging because of the poor soft-tissue cover and the need to reconstruct the extensor mechanism. Reconstructive techniques include implantation of massive endoprosthesis (megaprosthesis), osteoarticular allografts (OAs), or allograft-prosthesis composites (APCs). METHODS: This was a retrospective analysis of clinical data relating to patients who underwent proximal tibial arthroplasty in our regional bone tumour centre from 2010 to 2018. RESULTS: A total of 76 patients fulfilled the inclusion criteria and were included in the study. Mean age at surgery was 43.2 years (12 to 86 (SD 21)). The mean follow-up period was 60.1 months (5.4 to 353). In total 21 failures were identified, giving an overall failure rate of 27.6%. Prosthesis survival at five years was 75.5%, and at ten years was 59%. At last follow-up, mean knee flexion was 89.8° (SD 36°) with a mean extensor lag of 18.1° (SD 24°). In univariate analysis, factors associated with better survival of the prosthesis were a malignant or metastatic cancer diagnosis (versus benign), with a five- and ten-year survival of 78.9% and 65.7% versus 37.5% (p = 0.045), while in-hospital length of stay longer than nine days was also associated with better prognosis with five- and ten-year survival rates at 84% and 84% versus 60% and 16% (p < 0.001). In multivariate analysis, only in-hospital length of stay was associated with longer survival (hazard ratio (HR) 0.23, 95% confidence interval (CI) 0.08 to 0.66). CONCLUSION: We have shown that proximal tibial arthroplasty with endoprosthesis is a safe and reliable method for reconstruction in patients treated for orthopaedic oncological conditions. Either modular or custom implants in this series performed well.Cite this article: Bone Jt Open 2022;3(9):733-740.

A genetic model for central chondrosarcoma evolution correlates with patient outcome.

BACKGROUND: Central conventional chondrosarcoma (CS) is the most common subtype of primary malignant bone tumour in adults. Treatment options are usually limited to surgery, and prognosis is challenging. These tumours are characterised by the presence and absence of IDH1 and IDH2 mutations, and recently, TERT promoter alterations have been reported in around 20% of cases. The effect of these mutations on clinical outcome remains unclear. The purpose of this study was to determine if prognostic accuracy can be improved by the addition of genomic data, and specifically by examination of IDH1, IDH2, and TERT mutations. METHODS: In this study, we combined both archival samples and data sourced from the Genomics England 100,000 Genomes Project (n = 356). Mutations in IDH1, IDH2, and TERT were profiled using digital droplet PCR (n = 346), whole genome sequencing (n=68), or both (n = 64). Complex events and other genetic features were also examined, along with methylation array data (n = 84). We correlated clinical features and patient outcomes with our genetic findings. RESULTS: IDH2-mutant tumours occur in older patients and commonly present with high-grade or dedifferentiated disease. Notably, TERT mutations occur most frequently in IDH2-mutant tumours, although have no effect on survival in this group. In contrast, TERT mutations are rarer in IDH1-mutant tumours, yet they are associated with a less favourable outcome in this group. We also found that methylation profiles distinguish IDH1- from IDH2-mutant tumours. IDH wild-type tumours rarely exhibit TERT mutations and tend to be diagnosed in a younger population than those with tumours harbouring IDH1 and IDH2 mutations. A major genetic feature of this group is haploidisation and subsequent genome doubling. These tumours evolve less frequently to dedifferentiated disease and therefore constitute a lower risk group. CONCLUSIONS: Tumours with IDH1 or IDH2 mutations or those that are IDHwt have significantly different genetic pathways and outcomes in relation to TERT mutation. Diagnostic testing for IDH1, IDH2, and TERT mutations could therefore help to guide clinical monitoring and prognostication.

Osteosarcoma: Novel prognostic biomarkers using circulating and cell-free tumour DNA.

AIM: Osteosarcoma (OS) is the most common primary bone tumour in children and adolescents. Circulating free (cfDNA) and circulating tumour DNA (ctDNA) are promising biomarkers for disease surveillance and prognostication in several cancer types; however, few such studies are reported for OS. The purpose of this study was to discover and validate methylation-based biomarkers to detect plasma ctDNA in patients with OS and explore their utility as prognostic markers. METHODS: Candidate CpG markers were selected through analysis of methylation array data for OS, non-OS tumours and germline samples. Candidates were validated in two independent OS datasets (n = 162, n = 107) and the four top-performing markers were selected. Methylation-specific digital droplet PCR (ddPCR) assays were designed and experimentally validated in OS tumour samples (n = 20) and control plasma samples. Finally, ddPCR assays were applied to pre-operative plasma and where available post-operative plasma from 72 patients with OS, and findings correlated with outcome. RESULTS: Custom ddPCR assays detected ctDNA in 69% and 40% of pre-operative plasma samples (n = 72), based on thresholds of one or two positive markers respectively. ctDNA was detected in 5/17 (29%) post-operative plasma samples from patients, which in four cases were associated with or preceded disease relapse. Both pre-operative cfDNA levels and ctDNA detection independently correlated with overall survival (p = 0.0015 and p = 0.0096, respectively). CONCLUSION: Our findings illustrate the potential of mutation-independent methylation-based ctDNA assays for OS. This study lays the foundation for multi-institutional collaborative studies to explore the utility of plasma-derived biomarkers in the management of OS.

Predicting length of stay after proximal femoral endoprosthetic replacement for oncological conditions.

BACKGROUND: Endoprosthetic replacement of the proximal femur plays a vital role in managing metastatic and primary bone tumours1. Length of stay (LOS) has important resource implications but is driven by patient and disease factors over and above the procedure itself. The aim of this project was to identify factors that drive LOS in patients undergoing proximal femoral replacement (PFR). METHODS: This was a retrospective analysis of clinical records from a single centre (RNOH). 144 cases were identified over a 4 year-period. These were divided into 3 diagnostic categories: primary bone tumour with chemotherapy, primary bone tumour without chemotherapy and metastatic bone disease. Several factors were considered that could influence the length of stay including age, ASA grade, gender, admission to the high dependency unit (HDU), diagnosis, saving the greater trochanter, pre-operative radiotherapy, admission with a fracture and return to theatre. RESULTS: The median LOS for PFR was 15 days, with 79% admitted to HDU. LOS was almost doubled for patients returning to theatre (P = 0.04). Patients with ASA grades of 3 and 4 had a 75% longer LOS compared to those with grade 1. Additionally, a 10-year increase in age was associated with a 6-8% increase in LOS. Incorporating these factors produced a model which explained 27% of the variability of LOS. CONCLUSION: Majority of the variables which were tested were significantly associated with LOS. However, factors other than those in our model drive length of stay. This analysis can support conversations with patients and service planning around LOS.

Current approaches to management of bone sarcoma in adolescent and young adult patients.

Bone tumors are a group of histologically diverse diseases that occur across all ages. Two of the commonest, osteosarcoma (OS) and Ewing sarcoma (ES), are regarded as characteristic adolescent and young adult (AYA) cancers with an incidence peak in AYAs. They are curable for some but associated with unacceptably high rates of treatment failure and morbidity. The introduction of effective new therapeutics for bone sarcomas is slow, and to date, complex biology has been insufficiently characterized to allow more rapid therapeutic exploitation. This review focuses on current standards of care, recent advances that have or may soon change that standard of care and challenges to the expert clinical research community that we suggest must be met.

Development of a scoring system for survival following surgery for metastatic bone disease.

AIMS: The incidence of bone metastases is between 20% to 75% depending on the type of cancer. As treatment improves, the number of patients who need surgical intervention is increasing. Identifying patients with a shorter life expectancy would allow surgical intervention with more durable reconstructions to be targeted to those most likely to benefit. While previous scoring systems have focused on surgical and oncological factors, there is a need to consider comorbidities and the physiological state of the patient, as these will also affect outcome. The primary aim of this study was to create a scoring system to estimate survival time in patients with bony metastases and to determine which factors may adversely affect this. METHODS: This was a retrospective study which included all patients who had presented for surgery with metastatic bone disease. The data collected included patient, surgical, and oncological variables. Univariable and multivariable analysis identified which factors were associated with a survival time of less than six months and less than one year. A model to predict survival based on these factors was developed using Cox regression. RESULTS: A total of 164 patients were included with a median survival time of 1.6 years (interquartile range 0.5 to 3.1) after surgery. On multivariable analysis, a higher American Society of Anesthesiologists grade (p < 0.001), a high white cell count (p = 0.002), hyponatraemia (p = 0.001), a preoperative resting heart rate of > 100 bpm (p = 0.052), and the type of primary cancer (p = 0.026) remained significant predictors of reduced survival time. The predictive model developed showed good discrimination and calibration to predict both six- and 12-month survival in patients with metastatic bone disease. CONCLUSION: In addition to surgical and oncological factors, the level of comorbidity and physiological state of the patient has a significant impact on survival in patients with metastatic bone disease. These factors should be considered when assessing the appropriateness of surgical intervention. This is the first study to examine other patient factors alongside surgical and oncological data to identify a relationship between these and survival. Cite this article: Bone Joint J 2021;103-B(11):1725-1730.

Osteointegration of hydroxyapatite-coated collars in cemented massive endoprostheses following revision surgery.

AIMS: Hydroxyapatite (HA)-coated collars have been shown to reduce aseptic loosening of massive endoprostheses following primary surgery. Limited information exists about their effectiveness in revision surgery. The aim of this study was to radiologically assess osteointegration to HA-coated collars of cemented massive endoprostheses following revision surgery. METHODS: Retrospective review of osseointegration frequency, pattern, and timing to a specific HA-coated collar on massive endoprostheses used in revision surgery at our tertiary referral centre between 2010 to 2017 was undertaken. Osseointegration was radiologically classified on cases with a minimum follow-up of six months. RESULTS: In all, 39 patients underwent radiological review at mean 43.5 months; 22/39 (56.4%) showed no osseointegration to the collar. Revision endoprostheses for aseptic loosening were less likely to show osseointegration compared with other indications for revision. Oncological cases with previous or current infection were more likely to show osseointegration to ≥ 1 collar side than those without evidence of prior infection. CONCLUSION: This seven-year review identified osseointegration of HA-coated collars after revision surgery is less likely (43.6%, 17/39) than after primary surgery. Young patients who undergo revision surgery following initial oncological indication may benefit the most from this collar design. Use in revision oncological cases with a history of infection may be beneficial. HA-coated collars showed limited benefit for patients undergoing revision for failed arthroplasty with history of infection. Cite this article: Bone Jt Open 2021;2(6):371-379.