Aims

For rare cases when a tumour infiltrates into the hip joint, extra-articular resection is required to obtain a safe margin. Endoprosthetic reconstruction following tumour resection can effectively ensure local control and improve postoperative function. However, maximizing bone preservation without compromising surgical margin remains a challenge for surgeons due to the complexity of the procedure. The purpose of the current study was to report clinical outcomes of patients who underwent extra-articular resection of the hip joint using a custom-made osteotomy guide and 3D-printed endoprosthesis.

Aims

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.

Aims

Treatment of high-grade limb bone sarcoma that invades a joint requires en bloc extra-articular excision. MRI can demonstrate joint invasion but is frequently inconclusive, and its predictive value is unknown. We evaluated the diagnostic accuracy of direct and indirect radiological signs of intra-articular tumour extension and the performance characteristics of MRI findings of intra-articular tumour extension.

Aims

Periprosthetic joint infection (PJI) is a challenging complication of any arthroplasty procedure. We reviewed our use of static antibiotic-loaded cement spacers (ABLCSs) for staged management of PJI where segmental bone loss, ligamentous instability, or soft-tissue defects necessitate a static construct. We reviewed factors contributing to their failure and techniques to avoid these complications when using ABLCSs in this context.

The October 2024 Oncology Roundup³⁶⁰ looks at: Composite reconstruction: is it the answer for pelvic resections?; Can the cartilaginous thickness determine the risk of malignancy in pelvic cartilaginous tumours, and how accurate is the preoperative biopsy of these tumours?; Incidence and survival outcomes of patients with high-grade appendicular bone sarcoma and isolated regional lymph node metastasis; Improved metastatic-free survival after systematic re-excision following complete macroscopic unplanned excision of limb or trunk soft-tissue sarcoma; UK guidelines for the management of soft-tissue sarcomas; Current management of desmoid tumours: a review.

Aims

Endoprosthetic reconstruction following distal femur tumour resection has been widely advocated. In this paper, we present the design of an uncemented endoprosthesis system featuring a short, curved stem, with the goal of enhancing long-term survivorship and functional outcomes.

Aims

Venous tumour thrombus (VTT) is a rare finding in osteosarcoma. Despite the high rate of VTT in osteosarcoma of the pelvis, there are very few descriptions of VTT associated with extrapelvic primary osteosarcoma. We therefore sought to describe the prevalence and presenting features of VTT in osteosarcoma of both the pelvis and the limbs.

The June 2024 Research Roundup³⁶⁰ looks at: Do the associations of daily steps with mortality and incident cardiovascular disease differ by sedentary time levels?; Large-scale assessment of ChatGPT in benign and malignant bone tumours imaging report diagnosis and its potential for clinical applications; Long-term effects of diffuse idiopathic skeletal hyperostosis on physical function: a longitudinal analysis; Effect of intramuscular fat in the thigh muscles on muscle architecture and physical performance in the middle-aged females with knee osteoarthritis; Preoperative package of care for osteoarthritis an opportunity not to be missed?; Superiority of kinematic alignment over mechanical alignment in total knee arthroplasty during medium- to long-term follow-up: a meta-analysis and trial sequential analysis.

The June 2024 Oncology Roundup. 360. looks at: Chondrosarcoma of the femur: is local recurrence influenced by the presence of an extraosseous component?; Diagnostic challenges in low-grade central osteosarcoma; Single osteotomy technique for frozen autograft (pedicled freezing) in patients with malignant bone tumours; Unplanned resection for small superficial soft-tissue sarcomas: disastrous or simply bad?; Inactivation and replantation of the knee joint: an infeasible surgical method; Active surveillance of diffuse-type tenosynovial giant cell tumours: a retrospective, multicentre cohort study

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. Cite this article: Bone Joint J 2024;106-B(5):425–429

Aims

The aim of this study was to investigate the safety and efficacy of 3D-printed modular prostheses in patients who underwent joint-sparing limb salvage surgery (JSLSS) for malignant femoral diaphyseal bone tumours.

The April 2024 Research Roundup³⁶⁰ looks at: Prevalence and characteristics of benign cartilaginous tumours of the shoulder joint; Is total-body MRI useful as a screening tool to rule out malignant progression in patients with multiple osteochondromas?; Effects of vancomycin and tobramycin on compressive and tensile strengths of antibiotic bone cement: a biomechanical study; Biomarkers for early detection of Charcot arthropathy; Strong association between growth hormone therapy and proximal tibial physeal avulsion fractures in children and adolescents; UK pregnancy in orthopaedics (UK-POP): a cross-sectional study of UK female trauma and orthopaedic surgeons and their experiences of pregnancy; Does preoperative weight loss change the risk of adverse outcomes in total knee arthroplasty by initial BMI classification?.

The April 2024 Oncology Roundup. 360. looks at: Midterm outcomes of total hip arthroplasty after internal hemipelvectomy and iliofemoral arthrodesis; Intraosseous conventional central chondrosarcoma does not metastasize irrespective of grade in pelvis, scapula, and in long bone locations; Oncological and functional outcomes after resection of malignant tumours of the scapula; Reconstruction following oncological iliosacral resection – a comparison of techniques; Does primary tumour resection improve survival for patients with sarcomas of pelvic bones, sacrum, and coccyx who have metastasis at diagnosis?; Older patients with Ewing’s sarcoma: an analysis of the National Cancer Database; Diagnostic challenges in low-grade central osteosarcoma; Effect of radiotherapy on local recurrence, distant metastasis, and overall survival in 1,200 limb soft-tissue sarcoma patients: a retrospective analysis using inverse probability of treatment weighting-adjusted models

The February 2024 Oncology Roundup³⁶⁰ looks at: Does primary tumour resection improve survival for patients with sarcomas of the pelvis with metastasis at diagnosis?; Proximal femur replacements for an oncologic indication offer a durable endoprosthetic reconstruction option: a 40-year experience; The importance of awaiting biopsy results in solitary pathological proximal femoral fractures: do we need to biopsy solitary pathological fractures?; Effect of radiotherapy on local recurrence, distant metastasis, and overall survival in 1,200 extremity soft-tissue sarcoma patients; What to choose in bone tumour resections? Patient-specific instrumentation versus surgical navigation; Optimal timing of re-excision in synovial sarcoma patients: immediate intervention versus waiting for local recurrence; Survival differences of patients with resected extraskeletal osteosarcoma receiving two different (neo) adjuvant chemotherapy regimens; Solitary versus multiple bone metastases in the appendicular skeleton: should the surgical treatment be different?.

Aims

The epiphyseal approach to a chondroblastoma of the intercondylar notch of a child’s distal femur does not provide adequate exposure, thereby necessitating the removal of a substantial amount of unaffected bone to expose the lesion. In this study, we compared the functional outcomes, local recurrence, and surgical complications of treating a chondroblastoma of the distal femoral epiphysis by either an intercondylar or an epiphyseal approach.

Aims

Due to its indolent clinical behaviour, the treatment paradigm of atypical cartilaginous tumours (ACTs) in the long bones is slowly shifting from intralesional resection (curettage) and local adjuvants, towards active surveillance through wait-and-scan follow-up. In this retrospective cohort study performed in a tertiary referral centre, we studied the natural behaviour of ACT lesions by active surveillance with MRI. Clinical symptoms were not considered in the surveillance programme.

The December 2023 Oncology Roundup. 360. looks at: A single osteotomy technique for frozen autograft; Complications, function, and survival of tumour-devitalized autografts used in patients with limb-sparing surgery; Is liquid nitrogen recycled bone and vascular fibula the biological reconstruction of choice?; Solitary pulmonary metastases at first recurrence of osteosarcoma; Is a radiological score able to predict resection-grade chondrosarcoma in primary intraosseous lesions of the long bones?; Open versus core needle biopsy in lower-limb sarcoma – current practice patterns and patient outcomes; Natural history of intraosseous low-grade chondroid lesions of the proximal humerus; Local treatment modalities and event-free survival in patients with localized Ewing’s sarcoma; Awaiting biopsy results in solitary pathological proximal femoral fractures

Aims

To evaluate mid-to long-term patient-reported outcome measures (PROMs) of endoprosthetic reconstruction after resection of malignant tumours arising around the knee, and to investigate the risk factors for unfavourable PROMs.

The December 2023 Foot & Ankle Roundup³⁶⁰ looks at: Subchondral bone cysts remodel after correction of varus deformity in ankle arthritis; 3D-printed modular endoprosthesis reconstruction following total calcanectomy; Percutaneous partial bone excision in the management of diabetic toe osteomyelitis; Hemiepiphysiodesis is a viable surgical option for Juvenile hallux valgus; Ankle arthroplasty vs arthrodesis: which comes out on top?; Patient-related risk factors for poorer outcome following total ankle arthroplasty; The Outcomes in Ankle Replacement Study.

Aims

The scapula is a rare site for a primary bone tumour. Only a small number of series have studied patient outcomes after treatment. Previous studies have shown a high rate of recurrence, with functional outcomes determined by the preservation of the glenohumeral joint and deltoid. The purpose of the current study was to report the outcome of patients who had undergone tumour resection that included the scapula.

The October 2023 Oncology Roundup. 360. looks at: Are pathological fractures in patients with osteosarcoma associated with worse survival outcomes?; Spotting the difference: how secondary osteosarcoma manifests in retinoblastoma survivors versus conventional cases; Accuracy of MRI scans in predicting intra-articular joint involvement in high-grade sarcomas around the knee; Endoprosthetic reconstruction for lower extremity soft-tissue sarcomas with bone involvement; Local relapse of soft-tissue sarcoma of the extremities or trunk wall operated on with wide margins without radiation therapy; 3D-printed, custom-made prostheses in patients who had resection of tumours of the hand and foot; Long-term follow-up for low-grade chondrosarcoma; Evaluation of local recurrence and diagnostic discordance in chondrosarcoma patients undergoing preoperative biopsy; Radiological scoring and resection grade for intraosseous chondrosarcoma

The October 2023 Research Roundup³⁶⁰ looks at: Gut microbiota in high-risk individuals for rheumatoid arthritis associated with disturbed metabolome and initiates arthritis by triggering mucosal immunity imbalance; International Consensus on Anaemia Management in Surgical Patients (ICCAMS); Sleep disturbance trends in the short-term postoperative period for patients undergoing total joint replacement; Achilles tendon tissue turnover before and immediately after an acute rupture; Quadriceps or hip exercises for patellofemoral pain? A randomized controlled equivalence trial; Total-body MRI for screening in patients with multiple osteochondromas.

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.

Cite this article: Bone Joint J 2023;105-B(8):850–856.

The August 2023 Oncology Roundup360 looks at: Giant cell tumour of bone with secondary aneurysmal bone cyst does not have a higher risk of local recurrence; Is bone marrow aspiration and biopsy helpful in initial staging of extraskeletal Ewing’s sarcoma?; Treatment outcomes of extraskeletal Ewing’s sarcoma; Pathological complete response and clinical outcomes in patients with localized soft-tissue sarcoma treated with neoadjuvant chemoradiotherapy or radiotherapy; Long-term follow-up of patients with low-grade chondrosarcoma in the appendicular skeleton treated by extended curettage and liquid nitrogen; Cancer-specific survival after limb salvage versus amputation in osteosarcoma; Outcome after surgical treatment of dermatofibrosarcoma protuberans: does it require extensive follow-up, and what is an adequate resection margin?; Management of giant cell tumours of the distal radius: a systematic review and meta-analysis

Aims. The preoperative grading of chondrosarcomas of bone that accurately predicts surgical management is difficult for surgeons, radiologists, and pathologists. There are often discrepancies in grade between the initial biopsy and the final histology. Recent advances in the use of imaging methods have shown promise in the ability to predict the final grade. The most important clinical distinction is between grade 1 chondrosarcomas, which are amenable to curettage, and resection-grade chondrosarcomas (grade 2 and 3) which require en bloc resection. The aim of this study was to evaluate the use of a Radiological Aggressiveness Score (RAS) to predict the grade of primary chondrosarcomas in long bones and thus to guide management. Methods. A total of 113 patients with a primary chondrosarcoma of a long bone presenting between January 2001 and December 2021 were identified on retrospective review of a single oncology centre’s prospectively collected database. The nine-parameter RAS included variables from radiographs and MRI scans. The best cut-off of parameters to predict the final grade of chondrosarcoma after resection was determined using a receiver operating characteristic curve (ROC), and this was correlated with the biopsy grade. Results. A RAS of ≥ four parameters was 97.9% sensitive and 90.5% specific in predicting resection-grade chondrosarcoma based on a ROC cut-off derived using the Youden index. Cronbach’s α of 0.897 was derived as the interclass correlation for scoring the lesions by four blinded reviewers who were surgeons. Concordance between resection-grade lesions predicted from the RAS and ROC cut-off with the final grade after resection was 96.46%. Concordance between the biopsy grade and the final grade was 63.8%. However, when the patients were analyzed based on surgical management, the initial biopsy was able to differentiate low-grade from resection-grade chondrosarcomas in 82.9% of biopsies. Conclusion. These findings suggest that the RAS is an accurate method for guiding the surgical management of patients with these tumours, particularly when the initial biopsy results are discordant with the clinical presentation. Cite this article: Bone Joint J 2023;105-B(7):808–814

The June 2023 Oncology Roundup. 360. looks at: A size-based criteria for flap reconstruction after thigh-adductor soft-tissue sarcoma resection; Surgical treatment of infected massive endoprostheses implanted for musculoskeletal tumours; Free vascularized fibula for proximal humerus oncological reconstruction in children; The national incidence of chondrosarcoma of bone; a review; Bone sarcoma follow-up: when do events happen?; Osteosarcomas in older adults: a report from the Cooperative Osteosarcoma Study Group

Aims

Intra-articular (IA) tumours around the knee are treated with extra-articular (EA) resection, which is associated with poor functional outcomes. We aim to evaluate the accuracy of MRI in predicting IA involvement around the knee.

Aims

Internal hemipelvectomy without reconstruction of the pelvis is a viable treatment for pelvic sarcoma; however, the time it takes to return to excellent function is quite variable. Some patients require greater time and rehabilitation than others. To determine if psoas muscle recovery is associated with changes in ambulatory function, we retrospectively evaluated psoas muscle size and limb-length discrepancy (LLD) before and after treatment and their correlation with objective functional outcomes.

Aims

The aim of this study was to investigate the incidence and characteristics of instrumentation failure (IF) after total en bloc spondylectomy (TES), and to analyze risk factors for IF.

Aims

This study aimed to analyze the accuracy and errors associated with 3D-printed, patient-specific resection guides (3DP-PSRGs) used for bone tumour resection.

The February 2023 Oncology Roundup. 360. looks at: Is the number of national database research studies in musculoskeletal sarcoma increasing, and are these studies reliable?; Re-excision after unplanned excision of soft-tissue sarcoma is associated with high morbidity; Adjuvant radiation in atypical lipomatous tumours; The oncological outcomes of isolated limb perfusion and neoadjuvant radiotherapy in soft-tissue sarcoma patients - a nationwide multicentre study; Can low-grade chondrosarcoma be treated with intralesional curettage and cryotherapy?; Efficacy and safety of carbon ion radiotherapy for bone sarcomas: a systematic review and meta-analysis; Doxorubicin-polymeric meshes prevent local recurrence after sarcoma resection while avoiding cardiotoxicity; How important are skip lesions in Ewing’s sarcoma?; Improving outcomes for amputees: the health-related quality of life and cost utility analysis of osseointegration prosthetics in transfemoral amputees

Tumours of the sacrum are difficult to manage. The sacrum provides the structural connection between the torso and lower half of the body and is subject to both axial and rotational forces. Thus, tumours or their treatment can compromise the stability of the spinopelvic junction. Additionally, nerves responsible for lower limb motor groups as well as bowel, bladder, and sexual function traverse or abut the sacrum. Preservation or sacrifice of these nerves in the treatment of sacral tumours has profound implications on the function and quality of life of the patient. This annotation will discuss current treatment protocols for sacral tumours.

Cite this article: Bone Joint J 2022;104-B(12):1284–1291.

The December 2022 Oncology Roundup³⁶⁰ looks at: Is high-dose radiation therapy associated with early revision with a cemented endoprosthesis?; Neoadjuvant chemotherapy and endoprosthetic reconstruction for lower extremity sarcomas: does timing impact complication rates?; Late amputation after treatment for lower extremity sarcoma; Osteosarcoma prediagnosed as another tumour: a report from the Cooperative Osteosarcoma Study Group; The influence of site on the incidence and diagnosis of solitary central cartilage tumours of the femur: a 21st century perspective.

Aims

Acridine orange (AO) demonstrates several biological activities. When exposed to low doses of X-ray radiation, AO increases the production of reactive radicals (radiodynamic therapy (AO-RDT)). We elucidated the efficacy of AO-RDT in breast and prostate cancer cell lines, which are likely to develop bone metastases.

Aims

Dislocation of the hip remains a major complication after periacetabular tumour resection and endoprosthetic reconstruction. The position of the acetabular component is an important modifiable factor for surgeons in determining the risk of postoperative dislocation. We investigated the significance of horizontal, vertical, and sagittal displacement of the hip centre of rotation (COR) on postoperative dislocation using a CT-based 3D model, as well as other potential risk factors for dislocation.

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).

Aims. Socioeconomic and racial disparities have been recognized as impacting the care of patients with cancer, however there are a lack of data examining the impact of these disparities on patients with bone sarcoma. The purpose of this study was to examine socioeconomic and racial disparities that impact the oncological outcomes of patients with bone sarcoma. Methods. We reviewed 4,739 patients diagnosed with primary bone sarcomas from the Surveillance, Epidemiology and End Results (SEER) registry between 2007 and 2015. We examined the impact of race and insurance status associated with the presence of metastatic disease at diagnosis, treatment outcome, and overall survival (OS). Results. Patients with Medicaid (odds ratio (OR) 1.41; 95% confidence interval (CI) 1.15 to 1.72) and uninsured patients (OR 1.90; 95% CI 1.26 to 2.86) had higher risks of metastatic disease at diagnosis compared to patients with health insurance. Compared to White patients, Black (OR 0.63, 95% CI 0.47 to 0.85) and Asian/Pacific Islander (OR 0.65, 95% CI 0.46 to 0.91) were less likely to undergo surgery. In addition, Black patients were less likely to receive chemotherapy (OR 0.67, 95% CI 0.49 to 0.91) compared to White patients. In patients with chondrosarcoma, those with Medicaid had worse OS compared to patients with insurance (hazard ratio (HR) 1.65, 95% CI 1.06 to 2.56). Conclusion. In patients with a bone sarcoma, the cancer stage at diagnosis varied based on insurance status, and racial disparities were identified in treatment. Further studies are needed to identify modifiable factors which can mitigate socioeconomic and racial disparities found in patients with bone sarcomas. Cite this article: Bone Joint Res 2022;11(5):278–291

Aims. Iliosacral sarcoma resections have been shown to have high rates of local recurrence (LR) and poor overall survival. There is also no universal classification for the resection of pelvic sarcomas invading the sacrum. This study proposes a novel classification system and analyzes the survival and risk of recurrence, when using this system. Methods. This is a retrospective analysis of 151 patients (with median follow-up in survivors of 44 months (interquartile range 12 to 77)) who underwent hemipelvectomy with iliosacral resection at a single centre between 2007 and 2019. The proposed classification differentiates the extent of iliosacral resection and defines types S1 to S6 (S1 resection medial and parallel to the sacroiliac joint, S2 resection through the ipsilateral sacral lateral mass to the neuroforamina, S3 resection through the ipsilateral neuroforamina, S4 resection through ipsilateral the spinal canal, and S5 and S6 contralateral sacral resections). Descriptive statistics and the chi-squared test were used for categorical variables, and the Kaplan-Meier survival analysis were performed. Results. Resections were S1 in 25/151 patients (17%), S2 in 70/151 (46%), S3 in 33/151 (22%), S4 in 77/151 (11%), S5 in 4/151 (3%), and S6 in 2/151 (1%). An internal hemipelvectomy was performed in 113/151 patients (75%), and 38/151 patients (25%) had an external hemipelvectomy. The predominant types of sarcoma were high-grade osteosarcoma in 48/151 patients (32%), chondrosarcoma in 41/151 (27%), Ewing sarcoma in 33/151 (22%), pleomorphic sarcoma in 17/151 (11%), and others in 2/151 (8%). LR was found in 24/151 patients (15%) with S3, S5, with S6 resections showing the highest rate of LR (p = 0.038). Overall, 19/151 patients (16%) had evidence of metastastic disease at the time of surgery and these patients showed poorer survival when compared to patients with no metastasis. Conclusion. The proposed classification can help to report and compare different surgical and reconstructive approaches in these difficult cases who are still have a considerable risk of LR. Cite this article: Bone Joint J 2022;104-B(2):290–296

Aims

The modified Glasgow Prognostic Score (mGPS) uses preoperative CRP and albumin to calculate a score from 0 to 2 (2 being associated with poor outcomes). mGPS is validated in multiple carcinomas. To date, its use in soft-tissue sarcoma (STS) is limited, with only small cohorts reporting that increased mGPS scores correlates with decreased survival in STS patients.

Aims

Proximal femoral endoprosthetic replacements (PFEPRs) are the most common reconstruction option for osseous defects following primary and metastatic tumour resection. This study aimed to compare the rate of implant failure between PFEPRs with monopolar and bipolar hemiarthroplasties and acetabular arthroplasties, and determine the optimum articulation for revision PFEPRs.

Aims

Cell-free DNA (cfDNA) and circulating tumour DNA (ctDNA) are used for prognostication and monitoring in patients with carcinomas, but their utility is unclear in sarcomas. The objectives of this pilot study were to explore the prognostic significance of cfDNA and investigate whether tumour-specific alterations can be detected in the circulation of sarcoma patients.

Aims

Orthopaedic and reconstructive surgeons are faced with large defects after the resection of malignant tumours of the sacrum. Spinopelvic reconstruction is advocated for resections above the level of the S1 neural foramina or involving the sacroiliac joint. Fixation may be augmented with either free vascularized fibular flaps (FVFs) or allograft fibular struts (AFSs) in a cathedral style. However, there are no studies comparing these reconstructive techniques.

Aims

Rotating-hinge knee prostheses are commonly used to reconstruct the distal femur after resection of a tumour, despite the projected long-term burden of reoperation due to complications. Few studies have examined the factors that influence their failure and none, to our knowledge, have used competing risk models to do so. The purpose of this study was to determine the risk factors for failure of a rotating-hinge knee distal femoral arthroplasty using the Fine-Gray competing risk model.