Statistics of bone sarcoma in Japan: report from the population-based cancer registry in Japan.

BACKGROUND: No previous reports have characterized national bone sarcoma profiles overall. We examined the nationwide statistics for bone sarcoma in Japan using data from the National Cancer Registry (NCR), a population-based cancer registry. METHODS: We identified 3,755 patients with bone sarcomas entered in the NCR during 2016-2019 using International Classification of Diseases-Oncology, Third Edition codes for cancer topography and morphology. We extracted data on patient demographics, tumor details (reason for diagnosis, tumor location, histology, extent of disease), hospital volume/type, treatment, and prognosis for each patient. RESULTS: Bone sarcoma showed a slight male preponderance. The age distribution peaked at ages 10-20 and 60-80; approximately 44% of patients were aged over 60 years. Chordoma, chondrosarcoma, and malignant fibrous histiocytoma of bone peaked in the elderly, and Ewing's sarcoma peaked in children. Osteosarcoma had two peaks in Japan as well as in Western countries. The most frequent tumor locations were the limb (45%) and the pelvis (21%). Extent of disease was categorized as: "localized" (39%), "regional" (27%), and "distant" (11%). We found significant associations between overall survival and age, tumor location, facility type, hospital volume, histologic subtype, reason for diagnosis, and extent of disease. The latter had the poorest survival. CONCLUSIONS: This is the first study to outline the epidemiology, clinical features, treatment, prognosis, and significant factors affecting prognosis of bone sarcoma in Japan using the NCR. Documenting our data regarding elderly patients' outcomes is essential so other countries showing similar population-aging trends can learn from our experiences. LEVEL OF EVIDENCE: Prognostic studies, Level III.

Infection of surgery for bone and soft tissue sarcoma with biological reconstruction: Data from the Japanese nationwide bone tumor registry.

BACKGROUND: Although biological reconstruction (such as recycled autograft, vascularized autograft, allograft, or bone transport) is possible for bone defects after malignant bone or soft tissue tumor resection, a high incidence of postoperative complications, including infection, poses a problem. The difficulty in accumulating cases has resulted in a lack of reliable etiological information, such as the incidence and risk factors of postoperative infections. METHODS: We conducted a retrospective study on the nationwide registry data. The primary endpoint was the need for additional surgical intervention for infection control. The overall incidence of postoperative infection and the related risk factors were analyzed. RESULTS: We included 707 malignant bone and soft tissue tumors with biological reconstruction, including recycled autograft, vascularized autograft, allograft, bone transport, and combinations of these. The incidence of postoperative infection was 10.8%. Patients reconstructed by pedicled autograft showed a higher incidence of infection, while cases involving the combination of recycled and pedicled autograft or allograft showed a lower incidence. Independent risk factors for infection included age over 17, tumor diameter over 10 cm, the tumor located on the trunk or being high grade, reconstruction by pedicled autograft, and delayed wound healing. CONCLUSION: Infection incidence was comparable to those in previous reports. Several conventional and novel risk factors were extracted by administering nationwide registry data. Data from the nationwide registry was informative for analyzing the incidence of postoperative infection in biological reconstruction with malignant bone and soft tissue tumor resection.

Histological diagnostic discrepancy and its clinical impact in bone and soft tissue tumors referred to a sarcoma center.

Histological diagnosis of sarcomas (malignant bone and soft tissue tumors) is challenging due to their rarity, morphological diversity, and constantly evolving diagnostic criteria. In this study, we aimed to assess the concordance in histological diagnosis of bone and soft tissue tumors between referring hospitals and a tertiary sarcoma center and analyzed the clinical impact of the diagnostic alteration. We analyzed 628 consecutively accessioned specimens from 624 patients who visited a specialized sarcoma center for treatment. The diagnoses at referring hospitals and those at the sarcoma center were compared and classified into four categories: agreed, disagreed, specified, and de-specified. Of the 628 specimens, the diagnoses agreed in 403 (64.2%) specimens, whereas some changes were made in 225 (35.8%) specimens: disagreed in 153 (24.3%), specified in 52 (8.3%), and de-specified in 20 (3.2%) cases. The benign/intermediate/malignant judgment changed for 92 cases (14.6%). The diagnostic change resulted in patient management modification in 91 cases (14.5%), including surgical and medical treatment changes. The main inferred reason for the diagnostic discrepancies was a different interpretation of morphological findings of the tumor, which accounted for 48.9% of the cases. This was followed by the unavailability of specialized immunohistochemical antibodies and the unavailability of genetic analysis. In summary, our study clarified the actual clinical impact of diagnostic discrepancy in bone and soft tissue tumors. This may underscore the value of pathology consultation, facilitating access to specialized diagnostic tools, and continued education. These measures are expected to improve diagnostic precision and ultimately benefit patients.

Establishment and characterization of two novel patient-derived cell lines from giant cell tumor of bone: NCC-GCTB8-C1 and NCC-GCTB9-C1.

Giant cell tumor of bone (GCTB) is a rare osteolytic bone tumor consisting of mononuclear stromal cells, macrophages, and osteoclast-like giant cells. Although GCTB predominantly exhibits benign behavior, the tumor carries a significant risk of high local recurrence. Furthermore, GCTB can occasionally undergo malignant transformation and distal metastasis, making it potentially fatal. The standard treatment is complete surgical resection; nonetheless, an optimal treatment strategy for advanced GCTB remains unestablished, necessitating expanded preclinical research to identify appropriate therapeutic options. However, only one GCTB cell line is publicly available from a cell bank for research use worldwide. The present study reports the establishment of two novel cell lines, NCC-GCTB8-C1 and NCC-GCTB9-C1, derived from the primary tumor tissues of two patients with GCTB. Both cell lines maintained the hallmark mutation in the H3-3A gene, which is associated with tumor formation and development in GCTB. Characterization of these cell lines revealed their steady growth, spheroid-formation capability, and invasive traits. Potential therapeutic agents were identified via extensive drug screening of the two cell lines and seven previously established GCTB cell lines. Among the 214 antitumor agents tested, romidepsin, a histone deacetylase inhibitor, and mitoxantrone, a topoisomerase inhibitor, were identified as potential therapeutic agents against GCTB. Conclusively, the establishment of NCC-GCTB8-C1 and NCC-GCTB9-C1 provides novel and crucial resources that are expected to advance GCTB research and potentially revolutionize treatment strategies.

Outcomes of Sling Procedure Using a Free Vascularized Fibular Graft After Resection of the Proximal Humerus.

Background: The proximal humerus is a common site for both primary and metastatic bone tumors. Although various methods have been developed for reconstruction following resection of the proximal humerus, a consensus on which technique is best has not been established. We focused on the sling procedure using a free vascularized fibular graft (FVFG) and conducted what we believe to be the largest retrospective study of patients to undergo this surgery to date. Methods: We retrospectively reviewed the data of 19 patients who underwent the sling procedure with use of an FVFG at our hospital between 1998 and 2022. The median age was 20 years, and the median follow-up duration was 63.1 months. Surgical data, oncological outcomes, the postoperative course, complications, and functional outcomes as measured with use of the Musculoskeletal Tumor Society (MSTS) score were thoroughly reviewed. Results: The median operative duration was 555 minutes, and the median blood loss was 374 mL. The median length of the bone defect was 17.0 cm, and the median length of the graft was 20.0 cm. With respect to oncological outcomes, 9 patients were continuously disease-free, 9 patients had no evidence of disease, and 1 patient was alive with disease. Bone union was present in 13 of the 17 patients for whom it was evaluable. The median time to bone union was 4 months. Graft growth was observed in 2 pediatric patients. Postoperative fracture was a major complication at the recipient site. The incidence of pseudarthrosis significantly increased when the FVFG could not be inserted into the remaining humeral bone or was split in half (p = 0.002). Although a few patients demonstrated peroneal nerve palsy at the donor site, the symptom was temporary. The overall functional outcome was favorable, with an average MSTS score of 66.9%. Conclusions: The sling procedure demonstrated a low complication rate and a favorable functional outcome overall. Therefore, we believe that this procedure is a useful reconstruction method for patients in a broad age range who have a wide defect of the proximal humerus. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Incidence and risk of infection in malignant soft tissue tumor resection: Data from the nationwide soft tissue tumor registry.

BACKGROUND: Postoperative infection is a devastating complication in limb salvage surgery for malignant soft tissue tumors. The low absolute case numbers of these rare cancers represent a bottleneck for data collection and analysis. The administration of nationwide registry data is a practical option for the accumulation of cases. METHODS: Data on malignant soft tissue tumor resection were extracted from the Bone and Soft Tissue Tumor Registry in Japan. The incidence of postoperative infection and its risk factors were analyzed. RESULTS: A total of 14,460 cases were included. The incidence of infection was 2.6%. Significant risks for infection were male sex, lower extremity or trunk location, tumor diameter of over 10 cm, trans-compartmental invasion, high grade, autologous bone graft, myocutaneous flap, vascular reconstruction, reconstruction by prosthesis, postoperative radiotherapy, and delayed wound healing. CONCLUSIONS: The incidence was lower than those in the previous studies, perhaps because of less frequent radiotherapy application. Some of the significant risk factors represented local invasiveness of the tumor, suggesting the importance of the preservation of soft tissue for infection prevention. The administration of nationwide registry data was informative for the analysis of infection in malignant soft tissue tumor resection.

Incidence and risk of surgical site infection/periprosthetic joint infection in tumor endoprosthesis-data from the nationwide bone tumor registry in Japan.

BACKGROUND: Surgical site infection (SSI)/periprosthetic joint infection (PJI) is a devastating complication in limb salvage surgery with endoprosthesis reconstruction for malignant bone tumors. The main bottleneck for data collection and analysis for the status of SSI/PJI in tumor endoprosthesis is the low absolute case numbers of this rare cancer. The accumulation of many cases is possible by administrating nationwide registry data. METHODS: The data on malignant bone tumor resection with tumor endoprosthesis reconstruction were extracted from the Bone and Soft Tissue Tumor Registry in Japan. The primary endpoint was defined as the need for additional surgical intervention for infection control. The incidence of postoperative infection and its risk factors were analyzed. RESULTS: A total of 1342 cases were included. The incidence of SSI/PJI was 8.2%. The incidence of SSI/PJI in the proximal femur, distal femur, proximal tibia, and pelvis were 4.9%, 7.4%, 12.6%, and 41.2%, respectively. Location in the pelvis or proximal tibia, tumor grade, indication of myocutaneous flaps, and delayed wound healing proved to be independent risks for SSI/PJI, whereas age, sex, previous surgery, tumor size, surgical margin, application of chemotherapy and radiotherapy were not significant. CONCLUSIONS: The incidence was equal to those in previous studies. The result reconfirmed the high incidence of SSI/PJI in pelvis and proximal tibia cases and cases with delayed wound healing. Novel risk factors such as tumor grade and application of myocutaneous flaps were marked. The administration of nationwide registry data was informative for the analysis of SSI/PJI in tumor endoprosthesis.

Establishment and characterization of NCC-DFSP4-C1: a novel cell line from a patient with dermatofibrosarcoma protuberans having the fibrosarcomatous transformation.

Dermatofibrosarcoma protuberans (DFSP) is a superficial low-grade sarcoma, genetically characterized by a fusion gene in collagen type I α (COL1A1) gene and platelet-derived growth factor subunit ß (PDGFB). DFSP is locally aggressive and does not typically metastasize. However, DFSP with fibrosarcomatous transformation, which occurs in 7-16% of DFSP cases, demonstrates a poor prognosis than classic DFSP with a higher local recurrence rate and metastatic potential. Although imatinib, a PDGF receptor inhibitor, is a potent therapeutic agent for classic DFSP, it is less effective for DFSP with fibrosarcomatous transformation. The development of definitive chemotherapies for DFSP with fibrosarcomatous transformation is required. Patient-derived tumor cell lines are indispensable tools for preclinical research to discover novel therapeutic agents. However, only seven cell lines were derived from DFSP, out of which only two were established from DFSP with fibrosarcomatous transformation. Hence, in the present study, we established a novel DFSP cell line, NCC-DFSP4-C1, from a surgically resected DFSP tumor specimen with fibrosarcomatous transformation. NCC-DFSP4-C1 harbored an identical COL1A1-PDGFB fusion gene as its donor tumor. NCC-DFSP4-C1 cells retained the morphology of their donor tumor and demonstrated constant proliferation, spheroid formation, and invasion capability in vitro. By screening a drug library, we found that bortezomib and romidepsin demonstrated the strongest suppressive effects on the proliferation of NCC-DFSP4-C1 cells. In conclusion, we report a novel cell line of DFSP with fibrosarcomatous transformation, and demonstrate its utility in the development of novel therapeutic agents for DFSP.

A vessel sealing system can help reduce the risk of postoperative complications after tumour resection in the medial thigh.

Aims: The risk of postoperative complications after resection of soft-tissue sarcoma in the medial thigh is higher than in other locations. This study investigated whether a vessel sealing system (VSS) could help reduce the risk of postoperative complications after wide resection of soft-tissue sarcoma in the medial thigh. Methods: Of 285 patients who underwent wide resection for soft-tissue sarcoma between 2014 and 2021 at our institution, 78 patients with tumours in the medial thigh were extracted from our database. Information on clinicopathological characteristics, preoperative treatment, surgical treatment (use of VSS, blood loss volume, operating time), and postoperative course (complications, postoperative haemoglobin changes, total drainage volume, and drainage and hospitalization durations) were obtained from medical records. We statistically compared clinical outcomes between patients whose surgery did or did not use VSS (VSS and non-VSS groups, respectively). Results: There were 24 patients in the VSS group and 54 in the non-VSS group. There were no significant differences between the two groups in terms of clinicopathological background. The total drainage volume in the VSS group was significantly less than that in the non-VSS group (1,176 ml vs 3,114 ml; p = 0.018). Moreover, the drainage and hospitalization durations were significantly shorter in the VSS group compared to the non-VSS group (p = 0.017 and p = 0.024, respectively). Conclusion: Our results suggest that use of VSS can help reduce the risk of postoperative complications after wide resection of soft-tissue sarcoma in the medial thigh.

Predictive value of peripheral blood markers in soft tissue sarcoma patients treated with eribulin.

OBJECTIVE: eribulin, an anticancer agent that inhibits microtubule growth, along with trabectedin and pazopanib, has been approved for the treatment of advanced soft tissue sarcoma (STS). However, there has been no consensus on the optimal second-line therapy among these three agents following treatment failure with doxorubicin. Recently, the effects of eribulin on the tumor microenvironment and immunity have been reported in breast cancer, and peripheral blood immune markers have also been reported to be a predictor of eribulin efficacy, though this remains unverified in STS. We aimed to evaluate the predictive value of various peripheral blood immune markers in STS patients treated with eribulin. METHODS: we retrospectively reviewed the medical records of STS patients treated with eribulin and examined whether peripheral blood immune markers at different time points could be prognostic factors for STS patients treated with eribulin. RESULTS: several peripheral blood immune markers were significantly associated with progression-free survival (PFS), specifically neutrophil-to-lymphocyte ratio (NLR) prestart (NLR before the initial administration of eribulin) (P = 0.019) and absolute lymphocyte count (ALC)8D (ALC on Day 8 of the first administration of eribulin) (P = 0.037). NLR prestart (P = 0.001) was significantly associated with overall survival. The combination of NLR prestart and ALC8D determined the PFS of STS patients treated with eribulin. CONCLUSIONS: the combined indicator of low NLR prestart and high ALC8D predicted the survival of patients treated with eribulin as well as the histology of L-sarcoma. Though further validation was needed, this finding would provide valuable prognostic factor that help treatment decision in the absence of consensus on the optimal second-line therapy following doxorubicin treatment in STS patients.

Clinical analysis of multimodal treatment for localized synovial sarcoma: A multicenter retrospective study.

INTRODUCTION: Several prognostic factors for survival in synovial sarcoma have been proposed, but the role of adjuvant chemotherapy and radiotherapy is a matter of debate. The study aim was to clarify the effect of high-dose ifosfamide-containing chemotherapy and adjuvant radiotherapy for patients with localized synovial sarcoma. MATERIALS AND METHODS: Five tertiary musculoskeletal oncology hospitals participated in this retrospective study. The records of the patient diagnosed with synovial sarcoma without metastasis at diagnosis from 1990 to 2011 have been collected and reviewed. Overall, distant failure-free, and local failure-free survivals were calculated, and prognostic factors for each survival were evaluated by performing univariate and multivariate analyses. RESULTS: A total of 162 patients were enrolled in this study with a median follow-up period of 67 months (range, 5-267 months) for all surviving patients. The 5-year overall, distant failure-free, and local failure-free survival rates were 79.7%, 66.3%, and 98.4%, respectively. Univariate analyses demonstrated that high-dose ifosfamide-containing chemotherapy was significantly associated with better overall (p = 0.014) and distant failure-free survival (p = 0.0043) than that of low-dose or no ifosfamide-containing chemotherapy if we analyzed only patients with tumors >5 cm in size. Addition of radiotherapy was not a significant prognostic factor for overall survival in the univariate and multivariate analyses, but it did improve the overall survival of the patients with R1 resection (p = 0.053). CONCLUSION: Patients with localized synovial sarcoma >5 cm in size had better overall and distant failure-free survival after receiving adjuvant chemotherapy containing high-dose ifosfamide comparing to low-dose or no ifosfamide-containing chemotherapy. The addition of adjuvant radiotherapy was beneficial for the patients who received R1 resection. Alternatively, adjuvant radiotherapy could be avoided for patients who achieved an R0 margin.

Operative management of metastatic disease of the acetabulum: review of the literature and prevailing concepts.

Metastatic disease of the periacetabular region is a common problem in orthopaedic oncology, associated with severe pain, decreased mobility, and substantial decline of the quality of life. Conservative management includes optimisation of pain management, activity modification, and radiation therapy. However, patients with destructive lesions affecting the weight-bearing portion of the acetabulum often require reconstructive surgery to decrease pain and restore mobility. The goal of surgery is to provide an immediately stable and durable construct, allowing immediate postoperative weight-bearing and maintaining functional independence for the remaining lifetime of the patient. A variety of surgical techniques have been reported, most of which are based upon cemented total hip arthroplasty, but also include porous tantalum implants and percutaneous cementoplasty. This review discusses the various reconstructive concepts and options, including their respective indications and outcome. A reconstructive algorithm incorporating different techniques and strategies based upon location and quality of remaining bone is also presented.

Laser-driven multi-MeV high-purity proton acceleration via anisotropic ambipolar expansion of micron-scale hydrogen clusters.

Multi-MeV high-purity proton acceleration by using a hydrogen cluster target irradiated with repetitive, relativistic intensity laser pulses has been demonstrated. Statistical analysis of hundreds of data sets highlights the existence of markedly high energy protons produced from the laser-irradiated clusters with micron-scale diameters. The spatial distribution of the accelerated protons is found to be anisotropic, where the higher energy protons are preferentially accelerated along the laser propagation direction due to the relativistic effect. These features are supported by three-dimensional (3D) particle-in-cell (PIC) simulations, which show that directional, higher energy protons are generated via the anisotropic ambipolar expansion of the micron-scale clusters. The number of protons accelerating along the laser propagation direction is found to be as high as 1.6 [Formula: see text] [Formula: see text] 10[Formula: see text]/MeV/sr/shot with an energy of 2.8 [Formula: see text] MeV, indicating that laser-driven proton acceleration using the micron-scale hydrogen clusters is promising as a compact, repetitive, multi-MeV high-purity proton source for various applications.

Prospective Clinical Genomic Profiling of Ewing Sarcoma: ERF and FGFR1 Mutations as Recurrent Secondary Alterations of Potential Biologic and Therapeutic Relevance.

PURPOSE: Ewing sarcoma (ES) is a primitive sarcoma defined by EWSR1-ETS fusions as the primary driver alteration. To better define the landscape of cooperating secondary genetic alterations in ES, we analyzed clinical genomic profiling data of 113 patients with ES, a cohort including more adult patients (> 18 years) and more patients with advanced stage at presentation than previous genomic cohorts. METHODS: The data set consisted of patients with ES prospectively tested with the US Food and Drug Administration-cleared Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets large panel, hybrid capture-based next-generation sequencing assay. To assess the functional significance of ERF loss, we generated ES cell lines with increased expression of ERF and lines with knockdown of ERF. We assessed cell viability, clonogenic growth, and motility in these ES lines and performed transcriptomic and epigenetic analyses. Finally, we validated our findings in vivo using cell line xenografts. RESULTS: Novel subsets were defined by recurrent secondary alterations in ERF, which encodes an ETS domain transcriptional repressor, in 7% of patients (five truncating mutations, one deep deletion, and two missense mutations) and in FGFR1 in another 2.7% (one amplification and two known activating mutations). ERF alterations were nonoverlapping with STAG2 alterations. In vitro, increased expression of ERF decreased tumor cell growth, colony formation, and motility in two ES cell lines, whereas ERF loss induced cellular proliferation and clonogenic growth. Transcriptomic analysis of cell lines with ERF loss revealed an increased expression of genes and pathways associated with aggressive tumor biology, and epigenetic, chromatin-based studies revealed that ERF competes with EWSR1-FLI1 at ETS-binding sites. CONCLUSION: Our findings open avenues to new insights into ES pathobiology and to novel therapeutic approaches in a subset of patients with ES.

Geographic Access to High-Volume Care Providers and Survival in Patients with Bone Sarcomas: Nationwide Patterns in the United States.

BACKGROUND: Clinical practice guidelines recommend centralized care for patients with bone sarcoma. However, the relationship between the distance that patients travel to obtain care, institutional treatment volume, and survival is unknown. METHODS: We used the National Cancer Database to examine associations between travel distance and survival among 8,432 patients with bone sarcoma diagnosed from 2004 to 2015. Associations were identified using multivariable Cox regression analyses that controlled for sociodemographic, clinical, and hospital-level factors; subgroup analyses stratified patients by histological diagnosis, tumor stage, and pediatric or adult status. RESULTS: Mortality risk was lower among patients who traveled ≥50 miles (≥80.5 km) than among patients who traveled ≤10 miles (≤16.1 km) (hazard ratio [HR], 0.69 [95% confidence interval (CI), 0.63 to 0.76]). Among hospital-level factors, facility volume independently affected survival: mortality risk was lower among patients at high-volume facilities (≥20 cases per year) than at low-volume facilities (≤5 cases per year), with an HR of 0.72 (95% CI, 0.66 to 0.80). The proportion of patients who received care at high-volume facilities varied by distance traveled (p < 0.001); it was highest among patients who traveled ≥50 miles (53%) and lower among those who traveled 11 to 49 miles (17.7 to 78.9 km) (32%) or ≤10 miles (18%). Patients who traveled ≥50 miles to a high-volume facility had a lower risk of mortality (HR, 0.65 [95% CI, 0.56 to 0.77]) than those who traveled ≤10 miles to a low-volume facility. In subgroup analyses, this association was evident among patients with all 3 major histological subtypes; those with stage-I, II, and IV tumors; and adults. CONCLUSIONS: This national study showed that greater travel burden was associated with higher survival rates in adults, a finding attributable to patients traveling to receive care at high-volume facilities. Despite the burdens associated with travel, modification of referral pathways to specialized centers may improve survival for patients with bone sarcoma. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Periacetabular reconstruction following limb-salvage surgery for pelvic sarcomas.

Limb-salvage surgery for pelvic sarcomas remains one of the most challenging surgical procedures for musculoskeletal oncologists. In the past several decades, various surgical techniques have been developed for periacetabular reconstruction following pelvic tumor resection. These methods include endoprosthetic reconstruction, allograft or autograft reconstruction, arthrodesis, and hip transposition. Each of these procedures has its own advantages and disadvantages, and there is no consensus or gold standard for periacetabular reconstruction. Consequently, this review provides an overview of the clinical outcomes for each of these reconstructive options following pelvic tumor resections. Overall, high complication rates are associated with the use of massive implants/grafts, and deep infection is generally the most common cause of reconstruction failure. Functional outcomes decline with the occurrence of severe complications. Further efforts to avoid complications using innovative techniques, such as antibiotic-laden devices, computer navigation, custom cutting jigs, and reduced use of implants/grafts, are crucial to improve outcomes, especially in patients at a high risk of complications.

Long-term competing risks for overall and cause-specific failure of rotating-hinge distal femoral arthroplasty for tumour reconstruction.

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. METHODS: We retrospectively reviewed 209 consecutive patients who, between 1991 and 2016, had undergone resection of the distal femur for tumour and reconstruction using a rotating-hinge knee prosthesis. The study endpoint was failure of the prosthesis, defined as removal of the femoral component, the tibial component, or the bone-implant fixation; major revision (exchange of the femoral component, tibial component, or the bone-implant fixation); or amputation. RESULTS: Multivariate Fine-Gray regression analyses revealed different hazards for each Henderson failure mode: percentage of femoral resection (p = 0.001) and extent of quadriceps muscle resection (p = 0.005) for overall prosthetic failure; extent of quadriceps muscle resection (p = 0.002) and fixation of femoral component (p = 0.011) for type 2 failure (aseptic loosening); age (p = 0.009) and percentage of femoral resection (p = 0.019) for type 3 failure (mechanical failure); and type of joint resection (p = 0.037) for type 4 (infection) were independent predictors. A bone stem ratio of > 2.5 reliably predicted aseptic loosening. CONCLUSION: We identified independent risk factors for overall and cause-specific prosthetic failure after rotating-hinge knee distal femoral arthroplasty using a competing risk Fine-Gray model. A bone stem ratio > 2.5 reliably predicts aseptic loosening. An accurate knowledge of the risks of distal femoral arthroplasty after resection for tumour assists surgical planning and managing patient expectations. Cite this article: Bone Joint J 2021;103-B(8):1405-1413.

Greater travel distance to specialized facilities is associated with higher survival for patients with soft-tissue sarcoma: US nationwide patterns.

PURPOSE: The survival impact of geographic access to specialized care remains unknown in patients with soft-tissue sarcomas (STS). This study aimed to clarify the association between the patient travel distance and survival outcome and investigate the factors lying behind it. METHODS: A total of 34 528 patients with STS registered in the National Cancer Data Base, diagnosed from 2004-2016, were investigated. RESULTS: Tumor stage correlated with travel distance: patients with metastatic disease stayed closer to home. However, the type of facility showed greatest variation: 37.0%, 51.0%, 73.5%, and 75.9% of patients with ≤10 miles, 10.1-50 miles, 50.1-100 miles, and >100 miles, respectively (P<0.001), had a sarcoma care at academic/research centers. On a multivariable analysis, reduced mortality risk was associated with longer (versus short) travel distance (>100 miles: HR = 0.877; P = 0.001) and management at academic/research (versus non-academic/research) centers (HR = 0.857; P<0.001). The greatest divergence was seen in patients traveling very long distance (>100 miles) to an academic/research center, with a 26.9% survival benefit (HR = 0.731; P<0.001), compared with those traveling short distance (≤10 miles; 95.4% living in metropolitan area) to a non-academic/research center. There was no significant correlation between travel distance and survival in patients who had care at academic/research centers, whereas a survival benefit of management at academic/research centers was observed in every group of travel distance, regardless of tumor stage. CONCLUSIONS: This national study demonstrated that increased travel distance was associated with superior survival, attributable to a higher proportion of patients receiving sarcoma care at distant academic/research centers. These data support centralized care for STS. Overcoming referral and travel barriers may enable more patients to be treated at specialized centers and may further improve survival rates for patients with STS, even when it imposes an increased travel burden.

Patients with an increased time to treatment initiation have a poorer overall survival after definitive surgery for localized high-grade soft-tissue sarcoma in the extremity or trunk : report from the National Cancer Database.

AIMS: Time to treatment initiation (TTI) is generally defined as the time from the histological diagnosis of malignancy to the initiation of first definitive treatment. There is no consensus on the impact of TTI on the overall survival in patients with a soft-tissue sarcoma. The purpose of this study was to determine if an increased TTI is associated with overall survival in patients with a soft-tissue sarcoma, and to identify the factors associated with a prolonged TTI. METHODS: We identified 23,786 patients from the National Cancer Database who had undergone definitive surgery between 2004 and 2015 for a localized high-grade soft-tissue sarcoma of the limbs or trunk. A Cox proportional hazards model was used to examine the relationship between a number of factors and overall survival. We calculated the incidence rate ratio (IRR) using negative binomial regression models to identify the factors that affected TTI. RESULTS: Patients in whom the time to treatment initiation was prolonged had poorer overall survival than those with a TTI of 0 to 30 days. These were: 31 to 60 days (hazard ratio (HR) 1.08, p = 0.011); 61 to 90 days (HR 1.11, p = 0.044); and 91 days (HR 1.22; p = 0.003). The restricted cubic spline showed that the hazard ratio increased substantially with a TTI longer than 50 days. Non-academic centres (vs academic centres; IRR ranging from 0.64 to 0.86; p < 0.001) had a shorter TTI. Those insured by Medicaid (vs private insurance; IRR 1.34), were uninsured (vs private insurance; IRR 1.17), or underwent a transition in care (IRR 1.62) had a longer TTI. CONCLUSION: A time to treatment initiation of more than 30 days after diagnosis was independently associated with poorer survival. The hazard ratio showed linear increase, especially if the TTI was more than 50 days. We recommend starting treatment within 30 days of diagnosis to achieve the highest likelihood of cure for localized high-grade soft-tissue sarcomas in the limbs and trunk, even when a patient needs to be referred to a specialist centre. Cite this article: Bone Joint J 2021;103-B(6):1142-1149.