Incidence of skeletal-related events in patients with Ewing sarcoma: An observational retrospective study in Japan.

BACKGROUND: Skeletal-related events (SREs), including the pathological fracture, surgical treatment or radiation of bone lesions, malignant spinal cord compression, hypercalcemia, are important considerations when managing metastatic bone tumors; however, owing to their rarity, the incidence of SREs in patients with Ewing sarcoma remains unknown. METHODS: We retrospectively reviewed the clinical data from 146 patients with Ewing sarcoma treated at a single institution from 2005 to 2019. The median age at diagnosis was 22.7 years. Fifty patients (34.2%) had metastatic disease at diagnosis. The primary outcome was the SRE-free rate among patients with Ewing sarcoma. Moreover, we identified the risk factors for SREs using univariate or multivariate analyses. RESULTS: During the observational period (median, 2.6 years), SREs occurred in 23 patients. Radiation to the bone, malignant spinal cord compression, and hypercalcemia were documented as the initial SREs in 12 patients (52.2%), 10 patients (43.5%), and one patient (4.3%), respectively. The SRE-free rate was 94.2 ± 2.0, 87.3 ± 3.0, and 79.6 ± 3.8% at 1, 2, and 3 years after the initial visit, respectively. Multivariate analysis revealed bone metastasis at diagnosis (hazard ratio [HR] = 4.41, p = 0.007), bone marrow invasion (HR = 34.08, p < 0.001), and local progression or recurrence after definitive treatment (HR = 3.98, p = 0.012) as independent risk factors for SREs. CONCLUSIONS: SREs are non-rare events that can occur during the treatment course for Ewing sarcoma, with an especially high incidence of malignant spinal cord compression. Patients with metastatic disease at diagnosis, especially in the bone or bone marrow, or with local progression or recurrence after definitive treatment, should be carefully monitored for the occurrence of SREs. The most effective methods to monitor the occurrence of SREs and new preventative therapies for SREs should be investigated in the future.

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.

Establishment and characterization of NCC-ASPS2-C1: a novel patient-derived cell line of alveolar soft part sarcoma.

Alveolar soft part sarcoma (ASPS) is a rare mesenchymal tumor characterized by rearrangement of the ASPSCR1 and TFE3 genes and a histologically distinctive pseudoalveolar pattern. ASPS progresses slowly, but is prone to late metastasis. As ASPS is refractory to conventional chemotherapy, the only curative treatment is complete surgical resection. The prognosis of advanced and metastatic cases is poor, highlighting the need for preclinical research to develop appropriate treatment options. However, ASPS is extremely rare, accounting for < 1% of all soft tissue sarcomas, and only one patient-derived ASPS cell line is available from public cell banks worldwide for research. This study reports the establishment of a novel ASPS cell line derived from the primary tumor tissue of an ASPS patient, named NCC-ASPS2-C1. This cell line retains the ASPSCR1-TFE3 fusion gene, which is characteristic of ASPS. The characterization of this cell line revealed stable growth, spheroid formation, and invasive properties. By screening a drug library using NCC-ASPS2-C1, we identified several drugs that inhibited the proliferation of ASPS cells. In conclusion, the establishment of NCC-ASPS2-C1 provides a valuable resource for advancing ASPS research and developing novel treatments for this challenging disease.

Current status of head and neck sarcomas in Japan in 2016-2019: an analysis using the national cancer registry.

BACKGROUND: Head and neck sarcomas are especially rare in Asia, leading to limited clinical evidence. This study aimed to investigate the incidence, clinical features, treatment status, and outcome of these sarcomas using data from the National Cancer Registry in Japan. METHODS: All head and neck sarcomas diagnosed between 2016 and 2019 and recorded in the National Cancer Registry were analyzed. Data on sex, age, primary site, histological type, stage, treatment modality, and prognostic information were collected. Age-adjusted incidence and 3-year survival rates of patients with head and neck sarcomas were calculated. RESULTS: Overall, 635 head and neck sarcoma patients were identified. Head and neck sarcoma occurred more frequently in men and patients in their 70 s. The age-adjusted annual incidence rate was 0.125 per 100,000 patients in the 2015 Japanese model or 0.089 per 100,000 patients in the world population model. The nasal cavity and paranasal sinuses were the most frequent primary sites, with rhabdomyosarcoma as the most common histologic type. Treatment typically involved chemotherapy and/or radiation therapy for rhabdomyosarcoma and Ewing's sarcoma, whereas surgical approaches for other types. Three-year survival rate of head and neck sarcoma patients was 64.8%. CONCLUSIONS: Head and neck sarcomas occurred rarely, but most frequently in the nasal cavity and paranasal sinuses in Japan. Poor outcomes were observed for sarcoma patients than for non-sarcoma head and neck cancer patients.

Establishment and characterization of NCC-DFSP5-C1: a novel patient-derived dermatofibrosarcoma protuberans cell line.

Dermatofibrosarcoma protuberans (DFSP) is the most prevalent dermal sarcoma, characterized by the presence of the fusion of the collagen type I alpha 1 (COL1A1) gene with the platelet-derived growth factor beta chain (PDGFB) gene. Although PDGF receptor inhibitor imatinib mesylate was approved for the treating patients with unresectable or metastatic DFSP, disease progression was shown in 9.2% of the patients. Therefore, developing novel therapeutic strategies is crucial for improving the prognosis of DFSP. Patient-derived cell lines play a vital role in preclinical studies; however, only a limited number of DFSP cell lines are currently available in public cell banks. Here, we successfully established a novel DFSP cell line (NCC-DFSP5-C1) using surgically resected tumor tissue from a patient with DFSP. NCC-DFSP5-C1 cells were confirmed to carry the COL1A1-PDGFB translocation and maintain the same mutation as the original tumor tissue. They exhibited consistent growth, formed spheroids, and were invasive. By screening a drug library using NCC-DFSP5-C1 and four previously established DFSP cell lines, we identified anti-cancer drugs that inhibit DFSP cell proliferation. Our observations suggest that the NCC-DFSP5-C1 cell line holds promise as a valuable tool for conducting fundamental and preclinical studies for DFSP.

Clinical outcomes in patients with adamantinoma: Report from the bone and soft tissue tumor registry in Japan.

BACKGROUND: Adamantinomas are rare malignant bone tumors. Due to their low incidence, there are few reports on the clinical results of adamantinoma. OBJECTIVES: This study aims to clarify outcomes in patients with adamantinoma using data from the National Bone and Soft Tissue Tumor Registry. METHODS: From 2006 to 2019, 38 cases of tibial origin were included. Twenty-four were male and 14 were female, with a mean age of 37 (6-87) years and a mean follow-up of 35 (1-128) months. RESULTS: Surgery was performed in 33 cases (87%) (curettage: 4 cases, wide resection: 27 cases, amputation: 2 cases). Reconstruction was performed in 27 patients who underwent wide resection. A total of 12 additional surgeries were performed in 11 patients. The main reason for the additional surgeries was nonunion of grafting bone in 6 cases. Oncologic outcomes were DOC (death from other causes) in one case and NED (no evidence of disease) in 37 cases. CONCLUSIONS: The results of treatment of adamantinomas in Japan have been extremely favorable. This may be due in part to the large number of cases with wide resection.

Prognostic factors and treatment outcomes in patients with pleomorphic rhabdomyosarcoma: a population-based cohort study.

BACKGROUND: Pleomorphic rhabdomyosarcoma is a rare sarcoma in adults. The clinical characteristics, outcomes and prognostic factors associated with pleomorphic rhabdomyosarcoma remain unclear. METHODS: We retrospectively analyzed data from the Bone and Soft Tissue Tumor Registry of Japan, and enrolled patients with pleomorphic rhabdomyosarcoma. Disease-specific overall survival, local recurrence-free survival and distant metastasis-free survival were estimated using the Kaplan-Meier method; Cox regression model was used to identify prognostic factors. RESULTS: In total, 182 patients with pleomorphic rhabdomyosarcoma were included. Median age was 63 (range 20-95) years. The lower extremity (48%) was the most frequent tumor origin site, while head and neck were rare (4%). A total of 43 patients (24%) had distant or regional nodal metastases at first presentation. In all cases, the 2-year and 5-year survival rates were 66.3% and 54.1%, respectively. Distant metastasis was a significant poor prognostic factor (Hazard ratio 6.65; 95% confidence intervals, 3.00-14.75, P < 0.0001), with median survival of such patients being 9.4 (95% confidence intervals: 5.3-12.2) months. In 134 localized cases, the 2-year and 5-year survival rates were 91.5% and 68.3%, respectively. Large tumor size and older age were associated with poorer prognosis. Through data from localized and locally curative cases extracted and adjusted by propensity score matching, we found that perioperative chemotherapy did not improve disease-specific overall survival, distant metastasis-free survival or local recurrence-free survival. CONCLUSIONS: Clinical characteristics and outcomes of pleomorphic rhabdomyosarcoma are similar to those of other high-grade soft tissue sarcomas. Pleomorphic rhabdomyosarcoma may be less chemosensitive, and a strategy other than the standard cytotoxic chemotherapy is required to improve its prognosis.

Establishment and characterization of NCC-LMS3-C1: a novel patient-derived cell line of leiomyosarcoma.

Leiomyosarcoma (LMS) is an aggressive mesenchymal malignancy, which originates from the smooth muscle cells or from the precursor mesenchymal stem cells that potentially differentiate into smooth muscle cells. LMS is one of the most common sarcomas. LMS has genomic instability, reflecting complex and unbalanced karyotypes, and the cytogenetic and molecular changes in LMS are not consistent. The standard treatment of the primary LMS is complete resection, and the metastasis is often observed even after curative surgery. Patient-derived cancer models are a key bioresource to develop a novel therapy, and we aimed to establish and characterize a novel cell line for LMS. We established a cell line from tumor tissues of the patient with LMS and named it NCC-LMS3-C1. We maintained NCC-LMS3-C1 cells for 12 months and passed them more than 30 times. Genome-wide copy number analysis demonstrated that NCC-LMS3-C1 cells harbored genetic abnormalities. NCC-LMS3-C1 cells exhibited aggressive phenotypes such as continuous growth, spheroid formation, and invasion in the tissue culture condition, which may reflect the clinical behaviors of LMS. We performed a drug screening using NCC-LMS3-C1 cells and found that four anti-cancer agents, such as bortezomib, dasatinib, mitoxantrone, and romidepsin, had remarkable anti-proliferative effects on NCC-LMS3-C1 cells. We conclude that NCC-LMS3-C1 cells will be a useful resource for the study of LMS.

Inflammatory Rhabdomyoblastic Tumor: Clinicopathologic and Molecular Analysis of 13 Cases.

Inflammatory rhabdomyoblastic tumors (IRMTs) are newly recognized skeletal muscle tumors with uncertain malignant potential. We investigated 13 IRMTs using clinicopathologic, genetic, and epigenetic methods. The cohort included 7 men and 6 women, aged 23 to 80 years (median, 50 years), of whom 2 had neurofibromatosis type 1. Most tumors occurred in the deep soft tissues of the lower limbs, head/neck, trunk wall, and retroperitoneum/pelvis. Two tumors involved the hypopharyngeal submucosa as polypoid masses. Eight tumors showed conventional histology of predominantly spindled cells with nuclear atypia, low mitotic activity, and massive inflammatory infiltrates. Three tumors showed atypical histology, including uniform epithelioid or plump cells and mitotically active histiocytes. The remaining 2 tumors demonstrated malignant progression to rhabdomyosarcoma; one had additional IRMT histology and the other was a pure sarcoma. All 11 IRMTs without malignant progression exhibited indolent behavior at a median follow-up of 43 months. One of the 2 patients with IRMTs with malignant progression died of lung metastases. All IRMTs were positive for desmin and PAX7, whereas myogenin and MyoD1 were expressed in a subset of cases. Targeted next-generation sequencing identified pathogenic mutations in NF1 (5/8) and TP53 (4/8). All TP53 mutations co-occurred with NF1 mutations. TP53 variant allele frequency was much lower than that of NF1 in 2 cases. These tumors showed geographic (subclonal) strong p53 immunoreactivity, suggesting the secondary emergence of a TP53-mutant clone. DNA methylation-based copy number analysis conducted in 11 tumors revealed characteristic flat patterns with relative gains, including chromosomes 5, 18, 20, 21, and/or 22 in most cases. Widespread loss of heterozygosity with retained biparental copies of these chromosomes was confirmed in 4 tumors analyzed via allele-specific profiling. Based on unsupervised DNA methylation analysis, none of the 11 tumors tested clustered with existing reference entities but formed a coherent group, although its specificity warrants further study.

Myxoid liposarcoma with nuclear pleomorphism: a clinicopathological and molecular study.

Myxoid liposarcoma (MLS) is a common type of liposarcoma. It is characterized by variably lipogenic uniform cells in myxoid stroma with arborizing capillaries and DDIT3 fusion. Nuclear uniformity is the rule, which is maintained even in high-grade round cell examples. In this study, we conducted an in-depth investigation of four MLS tumors that demonstrated nuclear pleomorphism in three patients. These cases accounted for 2.1% of 142 patients with MLS. All patients were male aged 26, 33, and 49 years. Nuclear pleomorphism was observed in both primary and metastatic tumors in one patient, a primary tumor in one patient, and a metastatic tumor in another patient. Pleomorphism was severe in three tumors and moderate in one. Histology resembled that of dedifferentiated liposarcoma with myxoid features, pleomorphic liposarcoma with myxoid features, or myxoid pleomorphic liposarcoma in two tumors, pleomorphic sarcoma with focal cartilaginous and rhabdomyoblastic differentiation in one tumor, and epithelioid pleomorphic liposarcoma in one tumor. All tumors harbored FUS::DDIT3 fusions and immunohistochemically expressed DDIT3. All tumors had TP53 mutations, whereas previous specimens with uniform cytology from the same patients lacked TP53 mutations. One tumor showed RB1 deletion and complete loss of Rb expression, which was unclassifiable using DNA methylation-based methods. The rare occurrence of nuclear pleomorphism is underrecognized in MLS and increases the complexity to the diagnosis of liposarcoma. DDIT3 evaluation can be liberally considered in liposarcoma assessment even in the presence of nuclear pleomorphism.

Preoperative physical activity is associated with prognosis in patients with esophageal cancer undergoing thoracoscopic-laparoscopic esophagectomy after neoadjuvant chemotherapy.

OBJECTIVE: This study examined the association between a single preoperative physiotherapy session during neoadjuvant chemotherapy and physical function and that between preoperative physical activity and prognosis. METHODS: In this retrospective, single-center, observational study, we evaluated data from 234 patients scheduled for neoadjuvant chemotherapy and thoracoscopic-laparoscopic esophagectomy who underwent a single preoperative physiotherapy session. The five-repetition sit-to-stand test was performed before and after neoadjuvant chemotherapy. After neoadjuvant chemotherapy, patients were classified into high- and low-physical activity groups based on preoperative physical activity. To examine the association between preoperative physiotherapy and changes in physical function, a multivariate regression analysis was performed. The Cox proportional hazards model was used to investigate the association between preoperative physical activity and overall survival. RESULTS: The median percentage change in the five-repetition sit-to-stand test score was - 3.36%. In the multivariate regression analysis, the regression coefficient of the constant term was - 23.93 (95% confidence interval - 45.31 to - 2.56; P = 0.028). Low physical activity was significantly associated with overall survival after adjustment for confounding factors (P = 0.040). CONCLUSIONS: This study demonstrated that a single preoperative physiotherapy session during neoadjuvant chemotherapy improves physical function, and preoperative physical activity is significantly associated with prognosis.

Is perioperative chemotherapy effective in patients with localized myxoid liposarcoma?

BACKGROUND: This study aimed to compare the local recurrence, distant metastasis and disease-specific survival rates of patients with localized myxoid liposarcoma in the surgery and adjuvant chemotherapy group versus the surgery alone group. METHODS: A total of 456 patients in the Japanese National Bone and Soft Tissue Tumour Registry database who had localized myxoid liposarcoma and underwent surgery and adjuvant chemotherapy or surgery alone between 2001 and 2019 were included in this retrospective study. The study adjusted for background differences between patients who underwent surgery and adjuvant chemotherapy (n = 228) or surgery alone (n = 228) using propensity score matching. RESULTS: Univariate analysis showed no significant difference in local recurrence rate between the two groups (5-year local recurrence-free survival: 98.6% [95% confidence interval: 95.9-99.6] vs. 94.0% [95% confidence interval: 89.7-96.6], P = 0.052). Univariate analysis showed no difference in the incidence of distant metastases between the two groups (5-year distant metastasis-free survival: 80.5% [95% confidence interval: 73.9-85.8] vs. 75.1% [95% confidence interval: 67.7-81.2], P = 0.508). Univariate analysis showed no difference in disease-specific survival between the two groups (5-year disease-specific survival: 92.6% [95% confidence interval: 86.1-96.2] vs. 93.2% [95% confidence interval: 87.6-96.4], P = 0.804). In the high-risk group (n = 203) with high-grade tumours and tumour size ≥10 cm, there were no significant differences in the local recurrence, distant metastasis and disease-specific survival rates between the surgery and adjuvant chemotherapy group and the surgery alone group. CONCLUSION: The effect of adjuvant chemotherapy on localized myxoid liposarcoma appears to be limited.

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.

Factors associated with survival in patients with clear cell sarcoma.

Aims: Clear cell sarcoma (CCS) of soft-tissue is a rare melanocytic subtype of mesenchymal malignancy. The aim of this study was to investigate the clinical and therapeutic factors associated with increased survival, stratified by clinical stage, in order to determine the optimal treatment. Methods: The study was a retrospective analysis involving 117 patients with histologically confirmed CCS, between July 2016 and November 2017, who were enrolled in the Bone and Soft Tissue Tumour Registry in Japan. Results: The five- and ten-year survival rates were 41% (95% confidence interval (CI) 29 to 52) and 37% (95% CI 25 to 49), respectively. On multivariable analysis, the size of the tumour of > 10 cm (p = 0.006), lymph node metastasis at the time of diagnosis (p < 0.001), distant metastases at the time of diagnosis (p < 0.001), and no surgery for the primary tumour (p = 0.019) were independently associated with a poor survival. For N0M0 CCS (n = 68), the development of distant metastases was an independent prognostic factor for survival (early (< 12 months), hazard ratio (HR) 116.78 (95% CI 11.69 to 1,166.50); p < 0.001; late (> 12 months), HR 14.79 (95% CI 1.66 to 131.63); p = 0.016); neoadjuvant/adjuvant chemotherapy (p = 0.895) and/or radiotherapy (p = 0.216) were not significantly associated with survival. The five-year cumulative incidence of local recurrence was 19% (95% CI 8 to 35) and the size of the tumour was significantly associated with an increased rate of local recurrence (p = 0.012). For N1M0 CCS (n = 18), the risk of mortality was significantly lower in patients who underwent surgery for both the primary tumour and lymph node metastases (HR 0.03 (95% CI 0.00 to 0.56); p = 0.020). For M1 CCS (n = 31), excision of the primary tumour was independently associated with better survival (HR 0.26 (95% CI 0.09 to 0.76); p = 0.013). There was no significant difference in survival between the different types of systemic treatment (p = 0.523). Conclusion: Complete excision of the primary tumour and lymph nodes is associated with a better survival in patients with CCS. Systemic treatment appears to provide limited benefits, demonstrating a pressing need for novel systemic agents.

What Are the Complication Rates and Factors Associated With Total Femur Replacement After Tumor Resection? Findings From the Japanese Musculoskeletal Oncology Group.

BACKGROUND: Patients undergoing massive tumor resection and total femur replacement (TFR) face a substantial risk of hip dislocation and infection, often resulting in multiple implant revisions or hip disarticulation. These complications can impact their independence and prognosis. Additionally, their shorter life expectancy is influenced by challenges in achieving local radical resection and controlling metastases. Identifying suitable candidates for TFR is vital, necessitating investigations into dislocation, infection, implant failure rates, local recurrence, overall survival, and associated factors. QUESTIONS/PURPOSES: (1) What is the postsurgical complication (hip dislocation and infection) rate and factors associated with postsurgical complications in patients who underwent TFR after tumor resection? (2) What is the local recurrence rate, implant failure rate, overall survival rate, and factors associated with local recurrence and implant failure? METHODS: We retrospectively evaluated 42 patients (median [range] age 47 years [10 to 79 years]) who underwent TFR and tumor resection at the time of the same surgical procedure between 1990 and 2020 at 12 registered institutions that specialized in tumor treatment in Japan. A total of 55% (23) of the patients were men, and 79% (33) had bone sarcoma. The median (range) follow-up period was 36.5 months (2 to 327 months). Of the 42 patients, 12% (5) were lost to follow-up before 2 years without meeting a study endpoint (postsurgical complications, revision, or amputation), and another 19% (8) died before 2 years with implants intact, leaving 69% (29) of the original group who had either follow-up of at least 2 years or met a study endpoint before the minimum surveillance duration. Another 10% (4) had a minimum of 2 years of follow-up but had not been seen in the past 5 years. Infection was defined as deep-seated infection involving soft tissues, bones, joints, and the area around the implant. We did not consider superficial infections. Implant failure was defined when a patient underwent reimplantation or amputation. The complication and implant failure rates were assessed by the cumulative incidence function method, considering competing events. The Kaplan-Meier method was used to estimate the overall survival rate. RESULTS: The 1-month, 6-month, 1-year, and 2-year dislocation rates were 5%, 12%, 14%, and 14%, respectively. The 1-month, 6-month, 1-year, and 2-year infection rates were 5%, 7%, 10%, and 15%, respectively. Multivariable analyses for hip dislocation and infection revealed that resection of the abductor muscles and large tumor size were positively associated with hip dislocation. The 6-month, 1-year, and 2-year local recurrence rates were 5%, 15%, and 15%, respectively. The 6-month, 1-year, 2-year, and 5-year implant failure rates were 5% (95% confidence interval 1% to 15%), 7% (95% CI 2% to 18%), 16% (95% CI 6% to 29%), and 16% (95% CI 6% to 29%), respectively. Multivariable analyses of local recurrence and implant failure that led to reimplantation or amputation revealed that a positive surgical margin was positively associated with local recurrence. The 1-year, 2-year, and 5-year overall patient survival rates were 95% (95% CI 87% to 102%), 77% (95% CI 64% to 91%), and 64% (95% CI 48% to 81%), respectively. CONCLUSION: Hip dislocation, infection, and local recurrence were frequently observed in patients who received massive tumor resection and TFR in our study, eventually leading to reimplantation or amputation. Preserving the abductor muscles and resecting the tumor with a wide margin can prevent postoperative dislocation and local recurrence. Future research should focus on patient selection criteria, prevention of hip dislocation, and innovative treatments. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Safety and Efficacy of NY-ESO-1 Antigen-Specific T-Cell Receptor Gene-Transduced T Lymphocytes in Patients with Synovial Sarcoma: A Phase I/II Clinical Trial.

PURPOSE: To determine, for patients with advanced or recurrent synovial sarcoma (SS) not suitable for surgical resection and resistant to anthracycline, the safety and efficacy of the infusion of autologous T lymphocytes expressing NY-ESO-1 antigen-specific T-cell receptor (TCR) gene and siRNA to inhibit the expression of endogenous TCR (product code: TBI-1301). PATIENTS AND METHODS: Eligible Japanese patients (HLA-A*02:01 or *02:06, NY-ESO-1-positive tumor expression) received cyclophosphamide 750 mg/m2 on days -3 and -2 (induction period) followed by a single dose of 5×109 (±30%) TBI-1301 cells as a divided infusion on days 0 and 1 (treatment period). Primary endpoints were safety-related (phase I) and efficacy-related [objective response rate (ORR) by RECIST v1.1/immune-related RECIST (irRECIST); phase II]. Safety- and efficacy-related secondary endpoints were considered in both phase I/II parts. RESULTS: For the full analysis set (N = 8; phase I, n = 3; phase II, n = 5), the ORR was 50.0% (95% confidence interval, 15.7-84.3) with best overall partial response in four of eight patients according to RECIST v1.1/irRECIST. All patients experienced adverse events and seven of eight patients (87.5%) had adverse drug reactions, but no deaths were attributed to adverse events. Cytokine release syndrome occurred in four of eight patients (50.0%), but all cases recovered with prespecified treatment. Immune effector cell-associated neurotoxicity syndrome, replication-competent retrovirus, and lymphocyte clonality were absent. CONCLUSIONS: Adoptive immunotherapy with TBI-1301 to selectively target NY-ESO-1-positive tumor cells appears to be a promising strategy for the treatment of advanced or recurrent SS with acceptable toxicity.

Comparison of pre-operative and post-operative radiotherapy in patients with localized myxoid liposarcoma.

BACKGROUND: Myxoid liposarcoma is more radiosensitive than other soft tissue sarcomas, and radiotherapy has been reported to reduce tumour size. This study was performed to compare the rates of local recurrence, survival and wound complications between pre- and post-operative radiotherapy for localized myxoid liposarcoma. METHODS: From the Japanese Nationwide Bone and Soft Tissue Tumor Registry database, 200 patients with localized myxoid liposarcoma who received pre- (range, 30-56 Gy) or post-operative (range, 45-70 Gy) radiotherapy and surgery were included in this retrospective study. Propensity score matching was used to adjust for background differences between patients who received pre- and post-operative radiotherapy. RESULTS: Local recurrence occurred in five (5.0%) and nine (9.0%) patients in the pre- and post-operative radiotherapy groups, respectively (both n = 100). The median follow-up time from diagnosis was 40.5 months (IQR, 26.3-74). Univariate analysis showed a similar risk of local recurrence between the pre- and post-operative radiotherapy groups (5-year local recurrence-free survival 94.9% [95% CI 87.0-98.1] vs. 89.0% [95% CI 79.6-94.3]; P = 0.167). Disease-specific survival was similar between the pre- and post-operative radiotherapy groups (5-year disease-specific survival 88.1% [95% CI 75.5-94.6] vs. 88.4% [95% CI 77.3-94.5]; P = 0.900). The incidence of wound complications was similar between the pre- and post-operative radiotherapy groups (7.0% vs. 12.0%; P = 0.228). CONCLUSIONS: There was no difference in local recurrence, survival or incidence of wound complications between pre- and post-operative radiotherapy for localized myxoid liposarcoma. Therefore, pre-operative radiotherapy for myxoid liposarcoma provides clinical results equivalent to post-operative radiotherapy.

IDH-negative chondrosarcoma with metachronous dedifferentiation only in the metastatic site-A diagnostic pitfall.

Dedifferentiated chondrosarcoma is a subtype of chondrosarcoma with a biphasic histological appearance of a chondrosarcoma component transitioning to a high-grade, noncartilaginous sarcoma. It is particularly difficult to confirm the diagnosis when a sarcoma lacking cartilaginous component occurs at a distant location from the primary lesion. The patient was a 72-year-old woman with multiple lesions in the pelvis, lungs, and liver, 18 months after resection of grade 2 central chondrosarcoma of the sternum. Imaging showed no cartilage component in any location. Although a needle biopsy from the pelvic region confirmed the diagnosis as high-grade sarcoma without a cartilage component, it was difficult to distinguish between a new primary sarcoma and metachronous metastatic lesions from patient's known prior dedifferentiated chondrosarcoma. We therefore performed a comparative molecular analysis by whole-exome sequencing of the biopsy sample and the resected sternal central chondrosarcoma. Both lesions had no IDH1/2 mutations but shared 19 somatic mutations and wide-range chromosomal losses, indicating similar origin. This case illustrates the challenge is coupling a diagnosis of metastatic dedifferentiated chondrosarcoma when no chondroid component is evident. Our study also highlights the benefit of genomic analysis in this differential diagnosis, especially in the context of dedifferentiated chondrosarcoma lacking IDH1/2 mutations.