Novel candidate metastasis-associated genes for synovial sarcoma.

Synovial sarcoma (SS) is an aggressive soft tissue sarcoma with poor prognosis due to late recurrence and metastasis. Metastasis is an important prognostic factor of SS. This study aimed to identify the core genes and mechanisms associated with SS metastasis. Microarray data for GSE40021 and GSE40018 were obtained from the Gene Expression Omnibus database. 186 differentially expressed genes (DEGs) were identified. The biological functions and signalling pathways closely associated with SS metastasis included extracellular matrix (ECM) organization and ECM-receptor interaction. Gene set enrichment analysis showed that the terms cell cycle, DNA replication, homologous recombination and mismatch repair were significantly enriched in the metastasis group. Weighted gene co-expression network analysis identified the most relevant module and 133 hub genes, and 31 crossover genes were identified by combining DEGs. Subsequently, four characteristic genes, EXO1, NCAPG, POLQ and UHRF1, were identified as potential biomarkers associated with SS metastasis using the least absolute shrinkage and selection operator algorithm and validation dataset verification analysis. Immunohistochemistry results from our cohort of 49 patients revealed visible differences in the expression of characteristic genes between the non-metastatic and metastatic groups. Survival analysis indicated that high expression of characteristic genes predicted poor prognosis. Our data revealed that primary SS samples from patients who developed metastasis showed activated homologous recombination and mismatch repair compared to samples from patients without metastasis. Furthermore, EXO1, NCAPG, POLQ and UHRF1 were identified as potential candidate metastasis-associated genes. This study provides further research insights and helps explore the mechanisms of SS metastasis.

The clinical effectiveness and safety of Zone III REBOA for resection of sacropelvic tumors in patients older than 70 years.

BACKGROUND: REBOA is a method used to manage bleeding during surgery involving sacropelvic tumors. Nevertheless, studies on the use of REBOA among elderly people are lacking. The aim of this research was to investigate the efficacy and safety of Zone III REBOA in patients aged more than 70 years. METHODS: A comparative study was conducted using case-control methods. A group of patients, referred to as Group A, who were younger than 70 years was identified and paired with a comparable group of patients, known as Group B, who were older than 70 years. Continuous monitoring of physiological parameters was conducted, and blood samples were collected at consistent intervals. RESULTS: Totally, 188 participants were enrolled and received REBOA. Among the 188 patients, seventeen were aged more than 70 years. By implementing REBOA, the average amount of blood loss was only 1427 ml. Experiments were also conducted to compare Group A and Group B. No notable differences were observed in terms of demographic variables, systolic blood pressure (SBP), arterial pH, lactate levels, blood creatinine levels, potassium levels, or calcium levels at baseline. Additionally, after the deflation of the REBOA, laboratory test results, which included arterial pH, lactate, potassium concentration, calcium concentration, and blood creatinine concentration, were not significantly different (P > 0.05). CONCLUSION: This study indicated that in selected patients aged more than 70 years can achieve satisfactory hemodynamic and metabolic stability with Zone III REBOA. LEVEL OF EVIDENCE: Therapeutic study, Level III.

Efficacy and safety of a 3D-printed arthrodesis prosthesis for reconstruction after resection of the proximal humerus: preliminary outcomes with a minimum 2-year follow-up.

BACKGROUND: The purpose of this study was to investigate the feasibility of using a three-dimensional (3D)-printed arthrodesis prosthesis for reconstruction of the proximal humeral defect after tumor resection. METHODS: A novel proximal humeral prosthesis was designed to restore bone continuity and shoulder arthrodesis and was fabricated via 3D printing technology. Ten patients with primary malignancies in the proximal humerus underwent intra-articular resection and replacement with this prosthesis from 2017 to 2019. Baseline and operative data, oncological and prosthetic survival, and functional status were summarized. RESULTS: This cohort consisted of 9 males and 1 female with a mean age of 32.1 ± 16.1 years. Diagnoses included 5 cases of osteosarcoma, 3 cases of chondrosarcoma and 1 each case of undifferentiated pleomorphic sarcoma and malignant myoepithelioma. The mean operative duration, intraoperative hemorrhage and postoperative length of hospitalization were 151.5 ± 61.0 min, 410.0 ± 353.4 ml and 5.3 ± 1.9 d, respectively. The mean follow-up duration was 29.3 ± 6.4 months, with a minimum of 24 months for the surviving patients. Two patients experienced local recurrence, and four patients developed distant metastases. Detachment of the taper occurred in two patients. One was managed conservatively, and the other received amputation due to concurrent tumor recurrence. The mean MSTS-93 and ASES scores and ranges of forwards flexion and abduction were 24.9 ± 3.1, 79.4 ± 8.3, 71.3 ± 19.4°, and 61.3 ± 16.4°, respectively. The functional outcomes were independent of the preservation of the axillary nerve. Histological study of the glenoid component showed evidence of bone ingrowth at the bone-prosthesis porous interface. CONCLUSION: Application of the 3D-printed arthrodesis prosthesis might be a safe and efficacious method for functional reconstruction in patients who underwent resection of the proximal humerus, especially for those without preservation of the axillary nerve.

A clinical study of the hemodynamic and metabolic effects of Zone 3 REBOA for sacral and pelvic tumor resections.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a key procedure in sacral and pelvic tumor resection that provides hemorrhage control. However, few studies have been performed to capture the effects of REBOA in a nonshock condition and provide a detailed description of the changes occurring with prolonged occlusion time. This study aimed to examine the hemodynamic and metabolic effects of Zone 3 REBOA for sacral and pelvic tumor resections following different periods of REBOA. METHODS: In total, 121 patients who underwent surgical tumor resections of the pelvis and/or the sacrum with the use of aortic balloon occlusion were prospectively enrolled from October 2020 to December 2021. All cases were divided into Group A (occlusion time ≤ 60 min, n = 57) and Group B (occlusion time ≥ 90 min, n = 64). Physiologic parameters were continuously recorded, and laboratory specimens were obtained at regular intervals. RESULTS: Balloon inflation resulted in a significant increase in SBP from 106 to 120 mmHg and decreased to 96 mmHg immediately following balloon deflation. With the application of REBOA, the median blood loss was only 1200 ml (range, 400-7900). When deflating the REBOA, the arterial pH was lower than baseline (7.36 vs. 7.41, p < 0.01), the arterial lactate concentration increased from 0.9 to 1.4 mmol/L (p < 0.01), serum potassium measurements increased from 3.99 to 4.12 mmol/L, serum calcium measurements decreased from 2.31 to 2.04 mmol/L, and blood creatinine decreased from 64 to 60 µmol/L. The operating time of Group B was longer than that of patients in Group A, and the patients in Group B needed more blood units to be transfused. Although laboratory measurements, including pH, potassium, calcium, and blood creatinine, were at the same level in two groups comparison, the lactate was significantly higher in Group B after deflation (p = 0.01). CONCLUSIONS: The results of this study showed that acceptable hemodynamic and metabolic stability can be attained when the occlusion time of REBOA is more than 90 min, although the long duration of occlusion caused relatively higher lactate levels.

Analysis for clinical feature and outcome of chondroblastoma after surgical treatment: A single center experience of 92 cases.

BACKGROUND: Chondroblastoma is a rare, benign, cartilaginous bone tumor derived from epiphyseal chondrocytes. Although the clinical characteristics and experience of surgical treatment of the smaller number of patients has been reported in the literature, it is difficult to draw conclusions about the clinical and radiographic features and the outcome for surgical treatment of this disease due to the rarity of chondroblastoma. This study was aiming to review the epidemiologic characteristics and outcome of surgical management for patients with chondroblastoma. METHODS: We performed a retrospective analysis of 92 patients with chondroblastoma. Clinical data, radiographic images, surgical treatment and outcome were analyzed. Eighty-two patients received the extensive intralesional curettage and ten cases had the En-block resection. RESULTS: The most common site of disease was proximal femur (20.7%, 19/92), followed by distal femur (18.5%, 17/92) and proximal tibia (16.3%, 15/92). The secondary aneurysmal bone cyst component was most common for chondroblastoma of the small irregular bones, such as patella and foot. Four (4.3%, 4/92) cases receiving the extensive intralesional curettage developed the local recurrence, respectively two at the proximal tibia, one at the pelvis and one at the calcaneus. Time to local recurrence were respectively 14.5, 8.8, 27.0 and 5.6 months, with the average 14 months. Kaplan-Meier estimated survivorship curve of local recurrence-free survival rates of one, two and five years were respectively 97.7%, 96.2% and 93.9%. The mean Musculoskeletal Tumor Society (MSTS) score was 29.4. At the last follow-up, no one had the pulmonary metastasis and death associated with the disease. CONCLUSION: Intralesional curettage plus local adjuvants can obtain satisfactory outcome for chondroblastoma. LEVEL OF EVIDENCE: Level IV.

Anlotinib, Vincristine, and Irinotecan for Advanced Ewing Sarcoma After Failure of Standard Multimodal Therapy: A Two-Cohort, Phase Ib/II Trial.

BACKGROUND: Both protracted irinotecan and antiangiogenesis therapy have shown promising efficacy against Ewing sarcoma (EWS). METHODS: Patients diagnosed with recurrent or refractory EWS were enrolled and further categorized into cohort A (≥16 years) or cohort B (<16 years). In the dose-defining phase Ib portion, anlotinib was given daily at a fixed dose, while a 3+3 design with dose de-escalation was used to determine the dose of irinotecan. The next dose-expanding phase II portion employed a conventional two-stage study design model. The primary endpoint was objective response rate at 12 weeks (ORR12w ). RESULTS: A total of 41 patients finally received the treatment regimen, including 29 in cohort A and 12 in cohort B. For cohort A, the first five patients were treated at the initial level of 20 mg/m2 /d d × 5 × 2, and two of them subsequently a dose-limiting toxicity (DLT). An additional six patients were then treated at 15 mg/m2 without any DLT, and the RP2D was determined. Notably, 23 out of 24 patients in cohort A were available for response evaluation at 12 weeks. ORR12w was determined to be 62.5%. For cohort B, no DLT was observed in the first six patients at the initial dose level. At last, 12 patients were included in cohort B. The ORR12w was 83.3%. The most frequently observed grade 3/4 adverse events were leukopenia (28.5%), neutropenia (24.4%), anemia (8.7%), and diarrhea (3.7%). CONCLUSION: The combination of vincristine, irinotecan, and anlotinib demonstrated an acceptable toxicity profile and promising clinical efficacy in patients with advanced EWS. IMPLICATIONS FOR PRACTICE: This is the first trial to evaluate an irinotecan-based regimen in combination with antiangiogenesis tyrosine kinase inhibitors in Ewing sarcoma (EWS). A 3+3 design with dose de-escalation was used to determine the most appropriate dose of irinotecan in each cohort. The next dose-expanding phase II portion employed a conventional two-stage study design model. The objective response rate was 62.5% for adults and 83.3% for children. Median overall survival was not matured. This study shows that the combination of vincristine, irinotecan, and anlotinib demonstrates an acceptable toxicity profile and promising clinical efficacy in patients with advanced EWS.

Intercalary prosthetic replacement is a reliable solution for metastatic humeral shaft fractures: retrospective, observational study of a single center series.

BACKGROUND: Treatments for metastatic fracture of the humeral shaft continue to evolve as advances are made in both oncological and operative management. The purposes of this study were to critically evaluate the effectiveness of intercalary endoprostheses in treating metastatic humeral shaft fractures and to clarify the surgical indications for this technique. METHODS: Sixty-three patients treated surgically for 66 metastatic fractures of the humerus shaft were retrospectively reviewed. Intramedullary nailing (IMN) was performed in 16 lesions, plate fixation (PF) in 33 lesions, and prosthetic replacement in 17 lesions. The operative time, intraoperative blood loss, and postoperative complications were noted. The function of the upper extremities was assessed by the Musculoskeletal Tumor Society (MSTS) score and American Shoulder and Elbow Surgeons (ASES) score. All included patients were followed until reconstructive failure or death. RESULTS: The operative time was relatively shorter in the prosthesis group than in either the IMN group (p = 0.169) or PF group (p = 0.002). Notably, intraoperative blood loss was significantly less in the prosthesis group than in either the IMN group (p = 0.03) or PF group (p = 0.012). The average follow-up time was 20.3 (range, 3-75) months, and the overall survival rate was 59.7% at 12 months and 46.7% at 24 months. One rotator cuff injury, 3 cases of iatrogenic radial nerve palsy, 5 cases of local tumor progression, and 1 mechanical failure occurred in the osteosynthesis group, whereas one case of aseptic loosening of the distal stem and one case of local relapse were observed in the prosthesis group. There were no significant differences in functional scores among the three groups. CONCLUSIONS: Intercalary prosthetic replacement of the humeral shaft may be a reliable solution for pathologic fractures patients; it is indicated for lesions with substantial bone loss, or accompanied soft tissue mass, or for those patients with better prognosis.

Surgical treatment of benign osteolytic lesions in the femoral head and neck: a systematic review.

BACKGROUND AND OBJECTIVES: Treatment of benign osteolytic lesions in the femoral head and neck can be extremely challenging, particularly in children with open physis or for aggressive tumors with pathological fracture. There remains the difficult management decision as to whether to perform complete excision of the involved area or only curettage. Moreover, there is no agreed consensus on the optimal approach to lesion access when performing curettage, which included the transcervical, open and direct approach. The current systematic review aims to provide guidance for selection of surgical methods in clinical practice by comparing the advantages and drawbacks of different procedures. METHODS: A comprehensive literature search of PubMed, Embase and Web of Science databases were executed for human studies restricted to the English language. The search was filtered to include studies published from January 1980 to January 2020. RESULTS: A total of 33 articles including 274 patients were enrolled in the final analysis. The most common diagnosis was chondroblastoma (CBT) (104, 38.0%), followed by giant cell tumor (GCT) (56, 20.4%). There were 57 (20.8%) patients with pathological fracture. Intralesional curettage was performed in 257 (93.8%) patients with the local recurrence of 12.5% at the mean follow-up of 51.5 months. The patients who were presented with open physis or curetted via transcervical approach developed higher local recurrence in patients with CBT (P < 0.001). The local recurrence rate of GCT is 33.3% after curettage, while 8 of 9 (88.9%) patients with fracture were treated successfully with joint preservation. Two of 45 (4.4%) patients developed avascular necrosis (AVN) of femoral head after surgical hip dislocation. The reported Musculoskeletal Tumor Society (MSTS) Score was comparable among patients with different approaches to curettage. CONCLUSION: The majority of benign osteolytic lesions in the femoral head and neck can be treated with intralesional curettage with acceptable local tumor control and satisfactory function. The incidence of local recurrence might be decreased dramatically for lesion access under direct visualization. The native joint maintenance could be achieved even in patients with aggressive lesions presenting pathological fracture.

Surgical Strategy of Pediatric Benign Sacral Tumors.

BACKGROUND: Primary benign osseous tumors and tumor-like lesions at the sacrum are rare in the pediatric population and exact surgical strategy is still unclear. In this study, we evaluate the outcome for pediatric patients with benign tumors and tumor-like lesions at the sacrum who were receiving surgical treatment according to our proposed surgical strategy and classification. METHODS: We analyzed 49 pediatric patients with sacral benign tumors or tumor-like lesions aged 18 years and below from 2005 to 2018. There were 23 men and 26 women with a mean age of 14.0±3.8 years. Nineteen patients had giant cell tumors (GCTs), 9 aneurysmal bone cysts, 5 osteoblastomas, 5 neurogenic tumors, 3 hemangiomas, 3 teratomas, 2 Langerhans cell histiocytosis, 1 chondroblastoma, 1 fibrous dysplasia, and 1 GCT of tendon sheath. We proposed our surgical plan and surgical classification for pediatric patients with sacral benign tumors or tumor-like lesions. RESULTS: The mean follow-up duration was 6.2 years (range, 1.0 to 18.9 y). GCTs (39%, 19/49) and primary aneurysmal bone cysts (18%, 9/49) are the top 2 common histologic types. Preoperative selective arterial embolization (SAE) was performed in 12 cases and 24 patients received intraoperative aortic balloon occlusion (ABO) as the preoperative surgical plan. Furthermore, according to tumor location at the sacrum, we classified surgical excision of sacral benign tumors and tumor-like lesions into 3 types. Fourteen cases were classified as type I, 27 as type II, 3 as type III, and 5 patients with neurogenic tumors cannot be classified into this surgical classification. Ten patients had wound complications. Two had femoral artery thrombosis because of ABO application. One had mechanical failure. Rate of local recurrence was 16%. Seven patients with GCTs and 1 with neurogenic tumor had local recurrence. No patient died of disease at the last follow-up. For the assessment of neurological function, the rate of neurological dysfunction was 12% (6/49). Four cases had urinary incontinence, 3 fecal incontinence, and 3 had bowel obstruction. Next, univariate analysis for influence of preoperative SAE and intraoperative ABO on complications demonstrated that both of them exerted no significant influence on the occurrence of oncological and nononcological complications. CONCLUSIONS: The proposed surgical strategy can provide an excellent therapeutic effect for pediatric benign tumors and tumor-like lesions at the sacrum. Preoperative SAE and intraoperative ABO can safeguard pediatric patients with high vascularity of benign tumor at the sacrum during the operation. LEVEL OF EVIDENCE: Level IV.

Pulmonary metastasis of giant cell tumour: a retrospective study of three hundred and ten cases.

BACKGROUND: Giant cell tumour (GCT) is an invasive benign bone tumour, and the incidence of pulmonary metastasis is rare. We are aiming to analyze risk factors of pulmonary metastasis and clinical prognosis for giant cell tumour patients with pulmonary metastasis. METHOD: We performed a retrospective study of 310 patients with GCT between December 2004 and December 2016. Risk factors of pulmonary metastasis were analyzed by univariate and multivariate logistic regression analysis. Then, the influence of risk factors of overall LR (local recurrence), recurrent tumor at presentation, LR after our therapy, and with soft tissue mass on the pulmonary metastasis-free survival rates was analyzed. RESULTS: The mean follow-up of the present cohort was 45.6 ± 35.3 months (median, 36.6 months; range, 6.1-193.4 months). Eighteen (5.8%) of 310 patients developed pulmonary metastasis. The average interval from surgery of primary tumour to detection of pulmonary metastasis was 15 months. Multivariate logistic regression analysis showed overall local recurrence was the independent risk factor of developing pulmonary metastasis. Among 18 patients with pulmonary metastasis, sixteen cases had history of local recurrence (88.9%, 16/18), including eleven (68.8%, 11/16) with local recurrence at presentation before receiving our therapy and seven (43.8%, 7/16) with local recurrence after receiving treatment in our hospital. Time to local recurrence had obvious difference between patients with and without pulmonary metastasis. Patients with pulmonary metastasis were prone to recur earlier. Furthermore, overall local recurrence, local recurrence after our therapy, recurrent tumor at presentation, and tumour with a soft tissue mass showed statistical differences in the pulmonary metastasis-free survival rates. CONCLUSIONS: Giant cell tumour patients with soft tissue mass and overall local recurrence are prone to develop pulmonary metastasis. Although giant cell tumour is a benign tumor, more attention should be paid to the problem of pulmonary metastatic lesions, and chest CT scan should be recommended during follow-up.

Epidemiological characteristics of 1385 primary sacral tumors in one institution in China.

BACKGROUND: Sacral tumors and tumor-like lesions are a rare group of lesions that can affect children and adults of all ages. Little is known about clinical characteristics of age, gender, histologic type, and anatomic site in China. METHODS: A total of 1385 patients with sacral tumors and tumor-like lesions, which had the clinical record at our bone tumor center from January 2000 to November 2018 were analyzed. The metastatic cancers were not included in the present study. RESULTS: A total of 51.7% (716 cases) were malignant and 48.3% (669 cases) were benign tumors or tumor-like lesions. Of malignant tumors, chordoma was the most common malignant tumor (316 cases, 22.8% of all tumors), followed by chondrosarcoma, myeloma, and other histologic types. The most common histological type of benign tumors was a giant cell tumor accounting for 14.8% (205 cases) of all tumors, followed by neurofibroma, schwannoma, and other types. The most common age group affected by malignant bone tumors was the 51- to 60-year-old group, followed by the 41- to 50-year-old group. The most commonly affected age group for benign tumors and tumor-like lesions was the 31- to 50-year-old group, followed by the 21- to 30-year old group. Furthermore, the following histologic types had gender predilection. Chordoma, chondrosarcoma, myeloma, and osteosarcoma affected more frequently males than females. Malignant peripheral nerve sheath tumor, lymphoma, giant cell tumor, neurofibroma, tuberculosis, teratoma, and epidermoid cyst more frequently affected females than males. CONCLUSIONS: The large cohort of sacral tumors and tumor-like lesions in our database may reveal their clinical characteristics of age, gender, histologic type, and anatomic site in China and features of sacral tumors and tumor-like lesions are fairly distinct from the mobile spine and extremities.

Prognosis and risk factors for malignant peripheral nerve sheath tumor: a systematic review and meta-analysis.

BACKGROUND: No available meta-analysis was printed to systematically introduce the MPNST clinic outcome and risk factors based on largely pooled data. This systematic review and meta-analysis aimed to investigate 5-year OS rate, 5-year EFS rate, and LR rate for MPNST, and to assess potential risk factors for prognosis. METHODS: Electronic articles published between January 1, 1966 and February 29, 2020 were searched and critically evaluated. The authors independently reviewed the abstracts and extracted data for 5-year OS rate, 5-year EFS rate, LR rate, and potential risk factors for prognosis. RESULTS: Twenty-eight literatures were finally included for meta-analysis. The pooled 5-year OS rate, 5-year EFS rate, and LR rate were 49%, 37%, and 38%, respectively. The significant prognostic factors for survival were NF1 status, tumor size, depth, location, malignant grade, margin status, chemotherapy, and radiotherapy. Age and sex were not associated with survival. CONCLUSION: Survival and local recurrence of MPNST are poor. Worse prognosis is mainly associated with NF 1, large size, deep to fascia, high grade, metastases, and location (trunk and head and neck). Complete resection with adequate surgical margins is the mainstay protective factor of MPNST patients, following necessary adjuvant therapies.

Multiple primary tumors: a case report and review of the literature.

BACKGROUND: Multiple primary tumors, especially quadruple primary neoplasms is extremely rare. Fibrous dysplasia (FD), osteosarcoma (OS), and giant cell tumor of bone (GCTB) are three bone tumors with low incidence while primary pulmonary meningioma is a rare disease. In this case report, we present a unique synchronous occurrence of these four separate pathological conditions. CASE PRESENTATION: A 53-year-old male previously underwent resection of OS of fifth rib and FD of eighth rib 1 year ago. Recently, a discontinuous pain at right knee developed. Serial X-ray films showed a progressively pure osteolytic lesion of proximal tibia which extended gradually. The incisional biopsy revealed that this tumor was confirmed as GCTB, and the tumor was successfully managed by extensive curettage and bone cement filling. The diagnosis of GCTB was re-confirmed by the postoperative histopathologic examinations. High-throughput sequencing from the GCTB exhibited a somatic mutation of H3.3A (G35W exon2). Germline testing revealed a germ-cell variant in gene of BRCA2 (exon 8 V220Ifs*4). CONCLUSIONS: This is a unique case with quadruple primary tumors. Germline mutation in gene of BRCA2 may be associated with the occurrence of multiple primary tumors in this patient.

Outcome of surgical treatment of children and adolescents with primary malignant sacral tumours.

BACKGROUND: Little is known about the clinical outcome of children and adolescent patients with primary malignant sacral tumours. METHOD: We retrospectively reviewed 40 patients with malignant sacral tumours aged ≤ 18 years, receiving surgery based on the previous proposed surgical resection classification at our centre from 2003 to 2018. The following data were collected in the present study: age, gender, radiological images, detailed information of the surgical procedure, pulmonary and other metastasis at presentation, complications, local recurrence, metastasis, and death during the follow-up were recorded from the clinical and follow-up files. RESULTS: The mean follow-up was 30.7 months (range, 5.2-146.7 months). The incidence of local recurrence was 27.5% (11/40). Seven cases had surgical site infection and there were 12 cases of wound dehiscence. One had a deep venous thrombosis and one had femoral artery thrombosis. Three had fixation breakage and then received a revision. Tenty-two patients (22/40, 55%) were free of disease. A total of 13 deaths (13/40, 32.5%) were observed and the mean overall survival period was 17.1 months (range, 6.3-34.2 months), and a pulmonary metastasis occurred in 18 patients (45%, 18/45) at the 12.0 ± 10.3 months (range, 2.2-35.3 months) after initial surgery. The overall survival rates at one, two and five years were respectively 88.3%, 62.5%, and 51.9%. In the stratification analysis of young patients with primary malignant tumours at the sacrum after surgery, it revealed the influence of pathological grade, location, and age on the oncological outcomes. Kaplan-Meier estimated a survivorship curve of patients with high and low-grade malignant tumours and showed statistical differences in the overall survival and distant relapse-free survival rates between two groups. Afterwards, the result demonstrated that paediatric patients aged ≤ 14 years had worse prognosis than those aged > 14 years. CONCLUSIONS: It is satisfactory for the outcome of surgical treatment of children and adolescent patients with primary malignant sacral tumours based on proposed surgical classification. Furthermore, paediatric patients aged ≤ 14 years have the tendency of poor prognosis compared to adolescent aged > 14 years.

Apatinib for Advanced Osteosarcoma after Failure of Standard Multimodal Therapy: An Open Label Phase II Clinical Trial.

BACKGROUND: Antiangiogenesis tyrosine kinase inhibitors (TKIs) have been shown to prolong progression-free survival (PFS) in advanced osteosarcoma. Methylsulfonic apatinib is a TKI that specifically inhibits vascular endothelial growth factor receptor-2. We aim to assess apatinib in patients with advanced high-grade osteosarcoma progressing upon chemotherapy. MATERIALS AND METHODS: This phase II trial was conducted at Peking University People's Hospital. We enrolled participants (≥16 years of age) with progressive relapsed or unresectable osteosarcoma. Participants received 750 mg or 500 mg of apatinib according to body surface area once daily until disease progression or unacceptable toxicity. The primary endpoint was objective response rate and PFS at 4 months. RESULTS: A total of 37 participants were finally included into the analysis. Until final follow-up, the objective response rate (complete response + partial response) was 43.24% (16/37). The 4-month PFS rate was 56.76% (95% confidence interval [CI], 39.43%-70.84%). Median PFS and overall survival were 4.50 (95% CI, 3.47-6.27) and 9.87 (95% CI 7.97-18.93) months, respectively. Toxic effects led to dose reductions or interruptions in a total of 25 of 37 (67.57%) patients. The most common grade 3-4 adverse events were pneumothorax in six (16.22%) patients, wound dehiscence in four (10.81%), proteinuria in three (8.11%), diarrhea in three (8.11%), and palmar-plantar erythrodysesthesia syndrome in three (8.11%). No other serious adverse events were reported during the trial. There were no treatment-related deaths. CONCLUSION: Apatinib is a sensitive drug for advanced osteosarcoma with a high response rate after failure of chemotherapy, with similar duration of response compared to other TKIs. IMPLICATIONS FOR PRACTICE: For advanced osteosarcoma progressing upon chemotherapy, antiangiogenesis tyrosine kinase inhibitors (TKIs) have been proved to be effective in prolonging the progression-free survival in previous multicenter trials and have been included into new National Comprehensive Cancer Network guidelines as second-line therapy. Apatinib is a TKI that specifically inhibits vascular endothelial growth factor receptor-2, which is domestically made in China. This phase II trial supports the use of apatinib in patients with advanced osteosarcoma progressing after chemotherapy.

Modified score based on revised Tokuhashi score is needed for the determination of surgical intervention in patients with lung cancer metastases to the spine.

BACKGROUND: Revised Tokuhashi score (RTS) is no longer accurate to predict the survival of patients with lung cancer metastases to the spine. This study is to identify additional prognostic factors in those patients, develop a modified prognostic score based on RTS, and verify the accuracy of the score in prediction. METHODS: Our study included patients with lung cancer metastases to the spine who underwent surgery for spine metastasis. Potential prognostic factors were analyzed. Points were allocated for prognostic factors obtained from survival analyses. A modified score was developed by including prognostic factors and their points to RTS. Accuracy of the modified score was evaluated by comparing the coincidence between predicted and observed survival. Kaplan-Meier analysis and Cox regression models were used. Predictive values of scores for 6-month survival were measured via receiver operating characteristic (ROC) curves. RESULTS: Targeted therapy and tumor markers were additional independent prognostic factors. In the modified score, 2 and 1 points were allocated to the new evaluation factors. The points for factors based on RTS remained the same, and two prognostic groups were redefined. For group A patients who were predicted to live for less than 6 months, conservative procedures would be recommended. For group B patients who were predicted to live for 6 months or more, palliative surgery would be recommended. When comparing the modified score to RTS, the area under the receiver operating characteristic curve (AUCROC) and accuracy of score were improved. CONCLUSIONS: The modified RTS has improved prognostic accuracy in patients with lung cancer metastases to the spine.

Novel "double-strut" fibula ankle arthrodesis for large tumor-related bone defect of distal tibia.

BACKGROUND: Reconstruction for large bone defect of distal tibia after wide resection of tumor is difficult, and the best option remains controversial. This study presents a novel "double-strut" fibula ankle arthrodesis for this issue. METHODS: Nine patients with malignant or aggressive tumors of distal tibia underwent novel "double-strut" fibula ankle arthrodesis after wide tumor resection were retrospectively reviewed. We assessed the bone union time, complications and oncology outcome clinically and radiographically. The Musculoskeletal Tumor Society (MSTS) score and the Foot and Ankle Outcome Score (FAOS) were used to evaluate the functional outcome. RESULTS: The average followup period was 53 ± 46 months. There was no deep infection or graft fracture observed in this series. Internal fixation loosening was found in one case. In these patients, eight achieved union at both proximal and distal junctions, while one achieved union only distally. The mean union time of the proximal junctions and distal junctions was 10.5 ± 1.6 months and 8.7 ± 2.3 months, respectively. The mean postoperative MSTS score was 83% ± 8%. The subscales of FAOS indicating the most problem was Sport and Recreation Function with a mean score of 18 ± 11. At the final follow-up, one of them (1/9, 11%) experienced local recurrence in soft tissue and received another resection surgery, and four (4/9, 44%) patients developed lung metastases. CONCLUSIONS: For large bone defect of distal tibia, this novel "double-strut" fibula reconstruction can be a viable alternative, which is capable of achieving durable ankle fusion and functional salvaged limb with low rate of complications.

Apatinib for advanced sarcoma: results from multiple institutions' off-label use in China.

BACKGROUND: Anti-angiogenesis Tyrosine kinase inhibitors (TKIs) have been proved to show promising effects on prolonging progression-free survival (PFS) for advanced sarcoma after failure of standard multimodal Therapy. Methylsulfonic apatinib is one of those TKIs which specifically inhibits VEGFR-2. This paper summarizes the experience of three Peking University affiliated hospitals in off-label use of apatinib in the treatment of extensively pre-treated sarcoma. METHODS: We retrospectively analysed files of patients with advanced sarcoma not amenable to curative treatment, who were receiving an apatinib-containing regimen between June 1, 2015 and December 1, 2016. Fifty-six patients were included: 22 osteosarcoma, 10 Ewing's sarcoma, 3 chondrosarcoma and 21 soft tissue sarcoma. RESULTS: With median follow-up time of 6 months (range, 0.7-18.0 m), thirty-five (62.5%) patients had partial response, and disease was stable in 11 (19.6%). The 4-month and 6-month progression-free survival rates were 46.3 and 36.5%, respectively. The median duration of response was 3.8 months (95% CI 1.9-5.6 m), with much variability among disease subtypes. The median overall survival was 9.9 months (95% CI 7.6-12.2 m). Grade 3 and 4 toxicities were observed in 8 (14.3%) patients, the most common being hypertension, pneumothorax, wound-healing problems, anorexia, and rash or desquamation. CONCLUSIONS: Apatinib might be effective, with a high objective response rate, in an off-label study of sarcoma patients with advanced, previously treated disease. The duration of response was consistent with reports in different subtypes of sarcomas. Prospective trials of apatinib in the treatment of selected subtypes of sarcomas are needed. TRIAL REGISTRATION: Retrospectively registered in the Medical Ethics Committee of Peking University People's Hospital, Peking University Shougang Hospital and Peking University International Hospital. The trial registration number is 2017PHB176-03 and the date of registration is January 20th 2017.

Can Aortic Balloon Occlusion Reduce Blood Loss During Resection of Sacral Tumors That Extend Into the Lower Lumber Spine?

BACKGROUND: Although aortic balloon occlusion has been shown to reduce blood loss during sacral tumor resections, it has not been validated in larger sacral tumors involving the lower lumbar spine. If such an approach were shown to be associated with less blood loss, it might aid the tumor surgeon in resecting these difficult tumors. QUESTIONS/PURPOSES: (1) Is the use of aortic balloon occlusion associated with reduced blood loss in sacral tumor resections when the lower lumbar spine is also involved? (2) Does the use of the aortic balloon prolong total operating time? (3) What complications are associated with the use of a balloon? METHODS: We retrospectively studied all 56 patients diagnosed with sacral tumors involving the lower lumbar spine (L4, L5) who were treated surgically between 2004 and 2015 at our institute. During that time, 30 of the patients received aortic balloon occlusion therapy, whereas 26 of the patients did not. We generally used aortic balloon occlusion during procedures for hypervascular lesions (for example, giant cell tumors or metastatic renal cancers), primary malignant lesions, and recurrent lesions. We generally avoided use of aortic balloon occlusion in patients with anatomic defects of the aorta (aortic dissection or aneurysm was strictly contraindicated), renal artery bifurcation caudal to the L2 to L3 disc, age older than 70 years or younger than 12 years, history of Stage 2 hypertension [], history of balloon use in previous surgeries, and presence of unstable plaque on abdominal CT. The demographic data, intraoperative blood loss, transfusion volume, operating time, and postoperative wound drainage between the two groups were collected and analyzed. Balloon-related complications were identified. Followup in terms of balloon-related complications was conducted in all 56 patients for at least 6 months after surgery. RESULTS: Intraoperative blood loss was determined to be less in patients treated with the balloon compared with those treated without the balloon (median volume, 2000 mL, range, 400-6000 mL versus 2650 mL, range, 550-6800 mL, respectively; median difference, 605 mL; 95% confidence interval [CI], 100-1500 mL; p = 0.035). Total operative time was not prolonged in the balloon group (including balloon insertion time) compared with those treated without it (median time, 215 minutes, range, 110-430 minutes versus 225 minutes, range, 115-340 minutes, respectively; median difference, 10 minutes; 95% CI, -40 to 30 minutes; p = 0.902). Balloon-related vascular complications included local hematoma at the puncture site in five patients, femoral artery spasm in three patients, lower limb ischemia in one patient, and femoral artery pseudoaneurysm in one patient. Acute kidney injury was found in two patients in the balloon group. CONCLUSIONS: This study demonstrated that placement of the aortic balloon at a level just caudal to the renal artery bifurcation was associated with lower intraoperative blood loss and transfusion in lumbosacral tumor resections. However, procedure-specific complications were common and there was no benefit to total operative time. We suggest that the surgical procedures still need to be further refined to minimize complications. We also recommend that prospective studies be undertaken to confirm the efficacy of aortic balloon occlusion in surgery for lumbosacral tumors. LEVEL OF EVIDENCE: Level III, therapeutic study.

Is a Modular Pedicle-hemipelvic Endoprosthesis Durable at Short Term in Patients Undergoing Enneking Type I + II Tumor Resections With or Without Sacroiliac Involvement?

BACKGROUND: Functional reconstruction after Enneking Type I + II resections of the pelvis (those involving both the ilium and the acetabulum) is challenging, especially if resection of part of the sacrum is included. To assess the clinical outcomes of a newly designed modular pedicle-hemipelvic endoprosthesis, we performed a preliminary retrospective study on its clinical use in a small group of patients. QUESTIONS/PURPOSES: The purposes of this study were (1) to evaluate in a small case series whether the new endoprosthesis restored lower limb function and lumbopelvic stability in the short term; (2) to identify the complications associated with use of the new prosthesis; and (3) to assess the 5-year cumulative survival, the cumulative incidence of a major postoperative event, and the cumulative incidence of implant failure in this group of patients. METHODS: Between August 2012 and August 2014, our center performed 274 internal hemipelvectomies for oncologic indications. Among these, 20 were treated with the new endoprosthesis, which was designed for fixation both to the residual sacrum as well as the lumbar spine. An earlier version of the device had been removed from the market because of an unacceptable risk of serious complications. All of the 20 tumors were sarcomas necessitating en bloc resection. The implant is modular and can meet the different-sized defects in each patient. The general indication for use of the new implant was a total acetabular defect with extensive iliac involvement or total loss of the sacroiliac joint and/or hemisacrum. All 20 patients were followed up for a minimum of 24 months or until death in those patients who survived < 2 years (median, 36 months; range, 6-60 months). The clinical data were retrieved from the database and the study endpoints (function according to the Musculoskeletal Tumor Society [MSTS] score, complications, and survivorship of patients and implants) were ascertained by chart review. Lumbopelvic stability was defined as an excellent or good rating according to the International Society of Limb Salvage radiologic implant evaluation system. The cumulative survival of patients was estimated using the Kaplan-Meier approach. The cumulative incidence of major postoperative events including local recurrence, metastasis, and reoperation was estimated using a competing events analysis; the cumulative incidence of implant failure, including mechanical failure or deep infection, in patients who underwent reoperation was also estimated using a competing events analysis. RESULTS: In the 16 patients who survived > 12 months, the median MSTS score was 19 of 30 (range, 5-26). Radiographic assessments demonstrated lumbopelvic stability in all of the 16 patients. Twelve of 20 patients developed postoperative complications, primarily including deep infection (one), hip dislocation (two), and local recurrence (three). Major revision surgery was performed in five of 20 patients. The estimated 5-year Kaplan-Meier patient survival rate was 69% (95% confidence interval [CI], 59%-79%), whereas the cumulative incidence of major postoperative events and implant failure using the competing risk estimator was 42% (95% CI, 23%-60%) and 15% (95% CI, 4%-34%) at 5 years, respectively. CONCLUSIONS: Preliminary results with hemipelvic reconstruction using this new endoprosthesis achieved fair functional results and the complications that were observed appeared comparable to other reconstruction options at short-term followup. Longer-term surveillance is called for to see whether this implant will be durable compared with other available reconstructive alternatives such as a custom-made megaendoprosthesis or an autograft/allograft-prosthetic composite. LEVEL OF EVIDENCE: Level IV, therapeutic study.