Objective:To understand the genetic variation of soft tissue sarcomas, and to provide a scientific evidence for the individualized treatment.Methods:The somatic mutation and germline mutation of 45 adult soft tissue sarcomas had been detected by high-throughput sequencing technology, the clinical data were also analyzed.Results:A total of 88 gene mutations were detected in 45 samples, including 78 single nucleotide variation (SNV), 13 insertion/deletion (Indel) and 19 copy number variation (CNV). The most common mutant genes are TP53, CDKN2A, MDM2, CDK4, NF1 and PTEN. Among them, the mutation rates of TP53-MDM2/MDM4-CDKN2A pathway, CDKN2A/CDK4/RB1 pathway, and RAS/NF1/PTEN/PI3K pathway were more frequent (32/88, 36%). In terms of immunotherapy biomarkers among 10 samples, the median value of tumor mutation burden was 2.02 muts/Mb (0-4.24 muts/Mb), and all were microsatellite stable.Conclusions:This study analyzes the genetic variation of soft tissue sarcoma, and determines the high-frequency gene mutations and pathways, which may be the potential drug targets. This finding can provide scientific evidences for the personalized treatment of soft tissue sarcoma.

Objective:To understand the genetic variation of soft tissue sarcomas, and to provide a scientific evidence for the individualized treatment.Methods:The somatic mutation and germline mutation of 45 adult soft tissue sarcomas had been detected by high-throughput sequencing technology, the clinical data were also analyzed.Results:A total of 88 gene mutations were detected in 45 samples, including 78 single nucleotide variation (SNV), 13 insertion/deletion (Indel) and 19 copy number variation (CNV). The most common mutant genes are TP53, CDKN2A, MDM2, CDK4, NF1 and PTEN. Among them, the mutation rates of TP53-MDM2/MDM4-CDKN2A pathway, CDKN2A/CDK4/RB1 pathway, and RAS/NF1/PTEN/PI3K pathway were more frequent (32/88, 36%). In terms of immunotherapy biomarkers among 10 samples, the median value of tumor mutation burden was 2.02 muts/Mb (0-4.24 muts/Mb), and all were microsatellite stable.Conclusions:This study analyzes the genetic variation of soft tissue sarcoma, and determines the high-frequency gene mutations and pathways, which may be the potential drug targets. This finding can provide scientific evidences for the personalized treatment of soft tissue sarcoma.

Objective: To evaluate the efficacy and prognostic factors of comprehensive treatment of undifferentiated high grade pleomorphic sarcoma (UHGPS) in extremities and trunk, including surgery, radiotherapy and chemotherapy. Methods: A retrospective analysis and follow-up of 131 UHGPS cases with clinical stage Ⅱ or Ⅲ in extremities and trunk soft tissue was performed to analyze the prognostic factors. Survival data were collected through follow-up. The survival rate was calculated with life table method and Kaplan-Meier survival curves were drawn. Survival rate between the two groups was compared using Log rank test. The multivariate analysis was performed using Cox regression model. Results: The median survival time of 131 patients was 41.6 months. The 1-year, 3-year and 5-year survival rates were 95.0%, 82.0%, and 77.0%, respectively. The 5-year recurrence-free survival rate was 81.0%, and the 5-year metastasis-free survival rate was 72.0%. Univariate analysis showed that the tumor size, initial or recurrence, surgical margin, AJCC stage, and with/without standard treatment were associated with overall survival (all P<0.05). Stratification analysis according to the American Joint Committee of Cancer (AJCC) stage showed that 5-year survival rate of stage Ⅱ patients with radiotherapy was 100.0%, which was higher than that of patients without radiotherapy (79.6%) and the difference was statistically significant (P=0.010); but no statistical significance of radiotherapy for stage Ⅲ and chemotherapy for stage Ⅱ or Ⅲ patients (all P>0.05). The multivariate analysis showed surgical margin (HR=4.220, P=0.002), with/without standard treatment (HR=4.040, P=0.030) were independent risk factors associated with prognosis of UHGPS patients. Conclusions For UHGPS with stage Ⅱ or stage Ⅲ in extremities and trunk soft tissue, patients with complete resection and standard treatment have improved prognosis. Therefore, standard treatment, including extensive resection for the first surgery, should be performed according to expert consensus in order to increase the long-term survival rate. Adjuvant radiotherapy should be performed for stage Ⅱ patients.

Objective: To evaluate the clinical value of preoperative ¹⁸F-Fludeoxyglucose (¹⁸F-FDG PET-CT) in lymphatic metastasis diagnosis of cutaneous melanoma on extremities and trunk. Methods: 112 patients with cutaneous melanoma pathologically of extremities and trunk from January 2006 to December 2016, who received ¹⁸F-FDG PET-CT examination preoperatively, were retrospectively reviewed. The correlations between the maximal diameters of lymph nodes, the maximal standard uptake value (SUV) and the diagnostic impression grades of PET-CT examination, and the final pathological diagnosis were analyzed. The correlations between Breslow thickness of primary lesions and the diagnostic impression of PET-CT examination were also analyzed. All the above were analyzed with Receiver Operating Characteristic (ROC) curve to get the cut-off value. Based on the final results of pathological diagnosis of lymph nodes as the golden standard, the statistically significant indicators of ROC curve analysis were used to evaluate the diagnostic effect, as well as to calculate the sensitivity, specificity and accuracy. With gender, age, maximal diameter of lymph nodes, maximal SUV, diagnosis impressions, and Breslow thickness as the independent variables and pathological diagnosis results of lymph nodes as the dependent variable, two-class stepwise Logistic regression analysis was used to determine the independence of diagnostic indicators. ROC curve analysis and log rank test were used to analyze the relationship between Breslow thickness and patient survival. Results: To evaluate melanoma patients′ lymph node status, the results of ROC curve analysis showed that the area under the curve of lymph node maximal diameter, maximal SUV, diagnosis impression of PET-CT examinations were 0.789, 0.786 and 0.816, respectively (all P<0.05). The cut-off values were 0.85 cm, 1.45 and 2.5, respectively. The sensitivity of the cut-off values to determine the status of lymph nodes in melanoma patients were 71.4%, 64.9% and 72.1% respectively, and the specificities were 85.2%, 88.7% and 87.0% respectively. Multivariate Logistic regression analysis showed that PET-CT diagnosis impressions had independent diagnostic significance for the lymph node status of melanoma patients (OR=11.296, 95%CI: 2.550~50.033). The area under the curve of Breslow thickness evaluating PET-CT diagnostic impression is 0.664 (P=0.042) and the cut-off value was 4.25 mm. The survival rate of the patients with Breslow thickness ≥ 4.25 mm was lower than that in the group <4.25 mm (P=0.006). Conclusions ¹⁸F-FDG PET-CT can help to evaluate metastases and make treatment decisions for cutaneous melanoma of extremities and trunk, especially for patients whose primary lesion′s Breslow thickness has reached more than 4.25 mm. For the patients whose maximal SUV of regional lymph node is higher than 1.45 and short diameter of the largest lymph node is larger than 0.85cm, the possibility of metastases should be considered.

Objective: To evaluate the clinicopathological characteristics of foot and ankle soft tissue and bone tumor, and to analyze the prognosis and the related factors of malignant tumors in this site. Methods: 74 patients with soft tissue and bone tumors of foot and ankle from January 2006 to February 2017 were retrospectively analyzed. The clinicopathological characteristics, the treatment and survival status of malignant tumors were followed up, and the clinical and therapeutic factors related to prognosis were analyzed. Results: Of the 74 patients, 34 were males and 40 were females. The male to female ratio was 1∶1.18; the age ranged from 12 to 64 years and the median age was 42 years. Tumors located in forefoot of 22 cases, 22 in midfoot, 10 in hind foot, 14 in ankle joint and 6 in multiple sites. 14 cases were bone tumors, including 7 benign and 7 malignant, and 60 cases were soft tissue tumors, including 14 benign and 46 malignant. The most common malignant soft tissue tumors were synovial sarcomas (13 cases), and the most common benign soft tissue tumors were hemangiomas (4 cases). 44 cases of malignant tumors underwent surgery were followed up, of which were 7 bone and 37 soft tissue malignant tumors. Limb salvage surgeries were performed in 33 cases and amputation in 11 cases. The median follow-up time was 69.8 months, and the median survival time was 40.7 months. The 1-year, 3-year and 5-year survival rate of soft tissue malignant tumors was 88.0%, 73.0%, and 63.0%, respectively. The 1-year, 3-year and 5-year survival rate of bone malignant tumors was 86.0%, 57.0% and 57.0%, respectively. Univariate analysis showed that the prognostic factors affecting 5-year survival rate were tumor size and adjuvant therapy (P<0.05). Patient′s gender, age, tumor location, histological type and surgical procedure had no effect on overall survival(P>0.05). Multivariate analysis showed that tumor size was an independent prognostic factor (RR=7.262, P=0.005). Conclusions Forefoot and midfoot are more common in foot and ankle soft tissue and bone tumors. Synovial sarcoma is the most common diagnosis in malignant soft tissue tumors, and hemangioma is the most common diagnosis in benign soft tissue tumors. The prognostic factor of malignant soft tissue and bone tumors in foot and ankle is tumor size. Patients with the tumor size of 5 cm or more have a worse prognosis.

Soft tissue sarcomas (STS) consist of a heterogeneous group of rare malignancies with mesenchymal origin. Surgical resec-tion is the primary treatment for STS, but radiation therapy (RT) also plays an important role in the treatment. Radiotherapy for STS has advanced significantly over the past 50 years. Both preoperative and postoperative radiotherapies are equivalent in local control but are associated with different toxicity profiles. Boost techniques for STS include brachytherapy, intraoperative radiation therapy (IORT), and external beam. Long-term toxicities of RT to normal tissues have been reduced because of improvements in image guid-ance and intensity-modulated radiotherapy, which significantly increase the precision and delivery of RT. This review discusses RT tech-nologies and their acceptable treatment principles.

Objective: To investigate the clinicopathological features and prognosis of malignant peripheral nerve sheath tumors (MPNST). Methods: We retrospectively reviewed the clinical data of MPNST patients who were treated at Cancer Institute & Hospital, Chinese Academy of Medical Science from January 1999 to January 2016. A total of 140 patients with 66 male and 74 female with MPNST were enrolled in the study. The median age was 40 at the time of diagnosis. Survival analysis were estimated by Kaplan-Meier method and Log rank test. Multivariate analysis were estimated by Cox proportional hazards regression model. Results: The median follow-up time was 43.0 months. The 3- and 5-year overall survival (OS) rates were 56.4% and 48.6%, respectively. The 3-year local recurrence (LR) rate and distant metastasis (DM) rates were 42.9% and 49.3%, respectively. Univariate analysis showed that the tumor location, AJCC stage, S-100, radiotherapy and margin status affected 5-year OS rate (all P<0.05). The tumor location, AJCC stage, S-100, Ki-67 staining, margin status, radiotherapy and chemotherapy affected 3-year LR rate (all P<0.05). The tumor location, AJCC stage, S-100, Ki-67 staining and margin status affected 3-year DM rate (all P<0.05). Multivariate analysis showed that the tumor location, AJCC stage, S-100 were independent factors for 5-year OS rate (all P<0.05). The tumor location, Ki-67 staining and chemotherapy were independent factors for LR (all P<0.05) while the AJCC stage, margin status and Ki-67 staining were independent factors for DM (all P<0.05). Conclusions MPSNT is an aggressive tumor with poor prognosis. Multiple factors were identified in this study. Patients with the tumor located at head and neck, advanced AJCC stage and negative S-100 usually have a low 5-year overall survival rate. Patients with the tumor located at head and neck, Ki-67 staining ≥ 20% and without chemotherapy had a higher tendency of local recurrence. Poor prognosis factors for DM were advanced AJCC stage, positive margin and Ki-67 staining ≥ 20%.

ObjectiveTo investigate the in vivo biological performance of 5 porous bioceramic scaffolds,which were bioglass,β-tricalcium phosphate (β-TCP),hydroxyapatite (HA),β-calcium silicate (β-CS) and α-CS,implanted in rabbit dorsal muscle.MethodsThe 5 porous bioceramic scaffolds were fabricated by adding pore-forming materials and sintering,and then were investigated by X-ray diffraction,porosity mensuration and biomechanics test.The scaffolds were implanted into rabbit dorsal muscle for 4,8,12,16 weeks,respectively.The samples were analyzed by X-ray,Micro-CT,histological analysis,scanning electron microscope (SEM) and energy dispersive spectrometer (EDS).The expression of bone morphogenetic protein(BMP-2) and BMP-7 in the muscle in touch with bioceramic scaffolds were also investigated by polymerase chain reaction(PCR).ResultsThe characteristic analysis of 5 scaffolds showed that the sequence of compressive strength was bioglass＞α-CS＞β-CS＞β-TCP＞HA,the sequence of elasticity modulus was α-CS＜β-TCP＜HA＜β-CS＜bioglass.It was confirmed by X-ray,Micro-CT and histological analysis that the sequence of biodegradability was β-CS＞α-CS＞β-TCP＞bioglass＞HA.The histological observation showed no new bone formation in five scaffolds.A Ca-P layer was formed in the surface of bioglass,α-CS and β-CS,which suggested their in vivo bioactivity.After 16 weeks,the expression of BMP-2 and BMP-7 was found only in β-CS.Conclusion The porous calcium silicate scaffold,which was promising for bone tissue engineering,was with good in vivo bioactivity and biodegradability,without in vivo osteoinductivity.

Objective To investigate technique and effect of reconstruction with alcohol-inactivated autograft-prosthesis composite after en bloc resection of giant cell tumor of bone around the knee.Methods From January 2007 to October 2008,8 patients with Campanacci grade Ⅲ giant cell tumor of bone around the knee underwent en bloc resection of tumor and reconstruction with alcohol-inactivated autograft-prosthesis composite in our hospital.There were 5 males and 3 females,aged from 20 to 43 years (average,31years).The tumor located in distal femur in 5 cases and proximal tibia in 3 cases.There were 4 cases of primary tumor and 4 cases of recurrent tumor.Two patients combined with pathological fracture.The Musculoskeletal Tumor Society (MSTS) score was used to evaluate limb function,and the International Society of Limb Salvage (ISOLS) score was used for radiographic evaluation.Results All patients were followed up for 38 to 67 months (average,54 months).No recunrence,metastasis,prosthesis loosening were found.The mean healing time of autograft and host bone was 5.5 months.At final follow-up,the MSTS score ranged from 25 to 29 [average,26.3 (88％)]; the ISOLS score ranged from 28 to 35 [average,32.8 (88.5％)].Creeping substitution was possibly the main way of bone union.The healing time in femoral lesion was faster than that in tibial lesion.Conclusion For Campanacci grade Ⅲ giant cell tumor of bone around the knee,en bloc resection and reconstruction with alcohol-inactivated autograft-prosthesis composite is an effective method,which can provide satisfactory results.

Objective To evaluate the clinical outcome of alcohol-deactivated autograft-prosthesis composite after resection of bone giant cell tumor in distal femur.Methods From January 2007 to October 2008,5 patients with bone giant cell tumor in distal femur were treated with alcohol-deactivated autograftprosthesis composite,including 3 males and 2 females with an average age of 29.6 years(range,22-40).Three patients were diagnosed with postoperative recurrence,and 2 with pathological fracture.All patients were of Campanacci Ⅲ.Three-dimensional finite element models with 40% bone defect in distal femur were established based on CT images of a healthy volunteer.Three times of body mass load corresponding to the normal walking gait cycle was applied.The influence on stress distribution of femur-cement and prosthesis stem was analyzed.Results All patients were followed up for average 37 months,there was no infection,recurrence,loosening and limb length inequality.The bony healing time was 6 to 11 months.The mean MSTS function score was 25.7(range,25-27).The mean ISOLS graft score was 31.4 (range,28-35).The finite element analysis showed that for the short-term model,the maximum stress was 145.82 MPa in the proximal femur,40.90 MPa in the medial side of 1/4 proximal cement,and 389.24 MPa in the proximal prosthesis stem.The maximum stress was not exceeding the fatigue strength in three sites.For the long-term model,with the bone healing,the maximum stress on three sites decreased to 139.05,36.95,and 253.65 MPa,respectively.Conclusion These results suggest that the alcohol-deactivated autograft-prosthesis composite after resection ot bone giant cell tumor in distal femur can reduce the tumor recurrence and improve the short-term limb function,It is stable in short term and can reduce stress shielding in long term.