Genomic and transcriptomic characterization of pre-operative chemotherapy response in patients with osteosarcoma.

Osteosarcoma is a heterogeneous disease with regard to its chemotherapy response and clinical outcomes. This study aims to investigate the genomic and transcriptomic characteristics related to pre-operative chemotherapy response. Samples from 25 osteosarcoma patients were collected to perform both whole exome and transcriptome sequencing. Osteosarcoma had significant amount of chromosomal copy number variants (CNVs). Chemotherapy responders showed the higher chromosomal CNV burden than non-responders (p = 0.0775), but the difference was not significant. The percentage of COSMIC signature 3, associated with homologous recombination repair deficiency, was higher in responders (56%) than in non-responders (45%). Transcriptomic analysis suggested that 11 genes were significantly up-regulated in responders and 18 genes were up-regulated in non-responders. Both GSEA and KEGG enrichment analysis indicted that four pathways related to cardiomyopathy were up-regulated in responders, while neuroactive ligand - receptor interaction was up-regulated in non-responders. Finally, a previously published chemoresistant model was validated using our dataset, with the area under the curve of 0.796 (95% CI, 0.583-1.000). Osteosarcoma had the heterogeneous mutational profile with frequent occurrence of CNVs. Transcriptomic analysis identified several signaling pathways associated with chemotherapy responsiveness to osteosarcoma. Transcriptomic signatures provides a potential research direction for predicting the chemotherapy response.

A comparative study of reconstruction modalities after knee joint-preserving tumor resection: reconstruction with a custom-made endoprosthesis versus reconstruction with a liquid nitrogen-inactivated autologous bone graft.

BACKGROUND: This study evaluated the feasibility, complications, graft survival rate, and clinical outcomes of joint-preserving resection using a custom-made endoprosthesis and liquid nitrogen-inactivated autologous bone graft reconstruction in patients with malignant bone tumors around the knee joint. METHODS: We retrospectively analyzed 23 consecutive patients who underwent joint preservation surgery between 2008 and 2018 at our center. The study cohort included 13 patients who underwent custom-made endoprosthesis reconstruction and 10 who underwent liquid nitrogen-inactivated autologous bone graft reconstruction. The resected bone length, distance between the resection line and the joint, intraoperative blood loss, operation time, complications, and MSTS were compared between the two groups. RESULTS: The median follow-up time was 68.5 months in the endoprosthesis group and 65.3 months in the inactivated autograft group. There were no significant differences in baseline characteristics, resected bone length, distance between the resection line and the joint, or intraoperative blood loss between the two groups. The operative time was longer in the inactivated bone graft group than in the endoprosthesis group (p < 0.001). The endoprosthesis group had more complications (six patients) and reoperations due to complications (five) than the inactivated autograft group (one), but there was no significant difference in the incidence of complications between the two groups (p = 0.158). The inactivated autograft group had one patient with type 1b complications, while the endoprosthesis group had one with type 1b complications, one with type 2b complications, and one with type 4a complications. One patient in the endoprosthesis group with type 5a complications experienced two soft tissue recurrences. The overall 5-year survival rate was 86.5% and the graft survival and final limb salvage rates were 100% in both groups. After the follow-up period, the mean MSTS scores were 91% ± 7% in the endoprosthesis group and 94% ± 6% in the inactivated autograft group, with no significant difference (p = 0.280). CONCLUSION: Joint-preserving resection is a reliable and effective tumor resection method that can achieve good postoperative function. There were no significant differences in the incidence of complications, overall survival rate, or graft survival rate between the two groups.

Parallel reconstruction of vascularized fibula autograft for treatment of complications after resection of malignant tumor from the thigh.

SUMMARY: The authors herein introduce a modification of parallel reconstruction with a vascularized fibula autograft (VFA) for cases of femur allograft complications. Conventional parallel reconstruction, in which the fibula with its vascular pedicle is placed on the medial side of the femur and allogeneic bone, may be an effective means to solve the allograft complications. However, the limited contact area between the fibula and femur/allogeneic bone can affect the bone healing ability. Furthermore, the rigid internal fixation method for the VFA may cause stress shielding and result in bone resorption. The authors propose the use of modified parallel reconstruction of the VFA with fibula expansion and titanium cable fixation for patients with allograft-host junction nonunion, allogeneic bone fracture, and femoral shaft fracture after surgical removal of a malignant tumor from the thigh. The modified parallel reconstruction has been performed on 5 patients (2 patients underwent fibular expansion). All 5 patients with 7 nonunion of allograft-host junction or fracture were followed up 33.2 months. The length of fibular graft is 10-20cm, with an average of 15.0 cm. The union rate of allograft-host junction and fracture was 100% (7/7), and the union time 15.9 months. This modified parallel reconstruction technique can achieve satisfactory union in treatment of the above complications.

Avoiding Misdiagnosis and Missed Diagnosis for Appropriately Treating Spinal Osteoid Osteomas: A Single-Center Experience.

OBJECTIVES: To analyze the causes of misdiagnosis and missed diagnosis in spinal osteoid osteoma, and to put forward solutions to improve diagnosis accuracy and treatment efficacy in patients. METHODS: We performed a retrospective cohort study on patients with spinal osteoid osteoma in Beijing Jishuitan Hospital from January 1983 to September 2019. All patients underwent surgery. The outcome measures were the extent of local pain, nocturnal pain, radicular symptoms of extremities after surgery, and reduction or disappearance of lesions on CT after surgery. RESULTS: Thirty-seven patients with spinal osteoid osteoma were recruited in the study. A total of 27% were female, and the mean (SD) age at diagnosis was 21.3 (8.7) years. A total of 87.0% of patients presented with nocturnal pain, and 94.7% of patients were responsive to NSAIDS treatment. The mean (SD) time from the initial onset of symptoms to the final diagnosis was 14.7 (12.5) months. Only four of 37 (10.8%) patients were correctly diagnosed with spinal osteoid osteoma on the first visit to the local hospital. CT is associated with a higher diagnosis rate than X-ray or MRI on the first visit. Surgical navigation was used in 88.9% of patients who underwent curettage resection, and in 10% of patients who underwent en bloc resection. A total of 37 of 37 patients (100%) reported relief of local pain and radicular symptoms of extremities after surgery, and no recurrence of tumors was found during follow-ups. CONCLUSIONS: Spinal CTs are recommended to be performed if osteoid osteoma is suspected based on clinical manifestation, including nocturnal pain and responsiveness to NSAIDS treatment, to avoid misdiagnosis and missed diagnosis of spinal osteoid osteoma.

Bone defect reconstruction with autologous bone inactivated with liquid nitrogen after resection of primary limb malignant tumors: An observational study.

Surgical treatment of malignant bone tumors comprises tumor resection and reconstruction. The most commonly used reconstruction method is prosthesis replacement, which achieves good early function, but has a high long-term incidence of complications. Another reconstruction option is autologous bone replantation, which has the advantages of anatomical matching and no need for large bone bank support. Few studies have evaluated reconstruction with liquid nitrogen-inactivated autogenous bone.The present study aimed to evaluate the oncological results, bone healing results, complications, and indications of reconstruction with liquid nitrogen-inactivated autogenous bone grafts.The study population comprised 21 consecutive patients. The tumor site was the tibia in 9 cases, femur in 8, and humerus in 4. There were 37 osteotomy ends in total. After freezing and rewarming, the medullary cavity of the autogenous bone was filled with antibiotic bone cement. Seventeen patients received bilateral plate fixation, 2 received intramedullary nail and distal plate fixation, and 2 received single plate fixation.The average follow-up was 31 ±â€Š6 months. Eighteen patients survived without tumors, and the 3-year survival rate was 80.4%. All cases had adequate surgical margins, but recurrence developed in 1 patient. Metastasis occurred in 3 patients, who all died of metastasis. Intraoperative inactivated bone fracture occurred in 1 patient, and screw breakage was found in 1 patient. Nonunion occurred at 1 humeral diaphysis osteotomy site, and 1 patient was lost to follow-up; the average healing time of the other 35 ends was 13 ±â€Š6 months, and the bone healing rate was 97.2%. The average bone healing times in the metaphysis and diaphysis were 9 ±â€Š3 months and 15 ±â€Š6 months (P = .003). The average bone healing times in the upper and lower limbs were 16.6 ±â€Š7.4 months and 12.3 ±â€Š5.8 months (P = .020). The average Muscle and Skeletal Tumor Society score was 28 ±â€Š3 (21-30) in the 18 survivors.Liquid nitrogen-inactivated autologous bone replantation for primary malignant limb tumor was safe and effective, as shown by the relatively low complication rate, high bone healing rate, and satisfactory postoperative function. This is a reliable biological reconstruction method for malignant bone tumors with specific site and bone destruction characteristics.

[Non-cemented modular prosthetic reconstruction for bone defect after tumor resection in lower extremities].

OBJECTIVE: To report the preliminary clinical results and analyze the prognostic factors of prosthetic failures with non-cemented modular prosthetic reconstruction after tumor resection in lower extremities. METHODS: A clinical data of 150 patients with lower extremity tumors treated with MEGASYSTEM-C non-cemented modular prosthetic reconstruction between October 2011 and September 2016 was retrospectively analyzed. There were 88 males and 62 females, aged from 12 to 81 years, with a median age of 24 years. According to World Health Organization (WHO) classification of bone tumors, 120 cases were primary malignant tumors, 27 cases were intermediate tumors, and 3 cases were metastatic tumors. Among them, 134 cases underwent primary operation and 16 cases underwent reoperation after recurrence. Eighty-seven patients with malignant tumors received chemotherapy before and after operation, and no patient received local radiotherapy during perioperative period. Proximal femur was reconstructed in 32 cases, distal femur in 83 cases, and proximal tibia in 35 cases. The postoperative follow-up time, the results of oncology (survival status and tumor recurrence), and prosthesis failure (prosthesis survival rate, reasons for failure, treatment plan after failure) were recorded. The reason of the prosthesis failure was classified into 5 types according to the classification defined by Henderson et al. Kaplan-Meier survival analysis and Log-Rank test were used to analyze patient and prosthesis survival. Lower extremity function was assessed by using the Musculoskeletal Tumor Society (MSTS) scoring system and MSTS scores were compared for patients with different reconstruction sites. RESULTS: All patients were followed up 5-84 months, the median follow-up time was 39 months. During the follow-up period, there were 116 cases of tumor-free survival, 10 cases of tumor-bearing survival, and 24 died of lung metastasis or multiple metastases. The 3-year and 5-year survival rates of 120 patients with primary malignant tumors were 83.1% and 76.6%. There was no significant difference in survival rate between different reconstruction sites ( P=0.851). Seven cases (4.7%) had local recurrence at 7-21 months after operation. The 3-year and 5-year survival rates of the prosthesis in 150 patients were 94.4% and 92.5%. There was no significant difference in survival rate between different reconstruction sites ( P=0.765). There were 26 failures in 24 patients (16.0%) during the follow-up period. There were 9 cases of type 1 failure, 1 case of type 2 failure, 3 cases of type 3 failure, 5 cases of type 4 failure, and 8 cases of type 5 failure. At last follow-up, 120 of the 126 patients survived without prosthetic failure. Except that the influence of different parts of prosthesis on the incidence of type 4 failure ( P=0.029), the influence of chemotherapy on the incidence of type 5 failure ( P=0.002) were significant, the influence of other types of failure on different reconstructed parts of prosthesis, initial operation, and perioperative chemotherapy had no significant difference ( P>0.05). There were 5 cases of amputation (4 cases of type 5 failure, 1 case of type 4 failure), 3 cases of prosthesis removal (1 case of type 2 failure, 1 case of type 3 failure, 1 case of type 4 failure), 3 cases of revision while keeping the original prosthesis (2 cases of type 1 failure, 1 case of type 5 failure). The overall MSTS score was 24±3. The MSTS scores were 24±3, 25±3, and 23±3 in patients whose reconstruction sites located in proximal femur, distal femur, and proximal tibia, respectively, showing no significant difference ( F=3.014, P=0.052). CONCLUSION: The short-term follow-up showed a lower incidence of complications and good function for MEGASYSTEM-C non-cement modular prosthesis system in treatment of bone defects after lower limb tumor resection. The main factors affecting the early survival of prosthesis were tumor progression and infection.

Comparative Analysis of Early Follow-up of Biologic Fixation and Cemented Stem Fixation for Femoral Tumor Prosthesis.

OBJECTIVE: To compare the safety and efficacy between biologic fixation and traditional cement stems for the fixation of distal femoral prostheses for reconstruction following tumor resection. METHODS: Retrospective analysis was performed of patients who received a first distal femoral tumor prosthesis, with a rotating hinge, in the Department of Orthopaedic Oncology of Beijing Jishuitan Hospital between October 2011 and January 2016. Two hundred and sixty eligible cases were enrolled, with a cemented fixation used in 199 of these cases and a biologic fixation in 61 cases. Survival rates and survival time of prostheses were analyzed, with prosthetic failure considered as the endpoint event for survival time of the prosthesis. Kaplan-Meier survival curve and the log-rank test were used to compare survival rates between the two types of fixation methods, and factors that may affect the survival rate of prosthesis were evaluated. RESULTS: Of the 260 cases forming our study group, 138 were males and 122 females, with 102 males and 97 females in the cemented fixation group (mean age, 25.8 years; range, 8-72 years) and 36 males and 25 females in the biologic fixation group (mean age, 25.5 years; range, 12-59 years). Osteosarcoma was the most common type of tumor (188 cases, 72.3%), of which 145 cases (72.9%) were in the cemented and 45 cases (72.1%) in the biologic fixation group. Among the 260 cases enrolled into the study group, 13 patients were lost to follow-up. The average duration of follow-up for the remaining 247 cases was 28.8 months (median, 28.8 months; range, 4-61 months). The 3-year overall survival rate of prostheses was 87.2% for the biologic fixation group and 80.4% in the cemented fixation group (P = 0.389). The 3-year mechanical survival rate (excluding cases of infection and oncologic progression) was 100% for the biologic fixation and 97.6% for the cemented fixation group (P = 0.468). Complications were identified in 21 cases: 3 cases (5%) in the biologic and 18 cases (9.6%) in the cemented fixation group (P = 0.264). Two revisions were required in the cemented fixation group, but no revision was required in the biologic fixation group. A total of 10 patients required amputation after prosthesis implantation. Of these, 7 cases (4 cement and 3 biologic) were due to tumor recurrence; 3 cases were due to infection, with all cases occurring in the cement fixation group. CONCLUSION: The current study provides a baseline reference for future mid-term to long-term follow-up, laying the foundation for further studies and comparison of the incidence of aseptic loosening of both types of prosthesis.

[Application of proximal tibial hemiprosthesis replacement and second-stage revision for proximal tibial osteosarcoma in three children].

Objective: To investigate the feasibility and effectiveness of proximal tibial hemiprosthesis replacement in the first stage and prosthesis revision in the second stage in reducing the risk of length discrepancy of limbs in children with proximal tibial osteosarcoma. Methods: Between 2009 and 2013, 3 children with conventional osteosarcoma at the proximal tibia (stage ⅡB) were treated. There were 2 boys and 1 girl. They were 12, 13, and 13 years old, respectively. After 4 courses of preoperative chemotherapy, the proximal tumor segmental resection and proximal tibial hemiprosthesis replacement were performed. Then the patients underwent prosthetic revision in the second stage when they were 20, 17, and 17 years old, respectively. Results: All patients successfully completed two stages of operations. The length discrepancy of lower limb after the second stage operation were 19, 7, and 21 mm, respectively. Three patients were followed up 13, 3, and 27 months after the second stage operation, and the lower extremities functions were satisfactory. The Musculoskeletal Tumor Society (MSTS) score was 26, 27, and 25, respectively. Conclusion: The proximal tibial hemiprosthesis replacement in the first stage combined with prosthesis revision in the second stage for treating the proximal tibia osteosarcoma in children can keep the distal femur growth ability, reduce the length discreapancy of lower limb, and obtain satisfactory stability and good function.

Diagnosing giant cell tumor of the bone using positron emission tomography/computed tomography: A retrospective study of 20 patients from a single center.

The aim of the present study was to evaluate the sensitivity of positron emission tomography/computed tomography (PET/CT) in the diagnosis of giant cell tumor of the bone (GCTB) using the maximum standard uptake value (SUVmax), which indicates the metabolic rate of tissue. Patients diagnosed with pathologically confirmed GCTB between January 2006 and July 2015 were included in the study. Data from PET/CT scans and pathological and clinical reports for all patients were retrospectively reviewed. The SUVmax value from the PET/CT scan of each patient was retrieved and analyzed. A total of 20 patients [12 male and 8 female; age range, 12-45 years; mean age ± standard deviation (SD), 33.5±15.7] with complete PET/CT data and a pathologically and clinically confirmed diagnosis were examined. The SUVmax of GCTB was between 1.8 and 18.6, with a mean ± SD of 9.2±3.8. Although GCTB is not considered to be a malignant lesion, PET/CT scans of the tumors reveal high-grade malignant osseous sarcomas. It is, therefore, important not to mistake such lesions for osteosarcomas or metastatic malignancies of the bone.