Nong Lin

Response of osteogenic sarcoma to neoadjuvant therapy: evaluated by 18F-FDG-PET

ObjectiveThe aim of this study was to evaluate the potential role of F-18-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in assessing the chemotherapy response of osteosarcoma when compared with histologically assessed tumor necrosis.MethodsFifteen patients were examined with whole-body FDG-PET prior to and following neoadjuvant therapy. The maximum standard uptake value (SUVmax) of tumor and tumor to background ratio (TBR) prior to and following chemotherapy was used for semiquantitative PET imaging analysis. The SUVmax of prechemotherapy and post-chemotherapy was recorded as SUV1 and SUV2. TBR1 and TBR2 represented prechemotherapy and post-chemotherapy TBR. TBR was calculated by drawing an identical region of interest over the tumor and the contralateral normal limb or pelvis. Tumor necrosis was classified according to Salzer-Kuntschik’s criteria.ResultsEight patients with more than 90% tumor necrosis were classified as showing good responses and seven patients with less than 90% tumor necrosis as showing poor responses. SUV2/SUV1, TBR2/TBR1, and TBR2 were significantly correlated with the tumor necrosis degree (P < 0.01, P < 0.001, P < 0.001). TBR2/TBR1 were below 0.46 in all the patients with favorable responses, and higher than 0.49 in all the patients with unfavorable responses. However, it was difficult to distinguish good responses from poor responses by SUV2/SUV1.ConclusionsFDG-PET is a promising tool to assess the chemotherapy response of osteosarcoma noninvasively. The TBR was better than SUVmax in evaluating the chemotherapy response in this study.

Intraosseous lipoma of the pelvis and spine: two cases reports

Case one: A 53-year-old woman presented with pain in her right hip for one week after minor trauma. No swelling, tenderness or limitation of movement was present. Plain radiographs showed a well defined, expansile, radiolucent lesion involving the right acetabulum. The lesion was surrounded by sclerosis and contained osseous septations (Fig. 1). Computed tomography (CT) showed a hypodense lesion with expanded cortex (Fig. 2). Magnetic resonance imaging (MRI) showed high signal intensity on T1 weighted images, similar to subcutaneous adipose tissue (Fig. 3), and decreased signal intensity on short-T inversion recovery (STIR) images. Surgery consisting of curettage and bone grafting was performed. At surgery, the lesion was grossly yellow in color and fatty in consistency. Histologically, mature lipocytes and fine fibrovascular septa were noted (Fig. 4). Case two: A 37-year-old woman was sent to our hospital because of a swelling in her neck for 6 months. No pain or limitation of neck movement was present. Plain radiographs showed a clearly defined radiolucent osseous expansile tumor originating in the spinous processes of the third cervical vertebrae (Fig. 5). CT showed no apparent periosteal reaction, no evidence of soft tissue tumor, and multilocular change within the bone tumor (Fig. 6). MRI showed that the spinous processes and the lamina of the third cervical vertebra were damaged. The tumor

Recurrence of Giant Cell Tumor of the Spine after Resection: A Report of 10 Cases: Recurrence of SGCT

To review the clinical details and further treatments for recurrent spinal giant cell tumors (SGCT), and to analyze the risk factors of recurrence and shed new light on the treatment options and prognosis of recurrent SGCT.

Melatonin inhibits osteosarcoma stem cells by suppressing SOX9-mediated signaling

Aims: Melatonin (N‐acetyl‐5‐methoxytryptamine) has been reported to suppress epithelial‐mesenchymal transition and cancer stem cells in some types of cancer. However, the effects of melatonin on the osteosarcoma stem cells, epithelial‐mesenchymal transition and metastasis of osteosarcoma are still not clear. The present study was conducted to dissect the activity of melatonin on the osteosarcoma stem cells and the underlying mechanisms. Main methods: MTT, wound healing, transwell assay and western blotting were conducted to determine the effect of melatonin on osteosarcoma cell invasion and migration and downregulation of SOX9‐mediated signaling. Tumor spheroid assay and FACS analysis were performed to analyze the inhibition of the osteosarcoma stem cells. In vivo model for tumor formation and metastasis from single cell clone was used to evaluate the suppression of osteosarcoma stem cells by melatonin. Key findings: We demonstrated that melatonin potently suppresses the migration and invasion of osteosarcoma cells. Furthermore, melatonin significantly inhibits the sarcosphere formation of osteosarcoma stem cells and regulates EMT markers of osteosarcoma cells. In vivo mice model showed that melatonin significantly inhibits the initiation and metastasis of osteosarcoma. SOX9 is the key transcription factor mediating the effect of melatonin. Melatonin inhibited of cancer stem cell by down‐regulation of SOX9‐mediated signaling pathway in osteosarcoma. Significance: Collectively, these results deepen the understanding of the biological functions of melatonin and provide new insights for the intervention of osteosarcoma stem cells.

Open Surgery for Osteoid Osteoma with Three Dimensional C-arm Scan under the Guidance of Computer Navigation.

To evaluate the clinical outcomes of open surgery for osteoid osteoma with three‐dimensional (3‐D) C‐arm scan under the guidance of computer navigation.

Bone transport for reconstruction of large bone defects after tibial tumor resection: a report of five cases

This study was performed to explore the clinical efficacy of bone transport using external fixation for treatment of large bone defects after tibial tumor resection in five patients. Bone transport started 14 days postoperatively at 1 mm/day and was adjusted according to the callus-to-diameter ratio. The bone transport time, bone graft fusion, relapse, and metastasis were recorded. Clinical efficacy was evaluated using the Musculoskeletal Tumor Society (MSTS) scoring system. The tumors included osteosarcoma (n=2), Ewing sarcoma (n=1), malignant schwannoma (n=1), and hemangioma (n=1). The average bone defect length after resection was 11.6 cm. The five patients were followed up for an average of 50.8 months, and the average bone transport time was 15.5 months. Three patients who underwent postoperative chemotherapy were followed for 22.7 months, and two who did not undergo chemotherapy were followed for 4.75 months. Four patients underwent iliac bone grafting, and one underwent vascular pedicle fibular transplantation. The average MSTS score was 21.2 (19.3 for patients who underwent chemotherapy and 24.0 for patients who did not). No relapse or metastasis was observed. Bone transport is effective for reconstruction of large bone defects after tibial tumor resection as well as tibial malignancies with high doses of chemotherapy.

Valproic Acid Combined with Zoledronate Enhance γδ T Cell-Mediated Cytotoxicity against Osteosarcoma Cells via the Accumulation of Mevalonate Pathway Intermediates

The long-term survival of osteosarcoma has remained unchanged in the last several decades. Immunotherapy is proved to be a promising therapeutic strategy against osteosarcoma, especially for those with metastasis. Our previous study explored the sensibilization of zoledronate (ZOL) in γδ T cell-mediated cytotoxicity against osteosarcoma, but we have not yet elucidated the specific mechanism. Besides, high concentration is required to achieve these effects, whereas plasma ZOL concentration declines rapidly in the circulation. Valproic acid (VPA), a histone deacetylase inhibitor commonly used as the antiepileptic drug, has attracted much attention due to its synergistic antitumor efficacy with chemotherapy or immunotherapy. Here, we demonstrated that VPA combined with ZOL revealed the synergistic effect in enhancing antitumor efficacy of γδ T cells against osteosarcoma cells. This enhancement was mainly TCR-mediated and largely dependent on granule exocytose pathway. Of note, our findings indicated that ZOL sensitized osteosarcoma cells to γδ T cells by increasing the accumulation of the mevalonate pathway intermediates, which could be facilitated by VPA. We also found that this combination had similar effects on primary osteosarcoma cells. All the results suggested that VPA combined with ZOL could reduce the dose required to achieve a significant antitumor effect of γδ T cells, promoting it to be a novel therapy against osteosarcoma.

Survival Prediction in High-grade Osteosarcoma Using Radiomics of Diagnostic Computed Tomography

The poor 5-year survival rate in high-grade osteosarcoma (HOS) has not been increased significantly over the past 30 years. This work aimed to develop a radiomics nomogram for survival prediction at the time of diagnosis in HOS. In this retrospective study, an initial cohort of 102 HOS patients, diagnosed from January 2008 to March 2011, was used as the training cohort. Radiomics features were extracted from the pretreatment diagnostic computed tomography images. A radiomics signature was constructed with the lasso algorithm; then, a radiomics score was calculated to reflect survival probability by using the radiomics signature for each patient. A radiomics nomogram was developed by incorporating the radiomics score and clinical factors. A clinical model was constructed by using clinical factors only. The models were validated in an independent cohort comprising 48 patients diagnosed from April 2011 to April 2012. The performance of the nomogram was assessed with respect to its calibration, discrimination, and clinical usefulness. Kaplan–Meier survival analysis was performed. The radiomics nomogram showed better calibration and classification capacity than the clinical model with AUC 0.86 vs. 0.79 for the training cohort, and 0.84 vs. 0.73 for the validation cohort. Decision curve analysis demonstrated the clinical usefulness of the radiomics nomogram. A significant difference (p-value <.05; log-rank test) was observed between the survival curves of the nomogram-predicted survival and non-survival groups. The radiomics nomogram may assist clinicians in tailoring appropriate therapy.

Upshifting the Ipsilateral Proximal Femur May Provide Satisfactory Reconstruction of Periacetabular Pelvic Bone Defects After Tumor Resection

Background Pelvic ring reconstruction after resection of pelvic malignancies or aggressive benign tumors remains challenging, especially when the tumor invades periacetabular bone, resulting in a Type II resection as classified by Enneking and Dunham (removal of part or all of the acetabulum). Although numerous treatment approaches are in use, none is clearly superior to the others. An alternative involving use of the ipsilateral proximal femur as an autograft has not been well characterized, so we present our preliminary experience with this approach. Questions/purposes (1) What were the oncologic outcomes after using an ipsilateral proximal femur autograft for reconstruction after Type II pelvic resection in a small series of patients who underwent this reconstructive approach? (2) What were the Musculoskeletal Tumor Society (MSTS) scores after this reconstruction? (3) What complications were observed? Methods Between October 2006 and May 2016, we treated 67 patients with Type II malignant or aggressive benign tumors of the ilium. Of those, we used an ipsilateral proximal femur and a prosthesis as a reconstruction method for 11 patients with pelvic tumors. In general, we performed this approach in young or middle-aged patients with primary malignant or aggressive benign tumors involving pelvic area II and in whom the tumor did not invade the hip. The method used for resection of pelvic tumors included osteotomy of the femoral shaft, harvesting the proximal femur as a graft. The length of the femoral graft was determined by the extent of the pelvic defect. The proper placement was selected after a comparison of the proximal femur and the pelvic defect. A curved reconstruction plate and cancellous bone screws were used for pelvic fixation. The operative duration and total blood loss were recorded. Of the 11 patients who underwent this approach, all but one had at least 2 years of followup unless death occurred earlier, and all but one have been seen within the last year for evaluation. Functional outcomes were assessed using the MSTS scoring system. Local recurrence, metastases, and deaths were recorded as were complications including infection, bone nonunion, mechanical failure and sciatic nerve palsy. Results The followup was a mean of 37 months (range, 13-96 months). One patient was lost to followup. Three patients died of disease owing to local recurrence or lung metastasis. The other seven patients lived without evidence of tumor. The main complications included mechanical failure in two patients, nonunion in one patient, infection in two patients, and sciatic nerve palsy in one patient. The median MSTS function score was 70% (21 of 30 points; range, 11-25 points). Conclusions Our preliminary results show that this technique of using the ipsilateral proximal femur may be an alternative method for reconstruction of pelvic bone defects after tumor resection. Even with this short followup, complications were common, but short-term function appears to be comparable to studies of other options. Longer term followup with more patients is necessary to confirm our results. Level of Evidence: Level IV, therapeutic study.

Prognostic factors for survival among patients with primary bone sarcomas of small bones

Background Primary bone sarcomas of the hands or feet are rare lesions and poorly documented. Moreover, the prognostic determinants of bone sarcomas of the hands or feet have not been reported. Materials and methods The Surveillance, Epidemiology, and End Results (SEER) program database was used to screen patients with bone sarcomas of the hands or feet from 1973 to 2013, with attention paid to chondrosarcoma, Ewing sarcoma, and osteosarcoma. The prognostic values of overall survival (OS) and cancer-specific survival (CSS) were assessed using Cox proportional hazards regression model with univariate and multivariate analyses. The Kaplan–Meier method was used to obtain OS and CSS curves. Results A total of 457 cases were selected from the SEER database. Chondrosarcoma was the most common form of lesion in hands or feet or both, followed by Ewing sarcoma and osteosarcoma. The 5- and 10-year OS rates of the entire group were 75.7% and 66.1%, respectively. The 5- and 10-year CSS rates were 78.7% and 73.7%, respectively. Multivariate analysis revealed that age under 40 years, localized stage, low grade, surgical treatment, and first primary tumor were associated with improved OS, and decade of diagnosis, stage, grade, and surgery were independent predictors of CSS. However, no significant differences were observed in OS and CSS among patients with different primary tumor locations and tumor subtypes. Additionally, the most significant prognostic factor was whether metastasis had occurred at the time of initial diagnosis. Conclusion Among patients with primary bone sarcomas of the hands or feet, younger age (<40 years), localized stage, low grade, surgical treatment, and first primary tumor are favorable factors for prolonging survival.