Objective To review the research progress of the treatment of osteosarcoma, and to thoroughly understand its current state of research and prospect so as to lay a sol id foundation for the cl inical treatment. Methods The cl inical and experimental research l iteratures about treatment of osteosarcoma were extensively reviewed and analyzed. Results The present treatment of osteosarcoma is still need to comprehensive therapy which combine chemotherapy and surgical treatment. There are some progresses in gene therapy and molecular targeting therapy which can improve survival rate. Furthermore, well-designed studies and cl inical trials are needed to evaluate the potential therapeutic impact before they are used in cl inical. Conclusion Advancement in chemotherapeutic regimens has improved survival and l imb-sparing surgery in the treatment of osteosarcoma, but the progress of gene therapy and molecular targeting therapy gives new hope for osteosarcoma patients.
Objective To assess the efficacy of high-dose chemotherapy versus moderate-dose chemotherapy in the treatment of osteosarcoma. Methods We searched MEDLINE, EMbase, OVID database, CBMdisc, Cochrane CENTRAL Register of Controlled Trials in The Cochrane Library, and handsearched Journal of Chinese Oncology, Journal of Chinese Clinical Oncology and Tumor. The search time was updated to Feburary 2006.The quality of the included studies was evaluated by two reviewers and meta-analyses were performed on the results of homogenous studies. Results Four studies involving 937 participants with primary, high-grade and non-metastatic extremity osteosarcoma were included. All the included studies were judged to be inadequate at reporting randomization and blinding, only one reported allocation concealment. All included studies reported the number of withdrawals and the reasons for these. The meta-analyses showed that there were no significant differences in 5-year event free survival (EFS) (RR 1.10, 95% CI 0.96 to1.25), 5-year overall survival (OS) (RR 1.08, 95% CI 0.97 to1.20), local recurrence rate (RR 0.92, 95% CI 0.54 to 1.57), proportion of good histological response (RR 0.93, 95% CI 0.81 to 1.07), proportion of limb salvage [RR 0.97, 95% CI 0.92 to 1.02) between the high-dose group and the moderate-dose group. The 5-year EFS of the good histological response group was significantly higher than in the poor histological response group [OR 2.45, 95% CI 1.76 to 3.39,Plt;0.00001 ). Conclusions No advantage is shown for high-dose chemotherapy over moderate-dose chemotherapy in 5-year EFS, 5-year OS, local recurrence rate, proportion of good histological response and proportion of limb salvage. Histological response to preoperative chemotherapy is an independent prognosis factor for osteosarcoma. Due to the potential risk of selection bias, performance bias and publication bias, the evidence is not b enough to judge whether high-dose chemotherapy is better than moderate-dose chemotherapy in the treatment of osteosarcoma. Our conclusion suggests that large-scale randomized trials should be performed.
Objective To investigate the effect of limb salvage on treating osteosarcoma with pathological fracture. Methods From October 2002 to January 2003, 2 cases of osteosarcoma with pathological fracture were treated by limb salvage. Intraarterial chemotherapy was given by subcutaneous implantable delivery system with caffeine. Replacement with prosthesis was performed after 5 times of chemotherapy. Results Two patients were followed up for twenty-four months and 21 months respectively. No infection, aseptic loosening, local recurrence or metastasis occurred, and function recovery of joints was satisfactory. Conclusion Limb salvage can be considered in condition that primary osteosarcoma with pathological fracture can be treated by effective and comprehensive chemotherapy.
Objective To explore the effect of pyropheophorbide-a methyl ester-mediated photodynamic therapy (MPPa-PDT) on the apoptosis in human osteosarcoma cell line MG63 and the underlying mechanism. Methods Human osteosarcoma MG63 cells in logarithmic growth phase were divided into 4 groups: blank control group (control group), the MPPa treatment group (MPPa group), the light irradiation group (LED group), and MPPa-PDT treatment group (MPPa-PDT group). MPPa-PDT group and MPPa group were incubated with MPPa (0.75 μmol/ L) for 20 hours in dark condition; control group and LED group were incubated with equal volume of fresh medium for 20 hours in the same condition. After washing with PBS and replacement with fresh culture medium, LED group and MPPa-PDT group cells were exposed to light (4.8 J/cm2) for 120 seconds. After light exposure, all groups were cultured in dark condition again. Then cellular morphology changes were observed by an inverted phase contrast microscopy, endoplasmic reticulum morphology changes were observed by transmission electron microscopy, cellular apoptosis was detected by Hoechst33258 nuclear staining, cell apoptotic rate and the levels of Ca in cells were analyzed by flow cytometry, the expression of p-PERK, C/EBP homologous protein (CHOP), cleaved-Caspase-12 were assayed by Western blot. Results In MPPa-PDT group, the retracted and round cells were observed; Hoechst33258 nuclear staining showed nuclear condensation, fragmentation, and other typical apoptotic morphological changes; the cell apoptotic rate (48.76%±3.54%) was significantly higher than that of control group (5.04%±0.41%), MPPa group (5.33%±0.38%), and LED group (6.48%±0.46%) (P < 0.05); the levels of Ca2+ in cells (485.29±58.77) was also significantly higher than that of control group (97.24±4.77), MPPa group (97.95±6.30), and LED group (101.17±5.26) (P < 0.05); swelling endoplasmic reticulum was observed under transmission electron microscope; the expressions of p-PERK, CHOP, and cleaved-Caspase-12 gradually increased at 1, 3, and 6 hours after treatment respectively, which were significantly higher than those of the other groups (P < 0.05). There was no typical apoptotic morphological changes and endoplasmic reticulum morphological changes in control group, MPPa group, and LED group, and there was no significant difference in the above indexes among 3 groups (P > 0.05). Conclusion MPPa-PDT can significantly induce apoptosis in MG63 cells. The endoplasmic reticulum stress pathway is involved in the MPPa-PDT induced apoptosis.
Objective To investigate the possibility of using extendible distal femoral replacements in the treatment of osteosarcoma in growing individuals. Methods From December 1999 to March 2003, 3 cases (2 were typeⅡB, 1 was type ⅡA) with osteosarcoma were treated byextendible distal femoral replacements. Of the 3 cases, 2 underwent prosthesis extention operation, 1 was not operated. Results After the removal of tumor, the extremities of 2 patients were shortened by 4 to 5 cm within 2 to 3 years. After the lengthening procedure, the affected extremities were of equal length to the unaffected extremities and no drag symptoms of blood vessel and nerves were observed. Follow-up was done for 2 months to 3 years. There was no aseptic loosening. The function of joints was fairly good. Conclusion Extendible distal femoral replacements is an easy, convenient, and effective way to treat osteosarcoma.
Objective To investigate the clinical application and early results of combined epiphyseal preservation and autograft bone transfer for limb salvage in children with osteosarcoma. Methods Between March 2010 and March 2011, 3 children with osteosarcoma were treated with epiphyseal preservation and autograft bone transfer. There were 1 boy and 2 girls with the age of 10-14 years. The disease duration was 2 weeks to 3 months. The tumors were rated as type II according to San-Julian radiological classification and as type IIB according to Enneking surgical classification. The locations were the distal femur in 1 case and the proximal tibia in 2 cases. The surgical technique included preoperative neoadjuvant chemotherapy, excision of part of the epiphysis, preservation of subarticular epiphysis, external fixation with Ilizarov apparatus and transport osteogenesis treatment. Safe excision border was confirmed by histological examination. Postoperative observation included the wound healing, local recurrence or distant metastasis, length, speed, alignment, and regeneration of transplanted bone, the length and function of the affected limb. Results The postoperative histological examination proved the safe surgical margin in all 3 patients. The incision healing by first intention was obtained at distal femur in 1 case and by second intention at proximal tibia in 2 cases at 4 weeks after changes of dressing. Three patients were followed up 12, 18, and 24 months, respectively. There was no local recurrence or distant metastasis during follow-up. Two cases had pin-tract infection at 10 months after external fixation and were cured after changes of dressing and antibiotics administration. The length of transplanted osteogenisis was 18.0, 9.5, and 16.0 cm, respectively. The speed of lengthening was 2.57, 2.07, and 1.20 cm/month, respectively. One patient had alignment deviation during lengthening, which was adjusted under anaesthesia. Bony healing was achieved at 8 months after lengthening end in 2 cases and external fixation was removed; 1 patient had poor bone growth and was given retraction for promoting bone growth. At last follow-up, the length of the affected limbs was 1.0-1.5 cm shorter than that of normal limbs, but no abnormalities was observed at donor sites. The affected knee flexion reached 90° and 120° in 2 patients and poor knee function was observed in 1 patient for external fixation. Conclusion The combined epiphyseal preservation and transport osteogenesis technique can be used for bone defect repair by lengthening the residual bone. It is a promising limb salvage treatment for children with osteosarcoma.
ObjectiveTo reporte the nursing experience of non-healing incision due to allograft rejection after osteosarcoma surgery. MethodsOne patient with non-healing incision due to allograft rejection after osteosarcoma surgery treated in September 2013 was selected. The suitable moist healing dressings was chosen to control inflammation, prevent infection, manage exudation, promote the growth of granulation, protect the surrounding skin, shorten the dressing time and reduce the suffering of patients. ResultThe wound healed well after 65 days of dressing with the function of the right upper limb recovered. ConclusionThe moist healing dressing not only improved the quality of patient's life and increased the patient's confidence of overcoming the disease, but also made the patients more active to cooperate in the next treatment.
ObjectiveTo investigate the value of integrin αvβ3 targeted microPET/CT imaging with 68Ga-NODAGA-RGD2 as radiotracer for the detection of osteosarcoma and theranostics of osteosarcoma lung metastasis.MethodsThe 68Ga-NODAGA-RGD2 and 177Lu-NODAGA-RGD2 were prepared via one-step method and their stability and integrin αvβ3 binding specificity were investigated in vitro. Forty-one nude mice were injected with human MG63 osteosarcoma to established the animal model bearing subcutaneous osteosarcoma (n=21), osteosarcoma in tibia (n=5), and osteosarcoma pulmonary metastatic (n=15). The microPET-CT imaging was carried out in 3 animal models at 1 hour after tail vein injection of 68Ga-NODAGA-RGD2. Biodistribution study of 68Ga-NODAGA-RGD2 was performed in animal model bearing subcutaneous osteosarcoma at 10, 60, and 120 minutes. The animal model bearing pulmonary metastatic osteosarcoma was injected with 177Lu-NODAGA-RGD2 at 7 weeks after model establishment to observe the therapeutic effect of pulmonary metastatic osteosarcoma. Histological and immunohistochemistry examinations were also done to confirm the establishment of animal model and integrin β3 expression in animal models bearing subcutaneous osteosarcoma and bearing pulmonary metastatic osteosarcoma.Results68Ga-NODAGA-RGD2 and 177Lu-NODAGA-RGD2 had good stability in vitro with the 50% inhibitory concentration value of (5.0±1.1) and (6.5±0.8) nmol/L, respectively. The radiochemical purity of 68Ga-NODAGA-RGD2 at 1, 4, and 8 hours was 98.5%±0.3%, 98.3%±0.5%, and 97.9%±0.4%; while the radiochemical purity of 177Lu-NODAGA-RGD2 at 1, 7, and 14 days was 99.3%±0.7%, 98.7%±1.2%, and 96.0%±2.8%. 68Ga-NODAGA-RGD2 microPET-CT showed that the accumulation of 68Ga-NODAGA-RGD2 in animal models bearing subcutaneous osteosarcoma and osteosarcoma in tibia and in lung metastasis as small as 1-2 mm in diameter of animal model bearing pulmonary metastatic osteosarcoma. Biodistribution study of 68Ga-NODAGA-RGD2 in animal model bearing subcutaneous osteosarcoma revealed rapid clearance from blood with tumor peak uptake of (3.85±0.84) %ID/g at 120 minutes. The distribution of 177Lu-NODAGA-RGD2 in lung metastasis was similar with 68Ga-NODAGA-RGD2. The number and size of osteosarcoma metastasis decreased at 2 weeks after 177Lu-NODAGA-RGD2 administration and integrin targeting specificity was confirmed by pathology examination.Conclusion68Ga-NODAGA-RGD2 was potential for positive imaging and early detection of osteosarcoma and metastasis. Targeted radiotherapy with 177Lu-NODAGA-RGD2 was one potential alternative for osteosarcoma lung metastasis.
Objective To investigate the feasibility of the preservation of the epiphysis and joint function of the distal femur in children with osteosarcoma with epiphyseal distraction by external fixator. Methods Between July 2007 and May 2011, 6 children with osteoblastic osteosarcoma of the distal femur underwent epiphyseal distraction by external fixator, combined with tumor resection and repair with massive allograft bone transplantation to preserve the epiphysis and joint function of the distal femur. There were 4 boys and 2 girls, aged from 9 to 14 years (mean, 10.5 years). According to Enneking clinical staging, 4 cases were in stage II A and 2 cases in stage II B. According to San-Julian et al. typing for metaphyseal tumor invasion, 3 cases were in type I and 3 cases in type II. The size of tumor ranged from 6 cm × 4 cm to 12 cm × 9 cm. All patients received 2 cycles of COSS 86 chemotherapy before operation and 4 cycles after operation. Results Poor healing of incision was observed in 1 case because of rejection of allograft bone and good healing was obtained after the symptomatic treatment, healing of incision by first intention was achieved in the other children. All 6 cases were followed up 11 to 56 months (mean, 37.5 months). One case died of lung metastasis at 2 years after operation. X-ray films showed no complication of internal fixator loosening and broken or bone nonunion. According to the functional evaluation criteria of International Society of Limb Salvage (ISOLS) at last follow-up, the results were excellent in 3 cases, good in 2 cases, and fair in 1 case; the excellent and good rate was 83.3%. The length of operated limb was (62.97 ± 7.51) cm, showing significant difference when compared with that of normal limb [(64.03 ± 7.47) cm] (t=0.246 6, P=0.813 4). Conclusion On the premise of adaptable indication, effective chemotherapy, and thoroughly tumor resection, the epiphyseal distraction by external fixator can obtain satisfactory results in limb-length and limb function in children with osteoblastic osteosarcoma of the distal femur.
ObjectiveTo explore the effectiveness and safety of high-intensity focused ultrasound (HIFU) for bone tumors, so as to provide a reference for clinical decision. MethodsPubMed, EMbase, The Cochrane Library, CNKI and VIP databases were systematically searched for clinical effectiveness and safety studies of HIFU for bone tumors up to August 2014. Study selection, data extraction and quality assessment were applied independently by two reviewers, and then RevMan 5.1 software was used for conducting meta-analysis. If the data cannot be synthesized, the research outcome was described with a qualitative analysis. ResultsA total of 10 case series including 257 patients (157 males, 100 females) were included. The current evidence indicated that overall survival rates for all primary bone malignancy at 1-, 2-, 3- and 5-year were 89.8%, 72.3%, 60.5% and 50.5%, respectively. For the patients with clinical stage Ⅱb, the rates were 93.3%, 82.4%, 75% and 63.7%, respectively. For those with clinical stage Ⅲ, the rates were 79.2%, 42.2%, 21.1% and 15.8%, respectively. The local recurrence rate of HIFU for bone tumors was 7% to 9%, and recurrences at 1-, 2-, 3- and 5-year were 0%, 6.2%, 11.8% and 11.8%, respectively. The amputation rate was 2% to 7%. The adverse reaction rate was 27.2% (70/257), and among them the main was mild skin burn (21/257, 8.2%), followed by I degree burns (16/257, 6.2%), nerve damage (10/257, 3.9%) and fracture (6/257, 2.3%). ConclusionHIFU provide an alternative choice for patients with bone malignancy, with a certain effectiveness and safety. However, high-quality, large-scale randomized controlled trials or cohort studies which may focus on vary kinds of tumors, clinical stage and site of lesions are urgently needed, so that clinicians can use sufficient evidence for their clinical decision-making.