Tumor-induced Osteomalacia Successfully Treated by En Bloc Tumor Excision and Reconstruction Using a Tumor-bearing Frozen Autograft: A Case Report.

BACKGROUND/AIM: Tumor-induced osteomalacia (TIO) is a rare pathology caused by overproduction of fibroblast growth factor 23 (FGF23). Its common clinical features include generalized muscle weakness, bone pain, and fractures. Complete resection of the offending tumor is the mainstay treatment. In this report, we present the first case of TIO by an FGF23 producing tumor treated using a tumor-bearing autograft treated with liquid nitrogen. CASE REPORT: A 63-year old female presented with generalized body pain, particularly in the left arm. The patient was diagnosed with a FGF23 producing tumor of the left humerus. Wide resection of the involved tumor was performed using a tumor-bearing autograft that was treated with liquid nitrogen. Postoperatively, the FGF23 and alkaline phosphatase (ALP) levels significantly decreased and inorganic phosphate normalized. There was also subsequent relief of generalized body pain. Immediately after the operation, range of motion of the left shoulder and elbow was initiated. The patient was instructed to perform forward flexion and abduction up to 90° with a rotational restraint. Almost complete bone union was observed at 12 months post procedure. Postoperative functional results were as follows: Musculoskeletal Tumor Society (MSTS) score of 27/30, 90% and International Society of Limb Salvage (ISOLS) score of 26/30, 87%. Ten years after the surgery, osteotomy line was completely obscured based on radiographs. The patient was disease free and without activity limitation. CONCLUSION: This is the first case report of wide excision of a FGF23 producing tumor and reconstruction using a tumor-bearing frozen autograft performed with excellent outcomes.

Treatment of infected calcific myonecrosis with chronically discharging sinus caused by iatrogenic aspiration: A case report.

INTRODUCTION AND IMPORTANCE: Calcific myonecrosis (CM) is a rare, benign post-traumatic sequela which is often challenging to differentiate from soft tissue tumors. Infected CM is recalcitrant and sometimes requires invasive treatment despite its benign nature. We present a case of infected CM in which MRI and 201Tl scintigraphy proved useful for diagnosis and intralesional debridement with prolonged placement of a suction tube allowed for successful treatment. CASE PRESENTATION: A 71-year-old man had undergone repeated aspiration for swelling of the lower leg and presented with a sustained pyogenic discharging wound. He underwent intralesional debridement of purulent necrotic tissue followed by prolonged suction tube placement. Enterobacter cloacae was detected in the discharge, and specific antibiotics were administered. Once the wound closed, a new sinus recurred four months after surgery, warranting reoperation with debridement of the remnant fascia and necrotic tissue with suction tube replacement. The wound healed eight months after the first surgery with no signs of recurrence. CLINICAL DISCUSSION: CM can be diagnosed based on its unique imaging features and a history of compartment syndrome. To avoid infection, CM must be treated conservatively without surgical invasions, such as biopsy or aspiration. Extensive debridement with a myocutaneous flap is nevertheless recommended for infected CM treatment, despite significant invasion including intraoperative bleeding being problematic. CONCLUSION: MRI and 201Tl scintigraphy can help diagnose CM and avoid biopsy to exclude malignancy. Intralesional debridement of necrotic tissue with prolonged suction tube placement could be a valid treatment alternative to reduce the invasiveness of infected CM.

Current status of immunotherapy for sarcomas.

Although the development of anticancer drugs has improved the outcomes of bone and soft tissue sarcomas, the clinical outcome of patients with relapsed sarcomas remains unsatisfactory due to therapeutic toxicities and resistance to anticancer drugs. Therefore, novel therapeutic modalities are needed to improve the outcome of patients with bone and soft tissue sarcomas. Dendritic cells present tumor antigens and stimulate immune responses, and immune cells, such as cytotoxic T lymphocytes, kill tumor cells by recognizing tumor antigens. However, immune-suppressive conditions by immune regulator PD-1, CTLA-4 and regulatory T cells help tumor growth and progression. In this report, current immunotherapies including cellular immunotherapy and checkpoint inhibitors are introduced, and the advantages and disadvantages of the treatments are discussed.

Knee joint preservation surgery in osteosarcoma using tumour-bearing bone treated with liquid nitrogen.

PURPOSE: To preserve the joint structure in order to maintain good limb function in patients with osteosarcoma, we perform epiphyseal or metaphyseal osteotomy and reconstruction using frozen autografts that contain a tumour treated with liquid nitrogen. There are two methods of using liquid nitrogen-treated autografts: the free-freezing method and the pedicle-freezing method. The purpose of this study was to evaluate the results of intentional joint-preserving reconstruction using the free-freezing method and the pedicle-freezing method in patients with osteosarcoma. METHODS: Between 2006 and 2014, we performed joint-preserving surgery (12 with the free-freezing method and six with the pedicle freezing method) to treat 18 cases of osteosarcoma (12 distal femurs and six proximal tibias) in patients who had achieved a good response to neoadjuvant chemotherapy. RESULTS: Among the 18 patients (nine boys and nine girls) who had a mean age of 11.6 years, 13 remained continuously disease-free, three showed no evidence of disease, one was alive with the disease, and one died from the disease. Functional outcomes were assessed as excellent in 15 patients and poor in three, with a mean follow-up period of 46.1 months. The mean Musculoskeletal Tumour Society (MSTS) score was 90.2%. Except for one patient who underwent amputation, all patients could bend their knee through >90° flexion, and nine achieved full ROM. All but two patients could walk without aid, and 11 were able to run normally throughout the follow-up period. No intraoperative complications were observed, such as surrounding soft-tissue damage, neurovascular injury, or recurrence from frozen bone. CONCLUSIONS: Joint-preserving reconstruction using frozen autografts yielded excellent function in patients with osteosarcoma.

Mandibular Reconstruction by Using a Liquid Nitrogen-Treated Autograft in a Dog with an Oral Tumor.

A 10 yr old intact female German shepherd dog presented with a large peripheral odontogenic fibroma and malignant melanoma on her lower jaw. The tumor was resected with a unilateral subtotal rostral hemimandibulectomy. After the mandible was removed, it was devitalized intraoperatively by freezing it in liquid nitrogen. It was subsequently reimplanted. New bone tissue formed in the gap between the frozen bone and the host bone. The regenerated bone contained osteocytes, osteoblasts, and blood vessels. The cosmetic appearance of the dog was preserved. The dog had normal mastication. The malignant melanoma recurred rostral of the left canine tooth at 159 days after the reconstruction surgery. A subtotal hemimandibulectomy was consequently performed. This is the first reported case of mandibular reconstruction using a liquid nitrogen-treated autograft in a dog with oral tumors.

Phase 1/2 study of immunotherapy with dendritic cells pulsed with autologous tumor lysate in patients with refractory bone and soft tissue sarcoma.

BACKGROUND: There are limited options for the curative treatment of refractory bone and soft tissue sarcomas. The purpose of this phase 1/2 study was to assess the immunological and clinical effects of dendritic cells (DCs) pulsed with autologous tumor lysate (TL) in patients with advanced bone and soft tissue sarcomas. METHODS: Thirty-seven patients with metastatic or recurrent sarcomas were enrolled in this study. Peripheral blood mononuclear cells obtained from the patients were suspended in media containing interleukin 4 (IL-4) and granulocyte-macrophage colony-stimulating factor. Subsequently, these cells were treated with TL, tumor necrosis factor α, and OK-432. The DCs were injected into the inguinal or axillary region. One treatment course comprised 6 weekly DC injections. The toxicity, clinical response (tumor volume, serum interferon-γ [IFN-γ], and serum IL-12), and oncological outcomes were observed. RESULTS: In total, 47 courses of DC therapy were performed in 37 patients. No severe adverse events or deaths associated with the DC injections were observed in the study patients. Increased serum IFN-γ and IL-12 levels were observed 1 month after the DC injection. Among the 37 patients, 35 patients were assessed for clinical responses: 28 patients showed tumor progression, 6 patients had stable disease, and 1 patient showed a partial response 8 weeks after the DC injection. The 3-year overall and progression-free survival rates of the patients were 42.3% and 2.9%, respectively. CONCLUSIONS: Although DC therapy appears safe and resulted in an immunological response in patients with refractory sarcoma, it resulted in an improvement of the clinical outcome in only a small number of patients. Cancer 2017;123:1576-1584. © 2017 American Cancer Society.

Clinical Outcome of Reconstruction Using Frozen Autograft for a Humeral Bone Tumor.

BACKGROUND: We developed a frozen autograft technique in which a tumor-bearing bone was treated with liquid nitrogen for reconstruction. The purpose of this study was to evaluate the functional outcomes of this technique after resection of humeral bone tumors. PATIENTS AND METHODS: Eight patients were included in the study. The freezing range was classified into 2 groups, depending on whether the joint surface of the humeral head was frozen. RESULTS: In the joint freezing group, the mean active shoulder abduction and flexion were 43.8° and 55.0°, and the mean International Society of Limb Salvage (ISOLS) score was 70.8%. In the joint preservation group, the mean active shoulder abduction and flexion were 130° and 132°, and the mean ISOLS score was 90.8%. Progressive and massive bone absorption was seen in 3 cases. DISCUSSION: Reconstruction using frozen autograft after resection of humeral bone tumor is our preferred option, especially in shoulder joint preservation surgery.

Efficacy of glycogen synthase kinase-3ß targeting against osteosarcoma via activation of ß-catenin.

Development of innovative more effective therapy is required for refractory osteosarcoma patients. We previously established that glycogen synthase kinase-3ß (GSK- 3ß) is a therapeutic target in various cancer types. In the present study, we explored the therapeutic efficacy of GSK-3ß inhibition against osteosarcoma and the underlying molecular mechanisms in an orthotopic mouse model. Expression and phosphorylation of GSK-3ß in osteosarcoma and normal osteoblast cell lines was examined, together with efficacy of GSK-3ß inhibition on cell survival, proliferation and apoptosis and on the growth of orthotopically-transplanted human osteosarcoma in nude mice. We also investigated changes in expression, phosphorylation and co-transcriptional activity of ß-catenin in osteosarcoma cells following GSK-3ß inhibition. Expression of the active form of GSK- 3ß (tyrosine 216-phosphorylated) was higher in osteosarcoma than osteoblast cells. Inhibition of GSK-3ß activity by pharmacological inhibitors or of its expression by RNA interference suppressed proliferation of osteosarcoma cells and induced apoptosis. Treatment with GSK-3ß-specific inhibitors attenuated the growth of orthotopic osteosaroma in mice. Inhibition of GSK-3ß reduced phosphorylation at GSK- 3ß-phospho-acceptor sites in ß-catenin and increased ß-catenin expression, nuclear localization and co-transcriptional activity. These results suggest the efficacy of GSK-3ß inhibitors is associated with activation of ß-catenin, a putative tumor suppressor in bone and soft tissue sarcoma and an important component of osteogenesis. Our study thereby demonstrates a critical role for GSK-3ß in sustaining survival and proliferation of osteosarcoma cells, and identifies this kinase as a potential therapeutic target against osteosarcoma.

Successful correction of tibial bone deformity through multiple surgical procedures, liquid nitrogen-pretreated bone tumor autograft, three-dimensional external fixation, and internal fixation in a patient with primary osteosarcoma: a case report.

BACKGROUND: In a previous report, we described a method of reconstruction using tumor-bearing autograft treated by liquid nitrogen for malignant bone tumor. Here we present the first case of bone deformity correction following a tumor-bearing frozen autograft via three-dimensional computerized reconstruction after multiple surgeries. CASE PRESENTATION: A 16-year-old female student presented with pain in the left lower leg and was diagnosed with a low-grade central tibial osteosarcoma. Surgical bone reconstruction was performed using a tumor-bearing frozen autograft. Bone union was achieved at 7 months after the first surgical procedure. However, local tumor recurrence and lung metastases occurred 2 years later, at which time a second surgical procedure was performed. Five years later, the patient developed a 19° varus deformity and underwent a third surgical procedure, during which an osteotomy was performed using the Taylor Spatial Frame three-dimensional external fixation technique. A fourth corrective surgical procedure was performed in which internal fixation was achieved with a locking plate. Two years later, and 10 years after the initial diagnosis of tibial osteosarcoma, the bone deformity was completely corrected, and the patient's limb function was good. CONCLUSION: We present the first report in which a bone deformity due to a primary osteosarcoma was corrected using a tumor-bearing frozen autograft, followed by multiple corrective surgical procedures that included osteotomy, three-dimensional external fixation, and internal fixation.

Frozen Autograft-Prosthesis Composite Reconstruction in Malignant Bone Tumors.

Several methods are available using an endoprosthesis or biological reconstruction for malignant bone tumors. Methods that use allograft-prosthesis composites have shown promising results. In 1999, the authors developed a method of reconstruction that uses a tumor-bearing autograft treated with liquid nitrogen. This technique was modified to produce a pedicle frozen autograft to maintain anatomical continuity on one side. In this study, the results of bone reconstructions using frozen autograft-prosthesis composites were retrospectively evaluated. The demographic data, histological records, surgical procedures, functional scores, and complications of 22 patients who had bone sarcoma or metastasis and at least 2 years of follow-up were reviewed. There were 19 patients with primary bone sarcoma and 3 with bone metastasis. Average age was 36 years (range, 9-73 years), and mean follow-up was 63 months (range, 24-176 months). Reconstructions were performed on 10 proximal femurs, 5 distal femurs, 4 proximal tibias, 1 proximal humerus, 1 proximal radius, and 1 hemipelvis. There were 12 pedicle-freezing and 10 free-freezing procedures. Union rate was 90% (9/10), and average union time was 9.5 months. Average Musculoskeletal Tumor Society score was 89.3%. Complications included 1 fracture, 2 infections, 3 soft tissue recurrences, and 1 posterior interosseous nerve palsy. The authors concluded that the frozen autograft-prosthesis composite demonstrated excellent Musculoskeletal Tumor Society scores, a low complication rate, and a good union rate and was superior when used with the pedicle-freezing technique.

Salvage method for unplanned excision of soft tissue sarcoma: long-term results of second-look surgery following radio-hyperthermo-chemotherapy.

We have established a "second-look operation" protocol that consists of whole biopsy of surgical scar tissue following radio-hyperthermo-chemotherapy (RHC) after unplanned excision of soft tissue sarcoma. Out of 30 patients who underwent RHC for soft tissue sarcoma at our Institution, 6 were enrolled into this study to undergo a second-look operation for unplanned excision. Radiotherapy was given to a total dose of 32 Gy. Hyperthermia was conducted once a week, for a total of five sessions. Chemotherapy was performed at weekly intervals. Surgery was performed to excise the scar tissue that was enhanced on preoperative MRI. In all six cases, no residual tumors were identified in resected scar tissue; thus, no additional wide excision was performed. The average follow-up period was 10.9 years. There were no local recurrences, and all patients were alive at their final follow-up. Long-term follow-up confirmed that RHC can replace additional wide excision for unplanned excision of soft tissue sarcoma.

Efficacy of triplet regimen antiemetic therapy for chemotherapy-induced nausea and vomiting (CINV) in bone and soft tissue sarcoma patients receiving highly emetogenic chemotherapy, and an efficacy comparison of single-shot palonosetron and consecutive-day granisetron for CINV in a randomized, single-blinded crossover study.

The first aim of this study was to evaluate combination antiemetic therapy consisting of 5-HT3 receptor antagonists, neurokinin-1 receptor antagonists (NK-1RAs), and dexamethasone for multiple high emetogenic risk (HER) anticancer agents in bone and soft tissue sarcoma. The second aim was to compare the effectiveness of single-shot palonosetron and consecutive-day granisetron in a randomized, single-blinded crossover study. A single randomization method was used to assign eligible patients to the palonosetron or granisetron arm. Patients in the palonosetron arm received a palonosetron regimen during the first and third chemotherapy courses and a granisetron regimen during the second and fourth courses. All patients received NK-1RA and dexamethasone. Patients receiving the palonosetron regimen were administered 0.75 mg palonosetron on day 1, and patients receiving the granisetron regimen were administered 3 mg granisetron twice daily on days 1 through 5. All 24 patients in this study received at least 4 chemotherapy courses. A total of 96 courses of antiemetic therapy were evaluated. Overall, the complete response CR rate (no emetic episodes and no rescue medication use) was 34%, while the total control rate (a CR plus no nausea) was 7%. No significant differences were observed between single-shot palonosetron and consecutive-day granisetron. Antiemetic therapy with a 3-drug combination was not sufficient to control chemotherapy-induced nausea and vomiting (CINV) during chemotherapy with multiple HER agents for bone and soft tissue sarcoma. This study also demonstrated that consecutive-day granisetron was not inferior to single-shot palonosetron for treating CINV.

Outcomes and complications of reconstruction using tumor-bearing frozen autografts in patients with metastatic bone tumors.

BACKGROUND: Tumor-bearing frozen autografts have been used for reconstruction of bone defects after resection of bone tumors. In the present study, outcomes and complications of reconstruction using frozen autografts were assessed to determine indications for this procedure in patients with metastatic bone lesions. PATIENTS AND METHODS: Twenty-two patients were treated with reconstruction using frozen autografts. The surgical technique involved excision of the bone lesion, curettage, freezing in liquid nitrogen, thawing and reconstruction. RESULTS: Limb function was evaluated in 11 patients; wa found excellent in 10 patients and good in 1 patient. Five-year overall survival and disease-free survival rates were 46.7% and 26.3%, respectively. Five-year fracture-free survival and recurrence-free survival rates were 79.9% and 100%, respectively. Complications were observed in 6 patients and included fractures (4), deep infection (1) and osteoarthritis (1). CONCLUSION: Reconstruction using frozen autografts is a beneficial treatment option in patients with long expected survival or complete cure of the primary cancer.

Antimicrobial megaprostheses supported with iodine.

Deep infection associated with implants remains a serious complication of orthopedic surgery. We developed iodine coating for titanium implants. In this study, we performed a clinical trial of iodine-coated megaprostheses to evaluate its safety and antibacterial effects. Forty-seven patients with malignant bone tumor or pyogenic arthritis were treated using iodine-supported titanium megaprostheses between July 2008 and May 2013. The mean age was 53.6 years (range, 15-85 years). Twenty-six patients were males and 21 were females. The diagnoses included malignant bone tumor in 29 cases, infected total knee arthroplasty in 11 cases, chronic osteomyelitis due to pyogenic arthritis in six cases and loosening of total knee arthroplasty in one case. The iodine-supported implants used were 42 Kyocera Limb Salvage System and five KOBELCO K-MAX K-3. These megaprostheses were used to prevent infection in 21 patients, treat active infections in 26 patients. The mean follow-up period was 30.1 months (range, 8-50). Infection was prevented in 20 out of 21 patients. Only one patient had surgical site infection caused by Pseudomonas aeruginosa and was cured by intravenous administration of antibiotics alone without removal of the implant. In 26 treatment cases involving one- or two-stage revision surgery, infection subsided without any additional surgery. In all cases, there were no signs of infection at the time of the last follow-up. White blood cell and C-reactive protein levels returned to normal within four weeks after surgery. To confirm systemic effects of iodine, thyroid hormone levels in the blood were examined. Abnormalities of thyroid gland function were not detected. Loosening of the implants was not observed. Excellent bone ingrowth and ongrowth were found around iodine-supported megaprostheses. The iodine-supported titanium megaprostheses are highly effective and show promise for the prevention and treatment of infections in large bone defects. No cytotoxicity or adverse effects were detected with this treatment.

Synovial sarcoma in knee joint, mimicking low-grade sarcoma confirmed by molecular detection of SYT gene split.

A 10-year-old boy underwent arthroscopic curettage for an intra-articular mass in knee joint. The tumor was diagnosed as low-grade fibrous sarcoma. Five years later, the patient presented with a recurrent tumor. The patient underwent a marginal excision with knee joint preservation and without adjuvant therapy. Two years after the last surgery, the patient is thriving with no evidence of recurrent or metastatic disease. The final diagnosis was synovial sarcoma confirmed via a SYT gene split performed with fluorescent in situ hybridization (FISH), although the tumor appeared as a low-grade fibrous type in a hematoxylin-eosin section. The first curetted specimen was also confirmed to bear a SYT gene split. Synovial sarcoma has been conventionally recognized as a high-grade sarcoma. Our patient had a tumor that exhibited the characteristics of both a histologically and clinically low-grade tumor. From the present case, we consider that low-grade variants of synovial sarcoma do exist although their existence remains controversial.

Pedicle versus free frozen autograft for reconstruction in malignant bone and soft tissue tumors of the lower extremities.

BACKGROUND: Of the biological reconstruction methods for malignant bone and soft tissue tumors, reconstruction with liquid nitrogen has the advantage of maintaining continuity on the distal side of the tumor bone site (pedicle freezing procedure; PFP). This method is expected to result in early blood flow recovery, with early union and low complication rate. The purpose of this study was to compare the outcomes of the PFP and free freezing procedure (FFP) in the lower extremities. METHODS: The study included 20 patients (12 men and 8 women) with frozen autografts (FFP, 13 cases; PFP, 7 cases). The mean age of the subjects was 36.3 years (range 11-79 years), and the mean follow-up period was 56.4 months (range 12-142 months). RESULTS: Final bone union occurred in 11 patients in the FFP group (84.6%) and in 7 patients in the PFP group (100%). The mean union period in patients who did not need additional surgery was 9.8 months (range 4-21 months) in the FFP group and 4.8 months (range 2-7 months) in the PFP group. Postoperative complications occurred in 8 cases: infection in 3 cases, fracture in 3 cases, and joint destruction in 2 cases. Six FFP patients, and 2 PFP patients (two cases of fracture), developed postoperative complications. CONCLUSIONS: The union period was shorter and the rate of postoperative complications was lower with the PFP than with the FFP. We considered that early blood flow recovery might have led to the above results in the PFP.

Diagnosis and treatment of low-grade osteosarcoma: experience with nine cases.

BACKGROUND: Low-grade osteosarcoma, including low-grade central osteosarcoma and parosteal osteosarcoma, is an extremely rare variant, and the diagnosis is occasionally difficult. In this article we present cases of low-grade osteosarcomas that should be reviewed by a clinical oncologist. PATIENTS AND METHODS: Nine cases of histologically diagnosed Broder grade 1 osteosarcoma were retrospectively reviewed. The pathological diagnoses included parosteal osteosarcoma, low-grade central osteosarcoma, and low-grade chondroblastic osteosarcoma in four, four, and one cases, respectively. RESULTS: Duration from initial surgical intervention including biopsy to final diagnosis as low-grade osteosarcoma was a mean of 9.4 months. The initial benign diagnoses on biopsy specimens included fibrous dysplasia in three cases, chondroblastoma in one case, and a giant cell tumor in one case. The average number of histological examinations was 1.8. Low-grade osteosarcomas are well suited for biological reconstruction: seven cases were reconstructed by frozen autografts, distraction osteogenesis, or vascularized bone grafts. CONCLUSION: Low-grade osteosarcomas can be misdiagnosed as benign lesions, especially fibrous dysplasia. If the diagnosis of a low-grade osteosarcoma is not established on the basis of radiologic findings, care should be exercised, even when a biopsy suggests a benign lesion. Low-grade osteosarcomas should be treated with wide excision, even after an intralesional excision. Biological reconstruction might be a better option for low-grade osteosarcomas.

Correction of a severe poliomyelitic equinocavovarus foot using an adjustable external fixation frame.

One-stage surgical correction of severe equinocavovarus deformity can result in complications ranging from skin necrosis to tibial nerve palsy. Fewer complications have been reported when severe deformities were treated by gradual correction using external frames such as the Ilizarov external fixator or the Taylor Spatial Frame™. We describe a case of a 64-year-old female patient with severe poliomyelitic equinocavovarus whose deformity required her to ambulate using the dorsum of her right foot as a weightbearing surface. We treated the deformity with gradual correction using a Taylor Spatial Frame™, followed by ankle arthrodesis. At the most recent postoperative evaluation, 20 months after the initial surgery, the patient was pain free and ambulating on the sole of her right foot.

Late recurrence of osteosarcoma: a report of two cases.

We report 2 cases of late recurrence of osteosarcoma after 6 and 7 years. One patient had pulmonary metastasis, and the other had soft tissue recurrence. Both patients underwent complete resection and chemotherapy. The first patient achieved complete remission and remained disease-free 47 months later and had no limitation in his daily life. The second patient had a re-recurrence and underwent further resection and chemotherapy. He remained disease-free 35 months later and could walk using a T-handled walking cane.

Prognostic value of radiological response to chemotherapy in patients with osteosarcoma.

BACKGROUND: Chemotherapy is essential to improve the prognosis of the patients with osteosarcoma, and the response to chemotherapy is an important prognostic factor. In this study, the impact of various radiological examinations on overall survival (OS) and event-free survival (EFS) was evaluated. METHOD: Eighty-two patients with high-grade osteosarcoma were included in this study, and we evaluated the following factors for prognostic significance: age (≥40 years), gender (male), tumor location (truncal site), metastatic disease, histological response to chemotherapy, radiological response to chemotherapy assessed using X-ray, angiography, CT, MRI, (201)Tl scintigraphy, and (99m)Tc-MIBI scintigraphy ((99m)Tc-MIBI), and combined radiological score (CRS). RESULTS: Univariate analyses revealed that metastatic disease, histological response, (99m)Tc-MIBI, and CRS were significantly correlated with OS. Multivariate analyses showed that metastatic disease (OS: HR 35.9, P<0.001; EFS: HR 17.32, P<0.001) was an independent predictor of OS and EFS. Tumor location (HR 36.1, P = 0.003), histological response (HR 31.1, P = 0.036), and (99m)Tc-MIBI (HR 18.4, P = 0.038) were significant prognostic factors for OS. Moreover, CRS was a marginally significant predictor of OS and EFS. CONCLUSION: The chemotherapeutic effects evaluated by (99m)Tc-MIBI and CRS could be considered as prognostic factors in osteosarcoma.