Won Seok Song

Prediction Model of Chemotherapy Response in Osteosarcoma by 18F-FDG PET and MRI

Response to neoadjuvant chemotherapy is a significant prognostic factor for osteosarcoma; however, this information can be determined only after surgical resection. If we could predict histologic response before surgery, it might be helpful for the planning of surgeries and tailoring of treatment. We evaluated the usefulness of 18F-FDG PET for this purpose. Methods: A total of 70 consecutive patients with a high-grade osteosarcoma treated at our institute were prospectively enrolled. All patients underwent 18F-FDG PET and MRI before and after neoadjuvant chemotherapy. We analyzed the predictive values of 5 parameters, namely, maximum standardized uptake values (SUVs), before and after (SUV2) chemotherapy, SUV change ratio, tumor volume change ratio, and metabolic volume change ratio (MVCR) in terms of their abilities to discriminate responders from nonresponders. Results: Patients with an SUV2 of less than or equal to 2 showed a good histologic response, and patients with an SUV2 of greater than 5 showed a poor histologic response. The histologic response of a patient with an intermediate SUV2 (2 < SUV2 ≤ 5) was found to be predictable using MVCR. A patient with an MVCR of less than 0.65 is likely to be a good responder, whereas a patient with an MVCR of greater than or equal to 0.65 is likely to be a poor responder. According to our model, the predictive values for good responders and poor responders were 97% (31/32) and 95% (36/38), respectively. Conclusion: We found that combined information on 18F-FDG PET and MRI scans, acquired before and after chemotherapy, could be used to predict histologic response to neoadjuvant chemotherapy in osteosarcoma.

Results of Multiple Drilling Compared with Those of Conventional Methods of Core Decompression

We performed multiple drilling as a femoral head-preserving procedure for osteonecrosis of the femoral head thinking the therapeutic effects of core decompression could be achieved by this simpler procedure than core decompression. We retrospectively reviewed 136 patients (163 hips) who had multiple drilling using 9/64-inch Steinmann pins for treatment of nontraumatic osteonecrosis of the femoral head. The mean followup for patients who did not require additional surgery (113 hips) was 87 months (range, 60-134 months). We defined failure as the need for additional surgery or a Harris hip score less than 75. After a minimum 5-year followup, 79% (31/39) of patients with Stage I disease and 77% (62/81) of patients with Stage II disease had no additional surgery. All (15/15) small lesions (<25% involvement) and 84% (37/44) of medium-sized lesions (25-50% involvement) were considered successful. Survival rates of patients with Ficat Stages I or II lesions were greater than survival rates for patients with Stage III lesions. Hips with a large necrotic area had poor results. We had one instance of subtrochanteric fracture through drill entry holes. Multiple drilling is straightforward with few complications and produces results comparable to results of other core decompression techniques.Level of Evidence: Level IV, therapeutic study (case series). See the Guidelines for Authors for a complete description of levels of evidence.

Ezrin expression predicts survival in stage IIB osteosarcomas.

Ezrin, a cytoskeleton linker protein, has been reported to be involved in the metastasis of solid tumors in animal models and patients in small clinical studies. We analyzed the relationship between immunohistochemical expression of ezrin and the prognosis of osteosarcoma. We retrospectively identified 64 patients with Stage IIB osteosarcomas between 1995 and 2000. Tissue microarrays were constructed from incisional biopsy specimens and immunohistochemical staining was performed. Ezrin expression and other clinicopathologic variables such as age, gender, pathologic subtype, tumor size and location, and histologic response were compared with outcomes. The minimum followup was 12 months (mean, 78.2 months; range, 12-137 months). Twenty-three of 64 patients (35.9%) showed late distant metastasis; 33 of 64 patients (51.6%) showed expression of ezrin, and of these 33 patients, 22 (66.7%) had distant metastasis develop. Multivariate analysis revealed histologic response to preoperative chemotherapy and expression of ezrin predicted disease-free survival. Expression of ezrin in osteosarcoma biopsy specimens is promising as a marker to predict outcome in patients with osteosarcoma.Level of Evidence: Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Time dependency of prognostic factors in patients with stage II osteosarcomas

Although several clinicopathologic parameters may be related to metastasis-free survival in osteosarcoma, the importance of prognostic factors with time is largely unknown. Therefore, we asked whether the clinical characteristics of patients with osteosarcoma with metastasis after 2 years differed from those of patients with an earlier metastatic event. We retrospectively reviewed 420 patients with Stage IIB osteosarcoma treated with surgery and chemotherapy. The minimum followup was 3 months (mean, 71.4 months; range, 3-257 months). Among the 420 patients, 167 patients had a metastatic event. A large proportion (43%) of the 35 good responders showed metastasis after 2 years, whereas 24% of the 96 poor responders showed late metastasis. Histologic response and chondroblastic subtype showed time-related changes. Poor histologic response showed a gradual decline in prognostic value and lost its importance after 2 years. Most metastatic events occurred within 2 years after diagnosis; therefore, we recommend new predictive strategies and followup protocol for patients experiencing late relapse.Level of Evidence: Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Pasteurized autograft for intercalary reconstruction: an alternative to allograft.

Intercalary resection and reconstruction for tumors have become increasingly popular. We asked whether pasteurized autologous bone graft was comparable to other reported reconstruction methods regarding union rates, complications, and functional outcomes. We retrospectively analyzed the outcome of 21 intercalary pasteurized bones in lower extremities. Ultimate graft survival, union rate, and union time were evaluated as a function of clinical variables, such as age, gender, body mass index, location of intercalary segment, primary tumor type, use of chemotherapy, percentage and length of resected bone, type of junction, method of fixation, and iliac bone graft at index operation. The overall survival rate of pasteurized bone was 74% at 10 years. We identified no clinical variables associated with graft survival or union time. The union rate was related to length or percentage of resected segment and location of osteotomy. The rates of infection, fracture, and nonunion were three of 21, two of 21, and five of 21, respectively. Our results suggest reconstruction with pasteurized autograft is a simple and easily accessible method in limb salvage and an economic alternative to allograft, with low rates of ultimate failure and graft-related complications.Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Prognostic effect of pathologic fracture in localized osteosarcoma: a cohort/case controlled study at a single institute.

The negative prognostic role of pathologic fracture in osteosarcoma is not determined, as previous case–control and retrospective cohort studies have produced contradictory results.

Initial tumor size predicts histologic response and survival in localized osteosarcoma patients.

To evaluate the correlation between histologic response and size parameters, and to analyze the prognostic importance of size parameters on metastasis‐free survival in localized osteosarcoma patients.

Primary Osteosarcoma in Patients Older than 40 Years of Age

Among the 665 patients who registered at our hospital, we reviewed 39 cases of high grade primary osteosarcoma in patients who were older than 40 yr of age. The aim of this study was to determine if a primary osteosarcoma in older patients has different clinical features, and a poorer prognosis than in younger patients. Two evaluations were performed. In the first, an attempt was made to determine the possible prognostic factors such as gender, location, size, alkaline phosphatase, radiological findings, chemotherapy intensity, chemotherapy-induced tumor necrosis, and surgical margin. The second evaluation involved assessment of whether there were any significant clinical differences between older patients and adolescents. According to the results, a primary osteosarcoma in older patients did not reveal any significant prognostic variables. A primary osteosarcoma in older patients showed a poorer prognosis due to relatively unusual locations, common abnormal radiological findings, and a poor response to chemotherapy. Therefore, careful attention should be paid to making an accurate diagnosis and new strategies for more effective treatment, including chemotherapy, must to be developed in order to achieve long term survival in older patients with osteosarcoma.

Effect of increases in tumor volume after neoadjuvant chemotherapy on the outcome of stage II osteosarcoma regardless of histological response

BackgroundWe assessed volume changes after neoadjuvant chemotherapy and evaluated relations between tumor size changes and clinical characteristics. In addition, we sought to determine whether tumor size change influences patient outcome.MethodsThe records of 127 patients with stage II osteosarcoma who showed more than a 15% volume change after chemotherapy were retrospectively reviewed. Patients were divided into two groups depending on whether tumors increased or decreased in size. Fisher’s exact test was performed to analyze correlations between tumor size changes and clinicopathological variables. Five-year metastasis-free survival and overall survival were evaluated using univariate and multivariate analyses.ResultsA total of 71 patients (55.9%) showed a decrease in tumor volume, and 56 patients (44.1%) showed an increase. An increase in tumor volume after neoadjuvant chemotherapy was found to be positively correlated with a poor histological response and subsequent metastasis. Univariate analysis identified the following parameters as poor prognostic factors: age ≤15 years (P = 0.03), American Joint Committee on Cancer (AJCC) stage IIB (P = 0.02), a subtype other than osteoblastic (P < 0.01), a poor histological response (P < 0.001), and increased tumor volume after preoperative chemotherapy (P < 0.0001). Multivariate analysis revealed that AJCC stage IIB (P = 0.006) and an increase in tumor volume after preoperative chemotherapy (P < 0.001) both independently shortened metastasis-free survival. However, a poor histological response lost its prognostic significance (P = 0.34).ConclusionsIncreased tumor volume after neoadjuvant chemotherapy independently shortened metastasis-free and overall survival in AJCC stage II osteosarcoma patients. Tumor volume changes may serve as a basis for risk-adapted therapy when used in combination with other prognostic factors.

Osteogenic abilities of bone marrow stromal cells are not defective in patients with osteonecrosis

We investigated whether the proliferation activities and osteogenic capacities of bone marrow stromal cells (BMSCs) are depressed in patients with osteonecrosis of the femoral head (ONFH). BMSCs were isolated from fresh bone marrow of the iliac crests of 54 donors and were differentiated into osteogenic lineage in vitro. The results of 27 consecutive patients with ONFH (16 idiopathic and 11 alcohol-induced) were compared with those of 27 patients with a nonnecrotic hip disorder. The proliferative activities of BMSCs in patients with ONFH were not found to be reduced and their osteogenic capacities (alkaline phosphatase activity and calcium deposition amount) were unaltered during in vitro differentiation. Results from patients with idiopathic or alcohol-induced ONFH were similar to those of matched patients with nonnecrotic disorder. These findings suggest that the osteogenic potentials of BMSCs are not defective in patients with ONFH.RésuméNous pensions que la prolifération et l’activité des cellules ostéogéniques de la moelle osseuse (BMSCs) étaient diminuées chez les patients qui présentaient une ostéonécrose de la tête fémorale (ONFH). Matériel et méthodes : Les BMSCs ont été isolées de la moelle fraiche, prélevées sur la crête iliaque de 54 donneurs et classées selon leur lignée ostéogénique. Les résultats de 27 patients avec ostéonécrose, 16 idopathiques et 11 d’origine éthylique ont été comparés à 27 patients ne présentant pas de nécrose de hanche. Résultat : l’activité des cellules de moelle osseuse chez les patients avec ostéonécrose ont été trouvées diminuées et leur capacité ostéogénique (activité phosphatase alkaline et déposition calcique) ne sont pas altérées lors de l’examen in vitro. Résultat : les patients présentant une ostéonécrose idiopathique ou éthylique ont une activité ostéogénique similaire comparée à celle des patients ne présentant pas de troubles d’origine nécrotique.