The clinical outcome of hemicortical resection in extremity malignant bone tumors.

INTRODUCTION: Hemicortical resection is challenging when a huge fungating tumor is covering the osteotomy site. We report the clinical outcome of hemicortical resection and reconstruction for primary bone tumors, especially with high-grade histology and extensive circumferential involvement. MATERIALS AND METHODS: We retrospectively reviewed 44 patients (males, n = 18; females, n = 26) who underwent hemicortical resection from 2005 to 2014. RESULTS: The median follow-up period was 46.0 (23-178) months. Disease-specific, local recurrence-free, and metastasis-free survival rates of patients in the malignant group at 5 years were 96.6%, 84.5%, and 93.6%, respectively. Among 42 patients, there were local recurrences (n = 6), metastasis (n = 2), and death (n = 1). Surgical margin was an independent prognostic factor for local recurrence (hazard ratio = 5.7; p = 0.038). The recycled autograft and strut allograft groups did not show statistical difference in bone union. Failure rate was 31.8% and local recurrence was the most frequent, followed by infection. CONCLUSION: Hemicortical resection can be a feasible option for extremity malignant bone tumors. Regarding reconstruction, there were no difference between autograft and allograft in bone union rate. Surgical margin was an independent prognostic factor for local recurrence.

Clinical outcomes of endoprosthetic reconstruction for proximal femoral resection.

INTRODUCTION: The proximal femur is a common site for primary sarcomas and metastatic lesions. Although the early results of tumor prostheses are promising, the long-term results of reconstruction are unknown. The purpose of this study is to evaluate the prognostic factors affecting prosthesis survival and complications after proximal femoral resection and reconstruction. METHODS: We reviewed the results of 68 patients who underwent proximal femoral resection and reconstruction with a modular bipolar-type tumor prosthesis between 2005 and 2017. The mean follow-up was 55.6 months (range 6-172 months). There were 50 male and 18 female patients with a mean age of 41.5 years (range 11-80 years). Cumulative survival analysis was performed to analyze the risk factors of prosthesis survival. We also evaluated the complications after operation. RESULTS: Fourteen (21%) patients required further surgery at a mean 37 months post-operatively (range 5-125 months). There were three cases of infection (4%), six of local recurrence (9%), three of acetabular erosion (4%) and two of stem loosening (3%). The implant survival rates were 83.9% at 5 years and 59.8% at 10 years. Prosthesis survivals did not differ based on fixation method (P = 0.085), age (P = 0.329) or resection length (P = 0.61). Acetabular chondrolysis was identified in 18 (26%) patients and longer resection length (≥20 cm) showed a trend for risk of acetabular wear (P = 0.132). CONCLUSION: The results of proximal femoral resection and reconstruction with a modular bipolar-type prosthesis were found to be acceptable with infection and local recurrence as short-term complications and loosening and acetabular erosion as long-term complications.

Are Pasteurized Autografts Durable for Reconstructions After Bone Tumor Resections?

BACKGROUND: Pasteurized autograft is regarded as a biologic reconstructive option for managing bone defects after tumor resection; however, reports on long-term outcomes from large patient series are scarce. Contrary to previous favorable reports, we have observed many patients with failures, in particular as the duration of followup increased. Because pasteurized autografts are used in many countries as a reconstruction option, we wished to formally evaluate patients who underwent this approach at one specialty center. QUESTIONS/PURPOSES: (1) What is the graft survival and what proportion of patients achieved union when pasteurized autografts were used for bone defects after tumor resection? (2) What are the complications and causes of graft removal? (3) What factors are related to the likelihood of union and graft survival? (4) What is the survival and cause of failure by type of pasteurized autograft reconstruction? METHODS: Over a 26-year period from 1988 to 2013, we performed 1358 tumor resections in our center. Of these, 353 were reconstructed with pasteurized autograft. Other reconstructions included endoprostheses (508 patients), instant arthrodesis using an intramedullary nail and bone cement (286 patients), allografts (97 patients), and resection only (114 patients). During the period in question, we generally used this approach when tumor showed an osteoblastic pattern and less than one-third cortical destruction in osteolytic tumor. We generally avoided this approach when the tumor showed an extensive osteolytic pattern. We excluded 75 (21% [75 of 353]) patients, 21 (6% [21 of 353]) for incomplete clinical data and 54 (15% [54 of 353]) with a followup < 2 years or those lost to followup leaving 278 autografts eligible. The mean followup was 113 months (range, 25-295 months). Of these 278 patients, 242 patients had primary bone sarcomas, 22 patients had soft tissue tumor invading bone, seven patients had metastatic carcinoma, and seven patients had aggressive benign bone tumors. From a chart review, we obtained the age, sex, location, tumor volume, histologic diagnosis, use of chemotherapy, graft length, fixation modality, type of pasteurized bone used, proportion of union, complications, and oncologic outcome of the patients. In total, 377 junctional sites were assessed for union with serial radiographs. We defined junctions showing union < 2 years as union and > 2 years as delayed union. We grouped our patients into type of pasteurized bone use: pasteurized autograft-prosthesis composites (PPCs) were performed in 149, intercalary grafts in 71, hemicortical grafts in 15, osteoarticular in 12, and fusion of a joint in 31 patients. The endpoint of interest included removal of the autograft with implant loosening, infection, fracture of the graft, or any reoperation resulting in removal. Survival of the graft was determined by Kaplan-Meier plot and intergroup differences were determined using log-rank test. RESULTS: Five, 10-, and 20-year survival of 278 autografts was 73% ± 5.5%, 59% ± 6.7%, and 40% ± 13.6%, respectively. Of 278 autografts, 105 (38%) were removed with complications. Cause of removal included infection in 13% (33 patients), nonunion in 7% (18 patients), fracture of graft in 6% (16 patients), resorption of the graft in 5% (14 patients), and local recurrence in 4% (11 patients). Univariate survival analysis revealed that patient age ≤ 15 years (p = 0.027; hazard ratio [HR], 1.541), male sex (p = 0.004; HR, 1.810), and pelvic location (p = 0.05; HR, 2.518) were associated with graft removal. The 20-year survival rate of osteoarticular and hemicortical methods was 92% (95% confidence interval, -15.6% to +8.3%) and 80% ± 20%, respectively. For intercalary and fusion, it was 46% ± 15% and 28% ± 22%, respectively, although for PPC, it was 37% ± 22%. Log-rank survival analysis showed the osteoarticular and hemicortical groups had better graft survival compared with other types of reconstruction (p = 0.028; HR, 0.499). The most prevalent cause of graft removal in three major types of reconstruction was as follows: (1) PPC type was infection (30% [17 of 56]); (2) intercalary graft was infection, nonunion, and local recurrence in even proportions of 29% (86% [24 of 28]); and (3) fusion was infection (35% [six of 17]). Two hundred ten (56%) of 377 junctional sites showed union within 2 years (average, 14 months), 51 (13%) junctions showed delayed union after 2 years (average, 40 months), and the remaining 116 (31%) junctions showed nonunion. Diaphyseal junction (p = 0.029) and male sex (p = 0.004) showed a higher proportion of nonunion by univariate analysis. CONCLUSIONS: Compared with the favorable short-term and small cohort reports, survival of pasteurized autograft in this long-term large cohort was disappointing. We believe that pasteurized autograft should be used with caution in children and adolescents, in the pelvic region, and in PPC form. When bone stock destruction is minimal, it is worth considering this approach for small intercalary or distal long bone reconstruction. We believe this procedure is best indicated after hemicortical resection of long bone. LEVEL OF EVIDENCE: Level III, therapeutic study.

Higher Gemcitabine Dose Was Associated With Better Outcome of Osteosarcoma Patients Receiving Gemcitabine-Docetaxel Chemotherapy.

BACKGROUND: Efficacy of gemcitabine and docetaxel (GEM + DOC) chemotherapy in patients with recurrent or refractory osteosarcoma was evaluated. METHODS: Data of 53 patients from 9 institutions, who received GEM (675 or 900 mg/m(2) on days 1 and 8) and DOC (100 mg/m(2) on day 8), were retrospectively reviewed. RESULTS: GEM + DOC was administered as adjuvant (n = 25) or palliative chemotherapy (n = 28). Patients received a median 3 courses (range, 1-10 courses). Objective response rate (CR + PR, where CR is complete response and PR is partial response) and disease control rate (CR+ PR + SD, where SD is stable disease) were 14.3% and 28.6%, respectively. Disease control rate was higher in patients receiving 900 mg/m(2) GEM than in patients receiving 675 mg/m(2) (50.0% vs. 12.5%, P = 0.03). Higher GEM dose was associated with better survival, both in adjuvant (1-year overall survival, 90.9 ± 8.7% vs. 38.5 ± 13.5%, P = 0.002) and palliative settings (50.0 ± 14.4% vs. 31.3 ± 11.6%, P = 0.04). CONCLUSIONS: Further studies are necessary to investigate the efficacy of more aggressive and higher doses of GEM + DOC chemotherapy in osteosarcoma.

Development and external validation of nomograms predicting distant metastases and overall survival after neoadjuvant chemotherapy and surgery for patients with nonmetastatic osteosarcoma: A multi-institutional study.

BACKGROUND: In this era of individualized cancer treatment, data that could be applied to predicting the survival of patients with osteosarcoma are still limited because of the rarity of the disease and the difficulty in accumulating a sufficient number of patients. Therefore, a multi-institutional collaboration was implemented to develop and externally validate nomograms that would predict metastasis-free survival (MFS) and overall survival (OAS) for patients with nonmetastatic osteosarcoma. METHODS: This study retrospectively examined 1070 patients treated with neoadjuvant chemotherapy and surgery for nonmetastatic osteosarcoma. Data from Japanese patients (n = 557) were used to develop multivariate nomograms based on Cox regression. Six clinical and pathologic variables were built into nomograms estimating the probability of MFS and OAS 3 and 5 years after diagnosis. The model was internally validated for discrimination and calibration with bootstrap resampling and was externally validated with an independent patient cohort from Korea (n = 513). RESULTS: A patient's age, tumor site, and histologic response were found to have a stronger influence on MFS and OAS in the model than sex, tumor size, or pathologic fracture. The nomograms and calibration plots based on these results well predicted the probability of MFS (concordance index, 0.631) and OAS (concordance index, 0.679). The concordance indices for external validation were 0.682 for MFS and 0.665 for OAS. CONCLUSIONS: The nomograms were externally validated and verified to be useful for the prediction of MFS and OAS and for the assessment of the postoperative prognosis. They can be used for counseling patients and for establishing appropriate surveillance strategies after surgery.

Osteosarcoma in Asian Populations Over the Age of 40 Years: A Multicenter Study.

BACKGROUND: Elderly patients with osteosarcoma (OSA) are no longer uncommon; however, many questions remain regarding this population. We investigated the clinicopathological characteristics and prognostic factors of OSA in an Asian population over the age of 40 years. METHODS: This was a multi-national, multi-institutional study by the Eastern Asian Musculoskeletal Oncology Group (EAMOG). RESULTS: A total of 232 patients were enrolled (116 males and 116 females), with a median age of 50 years at diagnosis; 25 (10.8 %) patients exhibited initial metastasis. Median follow-up was 52 months for survivors. We observed 102 osteolytic and mixed radiographic findings for 173 lesions. Histological subtypes other than osteoblastic type were frequent. Radiation-associated OSA was seen in seven patients, with a 5-year overall survival (OS) of 16.7 %. No Paget's OSA was observed. High-grade spinopelvic OSA was seen in 29 (12.5 %) patients. The 5-year OS was 59.4 % in patients without initial metastasis and 45.2 % in patients with spinopelvic OSA. While surgery and initial metastasis were common prognostic factors for OS, chemotherapy was not. Histologic response to neoadjuvant chemotherapy was poor in 61 of 83 patients. CONCLUSION: This study revealed distinct clinicopathological features of OSA patients over 40 years of age compared with younger patients, such as the high incidence of axial tumors, common osteolytic and mixed radiographic findings, the high frequency of unusual histologic subtypes, and poor prognosis. Contrary to Western elderly patients with OSA, there was no Paget's OSA in this study, which may result in a lower incidence of secondary OSA. Prognostic factor analyses demonstrated chemotherapy did not influence OS.

Prediction of response to neoadjuvant chemotherapy in osteosarcoma using dual-phase (18)F-FDG PET/CT.

OBJECTIVES: We evaluated the ability of dual-phase (18)F-FDG PET/CT to predict the histological response after neoadjuvant chemotherapy (NAC) in osteosarcoma. METHODS: Thirty-one patients with osteosarcoma treated with NAC and surgery were prospectively enrolled. After injection of (18)F-FDG, both early (~60 min) and delayed (~150 min) PET were acquired before and after the completion of NAC. SUVmax, early/delayed SUVmax change (RImax), and early/delayed SUVmean change (RImean) of tumour were measured before (SUV1, RImax1, and RImean1) and after NAC (SUV2, RImax2, and RImean2). Then, we calculated the percentage changes between SUV1 and SUV2 (%SUV). RESULTS: Twelve patients (39%) exhibited good histological response after NAC. SUVmax, RImax, and RImean significantly decreased after NAC. Before NAC, only RImean1 predicted good histological response with the optimal criterion of < 10%, sensitivity of 92%, specificity of 57%, and accuracy of 71%. After NAC, %SUV, SUV2, and RImax2 predicted histological response. By using combined criterion of %SUV and RImax2 or SUV2 and RImean1 or SUV2 and RImax2, accuracies were 81%, 77%, and 77%, respectively. CONCLUSIONS: The histological response after NAC could be predicted by using RImean1 before the initiation of NAC in osteosarcoma. The combined use of SUV and RI values may provide a better prediction. KEY POINTS: • Pretreatment dual-phase FDG-PET was useful to predict histological response in osteosarcoma. • A combination of early and delayed PET may increase the predictive value. • Early/delayed SUV change of tumours significantly decreased after neoadjuvant chemotherapy.

Temporary hemiarthroplasty with a synthetic device in children with osteosarcoma around the knee as a bridging procedure until skeletal maturity.

BACKGROUND: We hypothesized that hemiarthroplasty with a synthetic device in skeletally immature patients with osteosarcoma around the knee would be functional due to high adaptability in the pediatric age group, and may decrease the number of surgeries until limb equalization by preserving the nearby physis. METHODS: We analyzed the outcomes of 25 hemiarthroplasties (12 distal femur, 13 proximal tibia). Average patient age was 11.8 years. We assessed (1) whether hemiarthroplasty could be considered as a viable option and could preserve growth of the nearby physis, and (2) whether these patients could reach the final goal of adult-type tumor prosthesis implantation within a preplanned number of surgeries. RESULTS: Three (12%) of 25 hemiarthroplasties showed failure. Average Musculoskeletal Tumor Society functional score of 23 patients was 25.1. Average tibial and femoral shortening for the corresponding reconstruction was 0.3 cm and 0.5 cm, respectively. In terms of number of surgeries for limb equalization, 19 patients (76%) had less, four (16%) had equal, and two (8%) had more surgeries than planned. CONCLUSIONS: Hemiarthroplasty is a sound option until skeletal maturity, allowing surgeons to choose the appropriate procedure based on the patient's growth status, and may reduce the amount of shortening by preserving nearby physis.

Usefulness of increased 18F-FDG uptake for detecting local recurrence in patients with extremity osteosarcoma treated with surgical resection and endoprosthetic replacement.

OBJECTIVE: To investigate the changes of increased F-18 fluorodeoxyglucose ((18)F-FDG) uptake around the prosthesis and its ability to differentiate local recurrence from postsurgical change after endoprosthetic replacement in extremity osteosarcoma. MATERIALS AND METHODS: A total of 355 positron emission tomography (PET)/computed tomography (CT) scans in 109 extremity osteosarcoma patients were retrospectively analyzed. All patients were followed up with (18)F-FDG PET/CT for more than 3 years after tumor resection. For semiquantitative assessment, we drew a volume of interest around the entire prosthesis of the extremity and measured the maximum standardized uptake value (SUV max). Independent samples t test was used to compare SUV max at each follow-up time. SUV max at 3 months (SUV1) and SUV max at the time of local recurrence in patients with recurrence or at the last follow-up in others (SUV2) were compared using the Mann-Whitney test. Diagnostic performances of PET parameters were assessed using ROC curve analyses. RESULTS: Nine patients (8 %) showed a local recurrence. Mean SUV max at 3, 12, 24, and 36 months was 3.1 ± 1.5, 3.8 ± 1.9, 3.6 ± 1.9, and 3.7 ± 1.5 respectively. In ROC curve analysis, the combination of SUV2 >4.6 and ΔSUV >75.0 was a more useful parameter for predicting local recurrence than SUV2 or ΔSUV alone. The sensitivity, specificity, and accuracy for identifying local recurrence were 89, 76, 77 % for SUV2; 78, 81, 81 % for ΔSUV; and 78, 94, 93 % for the combined criterion respectively. CONCLUSION: The combination of SUV2 and ΔSUV was more useful than the SUV2 or ΔSUV used alone for the prediction of local recurrence.

Clinical outcome of low-grade central osteosarcoma and role of CDK4 and MDM2 immunohistochemistry as a diagnostic adjunct.

INTRODUCTION: Low-grade osteosarcoma encompasses parosteal osteosarcoma (POS) and low-grade central osteosarcoma (LCOS), with LCOS more rare than POS. LCOS is also more likely to be misdiagnosed and inappropriately treated with an intralesional procedure, due to its misleading radiological features and the overlap of its pathological characteristics with those of benign bone tumors. Therefore, as a diagnostic adjunct for LCOS, immunohistochemical assay with murine double-minute type 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) have been tried with controversial results. We investigated (1) the clinical course and surgical outcome of LCOS, and (2) the diagnostic role of immune-histochemical markers (CDK4, MDM2) and their correlation with clinico-radiologic findings. MATERIALS AND METHODS: We retrospectively reviewed 16 LCOS patients with regard to age, gender, tumor location, plain radiographic pattern, tumor volume, extraosseous extension, initial diagnosis, initial treatment, definitive diagnosis, definitive treatment, surgical margins, histochemical markers, and oncological outcome. RESULTS: Final survival status was continuous disease-free in 14, alive with disease in 1, and remaining 1 patient died of other cancer. Except for 1 patient who had not undergone excision of their primary lesion, no patients developed a local recurrence. Eight tumors (50%) showed diffuse immunostaining for CDK4. Three of 8 tumors labeled for CDK4 were also positive for MDM2. Six (75%) of 8 CDK4-positive tumors displayed lytic lesions on a plain radiograph; in contrast, 2 (33%) of 6 tumors showing a sclerotic pattern on a plain radiograph were positive for CDK4. CONCLUSIONS: The diagnosis of LCOS is challenging; however, if it is properly diagnosed, there is a high chance of a cure with wide excision alone. Positive immunostaining for CDK4 or MDM2 may be used as a diagnostic adjunct, although negative immunostaining cannot rule out this tumor. The clinical, radiological, and typical pathological findings are vital in raising the suspicion of this rare tumor.

Spontaneous necrosis and additional tumor necrosis induced by preoperative chemotherapy for osteosarcoma: a case-control study.

BACKGROUND: Extent of spontaneous necrosis in untreated osteosarcoma may imply tumor aggressiveness. Reports regarding this issue are scarce and there are several points to be clarified; (1) the correlation between tumor size and extent of spontaneous necrosis displayed was conflicting, (2) whether there is difference in necrosis rate between intra- and extra-medullary portion of tumor is not described, if it does, its relation with other clinico-pathologic variables, (3) in patients with surgical treatment only, >20 % spontaneous necrosis was a poor prognostic factor, however, whether that cutoff is still valid in chemotherapy cohort remains to be determined, (4) expected additional tumor necrosis by chemotherapy was made by simply comparing the necrosis rates of untreated and treated osteosarcoma cohort. METHODS: We evaluated spontaneous necrosis in 43 osteosarcoma patients (39 Stage IIB, 4 Stage III). We evaluated overall necrosis rate and separately evaluated the necrosis rate of intra- and extra-medullary portion of tumor. These results were compared with other clinico-pathologic variables. To evaluate additional tumor necrosis induced by neoadjuvant chemotherapy, case (38 without preoperative chemotherapy)-control (76 with preoperative chemotherapy) study was performed. RESULTS: The mean spontaneous necrosis rate was 23 %. Overall spontaneous necrosis was not associated with tumor volume. Necrosis rate of extramedullary tumors was higher in cases of large tumors (p = 0.02). In patients with upfront surgery followed by chemotherapy, 5-year event-free survival rate of patients with >20 and <20 % spontaneous necrosis were 82 ± 17 and 79 ± 18.5 %, respectively (p = 0.75). After chemotherapy, regardless of tumor volume and location, control group tumors showed an increase in the tumor necrosis of approximately 50 %. CONCLUSION: In chemotherapy era, the extent of spontaneous necrosis has no relation with survival. The expected additional tumor-killing effect of preoperative chemotherapy is around 50 % of initial tumor volume.

Correlation between fluid-fluid levels on initial MRI and the response to chemotherapy in stage IIb osteosarcoma.

BACKGROUND: The presence of fluid-fluid levels (FFLs) on osteosarcoma magnetic resonance imaging (MRI) is underestimated as a nonspecific finding; however, we hypothesized that FFL in conventional osteosarcoma may be indicative of chemoresistance. METHODS: In 567 stage IIB osteosarcoma patients, we evaluated the following: the incidence of FFL and their correlation with other clinicopathological variables; tumor volume change after chemotherapy and survival according to the presence of FFL; and the relationship between survival and the extent of FFL. RESULTS: One hundred eight (19 %) tumors showed FFL on initial MRI. FFL were correlated with proximal humeral location (P = 0.017), osteolytic on plain radiographs (P < 0.001), tumor enlargement after chemotherapy (P < 0.001), and poor histological response (P = 0.005). Large tumor (P < 0.01), proximal tumor location (P = 0.01), and presence of FFL (P < 0.01) were independent predictors of poor survival. Compared to the extensive FFL (more than one third of the tumor), small foci of FFL (less than one third of the tumor) showed a high tendency for tumor enlargement after chemotherapy (P < 0.001), poor histologic response (P = 0.001), and worse survival (P < 0.001). CONCLUSIONS: FFL on initial MRI could predict tumor progression after chemotherapy. Notably, tumors with small foci of FFL (less than one third of the tumor) have a high propensity for poor outcome. Patients with this finding should be considered for risk-adapted therapy.

Early response monitoring to neoadjuvant chemotherapy in osteosarcoma using sequential ¹8F-FDG PET/CT and MRI.

PURPOSE: We evaluated the potential of sequential fluorine-18 fluorodeoxyglucose ((18) F-FDG) positron emission tomography (PET)/computed tomography (CT) and MRI (PET/MRI) after one cycle of neoadjuvant chemotherapy to predict a poor histologic response in osteosarcoma. METHODS: A prospective study was conducted on 30 patients with osteosarcoma treated with two cycles of neoadjuvant chemotherapy and surgery. All patients underwent PET/MRI before, after one cycle, and after the completion of neoadjuvant chemotherapy, respectively. Imaging parameters [maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and tumor volume based on magnetic resonance (MR) images (MRV)] and their % changes were calculated on each PET/MRI data set, and histological responses were evaluated on the postsurgical specimen. RESULTS: A total of 17 patients (57%) exhibited a poor histologic response after two cycles of chemotherapy. Unlike the little volumetric change in MRI, PET parameters significantly decreased after one and two cycles of chemotherapy, respectively. After one cycle of chemotherapy, SUVmax, MTV, and TLG predicted the poor responders. Among these parameters, either MTV ≥ 47 mL or TLG ≥ 190 g after one cycle of chemotherapy was significantly associated with a poor histologic response on multivariate logistic regression analysis (OR 8.98, p = 0.039). The sensitivity, specificity, and accuracy of these parameters were 71%, 85% and 77%; and 71%, 85% and 77 %, respectively. CONCLUSION: The histologic response to neoadjuvant chemotherapy in osteosarcoma can be predicted accurately by FDG PET after one course of chemotherapy. Among PET parameters, MTV and TLG were independent predictors of the histologic response.

Examination of the cutoff value of postchemotherapy increase in tumor volume as a predictor of subsequent oncologic events in stage IIB osteosarcoma.

BACKGROUND: Tumor enlargement after chemotherapy is a predictor of a poor histological response, poor survival, and local recurrence. However, the cutoff point of tumor enlargement for predicting subsequent oncologic events has not been determined. METHODS: We retrospectively reviewed 567 patients who were treated at our institute for stage IIB osteosarcoma. We used receiver operating characteristic (ROC) curve analysis of tumor volume increase for the prediction of subsequent metastasis or local recurrence, and calculated diagnostic indices for different cutoff values. RESULTS: A tumor volume increase of >15% predicted subsequent metastasis or local recurrence with a sensitivity of 64.7%, a specificity of 81.5%, a positive predictive value of 71.6%, and a negative predictive value of 76.1%. Increases in tumor volumes based on this cutoff value were able to predict subsequent oncologic events in all clinical subgroups, except in cases of rare pathologic subtypes. However, for tumors in the proximal humerus, a cutoff value of 25% had optimal predictive value. CONCLUSIONS: This study shows that a cutoff value of 15% for tumor volume increase is useful for predicting subsequent metastasis or local recurrence. Our results suggest that tumor enlargement after chemotherapy serves as an easily assessable clinical parameter for risk-adapted therapy.

Overlapping allograft for primary or salvage bone tumor reconstruction.

BACKGROUND: Compared with end-to-end allograft coaptation, overlapping allograft offer a superior union rate by increasing the contact area. However, reports on overlapping allograft are scarce. Therefore, we attempted to confirm the usefulness of this technique either after primary tumor resection or in salvaging a failed reconstruction. METHODS: We analyzed the outcome of 35 overlapping allografts reconstructions. Indications were primary reconstruction of a skeletal defect (n = 19) and salvage of a failed reconstruction (n = 16). Graft survival, union rate, and time to union were evaluated as a function of clinical variables such as age, use of chemotherapy, type of junction, method of fixation, length of overlapped bone, and method of overlapping. RESULTS: All 35 overlapping allografts showed union at a mean of 5.6 months (range, 3-14 months). One allograft was removed with local recurrence at 19 months post-operatively. Average length of overlapped bone was 3.5 cm (range, 1.4-6.5 cm). Patient age <15-years (P = 0.001) and circumferential overlapping (P = 0.011) shortened the time to union. CONCLUSIONS: In terms of graft failure rate, union rate, and time to union, overlapping allograft is an excellent technique, which overcomes the limitations of end-to-end fixation.

Proximal tumor location and fluid-fluid levels on MRI predict resistance to chemotherapy in stage IIB osteosarcoma.

BACKGROUND: Primary tumor growth during neoadjuvant chemotherapy is believed to be a sign of resistance to chemotherapy (chemoresistance), and often is associated with poor histologic response, local recurrence, and poorer survival. Currently there are no proven indicators to predict poor response to chemotherapy at the time of diagnosis. QUESTIONS/PURPOSES: We asked (1) what clinicopathologic factors present at diagnosis predict primary tumor growth during neoadjuvant chemotherapy, (2) what factors at presentation predict survival, and (3) when the factors at presentation and the treatment-related factors are considered, what factors independently correlate with survival. METHODS: We studied 567 patients with Stage IIB osteosarcomas. The factors assessed included age, sex, location, pattern on plain radiographs (radiodense, radiolucent, mixed), MRI findings, pathologic subtype, initial tumor volume determined by MRI, tumor volume change after chemotherapy, surgical margin, and histologic response to preoperative chemotherapy. Logistic modeling was used to identify risk factors. RESULTS: Independent risk factors associated with primary tumor growth after neoadjuvant chemotherapy were proximal tumor location (p < 0.01; relative risk [RR], 2.41; 95% CI, 1.5-3.86) and fluid-fluid level on initial MRI (p < 0.01; RR, 5.56; 95% CI, 3.48-8.87). Among factors at presentation, large initial tumor volume (p < 0.01; RR, 1.58; 95% CI, 1.22-2.04), proximal tumor site (p < 0.01; RR, 1.61; 95% CI, 1.19-2.19), and presence of fluid-fluid level (p < 0.01; RR, 1.83; 95% CI, 1.37-2.5) independently predicted reduced event-free survival. When we consider the factors at presentation and treatment-related factors, large initial tumor volume (p < 0.01; RR, 1.54), tumor growth after neoadjuvant chemotherapy (p < 0.01; RR, 3.88), inadequate surgical margin (p < 0.01; RR, 2.42), and poor histologic response (p = 0.03; RR, 1.43) were independent poor prognostic factors of event-free survival. CONCLUSIONS: Proximal tumor location and the presence of the fluid-fluid level on initial MRI were predictors of tumor progression and poor survival in patients presenting with Stage IIB osteosarcomas. If confirmed in other studies, patients with these risk factors should be considered for trials of other treatment strategy. LEVEL OF EVIDENCE: Level III, prognostic study. See the Instructions for Authors for a complete description of levels of evidence.

Secondary hematological malignancies in patients with sarcoma: A single­center retrospective study.

The present retrospective study investigated the clinical features and prognosis of secondary hematological malignancies (SHMs) in patients with sarcoma at Korea Cancer Center Hospital (Seoul, South Korea). Patients who had been diagnosed with SHMs after having received treatment for sarcoma between January 2000 and May 2023 were enrolled. Clinical data were collected from the patients' medical records. Clinical characteristics were analyzed, including SHM incidence, type and prognosis. Of 2,953 patients with sarcoma, 18 (0.6%) were diagnosed with SHMs. Their median age at the time of sarcoma diagnosis was 39.5 (range, 9-72) years, and 74% (n=14) of these patients were male. The histological features of sarcoma varied, with osteosarcoma diagnosed in nine patients (50%). All patients with sarcoma underwent surgical treatment, and 16 (88.8%) received chemotherapy. The most common type of SHMs was acute myeloid leukemia (n=6; 33.3%), followed by myelodysplastic syndrome (n=5; 27.7%). The median latency period between the sarcoma diagnosis and SHM identification was 30 (range, 11-121) months. A total of 13 (72.2%) patients received treatment for the SHM. The median overall survival after SHM diagnosis was 15.7 (range, 0.4-154.9) months. The incidence of SHMs in sarcoma in the present study was consistent with that reported previously. The presence of SHMs was associated with a poor patient prognosis, especially if treatment for SHMs was not administered.

¹8F-FDG PET SUVmax as an indicator of histopathologic response after neoadjuvant chemotherapy in extremity osteosarcoma.

PURPOSE: This study evaluated the usefulness of the maximum standardized uptake value (SUVmax) as a measure of histologic response to neoadjuvant chemotherapy in patients with extremity osteosarcoma. The correlation between [(18) F]FDG PET SUVmax values and histologic response to preoperative chemotherapy was also assessed prospectively using PET/MRI. METHODS: A total of 26 consecutive patients with high-grade osteosarcoma were prospectively enrolled. All patients underwent parallel PET and MRI scans before and after neoadjuvant chemotherapy. Using the PET and MRI images and pathologic mapping, we assessed the percentage necrosis by histology at the highest metabolic activity point in the tumors. This was defined as the minimum histologic response. The predictive values of SUVmax before (SUV1) and after (SUV2) chemotherapy and the SUV change ratio were determined. Correlations were also investigated among SUV2, minimum histologic response and histologic response. RESULTS: Histologically, 13 patients were classified as good responders and 13 as poor responders. Patients with an SUV2 of >5 showed a poor histologic response. A significant correlation was found between SUV2 and histologic response (Spearman's rho -0.642; P < 0.001), and SUV2 and histologic response were both found to be significantly correlated with minimum histologic response (Spearman's rho -0.515 and 0.911; P = 0.007 and P < 0.001, respectively). CONCLUSION: A SUVmax of more than 5 after neoadjuvant chemotherapy identified the majority of histologic nonresponders (sensitivity 61.3 %, PPV 88.9 %). Tumor necrosis at the point of maximum metabolic activity was found to be significantly correlated with the histologic response of entire resected specimen.

Young age at diagnosis, male sex, and decreased lean mass are risk factors of osteoporosis in long-term survivors of osteosarcoma.

BACKGROUND: Long-term survival of children with osteosarcoma has increased, but most suffer from osteoporosis in adulthood. The aim of this study was to investigate the prevalence and identify the risk factors of osteoporosis. METHODS: Forty long-term survivors of osteosarcoma and 55 controls were enrolled. The mean age of the survivors was 21.8 ± 5.2 years. They were diagnosed at younger than 23 years of age (mean, 14.9 + 5.0 y). Bone mineral densities (BMD) and body compositions were measured by dual-energy x-ray absorptiometry. RESULTS: Nineteen (47.5%) subjects had osteoporosis and 12 (30.0%) had osteopenia. The regions affected by osteoporosis were: femur neck of osteosarcoma site (47.5%), unaffected femur neck (12.5%), lumbar spine (12.5%), and total body (15.0%). Twelve subjects (30.0%) had 14 episodes of fractures. The identified risk factors of osteoporosis were young age at diagnosis, male sex, and low lean mass. Subjects diagnosed before attainment of puberty (male ≤ 16 y, female ≤ 14 y) were found to have a higher prevalence of osteoporosis (37.5% vs. 10.0%, P < 0.01). Males had a higher prevalence of osteopenia or osteoporosis than females (86.4% vs. 66.7%, P < 0.01). Total lean mass was positively correlated with unaffected femur neck BMD. Regional lean mass in affected limb was significantly reduced along with affected femur neck BMD. CONCLUSIONS: In long-term survivors of osteosarcoma, prevalence of osteoporosis and fracture was higher than expected. Initial evaluation and regular follow-up of BMD should be performed in all osteosarcoma patients, especially in those who did not attain puberty, males, and those with a low lean mass.