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.

Proximal Femur Salvage in Revision Knee Arthroplasty Due to Oncologic Indications: Long-term Results of Onlay and Overlapping Allograft in Revision Surgeries.

Background: Mechanical failures of tumor endoprosthesis in the distal femur usually require revision surgery. We investigated if the proximal femur host bone can be salvaged by onlay and overlapping allograft in revision surgeries due to aseptic loosening and stem fractures. Methods: We retrospectively reviewed 18 patients (7 men and 11 women) with osteosarcoma around the knee. The entire cohort was classified into three subgroups (no bone graft: 6, onlay allograft: 7, and overlapping allograft: 5) according to our treatment strategy. Results: The median interval from the initial surgery to the revision was 94.5 months (range, 21-219 months), and the median follow-up period from the revision surgery was 88.0 months (range, 24-179 months). At the last follow-up, 9 of the 18 patients maintained their endoprostheses, and the 5-year prosthesis survival rate was 57.9%. Limb survival was 100%. Five-year prosthesis survival rate was 66.7% in the no bone graft group, 85.7% in the onlay allograft group while 30.0% in the overlapping allograft group. In the no bone graft group and onlay allograft group, 66.7% (4/6) and 57.1% (4/7) maintained their revision prostheses while no prostheses survived in the overlapping allograft group. Recurrent stem loosening was observed in 14.2% (1/7) and 60.0% (3/5) of the onlay allograft and overlapping allograft groups, respectively, despite allograft bone union. The complication rate was 66.7% (12/18) in the entire cohort. The most common type of complication was infection (n = 6), followed by aseptic loosening (n = 4) and mechanical failure (n = 2). Conclusions: This study indicates that onlay allograft can be used as a supportive method in revising failed endoprosthesis if the extent of host bone destruction is extensive. However, applying overlapping allograft to secure bone stock showed a high rate of mechanical failures and infection in the long term. Future studies with a larger cohort are necessary to assess the prognostic factors for the higher complication rate in overlapping allograft and the need for overlapping allograft. Surveillance with consideration of the risk of anteromedial osteolysis in allograft and efforts for prevention of periprosthetic infection are essential.

Insulin syringe for anesthesia in ptosis surgery: a randomized, fellow eye-controlled clinical study.

PURPOSE: Unlike ordinary 30-gauge needles, insulin syringe needles are thinner and shorter and have a comparatively blunt tip. Therefore, insulin syringes may reduce injection discomfort, bleeding, and edema by minimizing tissue damage and vascular penetration. This study aimed to evaluate the potential benefits of using insulin syringes for local anesthesia in ptosis surgery. METHODS: This randomized, fellow eye-controlled study included 60 patients (120 eyelids), conducted at a university-based hospital. An insulin syringe was used on one eyelid, and a conventional 30-gauge needle was used on the other. Patients were instructed to score pain in both eyelids using a visual analog scale (VAS) ranging from 0 (no pain) to 10 (unbearable pain). Ten minutes after the injection, two observers scored degrees of hemorrhage and edema in both eyelids on five- and four-pointing grading scales (0-4 and 0-3) for each value, and the average score between the two observers was calculated and compared. RESULTS: The VAS score was 5.17 in the insulin syringe group and 5.35 in the 30-gauge needle group (p = 0.282). Ten minutes after the anesthesia, the median hemorrhage scores were 1.00 and 1.75 (p = 0.010), and the median eyelid edema scores were 1.25 and 2.00 (p = 0.007) in the insulin syringe and 30-gauge needle groups, respectively (Fig. 1). CONCLUSION: Injecting local anesthesia using an insulin syringe significantly reduces hemorrhage and eyelid edema, but not injection pain, before skin incision. Insulin syringes are useful in patients at high risk of bleeding because they can reduce the penetrative tissue damage caused by needle insertion.

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.

Prediction of Neoadjuvant Chemotherapy Response in Osteosarcoma Using Convolutional Neural Network of Tumor Center 18F-FDG PET Images.

We compared the accuracy of prediction of the response to neoadjuvant chemotherapy (NAC) in osteosarcoma patients between machine learning approaches of whole tumor utilizing fluorine-18fluorodeoxyglucose (18F-FDG) uptake heterogeneity features and a convolutional neural network of the intratumor image region. In 105 patients with osteosarcoma, 18F-FDG positron emission tomography/computed tomography (PET/CT) images were acquired before (baseline PET0) and after NAC (PET1). Patients were divided into responders and non-responders about neoadjuvant chemotherapy. Quantitative 18F-FDG heterogeneity features were calculated using LIFEX version 4.0. Receiver operating characteristic (ROC) curve analysis of 18F-FDG uptake heterogeneity features was used to predict the response to NAC. Machine learning algorithms and 2-dimensional convolutional neural network (2D CNN) deep learning networks were estimated for predicting NAC response with the baseline PET0 images of the 105 patients. ML was performed using the entire tumor image. The accuracy of the 2D CNN prediction model was evaluated using total tumor slices, the center 20 slices, the center 10 slices, and center slice. A total number of 80 patients was used for k-fold validation by five groups with 16 patients. The CNN network test accuracy estimation was performed using 25 patients. The areas under the ROC curves (AUCs) for baseline PET maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), metabolic tumor volume (MTV), and gray level size zone matrix (GLSZM) were 0.532, 0.507, 0.510, and 0.626, respectively. The texture features test accuracy of machine learning by random forest and support vector machine were 0.55 and 0. 54, respectively. The k-fold validation accuracy and validation accuracy were 0.968 ± 0.01 and 0.610 ± 0.04, respectively. The test accuracy of total tumor slices, the center 20 slices, center 10 slices, and center slices were 0.625, 0.616, 0.628, and 0.760, respectively. The prediction model for NAC response with baseline PET0 texture features machine learning estimated a poor outcome, but the 2D CNN network using 18F-FDG baseline PET0 images could predict the treatment response before prior chemotherapy in osteosarcoma. Additionally, using the 2D CNN prediction model using a tumor center slice of 18F-FDG PET images before NAC can help decide whether to perform NAC to treat osteosarcoma patients.

Preliminary Radiogenomic Evidence for the Prediction of Metastasis and Chemotherapy Response in Pediatric Patients with Osteosarcoma Using 18F-FDF PET/CT, EZRIN and KI67.

Chemotherapy response and metastasis prediction play important roles in the treatment of pediatric osteosarcoma, which is prone to metastasis and has a high mortality rate. This study aimed to estimate the prediction model using gene expression and image texture features. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) images of 52 pediatric osteosarcoma patients were used to estimate the machine learning algorithm. An appropriate algorithm was selected by estimating the machine learning accuracy. 18F-FDG PET/CT images of 21 patients were selected for prediction model development based on simultaneous KI67 and EZRIN expression. The prediction model for chemotherapy response and metastasis was estimated using area under the curve (AUC) maximum image texture features (AUC_max) and gene expression. The machine learning algorithm with the highest test accuracy in chemotherapy response and metastasis was selected using the random forest algorithm. The chemotherapy response and metastasis test accuracy with image texture features was 0.83 and 0.76, respectively. The highest test accuracy and AUC of chemotherapy response with AUC_max, KI67, and EZRIN were estimated to be 0.85 and 0.89, respectively. The highest test accuracy and AUC of metastasis with AUC_max, KI67, and EZRIN were estimated to be 0.85 and 0.8, respectively. The metastasis prediction accuracy increased by 10% using radiogenomics data.

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.

Early response monitoring of neoadjuvant chemotherapy using [18F]FDG PET can predict the clinical outcome of extremity osteosarcoma.

BACKGROUND: To propose a personalized therapeutic approach in osteosarcoma treatment, we assessed whether sequential [18F]FDG PET/CT (PET/CT) could predict the outcome of patients with osteosarcoma of the extremities after one cycle and two cycles of neoadjuvant chemotherapy. METHODS: A total of 73 patients with AJCC stage II extremity osteosarcoma treated with 2 cycles of neoadjuvant chemotherapy, surgery, and adjuvant chemotherapy were retrospectively analyzed in this study. All patients underwent PET/CT before (PET0), after 1 cycle (PET1), and after the completion of neoadjuvant chemotherapy (PET2), respectively. Maximum standardized uptake value (SUVmax) (corrected for body weight) and the % changes of SUVmax were calculated, and histological responses were evaluated after surgery. Receiver-operating characteristic (ROC) curve analyses and the Cox proportional hazards models were used to analyze whether imaging and clinicopathologic parameters could predict event-free survival (EFS). RESULTS: A total of 36 patients (49.3%) exhibited a poor histologic response and 17 patients (23.3%) showed events (metastasis in 15 and local recurrence in 2). SUVmax on PET2 (SUV2), the percentage change of SUVmax between PET0 and PET1 (Δ%SUV01), and between PET0 and PET2 (Δ%SUV02) most accurately predicted events using the ROC curve analysis. SUV2 (relative risk, 8.86; 95% CI, 2.25-34.93), Δ%SUV01 (relative risk, 5.97; 95% CI, 1.47-24.25), and Δ%SUV02 (relative risk, 6.00; 95% CI, 1.16-30.91) were independent predicting factors for EFS with multivariate analysis. Patients with SUV2 over 5.9 or Δ%SUV01 over - 39.8% or Δ%SUV02 over - 54.1% showed worse EFS rates than others (p < 0.05). CONCLUSIONS: PET evaluation after 1 cycle of presurgical chemotherapy can predict the clinical outcome of extremity osteosarcoma. [18F]FDG PET, which shows a potential role in the early evaluation of the modification of timing of local control, can be a useful modality for early response monitoring of neoadjuvant chemotherapy.

Metastasis risk prediction model in osteosarcoma using metabolic imaging phenotypes: A multivariable radiomics model.

BACKGROUND: Osteosarcoma (OS) is the most common primary bone tumor affecting humans and it has extreme heterogeneity. Despite modern therapy, it recurs in approximately 30-40% of patients initially diagnosed with no metastatic disease, with the long-term survival rates of patients with recurrent OS being generally 20%. Thus, early prediction of metastases in OS management plans is crucial for better-adapted treatments and survival rates. In this study, a radiomics model for metastasis risk prediction in OS was developed and evaluated using metabolic imaging phenotypes. METHODS AND FINDINGS: The subjects were eighty-three patients with OS, and all were treated with surgery and chemotherapy for local control. All patients underwent a pretreatment 18F-FDG-PET scan. Forty-five features were extracted from the tumor region. The incorporation of features into multivariable models was performed using logistic regression. The multivariable modeling strategy involved cross validation in the following four steps leading to final prediction model construction: (1) feature set reduction and selection; (2) model coefficients computation through train and validation processing; and (3) prediction performance estimation. The multivariable logistic regression model was developed using two radiomics features, SUVmax and GLZLM-SZLGE. The trained and validated multivariable logistic model based on probability of endpoint (P) = 1/ (1+exp (-Z)) was Z = -1.23 + 1.53*SUVmax + 1.68*GLZLM-SZLGE with significant p-values (SUVmax: 0.0462 and GLZLM_SZLGE: 0.0154). The final multivariable logistic model achieved an area under the curve (AUC) receiver operating characteristics (ROC) curve of 0.80, a sensitivity of 0.66, and a specificity of 0.88 in cross validation. CONCLUSIONS: The SUVmax and GLZLM-SZLGE from metabolic imaging phenotypes are independent predictors of metastasis risk assessment. They show the association between 18F-FDG-PET and metastatic colonization knowledge. The multivariable model developed using them could improve patient outcomes by allowing aggressive treatment in patients with high metastasis risk.

Prediction of Chemotherapy Response of Osteosarcoma Using Baseline 18F-FDG Textural Features Machine Learning Approaches with PCA.

Purpose: Patients with high-grade osteosarcoma undergo several chemotherapy cycles before surgical intervention. Response to chemotherapy, however, is affected by intratumor heterogeneity. In this study, we assessed the ability of a machine learning approach using baseline 18F-fluorodeoxyglucose (18F-FDG) positron emitted tomography (PET) textural features to predict response to chemotherapy in osteosarcoma patients. Materials and Methods: This study included 70 osteosarcoma patients who received neoadjuvant chemotherapy. Quantitative characteristics of the tumors were evaluated by standard uptake value (SUV), total lesion glycolysis (TLG), and metabolic tumor volume (MTV). Tumor heterogeneity was evaluated using textural analysis of 18F-FDG PET scan images. Assessments were performed at baseline and after chemotherapy using 18F-FDG PET; 18F-FDG textural features were evaluated using the Chang-Gung Image Texture Analysis toolbox. To predict the chemotherapy response, several features were chosen using the principal component analysis (PCA) feature selection method. Machine learning was performed using linear support vector machine (SVM), random forest, and gradient boost methods. The ability to predict chemotherapy response was evaluated using the area under the receiver operating characteristic curve (AUC). Results: AUCs of the baseline 18F-FDG features SUVmax, TLG, MTV, 1st entropy, and gray level co-occurrence matrix entropy were 0.553, 0538, 0.536, 0.538, and 0.543, respectively. However, AUCs of the machine learning features linear SVM, random forest, and gradient boost were 0.72, 0.78, and 0.82, respectively. Conclusion: We found that a machine learning approach based on 18F-FDG textural features could predict the chemotherapy response using baseline PET images. This early prediction of the chemotherapy response may aid in determining treatment plans for osteosarcoma patients.

Comparison of 99mTc-methyl diphosphonate bone scintigraphy and 18F-fluorodeoxyglucose positron emission tomography/computed tomography to predict histologic response to neoadjuvant chemotherapy in patients with osteosarcoma.

We compared the usefulness of Tc-methyl diphosphonate (Tc-MDP) bone scintigraphy and F-fluorodeoxyglucose (FDG) for positron emission tomography/computed tomography (PET/CT) in predicting histologic response in patients with osteosarcoma receiving neoadjuvant chemotherapy (NAC).We retrospectively reviewed 62 patients with high-grade osteosarcoma who had received 2 cycles of NAC and surgery. All patients underwent Tc-MDP bone scintigraphy and F-FDG PET/CT before and after NAC. Tc-MDP uptake in the primary tumor was measured quantitatively as the maximum tumor-to-nontumor ratio (T/NTmax) and F-FDG uptake was measured as the maximum standardized uptake value (SUVmax), before and after NAC. The percent changes of T/NTmax (percent changes of the maximum tumor-to-nontumor ratio [Δ%T/NTmax]) and SUVmax (percent changes of the maximum standardized uptake value [Δ%SUVmax]) after NAC were calculated and the correlations between these parameters were evaluated. After surgery, the effects of NAC were graded histopathologically (good vs poor) and the optimum cut-off values of Δ%T/NTmax and Δ%SUVmax for predicting histologic response were assessed using the receiver operating characteristic (ROC) curve analysis.Δ%T/NTmax and Δ%SUVmax were positively correlated with each other (r = 0.494, P < .01). Based on the ROC curve analysis, both Δ%T/NTmax (area under the curve [AUC] = .772, P < .01) and Δ%SUVmax (AUC = .829, P < .01) predicted good histologic response. However, there was no significant difference between the AUCs of Δ%T/NTmax and Δ%SUVmax (P = .44). The sensitivity and specificity for predicting good histologic response were 83.3% and 75.0%, for the criterion Δ%T/NTmax <-12.5%, and 80.0% and 81.3% for the criterion Δ%SUVmax <-49.0%, respectively.The Tc-MDP bone scan and F-FDG PET scan are non-inferior to each other in predicting the histologic response of osteosarcoma treatments. The Tc-MDP bone scan and F-FDG PET scan showed respective advantages with differing features. Therefore, physicians should consider which scan is appropriate for their own institute based on the advantages of each scan and the circumstances of the institute.

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.

Comparison of Pasteurized Autograft-Prosthesis Composite Reconstruction and Resection Hip Arthroplasty for Periacetabular Tumors.

BACKGROUND: Because of the high complication rate of anatomical reconstruction after periacetabular resection, the strategy of resection alone has been revisited. However, in terms of complications and functional outcome, whether resection hip arthroplasty (RHA) shows a superior result to that of pelvic ring reconstruction remains controversial. METHODS: We compared 24 RHAs and 16 pasteurized autograft-prosthesis composite (PPC) reconstructions regarding the complication rates, operative time, blood loss, and functional outcome. RESULTS: Compared to 16 PPC hips, 24 RHA hips showed lower major and minor complication rates (p < 0.001), shorter surgical time (p < 0.001), and superior Musculoskeletal Tumor Society scores (p < 0.001). Of the 24 RHA hips, bony neo-acetabulum was identified in 7 on computed tomography and partial neo-acetabulum in 9; the remaining 8 had no bony acetabular structure. The average time to bony neo-acetabulum formation was 7 months (range, 4 to 13 months). CONCLUSIONS: RHA for periacetabular tumors can be an excellent alternative to anatomical reconstruction. It offers short surgical time, low complication rates, and functional results comparable to those of other reconstruction methods. However, this procedure is indicated for patients who can accept some limb shortening, and a tumor should be confined to the periacetabular area.

Pasteurized Autograft-Prosthesis Composite Reconstruction May Not Be a Viable Primary Procedure for Large Skeletal Defects after Resection of Sarcoma.

BACKGROUND: Among various types of composite biological reconstruction, pasteurized autograft-prosthesis composite (PPC) is popular when allograft is unavailable. Previous limited cohort study indicated result comparable to tumor prosthesis. However, as case number and follow-up increase, we experienced more complications than anticipated. We questioned the usefulness of PPC as a viable reconstructive option. METHODS: We reviewed 142 PPCs and analyzed overall and location-related survival and factors associated with the failure of PPC. RESULTS: Twenty-year survival rate of 142 PPCs was 39.8 ± 10.0%. Fifty-two (36.6%) of 142 PPCs showed failure. Among various locations, the proximal femur showed best survival: 78.0 ± 9.9%. Final status of the 52 failed PPCs was modular tumor prosthesis in 23 (43%), arthrodesis in 11 (21%), pseudarthrosis in 7 (13%), amputation in 7 (13%), and allograft-prosthesis composite in 4 (8%). Tumor volume > 200 cc (p = 0.001), pasteurization length ≤ 10 cm (p = 0.002), male sex (p = 0.02), and locations in pelvis or tibia (p = 0.029) were poor prognostic factors. CONCLUSIONS: Long-term survival of PPCs was below expectations. Despite the complexity of the procedure, there is little survival gain over tumor prosthesis. PPC may be indicated when a modular prosthesis is not readily available.

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.

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.

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.

The Role of (18)F-FDG PET/CT as a Prognostic Factor in Patients with Synovial Sarcoma.

PURPOSE: This research aims to investigate the potential of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET) to predict pathologic response after neoadjuvant chemotherapy (NAC) and overall survival (OS) of patients with synovial sarcoma in Korea. METHODS: Twenty patients with synovial sarcoma from January 2001 to December 2011 were reviewed retrospectively. All patients underwent pre-treatment FDG PET and tumor removal. Patients were classified with the maximum SUV (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), age, sex, histologic subtype, tumor size, NAC, resection margin, and metastasis at diagnosis. Pathologic response was assessed using the French Federation of Cancer Centers system. Statistical analyses were analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards regression model, and Mann-Whitney test. RESULTS: Nine patients (45 %) showed pathologic response, and ten patients survived. Higher SUVmax, higher MTV, higher TLG, monophasic epithelial type, and metastasis at diagnosis were significantly related to poorer OS (p = 0.047, 0.016, 0.016, 0.045, and 0.018, respectively). By multivariate analysis, metastasis at diagnosis was significantly related to poorer OS (p = 0.012/HR = 5.9, 95 % CI 1.47 to 24.1). The SUVmax, MTV, and TLG of the non-responder group were significantly higher than those of the responder group (p = 0.020, 0.020, and 0.020, respectively). There was no significant difference in size between the two groups (p = 0.062). CONCLUSIONS: A higher SUVmax on the pre-treatment scan, monophasic epithelial type, and metastasis at diagnosis were significantly associated with a poorer OS, and pathologic responders showed a higher SUVmax before NAC. The PET parameters can be used to predict OS and pathologic response in patients with synovial sarcomas before NAC.

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.