Role of PRPS2 as a prognostic and therapeutic target in osteosarcoma.

AIMS: Osteosarcoma (OS) is the most common primary malignant tumour of the bone. However, further improvement in survival has not been achieved due to a lack of well-validated prognostic markers and more effective therapeutic agents. Recently, the c-Myc-phosphoribosyl pyrophosphate synthetase 2 (PRPS2) pathway has been shown to promote nucleic acid metabolism and cancer cell proliferation in malignant melanoma; phosphorylated mammalian target of rapamycin (p-mTOR) has been upregulated and an effective therapeutic target in OS. However, the p-mTOR-PRPS2 pathway has not been evaluated in OS. METHODS: In this study, the expression level of PRPS2, p-mTOR and marker of proliferation (MKI-67) was observed in a cohort of specimens (including 236 OS cases and 56 control samples) using immunohistochemistry, and the association between expression level and clinicopathological characteristics of patients with OS was analysed. RESULTS: PRPS2 protein level, which is related to tumour proliferation, was higher in OS cells (p=0.003) than in fibrous dysplasia, and the higher PRPS2 protein level was associated with a higher tumour recurrence (p=0.001). In addition, our statistical analysis confirmed that PRPS2 is a novel, independent prognostic indicator of OS. Finally, we found that the expression of p-mTOR was associated with the poor prognosis of patients with OS (p<0.05). CONCLUSIONS: PRPS2 is an independent prognostic marker and a potential therapeutic target for OS.

Parosteal Osteosarcoma: A Benign-Looking Tumour, Amenable to a Variety of Surgical Reconstruction.

Osteosarcoma arising from cortical surface is classified into parosteal, periosteal and high-grade surface osteosarcoma. Along the spectrum, parosteal osteosarcoma occupies the well-differentiated end. It is a relatively rare disease entity, comprised only 4% of all osteosarcomas and barely reported in the literature. The objective of this study is to describe cases of parosteal osteosarcoma as well as a variety of treatment options amenable to such entity. Six cases of parosteal osteosarcoma were identified based on histopathological reports in a tertiary referral hospital in Jakarta, Indonesia between January 2001 and December 2019. The mean age was 29.8 years old; four of them (66.7%) were male. Distal end of femur was the most commonly involved bone (five cases, 83.3%). The patients were treated with wide excision followed by several different reconstruction methods: replacement with endoprosthesis, extracorporeal irradiation, knee arthrodesis, or prophylactic fixation. One of our patients presented with dedifferentiated component, and therefore was treated by limb ablation. While two cases died of pulmonary metastasis, other patients reported fair to excellent functional outcome.

Is There an Association Between Prophylactic Femur Stabilization and Survival in Patients with Metastatic Bone Disease?

BACKGROUND: The femur is the most common site of metastasis in the appendicular skeleton, and metastatic bone disease negatively influences quality of life. Orthopaedic surgeons are often faced with deciding whether to prophylactically stabilize an impending fracture, and it is unclear if prophylactic fixation increases the likelihood of survival. QUESTIONS/PURPOSES: Is prophylactic femur stabilization in patients with metastatic disease associated with different overall survival than fixation of a complete pathologic fracture? METHODS: We performed a retrospective, comparative study using the national Veterans Administration database. All patient records from September 30, 2010 to October 1, 2015 were queried. Only nonarthroplasty procedures were included. The final study sample included 950 patients (94% males); 362 (38%) received prophylactic stabilization of a femoral lesion, and 588 patients (62%) underwent fixation of a pathologic femur fracture. Mean followup duration was 2 years (range, 0-7 years). We created prophylactic stabilization and pathologic fracture fixation groups for comparison using Common Procedural Terminology and ICD-9 codes. The primary endpoint of the analysis was overall survival. Univariate survival was estimated using the Kaplan-Meier method; between-group differences were compared using the log-rank test. Covariate data were used to create a multivariate Cox proportional hazards model for survival to adjust for confounders in the two groups, including Gagne comorbidity score and cancer type. RESULTS: After adjusting for comorbidities and cancer type, we found that patients treated with prophylactic stabilization had a lower risk of death than did patients treated for pathologic femur fracture (hazard ratio = 0.75, 95% CI, 0.62-0.89; p = 0.002). CONCLUSIONS: In the national Veterans Administration database, we found greater overall survival between patients undergoing prophylactic stabilization of metastatic femoral lesions and those with fixation of complete pathologic fractures. We could not determine the cause of this association, and it is possible, if not likely, that patients treated for fracture had more aggressive disease causing the fracture than did those undergoing prophylactic stabilization. Currently, most orthopaedic surgeons who treat pathological fractures stabilize the fracture prophylactically when reasonable to do so. We may be improving survival in addition to preventing a pathological fracture; further study is needed to determine whether the association is cause-and-effect and whether additional efforts to identify and treat at-risk lesions improves patient outcomes. LEVEL OF EVIDENCE: Level III, therapeutic study.

Pedicle frozen autograft-prosthesis composite reconstructions for malignant bone tumors of the proximal femur.

BACKGROUND: Limb salvage surgery is becoming increasingly popular after tumor resection in the lower extremity. Biological reconstruction and use of megaprosthesis are main methods for malignant bone tumors of the proximal femur, which remain controversial due to short- and long-term complication in the proximal femur. Tumor-bearing bone treated by liquid nitrogen is one of biological reconstruction. This study aimed to evaluate the mid- and long-term functional outcomes and complications in patients treated with frozen autograft-prosthesis composite (FAPC) reconstructions in the proximal femur. METHODS: This retrospective study included 19 patients (10 women, 9 men) with malignant tumors of the proximal femur who underwent tumor-wide resection and FAPC reconstruction (mean age, 46 years; range, 9-77 years). The mean follow-up period of 69 months (range, 9-179 months). Functional outcomes, oncological outcome and complications were evaluated by Musculoskeletal Tumor Society score, clinical and radiological examinations. RESULTS: The overall survival rate was 68.4%, and the mean Musculoskeletal Tumor Society functional score was 26.4 points (88%). FAPC survival rates were 100 and 50% at 5 and 10 years, respectively. Five of the 19 patients (26%) had complications: 2 required prosthesis removal and 2 developed a deep infection around acetabular. Wear of the acetabulum occurred in 2 cases, while disease recurrence was occurred in 1 case. There were no cases of greater trochanter avulsion, obvious absorption around frozen bone, prosthesis loosening or leg length discrepancy. CONCLUSIONS: Due to without femoral osteotomy, this technique features satisfactory functional outcome and provide biomechanical stability that is comparable to those of other methods of biological reconstruction or megaprosthesis.

The Metastatic Early Prognostic (MEP) score.

AIMS: The early mortality in patients with hip fractures from bony metastases is unknown. The objectives of this study were to quantify 30- and 90-day mortality in patients with proximal femoral metastases, and to create a mortality prediction tool based on biomarkers associated with early death. METHODS: This was a retrospective cohort study of consecutive patients referred to the orthopaedic department at a UK trauma centre with a proximal femoral metastasis (PFM) over a seven-year period (2010 to 2016). The study group were compared to a matched control group of non-metastatic hip fractures. Minimum follow-up was one year. RESULTS: There was a 90-day mortality of 46% in patients with metastatic hip fractures versus 12% in controls (89/195 and 24/192, respectively; p < 0.001). Mean time to surgery was longer in symptomatic metastases versus complete fractures (9.5 days (SD 19.8) and 3.4 days (SD 11.4), respectively; p < 0.05). Albumin, urea, and corrected calcium were all independent predictors of early mortality and were used to generate a simple tool for predicting 90-day mortality, titled the Metastatic Early Prognostic (MEP) score. An MEP score of 0 was associated with the lowest risk of death at 30 days (14%, 3/21), 90 days (19%, 4/21), and one year (62%, 13/21). MEP scores of 3/4 were associated with the highest risk of death at 30 days (56%, 5/9), 90 days (100%, 9/9), and one year (100%, 9/9). Neither age nor primary cancer diagnosis was an independent predictor of mortality at 30 and 90 days. CONCLUSION: This score could be used to predict early mortality and guide perioperative counselling. The delay to surgery identifies a potential window to intervene and correct these abnormalities with the aim of improving survival. Cite this article: Bone Joint J. 2020;102-B(1):72-81.

Preoperative surgical risk stratification in osteosarcoma based on the proximity to the major vessels.

AIMS: The aim of this study was to determine the risk of local recurrence and survival in patients with osteosarcoma based on the proximity of the tumour to the major vessels. PATIENTS AND METHODS: A total of 226 patients with high-grade non-metastatic osteosarcoma in the limbs were investigated. Median age at diagnosis was 15 years (4 to 67) with the ratio of male to female patients being 1.5:1. The most common site of the tumour was the femur (n = 103) followed by tibia (n = 66). The vascular proximity was categorized based on the preoperative MRI after neoadjuvant chemotherapy into four types: type 1 > 5 mm; type 2 ≤ 5 mm, > 0 mm; type 3 attached; type 4 surrounded. RESULTS: Limb salvage rate based on the proximity type was 92%, 88%, 51%, and 0% for types 1 to 4, respectively, and the overall survival at five years was 82%, 77%, 57%, and 67%, respectively (p < 0.001). Local recurrence rate in patients with limb-salvage surgery was 7%, 8%, and 22% for the types 1 to 3, respectively (p = 0.041), and local recurrence at the perivascular area was observed in 1% and 4% for type 2 and 3, respectively. The mean microscopic margin to the major vessels was 6.9 mm, 3.0 mm, and 1.4 mm for types 1 to 3, respectively. In type 3, local recurrence-free survival with limb salvage was significantly poorer compared with amputation (p = 0.025), while the latter offered no overall survival benefit. In this group of patients, factors such as good response to chemotherapy or limited vascular attachment to less than half circumference or longitudinal 10 mm reduced the risk of local recurrence. CONCLUSION: The proximity of osteosarcoma to major blood vessels is a poor prognostic factor for local control and survival. Amputation offers better local control for tumours attached to the blood vessels but does not improve survival. Limb salvage surgery offers similar local control if the tumour attachment to blood vessels is limited. Cite this article: Bone Joint J 2019;101-B:1024-1031.

Reconstrucción con prótesis modulares posterior a una resección oncológica. Evaluación de los fracasos y análisis de la supervivencia / Modular prosthesis reconstruction after tumour resection, evaluation of failures and survival

Objetivo: Analizar una serie de pacientes oncológicos tratados con prótesis modulares y evaluar: 1) Supervivencia del implante. 2) Causas de fracaso. 3) Tasa de reintervención. 4) Supervivencia del miembro. 5) Resultados funcionales y tiempo hasta la carga completa. Materiales y métodos: Se realizó una búsqueda retrospectiva en una base de datos oncológica entre marzo de 2001 y agosto de 2015 de pacientes con tumores óseos y pacientes con cirugía de revisión de trasplantes óseos reconstruidos con endoprótesis. Se incluyó a 106 pacientes con seguimiento mínimo de 2 años. Se dividió la población en 3 grupos: grupo 1, tumores óseos primarios; grupo 2, metástasis ósea; grupo 3, revisiones de trasplantes óseos masivos. Las causas de fracasos fueron clasificadas según Henderson et al. (2014) y la funcionalidad se evaluó según el la escala de la Musculoskeletal Tumor Society (MSTS). Se realizó análisis demográfico, estimación de la supervivencia y se compararon las diferencias entre grupos. Resultados: El seguimiento medio de los pacientes fue de 68 meses. La edad promedio fue de 43 años. La supervivencia global del implante fue del 86% a 2 años (IC 95%: 79-94) y del 73% a 5 años (IC 95%: 60-80). Diecinueve pacientes (18%) presentaron fracaso protésico, con revisión. La conservación del miembro en nuestra serie fue del 96% a 5 años(IC 95%: 91-99). Los resultados funcionales promedio según la escala de la MSTS fueron de 24 y el tiempo medio para carga completa de 2, 3 semanas. Conclusión: La cirugía de conservación de miembro representa el tratamiento de elección en pacientes con tumores óseos y la reconstrucción con endoprótesis resulta una alternativa válida, con índices de fracaso similares a otras reconstrucciones

Objective: To analyze a series of patients with bone tumours reconstructed with modular prostheses and to evaluate: 1) Survival of the implant. 2) Causes of failure. 3) Complication rates. 4) Limb salvage overall survival. 5) Functional results and full weight bearing. Materials and methods: A retrospective study from longitudinally maintained oncology databases was undertaken. All patients with bone tumours reconstructed with endoprosthesis were analysed. A toal of 106patients matched the inclusion criteria. They were divided into groups: group 1, primary bone tumours; group 2, bone metastasis; group 3, osteoarticular allograft reconstruction revisions. The type of failures were classified according to Henderson et al. (2014) and functional results assessed by the Musculoskeletal Tumor Society (MSTS). Demographic analysis, survival and the differences between groups were recorded. Result: The mean follow-up of the patients was 68 months. Mean age was 43 years. Overall implant survival was 86.4% at 2 years (95% CI: 79-94) and 73% at 5 years (95% CI: 60-80). Nineteen patients (18%) developed a prosthetic failure. The limb salvage overall survival was 96% at 5 years (95% CI: 91-99). The mean functional results according to the MSTS was 24 and mean time to full weight bearing was 2.3 weeks. Conclusions: Limb conservation surgery and endosprosthetic reconstruction is a valid option for patients with bone tumours with failure rates similar to other reconstruction methods

Modular prosthesis reconstruction after tumour resection, evaluation of failures and survival. / Reconstrucción con prótesis modulares posterior a una resección oncológica. Evaluación de los fracasos y análisis de la supervivencia.

OBJECTIVE: To analyze a series of patients with bone tumours reconstructed with modular prostheses and to evaluate: 1) Survival of the implant. 2) Causes of failure. 3) Complication rates. 4) Limb salvage overall survival. 5) Functional results and full weight bearing. MATERIALS AND METHODS: A retrospective study from longitudinally maintained oncology databases was undertaken. All patients with bone tumours reconstructed with endoprosthesis were analysed. A toal of 106patients matched the inclusion criteria. They were divided into groups: group 1, primary bone tumours; group 2, bone metastasis; group 3, osteoarticular allograft reconstruction revisions. The type of failures were classified according to Henderson et al. (2014) and functional results assessed by the Musculoskeletal Tumor Society (MSTS). Demographic analysis, survival and the differences between groups were recorded. RESULT: The mean follow-up of the patients was 68 months. Mean age was 43 years. Overall implant survival was 86.4% at 2 years (95% CI: 79-94) and 73% at 5 years (95% CI: 60-80). Nineteen patients (18%) developed a prosthetic failure. The limb salvage overall survival was 96% at 5 years (95% CI: 91-99). The mean functional results according to the MSTS was 24 and mean time to full weight bearing was 2.3 weeks. CONCLUSIONS: Limb conservation surgery and endosprosthetic reconstruction is a valid option for patients with bone tumours with failure rates similar to other reconstruction methods.

Should the Use of Biologic Agents in Patients With Renal and Lung Cancer Affect Our Surgical Management of Femoral Metastases?

BACKGROUND: Biologic agents may prolong survival of patients with certain kidney and lung adenocarcinomas that have metastasized to bone, and patient response to these agents should be considered when choosing between an endoprosthesis and internal fixation for surgical treatment of femoral metastases. QUESTIONS/PURPOSES: Among patients undergoing surgery for femoral metastases of lung or renal cell carcinoma, (1) Does survival differ between patients who receive only cytotoxic chemotherapy and those who either respond or do not respond to biologic therapy? (2) Does postsurgical incidence of local disease progression differ between groups stratified by systemic treatment and response? (3) Does implant survival differ among groups stratified by systemic treatment and response? METHODS: From our institutional longitudinally maintained orthopaedic database, patients were identified by a query initially identifying all patients who carried a diagnosis of renal cell carcinoma or lung carcinoma. Patients who underwent internal fixation or prosthetic reconstruction between 2000 and 2016 for pathologic fracture of the femur and who survived ≥ 1 year after surgery were studied. Patients who received either traditional cytotoxic chemotherapy or a biologic agent were included. Patients were classified as responders or nonresponders to biologic agents based on whether they had clinical and imaging evidence of a response recorded on two consecutive office visits over ≥ 6 months. Endpoints were overall survival from the time of diagnosis, survival after the femoral operation, evidence of disease progression in the femoral operative site, and symptomatic local disease progression for which revision surgery was necessary. Our analysis included 148 patients with renal (n = 26) and lung (n = 122) adenocarcinoma. Fifty-one patients received traditional chemotherapy only. Of 97 patients who received a biologic agent, 41 achieved a response (stabilization/regression of visceral metastases), whereas 56 developed disease progression. We analyzed overall patient survival with the Kaplan-Meier method and used the log-rank test to identify significant differences (p < 0.05) between groups. RESULTS: One-year survival after surgery among patients responsive to biologic therapy was 61% compared with 20% among patients nonresponsive to biologics (p < 0.001) and 10% among those who received chemotherapy only (p < 0.009). With the number of patients we had to study, we could not detect any difference in local progression of femoral disease associated with systemic treatment and response. Radiologic evidence of periimplant local disease progression developed in three (7%) of 41 patients who responded to biologic treatment, two (3%) of 56 patients nonresponsive to biologics, and one (2%) of 51 patients treated with traditional chemotherapy. With the numbers of patients we had, we could not detect a difference in patients who underwent revision. All three patients responsive to biologics who developed local recurrence underwent revision, whereas the two without a response to biologics did not. CONCLUSIONS: Biologic therapy improves the overall longevity of some patients with lung and renal metastases to the femur in whom a visceral disease response occurred. In our limited cohort, we could not demonstrate an implant survival difference between such patients and those with shorter survival who may have had more aggressive disease. However, an increased life expectancy beyond 1 year among patients responsive to biologics may increase risk of mechanical failure of fixation constructs. LEVEL OF EVIDENCE: Level III, therapeutic study.

Functional recovery after surgical stabilization and postoperative radiotherapy due to metastases of long bones.

PURPOSE: To reinvestigate the functional recovery after combined treatment with surgery and postoperative irradiation of complete or impending pathologic fractures of long bones. METHODS: We retrospectively evaluated the results of external beam radiation therapy (EBRT) carried out after 68 orthopedic stabilization procedures (femur, n = 55, 80.8%; humerus, n = 13, 19.2%) for actual or impending pathological fracture of long bone in 61 patients with skeletal metastases. The mean normalized total dose was 34.7 ± 7.8 Gy. Endpoints were patient's functional status (FS; 1 = normal pain free status; 2 = normal use with pain; 3 = significantly limited used; 4 = nonfunctional status), a need for a secondary procedure to the same site and overall survival following surgery. RESULTS: Overall, 75% of patients achieved normal functional status (FS 1-2) within 12 weeks after surgery. Functional recovery in surviving patients reached 93%. Median survival was 17 months (95% confidence interval 13.7-20.2). Secondary surgical intervention at the same location was necessary in 3 patients (4.4%). On multivariate analysis, only general status (p = 0.011) and growing potential of primary tumor (p = 0.049) were associated with achieving normal functional status within 12 weeks after surgery and radiotherapy. The applied radiation schemes demonstrated a comparable impact on functional recovery. CONCLUSIONS: Our results confirm the effectiveness of stabilizing surgery and fractionated postoperative radiotherapy in terms of functional recovery, supporting prior results assessing postsurgical radiotherapy versus follow-up. The patient's general status is a strong prognostic factor for functional recovery. Rapidly growing tumors may hinder achievement of a normal functional status.

Is Total Femur Replacement a Reliable Treatment Option for Patients With Metastatic Carcinoma of the Femur?

BACKGROUND: The majority of metastatic bone lesions to the femoral bone can be treated without surgery or with minimally invasive intramedullary nailing. In rare patients with extensive metastatic disease to the femur, total femur replacement may be the only surgical alternative to amputation; however, little is known about this approach. QUESTIONS/PURPOSES: In a highly selected small group of patients with metastatic carcinoma of the femur, we asked: (1) What was the patient survivorship after this treatment? (2) What was the implant survivorship free from all-cause revision and amputation, and what complications were associated with this treatment? (3) What functional outcomes were achieved by patients after total femur replacement for this indication? METHODS: Eleven patients (three men, eight women) with a mean age of 64 years (range, 41-78 years) received total femur replacements between 1986 and 2016; none were lost to followup. The most common primary disease was breast cancer. In general, during this period, our indications for this procedure were extensive metastatic disease precluding internal fixation or isolated proximal or distal femur replacement, and an anticipated lifespan exceeding 6 months. Our contraindication for this procedure during this time was expected lifespan less than 6 months. Patient survival was assessed by Kaplan-Meier analysis; implant survival free from revision surgery and amputation were assessed by competing risk analysis. Function was determined preoperatively and 6 to 12 weeks postoperatively with the Musculoskeletal Tumor Society (MSTS) score normalized to a 100-point scale, with higher scores representing better function from a longitudinally maintained institutional database. RESULTS: Eleven patients died at a median of 5 months (range, 1-31 months) after surgery. One-year revision-free and limb survival were 82% (95% CI, 51%-98%) and 91% (95% CI, 61%-99%), respectively. Reasons for reoperation were hip dislocation, infection and local recurrence in one patient each. The latter two complications resulted in amputation in two patients. The median MSTS score was 32 (range, 13-57). CONCLUSIONS: Despite attempts to select patients who might have anticipated greater life expectancy, eight of 11 patients died by 6 months after surgery, and an additional two patients had undergone an amputation at 8 and at 17 months postoperatively. Most patients undergoing total femur replacement in this series did not recover from the procedure by the time they died, despite our best attempts to perform the procedure in patients whom we thought would live at least 6 months. Based on this, we believe that most patients with extensive metastatic disease to the femur should be offered palliative care, rather than major reconstruction. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Durability of Hemiarthroplasty for Pathologic Proximal Femur Fractures.

BACKGROUND: The hip is a common location for metastatic tumors. Due to the high loads placed through the proximal femur, surgery is often indicated to provide pain relief and restore function. Historically, these lesions are reconstructed with a hemiarthroplasty; however, there are few reports on the outcome of these reconstructions. The purpose of this study is to evaluate the outcome of hemiarthroplasty for the treatment of proximal femur metastatic disease, with a specific focus on the rates of conversion to total hip arthroplasty (THA). METHODS: One hundred ninety-nine patients (102 women, 97 men) were treated using a hemiarthroplasty to reconstruct the proximal femur for metastatic disease between 1992 and 2014. Mean age and body mass index were 62 years and 27.4 kg/m2, respectively. The most common site of primary disease was the breast (n = 63). The most common location for the metastatic disease was the femoral neck (n = 148). Mean follow-up for surviving patients was 4 years. RESULTS: Over the course of the study, 2 (1%) patients underwent conversion to a THA due to groin pain and degenerative changes. In addition, complications occurred in 12% of patients, most commonly a deep venous thrombosis (n = 5). Following the procedure, mean Harris Hip Score and Musculoskeletal Tumor Society 1993 scores were 73 and 63%, respectively. CONCLUSION: Reconstruction of the proximal femur with a hemiarthroplasty endoprosthesis provides a majority of patients with a durable means of reconstruction, with a low rate of conversion to THA.

Outcomes of Intercalary Prosthetic Reconstruction for Pathological Diaphyseal Femoral Fractures Secondary to Metastatic Tumors.

OBJECTIVE: To evaluate the clinical outcomes and complications of segmental prosthetic reconstruction for pathological diaphyseal femoral fractures secondary to metastatic tumors. METHODS: Between 2011 and 2015, we retrospectively evaluated 16 patients (6 men and 10 women; 64.5 ± 11.4 years old at diagnosis) who underwent prosthetic reconstruction after segmental resection of diaphyseal femoral fractures due to metastatic lesions. Visual analog scale (VAS), functional outcomes, implant-related complications, and Mean postoperative Musculoskeletal Tumor Society (MSTS) score for each patient were collected. RESULTS: The mean length of bone defect was 10.2 ± 2.6 cm (range, 8-16 cm); follow-up was 9 ± 6.8 months (range, 2-25 months) for all patients, and 24 months (23 and 25 months) for the 2 patients still alive. At final follow-up, 14 patients were dead, indicating a mean survival of 6.9 ± 3.6 months (range, 2-14 months). Mean preoperative VAS score was 8.5 ± 1.0, which decreased to 2.5 ± 1.3 at day 2 postoperatively, indicating significant pain relief (P < 0.05). The MSTS score for lower extremities was 84.6% (range, 73%-90%). The range of motion and function of adjacent joints was within the normal limits in all cases. Three patients (33%) developed complications, including aseptic loosening because of disease progression (1), infection (1), and peri-prosthesis fracture (1). CONCLUSION: These findings demonstrated that this approach greatly relieves pain, and yields satisfactory functional outcomes with fewer complications in patients with pathological femoral fractures secondary to metastatic tumors; however, survival was not significantly improved.

Proximal femoral osteosarcoma: Diagnostic challenges translate into delayed and inappropriate management.

BACKGROUND: The proximal femuris is an uncommon site of osteosarcoma. The unusual manifestations at this site may lead to diagnostic and therapeutic mistakes. We therefore performed a retrospective study to estimate the proportions of patients with imaging study findings and/or clinical manifestations typical for osteosarcoma and/or inappropriate treatment decisions. HYPOTHESIS: Proximal femoral osteosarcoma often produces atypical clinical and radiological presentations. MATERIAL AND METHODS: Consecutive patients who underwent surgery at our center to treat proximal femoral osteosarcoma were included. For each patient, we collected the epidemiological characteristics, clinical symptoms, imaging study findings, treatment, and tumor outcome. Proportions were computed with their confidence intervals. RESULTS: Twelve patients had surgery for proximal femoral osteosarcoma between 1986 and 2015. Imaging findings were typical in 1 (8%) patient; they consisted of ill-defined osteolysis in 11/12 (92%) patients, a periosteal reaction in 1/12 (8%) patient, soft tissue involvement in 7/12 (58%) patients, and immature osteoid matrix in 11/12 (92%) patients. No patient had the typical combination of pain with a soft tissue swelling. Management was inappropriate in 2/12 (17%) patients, who did not undergo all the recommended imaging studies before surgery and were treated in another center before the correct diagnosis was established. At last follow-up, 4 patients had died (after a mean of 7 years) and 8 were alive (after a mean of 4 years). CONCLUSION: Proximal femoral osteosarcoma is uncommon and rarely produces the typical clinical and imaging study findings. The atypical presentation often results in diagnostic errors and inappropriate treatments. Ill-defined osteolysis on standard radiographs should prompt computed tomography or magnetic resonance imaging of the proximal femur. Treatment in a specialized center is imperative. LEVEL OF EVIDENCE: IV, retrospective study.

The push-through total femoral prosthesis offers a functional alternative to total femoral replacement: a case series.

PURPOSE: Oncologic resections or complications of segmental femoral prostheses can result in severe bone loss of the femur for which a total femoral prosthesis (TFP) is required. This study assesses whether the loss of stability and function caused by the loss of muscle attachments can be improved by using a push-through total femoral endoprosthesis (PTTF), because it saves parts of the femur and its muscle attachments. METHODS: In this retrospective case series, ten patients aged 25-77 (mean 54) who received a PTTF between 2005 and 2014 were included for baseline, complications and survival analysis with a mean follow-up of 5.3 (1.1-9.6) years. Functional outcome was assessed in six patients using the Musculoskeletal Tumor Society (MSTS) score, WHO performance scale, Toronto Extremity Salvage Score (TESS), SF36, EQ-5D, NRS pain score, fatigue score and satisfaction score. RESULTS: The mean MSTS score was 64% (23-93%). Five patients had a WHO performance scale of 1, one patient of 3. Mean TESS was 69% (13-90%). SF36 was most notably limited by physical functioning (mean 48), vitality (68) and general health (67). NRS score was 1.9, 1.8 and 8.3 for pain, fatigue and satisfaction, respectively. There were four failures: two infections (one resulting in amputation and one in a minor revision) and two mechanical failures (which required one revision to a TFP and one minor revision). Patient survival was 100%, limb survival 90%, and prosthesis survival 80%. CONCLUSION: The push-through total femoral endoprosthesis allows preservation of muscle attachments and offers a good alternative to total femoral prostheses.

Prognostic significance of chemotherapy-induced necrosis in osteosarcoma patients receiving pasteurized autografts.

BACKGROUND: Among various reconstruction methods after wide excision for osteosarcoma, pasteurized autograft is often preferred. While the whole area of the tumor can be assessed for chemotherapy-induced necrosis, one of the important prognostic factors, in other reconstructive techniques, only a portion removed from a wide-resection specimen is available when using pasteurized autograft method. The assessment, therefore, may be unreliable. We analyzed the prognostic significance of the chemotherapy-induced necrosis in osteosarcoma patients who underwent reconstruction with pasteurized autografts. PATIENTS AND METHODS: We reviewed the records of osteosarcoma patients who underwent treatment in our institution from 1998 to 2013. Cases of reconstruction with pasteurized autografts were defined as the patient group, and the same number of patients who underwent other reconstruction methods served as controls. Chemotherapy-induced necrosis was evaluated for removed extra-osseous and curetted intramedullary tumor tissues. RESULTS: A total of 22 patients were identified; the median age was 15.5 years, and there were 12 males. The most common tumor location was the distal femur. The most common histological subtype was osteoblastic. Median size was 8.1 cm. Disease status was stage IIB in 13 patients and IIA in 9. Median follow-up was 76 months. No differences between the patient and control groups were observed in potential prognostic factors, overall survival, metastasis-free survival, or recurrence-free survival. Univariate analyses demonstrated that histological response was a significant prognostic factor for metastasis-free survival and also significant for recurrence-free survival. CONCLUSION: Chemotherapy-induced necrosis grading, using only available tumor tissues, could be a prognostic factor for osteosarcoma patients receiving pasteurized autografts for reconstructive surgery.

What Are the Functional Results and Complications With Long Stem Hemiarthroplasty in Patients With Metastases to the Proximal Femur?

BACKGROUND: Traditional treatments for pathological fractures of the proximal femur resulting from metastatic bone disease include fixation with intramedullary nailing supplemented with polymethylmethacrylate, osteosynthesis with a plate-screw construct and polymethylmethacrylate, or endoprosthetic reconstruction. Despite the frequent practice of these treatments, treatment outcomes have not been rigorously compared. In addition, very few studies examine specific approaches to endoprosthetic reconstruction such as long stem hemiarthroplasty. QUESTIONS/PURPOSES: This study examines survival, functional outcomes, and complications associated with long stem hemiarthroplasty in a small group of patients treated for impending and actual pathologic fractures of the proximal femur resulting from metastatic bone disease. METHODS: Between 2012 and 2015, 21 patients were treated with long stem cemented hemiarthroplasty in 22 limbs. During that time, indications for this approach included lesions from metastases, myeloma, or lymphoma involving the proximal femur that resulted in an impending or actual pathological fracture. An impending fracture was classified as a painful lesion with at least 50% cortical erosion. During the study period, six patients with proximal femoral metastases not deemed to meet these indications were treated with other surgical approaches such as intramedullary nailing supplemented with polymethylmethacrylate and osteosynthesis with a plate-screw construct and polymethylmethacrylate. Mortality was tracked through medical records and phone calls to the patients and their families. Followup for the entire group of patients (n = 22) ranged from 1 to 27 months with a mean duration of 11 months. For patients with at least 1 year of followup (n = 11), the mean duration was 18 months (range, 12-27 months) and for patients with less than 1 year of followup (n = 11), the mean duration was 3 months (range, 1-11 months). Functional outcomes were evaluated according to the Musculoskeletal Tumor Society (MSTS) scoring system for lower extremities, the Eastern Cooperative Oncology Group (ECOG) Scale of Performance Status, and the Karnofsky Performance Scale (KPS) Index. Scores and complications were determined by direct patient examination, retrospective chart review, review of a longitudinally maintained institutional database, and followup phone calls. RESULTS: Ten patients died of disease within the followup period. Before surgery, the median total MSTS score for the entire group of patients (n = 22) was 4.5 (range, 0-23), the median ECOG score was 3.5 (range, 1-4), and the median KPS score was 40 (range, 30-70). Postoperatively, the median total MSTS score (measured at most recent followup) for the entire group of patients was 21 (range, 5-30), the median ECOG score was 2 (range, 0-3, 68% ≤ 2), and the median KPS score was 60 (range, 40-100). For the 11 patients with at least 1 year of followup, the median total MSTS score (measured at most recent followup) was 27 (range, 21-30), the median ECOG score was 1 (range, 0-2, 100% ≤ 2), and the median KPS score was 80 (range, 60-100). For the remaining 11 patients with less than 1 year of followup, the median total MSTS score (measured at most recent followup) was 11 (range, 5-25), the median ECOG score was 3 (range, 1-3, 36% ≤ 2), and the median KPS score was 40 (range, 40-80). Complications included one periprosthetic fracture resulting from a fall, three cases of radiation-induced edema, and two cases of sciatica that developed unrelated to the procedure. CONCLUSIONS: Long stem cemented hemiarthroplasty results in fair levels of function in a complex population of patients whose prognosis is sometimes measured only in months and who otherwise might be disabled by their metastatic lesions. Comparative trials applying consistent indications and inclusion criteria should be performed between this approach and fixation with intramedullary nailing supplemented with polymethylmethacrylate as well as osteosynthesis with a plate-screw construct and polymethylmethacrylate. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Effect of Unplanned Therapy on the Prognosis of Patients with Extremity Osteosarcoma.

Unplanned therapy for extremity osteosarcoma can result in erroneous surgical procedures and lack of neoadjuvant chemotherapy before the first operation. Our aim was to compare the prognosis between patients with extremity osteosarcoma who received unplanned therapy and those who received standard treatment. This was a retrospective review of patients with extremity osteosarcoma who received appropriate surgical treatment and neoadjuvant chemotherapy (n = 79) and those who received unplanned therapy (n = 24) between June 2000 and October 2014. Survival rate, local recurrence rate and metastasis rate were compared between the two groups. We found that patients who had unplanned therapy had a higher local recurrence rate (41.7% vs. 21.5%; P = 0.049) and a shorter mean time for recurrence (8.90 vs. 14.59 months; P = 0.018). There was no significant difference between groups in the 5-year survival rate (56.3% vs.67.8%; P = 0.356), metastasis rate (45.8% vs. 30.4%; P = 0.125) and mean time to metastasis (23.18 vs.18.24 months; P = 0.396). Our findings suggest that unplanned therapy for extremity osteosarcoma can result in failure of local control. The use of supplementary interventions after unplanned therapy, such as neoadjuvant chemotherapy and limb salvage surgery, may explain the similar survival and metastasis rates between patients receiving unplanned therapy and those receiving standard treatment.

Functional and oncologic outcome of cemented endoprosthesis for malignant proximal femoral tumors.

BACKGROUND: Cemented endoprosthetic replacement is an option for reconstruction of the proximal femur to achieve limb salvage. Existing outcome studies combine benign and malignant conditions, or group endoprostheses from multiple areas into one cohort. We sought to examine a series of endoprosthetic replacements of the proximal femur for a malignant process. METHODS: We reviewed 204 patients who underwent an endoprosthesis for a malignant process of the proximal femur with at least 2-year follow-up. Mean age was 59 years, with 55% being male. The most common pathology was metastatic disease (n = 120, 59%). Mean follow-up was 7 years (2-22 years). Mean time to death was 2 years (range 2 weeks-18 years). A bipolar component was used in 93% of patients. RESULTS: 5-year survival was 8% in patients with metastatic disease and 54% for patients with primary disease. Local recurrence and metastatic disease developed in 5 and 19 patients with a primary sarcoma. Following the procedure the mean Harris Hip and Musculoskeletal Tumor Society Scores were 75 and 18. CONCLUSION: Patients typically succumb to their disease prior to implant failure; however, endoprosthetic replacement provides patients with an acceptable means of functional recovery with an acceptable complication profile. J. Surg. Oncol. 2016;114:501-506. © 2016 Wiley Periodicals, Inc.

Serum CEACAM1 Level Is Associated with Diagnosis and Prognosis in Patients with Osteosarcoma.

Carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM1) is a trans-membrane multifunctional cell adhesion molecule associated with tumor cell proliferation, apoptosis, angiogenesis, invasion, and migration during tumor development. In the present study, we evaluated serum CEACAM1 level in osteosarcoma patients to explore its diagnostic and prognostic value for this particular malignancy. Sera from 113 patients with primary osteosarcoma, 98 patients with benign bone tumors and 126 healthy controls were obtained. Serum CEACAM1 level was measured with ELISA and correlation with clinicopathological characteristics was further analyzed. Receiver operating curves (ROC), Kaplan-Meier curves, and log-rank analyses as well as Cox proportional hazard models were used to evaluate diagnostic and prognostic significance. The results revealed that serum CEACAM1 level was significantly higher in osteosarcoma patients compared to benign bone tumors and healthy controls (455.2 ± 179.9 vs 287.4 ± 103.2, 260.8 ± 109.7 pg/ml, respectively). Osteosarcoma patients with larger tumors, later-tumor stages, low tumor grades, and distant metastases had much higher CEACAM1 compared to those with smaller tumors, earlier tumor stages, high tumor grades and non-distant metastases (P < 0.05 for all). Multivariate logistic regression analysis confirmed that high serum CEACAM1 level was an independent risk factor for distant metastases (OR = 3.02, 95%CI 1.65-4.17). To distinguish osteosarcoma patients from those with benign bone tumor and healthy controls, ROC/AUC analysis indicated an AUC of 0.81 (sensitivity 0.61; specificity 0.89) and an AUC of 0.77 (sensitivity 0.57; specificity 0.92), respectively. Osteosarcoma patients with higher CEACAM1 had relatively lower survival compared to those with low CEACAM1 (P < 0.01), and multivariate analyses for overall survival revealed that high serum CEACAM1 level was an independent prognostic factor for osteosarcoma (HR = 1.56, 95%CI 1.23-3.28). The present study suggested that elevated serum CEACAM1 level might be a novel diagnostic and prognostic biomarker for osteosarcoma patients.