Survival Prediction in Patients Treated Surgically for Metastases of the Appendicular Skeleton-An External Validation of 2013-SPRING Model.

INTRODUCTION: The aim of this study was to externally validate the 2013-SPRING model, a survival prediction tool for patients treated surgically for bone metastases in a retrospective patient cohort from a single institution. Moreover, subgroup analyses on patients treated with (A) endoprostheses or (B) osteosynthesis, as well as (C) upper limb and (D) lower limb metastases, were performed. METHODS: Altogether, 303 cancer patients (mean age: 67.6 ± 11.1 years; 140 males (46.2%)) with bone metastases to the extremities, treated surgically between March 2000 and June 2018 at a single tertiary sarcoma centre, were retrospectively included. Median follow-up amounted to 6.3 (interquartile range (IQR): 2.3-21.8) months, with all patients followed-up for at least one year or until death. The 2013-SPRING model was applied to assess the prognostication accuracy at 3, 6 and 12 months. Models were validated with area under the curve receiver operator characteristic (AUC ROC; the higher the better), as well as Brier score. RESULTS: Of the 303 patients, 141 had been treated with osteosynthesis (46.5%), and the remaining 162 patients with endoprosthesis (53.5%). Sixty-five (21.5%) metastases were located in the upper limbs, and two hundred and thirty-eight (78.5%) in the lower limbs. Using the 2013-SPRING model for the entire cohort, the accuracy of risk of death prediction at 3, 6 and 12 months, determined by the AUC ROC, was 0.782 (95% CI: 0.729-0.843), 0.810 (95% CI: 0.763-0.858) and 0.802 (95% CI: 0.751-0.854), respectively. Corresponding Brier scores were 0.170, 0.178 and 0.169 at 3, 6 and 12 months. In the subgroup analyses, predictive accuracy of the 2013-SPRING model was likewise encouraging, albeit being slightly higher in the osteosynthesis subgroup as compared with the endoprosthesis subgroup, and also higher in the upper limb in comparison to the lower limb metastasis subgroup. CONCLUSIONS: The current validation study of the 2013-SPRING model shows that this model is clinically relevant to use in an external cohort, also after stratification for surgical procedure and metastasis location.

Observational retrospective study on socio-economic and quality of life outcomes in 41 patients with adolescent idiopathic scoliosis 5 years after bracing combined with physiotherapeutic scoliosis-specific exercises (PSSE).

PURPOSE: We analysed socio-economic- and health-related quality of life (primary outcome) and radiological outcome (secondary outcome) 5 years after full time rigid bracing (FTRB) plus physiotherapeutic scoliosis-specific exercises (PSSE) in adolescent idiopathic scoliosis. METHODS: We included 41 patients (38 female and 3 male) treated with FTRB (Chênau brace) and PSSE (Schroth) between 2001 and 2010. The study protocol included a clinical and radiological examination, the completion of the SRS-24 questionnaire and acquisition of data on socio-economic factors (educational and employment status) and physical activity. Descriptive statistics were used to analyse the data; differences between patients with mild (< 30°) and severe curves (30°-50°) regarding hrQoL outcomes were analysed using the Mann-Whitney U Test. RESULTS: Primary outcomes showed full employment (higher education, 39%, and full-time work, 61%) and the majority of the patients (79.9%) performing moderate sports two to four times per week. The SRS-24 questionnaire produced a total mean score (MS) of 4.0 (79.9%). Patients with mild curves had a significantly better total score (MS 4.1 vs. MS 3.8, p = 0.020) and were more satisfied with the treatment (MS 4.3 vs MS 3.9, p = 0.020). As to the secondary outcomes, from start of bracing to follow-up (a mean of 6.7 years after brace weaning), the average Cobb angle changed from 28.6° to 25.6° (range 4°-48°); in 51.2% the curve angles could be maintained after weaning. CONCLUSIONS: Compared with the literature, our results showed similar curve development and hrQoL (pain, self-image and function) and better results regarding satisfaction with treatment. In comparison with the average population, there were no disadvantages as to occupation, education and sports. These slides can be retrieved under Electronic Supplementary Material.

When Do Orthopaedic Oncologists Consider the Implantation of Expandable Prostheses in Bone Sarcoma Patients?

INTRODUCTION: Indications discussed for the implantation of expandable prostheses in bone sarcoma patients are unclear. This survey aimed to analyse common practice with this implant type in orthopaedic oncology. METHODS: A web-based survey was sent to 98 orthopaedic oncology surgeons. Factors reported in literature to influence the decision on the implantation of a growing prosthesis were covered in individual questions and three case scenarios. RESULTS: The completion rate of the survey was 45% (n = 44). Twenty-seven of 44 surgeons (61%) had implanted between 1 and 15 expandable prostheses within three years. The minimum median patient age was 6.5 years, and 3-5 cm of predicted growth deficit was the minimum before implanting a growing prosthesis. One-third of surgeons do not use growth calculation methods. Two out of three surgeons would rather not implant a growing prosthesis in children with metastatic disease. CONCLUSIONS: Our survey confirmed the literature with 3-4 cm as the minimum estimated growth deficit. The minimum age for the implantation of a growing prosthesis is approx. 6.6 years, and therefore the patients are younger than those reported in previous publications. One-quarter of orthopaedic surgeons do not use growing prostheses at all. It remains unclear whether growing prostheses are indicated in patients with metastatic disease.

Video-game-assisted physiotherapeutic scoliosis-specific exercises for idiopathic scoliosis: case series and introduction of a new tool to increase motivation and precision of exercise performance.

BACKGROUND: It is important to monitor how patients with juvenile and adolescent idiopathic scoliosis comply with their physiotherapeutic scoliosis-specific exercises (PSSE). Physiogame, a newly developed video game using the Game-Trak 3D interactive game controller, combines correct PSSE performance with gaming. It tracks the position of the working limb in 3D space during the exercises as participants aim to hit certain targets and avoid others, and gives direct feedback by stopping the game if the working limb leaves the target 3D space, which is chosen to secure the corrective position according to the Schroth method. Physiogame records the quality and frequency of the exercises performed. We aimed to investigate the influence of this tool on motivation to perform regularly and, correctly, and with self-assessment of performance quality. METHODS: This case series included 8 consecutive patients with idiopathic scoliosis (thoracolumbar 7, lumbar 1), ages 7-13 years, all female and treated according to SOSORT guidelines; the COBB angle of primary curve at the start of brace therapy was 22-34°. In addition to Full Time Rigid Bracing (FTRB, Cheneau) and PSSE (Schroth), the participants were to perform two standardized Schroth exercises (muscle cylinder in standing position, mainly addressing the thoracic curve, and in side-lying position, mainly addressing the lumbar curve) with video game assistance every day for 6 months. The development (first to last month) of the following parameters was analyzed with descriptive methods: the actual training time to assess motivation, the ratio of the actual playing time versus total playing time to assess exercise improvement, and self-assessment of quality of performance. RESULTS: The average number of sessions with Physiogame was 217 per study participant (range 24 to 572, the study protocol targeted at least 180); actual training time decreased from 79 to 52 min (first to last month). Actual playing time increased from 73% of the total playing time to 83% (first to last month), and positive hits per second from 0.33 to 0.56. Self-assessment increased from "good" to "very good". The curve angles (°Cobb) were maintained over the study period (upper thoracic mean -1.3°, median -1°; lower thoracic mean 3°, median 2°; lumbar mean 0.5, median 0). CONCLUSIONS: The improvement we saw in exercise performance, is thought to result primarily from the direct given feedback during the game, as the exercises themselves were already familiar to the patients. The synchronous recording of actual training time allows evaluation of Schroth therapy for idiopathic scoliosis, since both prescribed training time and actual training time are captured. No comparable tool was found in literature.

Is superior tibiofibular joint resection necessary in extraarticular knee resection for sarcomas? A systematic review.

BACKGROUND: Sarcomas infiltrating the knee joint require extraarticular resection to achieve wide margins. Opinions differ as to whether the superior tibiofibular joint (STFJ) is part of the knee joint and should be removed in the course of extraarticular resection. Thus, we investigated the frequency of communication between the tibiofemoral joint (TFJ) and the STFJ, and the reported local recurrence rates (LRR) following extraarticular knee resection. METHODS: A systematic literature review on STFJ and TFJ communication and local recurrence rates following extraarticular knee resections was undertaken. RESULTS: Cadaver studies detected communication between the TFJ and STFJ in 10-64% of the cases. Direct arthrography with physical loading verified a 100% communication rate. Regarding the extent of extraarticular knee resection, two institutions where the STFJ was resected had a LRR of 4-8%, while studies from another three where the STFJ was not routinely resected reported a LRR of 0-21%. CONCLUSIONS: Since the literature reports about a 100% communication rate between the TFJ and the STFJ, resection of the STFJ in patients with sarcomas involving the knee joint would seem to be indicated, although it is not clear whether resection of the STFJ reduces local recurrence rates.

Predictive Value of Six Prognostic Scoring Systems for Spinal Bone Metastases: An Analysis Based on 1379 Patients.

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: The aim of this study was to assess and compare the predictive accuracy of six models designed to estimate survival of patients suffering from spinal bone metastases Just (SBMs). SUMMARY OF BACKGROUND DATA: On the basis of the estimated survival of patients with SBM, extent of treatment can be adjusted. To aid clinicians in the difficult task of assessing probability of survival, prognostic scoring systems have been developed by Tomita, Tokuhashi, Van der Linden, Bauer, Rades, and Bollen. METHODS: All patients who were treated for SBM between 2000 and 2010 were included in this international, multicenter, retrospective study (n = 1379). Medical records were reviewed for all items needed to use the scoring systems. Survival time was calculated as the difference between start of treatment for SBM and date of death. Survival curves were estimated using the Kaplan-Meier method and accuracy was assessed with the c-statistic. Survival rates of the worst prognostic groups were evaluated at 4 months. RESULTS: Median follow-up was 6.7 years [95% confidence interval (95% CI) 5.6-7.7] with a minimum of 2.3 years and a maximum of 12.3 years. The overall median survival was 5.1 months (95% CI 4.6-5.6). The most common primary tumors were breast (n = 388, 28%), lung (n = 318, 23%), and prostate cancer (n = 259, 19%). The Tokuhashi, Bauer, Tomita, and Van der Linden models performed similar with a c-statistic of 0.64 to 0.66 and a 4-month accuracy of 62% to 65%. The Rades model (c-statistic 0.44) and Bollen model (c-statistic 0.70) had a 4-month accuracy of 69% and 75%, respectively. CONCLUSION: The Bollen model performs better than the other models. However, improvements are still warranted to increase the accuracy. LEVEL OF EVIDENCE: 3.

Which one is a valuable surrogate for predicting survival between Tomita and Tokuhashi scores in patients with spinal metastases? A meta-analysis for diagnostic test accuracy and individual participant data analysis.

This study is to estimate the diagnostic accuracy of Tokuhashi and Tomita scores that assures 6-month predicting survival regarded as a standard of surgical treatment. We searched PubMed, EMBASE, European PubMed central, and the Cochrane library for papers about the sensitivities and specificities of the Tokuhashi and/or Tomita scores to estimate predicting survival. Studies with cut-off values of ≥9 for Tokuhashi and ≤7 for Tomita scores based on prior studies were enrolled. Sensitivity, specificity, diagnostic odds ratio (DOR), area under the curve (AUC), and the best cut-off value were calculated via meta-analysis and individual participant data analysis. Finally, 22 studies were enrolled in the meta-analysis, and 1095 patients from 8 studies were included in the individual data analysis. In the meta-analysis, the pooled sensitivity/specificity/DOR for 6-month survival were 57.7 %/76.6 %/4.70 for the Tokuhashi score and 81.8 %/47.8 %/4.93 for Tomita score. The AUC of summary receiver operating characteristic plots was 0.748 for the Tokuhashi score and 0.714 for the Tomita score. Although Tokuhashi score was more accurate than Tomita score slightly, both showed low accuracy to predict 6 months residual survival. Moreover, the best cut-off values of Tokuhashi and Tomita scores were 8 and 6, not 9 and 7, for predicting 6-month survival, respectively. Estimation of 6-month predicting survival to decide surgery in patients with spinal metastasis is quite limited by using Tokuhashi and Tomita scores alone. Tokuhashi and Tomita scores could be incorporated as part of a multidisciplinary approach or perhaps interpreted in the context of a multidisciplinary approach.

Examination of survivin expression in 50 chordoma specimens--A histological and in vitro study.

Chordomas mainly arise along the axial skeleton and are characterized by their slow but destructive growth. Prognosis and quality of life are poor because treatment options are mainly limited to surgery and radiotherapy. Survivin, a member of the apoptosis inhibitor protein family, functions as a key regulator of mitosis and programmed cell death, and is overexpressed in many tumor types. The aim of this study was to determine the role of survivin in chordomas. Survivin expression was investigated in 50 chordoma samples and three chordoma cell lines using immunohistochemistry. The intensity of immunostaining was evaluated in regard to the development of recurrences. The immunohistochemical results were correlated with clinical parameters like gender, age, tumor size, and location and were performed in primary chordomas as well as in recurrent lesions. Furthermore, survivin knockdown experiments on chordoma cell lines were performed. YM155 decreased the growth behavior of chordoma cells dose- and time dependently. Transient knockdown of survivin led to a G2/M arrest, decreased proliferation, consistently induced an increase of polyploidy and morphological changes, and induced apoptosis. The resultant data from this study suggest that survivin plays a cell cycle-progressive role in chordomas. Hence, regulation of survivin by YM155 is a promising new target for the development of new therapeutic drugs.

Evaluation of prognostic scoring systems for spinal metastases in 196 patients treated during 2005-2010.

PURPOSE: Estimating the survival time of patients with spinal metastases based on pre-treatment parameters is important for the best choice of therapy. Following two previous studies, this sequel analyzes possible changes in the impact of various parameters and scoring systems and includes a comparison to the previous dataset for the purpose to find the most predictive parameters and scores for this patient group. METHODS: Included were 196 patients retrospectively with confirmed spinal metastases treated between 2005 and 2010 (35% surgery, 65% conservative). Possible prognostic factors [primary tumor, Karnofsky Performance Scale (KPS), visceral metastases, number of bone metastases, pathological fracture and neurologic status] and six scoring systems (Tokuhashi original/revised, Tomita, van der Linden, Bauer original and modified) were analyzed using Kaplan-Meier curves and Cox-regression models. RESULTS: Median overall survival was 7 months with 9% of all patients alive at the time of analysis. Stepwise multivariate analysis showed significant influence on survival for visceral metastases (p<0.0001), primary tumor (p<0.0001), KPS (p<0.0001) and number of spinal metastases (p=0.0271). All scoring systems significantly predicted longer survival at a better score (absolute scores, p<0.001) in this dataset. Significant differentiation between the prognostic groups was seen only for the Tokuhashi original, the Bauer original and modified scores (p<0.001). In comparison to the previous dataset with varying age, gender and primary tumor distribution, the Bauer original and modified scores were the least influenced by the different patient collectives. CONCLUSIONS: The Bauer modified score has shown consistent impact on predicting the remaining survival in patients with spinal metastases and is simultaneously simple in clinical use.

Paley's multiplier method does not accurately predict adult height in children with bone sarcoma.

BACKGROUND: The majority of patients with osteosarcoma and Ewing's sarcoma are diagnosed before skeletal maturity. Paley's multiplier is used for height prediction in healthy children, and has been suggested as a method to make growth predictions for children with osteosarcoma and Ewing's sarcoma when considering limb salvage options. To our knowledge, no evaluation of this method in this particular patient group has been performed, but a temporary growth deficit has been observed in children undergoing chemotherapy. QUESTIONS/PURPOSES: We asked whether (1) Paley's formula reliably predicts growth in children who received polychemotherapy; (2) chemotherapy impairs growth velocity; and (3) final adult height is impaired in these patients. METHODS: Retrospectively, data for 94 patients with osteosarcoma and Ewing's sarcoma were retrieved from databases of two sarcoma centers. Onset before 14 years of age in girls and 16 years in boys and a minimum followup until 18 years were required (mean, 67 months; range, 31-124 months) criteria. Exclusion criteria were the intake of growth hormones or no chemotherapy. Thirty-three patients (35%) fulfilled all inclusion criteria. Predicted adult heights were compared with actual adult height. The development of a growth deficit was evaluated for 23 children (without chemotherapy for recurrence) using age- and gender-specific standard deviation scores for height (WHO Z-scores). RESULTS: Height prediction using Paley's method showed a high percentage of false predictions (outside ± 1 SD, 70%; outside ± 2 SD, 61%). On average, the mean total height of the patients was overestimated (2.3 cm). The median absolute error of prediction was 5.0 cm (range, -17 to 8). Patients with osteosarcoma and Ewing's sarcoma showed a significant growth impairment during polychemotherapy. A catchup phase in growth before skeletal maturity was observed in patients with osteosarcoma but not with Ewing's sarcoma. CONCLUSIONS: Owing to its lack of reliability in this patient group, methods other than Paley's should be evaluated to predict adult height. Although limited by a small number of patients, our study results indicate a decreased adult height in patients with bone sarcoma after chemotherapy. LEVEL OF EVIDENCE: Level III, therapeutic study. See the Instructions for Authors for complete description of levels of evidence.

Intercalary reconstructions with vascularised fibula and allograft after tumour resection in the lower limb.

Reconstruction with massive bone allograft and autologous vascularised fibula combines the structural strength of the allograft and the advantages of fibula's intrinsic blood supply. We retrospectively analysed the outcome of twelve patients (4 male, 8 female) who received reconstruction with massive bone allograft and autologous vascularised fibula after tumour resection in lower limb. Mean age was 17.8 years (range 11-31 years), with following primaries: Ewing's sarcoma (n = 6), osteosarcoma (n = 4), liposarcoma grade 2 (n = 1), and adamantinoma (n = 1). Mean followup was 38.7 months (median 25.7 months; range 2-88 months). Seven tumours were located in the femur and five in the tibia. The mean length of bone defect was 18.7 cm (range 15-25 cm). None of the grafts had to be removed, but there occurred four fractures, four nonunions, and two infections. Two patients developed donor side complication, in form of flexion deformity of the big toe. The event-free survival rate was 51% at two-year followup and 39% at three- and five-year followup. As the complications were manageable, and full weight bearing was achieved in all cases, we consider the combination of massive bone allograft and autologous vascularised fibula a stable and durable reconstruction method of the diaphysis of the lower limbs.

Central low-grade osteosarcoma with an unusual localization in the diaphysis of a 12-year old patient.

BACKGROUND: Low-grade central osteosarcoma is a very rare subtype of osteosarcoma with a predilection for the metaphysis of long bones and a peak incidence in the 3(rd) decade of life. Absence of specific clinical symptoms and a good prognosis after wide resection are the characteristics of this entity. Chemotherapy is not indicated in this highly differentiated tumour. CASE REPORT: A 12-year old girl presented with limping, swelling and pain in the mid of the left femur. Radiography showed a 12 cm long intraosseous expansion with lamellated periosteal reaction and contrast medium enhancement in MRI. Although radiology led to the differential diagnoses of Ewing's sarcoma, osteomyelitis and fibrous dysplasia, the histological specimen showed a hyopocellular spindle-cell proliferation arranged in fascicles with mild cytologic atypia and only single mitotic figures. In synopsis with radiology the diagnosis of low-grade central osteosarcoma was made and confirmed by reference pathology. The tumour was resected with wide margins and reconstruction was performed with a vascularized fibula, a homologous allograft and a plate. Staging was negative for recurrence and metastasis at a follow-up of 16 months. CONCLUSIONS: Low-grade osteosarcoma accounts for only 1% of all osteosarcomas with a peak incidence in the 3(rd) decade. The diaphyseal localization and the young age make this case special. To achieve the correct diagnosis of this rare low-grade entity and thereby the adequate treatment, despite a wide range of differential diagnoses, a multidisciplinary approach is essential.

Survival analysis of 254 patients after manifestation of spinal metastases: evaluation of seven preoperative scoring systems.

STUDY DESIGN: Retrospective study. OBJECTIVE: This study analyzed the predictive value of the scoring systems of Bauer, Bauer modified, Tokuhashi, Tokuhashi revised, Tomita, van der Linden, and Sioutos as well as the parameters included in these systems. SUMMARY OF BACKGROUND DATA: Metastases of the spinal column are a common manifestation of advanced cancer. Severe pain, pathologic fracture, and neurologic deficit due to spinal metastases need adequate treatment. Besides oncologic aspects and quality of life, treatment decisions should also include the survival prognosis. METHODS: Two hundred fifty-four patients with confirmed spinal metastases were investigated retrospectively (treatment 1998-2006; 62 underwent surgery and 192 had conservative treatment only). Factors related to survival, such as primary tumor, general condition (Karnofsky Performance Status Scale), neurologic deficit, number of spinal and extraspinal bone metastases, visceral metastases, and pathologic fracture, were analyzed. The survival period was calculated from date of diagnosis of the spinal metastases to date of death or last follow-up (minimum follow-up: 12 months). For statistical analysis, univariate and stepwise multivariate Cox regression analyses were performed. RESULTS: Median overall survival for all patients was 10.6 months. The following factors showed significant influence on survival in multivariate analysis: primary tumor (P < 0.0001), status of visceral metastases (P < 0.0001), and systemic therapy (P < 0.0001). Using the recommended group assignment for each system, only Bauer and Bauer modified showed significant results for the distinction between good, moderate, and poor prognosis. The other systems failed to distinguish significantly between good and moderate prognosis. The hazard ratio of the absolute score of all analyzed systems was, however, statistically significant, with a better score leading to lower risk of death. CONCLUSION: According to this analysis, the Bauer and the Bauer modified scores are the most reliable systems for predicting survival. Since the Bauer modified score furthermore consists of only four positive prognostic factors, we emphasize its impact and simplicity.

The threat of misdiagnosis of primary osteosarcoma over the age of 60: a series of seven cases and review of the literature.

BACKGROUND: Osteosarcoma is the most common, non-haematopoietic, primary malignant bone tumour with an incidence of 0.3-0.5 per 100,000. There is some discrepancy in literature concerning the peaks of incidence of osteosarcoma. Some describe only one peak which arises in adolescence, whilst others report a bimodal age distribution with a second peak over the age of 60. In this retrospective study, we evaluated osteosarcoma patients over age 60 treated at our department and reviewed previous studies from the literature. PATIENTS AND METHODS: Sixty-four patients (40 male, 24 female) with a mean age of 29 years (from 7 to 82) were treated for primary osteosarcomas. At the time of diagnosis, seven patients (two male and five female) were over 60 years of age with a mean follow-up of 46 months after definite diagnosis. RESULTS: Three out of seven osteosarcomas were primarily radiologically or histologically misdiagnosed, but only one was mistreated with intramedullary nailing at a trauma centre. At last follow-up, two patients had died from the disease, three were alive with disease, and two had no evidence of osteosarcoma. CONCLUSIONS: We did not find an increased incidence of primary osteosarcoma in the elderly; yet, older patients had a higher rate of misdiagnosis due to untypical radiological findings in combination with longer times from the onset of first symptoms to definite diagnosis. In cases of pathological fracture, it is essential to assess whether it is caused by mechanical stress or a primary or secondary tumour before leading into mistreatment, especially in older patients.