Development of a prognostic model for survival can assist in stratifying treatment according to the individual patients' risk, leading to risk- and response adaptive treatment strategies which allow ...for early decision making. The aim of this systematic review is to provide an overview of prognostic factors for overall survival (OS) and event-free survival (EFS) in Ewing sarcoma to be used in the development of prediction models and clinical trial design. A literature search was performed using Pubmed, Embase, Web of Science, Academic search premier and Cochrane databases. Studies were eligible if: 1) Sample size ≥100; 2) Follow-up ≥2 years or dead within 2 years; 3) Recruitment after 1975; 4) Outcome measure OS or EFS; 5) Multivariate analysis to assess the effect of prognostic factors on survival outcomes; 6) Study published in English. In case studies were derived from the same database the most all-embracing was selected. Study selection and quality assessment was performed by two reviewers independently. For each risk factor a level of evidence synthesis was performed. Kappa-statistic was used to determine inter-observer agreement. A total of 149 full-text articles were found, 21 eligible for inclusion. 24 prognostic factors were investigated, 14 relevant for this review. Prognostic factors associated with survival include metastasis at diagnosis, large tumors (volume ≥ 200 ml or largest diameter ≥ 8 cm), primary tumors located in the axial skeleton, especially pelvic and a histological response of less than 100%. These factors should be included as risk factors in the development of prediction models for ES.
•A systematic review of prognostic factors for survival in Ewing sarcoma.•Disease extent, tumor size, tumor location and histological response are strongly associated with survival.•Insight about the effect of surgical margins and local treatment modality requires further investigations.•Mentioned risk factors are useful for development of prognostic models and clinical trial design.
Background and aims
The aim of this systematic review is to describe the epidemiology of chordoma and to provide a clear overview of clinical prognostic factors predicting progression-free and ...overall survival.
Methods
Four databases of medical literature were searched. Separate searches were performed for each of the two objectives. Reference and citation tracking was performed. Papers were processed by two independent reviewers according to a protocol that included risk of bias analysis. Disagreement was resolved by discussion. Pooled analyses were planned if homogeneity of data would allow.
Results
Incidence—incidence rates ranged between 0.18 and 0.84 per million persons per year and varied between countries and presumably between races. On average patients were diagnosed in their late fifties and gender data indicate clear male predominance. Two of the largest studies (
n
= 400 and
n
= 544) reported different anatomical distributions: one reporting the skull base and sacrococcygeal area affected in 32% and 29% of cases, whereas the other reporting that they were affected in 26% and 45% of cases, respectively.
Prognostic factors
Statistically significant adverse prognostic factors predicting progression-free and overall survival include female sex, older age, bigger tumour size, increasing extent of tumour invasion, non-total resection, presence of metastasis, local recurrence, and dedifferentiated histological subtype.
Conclusions
Incidence rate and anatomical distribution vary between countries and presumably between races. Most chordomas arise in the skull base and sacrococcygeal spine, and the tumour shows clear male predominance. Multiple adverse prognostic factors predicting progression-free and overall survival were identified in subgroups of patients.
Graphical abstract
These slides can be retrieved under Electronic Supplementary Material.
BACKGROUND:A survival estimation for patients with symptomatic long bone metastases (LBM) is crucial to prevent overtreatment and undertreatment. This study analyzed prognostic factors for overall ...survival and developed a simple, easy-to-use prognostic model.
METHODS:A multicenter retrospective study of 1,520 patients treated for symptomatic LBM between 2000 and 2013 at the radiation therapy and/or orthopaedic departments was performed. Primary tumors were categorized into 3 clinical profiles (favorable, moderate, or unfavorable) according to an existing classification system. Associations between prognostic variables and overall survival were investigated using the Kaplan-Meier method and multivariate Cox regression models. The discriminatory ability of the developed model was assessed with the Harrell C-statistic. The observed and expected survival for each survival category were compared on the basis of an external cohort.
RESULTS:Median overall survival was 7.4 months (95% confidence interval CI, 6.7 to 8.1 months). On the basis of the independent prognostic factors, namely the clinical profile, Karnofsky Performance Score, and presence of visceral and/or brain metastases, 12 prognostic categories were created. The Harrell C-statistic was 0.70. A flowchart was developed to easily stratify patients. Using cutoff points for clinical decision-making, the 12 categories were narrowed down to 4 categories with clinical consequences. Median survival was 21.9 months (95% CI, 18.7 to 25.1 months), 10.5 months (95% CI, 7.9 to 13.1 months), 4.6 months (95% CI, 3.9 to 5.3 months), and 2.2 months (95% CI, 1.8 to 2.6 months) for the 4 categories.
CONCLUSIONS:This study presents a model to easily stratify patients with symptomatic LBM according to their expected survival. The simplicity and clarity of the model facilitate and encourage its use in the routine care of patients with LBM, to provide the most appropriate treatment for each individual patient.
LEVEL OF EVIDENCE:Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
A prospective follow-up study.
Assessment of the relation between accomplishment of pain relief through percutaneous vertebroplasty (PVP) in painful osteoporotic vertebral compression fractures ...(OVCFs) and the cemented fraction of the vertebral body and subsequent determination of the optimal intravertebral cement volume.
The mechanism of pain relief of PVP as a treatment modality for painful OVCFs remains unclear. Generally, benefit of PVP is thought to result from stabilization of micromovements and collapse of the fractured vertebral body. However, studies indicating a relation between intravertebral cement volume and pain relief are lacking and an optimal value of the intravertebral cement volume is unknown.
One hunderd six patients who received PVP for 196 painful OVCFs were prospectively followed on back pain (score 0-10) and occurrence of new OVCFs during the first postoperative year. Patients were classified as responders (average postoperative back pain ≤ 6) and nonresponders (average postoperative back pain >6). The cemented fraction of the vertebral body was determined using volumetric analysis of the postoperative CT scan of the treated levels. Analysis was performed using receiver-operating characteristic (ROC) analysis and multivariable regression techniques.
Twenty-nine patients (27.3%) were found to be nonresponders. Mean intravertebral cement volume in all 196 treated OVCFs was 3.94 mL (SD = 1.89, range 0.13-10.8). The mean cemented vertebral body fraction was significantly lower in nonresponders (0.15 vs. 0.21, P = 0.002). The ROC area-under-curve of the cemented fraction as a predictor of accomplishment of pain relief was 0.67 (95% CI: 0.57-0.78, P = 0.006). In subgroups without specific influential factors (new OVCFs, intravertebral clefts), significantly stronger associations were found. A vertebral body fraction of 24% was identified as the optimal fraction to be cemented. This fraction corresponded to a 93% to 100% specificity for accomplishment of pain relief (i.e., few to no cases without pain relief in the presence of adequate cementing) without being significantly associated with a higher risk of occurrence of cement leakage or new OVCFs. Corresponding values for the recommended (optimal) intravertebral cement volume were provided based on its governing characteristics (fracture level, fracture severity, and patient's sex).
An optimal intravertebral cement volume was identified for accomplishment of pain relief through PVP in painful OVCFs. Appropriate thresholds were provided to guide the operator.
The majority of the Earth's terrestrial carbon is stored in the soil. If anthropogenic warming stimulates the loss of this carbon to the atmosphere, it could drive further planetary warming. Despite ...evidence that warming enhances carbon fluxes to and from the soil, the net global balance between these responses remains uncertain. Here we present a comprehensive analysis of warming-induced changes in soil carbon stocks by assembling data from 49 field experiments located across North America, Europe and Asia. We find that the effects of warming are contingent on the size of the initial soil carbon stock, with considerable losses occurring in high-latitude areas. By extrapolating this empirical relationship to the global scale, we provide estimates of soil carbon sensitivity to warming that may help to constrain Earth system model projections. Our empirical relationship suggests that global soil carbon stocks in the upper soil horizons will fall by 30 ± 30 petagrams of carbon to 203 ± 161 petagrams of carbon under one degree of warming, depending on the rate at which the effects of warming are realized. Under the conservative assumption that the response of soil carbon to warming occurs within a year, a business-as-usual climate scenario would drive the loss of 55 ± 50 petagrams of carbon from the upper soil horizons by 2050. This value is around 12-17 per cent of the expected anthropogenic emissions over this period. Despite the considerable uncertainty in our estimates, the direction of the global soil carbon response is consistent across all scenarios. This provides strong empirical support for the idea that rising temperatures will stimulate the net loss of soil carbon to the atmosphere, driving a positive land carbon-climate feedback that could accelerate climate change.
Background
Management of fibrous dysplasia of the proximal femur is a progressive, often recurrent condition of bone that can cause skeletal deformity, fractures, and pain. Allogeneic cortical strut ...grafting to minimize the risk of fracture or as part of fracture treatment is a promising treatment option, but evidence is scarce on the intermediate- to long-term results of this procedure and there are no data on factors associated with graft failure.
Questions/purposes
The purposes of this study were (1) to evaluate the revision-free survivorship; (2) radiographic findings; (3) factors associated with failure; and (4) complications associated with cortical strut allograft to prevent or treat fractures of the proximal femur in patients with fibrous dysplasia.
Methods
Between 1980 and 2013 we performed cortical strut allografting in 30 patients for impending or actual fractures of the proximal femur, of whom 28 (93%) were available for followup at a minimum of 2 years (mean, 13 years; range, 4–37 years) and of whom 22 (73%) had also been evaluated within the last 5 years. During that time, the indications for cortical strut allografting were an impending fracture of the proximal femur, persistent pain, or an actual nondisplaced femoral fracture. In patients who presented with a diaphyseal fracture, a fracture with severe dislocation of severe varus deformity, which required an osteotomy, placement of a blade plate was instead performed and these patients are not included here. During that time, for patients with diaphyseal fractures, and in patients with a displaced femoral fracture of the proximal femur, placement of a blade plate without strut grafting was instead performed; these patients are not included here. The primary outcome was the success rate of allogeneic cortical strut grafting surgery as assessed by the absence of revision surgery for a newly sustained fracture, resorption of the graft, or progressive deformity of the proximal femur. The association of possible contributing factors to graft failure such as gender, age at surgery, preoperative fracture, and anchoring distances of the graft in healthy bone was also evaluated using Cox regression analysis.
Results
Revision surgery was performed in 13 patients, resulting in a mean survival time of 13 years (Kaplan-Meier 95% confidence interval CI, 10–16). Radiological resorption of the graft was observed in 15 of 28 patients (54%). However, revision surgery was not performed in all patients who developed graft resorption, because of the absence of a risk for fracture on the basis of the anatomical site of resorption. Identified risk factors for graft failure included preoperative fractures (hazard ratio HR, 4.5; 95% CI, 1.2–17.2; p = 0.028) and insufficient proximal anchoring of the graft in healthy bone (HR, 6.02; 95% CI, 1.3–27; p = 0.02). One patient sustained a refracture after surgery resulting from an in-hospital fall. The fracture was treated without further surgery, and it healed.
Conclusions
Our findings from this study suggest that cortical strut allografting may be a viable option for treatment of fibrous dysplasia of the proximal femur a without previous pathological fracture. Surgeons should pay particular attention to the proximal fixation point of the allograft to decrease the risk of failure. Patients with a fracture have an increased risk of failure and reoperation and so should be treated with an osteosynthesis.
Level of Evidence
Level IV, therapeutic study.
BACKGROUND:Improved survival rates for patients with primary bone tumors of the extremities have increased the demand for reliable and durable reconstruction techniques. Some authors have stated ...that, after successful ingrowth, allografts are a durable long-term solution. This hypothesis is largely based on small studies with short-to-midterm follow-up. In order to determine the durability of intercalary allograft reconstructions in the lower extremities, we evaluated the long-term clinical outcomes at a minimum of 10 years.
METHODS:All patients who received an intercalary allograft reconstruction in a lower extremity between 1980 and 2006 were included in this retrospective multicenter cohort study. One hundred and thirty-one patients with a median age of 19 years were included. Eighty-nine (68%) had a femoral reconstruction, and 42 (32%) had a tibial reconstruction. The most prevalent diagnoses were osteosarcoma (55%), Ewing sarcoma (17%), and chondrosarcoma (12%). The median follow-up was 14 years. A competing risk model was employed to estimate the cumulative incidences of mechanical failure and infection. Patient mortality or progression of the disease was used as a competing event.
RESULTS:Nonunion occurred in 21 reconstructions (16%), after a median of 16 months, and was associated with intramedullary nail-only fixation (p < 0.01) and fixation with nonbridging plate(s) (p = 0.03). Allograft fracture occurred in 25 reconstructions (19%) after a median of 42 months (range, 4 days to 21.9 years). Thirteen (52%) of the allograft fractures occurred within 5 years; 8 (32%), between 5 and 10 years; and 4 (16%), at >10 years. With failure for mechanical reasons as the end point, the cumulative incidences of reconstruction failure at 5, 10, and 15 years were 9%, 14%, and 21%, respectively.
CONCLUSIONS:Intercalary allograft reconstruction is an acceptable reconstructive option, mainly because of the absence of superior alternatives with a known track record. However, a considerable and continuing risk of mechanical complications should be taken into account.
LEVEL OF EVIDENCE:Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Mazabraud’s syndrome (MZB) is a rare condition in which fibrous dysplasia of bone/the McCune-Albright syndrome (FD/MAS) co-exists with intramuscular myxomas. Both FD and the myxomas harbor the
GNAS-
...mutation. Recent studies have shown that extraskeletal,
GNAS
-related features are associated with a more severe phenotype of FD/MAS. However, patients with MZB are often only seen by orthopedic surgeons. We therefore evaluated MZB patients seen in tertiary referral centers from the Netherlands (LUMC), USA (National Institutes of Health) and France (INSERM UMR 1033 (Lyos), Hôpital Edouard Herriot). All FD/MAS patients known in these centers with an additional diagnosis of a myxoma were included. Demographic information and data on disease extent and extraskeletal manifestations of FD/MAS such as precocious puberty (PP) or café-au-lait patches (CAL) were retrieved from patient’s medical records. Thirty MZB patients were included: 20 women (67%) and 10 men (33%). Patients received a diagnosis of MZB (median 42 years, range 16–19) significantly later than the diagnosis of FD/MAS (median 30 years, range 0–60),
p
< 0.01. Twenty-six patients were diagnosed with polyostotic disease (87%). In 97% the myxoma was located near the skeletal FD lesion. The combination of MZB and MAS was made in 13 patients in whom PP (
n
= 7), CAL (
n
= 7), GH-excess (
n
= 3) and hyperthyroidism (
n
= 3) were present. Other extraskeletal features were (multinodular) goiter (
n
= 2) and thyroid cysts (
n
= 1). Furthermore, in this cohort of patients with MZB several (pre-)malignant tumors were observed; ductal carcinoma in situ of the breast in 3 patients (10%), breast cancer in 1 patient (3.3%), intra pancreatic mucinous neoplasms in 3 patients (10%) and liver adenomas in 2 patients (6.6%). A total of 47% of patients with MZB had an additional extraskeletal feature such as an endocrinopathy. In MZB, 87% of patients suffer from polyostotic FD, 43% of patients have extraskeletal
GNAS
-features such as an hyperfunctioning endocrinopathy and 30% (pre-)malignant tumors. We therefore advocate that MZB patients should undergo a complete screening and long-term follow-up for extent of bone disease, but also extraskeletal
GNAS
features of FD/MAS.
Background
The saddle prosthesis originally was developed to reconstruct large acetabular defects in revision hip arthroplasty and was used primarily for hip reconstruction after periacetabular tumor ...resections. The long-term survival of these reconstructions is unclear.
Questions/purpose
We therefore examined the long-term function, complications, and survival in patients treated with saddle prostheses after periacetabular tumor resection.
Patients and Methods
Between 1987 and 2003 we treated 17 patients with a saddle prosthesis after periacetabular tumor resection (12 chondrosarcomas, three osteosarcomas, one malignant fibrous histiocytoma, one metastasis). During followup, 11 patients died, resulting in a median overall survival of 49 months (95% CI, 30–68 months). The remaining six patients were alive without disease (mean followup, 12.1 years; range, 8.3–16.8 years). In one patient the saddle prosthesis was removed after 3 months owing to dislocation and infection. We obtained SF-36 questionnaires, Toronto Extremity Salvage Scores (TESS), and Musculoskeletal Tumor Society (MSTS) scores.
Results
Thirteen of 17 patients used walking assists for mobilization at last followup: eight patients required two crutches, five needed one crutch, and one did not use any walking aids. The other three patients were not able to mobilize independently and only made bed to chair transfers. The mean hip flexion in the six surviving patients was 60° (range, 40°–100°) at last followup. Local complications were seen in 14 of the 17 patients: nine wound infections, seven dislocations, and two leg-length discrepancies requiring additional surgery. In the five surviving patients with their index prosthesis still in situ, the mean MSTS score at long-term followup was 47% (range, 20%–77%), the mean TESS score was 53% (range, 41%–67%), and the mean composite SF-36 physical and mental component summaries were 43.9 and 50.6, respectively.
Conclusion
Reconstruction with saddle prostheses after periacetabular tumor surgery has a high risk of complications and poor long-term function with limited hip flexion; therefore, we no longer use the saddle prosthesis for reconstruction after periacetabular tumor resections.
Level of Evidence
Level IV, retrospective case series. See the Guideline for Authors for a complete description of levels of evidence.
Malignant transformation of fibrous dysplasia lesions has been reported in patients with fibrous dysplasia/McCune-Albright syndrome (FD/MAS). Recently, we have observed an increased risk for breast ...cancer. In this study, the prevalence of skeletal and extraskeletal malignancies in patients with FD/MAS in the Netherlands was assessed by analyzing data from our cohort of FD/MAS patients, the Dutch Pathology Registry (PALGA), and the Netherlands Cancer Registry (NCR). We extracted data on sex, age at diagnosis of FD/MAS, type of FD/MAS, type of malignancy, and age at diagnosis of malignancy and histology of bone and malignant tissue when available, including
GNAS
-mutation analysis from patients’ medical records. Standardized Morbidity Ratios (SMRs) with 95% confidence intervals were calculated. Twelve malignancies were identified in the LUMC FD/MAS cohort and 100 in the PALGA cohort. In this cohort, SMR was increased for osteosarcoma (19.7, 95% CI 3.5–48.9), cervical cancer (4.93, 95%CI 1.7–8.2), thyroid cancer (3.71, 95% CI 1.1–7.8), prostate cancer (3.08, 95% CI 1.8–4.6), and melanoma (2.01, 95%CI 1.2–3.1). SMRs for pancreatic cancer or hepatocellular carcinoma could not be calculated due to low numbers. The small number of malignancies identified in our FD/MAS cohort precluded the calculation of SMRs for our cohort specifically. Our findings show that patients with FD/MAS appear to have an increased risk for osteosarcoma, cervical, thyroid, and prostate cancer and melanoma. However, these data should be interpreted with caution, as true incidence rates of the identified malignancies may be influenced by the inclusion of only patients with histologically confirmed FD/MAS. The etiology of this increased risk for malignancies still needs to be elucidated.
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