En-bloc spondylectomy in the lumbar spine: indications, results and complications in a series of 47 patients affected by primary malignant bone tumors.

INTRODUCTION: Wide Surgery is the reference treatment for malignant and aggressive benign primary bone tumors in the spine. When located in the lumbar spine, En-Bloc Spondylectomy (EBS) remains a complex challenge. Moreover, surgery is complicated by the presence of the diaphragm in the thoracolumbar junction and the hinderance of the iliac wings at the lumbosacral levels. Therefore, EBS in the lumbar spine frequently requires combined approaches. The purpose of this study is to describe clinical presentation, tumor characteristics and results of a series of 47 consecutive patients affected by malignant primary bone tumors of the lumbar spine who underwent EBS. MATERIALS AND METHODS: 47 patients were reviewed. Complications were distinguished in early and late whether they occurred before or after 30 days from surgery. Overall survival (OS), disease-free survival (DFS) and local recurrence-free survival (LRFS) were calculated by the Kaplan-Meier product-limit method from surgery until relapse or death. RESULTS: 27 patients presented to observation after a first intralesional approach in a non-specialized center. Chordoma was the most represented histotype. Vertebrectomies were: 23 one-level, 10 two-level, 12 three-level and 2 four-level. Reconstructions were always carried out with screws and rods. The main postoperative complication was blood loss, while hardware failure was the main long-term complication. The 5-year LRFS was 75.5%, the 5-year DFS was 54.3%, and 5-year OS was 63.6%. CONCLUSIONS: The surgical margin obtained during the index surgery was statistically associated with Local Recurrence, DFS and OS, underlining the importance of treating patients in reference centers.

MRI radiomics-based machine learning for classification of deep-seated lipoma and atypical lipomatous tumor of the extremities.

PURPOSE: To determine diagnostic performance of MRI radiomics-based machine learning for classification of deep-seated lipoma and atypical lipomatous tumor (ALT) of the extremities. MATERIAL AND METHODS: This retrospective study was performed at three tertiary sarcoma centers and included 150 patients with surgically treated and histology-proven lesions. The training-validation cohort consisted of 114 patients from centers 1 and 2 (n = 64 lipoma, n = 50 ALT). The external test cohort consisted of 36 patients from center 3 (n = 24 lipoma, n = 12 ALT). 3D segmentation was manually performed on T1- and T2-weighted MRI. After extraction and selection of radiomic features, three machine learning classifiers were trained and validated using nested fivefold cross-validation. The best-performing classifier according to previous analysis was evaluated and compared to an experienced musculoskeletal radiologist in the external test cohort. RESULTS: Eight features passed feature selection and were incorporated into the machine learning models. After training and validation (74% ROC-AUC), the best-performing classifier (Random Forest) showed 92% sensitivity and 33% specificity in the external test cohort with no statistical difference compared to the radiologist (p = 0.474). CONCLUSION: MRI radiomics-based machine learning may classify deep-seated lipoma and ALT of the extremities with high sensitivity and negative predictive value, thus potentially serving as a non-invasive screening tool to reduce unnecessary referral to tertiary tumor centers.

Diffusion-weighted MRI radiomics of spine bone tumors: feature stability and machine learning-based classification performance.

PURPOSE: To evaluate stability and machine learning-based classification performance of radiomic features of spine bone tumors using diffusion- and T2-weighted magnetic resonance imaging (MRI). MATERIAL AND METHODS: This retrospective study included 101 patients with histology-proven spine bone tumor (22 benign; 38 primary malignant; 41 metastatic). All tumor volumes were manually segmented on morphologic T2-weighted sequences. The same region of interest (ROI) was used to perform radiomic analysis on ADC map. A total of 1702 radiomic features was considered. Feature stability was assessed through small geometrical transformations of the ROIs mimicking multiple manual delineations. Intraclass correlation coefficient (ICC) quantified feature stability. Feature selection consisted of stability-based (ICC > 0.75) and significance-based selections (ranking features by decreasing Mann-Whitney p-value). Class balancing was performed to oversample the minority (i.e., benign) class. Selected features were used to train and test a support vector machine (SVM) to discriminate benign from malignant spine tumors using tenfold cross-validation. RESULTS: A total of 76.4% radiomic features were stable. The quality metrics for the SVM were evaluated as a function of the number of selected features. The radiomic model with the best performance and the lowest number of features for classifying tumor types included 8 features. The metrics were 78% sensitivity, 68% specificity, 76% accuracy and AUC 0.78. CONCLUSION: SVM classifiers based on radiomic features extracted from T2- and diffusion-weighted imaging with ADC map are promising for classification of spine bone tumors. Radiomic features of spine bone tumors show good reproducibility rates.

Feasibility of achieving planned surgical margins in primary spine tumor: a PTRON study.

OBJECTIVE: Oncological resection of primary spine tumors is associated with lower recurrence rates. However, even in the most experienced hands, the execution of a meticulously drafted plan sometimes fails. The objectives of this study were to determine how successful surgical teams are at achieving planned surgical margins and how successful surgeons are in intraoperatively assessing tumor margins. The secondary objective was to identify factors associated with successful execution of planned resection. METHODS: The Primary Tumor Research and Outcomes Network (PTRON) is a multicenter international prospective registry for the management of primary tumors of the spine. Using this registry, the authors compared 1) the planned surgical margin and 2) the intraoperative assessment of the margin by the surgeon with the postoperative assessment of the margin by the pathologist. Univariate analysis was used to assess whether factors such as histology, size, location, previous radiotherapy, and revision surgery were associated with successful execution of the planned margins. RESULTS: Three hundred patients were included. The surgical plan was successfully achieved in 224 (74.7%) patients. The surgeon correctly assessed the intraoperative margins, as reported in the final assessment by the pathologist, in 239 (79.7%) patients. On univariate analysis, no factor had a statistically significant influence on successful achievement of planned margins. CONCLUSIONS: In high-volume cancer centers around the world, planned surgical margins can be achieved in approximately 75% of cases. The morbidity of the proposed intervention must be balanced with the expected success rate in order to optimize patient management and surgical decision-making.

En bloc resection in patients younger than 16 years affected by primary spine tumors: indications, results and complications in a series of 22 patients.

PURPOSE: Review a series of 22 patients below the age of 16 affected by primary bone tumors of the spine who underwent en bloc resection, and describe the clinical presentation, tumor characteristics, results and complications associated with the surgical treatment, underlining the specific issues related to a younger age. METHODS: We performed a review of all patients < 16 years old affected by primary bone tumors of the spine, surgically treated with en bloc resection from 1996 to 2016. Clinical and radiological characteristics, therapy, complications and survival are reported. RESULTS: Only 12/22 cases had not been previously treated. 22.7% experienced at least one early complication; 18.2% and 4.1% experienced at least 2 and ≥ 3 early complications, respectively; 40.9% experienced at least one late complication, often related to hardware failure (27.3%); 18.2% and 4.5% at least 2 and ≥ 3 late complications. No early nor late complications were experienced in 12 out of 22 patients (54.54%). The overall survival and the local recurrence-free survival at 5 years were, respectively, 79.5% and 74.8%; considering only the patients with high-grade tumors, they were 70.9% and 65.5%, respectively. At 77.3 months of median follow-up, 17 patients are still alive, 16 of whom without any evidence of disease and 1 with evidence of local and systemic disease; four patients died with evidence of local disease and one with distant metastases but no local recurrence. CONCLUSIONS: Young people with primary malignant or locally aggressive bone tumors of the spine should be treated in specialized centers, and wide surgery should be performed. The most frequent problems are related to reconstruction in a growing spine and subsequent hardware failure that make later surgeries necessary. These slides can be retrieved under Electronic Supplementary Material.

En bloc spondylectomy in patients older than 60 years: indications, results and complications in a series of 37 patients.

PURPOSE: To review a series of patients > 60 years affected by primary spine bone tumors, who have undergone surgery, and to describe their clinical presentation, results and complications associated with surgical treatment. METHODS: A review of all patients > 60 years affected by primary spine bone tumor surgically treated with en bloc spondylectomy from 1993 to 2015 was performed. Thirty-seven cases were identified, and clinical and radiological characteristics, therapy, complications and survival were evaluated. RESULTS: Only 14/37 cases were not previously treated. Complications were quite frequent: 64% of patients experienced almost one early complication; 48% and 27% experienced 2 and ≥ 3 early complications, respectively; 37% of patients experienced almost one late complication; and 10% and 8% experienced 2 and ≥ 3 late complications, respectively. Massive blood loss and dural tear were the more frequent surgical complications; no deaths were reported during surgeries; one patient died during the first postoperative day due to hemorrhage and cardiac complications, one during the third postoperative day for the same cause despite of a savage surgery, and another one died at 7 days from index surgery due to myocardial infarction. The 5-year disease-related survival and global survival were 62.8% and 52.1%, respectively. Nineteen patients are still alive, 15 of whom without any evidence of disease. CONCLUSIONS: Primary malignant or locally aggressive bone tumors of the spine should be treated with wide surgery also in the older age, although the complications rate and the risk of patient survival can be considered high. These slides can be retrieved under Electronic Supplementary Material.

Solid bone tumors of the spine: Diagnostic performance of apparent diffusion coefficient measured using diffusion-weighted MRI using histology as a reference standard.

PURPOSE: To assess the diagnostic performance of mean apparent diffusion coefficient (mADC) in differentiating benign from malignant bone spine tumors, using histology as a reference standard. Conventional magnetic resonance imaging (MRI) sequences have good reliability in evaluating spinal bone tumors, although some features of benign and malignant cancers may overlap, making the differential diagnosis challenging. MATERIALS AND METHODS: In all, 116 patients (62 males, 54 females; mean age 59.5 ± 14.1) with biopsy-proven spinal bone tumors were studied. Field strength/sequences: 1.5T MR system; T1 -weighted turbo spin-echo (repetition time / echo time [TR/TE], 500/13 msec; number of excitations [NEX], 2; slice thickness, 4 mm), T2 -weighted turbo spin-echo (TR/TE, 4100/102 msec; NEX, 2; slice thickness, 4 mm), short tau inversion recovery (TR/TE, 4800/89 msec; NEX, 2; slice thickness, 4 mm, IT, 140 msec), axial spin-echo echo-planar diffusion-weighted imaging (DWI) (TR/TE 5200/72 msec; slice thickness 5 mm; field of view, 300; interslice gap, 1.5 mm; NEX, 6; echo-planar imaging factor, 96; no parallel imaging) with b-values of 0 and 1000 s/mm², and 3D fat-suppressed T1 -weighted gradient-recalled-echo (TR/TE, 500/13 msec; slice thickness, 4 mm) after administration of 0.2 ml/kg body weight gadolinum-diethylenetriamine pentaacetic acid. Two readers manually drew regions of interest on the solid portion of the lesion (hyperintense on T2 -weighted images, hypointense on T1 -weighted images, and enhanced after gadolinium administration on fat-suppressed T1 -weighted images) to calculate mADC. Histology was used as the reference standard. Tumors were classified into malignant primary tumors (MPT), bone metastases (BM), or benign primary tumors (BPT). Statistical tests: Nonnormality of distribution was tested with the Shapiro-Wilk test. The Kruskal-Wallis and Mann-Whitney U-test with Bonferroni correction were used. Sensitivity and specificity of the mADC values for BM, MPT, and BPT were calculated. Approximate receiver operating characteristic curves were created. Interobserver reproducibility was evaluated using the intraclass correlation coefficient (ICC). RESULTS: The mADC values of MPT (n = 35), BM (n = 65), and BPT (n = 16) were 1.00 ± 0.32 (0.59-2.10) × 10-3 mm2 /s, 1.02 ± 0.25 (0.73-1.96) × 10-3 mm2 /s, 1.31 ± 0.36 (0.83-2.14) × 10-3 mm2 /s, respectively. The mADC was significantly different between BPT and all malignant lesions (BM+MPT) (P < 0.001), BM and BPT (P = 0.008), and MPT and BPT (P = 0.008). No difference was found between BM and MPT (P = 0.999). An mADC threshold of 0.952 × 10-3 mm2 /s yielded 81.3% sensitivity, 55.0% specificity. Accuracy was 76% (95% confidence interval [CI] = 63.9%-88.1%). Interobserver reproducibility was almost perfect (ICC = 0.916; 95% CI = 0.879-0.942). CONCLUSION: DWI with mADC quantification is a reproducible tool to differentiate benign from malignant solid tumors with 76% accuracy. The mADC values of BPT were statistically higher than that of malignant tumors. However, the large overlap between cases may make mADC not helpful in a specific patient. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1034-1042.

Microenvironmental stimuli affect Endothelin-1 signaling responsible for invasiveness and osteomimicry of bone metastasis from breast cancer.

The present study was undertaken to clarify the function(s) of Endothelin-1 and its receptors ETAR and ETBR in osteolytic-bone metastasis from breast cancer, and their regulation by hepatocyte and transforming growth factors (HGF, TGF-ß) and hypoxia. The aim was to evaluate the adaptability of bone metastasis to microenvironmental stimuli through Endothelin-1-mediated epithelial-mesenchymal transition (EMT), or the reverse process MET, and through osteomimicry possible key features for bone colonization. We compared low (MCF-7) and high (MDA-MB231) invasive-breast carcinoma cells, and 1833-bone metastatic clone, with human pair-matched primary breast-carcinomas and bone metastases. Parental MDA-MB231 and the derived 1833-clone responded oppositely to the stimuli. In 1833 cells, TGF-ß and hypoxia increased Endothelin-1 release, altogether reducing invasiveness important for engraftment, while Endothelin-1 enhanced MDA-MB231 cell invasiveness. The Endothelin-1-autocrine loop contributed to the cooperation of intracellular-signaling pathways and extracellular stimuli triggering MET in 1833 cells, and EMT in MDA-MB231 cells. Only in 1833 cells, HGF negatively influenced transactivation and release of Endothelin-1, suggesting a temporal sequence of these stimuli with an initial role of HGF-triggered Wnt/ß-catenin pathway in metastatization. Then, Endothelin-1/ETAR conferred MET and osteomimetic phenotypes, with Runt-related transcription factor 2 activation and metalloproteinase 9 expression, contributing to colonization and osteolysis. Findings with human pair-matched primary ductal carcinomas and bone metastases gave a translational significance to the molecular study. Endothelin-1, ETAR and ETBR correlated with the acquisition of malignant potential, because of high expression already in the in situ carcinoma. These molecular markers might be used as predictive index of aggressive behavior and invasive/metastatic phenotype.

How do we estimate survival? External validation of a tool for survival estimation in patients with metastatic bone disease-decision analysis and comparison of three international patient populations.

BACKGROUND: We recently developed a clinical decision support tool, capable of estimating the likelihood of survival at 3 and 12 months following surgery for patients with operable skeletal metastases. After making it publicly available on www.PATHFx.org , we attempted to externally validate it using independent, international data. METHODS: We collected data from patients treated at 13 Italian orthopaedic oncology referral centers between 2010 and 2013, then applied to PATHFx, which generated a probability of survival at three and 12-months for each patient. We assessed accuracy using the area under the receiver-operating characteristic curve (AUC), clinical utility using Decision Curve Analysis (DCA), and compared the Italian patient data to the training set (United States) and first external validation set (Scandinavia). RESULTS: The Italian dataset contained 287 records with at least 12 months follow-up information. The AUCs for the three-month and 12-month estimates was 0.80 and 0.77, respectively. There were missing data, including the surgeon's estimate of survival that was missing in the majority of records. Physiologically, Italian patients were similar to patients in the training and first validation sets. However notable differences were observed in the proportion of those surviving three and 12-months, suggesting differences in referral patterns and perhaps indications for surgery. CONCLUSIONS: PATHFx was successfully validated in an Italian dataset containing missing data. This study demonstrates its broad applicability to European patients, even in centers with differing treatment philosophies from those previously studied.

Epithelioid hemangioendothelioma of the spine: results at seven years of average follow-up in a series of 10 cases surgically treated and a review of literature.

PURPOSE: To review a series of ten cases with epithelioid hemangioendothelioma of the spine, that have undergone surgery to describe clinical presentation, results and complications associated with surgical treatment; a review of literature reporting the main characteristics of the cases already published has been reported. METHODS: A review of patients affected by epithelioid hemangioendothelioma surgically treated by the senior author from 1995 to 2012 was carried out. Ten cases were identified and clinical and radiological characteristics, therapy, complications and survival were valued. RESULTS: Wide margin was achieved in two out of ten cases, marginal margin in seven and intralesional margin in one case. Average intraoperative blood loss was about 2,800 ml. Reported complications were one case of cord injury, one of dural tear, two cases of massive blood loss, a case of reconstruction failure, a wound dehiscence with deep infection, a pneumonia episode and a deep vein thrombosis with pulmonary embolism. Average follow-up was 84.4 months. Two local recurrences, after 32 and 37 months and two deaths for metastasis, after 14 and 36 months, were reported. Although several chemotherapy protocols are available for the treatment of EH of soft tissue, they are not relevant for the bone. CONCLUSIONS: Wide surgery is probably associated with a better prognosis. Indeed most deaths and local recurrences reported in literature happened after intralesional surgery or chemotherapy/RT alone. The presenting study suggests that the best approach to achieve long-term local control and a major survival could be wide surgery, nevertheless more cases series are necessary to verify survival rate.

Surgical treatment of sacral chordoma: prognostic variables for local recurrence and overall survival.

PURPOSE: Sacral chordomas (SC) are rare, locally invasive, malignant neoplasms. Despite surgical resection and adjuvant therapies, local recurrence (LR) is common and overall survival (OS) is poor. The objective of this study was to identify prognostic factors that have an impact on the local recurrence-free survival (LRFS) and OS of patients with SC. METHODS: Utilizing the AOSpine Knowledge Forum Tumor multicenter ambispective database, surgically treated SC cases were identified. Cox regression modeling was used to assess the effect of several clinically relevant variables on OS and LRFS. RESULTS: A total of 167 patients with surgically treated SC were identified. The male/female ratio was 98/69 with a mean age of 57 ± 15 years at the time of surgery. The LR was 35% (n = 57), death occurred in 30% of patients (n = 50) during the study period. The median OS was 6 years post-surgery and LRFS was 4 years. In the univariate analysis, previous tumor surgery at the same site (P = 0.002), intralesional resection (P < 0.001), and larger tumor volume (P = 0.030) were significantly associated with LR. Increasing age (P < 0.001) and a preoperative motor deficit of C or D (P = 0.003) were significantly associated with poor OS, and nerve root sacrifice showed a trend towards significance (P = 0.088). In the multivariate models, previous surgery and intralesional resection were significantly related to LR, while increasing age and motor deficit of C or D were associated with poor OS. CONCLUSIONS: This study identified two predictive variables for LRFS (previous tumor surgery and type of surgical resection) and two for OS (age and impaired motor function) in surgically treated SC patients. Our results indicate that en bloc resection reduces LR but does not influence OS. However, this was likely due to short follow-up (3.2 years).

Multilevel en bloc spondylectomy for tumors of the thoracic and lumbar spine is challenging but rewarding.

BACKGROUND: Over the years, en bloc spondylectomy has proven its efficacy in controlling spinal tumors and improving survival rates. However, there are few reports of large series that critically evaluate the results of multilevel en bloc spondylectomies for spinal neoplasms. QUESTIONS/PURPOSES: Using data from a large spine tumor center, we answered the following questions: (1) Does multilevel total en bloc spondylectomy result in acceptable function, survival rates, and local control in spinal neoplasms? (2) Is reconstruction after this procedure feasible? (3) What complications are associated with this procedure? (4) is it possible to achieve adequate surgical margins with this procedure? METHODS: We retrospectively investigated 38 patients undergoing multilevel total en bloc spondylectomy by a single surgeon (AL) from 1994 to 2011. Indications for this procedure were primary spinal sarcomas, solitary metastases, and aggressive primary benign tumors involving multiple segments of the thoracic or lumbar spine. Patients had to be medically fit and have no visceral metastases. Analysis was by chart and radiographic review. Margin quality was classified into intralesional, marginal, and wide. Radiographs, MR images, and CT scans were studied for local recurrence. Graft healing and instrumentation failures at subsequent followup were assessed. Complications were divided into major or minor and further classified as intraoperative and early and late postoperative. We evaluated the oncologic status using cumulative disease-specific and metastases-free survival analysis. Minimum followup was 24 months (mean, 39 months; range, 24-124 months). RESULTS: Of the 38 patients, 34 (89%) were alive and walking without support at final followup. Thirty-one (81%) had no evidence of disease. Two patients died postoperatively and another two died of systemic disease (without local recurrence). Only three patients (8%) had a local recurrence. There were 14 major complications and 22 minor complications in 25 patients (65%). Only one patient required revision of implants secondary to mechanical failure. Two cases of cage subsidence were noted but had no clinical significance. Wide margins were achieved in nine patients (23%), marginal in 25 (66%), and intralesional in four (11%). CONCLUSIONS: In patients with multisegmental spinal tumors, oncologic resections were achieved by multilevel en bloc spondylectomy and led to an acceptable survival rate with reasonable local control. Multilevel en bloc surgery was associated with a high complication rate; however, most patients recovered from their complications. Although the surgical procedure is challenging, our encouraging mid-term results clearly favor and validate this technique. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.

High SPARC Expression Starting from Dysplasia, Associated with Breast Carcinoma, Is Predictive for Bone Metastasis without Enhancement of Plasma Levels.

In order to become established in the skeleton, metastatic cells disseminating from the breast carcinoma need to acquire organ-specific traits. There are no effective predictors for who will develop bone metastasis to guide long-term predictive therapy. Our purpose was to individuate events critical for bone colonization to make a molecular classification of breast carcinoma useful for bone-metastasis outcome. In dysplasia adjacent to carcinoma and in pair-matched specimens of bone metastasis we examined SPARC expression and localization as well as Endothelin 1/ETAR signals by immunohistochemistry, and the evaluation of plasma levels of SPARC by ELISA was also performed. In patients with breast carcinoma metastasizing to bone, SPARC and Endothelin 1/ETAR axis were highly expressed from dysplasia until bone metastasis, but the SPARC plasma level was as low as that of normal women, in contrast to patients that never develop bone metastasis, suggesting that circulating SPARC was counter adhesive. Altogether, the early identification of SPARC/Endothelin 1/ETAR in dysplastic lesions would be important to devise therapies preventing metastasis engraftment, since often carcinoma cells spread to distant organs at the time or even before patients present with cancer.

Aneurysmal bone cysts of the spine: treatment options and considerations.

Aneurysmal bone cysts (ABCs) are benign bone lesions with annual incidences ranging from 1.4 to 3.2 cases per million people. Approximately, 10-30% of ABCs are found in the spine. Such lesions are traditionally treated with curettage or other intralesional techniques. Because ABCs can be locally aggressive, intralesional resection can be incomplete and result in recurrence. This has led to increased use of novel techniques, including selective arterial embolization (SAE). This study aims to: (1) compare outcomes based on extent of surgical resection, and (2) compare the efficacy of SAE versus surgical resection. Clinical data pertaining to 71 cases of spinal ABCs were ambispectively collected from nine institutions in Europe, North America, and Australia. Twenty-two spinal ABCs were treated with surgery, 32 received preoperative embolization and surgery, and 17 were treated with SAE. Most tumors were classified as Enneking stage 2 (n = 29, 41%) and stage 3 (n = 29, 41%). Local recurrence and survival were investigated and a significant difference was not observed between treatment groups. However, all three local recurrences occurred following surgical resection. Surgical resection was further categorized based on Enneking appropriateness. Recurrences only occurred following intralesional Enneking inappropriate (EI) resections (P = 0.10), a classification that characterized 47% of all surgical resections. Furthermore, 56% of intralesional resections were EI, compared to only 10% of en bloc resections (P = 0.01). Although SAE treatment did not result in any local recurrences, 35% involved more than five embolization procedures. Spinal ABCs can be effectively treated with intralesional resection, en bloc resection, or SAE. Preoperative embolization should be considered before intralesional resection to limit intraoperative bleeding. Treatment plans must be guided by lesion characteristics and clinical presentation.

En Bloc Surgery in the Thoracic Spine: Indications, Results, and Complications in a Series of Eighty-Five Patients Affected by Primary and Secondary Malignant Bone Tumors.

BACKGROUND: En bloc resection remains the cornerstone treatment for malignant bone tumors affecting the spine. The thoracic spine poses unique challenges because of the proximity of crucial structures. This study assesses outcomes of patients who underwent en bloc spondylectomy for malignant bone tumors at the thoracic level. METHODS: We retrospectively reviewed 85 cases of primary and secondary bone tumors in the thoracic spine, undergoing en bloc spondylectomy from 1996 to 2016. Evaluation encompassed clinical presentation, tumor characteristics, surgical outcomes, complications, survival, and recurrence. RESULTS: Of 85 patients, 40 presented directly, whereas 45 had undergone previous intralesional surgery. Chondrosarcoma and chordoma comprised the most prevalent primary histologic types; thyroid and kidney carcinomas were the most frequent secondary tumors. Pain was reported in 75 patients at diagnosis. Margins were adequate in 54 cases and intralesional in 31. Immediate postoperative deaths amounted to 4. Major complications included substantial blood loss, neurologic deterioration, and paraplegia. The 5-year local recurrence-free survival was 58.7%, significantly influenced by the surgical margin: patients with wide margins experienced a 5-year local recurrence-free survival of 85.7%, whereas those with marginal and intralesional margins had rates of 56.7% and 45.6%, respectively; overall recurrence was 22.3%, with no notable disparities between previously treated and untreated patients. The 5-year overall survival was 63.2% and 56.2% for primary and secondary tumors, respectively. The overall survival was not significantly influenced by surgical margins. CONCLUSIONS: Managing malignant thoracic bone tumors poses significant challenges. This study underscores the criticality of achieving adequate margins, particularly after previous intralesional approaches.

X-rays radiomics-based machine learning classification of atypical cartilaginous tumour and high-grade chondrosarcoma of long bones.

BACKGROUND: Atypical cartilaginous tumour (ACT) and high-grade chondrosarcoma (CS) of long bones are respectively managed with active surveillance or curettage and wide resection. Our aim was to determine diagnostic performance of X-rays radiomics-based machine learning for classification of ACT and high-grade CS of long bones. METHODS: This retrospective, IRB-approved study included 150 patients with surgically treated and histology-proven lesions at two tertiary bone sarcoma centres. At centre 1, the dataset was split into training (n = 71 ACT, n = 24 high-grade CS) and internal test (n = 19 ACT, n = 6 high-grade CS) cohorts, respectively, based on the date of surgery. At centre 2, the dataset constituted the external test cohort (n = 12 ACT, n = 18 high-grade CS). Manual segmentation was performed on frontal view X-rays, using MRI or CT for preliminary identification of lesion margins. After image pre-processing, radiomic features were extracted. Dimensionality reduction included stability, coefficient of variation, and mutual information analyses. In the training cohort, after class balancing, a machine learning classifier (Support Vector Machine) was automatically tuned using nested 10-fold cross-validation. Then, it was tested on both the test cohorts and compared to two musculoskeletal radiologists' performance using McNemar's test. FINDINGS: Five radiomic features (3 morphology, 2 texture) passed dimensionality reduction. After tuning on the training cohort (AUC = 0.75), the classifier had 80%, 83%, 79% and 80%, 89%, 67% accuracy, sensitivity, and specificity in the internal (temporally independent) and external (geographically independent) test cohorts, respectively, with no difference compared to the radiologists (p ≥ 0.617). INTERPRETATION: X-rays radiomics-based machine learning accurately differentiates between ACT and high-grade CS of long bones. FUNDING: AIRC Investigator Grant.

Bizarre parosteal osteochondromatous proliferation: an educational review.

Bizarre parosteal osteochondromatous proliferation (BPOP) is a surface-based bone lesion belonging to the group of benign chondrogenic tumors. The aim of this review is to familiarize the readers with imaging features and differential diagnosis of BPOP, also addressing pathological presentation and treatment options. The peak of incidence of BPOP is in the third and fourth decades of life, although it can occur at any age. Hands are the most common location of BPOP (55%), followed by feet (15%) and long bones (25%). On imaging, BPOP appears as a well-marginated mass of heterotopic mineralization arising from the periosteal aspect of the bone. Typical features of BPOP are contiguity with the underlying bone and lack of cortico-medullary continuity, although cortical interruption and medullary involvement have been rarely reported. Histologically, BPOP is a benign bone surface lesion characterized by osteocartilaginous proliferation with disorganized admixture of cartilage with bizarre features, bone and spindle cells. Differential diagnosis includes both benign-such as florid reactive periostitis, osteochondroma, subungual exostosis, periosteal chondroma and myositis ossificans-and malignant lesions-such as periosteal chondrosarcoma and surface-based osteosarcoma. Treatment consists of surgical resection. Local recurrences are common and treated with re-excision.Critical relevance statement Bizarre parosteal osteochondromatous proliferation is a benign mineralized mass arising from the periosteal aspect of bone cortex. Multi-modality imaging characteristics, pathology features and differential diagnosis are here highlighted to familiarize the readers with this entity and offer optimal patient care.

Efficacy of Flap-based Posterior Trunk Reconstruction after Vertebrectomy and Radiation Therapy: A Retrospective Cohort Study.

Background: Adjuvant radiation therapy following vertebrectomy is a major risk factor for local wound complications such as dehiscence, infection, and skin necrosis. In selected cases, well-vascularized coverage and modification of tension forces on the wound might reduce the risk of postoperative complications and reoperations. We aimed to demonstrate a reduction in general and specific complications in patients undergoing vertebral resection and flap coverage compared with vertebral resection alone. Methods: We retrospectively analyzed and collected data from patients diagnosed with a tumor involving the spine and requiring a total or partial posterior vertebrectomy between January 2012 and October 2022, referred to a single tertiary-level orthopedic and trauma center. We included only patients in whom primary closure of the wound was possible but judged to be under excessive tension. Results: A total of 145 patients underwent partial or total vertebrectomy for oncological reasons at our tertiary-level trauma hospital. Among these, 73 patients were eventually included according to the inclusion and exclusion criteria: 53 in the orthopedic group and 20 in the orthoplastic group. Considering only patients undergoing radiation therapy, the orthoplastic group showed significantly lower rates of overall complications (33% versus 69%) than the orthopedic group. Conclusions: Primary flap coverage, especially in patients receiving RT, reduces the risk of postoperative complications and avoids a second reconstructive operation, consequently reducing patient discomfort, length of hospital stay, and healthcare costs.

Outcomes of Surgical Treatment for Extradural Benign Primary Spinal Tumors in Patients Younger than 25 Years: An Ambispective International Multicenter Study.

Extradural primary spinal tumors were retrospectively analyzed from a prospective database of 1495 cases. All subjects with benign primary tumors under the age of 25 years, who were enrolled between 1990 and 2012 (Median FU was 2.4 years), were identified. Patient- and case-related characteristics were collected and statistically analyzed. Results: 161 patients (66f;95m; age 17.0 ± 4.7 years at time of diagnosis) were identified. The most common tumors were osteoblastomas n = 53 (32.9%), osteoid osteomas n = 45 (28.0%), and aneurysmal bone cysts n = 32 (19.9%). The tumor grade, according to the Enneking Classification S1/S2/S3, was 14/73/74 (8.7/45.3/46.0%), respectively. Tumor-related pain was present in 156 (96.9%) patients. Diagnosis was achieved by biopsies in 2/3 of the cases. Spinal fixation was used in >50% of the cases. Resection was Enneking appropriate in n = 100 (62.1%) of cases. Local recurrence occurred in 21 (13.1%) patients. Two patients died within a 10-year follow-up period. Conclusion: This is one of the largest international multicenter cohorts of young patients surgically treated for benign spinal tumors. The heterogenic young patient cohort presented at a mid-term follow-up without a correlation between the grade of aggressiveness in resection and local recurrence rates. Further prospective data are required to identify prognostic factors that determine oncological and functional outcomes for young patients suffering from these rare tumors.

Extradural Primary Malignant Spinal Tumors in a Population Younger than 25 Years: An Ambispective International Multicenter Study on Onco-Surgical Outcomes.

Extradural malignant primary spinal tumors are rare and outcome data, especially for younger patients, is limited. In a worldwide (11 centers) study (Predictors of Mortality and Morbidity in the Surgical Management of Primary Tumors of the Spine study; ClinicalTrials.gov Identifier NCT01643174) by the AO Spine Knowledge Forum Tumor, patients surgically treated for primary tumors of the spine between 1992 and 2012, were retrospectively analyzed from a prospective database of their medical history. Medical history, tumor characteristics, diagnostics, treatments, cross-sectional survival, and local recurrences were analyzed. Sixty-eight cases (32 f; 36 m), at an average age of 18.6 ± 4.7 years at the time of diagnosis, were identified (median follow-up 2.9 years). The most common entities were Ewing's sarcoma (42.6%). Of the patients, 28% had undergone previous spine tumor surgery in another center (84% with intralesional margins). Resection was considered "Enneking appropriate" (EA) in 47.8% of the cases. Of the patients, 77.9% underwent chemotherapy and 50% radiotherapy. A local recurrence occurred in 36.4%. Over a third of patients died within a 10-year follow-up period. Kaplan-Meier-analysis demonstrated statistically significant overall survival (p = 0.007) and local recurrence rates (p = 0.042) for tumors treated with EA surgery versus Enneking inappropriate surgery. Aggressive resection of extradural primary malignant spinal tumors combined with adjuvant therapy reveals low local recurrence rates and better outcomes overall in younger patients.