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radiograph of pelvic chronrosarcoma Chondrosarcoma is a type of cancer that forms in bone cartilage. The most frequent primary sites are the pelvis, shoulder, ribs, or at the ends of the arms and legs. Chondrosarcoma can occur at any age but is more common in people older than 40 years.

Mesenchymal chondrosarcoma is aggressive variant of chondrosarcoma, which tend to occur in younger people.

Extraskeletal chondrosarcoma is a rare type of chondrosarcomadoes, which forms in the soft tissues, rather than bone cartilage.

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Mesenchymal Chondrosarcoma
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Molecular Genetics of Chondrosarcoma

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    MeSH term: Chondrosarcoma
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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Kushlinskii NE, Alferov AA, Boulytcheva IV, et al.
Comparative analysis of the levels of soluble forms of receptor and ligand of the immunity control point PD-1/PD-L1 in the blood serum of patients with typical bone osteosarcoma and chondrosarcoma.
Klin Lab Diagn. 2020; 65(11):669-675 [PubMed] Related Publications
Results of ELISA investigation of the pretreatment sPD-1 and sPD-L1 content in blood serum of 133 bone neoplasms patients aged 6-70 years and 57 practically healthy control persons aged 12-70 years are described. In 14 patients the neoplasms were of a benign character, in 16 - borderline giant-cell bone tumor was diagnosed, and in 103 - malignant bone lesions including 39 osteosarcomas and 42 chondrosarcomas were revealed. The sPD-1 receptor concentrations in blood serum did not differ between control healthy persons and primary bone tumor patients, while serum sPD-L1 level in bone tumor patients was statistically significantly increased (p<0.0000001). By means of ROC curve construction a cut-off sPD-L1 level of 16.5 pg/ml was found that imposed 75,9% sensitivity and 75,4% specificity in relation to healthy control. However, the frequency of sPD-L1 levels exceeding 16.5 pg/ml was approximately similar in benign, borderline and malignant bone tumor patients. Analysis of the pattern of sPD-1 and sPD-L1 circulation in the peripheral blood of patients with the most prevalent malignant bone tumors - osteosarcoma and chondrosarcoma - demonstrated that in both sarcoma types sPD-L1 level was significantly higher than in control, but in patients with chondrogenic tumors the soluble ligand sPD-L1 dominates in the circulation, while in those with osteogenic tumors - sPD-1 receptor prevails. In particular, sPD-1 level is statistically significantly higher in patients with typical osteosarcoma than in those with typical chondrosarcoma (p=0.002437), and sPD-L1/sPD-1 concentration ratio in chondrosarcoma is highly significantly more than 2-fold higher than in osteosarcoma (0.81 and 0.35 respectively; p=0.000284). The sensitivity of sPD-L1 ≥16.5 pg/ml test in typical osteosarcoma patients' group comprised only 70.2%, and in those with typical chondrosarcoma - 84.6%. Serum sPD-1 and sPD-L1 concentrations in osteosarcoma and chondrosarcoma patients were not associated with the indices of tumor advancement, its histological grade, localization in the osseous system, and type of affected bone. Thus, it can be concluded that the ratio between circulating soluble forms of the receptor and the ligand of PD-1/PD-L signaling pathway differs between patients with chondrogenic and those with osteogenic tumors, sPD-L1 being diagnostically valuable mostly for chondrogenic bone neoplasms.

Tsuda Y, Tsoi K, Stevenson JD, et al.
Development and external validation of nomograms to predict sarcoma-specific death and disease progression after surgical resection of localized high-grade conventional primary central chondrosarcoma and dedifferentiated chondrosarcoma.
Bone Joint J. 2020; 102-B(12):1752-1759 [PubMed] Related Publications
AIMS: Our aim was to develop and validate nomograms that would predict the cumulative incidence of sarcoma-specific death (CISSD) and disease progression (CIDP) in patients with localized high-grade primary central and dedifferentiated chondrosarcoma.
METHODS: The study population consisted of 391 patients from two international sarcoma centres (development cohort) who had undergone definitive surgery for a localized high-grade (histological grade II or III) conventional primary central chondrosarcoma or dedifferentiated chondrosarcoma. Disease progression captured the first event of either metastasis or local recurrence. An independent cohort of 221 patients from three additional hospitals was used for external validation. Two nomograms were internally and externally validated for discrimination (c-index) and calibration plot.
RESULTS: In the development cohort, the CISSD at ten years was 32.9% (95% confidence interval (CI) 19.8% to 38.4%). Age at diagnosis, grade, and surgical margin were found to have significant effects on CISSD and CIDP in multivariate analyses. Maximum tumour diameter was also significantly associated with CISSD. In the development cohort, the c-indices for CISSD and CIDP at five years were 0.743 (95% CI 0.700 to 0.819) and 0.761 (95% CI 0.713 to 0.800), respectively. When applied to the validation cohort, the c-indices for CISSD and CIDP at five years were 0.839 (95% CI 0.763 to 0.916) and 0.749 (95% CI 0.672 to 0.825), respectively. The calibration plots for these two nomograms demonstrated good fit.
CONCLUSION: Our nomograms performed well on internal and external validation and can be used to predict CISSD and CIDP after resection of localized high-grade conventional primary central and dedifferentiated chondrosarcomas. They provide a new tool with which clinicians can assess and advise individual patients about their prognosis. Cite this article:

Matsumoto S, Lee SH, Imai R, et al.
Unresectable Chondrosarcomas Treated With Carbon Ion Radiotherapy: Relationship Between Dose-averaged Linear Energy Transfer and Local Recurrence.
Anticancer Res. 2020; 40(11):6429-6435 [PubMed] Related Publications
BACKGROUND/AIM: The local control rate of chondrosarcomas treated with carbon-ion radiotherapy (CIRT) worsens as tumour size increases, possibly because of the intra-tumoural linear energy transfer (LET) distribution. This study aimed to evaluate the relationship between local recurrence and intra-tumoural LET distribution in chondrosarcomas treated with CIRT.
PATIENTS AND METHODS: Thirty patients treated with CIRT for grade 2 chondrosarcoma were included. Dose-averaged LET (LET

Houdek MT, Bukowski BR, Athey AG, et al.
Comparison of reconstructive techniques following oncologic intraarticular resection of proximal humerus.
J Surg Oncol. 2021; 123(1):133-140 [PubMed] Related Publications
INTRODUCTION: The proximal humerus is a common site of primary and metastatic disease in the upper extremity. Historically, the goal of a hemiarthroplasty reconstruction was to provide a stable platform for hand and elbow function, with limited shoulder function. Techniques utilizing a reverse endoprosthesis (endoprosthetic replacement [EPR]) and allograft-prosthetic composite (APC) have been developed; however, there is a paucity of comparative studies.
METHODS: A total of 83 (42 females, 41 males) patients undergoing an intraarticular resection of the humerus were reviewed. Reconstructions included 30 reverse and 53 hemiarthroplasty; including hemiarthroplasty EPR (n = 36) and APC (n = 17), and reverse EPR (n = 20) and APC (n = 10).
RESULTS: Reverse reconstructions had improved forward elevation (85° vs. 44°, p < .001) and external rotation (30° vs. 21°; p < .001) versus a hemiarthroplasty. Reverse reconstructions had improved American Shoulder and Elbow Surgeons scores (65 vs. 57; p = .01) and Musculoskeletal Tumor Society 93 scores (72 vs. 63; p < .001) versus hemiarthroplasty. Subluxation of the reconstruction was a common (n = 23, 27%), only occurring in hemiarthroplasty patients (EPR [n = 13, 36%] and APC [n = 10, 59%]).
CONCLUSION: The current series highlights the improved functional outcome in patients undergoing reconstruction with a reverse arthroplasty compared to the traditional hemiarthroplasty. Currently reverse shoulder arthroplasty (APC or EPR) is our preferred methods of reconstruction in this patient population.

Kim H, Cho Y, Kim HS, et al.
A system-level approach identifies HIF-2α as a critical regulator of chondrosarcoma progression.
Nat Commun. 2020; 11(1):5023 [PubMed] Free Access to Full Article Related Publications
Chondrosarcomas, malignant cartilaginous neoplasms, are capable of transitioning to highly aggressive, metastatic, and treatment-refractory states, resulting in significant patient mortality. Here, we aim to uncover the transcriptional program directing such tumor progression in chondrosarcomas. We conduct weighted correlation network analysis to extract a characteristic gene module underlying chondrosarcoma malignancy. Hypoxia-inducible factor-2α (HIF-2α, encoded by EPAS1) is identified as an upstream regulator that governs the malignancy gene module. HIF-2α is upregulated in high-grade chondrosarcoma biopsies and EPAS1 gene amplification is associated with poor prognosis in chondrosarcoma patients. Using tumor xenograft mouse models, we demonstrate that HIF-2α confers chondrosarcomas the capacities required for tumor growth, local invasion, and metastasis. Meanwhile, pharmacological inhibition of HIF-2α, in conjunction with the chemotherapy agents, synergistically enhances chondrosarcoma cell apoptosis and abolishes malignant signatures of chondrosarcoma in mice. We expect that our insights into the pathogenesis of chondrosarcoma will provide guidelines for the development of molecular targeted therapeutics for chondrosarcoma.

Johnson JD, Rainer WG, Rose PS, Houdek MT
Utility of Bone Scintigraphy and PET-CT in the Surgical Staging of Skeletal Chondrosarcoma.
Anticancer Res. 2020; 40(10):5735-5738 [PubMed] Related Publications
BACKGROUND/AIM: Surgical staging is paramount to treatment of primary bone sarcomas. Often, bone scintigraphy and/or positron emission tomography-computed tomography (PET-CT) are used to exclude skeletal metastases; however, skeletal metastases in chondrosarcoma are rare. The purpose of this study was to assess the utility of these staging methods in patients with chondrosarcoma.
PATIENTS AND METHODS: We reviewed 138 (87 males, 51 female) patients, mean age 54±20 years, with a chondrosarcoma, who had completed a bone scintigraphy or PET/CT as part of surgical staging. Sensitivity, specificity, and positive/negative predictive value of the scans was calculated.
RESULTS: Seventeen (12%) patients had a positive bone scintigraphy or PET-CT for skeletal metastases. In cases of bone scintigraphy (n=11), 6 were benign and 5 were skeletal metastases. In cases of PET-CT, 6 were skeletal metastases, 3 were positive and 3 benign. All positive cases regarded dedifferentiated chondrosarcoma. The overall sensitivity and specificity of a bone scan or PET-CT was 100% and 93.1%; with a positive and negative predictive value of 47.1% and 100%, respectively.
CONCLUSION: Skeletal metastases at presentation of chondrosarcoma are rare and associated with dedifferentiated chondrosarcoma. Bone scintigraphy or PET-CT should only be performed in cases of high grade and dedifferentiated histology.

Jeong JY, Jeong W, Kim HJ
Promotion of Chondrosarcoma Cell Survival, Migration and Lymphangiogenesis by Periostin.
Anticancer Res. 2020; 40(10):5463-5469 [PubMed] Related Publications
BACKGROUND/AIM: Periostin exists as an extracellular matrix protein in several carcinomas and is related to metastasis and poor prognosis. It is mainly secreted from cancer associated fibroblasts, and not from carcinoma cells. As a tumor microenvironment component, periostin usually mediates tumor cell stemness, metastasis, angiogenesis and lymphangiogenesis. This study aimed to examine the role of periostin in chondrosarcoma.
MATERIALS AND METHODS: To evaluate the effect of periostin on the proliferation of chondrosarcoma cells, MTT assay was performed on SW1353 cells and periostin knockdown SW1353 cells. Migration activity was examined using Boyden chamber.
RESULTS: Periostin, secreted from chondrosarcoma cells, was found to support proliferation, and maintain stemness and migration of chondrosarcoma cells. Periostin also induced proliferation and migration of lymphatic endothelial cells.
CONCLUSION: Periostin plays an important role in chondrosarcoma development and disease progression.

Newman ET, van Rein EAJ, Theyskens N, et al.
Diagnoses, treatment, and oncologic outcomes in patients with calcaneal malignances: Case series, systematic literature review, and pooled cohort analysis.
J Surg Oncol. 2020; 122(8):1731-1746 [PubMed] Related Publications
BACKGROUND AND OBJECTIVES: Malignant tumors of the calcaneus are rare but pose a treatment challenge.
AIMS: (1) describe the demographics of calcaneal malignancies in a large cohort; (2) describe survival after amputation versus limb-salvage surgery for high-grade tumors.
METHODS: Study group: a "pooled" cohort of patients with primary calcaneal malignancies treated at two cancer centers (1984-2015) and systematic literature review. Kaplan-Meier analyses described survival across treatment and diagnostic groups; proportional hazards modeling assessed mortality after amputation versus limb salvage.
RESULTS: A total of 131 patients (11 treated at our centers and 120 patients from 53 published studies) with a median 36-month follow-up were included. Diagnoses included Ewing sarcoma (41%), osteosarcoma (30%), and chondrosarcoma (17%); 5-year survival rates were 43%, 73% (70%, high grade only), and 84% (60%, high grade only), respectively. Treatment involved amputation in 52%, limb salvage in 27%, and no surgery in 21%. There was no difference in mortality following limb salvage surgery (vs. amputation) for high-grade tumors (HR 0.38; 95% CI 0.14-1.05), after adjusting for Ewing sarcoma diagnosis (HR 5.15; 95% CI 1.55-17.14), metastatic disease at diagnosis (HR 3.88; 95% CI 1.29-11.64), and age (per-year HR 1.04; 95% CI 1.02-1.07).
CONCLUSIONS: Limb salvage is oncologically-feasible for calcaneal malignancies.

Roche ME, Lin Z, Whitaker-Menezes D, et al.
Translocase of the outer mitochondrial membrane complex subunit 20 (TOMM20) facilitates cancer aggressiveness and therapeutic resistance in chondrosarcoma.
Biochim Biophys Acta Mol Basis Dis. 2020; 1866(12):165962 [PubMed] Article available free on PMC after 01/12/2021 Related Publications
Chondrosarcoma is the second most common primary bone malignancy, representing one fourth of all primary bone sarcomas. It is typically resistant to radiation and chemotherapy treatments. However, the molecular mechanisms that contribute to cancer aggressiveness in chondrosarcomas remain poorly characterized. Here, we studied the role of mitochondrial transporters in chondrosarcoma aggressiveness including chemotherapy resistance. Histological grade along with stage are the most important prognostic biomarkers in chondrosarcoma. We found that high-grade human chondrosarcoma tumors have higher expression of the mitochondrial protein, translocase of the outer mitochondrial membrane complex subunit 20 (TOMM20), compared to low-grade tumors. TOMM20 overexpression in human chondrosarcoma cells induces chondrosarcoma tumor growth in vivo. TOMM20 drives proliferation, resistance to apoptosis and chemotherapy resistance. Also, TOMM20 induces markers of epithelial to mesenchymal transition (EMT) and metabolic reprogramming in these mesenchymal tumors. In conclusion, TOMM20 drives chondrosarcoma aggressiveness and resistance to chemotherapy.

Aljuboori Z, Ugiliweneza B, Wang D, et al.
Economics of the Management of Craniospinal Chordoma and Chondrosarcoma and the feasibility of the bundled payment model.
BMC Neurol. 2020; 20(1):312 [PubMed] Article available free on PMC after 01/12/2021 Related Publications
BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) created a new reimbursement model "Bundled Payment for Care Improvement (BPCI)" which reimburses providers a predetermined payment in advance to cover all possible services rendered within a certain time window. Chordoma and Chondrosarcoma are locally aggressive malignant primary bony tumors. Treatment includes surgical resection and radiotherapy with substantial risk for recurrence which necessitates monitoring and further treatment. We assessed the feasibility of the BPCI model in these neurosurgical diseases.
METHODS: We selected patients with chordoma/chondrosarcoma from inpatient admission table using the International Classification of Disease, 9th (ICD-9), and 10th (ICD-10) revision codes. We collected the patients' demographics and insurance type at the index hospitalization. We recorded the following outcomes length of stay, total payment, discharge disposition, and complications for the index hospitalization. For post-discharge, we collected the 30 days and 3/6/12 months inpatient admission, outpatient service, and medication refills. Continuous variables were summarized by means with standard deviations, median with interquartile and full ranges (minimum-maximum); Continuous outcomes were compared by nonparametric Wilcoxson rank-sum test. All tests were 2-sided with a significance level of 0.05. Statistical data analysis was performed in SAS 9.4 (SAS Institute, Inc, Cary, NC).
RESULTS: The population size was 2041 patients which included 1412 patients with cranial (group1), 343 patients with a mobile spine (group 2), and 286 patients with sacrococcygeal (group 3) chordoma and chondrosarcoma. For index hospitalization, the median length of stay (days) was 4, 6, and 7 for groups 1, 2, and 3 respectively (P<.001). The mean payments were ($58,130), ($84,854), and ($82,440), for groups 1, 2, and 3 respectively (P=.02). The complication rates were 30%, 35%, and 43% for groups 1, 2, and 3 respectively (P<.001). Twelve months post-discharge, the hospital readmission rates were 44%, 53%, and 65% for groups 1, 2, and 3, respectively (P<.001). The median payments for this period were ($72,294), ($76,827), and ($101,474), for groups 1, 2, and 3, respectively (P <.001).
CONCLUSION: The management of craniospinal chordoma and chondrosarcoma is costly and may extend over a prolonged period. The success of BPCI requires a joint effort between insurers and hospitals. Also, it should consider patients' comorbidities, the complexity of the disease. Finally, the adoptionof quality improvement programs by hospitals can help with cost reduction.

Claxton MR, Reynolds G, Wenger DE, et al.
Extraskeletal myxoid chondrosarcoma: A high incidence of metastatic disease to lymph nodes.
J Surg Oncol. 2020; 122(8):1662-1667 [PubMed] Related Publications
BACKGROUND: Extraskeletal myxoid chondrosarcoma (ESMC) is a rare type of soft-tissue sarcoma with limited series reporting outcome of treatment. Currently there is limited data on the incidence and impact on patient outcome in those with metastatic disease to lymph nodes in ESMC.
METHODS: Thirty (21 males, 9 females) patients, mean age 50 ± 16 years, with ESMC were reviewed. The tumors were most commonly located in the lower extremity (n = 23, 77%) and the mean tumor size and volume were 9 ± 5 cm and 490 ± 833 cm
RESULTS: Six (20%) patients either presented (n = 3, 10%) or developed (n = 3, 10%) lymph node metastatic disease. When comparing patients without, with lymph node metastasis and metastasis elsewhere, patients with lymph nodes metastasis had worse survival than those without metastasis, however better 10-year disease specific survival than those with metastasis elsewhere (100% vs 62% vs 0%; P < .001).
CONCLUSION: There is a high incidence of lymph node metastatic disease in patients with ESMC. Although survival in these patients is worse compared to those without metastasis, their survival is better than those with metastasis elsewhere. Due to the high incidence of lymph node metastatic disease, preoperative staging of the lymph node should be considered.

Solari D, Bove I, Esposito F, et al.
The nose lid for the endoscopic endonasal procedures during COVID-19 era: technical note.
Acta Neurochir (Wien). 2020; 162(10):2335-2339 [PubMed] Article available free on PMC after 01/12/2021 Related Publications
BACKGROUND: COVID-19 pandemic has disrupted the global health systems worldwide. According to the tremendous rate of interhuman transmission via aerosols and respiratory droplets, severe measures have been required to contain contagion spread. Accordingly, medical and surgical maneuvers involving the respiratory mucosa and, among them, transnasal transsphenoidal surgery have been charged of maximum risk of spread and contagion, above all for healthcare professionals.
METHOD: Our department, according to the actual COVID-19 protocol national guidelines, has suspended elective procedures and, in the last month, only three patients underwent to endoscopic endonasal procedures, due to urgent conditions (a pituitary apoplexy, a chondrosarcoma causing cavernous sinus syndrome, and a pituitary macroadenoma determining chiasm compression). We describe peculiar surgical technique modifications and the use of an endonasal face mask, i.e., the nose lid, to be applied to the patient during transnasal procedures for skull base pathologies as a further possible COVID-19 mitigation strategy.
RESULTS: The nose lid is cheap, promptly available, and can be easily assembled with the use of few tools available in the OR; this mask allows to both operating surgeon and his assistant to perform wider surgical maneuvers throughout the slits, without ripping it, while limiting the nostril airflow.
CONCLUSIONS: Transnasal surgery, transgressing respiratory mucosa, can definitely increase the risk of virus transmission: we find that adopting further precautions, above all limiting high-speed drill can help preventing or at least reducing aerosol/droplets. The creation of a non-rigid face mask, i.e., the nose lid, allows the comfortable introduction of instruments through one or both nostrils and, at the same time, minimizes the release of droplets from the patient's nasal cavity.

Miyakoshi N, Hongo M, Kasukawa Y, et al.
Inhibition of Autograft Bone Resorption by Antibone Resorptive Agents After Spinal Reconstruction Surgery for Extensive Cervical Chondrosarcoma: A Case Report with a 10-Year Follow-Up.
World Neurosurg. 2020; 142:239-245 [PubMed] Related Publications
BACKGROUND: For the surgical treatment of spinal malignant tumor, spinal reconstruction with bone graft and instrumentation is necessary after tumor resection, but postoperative complications, including grafted bone resorption, may arise.
CASE DESCRIPTION: A 42-year-old Asian woman presented with neck pain, tumorous masses on the neck, and left arm pain. Magnetic resonance imaging and computed tomography of the cervical spine showed extensive malignant spinal tumor. Histological examination of tumor biopsy revealed grade I chondrosarcoma. Complete resection of the tumor was performed using an anterior-posterior approach, followed by anterior iliac bone grafting and posterior spinal instrumentation. No tumor recurrence was observed on magnetic resonance imaging at final follow-up after 10 years. However, grafted bone resorption was identified immediately after surgery due to stress shielding by robust spinal instrumentation. To inhibit resorption of grafted bone, the bisphosphonate minodronate was administered for 5 years from 3 years postoperatively, before being replaced by denosumab from 8 years postoperatively. After use of these antibone resorptive agents, grafted bone resorption stopped.
CONCLUSIONS: Anteriorly grafted bone resorption due to stress shielding may occur after reconstructive cervical spine surgery with robust posterior spinal instrumentation. Bisphosphonates and denosumab may be considered to inhibit grafted bone resorption.

Lal DN, El-Zammar O, Naous R, Damron TA
Intra-articular Extraskeletal EWSR1-Negative NR4A3-Positive Myxoid Chondrosarcoma: A Case Report.
JBJS Case Connect. 2020 Apr-Jun; 10(2):e0614 [PubMed] Related Publications
CASE: Extraskeletal myxoid chondrosarcomas (EMCs) are rare soft-tissue malignancies. Intra-articular occurrence is even more rare. To our knowledge, this case is one of only 2 reported intra-articular EMC cases of the knee free of local recurrence and/or amputation at follow-up. This case is also distinctive for being fluorescence in-situ hybridization-negative for the typical EMC-balanced translocation t(9;22) which fuses EWSR1 with NR4A3, harboring instead a variant translocation resulting in fusion of NR4A3 with a less common gene fusion partner.
CONCLUSION: This is a unique case of intra-articular EMC of the knee with a rare molecular fingerprint and an unusually positive outcome.

Choi WH, Han EJ, Chang KB, Joo MW
Quantitative SPECT/CT for differentiating between enchondroma and grade I chondrosarcoma.
Sci Rep. 2020; 10(1):10587 [PubMed] Article available free on PMC after 01/12/2021 Related Publications
Although differentiation between central chondroid tumors is important, their parallelism makes it a diagnostic conundrum for clinicians and radiologists. The objective of this study was to evaluate the efficiency of quantitative single photon emission computed tomography (SPECT)/computed tomography (CT) in differentiating grade I chondrosarcomas from enchondromas. We reviewed SPECT/CT images of patients with enchondromas and grade I chondrosarcomas arising in the long bones. Volume, mean standardized uptake value (SUVmean), and maximum standardized uptake value (SUVmax) of tumors were calculated from SPECT/CT images. In addition, clinical characteristics and radiological information were assessed. Of a total of 34 patients, 14 had chondrosarcomas. Chondrosarcoma group had significantly larger volume, and higher SUVmean and SUVmax of tumors than enchondroma group. There was no significant difference in age and tumor size between two groups. Areas under the receiver-operating characteristic curve (AUCs) for tumor volume, SUVmean, and SUVmax were 0.727, 0.757, and 0.875. In pairwise analyses, SUVmax had larger AUC than SUVmean (p = 0.0216). With a cut-off value of 15.6 for SUVmax, its sensitivity and specificity were 86% and 75% for differentiating between enchondroma and grade I chondrosarcoma. Quantitative SPECT/CT is a potential method to differentiate grade I chondroarcomas from enchondromas in patients with central chondroid tumors.

Yapar A, Ulucaköy C, Sezgin EA, et al.
Diagnostic role of neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio in patients with enchondroma and low-grade chondrosarcoma.
Jt Dis Relat Surg. 2020; 31(2):286-290 [PubMed] Article available free on PMC after 01/12/2021 Related Publications
OBJECTIVES: This study aims to evaluate the role of elevated neutrophil-to-lymphocyte ratio (NLR) and monocyte-to- lymphocyte ratio (MLR) in differential diagnosis of enchondroma and low-grade chondrosarcoma.
PATIENTS AND METHODS: One-hundred-and-one patients (44 males, 57 females; mean age 53.6±11.5 years; range, 21 to 85 years) diagnosed with enchondroma and low-grade chondrosarcoma in Ankara Oncology Training and Research Hospital between January 2010 and December 2019 were included in this retrospective study. Patients' age, gender, location and type of tumor, and pre-treatment complete blood count results were acquired. One-hundred patients (48 males, 52 females; mean age 50.9±13.6 years; range, 19 to 76 years) with complete blood count results admitted to the same center for reasons other than fracture, infection or tumors with similar age and gender to the aforementioned study group were included as healthy controls.
RESULTS: Neutrophil-to-lymphocyte ratio and MLR of the study group were found to be significantly higher than the control group (p<0.001). Neutrophil-to-lymphocyte ratio and MLR held diagnostic importance with statistically significant cut-off values. Statistically significant cut-offs for NLR and MLR were ≥2.0 (sensitivity=73.3%, specificity=67%) and ≥0.2 (sensitivity=76.2%, specificity=63%), respectively. Multivariate logistic regression analysis was performed adjusting for age and gender and NLR ≥2 [odds ratio (OR)=3.1] or MLR ≥0.2 (OR=2.9) were found to be associated with approximately three-fold risk for diagnosis of enchondroma or low-grade chondrosarcoma.
CONCLUSION: The NLR and MLR have diagnostic value in cartilaginous tumors such as enchondroma and low-grade chondrosarcoma. However, our results do not support utilization of NLR and MLR as diagnostic value for differentiation of enchondroma and low-grade chondrosarcoma.

Keil L
Bone Tumors: Primary Bone Cancers.
FP Essent. 2020; 493:22-26 [PubMed] Related Publications
The three most common primary bone cancers are osteosarcoma, Ewing sarcoma, and chondrosarcoma. Osteosarcoma occurs most often in children and young adults, with a peak incidence at ages 10 to 14 years. It also can occur later in life due to malignant transformation of benign bone lesions. Osteosarcoma occurs most commonly around the knee, but can occur in other bones. Management varies depending on tumor characteristics and involves chemotherapy and surgery. Ewing sarcoma is most common in teenagers. It occurs most commonly in long bones but can occur in the pelvis and other bones. Management involves surgical resection when possible, along with chemotherapy and occasionally radiation therapy. Chondrosarcoma typically occurs in patients 40 years and older. It can occur as a primary tumor or from malignant transformation of benign bone tumors. Chondrosarcomas are relatively resistant to chemoradiation, so surgery is the standard therapy. When any of these tumors is suspected, patients should be instructed to avoid weight-bearing on the affected extremity to help prevent pathologic fracture while evaluation is completed. Imaging with x-rays and occasionally magnetic resonance imaging study are the initial diagnostic steps. If imaging suggests a primary bone cancer, prompt referral to an orthopedic oncology subspecialist is indicated.

Sofulu Ö, Erol B
Evaluation of factors affecting survival rate in primary bone sarcomas with extremity and pelvis involvement.
Acta Orthop Traumatol Turc. 2020; 54(3):234-244 [PubMed] Article available free on PMC after 01/12/2021 Related Publications
OBJECTIVE: This study is an evaluation of the overall survival rate and factors affecting survival in patients with osteosarcoma, chondrosarcoma, or Ewing's sarcoma. This study aimed to determine the effect of factors related to the preoperative period, patient, tumor, treatment, and postoperative period on survival.
METHODS: A total of 114 patients (64 male and 50 female) with osteosarcoma, chondrosarcoma, or Ewing's sarcoma treated between 2005 and 2013 were included in this study. All the patients received standard treatment and were followed up regularly. In all, 44 cases of (conventional and telangiectatic) osteosarcoma, 30 cases of Ewing's sarcoma, and 40 cases of high-grade chondrosarcoma were identified using the Bone and Soft Tissue Tumor Registry. Gender, age, tumor size and localization, pathological fractures, histopathological type, grade, surgical treatment, adjuvant treatments, relapse of the disease, and postoperative complication data were obtained from follow-up forms. The learning curve of institutional expertise was also evaluated. The patient survival rate was calculated using the Kaplan-Meier method, and log-rank statistical methods were used to compare survival rates.
RESULTS: The mean length of survival of the patients was 72 months. There was a 56% 5-year survival rate, and the event-free survival rate was 53%. The survival of patients with Ewing's sarcoma whose prodromal period was less than 12 weeks was significantly higher than that of the other groups (p=0.031). The survival of patients with tumor size greater than 150 cc, with local recurrence and distant metastases was low for all groups. Survival rates were significantly lower in osteosarcoma and Ewing's sarcoma patients with stage III tumor or metastasis at diagnosis. The survival of patients with osteosarcoma diagnosed between 2010 and 2013 was significantly higher than that of the earlier group (p=0.02).
CONCLUSION: Decreasing the prodromal period (early diagnosis) can improve survival by preventing the local and systemic spread of the tumor. Increase in the surgical experience is likely to have a positive effect on survival rates, especially for patients with osteosarcoma. The relapse of the disease is a poor prognostic factor for survival despite aggressive surgery and adjuvant therapies.
LEVEL OF EVIDENCE: Level IV, Therapeutic study.

Gitto S, Cuocolo R, Albano D, et al.
MRI radiomics-based machine-learning classification of bone chondrosarcoma.
Eur J Radiol. 2020; 128:109043 [PubMed] Related Publications
PURPOSE: To evaluate the diagnostic performance of machine learning for discrimination between low-grade and high-grade cartilaginous bone tumors based on radiomic parameters extracted from unenhanced magnetic resonance imaging (MRI).
METHODS: We retrospectively enrolled 58 patients with histologically-proven low-grade/atypical cartilaginous tumor of the appendicular skeleton (n = 26) or higher-grade chondrosarcoma (n = 32, including 16 appendicular and 16 axial lesions). They were randomly divided into training (n = 42) and test (n = 16) groups for model tuning and testing, respectively. All tumors were manually segmented on T1-weighted and T2-weighted images by drawing bidimensional regions of interest, which were used for first order and texture feature extraction. A Random Forest wrapper was employed for feature selection. The resulting dataset was used to train a locally weighted ensemble classifier (AdaboostM1). Its performance was assessed via 10-fold cross-validation on the training data and then on the previously unseen test set. Thereafter, an experienced musculoskeletal radiologist blinded to histological and radiomic data qualitatively evaluated the cartilaginous tumors in the test group.
RESULTS: After feature selection, the dataset was reduced to 4 features extracted from T1-weighted images. AdaboostM1 correctly classified 85.7 % and 75 % of the lesions in the training and test groups, respectively. The corresponding areas under the receiver operating characteristic curve were 0.85 and 0.78. The radiologist correctly graded 81.3 % of the lesions. There was no significant difference in performance between the radiologist and machine learning classifier (P = 0.453).
CONCLUSIONS: Our machine learning approach showed good diagnostic performance for classification of low-to-high grade cartilaginous bone tumors and could prove a valuable aid in preoperative tumor characterization.

Deckers C, Steyvers MJ, Hannink G, et al.
Can MRI differentiate between atypical cartilaginous tumors and high-grade chondrosarcoma? A systematic review.
Acta Orthop. 2020; 91(4):471-478 [PubMed] Related Publications
Background and purpose - Adequate staging of chondroid tumors at diagnosis is important as it determines both treatment and outcome. This systematic review provides an overview of MRI criteria used to differentiate between atypical cartilaginous tumors (ACT) and high-grade chondrosarcoma (HGCS).Patients and methods - For this systematic review PubMed and Embase were searched, from inception of the databases to July 12, 2018. All original articles describing MRI characteristics of pathologically proven primary central chondrosarcoma and ACT were included. A quality appraisal of the included papers was performed. Data on MRI characteristics and histological grade were extracted by 2 reviewers. Meta-analysis was performed if possible. The study is registered with PROSPERO, CRD42018067959.Results - Our search identified 2,132 unique records, of which 14 studies were included. 239 ACT and 140 HGCS were identified. The quality assessment showed great variability in consensus criteria used for both pathologic and radiologic diagnosis. Due to substantial heterogeneity we refrained from pooling the results in a meta-analysis and reported non-statistical syntheses. Loss of entrapped fatty marrow, cortical breakthrough, and extraosseous soft tissue expansion appeared to be present more often in HGCS compared with ACT.Interpretation - This systematic review provides an overview of MRI characteristics used to differentiate between ACT and HGCS. Future studies are needed to develop and assess more reliable imaging methods and/or features to differentiate ACT from HGCS.

Xie H, Mao JS, Hu WF
Insulin-Like Growth Factor 1 (IGF1) Pathway Member Polymorphisms Are Associated with Risk and Prognosis of Chondrosarcoma.
Med Sci Monit. 2020; 26:e923853 [PubMed] Article available free on PMC after 01/12/2021 Related Publications
BACKGROUND The insulin-like growth factor 1 (IGF1) pathway is deeply involved in cell proliferation, including tumorigenesis. Aberrant genetic alterations of IGF1 pathway members were revealed in certain malignancies, including chondrosarcoma (CHS). We proposed that genetic polymorphisms in IGF1 pathways might be associated with susceptibility to tumorigenesis and prognosis of CHS in Chinese populations. MATERIAL AND METHODS We recruited 112 pathologically diagnosed CHS cases and 104 cancer-free controls in this study. There were 5 single-nucleotide polymorphisms of IGF1 pathway members (IGF1R rs2016347, IGF1 rs1520220, IGF1 rs2946834, IGF3BP3 rs2270628, and IGF2 rs4320932) genotyped that subsequently underwent bioinformatic analyses. DNA from validated CHS cases was extracted from frozen blood samples preserved in liquid nitrogen, while DNA from tumor-free controls was extracted from fresh blood. SNP genotyping was conducted by PCR. RESULTS The variant T allele of IGF1R (rs2016347) is potentially correlated with poor outcome in patients with conventional CHS. The GT and TT genotypes of IGF1R rs2016347 predicted statistically significant higher risk of tumor metastasis and higher histological grade of CHS. CONCLUSIONS We hypothesized that IGF1 member polymorphisms are associated with chondrosarcoma. We found that genetic polymorphisms in IGF1 pathway members are associated with elevated risk and poor prognosis of conventional CHS patients in Chinese populations. IGF1R rs2016347 polymorphisms were associated with the risk of lung metastasis of CHS. The IGF1 pathway members do not appear to be involved in the tumorigenesis of CHS.

Martin SB, Reiche WS, Fifelski NA, et al.
Leucine and branched-chain amino acid metabolism contribute to the growth of bone sarcomas by regulating AMPK and mTORC1 signaling.
Biochem J. 2020; 477(9):1579-1599 [PubMed] Related Publications
Osteosarcoma and chondrosarcoma are sarcomas of the bone and the cartilage that are primarily treated by surgical intervention combined with high toxicity chemotherapy. In search of alternative metabolic approaches to address the challenges in treating bone sarcomas, we assessed the growth dependence of these cancers on leucine, one of the branched-chain amino acids (BCAAs), and BCAA metabolism. Tumor biopsies from bone sarcoma patients revealed differential expression of BCAA metabolic enzymes. The cytosolic branched-chain aminotransferase (BCATc) that is commonly overexpressed in cancer cells, was down-regulated in chondrosarcoma (SW1353) in contrast with osteosarcoma (143B) cells that expressed both BCATc and its mitochondrial isoform BCATm. Treating SW1353 cells with gabapentin, a selective inhibitor of BCATc, further revealed that these cells failed to respond to gabapentin. Application of the structural analog of leucine, N-acetyl-leucine amide (NALA) to disrupt leucine uptake, indicated that all bone sarcoma cells used leucine to support their energy metabolism and biosynthetic demands. This was evident from the increased activity of the energy sensor AMP-activated protein kinase (AMPK), down-regulation of complex 1 of the mammalian target of rapamycin (mTORC1), and reduced cell viability in response to NALA. The observed changes were most profound in the 143B cells, which appeared highly dependent on cytosolic and mitochondrial BCAA metabolism. This study thus demonstrates that bone sarcomas rely on leucine and BCAA metabolism for energy and growth; however, the differential expression of BCAA enzymes and the presence of other carbon sources may dictate how efficiently these cancer cells take advantage of BCAA metabolism.

Yang Z, Niu N, Tang J, et al.
Reconstruction of forearm support with ulnar translocation after resection of chondrosarcoma in the proximal radius.
Orthopade. 2020; 49(11):1006-1012 [PubMed] Related Publications
This is a report of the reconstructive surgery of a patient with chondrosarcoma in the proximal radius. After extensive resection of the proximal radius that contained the tumor, the skeleton of the forearm was reconstructed by ulnar translocation. This patient was followed for 2 years, no recurrence of the tumor was found and the function of the forearm was nearly normal. This case is reported and discussed and a literature review is presented.

Haralambiev L, Nitsch A, Jacoby JM, et al.
Cold Atmospheric Plasma Treatment of Chondrosarcoma Cells Affects Proliferation and Cell Membrane Permeability.
Int J Mol Sci. 2020; 21(7) [PubMed] Article available free on PMC after 01/12/2021 Related Publications
Chondrosarcoma is the second most common malign bone tumor in adults. Surgical resection of the tumor is recommended because of its resistance to clinical treatment such as chemotherapy and radiation therapy. Thus, the prognosis for patients mainly depends on sufficient surgical resection. Due to this, research on alternative therapies is needed. Cold atmospheric plasma (CAP) is an ionized gas that contains various reactive species. Previous studies have shown an anti-oncogenic potential of CAP on different cancer cell types. The current study examined the effects of treatment with CAP on two chondrosarcoma cell lines (CAL-78, SW1353). Through proliferation assay, the cell growth after CAP-treatment was determined. A strong antiproliferative effect for both cell lines was detected. By fluorescein diacetate (FDA) assay and ATP release assay, alterations in the cell membrane and associated translocation of low molecular weight particles through the cytoplasmic membrane were observed. In supernatant, the non-membrane-permeable FDA and endogenously synthesized ATP detected suggest an increased membrane permeability after CAP treatment. Similar results were shown by the dextran-uptake assay. Furthermore, fluorescence microscopic G-/F-actin assay was performed. G- and F-actin were selectively dyed, and the ratio was measured. The presented results indicate CAP-induced changes in cell membrane function and possible alterations in actin-cytoskeleton, which may contribute to the antiproliferative effects of CAP.

Soares do Brito J, Spranger A, Almeida P, et al.
Proximal Femur Chondrosarcoma Misdiagnosed as Hip Arthritis: A Case Report.
JBJS Case Connect. 2020 Jan-Mar; 10(1):e0324 [PubMed] Related Publications
CASE: A 60-year-old man presented with left hip pain, and a radiograph showed reduced joint space. During the surgical procedure for a total hip replacement, a proximal femur mass was identified and biopsy was subsequently interpreted as grade 2 chondrosarcoma. A wide resection was needed, but he developed local recurrence after 2 years and was treated with an external hemipelvectomy.
CONCLUSIONS: Chondrosarcoma does not always present with a classical clinical picture or imaging, and it can be misdiagnosed. Practitioners should be highly suspicious of malignant disease as a cause for hip pain even if there is no direct indication of a neoplasm such as chondrosarcoma.

Tap WD, Villalobos VM, Cote GM, et al.
Phase I Study of the Mutant IDH1 Inhibitor Ivosidenib: Safety and Clinical Activity in Patients With Advanced Chondrosarcoma.
J Clin Oncol. 2020; 38(15):1693-1701 [PubMed] Article available free on PMC after 20/05/2021 Related Publications
PURPOSE: Surgery is the primary therapy for localized chondrosarcoma; for locally advanced and/or metastatic disease, no known effective systemic therapy exists. Mutations in the isocitrate dehydrogenase 1/2 (IDH1/2) enzymes occur in up to 65% of chondrosarcomas, resulting in accumulation of the oncometabolite D-2-hydroxyglutarate (2-HG). Ivosidenib (AG-120) is a selective inhibitor of mutant IDH1 approved in the United States for specific cases of acute myeloid leukemia. We report outcomes of patients with advanced chondrosarcoma in an ongoing study exploring ivosidenib treatment.
PATIENTS AND METHODS: This phase I multicenter open-label dose-escalation and expansion study of ivosidenib monotherapy enrolled patients with mutant
RESULTS: Twenty-one patients (escalation, n = 12; expansion, n = 9) with advanced chondrosarcoma received ivosidenib (women, n = 8; median age, 55 years; range, 30-88 years; 11 had received prior systemic therapy). Treatment-emergent adverse events (AEs) were mostly grade 1 or 2. Twelve patients experienced grade ≥ 3 AEs; only one event was judged treatment related (hypophosphatemia, n = 1). Plasma 2-HG levels decreased substantially in all patients (range, 14%-94.2%), to levels seen in healthy individuals. Median progression-free survival (PFS) was 5.6 months (95% CI, 1.9 to 7.4 months); the PFS rate at 6 months was 39.5%. Eleven (52%) of 21 patients experienced stable disease.
CONCLUSION: In patients with chondrosarcoma, ivosidenib showed minimal toxicity, substantial 2-HG reduction, and durable disease control. Future studies of ivosidenib monotherapy or rational combination approaches should be considered in patients with advanced mutant

Song K, Lin K, Guan H, Li F
Conditional Survival Analysis for Spinal Chondrosarcoma Patients After Surgical Resection.
Spine (Phila Pa 1976). 2020; 45(16):1110-1117 [PubMed] Related Publications
STUDY DESIGN: Retrospective analysis.
OBJECTIVE: To evaluate conditional survival after surgical resection for spinal chondrosarcoma patients.
SUMMARY OF BACKGROUND DATA: Survival estimates are usually reported as survival from the time of surgery, but survival probabilities can change over time. Conditional survival, which is a measure of prognosis for patients who have survived a defined period of time, may be more clinically precise and relevant. However, data on conditional survival for spinal chondrosarcoma patients after surgical resection are still lacking.
METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database to identify 436 spinal chondrosarcoma patients who underwent surgical resection from 1994 and 2013. Kaplan-Meier analyses and Cox regression modeling were performed to evaluate prognostic factors associated with overall survival. Five-year conditional survival (i.e., probability of surviving an additional 5 years, given that a patient has already survived x years) was calculated as 5-CS(x) = OS(x+5)/OS(x). The effect of prognostic factors on conditional survival was also explored.
RESULTS: Four hundred thirty six patients were included in the study cohort. Overall, 1-, 3-, and 5-year overall survival were 92.8%, 79.1%, and 70.3%, respectively. Five-year conditional survival at 1, 3, and 5 years after surgery were 72.9%, 79.0%, and 87.5%. The overall survival rates were lower in cases of age more than or equal to 60 years, male patient, dedifferentiated subtype, Grade III tumor, tumor size more than or equal to 10 cm, distant metastasis, and radiotherapy. Conditional survival improved over time in each subgroup divided by age, sex, race, year of diagnosis, grade, tumor size, extent of disease (EOD), and radiotherapy. In addition, patients with the least favorable prognosis at baseline experienced the greatest increase in 5-year conditional survival over time (e.g., Grade I/II: 78.0%-89.7%, Δ11.7% vs. Grade III: 36.5%-66.6%, Δ30.1%; Localized/Regional: 72.9%-88.1%, Δ15.2% vs. Distant: 43.5%-74.1%, Δ30.6%).
CONCLUSION: Conditional survival for spinal chondrosarcoma patients after surgical resection improves over time, especially for patients with initial high-risk characteristics. Information derived from conditional survival analysis may provide individualized approaches to surveillance and treatment of spinal chondrosarcoma.

Carretta A, Ciriaco P, Bandiera A, et al.
Therapeutic strategy for tracheal chondrosarcoma: report of two cases.
Monaldi Arch Chest Dis. 2020; 90(1) [PubMed] Related Publications
Primary chondrosarcoma of the trachea is an extremely rare tumor. We report two cases of tracheal chondrosarcoma describing the role of surgical and conservative treatment. Endoscopic treatment with rigid bronchoscopy was performed in both patients to restore airway patency and obtain histological specimens for diagnosis. One of the patients subsequently underwent successful tracheal resection and reconstruction. The other patient, who had a contraindication to surgical treatment due to associated diseases underwent iterative endoscopic LASER treatment and is alive three years after the first diagnosis. Surgical treatment remains the treatment of choice of tracheal chondrosarcoma. When surgery is contraindicated endoscopic treatment may allow relatively longterm survival due to the slow growth of these tumors.

El Abiad JM, Robbins SM, Cohen B, et al.
Natural history of Ollier disease and Maffucci syndrome: Patient survey and review of clinical literature.
Am J Med Genet A. 2020; 182(5):1093-1103 [PubMed] Related Publications
Ollier disease (OD) and Maffucci syndrome (MS) are characterized by multiple enchondromas. Patients with MS also have benign vascular overgrowths that become malignant in 8.5% of cases. OD is characterized by multiple enchondromas, typically unilateral in distribution with a predilection for the appendicular skeleton. MS is characterized by multiple enchondromas bilaterally distributed in most of the cases. Both disorders feature multiple swellings on the extremity, deformity around the joints, limitations in joint mobility, scoliosis, bone shortening, leg-length discrepancy, gait disturbances, pain, loss of function, and pathological fractures. About 50% of patients with OD or MS develop a malignancy, such as chondrosarcoma, glioma, and ovarian juvenile granulosa cell tumor. To better understand the natural history of OD and MS, we reviewed 287 papers describing patients with OD and MS. We also created a survey that was distributed directly to 162 patients through Facebook. Here, we compare the review of the cases described in the literature to the survey's responses. The review of the literature showed that: the patients with OD are diagnosed at a younger age; the prevalence of chondrosarcomas among patients with OD or MS was ~30%; in four patients, vascular anomalies were identified in internal organs only; and, the prevalence of cancer among patients with OD or MS was ~50%. With these data, health care providers will better understand the natural history, severity, and prognosis of these diseases and the prevalence of malignancies in these patients. Here, we recommend new guidelines for the care of patients with OD and MS.

Thorkildsen J, Taksdal I, Bjerkehagen B, et al.
Risk stratification for central conventional chondrosarcoma of bone: A novel system predicting risk of metastasis and death in the Cancer Registry of Norway cohort.
J Surg Oncol. 2020; 121(7):1115-1125 [PubMed] Related Publications
BACKGROUND AND OBJECTIVES: Interobserver variability in histological grading of central conventional chondrosarcoma (CCCS) limits the quality of patient information and research progression. We aim to quantify known and new prognostic variables and propose a risk stratification model.
METHOD: We selected 149 cases from the Cancer Registry of Norway. Cox proportional hazard models were estimated. Based on these results a dichotomous risk classification was proposed and presented by Kaplan-Meier estimates for rates of local recurrence, metastasis, and disease-specific survival.
RESULTS: The influence of axial skeletal location (Hazard ratio [HR] = 19.06), a soft tissue component ≥1 cm (HR = 13.45), and histological grade 3 (HR = 16.46) are all significant in predicting the rate of metastasis. The creation of a variable combining axial skeletal location and a soft tissue component ≥1 cm strongly predicts the risk of metastasis (HR = 14.02; P < .001) and death (HR = 2.74; P = .030) at multivariate analysis, making the histological grade insignificant. Together with metastasis at diagnosis (HR = 285.65; P < .001), this forms the basis of our proposed risk stratification, producing a small high-risk group (39 cases with 33% risk of metastasis) and a large low-risk group (103 cases with 2% risk of metastasis) without a histological grade.
CONCLUSION: Axial skeletal location and a soft tissue component ≥1 cm combined divides a CCCS cohort into low- and high-risk groups without a histological grade.

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