Chondrosarcoma Patients Research Articles

The novel dynamic nomogram and risk classification system constructed for predicting post-surgical overall survival and mortality risk in primary chondrosarcoma: a population study based on SEER database.

Surgery is the predominant method to improve the prognosis of primary chondrosarcoma patients. We aimed to construct the first reliable nomogram to predict the post-surgical overall survival (OS) of primary chondrosarcoma patients. We downloaded all primary chondrosarcoma patients treated with surgery between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database, and randomized them into training set (60%) and validation set (40%). Cox proportional regression analysis was applied to the training set to identify independent prognostic variables, and then constructed a nomogram for predicting 3-, 5-, and 8-year OS. The Harrell's concordance index (C-index), receiver operating characteristic curve (ROC), the area under curve (AUC), calibration curve and decision curve analysis (DCA) was used to assess the predictive efficacy and clinical applicability of the nomogram. The nomogram was also compared with The American Joint Committee on Cancer (AJCC) staging system. A total of 1005 post-surgical primary chondrosarcoma patients were included in this study. We finally identified five independent prognostic variables to construct the nomogram, being age, grade, tumor size, disease stage and histological type. The C-index results showed that the prediction performance of the nomogram was significantly better than the AJCC staging system. In the training set, (C-index: 0.805, 95% CI 0.879-0.730 vs 0.686, 95% CI 0.606-0.766); in the validation set, (C-index: 0.811, 95% CI 0.895-0.727 vs 0.697, 95% CI 0.647-0.799). Additionally, the AUC values generated by the ROC were all greater than 0.8, which also indicated the excellent predictive performance of the nomogram. The calibration curves showed that the predicted survival rate was highly similar to the actual. Time-dependent ROC and DCA showed that the nomogram has better predictive performance and net clinical benefits than the AJCC staging system. Finally, a risk stratification system based on nomogram was constructed. We successfully constructed and validated the first nomogram that could reliably predict 3-, 5-, and 8-year post-surgical OS in primary chondrosarcoma patients. Furthermore, the web-based dynamic nomogram could be more conveniently applied to clinic, providing assistance to surgeons and patients.

Evaluation of Local Recurrence and Diagnostic Discordance in Chondrosarcoma Patients Undergoing Preoperative Biopsy.

Preoperative biopsy of chondroid lesions has demonstrated discordance between biopsy grade and surgical resection grade. Furthermore, there is evidence to suggest risk of tumor contamination during biopsy. We evaluated our large chondrosarcoma institutional cohort to compare the rates of local recurrence based on pre-surgical biopsy, as well as other tumor characteristics and disease-related outcomes. This was a retrospective review of patients who underwent surgical resection for chondrosarcoma at our Institution between 2005 and 2020. Outcomes included rates of local recurrence, metastasis, and overall survival. No significant differences were found in local recurrence and recurrence-free survival in cases of pre-operative biopsy. Thirteen (28.2%) patients had discordance between histological grade on biopsy and resection. Seven (63.6%) patients with dedifferentiation present on final resection were not identified on biopsy. The only independent predictor of recurrence-free survival and metastasis-free survival was the presence of dedifferentiation on resection. To our knowledge, this is the first study evaluating risk of local recurrence in the setting of pre-surgical biopsy in chondrosarcoma patients. Although pre-operative biopsy may contaminate biopsy tracts, appropriate surgical planning and final resection results in no difference in local recurrence rates in this cohort. However, discordance rates between preoperative biopsy and resected specimen must be considered while determining clinical treatment.

Delay in Diagnosis and Treatment of Primary Bone Tumors

Background. Delay in the diagnosis and treatment of bone tumors continues to be a common problem. Prolonged diagnosis can significantly reduce the chances of successful treatment of the disease. Accordingly, the aim of this study was to assess the delay in the diagnosis of primary bone tumors, identify the most common symptoms and analyze the course of the diagnostic and therapeutic path.Material and methods. Thirty-two (K=18; M=14) patients treated surgically for primary bone tumors were included in the retrospective study. Patient records were analyzed. Delay in diagnosis was defined as the time from the onset of symptoms to the initial diagnosis and referral to an orthopedic oncology center.Results. The median delay in diagnosis was 7 (3-12) months. For tumors located in the pelvis, the delay was 10 months, compared to 5 months for the upper limb and 7 months for the lower limb (p=0.2312). The delay was 6 months In patients with osteosarcoma, and 8 months in chondrosarcoma patients (p=0.1786). At the first office visit, an x-ray was ordered in 19 cases (59.4%), of whom 9 patients (47.4%) were referred on to the oncology center. The most common symptoms were pain in the affected area (90.6%), limited mobility (28.1%) and pathological fracture (25%). After admission to an orthopedic department, a biopsy was performed after 5.5 (3-8.2) days. The histology results were ready after another 14 (8-18) days, and surgical treatment was performed after 95 (76-100) days.Conclusions. 1. Although patients show typical symptoms of bone tumors, only a small proportion are referred directly to an oncology center. After a primary bone tumor is suspected, further diagnostic and therapeutic activities proceed efficiently, in accordance with the current guidelines.

Chondrosarcoma: an analysis of clinical characteristics, treatment outcomes, and prognostic factors in a decade-long single center experience

Aim: Management of chondrosarcoma patients is associated with histologic subtypes and clinical behaviors. This study describes our institution's management and outcome experience for 12 chondrosarcoma patients with higher grades in rarer locations. Materials and Methods: Pathologically diagnosed chondrosarcoma patients between January 2013 and January 2023 were retrospectively scanned. Patients under 18 years, duplicate records, second primary malignancy, index surgery at another hospital were excluded, and data of remaining 12 patients were statistically analyzed. Results: Twelve patients (6 female, 6 male) had median age of 62 (21-94) years. Locations of primary tumors were femur (n=4), larynx (n=1), left gluteus (n=1), lung (n=1), periscapular soft tissue (n=1), tarsal bone (n=1), distal metacarps (n=1), scapula (n=1), and sternum (n=1). There were local relapses in three cases (chest wall, ipsilateral femur, acetabulum, and ipsilateral gluteal region) and distant metastasis in three cases (contralateral lung, lung, bilateral lung, and pleura) during the follow-up. The median tumor size was 5.65cm (1.5-21.5cm). Histologic subtypes were Chondrosarcoma (Grade I) (n=4), Chondrosarcoma (Grade II) (n=1), Chondrosarcoma (Grade III) (n=2), Dedifferentiated Chondrosarcoma (Grade III) (n=2), Extraskeletal Mesenchymal Chondrosarcoma (n=3). Surgical treatment was eight wide resections, one lobectomy, one laryngectomy, one amputation, and one curettage. Five patients received chemotherapy (2 neoadjuvant chemotherapy, 3 adjuvant chemotherapy), two patients received low dose (50.4Gy) (3DCRT; IMRT), and two patients received high dose (>60Gy) (IMRT) adjuvant radiation therapy. The median follow-up was 26.5 months (2-121 months). The median survival was 26.5 months (2-121 months). Median relapse-free survival was three months (0-96 months). The overall and relapse-free survivals at two years were 81.5% and 50%; at five years, 71.3% and 25%. Conclusion: Our results demonstrate that surgery is the gold standard treatment, but well-managed adjuvant oncologic treatment provides undeniable advantage for overall survival in selected cases.

Association of FBXW11 levels with tumor development and prognosis in chondrosarcoma.

The E3 ubiquitin ligase FBXW11 exerts an oncogenic or tumor suppressive function in a cellular context-dependent manner. However, the clinical significance and biological role of FBXW11 in chondrosarcoma have not been clearly characterized. This study focuses on the expression profile, prognostic value and biological function of FBXW11 in chondrosarcoma. FBXW11 expression was analyzed by qRT-PCR and Western blot in six cases of chondrosarcoma specimens and the matched adjacent non-tumor tissues. The expression profile and prognostic value of FBXW11 were investigated in sixty-three cases of chondrosarcoma patients. Cell viability, colony formation, migration, invasion and apoptosis assays were further detected in SW1353 chondrosarcoma cells with restored FBXW11 expression. Downregulation of FBXW11 was remarkably detected in human chondrosarcoma specimens compared with the corresponding non-tumor tissues and benign cartilage tumors. Downregulated FBXW11 expression significantly correlated with high-grade chondrosarcoma and poor prognosis. Furthermore, FBXW11 was identified as an independent prognostic factor for the overall survival of chondrosarcoma patients. Restored expression of FBXW11 significantly suppressed chondrosarcoma cell growth and induced apoptosis. These findings establish that FBXW11 was markedly downregulated and recognized as an independent prognostic factor for patients with chondrosarcoma, and restored FBXW11 expression can suppress chondrosarcoma growth and induce apoptosis, highlighting a novel biological marker and potential therapeutic target against chondrosarcoma.

The Epidemiology of Chondrosarcoma in Iran Based on Iran National Cancer Registry

Background: Chondrosarcoma is regarded as the second most common primary bone malignancy following osteosarcoma. Objectives: The present study aimed at determining the epidemiology, incidence, and survival rate of chondrosarcoma in the Iranian population, according to the Iran National Cancer Registry (INCR). Methods: In an epidemiological study, patients with limb chondrosarcoma were evaluated based on INCR data between 2008 and 2015. Data included patients’ demographic characteristics, date of diagnosis, location of the tumor, patient’s survival, and type of tumor based on the International Classification of Diseases for Oncology (ICD-O-3; first revision, third edition) were collected and analyzed. Results: Out of 732 enrolled patients, 425 patients (58.06%) were male and 307 (41.94%) were female with a mean age of 44.08 (SD = 19.31) and 45.06 (SD = 18.72), respectively. Age-standardized incidence rates (ASIR) were 1.73 and 1.27 per 1 million person-years for males and females, respectively. Conventional chondrosarcoma was the most common subtype with ASIR 1.28 and constituted 84.7% of patients with chondrosarcoma. About 71.03% of all Chondrosarcoma patients (70.35% of males and 71.99% of females) were between 20 to 59 years old. The 1-, 3-, 5-, and 7-year survival rates of patients were 0.87, 0.73, 0.57, and 0.47, respectively. Also, the mean survival time was 6.12 years (95% CI: 5.85 - 7.39). Conclusions: The incidence of chondrosarcoma in Iran is not as high as in other countries, but as patients are younger in Iran, the survival rate is worse compared to other countries. Therefore, better case findings and better care are needed to improve the patients' outcomes in Iran.

Deep learning models for predicting the survival of patients with chondrosarcoma based on a surveillance, epidemiology, and end results analysis.

BackgroundAccurate prediction of prognosis is critical for therapeutic decisions in chondrosarcoma patients. Several prognostic models have been created utilizing multivariate Cox regression or binary classification-based machine learning approaches to predict the 3- and 5-year survival of patients with chondrosarcoma, but few studies have investigated the results of combining deep learning with time-to-event prediction. Compared with simplifying the prediction as a binary classification problem, modeling the probability of an event as a function of time by combining it with deep learning can provide better accuracy and flexibility.Materials and methodsPatients with the diagnosis of chondrosarcoma between 2000 and 2018 were extracted from the Surveillance, Epidemiology, and End Results (SEER) registry. Three algorithms—two based on neural networks (DeepSurv, neural multi-task logistic regression [NMTLR]) and one on ensemble learning (random survival forest [RSF])—were selected for training. Meanwhile, a multivariate Cox proportional hazards (CoxPH) model was also constructed for comparison. The dataset was randomly divided into training and testing datasets at a ratio of 7:3. Hyperparameter tuning was conducted through a 1000-repeated random search with 5-fold cross-validation on the training dataset. The model performance was assessed using the concordance index (C-index), Brier score, and Integrated Brier Score (IBS). The accuracy of predicting 1-, 3-, 5- and 10-year survival was evaluated using receiver operating characteristic curves (ROC), calibration curves, and the area under the ROC curves (AUC).ResultsA total of 3145 patients were finally enrolled in our study. The mean age at diagnosis was 52 ± 18 years, 1662 of the 3145 patients were male (53%), and mean survival time was 83 ± 67 months. Two deep learning models outperformed the RSF and classical CoxPH models, with the C-index on test datasets achieving values of 0.832 (DeepSurv) and 0.821 (NMTLR). The DeepSurv model produced better accuracy and calibrated survival estimates in predicting 1-, 3- 5- and 10-year survival (AUC:0.895-0.937). We deployed the DeepSurv model as a web application for use in clinical practice; it can be accessed through https://share.streamlit.io/whuh-ml/chondrosarcoma/Predict/app.py.ConclusionsTime-to-event prediction models based on deep learning algorithms are successful in predicting chondrosarcoma prognosis, with DeepSurv producing the best discriminative performance and calibration.

Extraskeletal myxoid chondrosarcoma: Clinicopathological features and outcomes from the United States sarcoma collaborative database.

This investigation described clinicopathological features and outcomes of extraskeletal myxoid chondrosarcoma (EMC) patients. EMC patients were identified from the United States Sarcoma Collaborative database between 2000 and 2016. Overall survival (OS) and recurrence-free survival (RFS) were calculated, and prognostic factors were analyzed. Sixty individuals with a mean age of 55 years were included, and 65.0% (n = 39) were male. 73.3% (n = 44) had a primary tumor. A total of 41.6% (n = 25) developed tumor relapse following resection. The locoregional recurrence rate was 30.0% (n = 18/60), and mean follow-up was 42.7 months. The 5-year OS was 71.0%, while the 5-year RFS was 41.4%. On multivariate analysis for all EMC, chemotherapy (hazard ratio[HR], 6.054; 95% confidence interval [CI], 1.33-27.7; p = 0.020) and radiation (HR, 5.07, 95% CI, 1.3-20.1; p = 0.021) were independently predictive of a worse RFS. Among patients with primary EMC only, the 5-year OS was 85.3%, with a 30.0% (n = 12) locoregional recurrence rate, though no significant prognostic factors were identified. Long-term survival with EMC is probable, however there exists a high incidence of locoregional recurrence. While chemotherapy and radiation were associated with a worse RFS, these findings were likely confounded by recurrent disease as significance was lost in the primary EMC-only subset.

Chondrosarcoma patient characteristics, management, and outcomes based on over 5,000 cases from the National Cancer Database (NCDB).

IntroductionChondrosarcoma, although relatively uncommon, represents a significant percentage of primary osseous tumors. Nonetheless, there are few large-cohort, longitudinal studies of long-term survival and treatment outcomes of chondrosarcoma patients and none using the National Cancer Database (NCDB).MethodsChondrosarcoma patients were identified from the 2004–2015 NCDB datasets and divided on three primary tumor sites: appendicular, axial, and other. Demographic, treatment, and long-term survival data were determined for each group. Multivariate Cox analysis and Kaplan-Meier survival curves were generated to assess long-term survival over time for each.ResultsIn total, 5,329 chondrosarcoma patients were identified, of which 2,686 were appendicular and 1,616 were axial. Survival was higher among the appendicular cohort than axial at 1-year, 5-year, and 10-year (89.52%, 75.76%, and 65.24%, respectively). Multivariate Cox analysis identified patients in the appendicular cohort to have significantly greater likelihood of death with increasing age category, distant metastases at presentation, and male sex (p<0.001 for each). Best outcomes for seen for those undergoing surgical treatment (p<0.001). Patients in the axial cohort were with increased likelihood of death with increasing age category and distant metastases (p<0.001), while surgical treatment with or without radiation were associated with a significant decrease (p<0.001). Kaplan-Meier survival analysis showed worst survival for the axial cohort (p<0.001) and patients with distant metastases at presentation (p<0.001). Survival was not significantly different between older (2004–2007) and more recent years (2012–2016) (p = 0.742).ConclusionsFor both appendicular and axial chondrosarcomas, surgical treatment remains the mainstay of treatment due to its continued superiority for the long-term survival of patients, although advancements in survival over the last decade have been insignificant. Presence of distant metastases and axial involvement are significant, poor prognostic factors perhaps because of difficulty in surgical excision or extent of disease.

Abstract LB200: Pdgf/Pi3k/akt axis activation by hey1-ncoa2 fusion and potential target in the treatment of mesenchymal chondrosarcoma

Abstract Mesenchymal chondrosarcoma is a rare and often aggressive cancer mostly affecting children and young adults. Genetically, this tumor is mainly characterized by the recurrent HEY1-NCOA2 fusion. Localized tumor is managed surgically; traditional chemotherapy and radiation therapy, however, did not appear to substantially improve the event-free survival rate of mesenchymal chondrosarcoma patients. It is clear that better therapeutic options are needed for the treatment of this tumor. In our previous study, an in vitro model for studying mesenchymal chondrosarcoma tumorigenesis was developed using stably transduced iPSC-derived mesenchymal stem cells (iPSC-MSCs) with inducible-expression of HEY1-NCOA2. With the in vitro model, we performed genome-wide chromatin immunoprecipitation sequencing (ChIP-seq) and RNA-seq to identify HEY1-NCOA2-dependent transcriptional regulation and demonstrated the dramatic activation of PDGF-PDGFR and PI3K-AKT signaling pathways (manuscript in review). Our data also suggested that PDGFB is one of the direct targets of HEY1-NCOA2 fusion protein. In the present study, with the in vitro iPSC-MSC model, we verified that HEY1-NCOA2 fusion protein, but not wild-type HEY1 or NCOA2, dramatically increased phospho-AKT (Ser473, a readout of PI3K) expression by western blotting. Further on, we tested the effect of two kinase inhibitors CP-673451 and PF-04691502, a potent and selective PDGFR inhibitor and the mTOR/PI3K inhibitor, respectively. Stably transfused iPSC-MSC were treated with the kinase inhibitors, respectively, at different dosages (0.1 µM, 0.5 µM and 1.0 µM) for one week. At the concentration of 1.0 µM, CP-673451 efficiently suppressed AKT phosphorylation by ~23% as well as suppressed cell growth by ~67% which is significantly higher than that observed in the controls (e.g. ~20% suppression in HEY1- and NCOA2- expression iPSC-MSCs). Similarly, at the concentration of 0.5 µM, PF-04691502 suppressed the HEY1-NCOA2-expression iPSC-MSCs growth by ~24% more than that in the control (p=0.02). In summary, both CP-673451 and PF-04691502 were active against the in vitro mesenchymal chondrosarcoma model tested. Based on these data, the potential benefit of targeting PDGF/PI3K/AKT signaling pathways in the treatment of mesenchymal chondrosarcoma was suggested. Citation Format: Wenqing Qi, Lu Wang. Pdgf/Pi3k/akt axis activation by hey1-ncoa2 fusion and potential target in the treatment of mesenchymal chondrosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB200.

Surgical subtype and survival in stage I chondrosarcoma: A National Cancer Database (NCDB) analysis.

e23502 Background: Chondrosarcoma is one of the most common primary malignancies of bone and commonly presents in adults in its early stages. Standard of care for chondrosarcoma is currently surgical intervention, with radiation therapy for cases where complete resection is not possible; chemotherapy is minimally effective. To the authors’ knowledge, there is little literature regarding different surgical subtypes for chondrosarcoma patients. To address this, the aim of our study is to assess survival outcomes in stage I chondrosarcoma patients based off of different surgical subtypes. Methods: Using the NCDB, patients diagnosed with stage I chondrosarcoma between 2004-2018 were identified using ICD-O-3 histology codes 9220 and 9221. The cohort was analyzed to determine if they received any form of surgical intervention and which surgical subtype they received. We then performed univariate analysis to assess patient length of survival for each surgical subtype. Data was analyzed using SPSS and statistical significance was set at α = 0.05. Results: A total of 5186 patients were included that had survival data, of which 4752 received surgical intervention. The mean survival time was 152.1 months for all patients. Surgical patients survived an average of 156.6 months while nonsurgical patients survived just 97.7 months (p &lt; .0001). Analysis of surgical types revealed local destruction and local excision had the longest mean survival but were not different from each other (p &gt; .05). Local excision had significantly longer survival than radical excision with limb sparing (p &lt; .05). Local, partial, and radical excision all resulted in longer survival than limb and major amputations (all p &lt; .01). Patients who underwent major amputation survived longer than limb amputation, but this difference was not significant (p &gt; .05). Conclusions: This study found that receipt of surgery is associated with improved survival in chondrosarcoma patients. Receiving different surgical interventions may influence survival as patients receiving local excision survived longer than radical excision with limb sparing. Future studies should investigate additional variables that may influence receipt of surgery such as patient demographics, insurance status, and treatment facility type.[Table: see text]

Anlotinib for Recurrent or Metastatic Primary Malignant Bone Tumor: A Multicenter, Single-Arm Trial.

ObjectiveAnlotinib, a novel multitarget kinase inhibitor of VEGFR, FGFR, PDGFR and c-Kit, has proven to be effective and safe for refractory soft tissue sarcoma patients, but has not been examined in recurrent or metastatic primary malignant bone tumors in a clinical trial setting.MethodsThis is a multicenter single-arm trial. Patients with pathologically proven recurrent or metastatic primary malignant bone tumors were eligible. Anlotinib was administered orally at 12 mg per day. Each cycle consisted of 2 weeks of treatment followed by 1-week off-treatment. The primary endpoint was progression-free survival (PFS), as assessed in the intention-to-treat (ITT) population. Secondary endpoints included objective response rate (ORR), disease control rate (DCR) and overall survival (OS). Adverse events (AEs) were assessed per NCI CTCAE version 4.03.ResultsA total of 42 patients were enrolled. Median PFS was 5.3 months (95% CI 3.5-8.4 months) in the overall analysis, 4.8 months (95%CI 3.5-7.1 months) in osteosarcoma patients and 2.8 months [95%CI 1.3 months to not reached (NR)] in chondrosarcoma patients. The median OS was 11.4 months (95% CI 10.1 months to NR) in the overall analysis, not reached (95% CI, NR, NR) in osteosarcoma patients and 11.4 months (95% CI 1.8 to 21.1 months) in chondrosarcoma patients. The ORR was 9.52% and DCR was 78.57%. Grade 3 or above AEs occurred in 54.76% of the patients, and included hypertension (19.05%), hypertriglyceridemia (9.52%) and pustulosis palmaris et plantaris (7.14%). No treatment-related death was reported.ConclusionAnlotinib demonstrated promising antitumor activities in recurrent or metastatic primary malignant bone tumors with manageable AEs.

LIM and SH3 protein 1 (LASP1) differentiates malignant chordomas from less malignant chondrosarcomas

PurposeChordomas are malignant tumors that develop along the neuraxis between skull-base and sacrum. Chondrosarcomas show similarities with chordomas, yet show less malignant behavior. LIM and SH3 protein 1 (LASP1) is a cytoskeletal protein known to promote the malignant behavior of tumors. LASP1 was previously identified as a possibly overexpressed protein in a chordoma proteomics experiment. In this study we compare LASP1 expression in chordoma and chondrosarcoma tissue.MethodsBiopsies of primary tumors were collected from surgically treated chordoma (n = 6) and chondrosarcoma (n = 6) patients, flash-frozen upon collection and collectively analyzed for LASP1 RNA (real-time PCR) and protein expression (western blotting). Additionally, tissue micro array (TMA)-based immunohistochemistry was applied to an archive of 31 chordoma and 1 chondrosarcoma specimen.ResultsIn chordoma samples, LASP1 mRNA was detected in 4/6 cases and a strong 36 kDa immunoreactive protein band was observed in 4/5 cases. In contrast, 0/6 chondrosarcoma samples showed detectable levels of LASP1 mRNA and only a weak 36 kDa band was observed in 4/5 cases. Immunohistochemical analysis showed LASP1 expression in all chordoma samples, whereas chondrosarcoma specimen did not show immunoreactivity.ConclusionLASP1 is strongly expressed in the majority of chordoma cases and shows low expression in chondrosarcoma tissue. Since LASP1 is known to function as oncogene and regulate cell proliferation in other tumor types, this study implicates a role for LASP1 in chordoma biology. Further studies are warranted to improve understanding of LASP1’s expression and functioning within chordoma, both in vitro and in vivo.

Risk Analysis of Distal Metastasis in Chondrosarcoma and the Development and Validation of a Novel Clinical Prediction Model: A Clinical Study Based on the SEER Database

Purpose. Distal metastasis in chondrosarcoma is associated with a poor prognosis. The aim of this study was to develop and validate columnar maps to predict the risk of distal metastasis in patients with chondrosarcoma, thereby contributing to clinical diagnosis and treatment. Methods. Data from chondrosarcoma patients obtained from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2016 were then screened by univariate and multifactorial logistic regressions to construct a predictive distal metastasis risk. The model discrimination of nomogram was assessed by calibration plots, while the predictive accuracy and clinical values were measured by decision curve analysis (DCA). In addition, predictive column line plots were validated in an in-house test set. Results. A total of 1,290 patients were included and randomized in a 7 to 3 ratio into a training group (n = 906) and a test group (n = 384). After logistic regression analysis, the significant variables were gender, tumor pathological grade, laterality, primary tumor stage, regional lymph node metastasis, surgical treatment, and chemotherapy. Calibration curves showed agreement between column line graph predictions and actual observations, while DCA showed the clinical utility of the nomogram. In addition, ROC showed good discrimination and calibration in the training (AUC = 0.937, 95% CI 0.919–0.952) and validation groups (AUC = 0.91, 95% CI 0.877–0.937). Conclusions. The nomogram for distal metastasis risk in patients with chondrosarcoma can effectively predict the individualized risk of distal metastasis and provide clinicians with enlightening information to optimize treatment options.

New Approach against Chondrosoma Cells-Cold Plasma Treatment Inhibits Cell Motility and Metabolism, and Leads to Apoptosis.

(1) Background: Chondrosarcoma (CS) is a malignant primary bone tumor with a cartilaginous origin. Its slow cell division and severely restricted vascularization are responsible for its poor responsiveness to chemotherapy and radiotherapy. The decisive factor for the prognosis of CS patients is the only adequate therapy—surgical resection. Cold atmospheric pressure plasma (CAP) is emerging as a new option in anti-cancer therapy. Its effect on chondrosarcomas has been poorly investigated. (2) Methods: Two CS cell lines—SW 1353 and CAL 78—were used. Various assays, such as cell growth kinetics, glucose uptake, and metabolic activity assay, along with two different apoptosis assays were performed after CAP treatment. A radius cell migration assay was used to examine cell motility. (3) Results: Both cell lines showed different growth behavior, which was taken into account when using the assays. After CAP treatment, a reduction in metabolic activity was observed in both cell lines. The immediate effect of CAP showed a reduction in cell numbers and in influence on this cell line’s growth rate. The measurement of the glucose concentration in the cell culture medium showed an increase after CAP treatment. Live-dead cell imaging shows an increase in the proportion of dead cells over the incubation time for both cell lines. There was a significant increase in apoptotic signals after 48 h and 72 h for both cell lines in both assays. The migration assay showed that CAP treatment inhibited the motility of chondrosarcoma cells. The effects in all experiments were related to the duration of CAP exposure. (4) Conclusions: The CAP treatment of CS cells inhibits their growth, motility, and metabolism by initiating apoptotic processes.

Establishment and validation of an individualized nomogram to predict distant metastasis in chondrosarcoma patients: a population-based study

BackgroundDistant metastasis is a significant factor influencing chondrosarcoma (CHS) patients’ treatment and prognosis. We aimed to establish a consistent and effective nomogram to better predict distant metastases of CHS individuals.MethodsThe Surveillance, Epidemiology and End Results (SEER) database was used to obtain the demographics and clinicopathological characteristics of CHS patients from 2010 to 2018. Independent risk factors were identified via univariate and multivariate logistic regressive analysis. A nomogram that predicts metastasis risk was established based on the training cohort, and its accuracy was validated through the validation cohort. The performance of this predictive model was assessed by the receiver operating characteristic (ROC) curve and Harrell’s concordance index (C-index). Finally, decision curve analysis (DCA) was conducted to test its clinical reliability.ResultsData of 1,066 patients were extracted, of these, 66 cases (6.19%) were with distant metastasis at initial diagnosis. The following features were shown to be linked to an increased risk of metastasis: high-grade tumor, T3 stage, and large tumor size; whereas unmarried and use of surgery were independent protective factors. Marital status, tumor grade, T stage, use of cancer-directed surgery and tumor size were incorporated to develop the novel nomogram. The ROC curves showed the effectiveness of the nomogram with the high area under the curves, the C-indices were 0.931 and 0.951 in the internal and external validation, respectively. The calibration plots indicated a good consistency and agreement of the nomogram, while the DCA illustrated that the nomogram had favorable potential clinical applicability due to great positive net benefit with wide ranges of the threshold probabilities.ConclusionsThis work developed a novel nomogram for predicting distant metastasis in CHS patients, which might assist clinicians to determine the optimal treatment plan by precisely predicting individualized metastatic risk.

Single-institution clinical experience using robust intensity modulated proton therapy in chordoma and chondrosarcoma of the mobile spine and sacrum: Feasibility and need for plan adaptation

BackgroundDue to its specific physical characteristics, proton irradiation is especially suited for irradiation of chordomas and chondrosarcoma in the axial skeleton. Robust plan optimization renders the proton beam therapy more predictable upon individual setup errors. Reported experience with the planning and delivery of robustly optimized plans in chordoma and chondrosarcoma of the mobile spine and sacrum, is limited. In this study, we report on the clinical use of robustly optimized, intensity modulated proton beam therapy in these patients. MethodsWe retrospectively reviewed patient, treatment and acute toxicity data of all patients with chordoma and chondrosarcoma of the mobile spine and sacrum, treated between 1 April 2019 and 1 April 2020 at our institute. Anatomy changes during treatment were evaluated by weekly cone-beam CTs (CBCT), supplemented by scheduled control-CTs or ad-hoc control-CTs. Acute toxicity was scored weekly during treatment and at 3 months after therapy according to CTCAE 4.0. Results17 chordoma and 3 chondrosarcoma patients were included. Coverage of the high dose clinical target volume was 99.8% (range 56.1–100%) in the nominal and 80.9% (range 14.3–99.6%) in the voxel-wise minimum dose distribution. Treatment plan adaptation was needed in 5 out of 22 (22.7%) plans. Reasons for plan adaptation were either reduced tumor coverage or increased dose to the OAR. ConclusionsRobustly optimized intensity modulated proton beam therapy for chordoma and chondrosarcoma of the mobile spine is feasible. Plan adaptations due to anatomical changes were required in approximately 23 percent of treatment courses.

DDX10 and BYSL as the potential targets of chondrosarcoma and glioma.

To provide reliable molecular markers and effective therapeutic targets for chondrosarcoma and glioma.Gene Set Enrichment (GSE) 29745 and GSE48420 were downloaded from the Gene Expression Omnibus (GEO) database. Differently expressed genes (DEGs) were identified by the GEO2R. We annotated the function of common DEGs through Digital Audio/Video Interactive Decoder (DAVID) and Metascape. Protein–protein interaction network construction was performed through STRING. Hub genes were identified by the two different algorithms (MCC, EPC). DDX10 and BYSL were key factors in embryo implantation and development, and plays a role in a variety of cancers. The role of the DDX10 and BYSL on the glioma derived from the chondrosarcoma would be explored by the clinical samples.A total of 1442 DEGs were identified. The variations in DEGs were mainly enriched in vasculature development, cell motion, blood vessel development, cell migration, regulation of cell proliferation, regulation of cell proliferation, wound healing, biological adhesion, growth factor binding, identical pathways in cancer, and p53 signaling pathway. Dead-box helicase 10 (DDX10), Bystin-like (BYSL), and WD repeat domain 12 (WDR12) were identified as the hub genes, and the three hub genes were up-regulated in the chondrosarcoma. Chondrosarcoma patients with high expression levels of DDX10 (Logrank P = .0052; HR (high) = 1.8; n (high) = 131, 50%), and BYSL (P = 6.5e-05; HR (high) = 2.3; n (high) = 131, 50%) had poorer overall survival times than those with low expression levels.DDX10 and BYSL genes may provide reliable molecular markers and effective therapeutic targets for chondrosarcoma and glioma.

Assessment of Radiation-Induced Optic Neuropathy in a Multi-Institutional Cohort of Chordoma and Chondrosarcoma Patients Treated with Proton Therapy.

Simple SummaryProton therapy is an effective therapeutic option for the treatment of skull-base tumors that require high radiation doses to be controlled. On rare occasions, patients suffer from radiation-induced optic neuropathy (RION) to the detriment of their post-treatment quality-of-life. We have collected multi-institutional data of 289 skull-base patients having received high doses to the optic apparatus from proton therapy or proton–photon mixed treatments and have observed a RION incidence rate (all grades) of 4.2% (12). We have furthermore confirmed older age and hypertension as risk factors for the onset of this side effect, with tumor involvement or its proximity to the optic apparatus and repeated surgical procedures showing moderate association. Our findings were consolidated into a NTCP model that can support pre-treatment patient segmentation into risk groups and the planning of necessary treatment countermeasures. However, further data and validation are necessary to confirm validity of the model. Radiation-induced optic neuropathy (RION) is a rare side effect following radiation therapy involving the optic structures whose onset is, due to the low amount of available data, challenging to predict. We have analyzed a multi-institutional cohort including 289 skull-base cancer patients treated with proton therapy who all received >45 GyRBE to the optic apparatus. An overall incidence rate of 4.2% (12) was observed, with chordoma patients being at higher risk (5.8%) than chondrosarcoma patients (3.2%). Older age and arterial hypertension, tumor involvement, and repeated surgeries (>3) were found to be associated with RION. Based on bootstrapping and cross-validation, a NTCP model based on age and hypertension was determined to be the most robust, showing good classification ability (AUC-ROC 0.77) and calibration on our dataset. We suggest the application of this model with a threshold of 6% to segment patients into low and high-risk groups before treatment planning. However, further data and external validation are warranted before clinical application.

Is Chemotherapy Associated with Improved Overall Survival in Patients with Dedifferentiated Chondrosarcoma? A SEER Database Analysis.

Dedifferentiated chondrosarcoma is a chondrosarcoma subtype associated with high rates of recurrence and a poor prognosis. Others have proposed treatment of dedifferentiated chondrosarcoma using osteosarcoma protocols, including perioperative chemotherapy. However, the rarity of this condition poses difficulties in undertaking single- institution studies of sufficient sample size. Is perioperative chemotherapy associated with improved overall survival in patients with dedifferentiated chondrosarcoma? We queried the Surveillance, Epidemiology, and End Results (SEER) 1973 to 2016 database for patients with a diagnosis of dedifferentiated chondrosarcoma (n = 308). As dedifferentiated chondrosarcoma was only classified as a distinct entity in SEER starting in 2000, only patients treated in 2000 and later were included. We excluded from our analyses those patients with distant disease at diagnosis, a primary site of disease other than bone or joints, and those who did not receive cancer-directed surgery. These criteria yielded 185 dedifferentiated chondrosarcoma patients for inclusion. We used Kaplan-Meier analyses and Cox proportional hazards models to assess the association of clinical, demographic, and treatment characteristics on overall survival (OS). After controlling for confounding variables, including age, sex, tumor size, stage, grade, location, and radiation treatment status, and after adjusting for missing data, no overall survival benefit was associated with receipt of chemotherapy in patients with dedifferentiated chondrosarcoma (hazard ratio 0.75 [95% confidence interval 0.49 to 1.12]; p = 0.16). Chemotherapy treatment of dedifferentiated chondrosarcoma was not associated with improved OS. These results must be viewed cautiously, given the limited granularity of information on chemotherapy treatment, the concerns regarding chemotherapy misclassification in SEER data, and the small sample of patients with dedifferentiated chondrosarcoma, all of which limit the power to detect a difference. Our findings are nevertheless consistent with those of prior reports in which no benefit of chemotherapy could be detected. Lack of clear benefit from perioperative chemotherapy in dedifferentiated chondrosarcoma argues that it should be used only after careful consideration, and ideally in the context of a clinical trial. Level III, therapeutic study.