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F1000Research 2018Chondrosarcomas constitute a heterogeneous group of primary bone cancers characterized by hyaline cartilaginous neoplastic tissue. They are the second most common... (Review)
Review
Chondrosarcomas constitute a heterogeneous group of primary bone cancers characterized by hyaline cartilaginous neoplastic tissue. They are the second most common primary bone malignancy. The vast majority of chondrosarcomas are conventional chondrosarcomas, and most conventional chondrosarcomas are low- to intermediate-grade tumors (grade 1 or 2) which have indolent clinical behavior and low metastatic potential. Recurrence augurs a poor prognosis, as conventional chondrosarcomas are both radiation and chemotherapy resistant. Recent discoveries in the biology, genetics, and epigenetics of conventional chondrosarcomas have significantly advanced our understanding of the pathobiology of these tumors and offer insight into potential therapeutic targets.
Topics: Bone Neoplasms; Chondrosarcoma; Epigenesis, Genetic; Humans; Prognosis; Therapeutics
PubMed: 30519452
DOI: 10.12688/f1000research.15953.1 -
Journal of Clinical Pathology Jul 2018Clinical outcome prediction is major concern to patients with cancer. Various molecular markers in various carcinomas have been identified in the past few decades.... (Review)
Review
Clinical outcome prediction is major concern to patients with cancer. Various molecular markers in various carcinomas have been identified in the past few decades. However, accurate predictors in chondrosarcoma have not been developed, even though chondrosarcoma is the second most common primary bone tumour. Chondrosarcoma is the cartilage-forming malignancy and shows a wide spectrum of clinicopathological behaviours. The majority of chondrosarcoma grows slowly and rarely metastasises, and adequate surgery leads to a good prognosis. However, wide surgical excision is acquired in high-grade chondrosarcoma, because this tumour is highly resistant to chemotherapy and radiotherapy. To decide best therapy, accurate diagnostic markers are also necessary in chondrosarcoma. It is reported that angiogenesis and lymphangiogenesis increase by chondrosarcoma staging, and they are promoted by leptin and adiponectin. Several microRNAs to regulate vascular endothelial growth factor (VEGF)-A and VEGF-C are also reported. Alpha-methylacyl-CoA racemase and periostin are proposed as new biomarkers for differential diagnosis of enchondroma and chondrosarcoma. This review summarises that chondrosarcoma diagnostic markers are currently reported.
Topics: Biomarkers, Tumor; Biopsy; Bone Neoplasms; Chondrosarcoma; Diagnosis, Differential; Humans; Immunohistochemistry; Neoplasm Grading; Neoplasm Staging; Predictive Value of Tests
PubMed: 29593061
DOI: 10.1136/jclinpath-2018-205071 -
Journal of Clinical Oncology : Official... May 2020Surgery is the primary therapy for localized chondrosarcoma; for locally advanced and/or metastatic disease, no known effective systemic therapy exists. Mutations in the...
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 advanced solid tumors, including chondrosarcoma. Ivosidenib was administered orally (100 mg twice daily to 1,200 mg once daily) in continuous 28-day cycles. Responses were assessed every other cycle using RECIST (version 1.1).
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 chondrosarcoma.
Topics: Adult; Aged; Aged, 80 and over; Chondrosarcoma; Enzyme Inhibitors; Female; Glycine; Humans; Male; Middle Aged; Pyridines
PubMed: 32208957
DOI: 10.1200/JCO.19.02492 -
International Journal of Molecular... Jan 2022Due to resistance to standard anticancer agents, it is difficult to control the disease progression in patients with metastatic or unresectable chondrosarcoma. Novel... (Review)
Review
Due to resistance to standard anticancer agents, it is difficult to control the disease progression in patients with metastatic or unresectable chondrosarcoma. Novel therapeutic approaches, such as molecule-targeting drugs and immunotherapy, are required to improve clinical outcomes in patients with advanced chondrosarcoma. Recent studies have suggested several promising biomarkers and therapeutic targets for chondrosarcoma, including and . Several molecule-targeting agents and immunotherapies have shown favorable antitumor activity in clinical studies in patients with advanced chondrosarcomas. This review summarizes recent basic studies on biomarkers and molecular targets and recent clinical studies on the treatment of chondrosarcomas.
Topics: Antineoplastic Agents; Biomarkers, Tumor; Bone Neoplasms; Chondrosarcoma; Collagen Type II; Humans; Isocitrate Dehydrogenase; Mutation
PubMed: 35163019
DOI: 10.3390/ijms23031096 -
Clinical Cancer Research : An Official... Jan 2020Chondrosarcomas are the second most common primary malignant bone tumors. Although histologic grade is the most important factor predicting the clinical outcome of...
PURPOSE
Chondrosarcomas are the second most common primary malignant bone tumors. Although histologic grade is the most important factor predicting the clinical outcome of chondrosarcoma, it is subject to interobserver variability. Isocitrate dehydrogenase 1 () and hotspot mutations were recently found to be frequently mutated in central chondrosarcomas. However, a few published articles have been controversial regarding the association between mutation status and clinical outcomes in chondrosarcomas.
EXPERIMENTAL DESIGN
We performed hotspot sequencing of and genes in 89 central chondrosarcomas and targeted next-generation sequencing in 54 of them, and then correlated the mutation status with the patient's clinical outcome.
RESULTS
Although no association was discovered between mutation status and the patient's overall survival, / mutation was found to be associated with longer relapse-free and metastasis-free survival in high-grade chondrosarcomas. Genomic profiling reveals gene amplification and mutation, for the first time, in addition to promoter mutation in a subset (6/30, 20%) of high-grade and dedifferentiated chondrosarcomas. These abnormalities in telomere genes are concurrent with / mutation and with deletion or mutation, suggesting a possible association and synergy among these genes in chondrosarcoma progression. We found 21% of patients with chondrosarcoma also had histories of second malignancies unrelated to cartilaginous tumors, suggesting possible unknown genetic susceptibility to chondrosarcoma.
CONCLUSIONS
mutations are associated with longer relapse-free and metastasis-free survival in high-grade chondrosarcomas, and they tend to co-occur with mutations and with and alterations in a subset of high-grade chondrosarcomas.
Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Bone Neoplasms; Chondrosarcoma; Cyclin-Dependent Kinase Inhibitor p16; Female; Genomics; High-Throughput Nucleotide Sequencing; Humans; Isocitrate Dehydrogenase; Male; Middle Aged; Mutation; Neoplasm Grading; Neoplasm Metastasis; Neoplasm Recurrence, Local; Survival Rate; Telomerase; Tumor Suppressor Protein p53; Young Adult
PubMed: 31615936
DOI: 10.1158/1078-0432.CCR-18-4212 -
International Journal of Molecular... Jan 2023This review provides an overview of histopathology, clinical presentation, molecular pathways, and potential new systemic treatments of high-grade chondrosarcomas (CS),... (Review)
Review
This review provides an overview of histopathology, clinical presentation, molecular pathways, and potential new systemic treatments of high-grade chondrosarcomas (CS), including grade 2−3 conventional, dedifferentiated, and mesenchymal CS. The diagnosis of CS combines radiological and histological data in conjunction with patient clinical presentations. Conventional CS is the most frequent subtype of CS (85%) and represents about 25% of primary bone tumors in adults; they can be categorized according to their bone location into central, peripheral, and periosteal chondrosarcomas. Central and peripheral CS differ at the molecular level with either IDH1/2 mutations or EXT1/2 mutations, respectively. CDKN2A/B deletions are also frequent in conventional CS, as well as COL2A1 mutations. Dedifferentiated CS develops when low-grade conventional CS transforms into a high-grade sarcoma and most frequently exhibits features of osteosarcoma, fibrosarcoma, or undifferentiated pleomorphic sarcoma. Their molecular characteristics are similar to conventional CS. Mesenchymal CS is a totally different pathological entity exhibiting recurrent translocations. Their clinical presentation and management are different too. The standard treatment of CSs is wide en-bloc resection. CS are relatively radiotherapy resistant; therefore, doses >60 Gy are needed in an attempt to achieve local control in unresectable tumors. Chemotherapy is possibly effective in mesenchymal chondrosarcoma and is of uncertain value in dedifferentiated chondrosarcoma. Due to resistance to standard anticancer agents, the prognosis is poor in patients with metastatic or unresectable chondrosarcomas. Recently, the refined characterization of the molecular profile, as well as the development of new treatments, allow new therapeutic options for these rare tumors. The efficiency of IDH1 inhibitors in other malignancies suggests that these inhibitors will be part of IDH1/2 mutated conventional CS management soon. Other treatment approaches, such as PIK3-AKT-mTOR inhibitors, cell cycle inhibitors, and epigenetic or immune modulators based on improving our understanding of CS molecular biology, are emerging.
Topics: Adult; Humans; Chondrosarcoma; Bone Neoplasms; Radiography; Osteosarcoma; Biology
PubMed: 36674874
DOI: 10.3390/ijms24021361 -
Neuroendocrinology 2020Skull base chordomas account for less than 0.2% and chondrosarcomas for less than 0.15% of all intracranial tumors. Although their clinical and imaging presentations are... (Review)
Review
Skull base chordomas account for less than 0.2% and chondrosarcomas for less than 0.15% of all intracranial tumors. Although their clinical and imaging presentations are similar, they derive from different origins. Chordomas arise from embryonic remnants of the primitive notochord and chondrosarcomas from primitive mesenchymal cells or from the embryonic rest of the cranial cartilaginous matrix. Both entities are characterized by infiltration and destruction of the surrounding bone and soft tissue and a high locoregional recurrence rate. Chondrosarcomas, when treated with similar complex strategies, display a much better prognosis than chordomas. The overall survival is approximately 65% for chordomas and 80% for chondrosarcomas at 5 years and 30 and 50%, respectively, at 10 years. Chordomas are divided into the following 3 histological types: classical (conventional), chondroid, and dedifferentiated. Chondrosarcomas have conventional, mesenchymal, clear cell, and dedifferentiated subgroups. Both tumor entities often present with nonspecific symptoms, and headaches are the most reported initial symptom. Computed tomography and magnetic resonance imaging are required to determine the tumor localization and the extent of tumor growth. The treatment philosophy is to maximize tumor resection, minimize morbidity, and preserve function. Neurosurgical approaches commonly used for the resection of intracranial chordomas and chondrosarcomas are transsphenoidal, transbasal, cranio-orbitozygomatic, transzygomatic extended middle fossa, transcondylar, and transmaxillary approaches. Chordomas and chondrosarcomas are not sensitive to chemotherapy and there are no approved drugs for their treatment. The present treatment concept is a combination of surgical resection with a maximal excision and preserving patients' quality of life by adjuvant radiotherapy for both chordomas and chondrosarcomas.
Topics: Chondrosarcoma; Chordoma; Humans; Skull Base Neoplasms
PubMed: 32541136
DOI: 10.1159/000509386 -
Cancer Science Jul 2022Chondrosarcoma is the second most common primary malignant bone tumor. In this multicenter study, we sought to evaluate the disease-specific survival (DSS) and...
Chondrosarcoma is the second most common primary malignant bone tumor. In this multicenter study, we sought to evaluate the disease-specific survival (DSS) and disease-free survival (DFS), and prognostic factors in patients with dedifferentiated chondrosarcoma (DDCS) or grade 3 chondrosarcoma (G3CS) in Japan. We retrospectively investigated the treatment outcomes and prognostic factors in 62 patients with DDCS and 19 patients with G3CS at 15 institutions participating in the Japanese Musculoskeletal Oncology Group. We also clarified significant clinicopathological factors for oncological outcomes. In surgery for primary lesions aimed at cure, a histologically negative margin (R0) was obtained in 93% (14/15) of patients with G3CS and 100% (49/49) of patients with DDCS. The 5-year DSS was 18.5% in patients with DDCS and 41.7% in patients with G3CS (p = 0.13). Local control was obtained in 80% (12/15) and 79.6% (39/49) of patients with G3CS and DDCS in the primary lesion after surgery with a wide surgical margin, respectively. In multivariate analysis, stage and no treatment/palliative treatment for the primary lesion were independent prognostic factors for DSS of DDCS, and age and no treatment/palliative treatment for DSS of G3CS. The 5-year DFS rate was 22.8% in 26 patients with DDCS who did not receive adjuvant chemotherapy, and 21.4% in 14 patients who received adjuvant chemotherapy. The prognosis of DDCS remains poor, although R0 resection was carried out in most cases. Effective and/or intensive chemotherapeutic regimens or agents should be considered or developed for patients with high-grade chondrosarcoma, particularly for those with DDCS.
Topics: Bone Neoplasms; Chondrosarcoma; Humans; Margins of Excision; Prognosis; Retrospective Studies; Treatment Outcome
PubMed: 35485870
DOI: 10.1111/cas.15382 -
Future Oncology (London, England) Mar 2017Chondrosarcoma is a malignant tumor of bones, characterized by the production of cartilage matrix. Due to lack of effective treatment for advanced disease, the clinical... (Review)
Review
Chondrosarcoma is a malignant tumor of bones, characterized by the production of cartilage matrix. Due to lack of effective treatment for advanced disease, the clinical management of chondrosarcomas is exceptionally challenging. Current research focuses on elucidating the molecular events underlying the pathogenesis of this rare bone malignancy, with the goal of developing new molecularly targeted therapies. Signaling pathways suggested to have a role in chondrosarcoma include Hedgehog, Src, PI3k-Akt-mTOR and angiogenesis. Mutations in IDH1/2, present in more than 50% of primary conventional chondrosarcomas, make the development of IDH inhibitors a promising treatment option. The present review discusses the preclinical and early clinical data on novel targeted therapeutic approaches in chondrosarcoma.
Topics: Angiogenesis Inhibitors; Animals; Antineoplastic Agents; Chondrosarcoma; Disease Management; Hedgehog Proteins; Histone Deacetylase Inhibitors; Humans; Isocitrate Dehydrogenase; Molecular Targeted Therapy; Mutation; Phosphatidylinositol 3-Kinases; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Signal Transduction; TOR Serine-Threonine Kinases; src-Family Kinases
PubMed: 28133974
DOI: 10.2217/fon-2016-0226 -
Head and Neck Pathology Mar 2014Laryngeal chondrosarcoma is a rare tumor requiring clinical, histologic, and radiographic correlation for definitive diagnosis. Although it typically presents with...
Laryngeal chondrosarcoma is a rare tumor requiring clinical, histologic, and radiographic correlation for definitive diagnosis. Although it typically presents with low-grade histology, even high-grade histology has a fairly indolent progression in this location, with a relatively low-likelihood for metastatic potential or recurrence. Because of this, conservative surgical excision with negative margins is recommended. We present a case of a laryngeal chondrosarcoma arising from the cricoid cartilage in a patient who presented with hoarseness, dysphagia, and odynophagia with subsequent head and neck computed tomography scan suggestive of the diagnosis. The patient was treated with hemicricoidectomy.
Topics: Chondrosarcoma; Humans; Laryngeal Neoplasms; Male; Middle Aged; Tomography, X-Ray Computed
PubMed: 23928862
DOI: 10.1007/s12105-013-0483-7