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Journal of Cancer Research and... Apr 2024Bone sarcomas encompass a group of spontaneous mesenchymal malignancies, among which osteosarcoma, Ewing sarcoma, chondrosarcoma, and chordoma are the most common... (Review)
Review
Bone sarcomas encompass a group of spontaneous mesenchymal malignancies, among which osteosarcoma, Ewing sarcoma, chondrosarcoma, and chordoma are the most common subtypes. Chondrosarcoma, a relatively prevalent malignant bone tumor that originates from chondrocytes, is characterized by endogenous cartilage ossification within the tumor tissue. Despite the use of aggressive treatment approaches involving extensive surgical resection, chemotherapy, and radiotherapy for patients with osteosarcoma, chondrosarcoma, and chordoma, limited improvements in patient outcomes have been observed. Furthermore, resistance to chemotherapy and radiation therapy has been observed in chondrosarcoma and chordoma cases. Consequently, novel therapeutic approaches for bone sarcomas, including chondrosarcoma, need to be uncovered. Recently, the emergence of immunotherapy and immune checkpoint inhibitors has garnered attention given their clinical success in various diverse types of cancer, thereby prompting investigations into their potential for managing chondrosarcoma. Considering that circumvention of immune surveillance is considered a key factor in the malignant progression of tumors and that immune checkpoints play an important role in modulating antitumor immune effects, blockers or inhibitors targeting these immune checkpoints have become effective therapeutic tools for patients with tumors. One such checkpoint receptor implicated in this process is programmed cell death protein-1 (PD-1). The association between PD-1 and programmed cell death ligand-1 (PD-L1) and cancer progression in humans has been extensively studied, highlighting their remarkable potential as biomarkers for cancer treatment. This review comprehensively examines available studies on current chondrosarcoma treatments and advancements in anti-PD-1/PD-L1 blockade therapy for chondrosarcoma.
Topics: Humans; Chondrosarcoma; B7-H1 Antigen; Programmed Cell Death 1 Receptor; Bone Neoplasms; Immune Checkpoint Inhibitors; Immunotherapy
PubMed: 38687921
DOI: 10.4103/jcrt.jcrt_2269_23 -
Cancer Medicine Sep 2023We conducted a retrospective multi-centre study to assess the real-world outcome of regorafenib (REGO) and cabozantinib (CABO) in recurrent/refractory bone tumours (BTs)...
Real-world experience of tyrosine kinase inhibitors in children, adolescents and adults with relapsed or refractory bone tumours: A Canadian Sarcoma Research and Clinical Collaboration (CanSaRCC) study.
OBJECTIVES
We conducted a retrospective multi-centre study to assess the real-world outcome of regorafenib (REGO) and cabozantinib (CABO) in recurrent/refractory bone tumours (BTs) including osteosarcoma (OST), Ewing sarcoma (EWS) and chondrosarcoma (CS)/extra-skeletal mesenchymal CS (ESMC).
METHODS
After regulatory approval, data from patients with recurrent BT (11 institutions) were extracted from CanSaRCC (Canadian Sarcoma Research and Clinical Collaboration) database. Patient characteristics, treatment and outcomes were collected. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method.
RESULTS
From July 2018 to May 2022, 66 patients received REGO or CABO; 39 OST, 18 EWS, 4 CS and 5 ESMC. Median age was 27.8 years (range 12-76); median starting dose was 60 mg for CABO (n = 37, range 40-60) and 120 mg for REGO (n = 29, range 40-160). Twenty-eight (42.4%) patients required dose reduction: hand-foot syndrome 7 (10.6%), nausea/vomiting 1 (1.5%), diarrhoea 1 (1.5%), 2 elevated LFTs (3%), elevated bilirubin 1 (1.5%) and mucositis 1 (1.5%). The median OS for patients with OST, EWS, CS and ESMC was 8.5 months (n = 39, 95% CI 7-13.1); 13.4 months (n = 18, 95% CI 3.4-27.2), 8.1 (n = 4, 95% CI 4.1-9.3) and 18.2 (n = 5, 95% CI (10.4-na), respectively. Median PFS for OST, EWS, CS and ECMS was 3.5 (n = 39, 95% CI 2.8-5), 3.9 (n = 18, 95% CI 2.1-5.9), 5.53 (n = 4. 95% CI 2.13-NA) and 11.4 (n = 5, 95% CI 1.83-14.7), respectively. Age, line of therapy, REGO versus CABO, or time from diagnosis to initiation of TKI were not associated with PFS on univariable analysis.
CONCLUSION
Our real-world data show that TKIs have meaningful activity in recurrent BT with acceptable toxicities when started at modified dosing. Inclusion of TKIs in earlier lines of treatment and/or maintenance therapy could be questions for future research.
Topics: Humans; Adult; Child; Adolescent; Young Adult; Middle Aged; Aged; Tyrosine Kinase Inhibitors; Neoplasm Recurrence, Local; Canada; Bone Neoplasms; Sarcoma; Sarcoma, Ewing; Osteosarcoma; Chondrosarcoma; Retrospective Studies; Soft Tissue Neoplasms
PubMed: 37724607
DOI: 10.1002/cam4.6515 -
Cureus Sep 2023Mesenchymal chondrosarcomas are extremely rare and aggressive tumors that primarily affect patients between the ages of 20 and 30. These neoplasms are typically found in...
Mesenchymal chondrosarcomas are extremely rare and aggressive tumors that primarily affect patients between the ages of 20 and 30. These neoplasms are typically found in the lower limbs and cranial region. Their occurrence within soft tissues is exceedingly rare, and the initial presentation often includes immediate metastatic dissemination. Given the extraordinarily low prevalence of extraskeletal mesenchymal chondrosarcoma, treatment approaches remain non-standardized. Surgical resection combined with neoadjuvant chemotherapy or radiotherapy is the most commonly favored strategy by medical teams. In this case report, we present the case of a 72-year-old patient with no specific medical history, who presented with a non-metastatic extraskeletal mesenchymal chondrosarcoma located in the popliteal fossa. The therapeutic intervention encompassed surgical resection followed by adjuvant radiotherapy. After 18 months of follow-up period, there was no evidence of local recurrence or distant metastases. The disparity between the patient's clinical characteristics and the existing medical literature may provide new insights into understanding this neoplastic entity.
PubMed: 37900409
DOI: 10.7759/cureus.45974 -
BMC Cancer Sep 2023Cancer cells are characterized by changes in cell cytoskeletal architecture and stiffness. Despite advances in understanding the molecular mechanisms of musculoskeletal...
BACKGROUND
Cancer cells are characterized by changes in cell cytoskeletal architecture and stiffness. Despite advances in understanding the molecular mechanisms of musculoskeletal cancers, the corresponding cellular mechanical properties remain largely unexplored. The aim of this study was to investigate the changes in cellular stiffness and the associated cytoskeleton configuration alterations in various musculoskeletal cancer cells.
METHODS
Cell lines from five main sarcoma types of the musculoskeletal system (chondrosarcoma, osteosarcoma, Ewing sarcoma, fibrosarcoma and rhabdomyosarcoma) as well as their healthy cell counterparts (chondrocytes, osteoblasts, mesenchymal stem cells, fibroblasts, skeletal muscle cells) were subjected to cell stiffness measurements via atomic force microscopy (AFM). Biochemical and structural changes of the cytoskeleton (F-actin, β-tubulin and actin-related protein 2/3) were assessed by means of fluorescence labelling, ELISA and qPCR.
RESULTS
While AFM stiffness measurements showed that the majority of cancer cells (osteosarcoma, Ewing sarcoma, fibrosarcoma and rhabdomyosarcoma) were significantly less stiff than their corresponding non-malignant counterparts (p < 0.001), the chondrosarcoma cells were significant stiffer than the chondrocytes (p < 0.001). Microscopically, the distribution of F-actin differed between malignant entities and healthy counterparts: the organisation in well aligned stress fibers was disrupted in cancer cell lines and the proteins was mainly concentrated at the periphery of the cell, whereas β-tubulin had a predominantly perinuclear localization. While the F-actin content was lower in cancer cells, particularly Ewing sarcoma (p = 0.018) and Fibrosarcoma (p = 0.023), this effect was even more pronounced in the case of β-tubulin for all cancer-healthy cell duos. Interestingly, chondrosarcoma cells were characterized by a significant upregulation of β-tubulin gene expression (p = 0.005) and protein amount (p = 0.032).
CONCLUSION
Modifications in cellular stiffness, along with structural and compositional cytoskeleton rearrangement, constitute typical features of sarcomas cells, when compared to their healthy counterpart. Notably, whereas a decrease in stiffness is typically a feature of malignant entities, chondrosarcoma cells were stiffer than chondrocytes, with chondrosarcoma cells exhibiting a significantly upregulated β-tubulin expression. Each Sarcoma entity may have his own cellular-stiffness and cytoskeleton organisation/composition fingerprint, which in turn may be exploited for diagnostic or therapeutic purposes.
Topics: Humans; Sarcoma, Ewing; Tubulin; Actins; Sarcoma; Osteosarcoma; Fibrosarcoma; Rhabdomyosarcoma; Chondrosarcoma; Soft Tissue Neoplasms; Biomarkers; Bone Neoplasms
PubMed: 37700272
DOI: 10.1186/s12885-023-11375-3 -
Journal of Neurosurgery. Case Lessons Aug 2023Mesenchymal chondrosarcoma (MCS) is an aggressive subtype of chondrosarcoma that occurs extremely rarely in the central nervous system. Patients often present with pain...
BACKGROUND
Mesenchymal chondrosarcoma (MCS) is an aggressive subtype of chondrosarcoma that occurs extremely rarely in the central nervous system. Patients often present with pain or sensorimotor deficits, and resection is considered the gold standard. The role of adjuvant radiation and/or chemotherapy is largely unknown.
OBSERVATIONS
A 22-year-old male presented with a 4-month history of progressive back and bilateral leg pain. He underwent imaging workup with magnetic resonance imaging of the lumbar spine and was found to have an intradural, extramedullary, heterogeneously enhancing mass spanning the L4-5 vertebral levels. Intraoperatively, a lobular, partially calcified mass with a ventral dural attachment displacing the nerve roots laterally was observed. The mass was removed en bloc, and the patient later underwent adjuvant radiotherapy, with no evidence of recurrence 2 years following surgery.
LESSONS
Spinal MCS is extremely rare and often presents with a more aggressive course than conventional chondrosarcoma. Radiological diagnosis is challenging, as the tumor mimics different pathologies. The presence of calcifications, heterogeneous enhancement, and a more rapid clinical course as well as the presence of HEY1::NCOA2 gene fusion, which can be detected by surrogate immunohistochemistry, aids in diagnosis. Resection is the standard of care, and adjuvant radiation may be considered to reduce local recurrence, although further studies are warranted.
PubMed: 37728306
DOI: 10.3171/CASE23317 -
Annals of Medicine and Surgery (2012) Jan 2024Mesenchymal chondrosarcoma (MC) is a rapidly progressive sarcoma that predominantly impacts the bones. Making up only 3% of chondrosarcomas, about one-third of these...
INTRODUCTION
Mesenchymal chondrosarcoma (MC) is a rapidly progressive sarcoma that predominantly impacts the bones. Making up only 3% of chondrosarcomas, about one-third of these tumours develop in extra-skeletal sites.
CASE PRESENTATION
The authors present a clinical case of a 42-year-old patient who was diagnosed with MC 8 years ago, now admitted to the hospital with a palpable epigastric mass. Clinical and laboratory examinations showed consistent results for MC tumours, with metastasis to the body and tail of the pancreas and invasion of the splenic vein. Surgical resection and systemic screening were performed to ensure that there were no lesions elsewhere. Regular follow-up has found no localized lesions or complications after 15 months.
CLINICAL DISCUSSION
Metastatic extra-skeletal mesenchymal chondrosarcoma of the pancreas is exceptionally rare. To our current understanding, only 14 such cases have been documented in medical literature. The symptoms of pancreatic metastasis are diverse and the radiographic features of metastatic mesenchymal chondrosarcoma are not typically distinct.
CONCLUSIONS
Although MC tumours do not frequently occur in sites other than the axial system, a tumour presenting later in a patient with a history of MC should be reviewed to confirm the diagnosis of metastatic MC. Treatment can vary between surgery, radiation therapy and systemic therapy.
PubMed: 38222770
DOI: 10.1097/MS9.0000000000001549 -
Cancer Reports (Hoboken, N.J.) Oct 2023Chondrosarcomas are an exceedingly rare form of cancer, impacting only a few individuals per million. Among chondrosarcomas, a small fraction belongs to the mesenchymal...
BACKGROUND
Chondrosarcomas are an exceedingly rare form of cancer, impacting only a few individuals per million. Among chondrosarcomas, a small fraction belongs to the mesenchymal sub-type. Furthermore, only one-third of mesenchymal chondrosarcomas manifest in extraskeletal locations.
CASE
A 38-year-old woman was referred by a midwife after experiencing pain in the right upper quadrant of her right breast for 2 months. The mass had been palpable for 1 week before the initial assessment. According to radiological evaluations, the tumor is outside breast tissue and not connected to the bones. Hence, a biopsy of the mass is done. The biphasic morphology of the tumor during pathological evaluation, in addition to immunohistochemistry testing, confirms the diagnosis of extraskeletal mesenchymal chondrosarcoma (EMCS). Finally, the mass was surgically removed, and 6 months of chemotherapy were administered to the patient.
CONCLUSION
Given the tumor's rarity and the lack of established guidelines, diagnosing EMCS can be challenging and prone to errors. As such, meticulous sampling, along with precise pathological and imaging investigations, is imperative to accurately establish the diagnosis of these tumors.
Topics: Female; Humans; Adult; Chondrosarcoma, Mesenchymal; Chondrosarcoma; Immunohistochemistry; Diagnostic Imaging; Bone Neoplasms
PubMed: 37559178
DOI: 10.1002/cnr2.1883 -
International Journal of Molecular... Feb 2024Recurrent gene fusions (GFs) in translocated sarcomas are recognized as major oncogenic drivers of the disease, as well as diagnostic markers whose identification is...
Recurrent gene fusions (GFs) in translocated sarcomas are recognized as major oncogenic drivers of the disease, as well as diagnostic markers whose identification is necessary for differential diagnosis. is a 'promiscuous' gene that can fuse with many different partner genes, defining different entities among a broad range of mesenchymal neoplasms. Molecular testing of translocation traditionally relies on FISH assays with break-apart probes, which are unable to identify the fusion partner. Therefore, other ancillary molecular diagnostic modalities are being increasingly adopted for accurate classification of these neoplasms. Herein, we report three cases with rare GFs involving in undifferentiated mesenchymal neoplasms with uncertain differential diagnoses, using targeted RNA-seq and confirming with RT-PCR and Sanger sequencing. Two GFs involved hormone nuclear receptors as 3' partners, and , which have not been previously reported. may functionally replace , the usual 3' partner in extraskeletal myxoid chondrosarcoma. The third GF, , has previously been reported in a subtype of astroblastoma and other rare entities, including a single case of a soft-tissue tumor that we discuss in this work. In conclusion, our findings indicate that the catalogue of mesenchymal neoplasm-bearing fusions continues to grow, underscoring the value of using molecular ancillary techniques with higher diagnostic abilities in the routine clinical setting.
Topics: Humans; Calmodulin-Binding Proteins; Chondrosarcoma; Neoplasms, Connective and Soft Tissue; Oncogene Proteins, Fusion; RNA-Binding Protein EWS; RNA-Binding Proteins; Sarcoma; Soft Tissue Neoplasms
PubMed: 38339014
DOI: 10.3390/ijms25031735 -
Indian Journal of Pathology &... Jul 2023
PubMed: 38391341
DOI: 10.4103/ijpm.ijpm_299_22 -
Cancers May 2024The Wnt receptor ROR1 has generated increased interest as a cancer therapeutic target. Research on several therapeutic approaches involving this receptor is ongoing;...
The Wnt receptor ROR1 has generated increased interest as a cancer therapeutic target. Research on several therapeutic approaches involving this receptor is ongoing; however, ROR1 tissue expression remains understudied. We performed an immunohistochemistry analysis of ROR1 protein expression in a large cohort of multiple tumor and histologic types. We analyzed 12 anonymized multi-tumor tissue microarrays (TMAs), including mesothelioma, esophageal and upper gastrointestinal carcinomas, and uterine endometrioid carcinoma, among other tumor types. Additionally, we studied 5 different sarcoma types of TMAs and 6 patient-derived xenografts (PDX) TMAs developed from 19 different anatomic sites and tumor histologic types. A total of 1142 patient cases from different histologic types and 140 PDXs placed in TMAs were evaluated. Pathologists assessed the percentage of tumor cells in each case that were positive for ROR1 and the intensity of staining. For determining the prevalence of staining for each tumor type, a case was considered positive if >1% of its tumor cells showed ROR1 staining. Our immunohistochemistry assays revealed a heterogeneous ROR1 expression profile. A high prevalence of ROR1 expression was found in mesothelioma (84.6%), liposarcoma (36.1%), gastrointestinal stromal tumors (33.3%), and uterine endometrioid carcinoma (28.9%). Other histologic types such as breast, lung, renal cell, hepatocellular, urothelial carcinoma, and colon carcinomas; glioblastoma; cholangiocarcinoma; and leiomyosarcoma showed less ROR1 overall expression, ranging between 0.9 and 13%. No ROR1 expression was seen in mesenchymal chondrosarcoma, rhabdomyosarcoma, or gastric adenocarcinoma cases. Overall, ROR1 expression was relatively infrequent and low in most tumor types investigated; however, ROR1 expression was infrequent but high in selected tumor types, such as gastroesophageal GIST, suggesting that ROR1 prescreening may be preferable for those indications. Further, mesothelioma exhibited frequent and high levels of ROR1 expression, which represents a previously unrecognized therapeutic opportunity. These findings can contribute to the development of ROR1-targeted therapies.
PubMed: 38791952
DOI: 10.3390/cancers16101874