UNASSIGNED: The incidence of chondrosarcomas is relatively high as it comes second to multiple myeloma as the most common primary malignant bony neoplasms in adults. They tend to occur mostly in the axial skeleton. Hence, they rarely develop in the proximal humerus. Although imaging can aid in the diagnosis of chondrosarcoma, histopathology is the cornerstone that correlates with prognosis and guides us toward the most appropriate treatment modality. Surgical treatment is the best option for chondrosarcomas as most of them are resistant to chemotherapy and radiotherapy. It is really challenging to settle on one surgical technique for proximal humerus chondrosarcomas as surgeons must balance between saving the patient from the oncological process and maintaining a good function of the shoulder joint.
UNASSIGNED: We present herein a rare case, the first in Lebanon, of chondrosarcoma hitting the left proximal humerus of a 62-year-old lady successfully managed by operative resection and reconstruction with a cemented shoulder hemiarthroplasty using the Modular Universal Tumor and Revision System (MUTARS®) system.
UNASSIGNED: Chondrosarcomas are relatively rare. Their resistance to chemotherapy and radiation therapy in addition to their proximal humerus localization is troublesome for both the patient and the surgeon. Hence, a relatively new technique (first in Lebanon and the Middle East), the MUTARS shoulder hemiarthroplasty is found to have promising results on terms of morbidity and mortality for the patient when indicated and properly done.

BACKGROUND: Chondrosarcomas rank as the second most common primary bone malignancy. Characterized by the production of a cartilaginous matrix, these tumors typically exhibit resistance to both radiotherapy (RT) and chemotherapy (CT), resulting in overall poor outcomes: a high rate of mortality, especially among children and adolescents. Due to the considerable resistance to current conventional therapies such as surgery, CT, and RT, there is an urgent need to identify factors contributing to resistance and discover new strategies for optimal treatment. Over the past decade, researchers have delved into the dysregulation of genes associated with tumor development and therapy resistance to identify potential therapeutic targets for overcoming resistance. Recent studies have suggested several promising biomarkers and therapeutic targets for chondrosarcoma, including isocitrate dehydrogenase (IDH1/2) and COL2A1. Molecule-targeting agents and immunotherapies have demonstrated favorable antitumor activity in clinical studies involving patients with advanced chondrosarcomas. In this systematic review, we delineate the clinical features of chondrosarcoma and provide a summary of gene dysregulation and mutation associated with tumor development, as well as targeted therapies as a promising molecular approach. Finally, we analyze the probable role of the tumor microenvironment in chondrosarcoma drug resistance.
METHODS: A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to 10 November 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to \"chondrosarcomas\", \"target therapies\", \"immunotherapies\", and \"outcomes\". The studies included in this review consist of randomized controlled trials, non-randomized controlled trials, and cohort studies reporting on the use of target therapies for the treatment of chondrosarcoma in human subjects.
RESULTS: Of the initial 279 articles identified, 40 articles were included in the article. The exclusion of 140 articles was due to reasons such as irrelevance, non-reporting of selected results, systematic literature review or meta-analysis, and lack of details on the method/results. Three tables highlighted clinical studies, preclinical studies, and ongoing clinical trials, encompassing 13, 7, and 20 studies, respectively. For the clinical study, a range of molecular targets, such as death receptors 4/5 (DR4 and DR5) (15%), platelet-derived growth factor receptor-alpha or -beta (PDGFR-α, PDGFR-β) (31%), were investigated. Adverse events were mainly constitutional symptoms emphasizing that to improve therapy tolerance, careful observation and tailored management are essential. Preclinical studies analyzed various molecular targets such as DR4/5 (28.6%) and COX-2 (28.6%). The prevalent indicator of antitumoral activity was the apoptotic rate of both a single agent (tumor necrosis factor-related apoptosis-inducing ligand: TRAIL) and double agents (TRAIL-DOX, TRAIL-MG132). Ongoing clinical trials, the majority in Phase II (53.9%), highlighted possible therapeutic strategies such as IDH1 inhibitors and PD-1/PD-L1 inhibitors (30.8%).
CONCLUSIONS: The present review offers a comprehensive analysis of targeted therapeutics for skull base chondrosarcomas, highlighting a complex landscape characterized by a range of treatment approaches and new opportunities for tailored interventions. The combination of results from molecular research and clinical trials emphasizes the necessity for specialized treatment strategies and the complexity of chondrosarcoma biology.

UNASSIGNED: Chondrosarcoma, although rare in the distal radius, poses significant challenges. Early diagnosis through incisional biopsy is essential. Surgical resection with margin control and fibular grafting can be effective, but vigilant surveillance is crucial due to its aggressive nature. Metastasis demands consideration of additional interventions or palliative care.
UNASSIGNED: Chondrosarcomas constitute a rarity in the upper limbs, and their occurrence in the distal radius is even rarer with only one case previously documented. We report a case of distal radius chondrosarcoma in a 35-year-old female patient who presented with pain and swelling in her left wrist. Following an initial examination, an incisional biopsy was performed, confirming the diagnosis of dedifferentiated chondrosarcoma. The patient underwent a marginal resection of the distal radius and first carpal with ipsilateral fibular and locking compression plate fixation. Unfortunately, despite the interventions, the patient experienced recurrent swelling and ultimately required below-elbow amputation, followed by above elbow amputation due to metastasis. Unfortunately, the patient passed away due to recurrence and metastasis.

Tumours of the sacrum are difficult to manage. The sacrum provides the structural connection between the torso and lower half of the body and is subject to both axial and rotational forces. Thus, tumours or their treatment can compromise the stability of the spinopelvic junction. Additionally, nerves responsible for lower limb motor groups as well as bowel, bladder, and sexual function traverse or abut the sacrum. Preservation or sacrifice of these nerves in the treatment of sacral tumours has profound implications on the function and quality of life of the patient. This annotation will discuss current treatment protocols for sacral tumours.Cite this article: Bone Joint J 2022;104-B(12):1284-1291.

OBJECTIVE: Socioeconomic and racial disparities have been recognized as impacting the care of patients with cancer, however there are a lack of data examining the impact of these disparities on patients with bone sarcoma. The purpose of this study was to examine socioeconomic and racial disparities that impact the oncological outcomes of patients with bone sarcoma.
METHODS: We reviewed 4,739 patients diagnosed with primary bone sarcomas from the Surveillance, Epidemiology and End Results (SEER) registry between 2007 and 2015. We examined the impact of race and insurance status associated with the presence of metastatic disease at diagnosis, treatment outcome, and overall survival (OS).
RESULTS: Patients with Medicaid (odds ratio (OR) 1.41; 95% confidence interval (CI) 1.15 to 1.72) and uninsured patients (OR 1.90; 95% CI 1.26 to 2.86) had higher risks of metastatic disease at diagnosis compared to patients with health insurance. Compared to White patients, Black (OR 0.63, 95% CI 0.47 to 0.85) and Asian/Pacific Islander (OR 0.65, 95% CI 0.46 to 0.91) were less likely to undergo surgery. In addition, Black patients were less likely to receive chemotherapy (OR 0.67, 95% CI 0.49 to 0.91) compared to White patients. In patients with chondrosarcoma, those with Medicaid had worse OS compared to patients with insurance (hazard ratio (HR) 1.65, 95% CI 1.06 to 2.56).
CONCLUSIONS: In patients with a bone sarcoma, the cancer stage at diagnosis varied based on insurance status, and racial disparities were identified in treatment. Further studies are needed to identify modifiable factors which can mitigate socioeconomic and racial disparities found in patients with bone sarcomas. Cite this article: Bone Joint Res 2022;11(5):278-291.

Chondrosarcomas are rare malignant cartilaginous tumor affecting adult and elderly patient. Pelvic and long bones are the most common location. We differentiate conventional chondrosarcoma which arises do novo from preexisting normal bone (primary chondrosarcoma) or within a preexisting lesion such as enchondromas or osteochondromas (secondary chondrosarcoma), Other rare subtypes of chondrosarcoma include clear cell chondrosarcoma, dedifferentiated chondrosarcoma, and mesenchymal chondrosarcoma, which will be considered separately. Although there are diverse clinical presentations depending on the anatomic extend, radiographic features of chondrosarcoma are very characteristic comprising frequently a combination of bone expansion and heterogeneous calcifications. We report a case of a 56-year-old male suffering from fixed mass adhering to the right pubic bone. MRI views showed a lytic lesion of right superior pubic rami, surgical biopsy was in favor of chondrosarcomas, then an en bloc resection was performed following a Pfannenstiel approach without any recurrence after three years of follow-up.

OBJECTIVE: Gross total resection (GTR) is the mainstay therapy for chordomas and chondrosarcomas to have the best prognosis. The aims of this study were to specify the limits of EEA, emphasize the need for additional combined approaches for tumors beyond these limitations for high resection rates, discuss the prognostic factors and operative nuances that affect GTR, and present the causes and characteristics of early and late recurrences.
METHODS: We retrospectively analyzed the endoscopic endonasal surgeries in the Pituitary Research Center and Neurosurgery Department of the Kocaeli University Faculty of Medicine, Turkey between January 2004 and December 2019. We retrospectively reviewed the medical data, radiological images, and surgical videos of patients, and 72 patients with chordoma and chondrosarcoma were included in the study.
RESULTS: Based on pathology reports, 72 patients (seven pediatric) were identified, to whom 91 endoscopic operations were performed. We determined the surgical limitations for each clival segment as superior, middle, and inferior. Then, we divided these into three subgroups according to whether the tumor shows dural invasion (extradural chordoma, large extradural - minimal intradural component, and minimal extradural - large intradural component). The tumors of 19 (26.4%), 25 (26.4%), and nine (12.5%) patients originated from the superior, middle, and inferior clivus, respectively. Nineteen (26.4%) patients had panclival involvement. GTR was performed in 47 (65.3%) the patients. The GTR rate in patients with panclival tumors was 47.3% (9/19). The experience, lateralization, dural involvement, and origin of the clivus affecting GTR were analyzed. Extradural - intradural extensions were verified as negative predictor factors for GTR, whereas tumors located in the superior (OR: 16.710, p=0.030) and middle (OR: 11.154, p=0.023) segments were positive predictive factors for GTR.
CONCLUSIONS: An increasing experience in endoscopic surgery significantly increases the GTR rates by widening the surgical limitations. Due to dense bone infiltration and adhesion to critical neurovascular structures, recurrence rates are high despite performing GTR. Although surgery and adjuvant treatments improve the 5-year survival of patients, the mortality rates remain high. Therefore, surgery of these tumors should be performed by experienced centers. In addition to surgical and adjuvant therapies, targeted molecular and translational biological therapies are also needed for chordomas and chondrosarcomas in the future.

OBJECTIVE: 3-Deazaneplanocin, DZNep, has been reported to inhibit the EZH2 histone methylase and to induce cell apoptosis in chondrosarcomas (CS). The present study aims to confirm the therapeutic potential of EZH2 inhibitors and investigate the molecular mechanisms of DZNep in chondrosarcomas.
METHODS: CS cell lines and primary cultures were used. Apoptosis was investigated using PARP cleavage, caspase 3/7 activity, or Apo2.7 expression. S-adenosylhomocysteine (SAH) and S-adenosylmethionine (SAM) were quantified by UHPLC-MS/MS. Differentially expressed genes in treated-chondrosarcomas and chondrocytes were researched by microarray analysis.
RESULTS: DZNep induced apoptosis in chondrosarcomas both in vivo and in vitro. However, this effect was not correlated to EZH2 expression nor activity, and EZH2 knock-down by siRNA did not reduce CS viability. Additionally, the reduction of H3K27me3 induced by GSK126 or tazemetostat (EPZ-6438) did not provoke chondrosarcoma death. However, as expected, DZNep induced SAH accumulation and reduced SAM:SAH ratio. Further, microarray analysis suggests a key role of EGFR in antitumoral effect of DZNep, and pharmacological inhibition of EGFR reduced chondrosarcoma survival.
CONCLUSIONS: EZH2 is not an adequate target for chondrosarcoma treatment. However, DZNep induces apoptosis in chondrosarcomas in vitro and in vivo, by a mechanism likely mediated though EGFR expression. Consequently, it would be worth initiating clinical trials to evaluating efficiency to S-adenosylhomocysteine hydrolase or EGFR inhibitors in patients with chondrosarcomas.

Skull base chondrosarcomas are rare tumors often invading the petrous apex and cavernous sinus, and many surgical approaches have been described. For most of them, these tumors grow slowly and their partial removal can be a first option before complementary radiotherapy. We described herein a minimally invasive approach that could be useful for soft non-calcified chondrosarcomas.
We report a case of right parasellar chondrosarcoma, for which an extra-intradural extracavernous subtemporal approach allowed a safe effective partial removal.
This surgical approach is indicated in selected cases to obtain good decompression or partial removal of lesions involving the parasellar space and the petrous apex.

BACKGROUND: We sought to evaluate the effectiveness of definitive or adjuvant external-beam proton therapy on local control and survival in patients with skull-base chondrosarcoma.
METHODS: We reviewed the medical records of 43 patients with a median age of 49 years (range, 23-80 years) treated with double-scattered 3D conformal proton therapy for skull-base chondrosarcomas between January 2007 and February 2016. Proton therapy-related toxicities were scored using CTCAE v4.0.
RESULTS: The median radiotherapy dose was 73.8 Gy(RBE) (range, 64.5-74.4 Gy[RBE]). Thirty-six (84%) and 7 (16%) patients underwent surgical resection or biopsy alone. Tumor grade distribution included: grade 1, 19 (44%) patients; grade 2, 22 (51%); and grade 3, 2 (5%). Forty patients had gross disease at the time of radiotherapy and 7 patients were treated for locally recurrent disease following surgery. The median follow-up was 3.7 years (range, 0.7-10.1 years). There were no acute grade 3 toxicities related to RT. At 4 years following RT, actuarial rates of overall survival, cause-specific survival, local control, and RT-related grade 3 toxicity-free survival were 95%, 100%, 89%, and 95%.
CONCLUSIONS: High-dose, double-scattered 3D conformal proton therapy alone or following surgical resection for skull-base chondrosarcoma is an effective treatment with a high rate of local control with no acute grade 3 radiation-related toxicity. Further follow-up of this cohort is necessary to better characterize long-term disease control and late toxicities.