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Desmoplastic small round blue cell tumor (DSRCT) is a highly aggressive fatal sarcoma without evidence‐based therapeutic guidelines. We present here seven patients with DSRCT including immunohistochemistry combined with fluorescence in situ hybridization (FISH), next generation sequencing (NGS, n = 6) as well as OncoScan array (n = 3) analyses and show consecutive therapeutic approaches. All seven DSRCT patients presented with an extended abdominal mass; median age at diagnosis was 24.8 years. NGS analyses revealed five class 4 or 5 sequence variants. Remarkably, OncoScan and targeted analyses by FISH identified genomic gains of CCND1 in two cases. Cyclin D1 expression was present in all seven tumors as shown by immunohistochemical staining. Multimodal therapeutic concepts included systemic therapies, resection, and radiation. Six patients were treated as first‐line therapy with conventional chemotherapy. All except one patient had a dismal therapy response. Subsequent therapy lines consisted of chemotherapeutic combinations followed by targeted therapies. Due to Cyclin D1 expression, the CDK4/6 inhibitor palbociclib was applied to four patients. The median therapy duration until disease progression in these patients was 4.5 months (range, 1.5–5 months). So, CCND1 genomic gain and Cyclin D1 expression are common features pointing to cell‐cycle deregulation as a possible therapeutic target. [ABSTRACT FROM AUTHOR]

Chordomas are very rare malignant neoplasms of the bone occurring almost exclusively along the spine. As the tumours are thought to arise from notochordal remnants, the vast majority of chordomas express the TBXT gene, resulting in detectable nuclear amounts of its gene product brachyury. This T-Box transcription factor is commonly recognised as being essential in chordoma cells, and limiting TBXT expression is thought to be the key factor in controlling this tumour. Although the tumour is rare, distinct molecular differences and vulnerabilities have been described with regard to its location and the progression status of the disease, rendering it mandatory for novel cell lines to reflect all relevant chordoma subtypes. Here, we describe a novel chordoma cell line arising from the pleural effusion of a disseminated, poorly differentiated chordoma. This cell line, U-CH22, represents a highly aggressive terminal chordoma and, therefore, fills a relevant gap within the panel of available cell culture models for this orphan disease. CDK7 and CDK9 inhibition was lately identified as being effective in reducing viability in four chordoma cell lines, most likely due to a reduction in brachyury levels. In this study, we determined the capability of the CDK7 inhibitor THZ1 and the CDK1/2/5/9 inhibitor dinaciclib to reduce TBXT expression at mRNA and protein levels in a broad range of nine cell lines that are models of primary, recurrent, and metastasised chordoma of the clivus and the sacrum. [ABSTRACT FROM AUTHOR]

Study Design: Systematic review. Objectives: The objective of this review paper was to summarize targeted molecular therapy options for spinal chordoma and chondrosarcoma, and to provide an update on the relevant clinical trials open for recruitment. Methods: A systematic review of the current literature was performed, according to PRISMA guidelines, to summarize the latest developments in non-surgical molecular treatment options for low grade malignant primary spinal tumours. We also summarize those actively recruiting clinical trials based on clinicaltrials.gov. Results: A total of 73 studies and completed clinical trials were reviewed. Twenty actively recruiting clinical trials (eight for chordoma and twelve for chondrosarcoma) were identified. Conclusions: There is a strong need to find new therapeutic options to complement surgical resection and radiation therapy, which remain the cornerstone of management. Targeted therapies against molecular pathways show promise as compared to conventional chemotherapy. [ABSTRACT FROM AUTHOR]

Study Design: Systematic review. Objective: In patients with extradural metastatic spine disease, we sought to systematically review the outcomes and complications of patients with intermediate Spinal Instability Neoplastic Score (SINS) lesions undergoing radiation therapy, percutaneous interventions, minimally invasive surgeries, or open spinal surgeries. Methods: Following PRISMA guidelines for systematic reviews, MEDLINE, EMBASE, Web of Science, the Cochrane Database of Systematic Reviews and the Cochrane Center Register of Controlled Trials were queried for studies that reported on SINS intermediate patients who underwent: 1) radiotherapy, 2) percutaneous intervention, 3) minimally invasive, or 4) open surgery. Dates of publication were between 2013-22. Patients with low- or high-grade SINS were excluded. Outcome measures were pain score, functional status, neurological outcome, ambulation, survival, and perioperative complications. Results: Thirty-nine studies (n = 4554) were included that analyzed outcomes in the SINS intermediate cohort. Radiotherapy appeared to provide temporary improvement in pain score; however, recurrent pain led to surgery in 15%–20% of patients. Percutaneous vertebral augmentation provided improvement in pain. Minimally invasive surgery and open surgery offered improvement in pain, quality of life, neurological, and ambulatory outcomes. Open surgery may be associated with more complications. There was limited evidence for radiofrequency ablation. Conclusion: In the SINS intermediate group, radiotherapy was associated with temporary improvement of pain but may require subsequent surgery. Both minimally invasive surgery and open spinal surgery achieved improvements in pain, quality of life, and neurological outcomes for patients with spine metastases. Open surgery may be associated with more complications. [ABSTRACT FROM AUTHOR]

Objectives: To explore the diagnostic value of MRI-based 3D texture analysis to identify texture features that can be used for discrimination of low-grade chondrosarcoma from enchondroma.Methods: Eleven patients with low-grade chondrosarcoma and 11 patients with enchondroma were retrospectively evaluated. Texture analysis was performed using mint Lesion: Kurtosis, entropy, skewness, mean of positive pixels (MPP) and uniformity of positive pixel distribution (UPP) were obtained in four MRI sequences and correlated with histopathology. The Mann-Whitney U-test and receiver operating characteristic (ROC) analysis were performed to identify most discriminative texture features. Sensitivity, specificity, accuracy and optimal cut-off values were calculated.Results: Significant differences were found in four of 20 texture parameters with regard to the different MRI sequences (p<0.01). The area under the ROC curve values to discriminate chondrosarcoma from enchondroma were 0.876 and 0.826 for kurtosis and skewness in contrast-enhanced T1 (ceT1w), respectively; in non-contrast T1, values were 0.851 and 0.822 for entropy and UPP, respectively. The highest discriminatory power had kurtosis in ceT1w with a cut-off ≥3.15 to identify low-grade chondrosarcoma (82 % sensitivity, 91 % specificity, accuracy 86 %).Conclusion: MRI-based 3D texture analysis might be able to discriminate low-grade chondrosarcoma from enchondroma by a variety of texture parameters.Key Points: • MRI texture analysis may assist in differentiating low-grade chondrosarcoma from enchondroma. • Kurtosis in the contrast-enhanced T1w has the highest power of discrimination. • Tools provide insight into tumour characterisation as a non-invasive imaging biomarker. [ABSTRACT FROM AUTHOR]