Dataset Information

Utility of Integrated PET/MRI for the Primary Diagnostic Work-Up of Patients with Ewing Sarcoma: Preliminary Results.

ABSTRACT:

Background

This study was conducted to evaluate the clinical applicability of integrated PET/MRI for staging and monitoring the effectiveness of neoadjuvant chemotherapy in Ewing sarcoma patients.

Methods

A total of 11 juvenile patients with confirmed Ewing sarcoma, scheduled for induction polychemotherapy, were prospectively enrolled for a PET/MR examination before, during and after the end of treatment. Two experienced physicians analysed the imaging datasets. They were asked to perform a whole-body staging in all three examinations and to define treatment response according to the RECIST1.1 and PERCIST criteria for each patient.

Results

In eight patients lymph node and/or distant metastases were detected at initial diagnosis. According to the reference standard, three patients achieved complete response, six patients partial response, and one patient showed stable disease while another patient showed progressive disease. RECIST1.1 categorized the response to treatment in 5/11 patients correctly and showed a tendency to underestimate the response to treatment in the remaining six patients. PERCIST defined response to treatment in 9/11 patients correctly and misclassified two patients with a PR as CR.

Conclusion

PET/MRI may serve as a valuable imaging tool for primary staging and response assessment of juvenile patients with Ewing sarcoma to induction chemotherapy, accompanied by a reasonable radiation dose for the patient.

SUBMITTER: Chodyla M

PROVIDER: S-EPMC9600118 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Utility of Integrated PET/MRI for the Primary Diagnostic Work-Up of Patients with Ewing Sarcoma: Preliminary Results.

Chodyla Michal M Barbato Francesco F Dirksen Uta U Kirchner Julian J Schaarschmidt Benedikt M BM Schweiger Bernd B Forsting Michael M Herrmann Ken K Umutlu Lale L Grueneisen Johannes J

Diagnostics (Basel, Switzerland) 20220921 10

<h4>Background</h4>This study was conducted to evaluate the clinical applicability of integrated PET/MRI for staging and monitoring the effectiveness of neoadjuvant chemotherapy in Ewing sarcoma patients.<h4>Methods</h4>A total of 11 juvenile patients with confirmed Ewing sarcoma, scheduled for induction polychemotherapy, were prospectively enrolled for a PET/MR examination before, during and after the end of treatment. Two experienced physicians analysed the imaging datasets. They were asked to ...[more]

PMID: 36291967

Similar Datasets

Project description:BackgroundThe clinical significance of GLI1 expression either through canonical Hedgehog signal transduction or through non-canonical mechanisms in rhabdomyosarcoma (RMS) or Ewing sarcoma (EWS) is incompletely understood. We tested a role for Hedgehog (HH) signal transduction and GL11 expression in development of vincristine (VCR) resistance in RMS and EWS.MethodsWe characterized baseline expression and activity of HH pathway components in 5 RMS (RD, Rh18, Ruch-2, Rh30, and Rh41) and 5 EWS (CHLA9, CHLA10, TC32, CHLA258, and TC71) cell lines. We then established VCR-resistant RMS and EWS cell lines by exposing cells to serially increasing concentrations of VCR and determining the IC50. We defined resistance as a ≥ 30-fold increase in IC50 compared with parental cells. We determined changes in gene expression in the VCR-resistant cells compared with parental cells using an 86-gene cancer drug resistance array that included GLI1 and tested the effect of GLI1 inhibition with GANT61 or GLI1 siRNA on VCR resistance.ResultsWe found evidence for HH pathway activity and GLI1 expression in RMS and EWS cell lines at baseline, and evidence that GLI1 contributes to survival and proliferation of these sarcoma cells. We were able to establish 4 VCR-resistant cell lines (Ruch-2VR, Rh30VR, Rh41VR, and TC71VR). GLI1 was significantly up-regulated in the Rh30VR, Rh41VR, and TC71VR cells. The only other gene in the drug resistance panel that was significantly up-regulated in each of these VCR-resistant cell lines compared with their corresponding parental cells was the GLI1 direct target and multidrug resistance gene, ATP-binding cassette sub-family B member 1 (MDR1). We established major vault protein (MVP), which was up-regulated in both vincristine-resistant alveolar RMS cell lines (Rh30VR and Rh41VR), as another direct target of GLI1 during development of drug resistance. Treatment of the VCR-resistant cell lines with the small molecule inhibitor GANT61 or GLI1 siRNA together with VCR significantly decreased cell viability at doses that did not reduce viability individually.ConclusionsThese experiments demonstrate that GLI1 up-regulation contributes to VCR resistance in RMS and EWS cell lines and suggest that targeting GLI1 may benefit patients with RMS or EWS by reducing multidrug resistance.

Project description:Adamantinoma-like Ewing sarcoma (ALES) has traditionally been considered a variant of Ewing sarcoma because it generally harbors EWSR1::FLI1 fusions despite showing diffuse positivity for keratins and p40. However, it has become increasingly recognized that different tumors can have identical translocations, including shared fusions between carcinomas and sarcomas, raising questions as to whether ALES might represent a separate entity. Using methylation profiling, we further explored the relationship between Ewing sarcoma and ALES. The archives of multiple institutions were searched for candidate cases of ALES. DNA methylation profiling was performed and results were compared to corresponding data from conventional Ewing sarcoma. Twelve cases of ALES (5 previously reported) were identified in 10 men and 2 women (aged 20-72 years; median age, 41.5 years). Cases included tumors arising in the parotid gland (3), sinonasal cavity (2), submandibular gland (2), thyroid gland (1), neck (1), gingiva (1), hypopharynx (1), and mandible (1). Histologic review consistently showed sheets and nests of basaloid cells within a fibromyxoid or hyalinized stroma. All tumors were positive for at least 1 keratin and CD99 expression, whereas all 10 cases tested were positive for p63 or p40; S100 protein expression was noted in 2 cases. Cases harbored either EWSR1::FLI1 fusions (n = 6), FUS::FLI1 fusions (n = 1), and/or EWSR1 rearrangements (n = 6). Methylation profiling was successful in 11/12 cases evaluated. Unsupervised clustering and dimensionality reduction (Uniform Manifold Approximation and Projection) of DNA methylation data revealed a distinct methylation cluster for all 11 cases, including the tumor with the FUS::FLI1 fusion, which clearly segregated them from the conventional Ewing sarcoma. Follow-up (n = 11, 1-154 months) revealed that 4 patients experienced recurrence and 6 developed metastatic disease. ALES demonstrates a distinct methylation signature from conventional Ewing sarcoma. This finding adds to the distinctive immunoprofile of ALES, suggesting that these 2 tumors should be considered distinct entities rather than histologic extremes of the same disease.

Project description:Background and purposeThe differentiation between Parkinson disease and atypical parkinsonian syndromes can be challenging in clinical practice, especially in early disease stages. Brain MR imaging can help to increase certainty about the diagnosis. Our goal was to evaluate the added value of SWI in relation to conventional 3T brain MR imaging for the diagnostic work-up of early-stage parkinsonism.Materials and methodsThis was a prospective observational cohort study of 65 patients presenting with parkinsonism but with an uncertain initial clinical diagnosis. At baseline, 3T brain MR imaging with conventional and SWI sequences was performed. After clinical follow-up, probable diagnoses could be made in 56 patients, 38 patients diagnosed with Parkinson disease and 18 patients diagnosed with atypical parkinsonian syndromes, including 12 patients diagnosed with multiple system atrophy-parkinsonian form. In addition, 13 healthy controls were evaluated with SWI. Abnormal findings on conventional brain MR imaging were grouped into disease-specific scores. SWI was analyzed by a region-of-interest method of different brain structures. One-way ANOVA was performed to analyze group differences. Receiver operating characteristic analyses were performed to evaluate the diagnostic accuracy of conventional brain MR imaging separately and combined with SWI.ResultsDisease-specific scores of conventional brain MR imaging had a high specificity for atypical parkinsonian syndromes (80%-90%), but sensitivity was limited (50%-80%). The mean SWI signal intensity of the putamen was significantly lower for multiple system atrophy-parkinsonian form than for Parkinson disease and controls (P < .001). The presence of severe dorsal putaminal hypointensity improved the accuracy of brain MR imaging: The area under the curve was increased from 0.75 to 0.83 for identifying multiple system atrophy-parkinsonian form, and it was increased from 0.76 to 0.82 for identifying atypical parkinsonian syndromes as a group.ConclusionsSWI improves the diagnostic accuracy of 3T brain MR imaging in the work-up of parkinsonism by identifying severe putaminal hypointensity as a sign indicative of multiple system atrophy-parkinsonian form.

Dataset Information

Utility of Integrated PET/MRI for the Primary Diagnostic Work-Up of Patients with Ewing Sarcoma: Preliminary Results.

Background

Methods

Results

Conclusion

Publications

Utility of Integrated PET/MRI for the Primary Diagnostic Work-Up of Patients with Ewing Sarcoma: Preliminary Results.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets