Assessment of treatment responses in children and adolescents with Ewing sarcoma with metabolic tumor parameters derived from 18F-FDG-PET/CT and circulating tumor DNA

Schmidkonz, Christian; Krumbholz, Manuela; Atzinger, Armin; Cordes, Michael; Goetz, Theresa Ida; Prante, Olaf; Ritt, Philipp; Schaefer, Christiane; Agaimy, Abbas; Hartmann, Wolfgang; Fröhlich, Birgit; Bäuerle, Tobias; Dirksen, Uta; Kuwert, Torsten; Metzler, Markus

doi:10.1007/s00259-019-04649-1

Cited by 16 publications

(19 citation statements)

References 37 publications

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“…As mentioned above, while several studies examined the validity of the combination of cfDNA or ctDNA with PET/CT for the estimation of tumour burden or baseline staging, there still is a lack of similar data on the role of such combination in the follow-up monitoring and evaluation of treatment response in advanced-stage cancer patients undergoing systemic therapy. In our study, we found significant correlations between the dynamics of ctDNA and MTV and TLG during the course of chemotherapy, which is in agreement with a study recently reported by Schmidkonz et al, however their study was focused on Ewing sarcoma (33). The role of ctDNA as a promising blood-based cancer biomarker in NSCLC has been intensively investigated in recent years.…”

Section: Discussionsupporting

confidence: 92%

Combination of Circulating Tumour DNA and¹⁸F-FDG PET/CT for Precision Monitoring of Therapy Response in Patients With Advanced Non-small Cell Lung Cancer: A Prospective Study

Fiala

Baxa

Svatoň

et al. 2022

Cancer Genomics Proteomics

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Background/Aim: Circulating tumour DNA (ctDNA) represents an emerging biomarker in non-small cell lung cancer (NSCLC). We focused on the combination of ctDNA and positron emission tomography/computed tomography (PET/CT) in the follow-up monitoring of advanced-stage NSCLC patients treated with chemotherapy. Patients and Methods: Eighty-four patients were enrolled in this study. 18 F-fluorodeoxyglucose PET/CT and ctDNA assessments were performed at baseline and after two cycles of chemotherapy (follow-up). Results: There was a correlation of ctDNA with metabolic tumour volume (MTV), total lesion glycolysis (TLG), and iodine concentration (IC) at baseline (p=0.001, p=0.001, p=0.003) and at follow-up (p=0.006, p=0.002, p=0.001). The objective response was associated with follow-up ctDNA (p<0.001) and the change of all PET/CT parameters. ROC analyses showed that the combination of follow-up ctDNA with changes in SUVmax is very promising for the estimation of objective response and progression-free survival. Conclusion: The combination of ctDNA assessment with PET/CT is a promising approach for the follow-up monitoring of therapy response and prognosis estimation of advanced-stage NSCLC patients.Lung cancer is one of the leading cancer-related causes of morbidity and mortality worldwide (1, 2), with non-small cell lung cancer (NSCLC) being the most common histological type, representing more than 80% of all cases (3). The management of locally advanced or metastatic NSCLC has been markedly changing in recent years with the introduction of targeted therapies and immune checkpoint inhibitors leading to significant improvements in patient survival. The establishment of personalised medicine based on molecular biomarkers has also brought a significant progress. Despite great advances in the field of therapeutic strategies, it is apparent that further progress is needed in the development of novel diagnostic tools enabling precision monitoring or prediction of therapy response. Notably a precision assessment of early therapy response could enable modification of the treatment strategy to prevent patients from staying on an ineffective therapy.

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Section: Discussionsupporting

confidence: 92%

Combination of Circulating Tumour DNA and¹⁸F-FDG PET/CT for Precision Monitoring of Therapy Response in Patients With Advanced Non-small Cell Lung Cancer: A Prospective Study

Fiala

Baxa

Svatoň

et al. 2022

Cancer Genomics Proteomics

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“…Pediatric patients in various clinical stages were all involved (including newly diagnosed cancer for an initial staging, restaging and therapy response assessment). Different backgrounds (liver, spleen and blood pool) were selected for thoroughly evaluation considering the variability in lesions and organs' uptake pattern, where the mediastinal blood pool, liver, and spleen serve as the cutoffs for PET positivity in the evaluation of the response assessment and post-treatment surveillance [34][35][36][37]. However, VOI determination could be still di cult due to the large difference in children's age, height and weight.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of pediatric malignancies using total-body PET/CT with half-dose [18F]-FDG

Chen

Liu

et al. 2022

Eur J Nucl Med Mol Imaging

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PurposeTo explore the effect of half 18 F-FDG dose on image quality of pediatric oncological patients using totalbody PET/CT. and investigate the ultra-low dose of administered tracer activity. Methods 100 pediatric oncological patients who underwent total-body PET/CT using the uEXPLORER scanner with half 18 F-FDG dose (1.85 MBq/kg) were retrospectively enrolled. The PET images were rstly reconstructed using all the 600s data, and then split into 300s, 180s, 60s, 40s and 20s duration groups. The subjective analysis method was assessed using a 5-point Likert scales. Objective quantitative metrics included the maximum standard uptake value (SUV max ), SUV mean , standard deviation (SD), signal to noise ratio (SNR) and SNR norm of the backgrounds. The variability in lesion SUV mean , SUV max , and tumor-to-background ratio (TBR) were also calculated. ResultsThe overall image quality scores in Group 600s, 300s, 180s and 60s were 4.9 ± 0.2, 4.9 ± 0.3, 4.4±0.5 and 3.5±0.5 respectively. All the lesions identi ed in half-dose images were localised down to G60s (1/20-dose) images; while 56% of the lesion could be clearly identi ed in G20s (1/60-dose) images. With stimulated reduced doses, SUV max and SD of backgrounds were gradually increased, while TBR values showed no statistically signi cant deviation among all the groups (all p > 0.1). Using the half-dose images as reference, the variability of lesion SUV max gradually increased from G180s to G20s, while lesion SUVmean remained stable for all the age groups. SNR norm was highly correlated with the age in a negative direction. ConclusionsThe total-body PET/CT with half 18 F-FDG dose achieved good performance in pediatric patients considering the su cient image quality and lesion conspicuity. Su cient image quality and lesion conspicuity could be maintained with an administered dose reduced down to 1/20-dose (0.185 MBq/kg, , estimated effective dose: 0.18-0.26 mSv).

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“…Targeted NGS panels of select EWSR1 introns obviate the need for a priori tumor profiling but are not as sensitive as PCR-based assays. In a series of studies evaluating the ability to detect ctDNA in patients with newly diagnosed localized and metastatic patients with EwS, ctDNA detection rates for PCR- and NGS-based assays were 137/146 (94%) and 61/100 (61%) of samples, respectively 80 , 91 , 94 – 96 . In patients in whom ctDNA is detectable by both droplet digital PCR and targeted NGS assays, a strong correlation between the two methodologies has been demonstrated 79 , 96 .…”

Section: Summary Of Evidence For Molecular Biomarkers For Risk-strati...mentioning

confidence: 99%

An international working group consensus report for the prioritization of molecular biomarkers for Ewing sarcoma

et al. 2022

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The advent of dose intensified interval compressed therapy has improved event-free survival for patients with localized Ewing sarcoma (EwS) to 78% at 5 years. However, nearly a quarter of patients with localized tumors and 60–80% of patients with metastatic tumors suffer relapse and die of disease. In addition, those who survive are often left with debilitating late effects. Clinical features aside from stage have proven inadequate to meaningfully classify patients for risk-stratified therapy. Therefore, there is a critical need to develop approaches to risk stratify patients with EwS based on molecular features. Over the past decade, new technology has enabled the study of multiple molecular biomarkers in EwS. Preliminary evidence requiring validation supports copy number changes, and loss of function mutations in tumor suppressor genes as biomarkers of outcome in EwS. Initial studies of circulating tumor DNA demonstrated that diagnostic ctDNA burden and ctDNA clearance during induction are also associated with outcome. In addition, fusion partner should be a pre-requisite for enrollment on EwS clinical trials, and the fusion type and structure require further study to determine prognostic impact. These emerging biomarkers represent a new horizon in our understanding of disease risk and will enable future efforts to develop risk-adapted treatment.

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Assessment of treatment responses in children and adolescents with Ewing sarcoma with metabolic tumor parameters derived from 18F-FDG-PET/CT and circulating tumor DNA

Cited by 16 publications

References 37 publications

Combination of Circulating Tumour DNA and¹⁸F-FDG PET/CT for Precision Monitoring of Therapy Response in Patients With Advanced Non-small Cell Lung Cancer: A Prospective Study

Combination of Circulating Tumour DNA and¹⁸F-FDG PET/CT for Precision Monitoring of Therapy Response in Patients With Advanced Non-small Cell Lung Cancer: A Prospective Study

Evaluation of pediatric malignancies using total-body PET/CT with half-dose [18F]-FDG

An international working group consensus report for the prioritization of molecular biomarkers for Ewing sarcoma

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Assessment of treatment responses in children and adolescents with Ewing sarcoma with metabolic tumor parameters derived from 18F-FDG-PET/CT and circulating tumor DNA

Cited by 16 publications

References 37 publications

Combination of Circulating Tumour DNA and18F-FDG PET/CT for Precision Monitoring of Therapy Response in Patients With Advanced Non-small Cell Lung Cancer: A Prospective Study

Combination of Circulating Tumour DNA and18F-FDG PET/CT for Precision Monitoring of Therapy Response in Patients With Advanced Non-small Cell Lung Cancer: A Prospective Study

Evaluation of pediatric malignancies using total-body PET/CT with half-dose [18F]-FDG

An international working group consensus report for the prioritization of molecular biomarkers for Ewing sarcoma

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Product

Resources

About

Combination of Circulating Tumour DNA and¹⁸F-FDG PET/CT for Precision Monitoring of Therapy Response in Patients With Advanced Non-small Cell Lung Cancer: A Prospective Study

Combination of Circulating Tumour DNA and¹⁸F-FDG PET/CT for Precision Monitoring of Therapy Response in Patients With Advanced Non-small Cell Lung Cancer: A Prospective Study