Associations between detectable circulating tumor DNA and tumor glucose uptake measured by 18F-FDG PET/CT in early-stage non-small cell lung cancer
Abstract Background The low level of circulating tumor DNA (ctDNA) in the blood is a well-known challenge for the application of liquid biopsies in early-stage non-small cell lung cancer (NSCLC) management. Studies of metastatic NSCLC indicate that ctDNA levels are associated with tumor metabolic ac...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-07-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-023-11147-z |
| _version_ | 1797774131192659968 |
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| author | Anine Larsen Ottestad Håkon Johansen Tarje Onsøien Halvorsen Hong Yan Dai Sissel Gyrid Freim Wahl Elisabeth Fritzke Emdal Bjørn Henning Grønberg |
| author_facet | Anine Larsen Ottestad Håkon Johansen Tarje Onsøien Halvorsen Hong Yan Dai Sissel Gyrid Freim Wahl Elisabeth Fritzke Emdal Bjørn Henning Grønberg |
| author_sort | Anine Larsen Ottestad |
| collection | DOAJ |
| description | Abstract Background The low level of circulating tumor DNA (ctDNA) in the blood is a well-known challenge for the application of liquid biopsies in early-stage non-small cell lung cancer (NSCLC) management. Studies of metastatic NSCLC indicate that ctDNA levels are associated with tumor metabolic activity as measured by 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT). This study investigated this association in NSCLC patients considered for potentially curative treatment and explored whether the two methods provide independent prognostic information. Method Patients with stage I-III NSCLC who had routinely undergone an 18F-FDG PET/CT scan and exploratory ctDNA analyses were included. Tumor glucose uptake was measured by maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) from the 18F-FDG PET/CT scans. ctDNA detectability and quantity, using variant allele frequency, were estimated by tumor-informed ctDNA analyses. Results In total, 63 patients (median age 70 years, 60% women, and 90% adenocarcinoma) were included. The tumor glucose uptake (SUVmax, MTV, and TLG) was significantly higher in patients with detectable ctDNA (n = 19, p < 0.001). The ctDNA quantity correlated with MTV (Spearman’s ρ = 0.53, p = 0.021) and TLG (Spearman’s ρ = 0.56, p = 0.013) but not with SUVmax (Spearman’s ρ = 0.034, p = 0.15). ctDNA detection was associated with shorter OS independent of MTV (HR: 2.70, 95% CI: 1.07–6.82, p = 0.035) and TLG (HR: 2.63, 95% CI: 1.06–6.51, p = 0.036). Patients with high tumor glucose uptake and detectable ctDNA had shorter overall survival and progression-free survival than those without detectable ctDNA, though these associations were not statistically significant (p > 0.05). Conclusion There was a positive correlation between plasma ctDNA quantity and MTV and TLG in early-stage NSCLC patients. Despite the correlation, the results indicated that ctDNA detection was a negative prognostic factor independent of MTV and TLG. |
| first_indexed | 2024-03-12T22:16:31Z |
| format | Article |
| id | doaj.art-10b2f79c6a824b28a9b2d9a9d2004e9d |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-03-12T22:16:31Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-10b2f79c6a824b28a9b2d9a9d2004e9d2023-07-23T11:17:07ZengBMCBMC Cancer1471-24072023-07-012311910.1186/s12885-023-11147-zAssociations between detectable circulating tumor DNA and tumor glucose uptake measured by 18F-FDG PET/CT in early-stage non-small cell lung cancerAnine Larsen Ottestad0Håkon Johansen1Tarje Onsøien Halvorsen2Hong Yan Dai3Sissel Gyrid Freim Wahl4Elisabeth Fritzke Emdal5Bjørn Henning Grønberg6Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU)Department of Radiology and Nuclear Medicine, St. Olavs Hospital, Trondheim University HospitalDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU)Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU)Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU)Department of Pathology, Clinic of Laboratory Medicine, St. Olavs Hospital, Trondheim University HospitalDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU)Abstract Background The low level of circulating tumor DNA (ctDNA) in the blood is a well-known challenge for the application of liquid biopsies in early-stage non-small cell lung cancer (NSCLC) management. Studies of metastatic NSCLC indicate that ctDNA levels are associated with tumor metabolic activity as measured by 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT). This study investigated this association in NSCLC patients considered for potentially curative treatment and explored whether the two methods provide independent prognostic information. Method Patients with stage I-III NSCLC who had routinely undergone an 18F-FDG PET/CT scan and exploratory ctDNA analyses were included. Tumor glucose uptake was measured by maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) from the 18F-FDG PET/CT scans. ctDNA detectability and quantity, using variant allele frequency, were estimated by tumor-informed ctDNA analyses. Results In total, 63 patients (median age 70 years, 60% women, and 90% adenocarcinoma) were included. The tumor glucose uptake (SUVmax, MTV, and TLG) was significantly higher in patients with detectable ctDNA (n = 19, p < 0.001). The ctDNA quantity correlated with MTV (Spearman’s ρ = 0.53, p = 0.021) and TLG (Spearman’s ρ = 0.56, p = 0.013) but not with SUVmax (Spearman’s ρ = 0.034, p = 0.15). ctDNA detection was associated with shorter OS independent of MTV (HR: 2.70, 95% CI: 1.07–6.82, p = 0.035) and TLG (HR: 2.63, 95% CI: 1.06–6.51, p = 0.036). Patients with high tumor glucose uptake and detectable ctDNA had shorter overall survival and progression-free survival than those without detectable ctDNA, though these associations were not statistically significant (p > 0.05). Conclusion There was a positive correlation between plasma ctDNA quantity and MTV and TLG in early-stage NSCLC patients. Despite the correlation, the results indicated that ctDNA detection was a negative prognostic factor independent of MTV and TLG.https://doi.org/10.1186/s12885-023-11147-z18F-FDG PET/CTCirculating tumor DNANon-small cell lung cancerGlucose metabolismLiquid biopsy |
| spellingShingle | Anine Larsen Ottestad Håkon Johansen Tarje Onsøien Halvorsen Hong Yan Dai Sissel Gyrid Freim Wahl Elisabeth Fritzke Emdal Bjørn Henning Grønberg Associations between detectable circulating tumor DNA and tumor glucose uptake measured by 18F-FDG PET/CT in early-stage non-small cell lung cancer BMC Cancer 18F-FDG PET/CT Circulating tumor DNA Non-small cell lung cancer Glucose metabolism Liquid biopsy |
| title | Associations between detectable circulating tumor DNA and tumor glucose uptake measured by 18F-FDG PET/CT in early-stage non-small cell lung cancer |
| title_full | Associations between detectable circulating tumor DNA and tumor glucose uptake measured by 18F-FDG PET/CT in early-stage non-small cell lung cancer |
| title_fullStr | Associations between detectable circulating tumor DNA and tumor glucose uptake measured by 18F-FDG PET/CT in early-stage non-small cell lung cancer |
| title_full_unstemmed | Associations between detectable circulating tumor DNA and tumor glucose uptake measured by 18F-FDG PET/CT in early-stage non-small cell lung cancer |
| title_short | Associations between detectable circulating tumor DNA and tumor glucose uptake measured by 18F-FDG PET/CT in early-stage non-small cell lung cancer |
| title_sort | associations between detectable circulating tumor dna and tumor glucose uptake measured by 18f fdg pet ct in early stage non small cell lung cancer |
| topic | 18F-FDG PET/CT Circulating tumor DNA Non-small cell lung cancer Glucose metabolism Liquid biopsy |
| url | https://doi.org/10.1186/s12885-023-11147-z |
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