dc.contributor.author | Aravind, P | |
dc.contributor.author | Popat, S | |
dc.contributor.author | Barwick, TD | |
dc.contributor.author | Soneji, N | |
dc.contributor.author | Lythgoe, M | |
dc.contributor.author | Sreter, KB | |
dc.contributor.author | Lozano-Kuehne, JP | |
dc.contributor.author | Bergqvist, M | |
dc.contributor.author | Patel, N | |
dc.contributor.author | Aboagye, EO | |
dc.contributor.author | Kenny, LM | |
dc.coverage.spatial | Switzerland | |
dc.date.accessioned | 2023-10-20T13:19:43Z | |
dc.date.available | 2023-10-20T13:19:43Z | |
dc.date.issued | 2023-07-22 | |
dc.identifier | ARTN 3718 | |
dc.identifier | cancers15143718 | |
dc.identifier.citation | Cancers, 2023, 15 (14), pp. 3718 - | en_US |
dc.identifier.issn | 2072-6694 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/6024 | |
dc.identifier.eissn | 2072-6694 | |
dc.identifier.eissn | 2072-6694 | |
dc.identifier.doi | 10.3390/cancers15143718 | |
dc.identifier.doi | 10.3390/cancers15143718 | |
dc.description.abstract | UNLABELLED: Thymidylate synthase (TS) remains a major target for cancer therapy. TS inhibition elicits increases in DNA salvage pathway activity, detected as a transient compensatory "flare" in 3'-deoxy-3'-[18F]fluorothymidine positron emission tomography (18F-FLT PET). We determined the magnitude of the 18F-FLT flare in non-small cell lung cancer (NSCLC) patients treated with the antifolate pemetrexed in relation to clinical outcome. METHOD: Twenty-one patients with advanced/metastatic non-small cell lung cancer (NSCLC) scheduled to receive palliative pemetrexed ± platinum-based chemotherapy underwent 18F-FLT PET at baseline and 4 h after initiating single-agent pemetrexed. Plasma deoxyuridine (dUrd) levels and thymidine kinase 1 (TK1) activity were measured before each scan. Patients were then treated with the combination therapy. The 18F-FLT PET variables were compared to RECIST 1.1 and overall survival (OS). RESULTS: Nineteen patients had evaluable PET scans at both time points. A total of 32% (6/19) of patients showed 18F-FLT flares (>20% change in SUVmax-wsum). At the lesion level, only one patient had an FLT flare in all the lesions above (test-retest borders). The remaining had varied uptake. An 18F-FLT flare occurred in all lesions in 1 patient, while another patient had an 18F-FLT reduction in all lesions; 17 patients showed varied lesion uptake. All patients showed global TS inhibition reflected in plasma dUrd levels (p < 0.001) and 18F-FLT flares of TS-responsive normal tissues including small bowel and bone marrow (p = 0.004 each). Notably, 83% (5/6) of patients who exhibited 18F-FLT flares were also RECIST responders with a median OS of 31 m, unlike patients who did not exhibit 18F-FLT flares (15 m). Baseline plasma TK1 was prognostic of survival but its activity remained unchanged following treatment. CONCLUSIONS: The better radiological response and longer survival observed in patients with an 18F-FLT flare suggest the efficacy of the tracer as an indicator of the early therapeutic response to pemetrexed in NSCLC. | |
dc.format | Electronic | |
dc.format.extent | 3718 - | |
dc.language | eng | |
dc.language.iso | eng | en_US |
dc.publisher | MDPI | en_US |
dc.relation.ispartof | Cancers | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.subject | 18F-FLT | |
dc.subject | NSCLC | |
dc.subject | PET | |
dc.subject | pemetrexed | |
dc.subject | thymidine kinase | |
dc.title | A Subset of Non-Small Cell Lung Cancer Patients Treated with Pemetrexed Show 18F-Fluorothymidine "Flare" on Positron Emission Tomography. | en_US |
dc.type | Journal Article | |
dcterms.dateAccepted | 2023-07-20 | |
dc.date.updated | 2023-10-20T13:19:08Z | |
rioxxterms.version | VoR | en_US |
rioxxterms.versionofrecord | 10.3390/cancers15143718 | en_US |
rioxxterms.licenseref.startdate | 2023-07-22 | |
rioxxterms.type | Journal Article/Review | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/37509378 | |
pubs.issue | 14 | |
pubs.organisational-group | ICR | |
pubs.organisational-group | ICR/Primary Group | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Clinical Studies/Thoracic Oncology | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Clinical Studies/Thoracic Oncology/Thoracic Oncology (hon.) | |
pubs.publication-status | Published online | |
pubs.publisher-url | http://dx.doi.org/10.3390/cancers15143718 | |
pubs.volume | 15 | |
dc.contributor.icrauthor | Popat, Sanjay | |
icr.provenance | Deposited by Mr Arek Surman on 2023-10-20. Deposit type is initial. No. of files: 1. Files: A Subset of Non-Small Cell Lung Cancer Patients Treated with Pemetrexed Show sup18supF-Fluorothymidine Flare on Positron Emi.pdf | |