David Mönnich1,2,3, Daniela Thorwarth1,2,3, Sara Leibfarth1, Christina Pfannenberg4, Gerald Reischl5, Paul-Stefan Mauz6, Konstantin Nikolaou4, Christian la Fougère7, Daniel Zips2,3,8, Stefan Welz8. 1. a Department of Radiation Oncology, Section for Biomedical Physics , University Hospital and Medical Faculty, Eberhard Karls University Tübingen , Tübingen , Germany. 2. b German Cancer Consortium (DKTK), Partner Site Tübingen , Tübingen , Germany. 3. c German Cancer Research Center (DKFZ) , Heidelberg , Germany. 4. d Department of Diagnostic and Interventional Radiology , University Hospital and Medical Faculty, Eberhard Karls University Tübingen , Tübingen , Germany. 5. e Department of Diagnostic and Interventional Radiology, Preclinical Imaging and Radiopharmacy , University Hospital and Medical Faculty, Eberhard Karls University Tübingen , Tübingen , Germany. 6. f Department of Otorhinolaryngology, Head and Neck Surgery , University Hospital and Medical Faculty, Eberhard Karls University Tübingen , Tübingen , Germany. 7. g Department of Radiology, Nuclear Medicine , University Hospital and Medical Faculty, Eberhard Karls University Tübingen , Tübingen , Germany. 8. h Department of Radiation Oncology , University Hospital and Medical Faculty, Eberhard Karls University Tübingen , Tübingen , Germany.
Abstract
BACKGROUND: PET imaging may be used to personalize radiotherapy (RT) by identifying radioresistant tumor subvolumes for RT dose escalation. Using the tracers [18F]-fluorodeoxyglucose (FDG) and [18F]-fluoromisonidazole (FMISO), different aspects of tumor biology can be visualized. FDG depicts various biological aspects, e.g., proliferation, glycolysis and hypoxia, while FMISO is more hypoxia specific. In this study, we analyzed size and overlap of volumes based on the two markers for head-and-neck cancer patients (HNSCC). MATERIAL AND METHODS: Twenty five HNSCC patients underwent a CT scan, as well as FDG and dynamic FMISO PET/CT prior to definitive radio-chemotherapy in a prospective FMISO dose escalation study. Three PET-based subvolumes of the primary tumor (GTVprim) were segmented: a highly FDG-avid volume VFDG, a hypoxic volume on the static FMISO image acquired four hours post tracer injection (VH) and a retention/perfusion volume (VM) using pharmacokinetic modeling of dynamic FMISO data. Absolute volumes, overlaps and distances to agreement (DTA) were evaluated. RESULTS: Sizes of PET-based volumes and the GTVprim are significantly different (GTVprim>VFDG>VH >VM; p < .05). VH is covered by VFDG or DTAs are small (mean coverage 74.4%, mean DTA 1.4 mm). Coverage of VM is less pronounced. With respect to VFDG and VH, the mean coverage is 48.7% and 43.1% and the mean DTA is 5.3 mm and 6.3 mm, respectively. For two patients, DTAs were larger than 2 cm. CONCLUSIONS: Hypoxic subvolumes from static PET imaging are typically covered by or in close proximity to highly FDG-avid subvolumes. Therefore, dose escalation to FDG positive subvolumes should cover the static hypoxic subvolumes in most patients, with the disadvantage of larger volumes, resulting in a higher risk of dose-limiting toxicity. Coverage of subvolumes from dynamic FMISO PET is less pronounced. Further studies are needed to explore the relevance of mismatches in functional imaging.
BACKGROUND: PET imaging may be used to personalize radiotherapy (RT) by identifying radioresistant tumor subvolumes for RT dose escalation. Using the tracers [18F]-fluorodeoxyglucose (FDG) and [18F]-fluoromisonidazole (FMISO), different aspects of tumor biology can be visualized. FDG depicts various biological aspects, e.g., proliferation, glycolysis and hypoxia, while FMISO is more hypoxia specific. In this study, we analyzed size and overlap of volumes based on the two markers for head-and-neck cancerpatients (HNSCC). MATERIAL AND METHODS: Twenty five HNSCCpatients underwent a CT scan, as well as FDG and dynamic FMISO PET/CT prior to definitive radio-chemotherapy in a prospective FMISO dose escalation study. Three PET-based subvolumes of the primary tumor (GTVprim) were segmented: a highly FDG-avid volume VFDG, a hypoxic volume on the static FMISO image acquired four hours post tracer injection (VH) and a retention/perfusion volume (VM) using pharmacokinetic modeling of dynamic FMISO data. Absolute volumes, overlaps and distances to agreement (DTA) were evaluated. RESULTS: Sizes of PET-based volumes and the GTVprim are significantly different (GTVprim>VFDG>VH >VM; p < .05). VH is covered by VFDG or DTAs are small (mean coverage 74.4%, mean DTA 1.4 mm). Coverage of VM is less pronounced. With respect to VFDG and VH, the mean coverage is 48.7% and 43.1% and the mean DTA is 5.3 mm and 6.3 mm, respectively. For two patients, DTAs were larger than 2 cm. CONCLUSIONS: Hypoxic subvolumes from static PET imaging are typically covered by or in close proximity to highly FDG-avid subvolumes. Therefore, dose escalation to FDG positive subvolumes should cover the static hypoxic subvolumes in most patients, with the disadvantage of larger volumes, resulting in a higher risk of dose-limiting toxicity. Coverage of subvolumes from dynamic FMISO PET is less pronounced. Further studies are needed to explore the relevance of mismatches in functional imaging.
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