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J Nucl Med. 2019 May 10. pii: jnumed.119.227744. doi: 10.2967/jnumed.119.227744. [Epub ahead of print]

Prospective evaluation of a tumor control probability model based on dynamic 18F-FMISO PET for head-and-neck cancer radiotherapy.

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Section for Biomedical Physics, Department of Radiation Oncology, University of Tübingen, Germany.
Department of Radiation Oncology, University of Tübingen, Germany.
Department of Radiology, Diagnostic and Interventional Radiology, University of Tübingen, Germany.
Department of Nuclear Medicine, University of Tübingen, Germany.
Department of Preclinical Imaging and Radiopharmacy, University of Tübingen, Germany.
Department of Otorhinolaryngology, University of Tübingen, Germany.
Department of Radiation Oncology, University of Heidelberg, Germany.
Department of Radiation Oncology, LMU Munich.


Purpose: To evaluate an imaging parameter response relationship between the extent of tumor hypoxia quantified by dynamic 18F-Fluoromisonidazole (18F-FMISO) PET/CT and the risk of relapse after radiotherapy (RT) in patients with head-and-neck cancer (HNC). Methods: A prospective cohort of n = 25 HNC patients was examined before starting radiotherapy with dynamic 18F-FMISO PET/CT 0-240min post tracer injection (pi). 18F-FMISO image parameters including a hypoxia metric MFMISO derived from pharmacokinetic modelling of dynamic 18F-FMISO as well as maximum tumor-to-muscle ratio at 4h pi (TMRmax), gross tumor volume (VGTV), relative hypoxic volume (rHV) based on MFMISO and a logistic regression model combining VGTV and TMRmax were assessed and compared to a previous training cohort (n = 15). Dynamic 18F-FMISO was used to validate a tumor-control-probability (TCP) model based on MFMISO. The prognostic potential with respect to local control of all potential parameters was validated using the concordance index (ci) for uni-variate cox regression models determined from the training cohort, in addition to Kaplan-Meier analysis including log-rank test. Results: The TCP model was confirmed indicating that dynamic 18F-FMISO allows to stratify patients into different risk groups according to radiotherapy outcome. In this study, the hypoxia metric MFMISO was the only parameter which was confirmed as prognostic in the independent validation cohort (ci=0.71, P = 0.004). All other investigated parameters, such as TMRmax, VGTV, rHV, and the combination of VGTV and TMRmax were not able to stratify patient groups according to outcome in this validation cohort (P = n.s.). Conclusion: In this study, the relationship between the hypoxia parameter MFMISO and the risk of relapse was prospectively validated. The data supports further evaluation and external validation of dynamic 18F-FMISO PET/CT as a promising method for patient stratification and hypoxia-based radiotherapy personalization including dose painting.


FMISO PET; PET/CT; Radiation Therapy Planning; head-and-neck cancer; hypoxia; outcome prediction; radiotherapy


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