Prospective Evaluation of a Tumor Control Probability Model Based on Dynamic 18F-FMISO PET for Head and Neck Cancer Radiotherapy

Daniela Thorwarth; Stefan Welz; David Mönnich; Christina Pfannenberg; Konstantin Nikolaou; Matthias Reimold; Christian La Fougère; Gerald Reischl; Paul-Stefan Mauz; Frank Paulsen; Markus Alber; Claus Belka; Daniel Zips

doi:10.2967/jnumed.119.227744

Prospective Evaluation of a Tumor Control Probability Model Based on Dynamic ¹⁸F-FMISO PET for Head and Neck Cancer Radiotherapy

J Nucl Med. 2019 Dec;60(12):1698-1704. doi: 10.2967/jnumed.119.227744. Epub 2019 May 10.

Authors

Daniela Thorwarth^{1

2}, Stefan Welz³, David Mönnich⁴, Christina Pfannenberg⁵, Konstantin Nikolaou⁵, Matthias Reimold⁶, Christian La Fougère⁶, Gerald Reischl⁷, Paul-Stefan Mauz⁸, Frank Paulsen³, Markus Alber^{4

9}, Claus Belka^{2

10}, Daniel Zips^{2

3}

Affiliations

¹ Section for Biomedical Physics, Department of Radiation Oncology, University of Tübingen, Tübingen, Germany daniela.thorwarth@med.uni-tuebingen.de.
² German Cancer Consortium, Tübingen, Germany, and German Cancer Research Center, Heidelberg, Germany.
³ Department of Radiation Oncology, University of Tübingen, Tübingen, Germany.
⁴ Section for Biomedical Physics, Department of Radiation Oncology, University of Tübingen, Tübingen, Germany.
⁵ Diagnostic and Interventional Radiology, Department of Radiology, University of Tübingen, Tübingen, Germany.
⁶ Department of Nuclear Medicine, University of Tübingen, Tübingen, Germany.
⁷ Department of Preclinical Imaging and Radiopharmacy, University of Tübingen, Tübingen, Germany.
⁸ Department of Otorhinolaryngology, University of Tübingen, Tübingen, Germany.
⁹ Department of Radiation Oncology, University of Heidelberg, Heidelberg, Germany; and.
¹⁰ Department of Radiation Oncology, LMU Munich, München, Germany.

Abstract

Our purpose was 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 in patients with head and neck cancer. Methods: Before a prospective cohort of 25 head and neck cancer patients started radiotherapy, they were examined with dynamic ¹⁸F-FMISO PET/CT 0-240 min after tracer injection. ¹⁸F-FMISO image parameters, including a hypoxia metric, M_FMISO, derived from pharmacokinetic modeling of dynamic ¹⁸F-FMISO and maximum tumor-to-muscle ratio (TMR_max) at 4 h after injection, gross tumor volume (GTV), relative hypoxic volume based on M_FMISO, and a logistic regression model combining GTV and TMR_max, were assessed and compared with a previous training cohort (n = 15). Dynamic ¹⁸F-FMISO was used to validate a tumor control probability model based on M_FMISO The prognostic potential with respect to local control of all potential parameters was validated using the concordance index for univariate Cox regression models determined from the training cohort, in addition to Kaplan-Meier analysis including the log-rank test. Results: The tumor control probability model was confirmed, indicating that dynamic ¹⁸F-FMISO allows stratification of patients into different risk groups according to radiotherapy outcome. In this study, M_FMISO was the only parameter that was confirmed as prognostic in the independent validation cohort (concordance index, 0.71; P = 0.004). All other investigated parameters, such as TMR_max, GTV, relative hypoxic volume, and the combination of GTV and TMR_max, were not able to stratify patient groups according to outcome in this validation cohort (P = not statistically significant). Conclusion: In this study, the relationship between M_FMISO and the risk of relapse was prospectively validated. The data support 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.

Keywords: 18F-FMISO PET/CT; TCP model; head and neck cancer; hypoxia; outcome prediction; radiotherapy.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Female
Head and Neck Neoplasms / diagnostic imaging*
Head and Neck Neoplasms / radiotherapy*
Humans
Male
Middle Aged
Misonidazole / analogs & derivatives*
Positron Emission Tomography Computed Tomography*
Probability
Prospective Studies

Substances

fluoromisonidazole
Misonidazole