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

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

Daniela Thorwarth  1   2 , Stefan Welz  3 , David Mönnich  4 , Christina Pfannenberg  5 , Konstantin Nikolaou  5 , Matthias Reimold  6 , Christian La Fougère  6 , Gerald Reischl  7 , Paul-Stefan Mauz  8 , Frank Paulsen  3 , Markus Alber  4   9 , Claus Belka  2   10 , Daniel Zips  2   3
Affiliations
Clinical Trial

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

Daniela Thorwarth et al. J Nucl Med. 2019 Dec.

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, MFMISO, derived from pharmacokinetic modeling of dynamic 18F-FMISO and maximum tumor-to-muscle ratio (TMRmax) at 4 h after injection, gross tumor volume (GTV), relative hypoxic volume based on MFMISO, and a logistic regression model combining GTV and TMRmax, 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 MFMISO 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, MFMISO 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 TMRmax, GTV, relative hypoxic volume, and the combination of GTV and TMRmax, 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 MFMISO 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.

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Figures

FIGURE 1.
FIGURE 1.
Study design.
FIGURE 2.
FIGURE 2.
TCP model defining expected local control rate for training cohort and whole patient group (including validation cohort) as function of MFMISO. Observed outcomes of all individual patients (1 = control, 0 = recurrence) are shown. Rug plot visualizes estimated control probabilities by TCP model for individual patients. Dashed lines indicate 95% confidence intervals. a.u. = arbitrary units.
FIGURE 3.
FIGURE 3.
Kaplan–Meier curves stratified according to MFMISO: training cohort (n = 15) (A), validation cohort (n = 22) (B), merged groups (n = 37) (C). P values are with respect to log-rank tests. Data in parentheses are 95% confidence intervals.
See this image and copyright information in PMC

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