Abstract
Hypoxia is associated with resistance to radiotherapy and chemotherapy in malignant gliomas, and it can be imaged by positron emission tomography with 18F-fluoromisonidazole (18F-FMISO). Previous results for patients with brain cancer imaged with 18F-FMISO at a single center before conventional chemoradiotherapy showed that tumor uptake via T/Bmax (tissue SUVmax/blood SUV) and hypoxic volume (HV) was associated with poor survival. However, in a multicenter clinical trial (ACRIN 6684), traditional uptake parameters were not found to be prognostically significant, but tumor SUVpeak did predict survival at 1 year. The present analysis considered both study cohorts to reconcile key differences and examine the potential utility of adding radiomic features as prognostic variables for outcome prediction on the combined cohort of 72 patients with brain cancer (30 University of Washington and 42 ACRIN 6684). We used both 18F-FMISO intensity metrics (T/Bmax, HV, SUV, SUVmax, SUVpeak) and assessed radiomic measures that determined first-order (histogram), second-order, and higher-order radiomic features of 18F-FMISO uptake distributions. A multivariate model was developed that included age, HV, and the intensity of 18F-FMISO uptake. HV and SUVpeak were both independent predictors of outcome for the combined data set (P < .001) and were also found significant in multivariate prognostic models (P < .002 and P < .001, respectively). Further model selection that included radiomic features showed the additional prognostic value for overall survival of specific higher order texture features, leading to an increase in relative risk prediction performance by a further 5%, when added to the multivariate clinical model..
Highlights
Evolving and immature tumor vasculature can lead to chronic tissue hypoxia, which is associated with resistance to radiotherapy and chemotherapy in malignant gliomas, leading to treatment failure and recurrence [1]
Previous studies at the University of Washington (UW) of 22 patients imaged with 18F-FMISO positron emission tomography (PET) following surgical resection and before radiotherapy with concomitant chemotherapy showed that the maximum 18F-FMISO tissue–blood ratio (T/Bmax) and the hypoxic volume (HV) were associated with shorter overall survival (OS) and TTP [4]
Differing significance of quantitative metrics for 18F-FMISO uptake resulted between a single-center cohort and a multicenter cohort of glioma patients for the assessment of hypoxia using 18F-FMISO PET before combined radiotherapy and chemotherapy
Summary
Evolving and immature tumor vasculature can lead to chronic tissue hypoxia, which is associated with resistance to radiotherapy and chemotherapy in malignant gliomas, leading to treatment failure and recurrence [1]. This tracer is irreversibly reduced and trapped when the level of O2 is below. Several studies have shown that metrics of brain tumor hypoxia measured by 18F-FMISO PET were associated with time-to-progression (TTP) and/or overall survival (OS) [3,4,5,6]. Previous studies at the University of Washington (UW) of 22 patients imaged with 18F-FMISO PET following surgical resection and before radiotherapy with concomitant chemotherapy showed that the maximum 18F-FMISO tissue–blood ratio (T/Bmax) and the hypoxic volume (HV) were associated with shorter OS and TTP [4]. The current analysis considered both the UW and ACRIN 6684 study cohorts with a view to examining differences in the analytical results, and to explore the utility of agnostic measures of 18FFMISO uptake using radiomic features to further assess patient risk on the combined cohort of patients
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