# Mid-treatment changes in intra-tumoural metabolic heterogeneity correlate to outcomes in oropharyngeal squamous cell carcinoma patients

## TL;DR

Changes in tumor metabolism during treatment can predict outcomes in oropharyngeal cancer patients.

## Contribution

Mid-treatment metabolic heterogeneity changes correlate with treatment outcomes in oropharyngeal squamous cell carcinoma.

## Key findings

- A 24% decrease in intra-tumoural metabolic heterogeneity was observed mid-treatment.
- Changes in MTV and AUC-CSH correlated with locoregional recurrence-free survival.
- Stratifying patients using ∆AUC-CSH and ∆MTV showed significant differences in recurrence rates.

## Abstract

This study evaluated mid-treatment changes in intra-tumoural metabolic heterogeneity and quantitative FDG-PET/CT imaging parameters and correlated the changes with treatment outcomes in oropharyngeal squamous cell cancer (OPSCC) patients. 114 patients from two independent cohorts underwent baseline and mid-treatment (week 3) FDG-PET. Standardized uptake value maximum (SUVmax), standardized uptake value mean (SUVmean), metabolic tumour volume (MTV), and total lesional glycolysis (TLG) were measured. Intra-tumoural metabolic heterogeneity was quantified as the area under a cumulative SUV-volume histogram curve (AUC-CSH). Baseline and relative change (%∆) in imaging features were correlated to locoregional recurrence free survival (LRRFS) using multivariate Cox regression analysis. Patients were stratified into three risk groups utilising ∆AUC-CSH and known prognostic features, then compared using Kaplan-Meier analysis.

Median follow up was 39 months. 18% of patients developed locoregional recurrence at 2 years. A decrease in heterogeneity (∆AUC-CSH: 24%) was observed mid-treatment. There was no statistically significant difference in tumour heterogeneity (AUC-CSH) at baseline (p = 0.134) and change at week 3 (p = 0.306) between p16 positive and p16 negative patients. Baseline imaging features did not correlate to LRRFS. However, ∆MTV (aHR 1.04; 95% CI 1.03–1.06; p < 0.001) and ∆AUC-CSH (aHR 0.96; 95% CI 0.94–0.98; p = 0.004) were correlated to LRRFS. Stratification using ∆AUC-CSH and p16 status into three groups showed significant differences in LRR (2 year LRRFS 94%, 79%, 17%; log rank p < 0.001). Stratification using ∆AUC-CSH and ∆MTV into three groups showed significant differences in LRR (2 year LRRFS 93%, 70%, 17%; log rank p < 0.001).

Mid-treatment changes in intra-tumoural FDG-PET/CT heterogeneity correlated with treatment outcomes in OPSCC and may help with response prediction. These findings suggest potential utility in designing future risk adaptive clinical trials.

The online version contains supplementary material available at 10.1186/s13550-025-01226-6.