Baseline PET/CT heterogeneity index shows limited independent value for predicting lung cancer treatment response
Investigators evaluated whether the heterogeneity index, derived from multiple threshold-based metabolic tumor volume measurements on baseline 18F-FDG PET/CT, could predict treatment response in 44 patients with stage III to IV lung cancer undergoing chemoradiotherapy. Patients with disease progression exhibited significantly higher heterogeneity index and metabolic tumor volume values, with both parameters yielding modest discriminative performance (AUC 0.677 to 0.682) but high sensitivity and low specificity. Multivariate analysis revealed that only advanced tumor stage independently predicted progression, as the heterogeneity index demonstrated near-perfect collinearity with metabolic tumor volume (r=0.997) and lost statistical significance. The study suggests that while this imaging parameter is readily calculable, it currently offers no incremental diagnostic advantage over standard volumetric PET metrics and requires larger prospective validation before clinical adoption.
The original study
Predictive value of the heterogeneity index in assessing treatment response using
- Authors
- Okar Y, Akkaş BE, Toyran R, Urhan M
- Journal
- Hellenic journal of nuclear medicine
- Type
- Journal Article
- PMID
- 42555491
Original abstract
OBJECTIVE: Intratumoral metabolic heterogeneity may influence treatment response in lung cancer, and the heterogeneity index (HI), derived from threshold-based metabolic tumor volume (MTV) measurements, has been proposed as a simple fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT)-based parameter to estimate this variability. This retrospective single-center study evaluated the predictive value of HI for treatment response in patients with locally advanced and advanced lung cancer undergoing chemoradiotherapy and compared its performance with conventional PET-derived volumetric parameters. SUBJECTS AND METHODS: Forty-four patients with stage III-IV lung cancer who underwent pretreatment 18F-FDG PET/CT followed by chemoradiotherapy were retrospectively analyzed. PET-derived parameters, including maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), MTV, total lesion glycolysis (TLG), and HI, were calculated from baseline scans. HI was derived from the slope of linear regression using MTV values measured at multiple threshold levels. Treatment response was classified as regression or progression based on follow-up imaging according to positron emission tomography response criteria in solid tumors (PERCIST). Receiver operating characteristic (ROC) analysis was used to evaluate the predictive performance of MTV and HI, and multivariate logistic regression was performed to identify independent predictors of disease progression. RESULTS: Of the 44 patients, 19 (43.2%) showed regression and 25 (56.8%) showed progression. Metabolic tumor volume and HI were significantly higher in patients with progression (P=0.047 and P=0.040, respectively). Receiver operating characteristic analysis demonstrated modest discriminative performance for MTV (area under the curve [AUC]: 0.677; 95% confidence interval [CI]: 0.519-0.810) and HI (AUC: 0.682; 95% CI: 0.525-0.814), with high sensitivity but low specificity for both parameters. Heterogeneity index showed an extremely strong correlation with MTV (r=0.997), indicating substantial overlap between the two measures. In multivariate analysis, only advanced tumor stage (T3-T4) remained an independent predictor of progression (odds ratio [OR]: 6.801; 95% CI: 1.271-36.398; P=0.025), whereas HI did not retain independent significance. CONCLUSION: These findings indicate that HI has limited but statistically significant predictive value for treatment response in locally advanced and advanced lung cancer and performs similarly to MTV. Given its extreme collinearity with MTV, HI should be interpreted primarily as a derivative parameter reflecting tumor burden rather than as an independent heterogeneity biomarker. Nevertheless, because of its simple calculation and broad availability, HI may serve as a practical adjunct metabolic parameter in clinical assessment, although larger prospective studies with external validation are needed to clarify its incremental clinical utility.