PET/CT-based quantification of intratumoral heterogeneity for predicting pathological complete response in breast cancer patients treated with neoadjuvant chemotherapy: A multicentre study.

purposeTo develop a quantitative measure of intratumoral heterogeneity (ITH) from pretreatment 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) images and to evaluate its potential for predicting pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in patients with breast cancer (BC). MATERIALS AND

methodsThis retrospective study included patients with BC who underwent NAC at four hospitals between 2013 and 2025. Tumour regions on pretreatment 18F-FDG PET/CT images were clustered to extract intratumoral ecological diversity features, while radiomic features were extracted from the entire tumour. Output probabilities from imaging-based extreme gradient boosting (XGBoost) models were used to generate an ITH index and a radiomics score, respectively. Logistic regression analysis was performed to identify variables associated with pCR. Significant variables, including clinicopathologic characteristics, radiomics score, and ITH index, were integrated into a combined predictive model (ICR-COME). Model performance and clinical utility were evaluated using receiver operating characteristic, calibration curve, and decision curve analyses (DCA). Survival differences between predicted pCR and non-pCR groups were assessed using Kaplan–Meier analysis. RNA sequencing data from 12 patients were analysed to further explore the biological basis of ICR-COME.

resultsThe study included 323 women (median age, 51 years ± 10[SD]). For predicting pCR in BC patients, ICR-COME achieved the area under the receiver operating characteristic curve (AUC) values of 0.95 in the training cohort and 0.87 and 0.88 in external test cohorts B and C, respectively, which were significantly superior to those of the clinicopath model and the conventional radiomics model using 18F-FDG PET/CT (all P < 0.05, DeLong test). Calibration curve and DCA indicated that ICR-COME achieved satisfactory concordance and provided the greatest clinical net benefit. Patients in all three cohorts predicted as non-pCR exhibited poorer prognosis (P < 0.05, log-rank test). Furthermore, RNA sequencing and multiplex immunofluorescence analyses revealed that high ICR-COME scores were associated with increased immune cell infiltration and enhanced activation of immune-related pathways.

conclusionsICR-COME, which integrates the ITH index, the radiomics score, and clinicopathologic variables, demonstrated strong predictive performance for pCR to NAC and prognosis in BC patients.