A deep-learning-based prognostic nomogram integrating microscopic digital pathology and macroscopic magnetic...

To explore the prognostic value of radiomics-based and digital pathology-based imaging biomarkers from macroscopic magnetic resonance imaging (MRI) and microscopic whole-slide images for patients with nasopharyngeal carcinoma (NPC).

We recruited 220 NPC patients and divided them into training (n = 132), internal test (n = 44), and external test (n = 44) cohorts. The primary endpoint was failure-free survival (FFS). Radiomic features were extracted from pretreatment MRI and selected and integrated into a radiomic signature. The histopathological signature was extracted from whole-slide images of biopsy specimens using an end-to-end deep-learning method. Incorporating two signatures and independent clinical factors, a multi-scale nomogram was constructed. We also tested the correlation between the key imaging features and genetic alternations in an independent cohort of 16 patients (biological test cohort).

Both radiomic and histopathologic signatures presented significant associations with treatment failure in the three cohorts (C-index: 0.689-0.779, all p < 0.050). The multi-scale nomogram showed a consistent significant improvement for predicting treatment failure compared with the clinical model in the training (C-index: 0.817 versus 0.730, p < 0.050), internal test (C-index: 0.828 versus 0.602, p < 0.050) and external test (C-index: 0.834 versus 0.679, p < 0.050) cohorts. Furthermore, patients were stratified successfully into two groups with distinguishable prognosis (log-rank p < 0.0010) using our nomogram. We also found that two texture features were related to the genetic alternations of chromatin remodeling pathways in another independent cohort.

The multi-scale imaging features showed a complementary value in prognostic prediction and may improve individualized treatment in NPC.