Integration of longitudinal deep-radiomics and clinical data improves the prediction of durable benefits to anti-PD-1/PD-L1 immunotherapy in advanced NSCLC patients
Benito Farina 1 2 , Ana Delia Ramos Guerra 3 4 , David Bermejo-Peláez 3 , Carmelo Palacios Miras 5 , Andrés Alcazar Peral 6 , Guillermo Gallardo Madueño 6 , Jesús Corral Jaime 6 , Anna Vilalta-Lacarra 7 , Jaime Rubio Pérez 5 , Arrate Muñoz-Barrutia 8 9 , German R Peces-Barba 5 10 , Luis Seijo Maceiras 6 10 , Ignacio Gil-Bazo 11 7 12 13 14 , Manuel Dómine Gómez 5 , María J Ledesma-Carbayo 3 4
Background: Identifying predictive non-invasive biomarkers of immunotherapy response is crucial to avoid premature treatment interruptions or ineffective prolongation. Our aim was to develop a non-invasive biomarker for predicting immunotherapy clinical durable benefit, based on the integration of radiomics and clinical data monitored through early anti-PD-1/PD-L1 monoclonal antibodies treatment in patients with advanced non-small cell lung cancer (NSCLC).
Methods: In this study, 264 patients with pathologically confirmed stage IV NSCLC treated with immunotherapy were retrospectively collected from two institutions. The cohort was randomly divided into a training (n = 221) and an independent test set (n = 43), ensuring the balanced availability of baseline and follow-up data for each patient. Clinical data corresponding to the start of treatment was retrieved from electronic patient records, and blood test variables after the first and third cycles of immunotherapy were also collected. Additionally, traditional radiomics and deep-radiomics features were extracted from the primary tumors of the computed tomography (CT) scans before treatment and during patient follow-up. Random Forest was used to implementing baseline and longitudinal models using clinical and radiomics data separately, and then an ensemble model was built integrating both sources of information.
Results: The integration of longitudinal clinical and deep-radiomics data significantly improved clinical durable benefit prediction at 6 and 9 months after treatment in the independent test set, achieving an area under the receiver operating characteristic curve of 0.824 (95% CI: [0.658,0.953]) and 0.753 (95% CI: [0.549,0.931]). The Kaplan-Meier survival analysis showed that, for both endpoints, the signatures significantly stratified high- and low-risk patients (p-value< 0.05) and were significantly correlated with progression-free survival (PFS6 model: C-index 0.723, p-value = 0.004; PFS9 model: C-index 0.685, p-value = 0.030) and overall survival (PFS6 models: C-index 0.768, p-value = 0.002; PFS9 model: C-index 0.736, p-value = 0.023).
Conclusions: Integrating multidimensional and longitudinal data improved clinical durable benefit prediction to immunotherapy treatment of advanced non-small cell lung cancer patients. The selection of effective treatment and the appropriate evaluation of clinical benefit are important for better managing cancer patients with prolonged survival and preserving quality of life.