A Framework of Analysis to Facilitate the Harmonization of Multicenter Radiomic Features in Prostate Cancer

Pooling radiomic features coming from different centers in a statistical framework is challenging due to the variability in scanner models, acquisition protocols, and reconstruction settings. To remove technical variability, commonly called batch effects, different statistical harmonization strategies have been widely used in genomics but less considered in radiomics. The aim of this work was to develop a framework of analysis to facilitate the harmonization of multicenter radiomic features extracted from prostate T2-weighted magnetic resonance imaging (MRI) and to improve the power of radiomics for prostate cancer (PCa) management in order to develop robust non-invasive biomarkers translating into clinical practice. To remove technical variability and correct for batch effects, we investigated four different statistical methods (ComBat, SVA, Arsynseq, and mixed effect). The proposed approaches were evaluated using a dataset of 210 prostate cancer (PCa) patients from two centers. The impacts of the different statistical approaches were evaluated by principal component analysis and classification methods (LogitBoost, random forest, K-nearest neighbors, and decision tree). The ComBat method outperformed all other methods by achieving 70% accuracy and 78% AUC with the random forest method to automatically classify patients affected by PCa. The proposed statistical framework enabled us to define and develop a standardized pipeline of analysis to harmonize multicenter T2W radiomic features, yielding great promise to support PCa clinical practice

Immune-related adverse events correlate with clinical outcomes in NSCLC patients treated with Nivolumab in the Italian NSCLC expanded access programme.

Abstract Background The incidence of any and of severe grade immune-related adverse events (irAEs) with second-line Nivolumab (N) monotherapy is 26% and 6% respectively. While potentially serious and even fatal, in the absence of appropriate therapy, such events might be an indicator of the activation of the immune system and, potentially, of efficacy. Methods We collected the records of 1.959 NSCLC patients (pts) including those with Squamous (S) and non-Squamous (non-S) histology, treated with N in the Italian expanded access programme and we recorded the appearance of any and of severe grade irAEs. We then retrospectively searched for potential correlations between this type of toxicity and efficacy parameters by using cox regression analysis. Results A total of 1.585 and 374 pts had non-S and S cell carcinoma respectively and 57% received N as second-third line of therapy. Overall 342 (17.8%) developed an irAE of any grade. We observed that pts developing any grade irAE achieved a significantly higher response rate (RR 27.2% vs 15.2%; p < 0.0001), disease control rate (DCR 60.5% vs 40.2%; p < 0.0001), median progression-free survival (mPFS 6.0 months [95% CI 4.9-7.1] vs 3.0 [95% CI: 2.8-3.2], p < 0.0001) and median overall survival (mOS 16.7 months [95% CI: 13.5-19.9] vs 9.4 [95% CI: 8.4-10.4], p < 0.00001) compared to pts who did not. IrAEs correlate with clinical outcomes in both non-S and S histology. At multivariate analysis the development of an irAE remained an independent indicator of N efficacy (HR 1.44[95% CI: 1.22-1.71] p < 0.0001). Conclusions This is the first report performed in a large series of Caucasian NSCLC pts showing that the activation of the immune system induced by N and documented by the appearance of irAEs correlates with outcome. A careful management of pts with such an event could lead to a maximum clinical benefit

Immune-related adverse events correlate with clinical outcomes in NSCLC patients treated with nivolumab: The Italian NSCLC expanded access program

Objectives: The incidence of any and of severe-grade immune-related adverse events (irAEs) with second-line nivolumab monotherapy is 31–65 % and 2–5 % respectively. While potentially serious and even fatal, in the absence of an appropriate therapy, such events might be indicators of the activation of the immune system and, potentially, of efficacy. Materials and Methods: We collected the records of 1959 non-small-cell lung cancer (NSCLC) patients treated with nivolumab in the Italian expanded access program, and we registered the appearance of any and of severe grade irAEs. We retrospectively searched for correlations between toxicity and efficacy parameters by using Cox's regression analysis. Results: Overall, 342 (17.8%) patients developed an irAE of any grade. We observed that patients developing irAE of any grade achieved a significantly higher response rate (RR 27.2% vs 15.2%; p < 0.0001), disease control rate (DCR 60.5% vs 40.2%; p < 0.0001), median progression-free survival (mPFS 6.0 months [95% CI 4.9–7.1] vs 3.0 [95% CI: 2.8–3.2], p < 0.0001) and median overall survival (mOS 16.7 months [95% CI: 13.5–19.9] vs 9.4 [95% CI: 8.4–10.4], p < 0.00001) compared to patients who did not. At multivariate analysis the development of an irAE remained an independent indicator of nivolumab efficacy (HR 1.44 [95% CI: 1.22–1.71] p < 0.0001)