Quantitative CT texture assessment of tumour heterogeneity to predict those patients with non-small cell lung cancer most likely to benefit from immune checkpoint inhibitors.

Background: Attempts to isolate reliable predictive biomarkers have been unsuccessful for the use of immunotherapy agents targeting PD-1 and PD-L1 immune checkpoint proteins in the treatment of non-small cell lung cancer (NSCLC). This study assessed whether CT texture analysis as a potential correlate for genomic heterogeneity could predict those patients most likely to benefit from Nivolumab. Methods: A single centre retrospective analysis was undertaken of patients with NSCLC previously treated with platinum doublet chemotherapy who underwent nivolumab immunotherapy. Texture analysis was used to quantify heterogeneity within the single largest tumour site identified on contrast enhanced CT of the thorax prior to commencement of immunotherapy. Based on histogram analysis of tumour regions processed to highlight image features of 4mm radius, tumours were classified as hyperdense (positive skewness) or hypodense (negative skewness) and then sub-classified based on their median standard deviation value (SD). Progression-free survival (PFS) was assessed for each group using Kaplan-Meier analysis. Results: A total of 47 patients were included in the study, median age 64 (47-84) years. Squamous (N = 21) and non-squamous (N = 26) histology were included. All patients had progressed on prior platinum doublet chemotherapy except one who developed toxicity. Nivolumab was discontinued (N = 37) due to progression (N = 34) and toxicity (N = 3), with treatment ongoing in the remaining patients (N = 10). With a median follow up of 18 months, hyperdense tumours with low SD (n = 14), findings consistent with tumour heterogeneity, showed significantly longer PFS compared to the hypodense group (median NR versus 1.5 months, Hazard Ratio: 2.05, p = 0.018). At 12 months more patients had not progressed in the hyperdense group (53%) versus the hypodense group (12%). Conclusions: This to date is the first preliminary study of quantitative CT texture assessment for tumour heterogeneity in NSCLC allowing us to identify patients who will benefit from immunotherapy in metastatic NSCLC. Further prospective trials will be required to assess its efficacy