The routine use of a digital tool for the tumor cell fraction quantification in molecular pathology: an international validation of QuANTUM

Objective. The absolute and relative quantification of tumor cell fraction (TCF) in tissue samples for molecular pathology testing is time-consuming and poorly reproducible.

Methods. Here we report the results of an international survey on non-small cell lung cancer (NSCLC), validating the Qupath Analysis of Nuclei from Tumor to Uniform Molecular tests (QuANTUM) automated computational pipeline for TCF quantification.

Results. The TCF obtained with QuANTUM is reliable, as demonstrated by the comparison with the manual counting of cells (ground truth, GT) in cell blocks, small biopsies and surgical specimens (overall correlation of 0.89). The visual evaluation of QuANTUMprocessed images increased the pathologists’ agreement with GT and QuANTUM of +0.16, +0.21, +0.09 and +0.17, +0.29, +0.21 across the three sample types, respectively. An overall increase in cases classified as containing ≥100 tumor cells for all sample types was noted after QuANTUM (from 75 cases, 63% to 96 cases, 80% among cell blocks, p = 0.003).

Conclusions. QuANTUM is an easy-to-use and reliable tool for the TCF assessment and its employment significantly modifies the visual estimation by pathologists, improving the assessment of NSCLC cases for molecular analysis