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

Abstract

Molecular pathology; Non-small cell lung cancer; Tumor cell fraction

Patología molecular; Cáncer de pulmón de células no pequeñas; Fracción de células tumorales

Patologia molecular; Càncer de pulmó de cèl·lules no petites; Fracció de cèl·lules tumorals

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 QuANTUM-processed 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.

The work has been funded by the project in the Italian Ministry of the University MUR Dipartimenti di Eccellenza 2023-2027 (l. 232/2016, art. 1, commi 314-337). This work was partially funded by the National Plan for NRRP Complementary Investments (PNC, established with the decree-law 6 May 2021, n. 59, converted by law n. 101 of 2021) in the call for the funding of research initiatives for technologies and innovative trajectories in the health and care sectors (Directorial Decree n. 931 of 06-06-2022) - project n. PNC0000003 - AdvaNced Technologies for Human-centrEd Medicine (project acronym: ANTHEM).