Same-day molecular testing for targetable mutations in solid tumor cytopathology—The next frontier of the rapid on-site evaluation

Introduction

This study aimed to assess the feasibility of implementing the Idylla system, an ultra-rapid, cartridge-based assay, as an extension of rapid on-site evaluation (ROSE) in cytology. The authors conducted a pilot validation study on specimens from non–small cell lung carcinoma, thyroid carcinoma, and melanoma, evaluating four assays designed to detect alterations in KRAS, EGFR, BRAF, gene fusions, and expression imbalances in ALK, ROS1, RET, NTRK1/2/3, and MET exon 14 skipping transcripts. They investigated the feasibility of providing accurate biomarker molecular testing results in a cytopathology laboratory within hours of specimen collection.

Methods

The authors evaluated the performance characteristics and turn-around-time of the Idylla system by testing a total of 144 cartridge assays across various specimen types, including fine-needle aspirate smears, formalin-fixed paraffin-embedded (FFPE) cell blocks, small tissue biopsy FFPE blocks, and control cell line FFPE scrolls.

Results

The average time from specimen input to results output was 2–3 hours. Accuracy across the four cartridge types was: KRAS assay: 100%, EGFR assay: 94%, BRAF assay: 100%, and GeneFusion assay: 94%. Analytical sensitivity ranged from 1% to 5% variant allele frequency for all assays. Inter-assay precision and analytical specificity were both 100%.

Conclusion

Using the Idylla system, actionable genetic alterations can be reliably detected within 2–3 hours from cytology and small biopsy samples with minimal input requirements. The findings of this study demonstrate the feasibility of incorporating same-day molecular testing as part of ROSE procedures in the cytopathology laboratory, ultimately shortening the time from procedure to personalized treatment for cancer patients.