Pre-submission Pathological Quality Control for FoundationOne CDx Comprehensive Genomic Profiling

Comprehensive genomic profiling (CGP) using FoundationOne CDx (F1CDx) requires formalin-fixed paraffin-embedded specimens with sufficient tumor area and DNA yield. Pre-submission pathological assessment is critical but has not been systematically evaluated in real-world practice. This study analyzed 371 consecutive F1CDx requests at a cancer genomic medicine designated hospital in Japan. Pre-submission quality checks assessed tumor surface area, estimated section numbers and residual specimen volume. Assay outcomes were classified as pre-submission cancellation, temporary suspension (insufficient DNA, suspected contamination, or technical issues), Qualified, or Pass. Of 371 requests, 52 (14.0%) were cancelled before submission, mainly due to insufficient specimen volume or clinical decision. Among 319 submitted cases, 22 (6.9%) were temporarily suspended. Among 297 cases with returned results, 256 (86.2%) achieved Pass quality and 41 (13.8%) were Qualified. Tumor content-related parameters including institutional tumor content, laboratory-assessed tumor content, and sequencing-estimated tumor content were all significantly lower in Qualified than in Pass case. In Qualified cases, evaluation of tumor mutational burden and microsatellite instability was successful in only 31.7% and 19.5%, respectively. In multivariable analysis, lower tumor content was the only independent predictor of QC failure. These findings indicate most F1CDx assay failures are attributable to insufficient tumor content or specimen volume. Strengthened pre-submission QC and coordinated workflows can meaningfully improve CGP success. Limitations include the retrospective single-institution design and lack of external validation.