Real-World Performance of a Comprehensive Genomic Profiling Test Optimized for Small Tumor Samples

Abstract

PURPOSE Tissue-based comprehensive genomic profiling (CGP) is increasingly used for treatment selection in patients with advanced cancer; however, tissue availability may limit widespread implementation. Here, we established real-world CGP tissue availability and assessed CGP performance on consecutively received samples. MATERIALS AND METHODS We conducted a post hoc, nonprespecified analysis of 32,048 consecutive tumor tissue samples received for StrataNGS, a multiplex polymerase chain reaction (PCR)–based comprehensive genomic profiling (PCR-CGP) test, as part of an ongoing observational trial ( NCT03061305 ). Sample characteristics and PCR-CGP performance were assessed across all tested samples, including exception samples not meeting minimum input quality control (QC) requirements (< 20% tumor content [TC], < 2 mm2 tumor surface area [TSA], DNA or RNA yield < 1 ng/µL, or specimen age > 5 years). Tests reporting ≥ 1 prioritized alteration or meeting TC and sequencing QC were considered successful. For prostate carcinoma and lung adenocarcinoma, tests reporting ≥ 1 actionable or informative alteration or meeting TC and sequencing QC were considered actionable. RESULTS Among 31,165 (97.2%) samples where PCR-CGP was attempted, 10.7% had < 20% TC and 59.2% were small (< 25 mm2 tumor surface area). Of 31,101 samples evaluable for input requirements, 8,089 (26.0%) were exceptions not meeting requirements. However, 94.2% of the 31,101 tested samples were successfully reported, including 80.5% of exception samples. Positive predictive value of PCR-CGP for ERBB2 amplification in exceptions and/or sequencing QC-failure breast cancer samples was 96.7%. Importantly, 84.0% of tested prostate carcinomas and 87.9% of lung adenocarcinomas yielded results informing treatment selection. CONCLUSION Most real-world tissue samples from patients with advanced cancer desiring CGP are limited, requiring optimized CGP approaches to produce meaningful results. An optimized PCR-CGP test, coupled with an inclusive exception testing policy, delivered reportable results for > 94% of samples, potentially expanding the proportion of CGP-testable patients and impact of biomarker-guided therapies.

Genomic Features of Lung-Recurrent Hormone-Sensitive Prostate Cancer

“…Tissue TF strongly influences sensitivity for detection of genomic alterations and does not always correlate with two-dimensional pathology estimates because of spatial microenvironmental heterogeneity in prostate cancer. 29,30 The sequencing-derived TF was higher in metastatic lung than primary tumor samples (median 53% v 17%, Mann-Whitney U test, P = 1.4 × 10 −6 ; Appendix Fig A1C). Sequencing-derived TF estimates of low-grade primary tumor foci (Gleason Grade Group ≤ 3) appeared to be lower than those for high-grade disease (median 12% v 23%, Mann-Whitney U test, P = .06; Appendix Fig A1D), and sequencing TF estimates were overall poorly correlated with histologic estimates ( R = 0.16, P = .20, Pearson correlation; Appendix Fig A1E).…”

“…Tissue TF strongly influences sensitivity for detection of genomic alterations and does not always correlate with twodimensional pathology estimates because of spatial microenvironmental heterogeneity in prostate cancer. 29,30 The sequencing-derived TF was higher in metastatic lung than primary tumor samples (median 53% v 17%, Mann-Whitney U test, P = 1.4 × 10 −6 ; Appendix Fig A1C primary and metastatic samples from 10 patients with lung-recurrent hormone-sensitive prostate cancer. Samples with undetectable TF (calculated bioinformatically) are excluded (Data Supplement).…”

An Expert, Multidisciplinary Perspective on Best Practices in Biomarker Testing in Intrahepatic Cholangiocarcinoma

“… 43 , 44 Despite attempts to standardize tissue acquisition and processing, biomarker testing remains a challenge for patients with BTC. In a real-world study of >30 000 solid tumor samples that underwent a polymerase chain reaction (PCR)-based comprehensive genomic profiling (CGP) test, only 29.9% of biliary samples ( n = 633) had tumor surface area >25 mm 2 and 19.3% had tumor cell content <20%, 45 both of which are under the standard thresholds for most NGS platforms.…”

Toward a More Just System of Care in Molecular Pathology

“…But just as only some patients are willing to risk receiving an expensive surprise bill, only some hospitals and institutions are willing to risk being underpaid or not paid. As stated earlier, NGS is the most expensive molecular technique and also the most poorly reimbursed 88–94 . The Centers for Medicare & Medicaid (CMS) has tried to outline broad indications and limitations of coverage but has missed critical diseases and circumstances in its determination, such as patients with diseases not requiring traditional staging, including diffuse gliomas and acute leukemia 95 .…”