Search

ImportancePersonalized medicine based on tumor profiling and identification of actionable genomic alterations is pivotal in cancer management. Although tissue biopsy is still preferred for diagnosis, liquid biopsy of blood-based tumor analytes, such as circulating tumor DNA, is a rapidly emerging technology for tumor profiling.ObservationsThis review presents a practical overview for clinicians and allied health care professionals for selection of the most appropriate liquid biopsy assay, specifically focusing on circulating tumor DNA and how it may affect patient treatment and case management across multiple tumor types. Multiple factors influence the analytical validity, clinical validity, and clinical utility of testing. This review provides recommendations and practical guidance for best practice. Current methodologies include polymerase chain reaction-based approaches and those that use next-generation sequencing (eg, capture-based profiling, whole exome, or genome sequencing). Factors that may influence utility include sensitivity and specificity, quantity of circulating tumor DNA, detection of a small vs a large panel of genes, and clonal hematopoiesis of indeterminate potential. Currently, liquid biopsy appears useful in patients unable to undergo biopsy or where mutations detected may be more representative of the predominant tumor burden than for tissue-based assays. Other potential applications may include screening, primary diagnosis, residual disease, local recurrence, therapy selection, or early therapy response and resistance monitoring.Conclusions and RelevanceThis review found that liquid biopsy is increasingly being used clinically in advanced lung cancer, and ongoing research is identifying applications of circulating tumor DNA-based testing that complement tissue analysis across a broad range of clinical settings. Circulating tumor DNA technologies are advancing quickly and are demonstrating potential benefits for patients, health care practitioners, health care systems, and researchers, at many stages of the patient oncologic journey.

BackgroundPD-L1 IHC 22C3 pharmDx is an FDA-approved companion diagnostic for pembrolizumab across multiple tumor types designed for use on the Autostainer Link 48 (AL48). Many pathology laboratories do not have access to the AL48 and therefore do not use PD-L1 IHC 22C3 pharmDx but instead assess PD-L1 using laboratory-developed tests (LDTs) on the Ventana BenchMark platform. We compared our PD-L1 22C3 antibody-based LDT on the BenchMark XT platform with PD-L1 IHC 22C3 pharmDx using cervical cancer (CC), head and neck squamous cell carcinoma (HNSCC), urothelial carcinoma (UC), esophageal SCC (ESCC), and triple-negative breast cancer (TNBC) samples.MethodsTumor specimens from patients with CC, HNSCC, UC, ESCC, and TNBC were stained with the 22C3 antibody, scored using the LDT on the BenchMark XT as previously described,1 and compared with PD-L1 IHC 22C3 pharmDx scored by a trained pathologist, who measured PD-L1 with the use of combined positive score (CPS) and standard cutoffs (HNSCC and CC, ≥1; UC, ESCC, and TNBC, ≥10). Agreement in PD-L1 CPS as determined using the LDT and the PD-L1 IHC 22C3 pharmDx was evaluated.Results423 samples with CC (n = 77), HNSCC (n = 126), UC (n = 121), ESCC (n = 80), and TNBC (n = 19) were evaluated in this study. The pan-tumor (CC, HNSCC, UC, and ESCC) intraclass correlation coefficient (ICC) of PD-L1 CPS as a continuous variable was 0.95 (95% CI, 0.94%–0.96%); Spearman correlations were 0.95. ICC (95% CI) was 0.92 (0.88–0.95) for CC, 0.97 (0.96–0.98) for HNSCC, 0.95 (0.92–0.97) for UC, and 0.92 (0.88–0.95) for ESCC; Spearman correlation was 0.93, 0.96, 0.92, and 0.89, respectively. The overall percentage agreement at the respective CPS cutoff was 96% (CC), 96% (HNSCC), 96% (UC), and 90% (ESCC). Staining patterns by 22C3 LDT and PD-L1 IHC 22C3 pharmDx were also very similar in our TNBC pilot study; however, correlation was not calculated because of the small sample numbers.ConclusionsThe PD-L1 22C3 antibody-based LDT on the BenchMark XT demonstrated high concordance with PD-L1 IHC 22C3 pharmDx. These findings suggest the comparability of PD-L1 IHC 22C3 pharmDx with an LDT based on the 22C3 antibody across several tumor types. Further validation for TNBC is ongoing to confirm the data from the pilot run.ReferenceNeuman T, et al. J Thorac Oncol. 2016;11:1863–1868.