Article

Method of Tissue Acquisition May Determine Success of Gene Sequencing in Lung Cancer

Author(s):

Successful comprehensive genomic profiling of tissue samples among patients with lung cancer was more likely to occur when samples were extracted via resections vs fluid cytology, biopsy, or fine-needle aspirations.

Tissue samples of patients with lung cancer were more likely to be successfully sequenced when extracted via resections, whereas use of fluid cytology, biopsy, and fine-needle aspirations (FNAs) were associated with reduced likelihood of comprehensive genomic profiling (CGP) success. Findings were published recently in Archives of Pathology & Laboratory Medicine.

Recent innovations in the comprehension of genomic alterations within lung cancer have led to the development of more efficacious targeted therapies and the identification of biomarkers that can predict response to therapy. However, challenges have been cited regarding genomic testing, in which researchers sought to investigate whether certain methods of tissue acquisition can affect lung cancer CGP success.

“Given its widespread adoption, it is important for proceduralists, oncologists, and pathologists to understand the preanalytic factors that may affect the success of CGP,” said the study authors. “The literature is mixed regarding how the procedure through which a specimen was obtained affects the success of CGP.”

They conducted a cross-sectional analysis of all patients with lung cancer whose specimens were submitted for CGP with the FoundationOneCDx next-generation sequencing assay between January and February 2020 at Foundation Medicine, Inc, in Cambridge, Massachusetts, or Morrisville, North Carolina.

Multiple quality control (QC) metrics were used to determine whether cases were successfully profiled, with the procedural techniques assessed including resections, biopsies, FNAs, fluid cytology, and bone biopsy.

“If such cases passed all postsequencing QC criteria and pathogenic genomic alterations were identified, a pass report was issued. If such cases failed 1 or more postsequencing QC criteria but pathogenic alterations were still identified, a qualified report was issued,” explained the researchers.

Of the 3312 patients with lung cancer included in the analysis (median [IQR] patient age, 69 [62-76] years; 51.3% male; 96.3% of cases were non–small cell lung cancer), 67.5% (n = 2236) of cases were obtained via biopsy, 13.0% (n = 432) were FNAs, 9.7% (n = 321) were resections, 5.3% (n = 174) were cell blocks derived from fluid cytology specimens, and 4.5% (n = 149) were bone biopsies.

Overall, 70.1% (n = 2321) of cases passed CGP, 15.4% (n = 510) were released as qualified reports, and 14.5% (n = 481) failed CGP. From the procedural techniques examined, tissue samples derived from resection were most likely to be successfully sequenced, failing in only 2.8% (n = 9) of instances, while fluid cytology specimens were the least likely to be successfully sequenced, failing in 23.0% (n = 40) of instances. Biopsy (14.5%, n = 324), FNA (18.5%, n = 80), and bone biopsy (18.8%, n = 28) specimens also failed at intermediate frequencies.

Moreover, findings of the multivariate logistic regression analysis of CGP success relative to resection samples indicated that fluid cytology (odds ratio [OR], 0.08; 95% CI, 0.03–0.19), biopsy (OR, 0.25; 95% CI, 0.11–0.52), FNA (OR, 0.14; 95% CI, 0.06–0.32), and bone biopsy (OR, 0.07; 95% CI, 0.03–0.17) specimens had decreased odds of CGP success.

“Among patients with successfully sequenced samples, 48.0% were eligible for at least 1 therapy, based on a companion diagnostic or National Comprehensive Cancer Network biomarker,” added the study authors. “Given the results of our study, it will be important to examine the type of specimen collection in other tumor types in the future.”

Reference

Mata DA, Harries L, Williams EA, et al. Method of tissue acquisition affects success of comprehensive genomic profiling in lung cancer. Arch Pathol Lab Med. Published online June 30, 2022. doi:10.5858/arpa.2021-0313-OA

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