Cancer Diagnosis Program | Biorepositories and Biospecimen Research Branch

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Circulating Cell-Free DNA Yield and Circulating-Tumor DNA Quantity from Liquid Biopsies of 12 139 Cancer Patients.

Author(s): Huang RSP, Xiao J, Pavlick DC, Guo C, Yang L, Jin DX, Fendler B, Severson E, Killian JK, Hiemenz M, Duncan D, Lin DI, Dennis L, Aiyer A, Gjoerup O, Oxnard G, Venstrom J, Elvin J, Ramkissoon SH, Ross JS

Publication: Clin Chem, 2021, Vol. , Page

PubMed ID: 34626187 PubMed Review Paper? No

Purpose of Paper

Conclusion of Paper

Studies

1. Study Purpose

   This study used retrospective plasma specimens to investigate if cfDNA concentration and ctDNA fraction were impacted by tumor type and stage, patient age and sex, and the presence of a genomic alterations. This study included 12,139 specimens that were received consecutively at FoundationOne for comprehensive genomic profiling. Blood was collected from patients diagnosed with a hematologic malignancy, neuroendocrine tumors, prostate carcinoma, breast carcinoma, gastrointestinal carcinoma, head and neck tumors, skin tumors, endocrine tumors, soft tissue tumors, genitourinary tumors, non-small cell lung cancer, gynecologic tumors, or central nervous system tumors; blood specimen were mailed to FoundationOne at ambient temperature.  Details of blood collection including tube type were not specified. Plasma was separated by centrifugation (speed and duration not specified), within 14 days of venipuncture. cfDNA was extracted (method unspecified) and quantified using a 4200 TapeStation. cfDNA was sequenced using a hybrid capture-based next generation sequencing assay. Differences were evaluated. ctDNA fraction was based on calculation of the tumor fraction estimator and the maximum somatic allele frequency.

   Summary of Findings:

   cfDNA yield differed among the tumor types evaluated (P<0.001, both tests), with higher than average levels observed in specimens from patients with hematologic malignancy, neuroendocrine tumors, prostate carcinoma, breast carcinoma, or gastrointestinal carcinoma and lower than average levels in specimens from patients with head and neck tumors, skin tumors, endocrine tumors, soft tissue tumors, genitourinary tumors (other than prostate carcinoma), non-small cell lung cancer, gynecologic tumors, and central nervous system tumors. Similarly, the ctDNA fraction was dependent on tumor type with the highest mean fraction found in patients with neuroendocrine tumors (23.2%) and the lowest mean fraction in specimens from patients with CNS tumors (4.3%, P<0.001 among tumor types, both tests).  As cancer stage increased, specimens had higher mean cfDNA yield (P<0.001, both tests) and mean ctDNA fraction (from 5.9% in stage 1 to 12.7% in stage 4, P<0.001, both tests).  While lower cfDNA yields were observed among older patients, the effect was not significant (P=0.0.119 by Rank Sum and P=0.510 by ANOVA). The mean ctDNA fraction was inversely related to patient age (progressive decline with age from 16.5% in patients <50 years to 9.9% in patients ≥80 years, P<0.001 both tests). There was no effect of patient sex on cfDNA yield (P=0.307 by Rank Sum and P=0.380 by ANOVA), but mean ctDNA fraction was significantly higher in specimens from males than females (13.1% versus 11.3%, P<0.001, both tests).  cfDNA yield was higher from specimens where a genomic alteration was detected than those without a genomic alteration (P<0.001). There was a significant positive effect of cfDNA concentration on specimens passing quality checks (Kruskal-Wallis Rank Sum test, P<0.001).

   Biospecimens

   • Bodily Fluid - Plasma

   Preservative Types

   • None (Fresh)

   Diagnoses:

   • Neoplastic - Carcinoma
   • Neoplastic - Sarcoma
   • Neoplastic - Melanoma
   • Neoplastic - Leukemia
   • Neoplastic - Lymphoma

   Platform:

   Analyte	Technology Platform
   DNA	Automated electrophoresis/Bioanalyzer
   DNA	Next generation sequencing

   Pre-analytical Factors:

   Classification	Pre-analytical Factor	Value(s)
   Preaquisition	Patient age	<50 years 50-59 years 60-69 years 70-79 years ≥ 80 years
   Preaquisition	Prognostic factor	Stage I Stage II Stage III Stage IV
   Preaquisition	Diagnosis/ patient condition	Hematologic malignancy Neuroendocrine tumors Prostate carcinoma Breast carcinoma Gastrointestinal carcinoma Head and neck tumors Skin tumors Endocrine tumors Soft tissue tumors Genitourinary tumors Non-small cell lung cancer Gynecologic tumors Central nervous system tumor
   Preaquisition	Patient gender	Female Male

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