Highlights
- •No formal guidelines were found that described sample bias due to tumor heterogeneity.
- •Forty-two percent of tissue sample data sets were not accompanied by pathology results.
- •Fifty-eight percent of tissue sample data sets were not diagnosed directly.
- •Forty-two percent of tissue sample data sets failed to report on tumor purity (reported ranges 10% to 100%)
- •The reporting standards for tumor tissue samples need to be improved.
Abstract
Objective
The objective of the study was to identify guidelines to assist systematic reviewers
or clinical researchers in identifying sampling bias due to tumor heterogeneity (TH)
in solid cancers assayed for somatic mutations. We also assessed current reporting
standards to determine the impact of TH on sample bias.
Study Design and Setting
We conducted a systematic review searching 13 databases (to January 2019) to identify
guidelines. A post hoc analysis was performed using 12 prostate tumor somatic mutation data sets from a
previous systematic review to assess reporting on TH.
Results
Searches identified 2,085 records. No formal guidelines were identified. Forty publications
contained incidental recommendations across five major themes: using multiple tumor
samples (n = 29), sample purity thresholds (n = 14), using specific sequencing methods (n = 8), using liquid biopsies (n = 4), and microdissection (n = 4). In post hoc analyses, 50% (6 of 12) clearly reported pathology methods. Forty-two percent (5
of 12) did not report pathology results. Forty-two percent (5 of 12) confirmed the
pathology of the sample by direct diagnosis rather than inference. Forty-two percent
(5 of 12) used multiple samples per patient. Fifty-eight percent (7 of 12) reported
on tumor purity (reported ranges 10% to 100%).
Conclusions
As precision medicine progresses to the clinic, guidelines are required to help evidence-based
decision makers understand how TH may impact sample bias. Authors need to clearly
report pathology methods and results and tumor purity methods and results.
Keywords
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Article info
Publication history
Published online: June 12, 2020
Accepted:
June 10,
2020
Footnotes
Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Disclosures: S.L.S., S.D., and S.H.L. are employees of KSR Ltd.; they have no other conflicts of interest.
Declarations of interest: None.
Compliance with ethics guidelines: This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors.
Data availability: Any additional data sets that are not provided as part of the manuscript or as supplementary materials are available from the corresponding author on reasonable request.
Authors' contributions: S.H.L. contributed to conceptualization, methodology, investigation, writing, reviewing, editing, and supervision. S.L.S contributed to methodology, investigation, writing, reviewing, and editing. S.D. contributed to search methodology and investigation, writing, reviewing, and editing.
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