Evidence map›Paper›PMID 31092276›Full record

ArticleBMC research notes2019

Monitoring dynamic cytotoxic chemotherapy response in castration-resistant prostate cancer using plasma cell-free DNA (cfDNA).

Katherin Patsch, Naim Matasci, Anjana Soundararajan, Patricia Diaz, David B Agus, Daniel Ruderman, Mitchell E Gross

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC research notes, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Katherin PatschLawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA, USA.
Naim MatasciLawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA, USA.
Anjana SoundararajanLawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA, USA.
Patricia DiazLawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA, USA.
David B AgusLawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA, USA.
Daniel RudermanLawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA, USA. ruderman@usc.edu.
Mitchell E GrossLawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA, USA. mitchell.gross@usc.edu.

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MYLES G COCKBURN · 1985 to 2026
$181.4M
National Cancer Institute Cancer Center P30CA014089NCI NIH HHS P30 CA014089
6 · The paper itself

Abstract

objectiveCell-free DNA (cfDNA) is an attractive cancer biomarker, as it is thought to reflect a component of the underlying genetic makeup of the tumor and is readily accessible in serial fashion. Because chemotherapy regimens are expected to act rapidly on cancer and cfDNA is cleared from the blood within minutes, we hypothesized that cfDNA would reflect immediate effects of treatment. Here, we developed a method for monitoring long cfDNA fragments, and report dynamic changes in response to cytotoxic chemotherapy.

resultsPeripheral blood was obtained from 15 patients with metastatic castration-resistant prostate cancer (CRPC) immediately before and after cytotoxic chemotherapy infusion. cfDNA was extracted and quantified for long interspersed nuclear elements (LINE1; 297 bp) using qPCR. Targeted deep sequencing was performed to quantify the frequency of mutations in exon 8 of the androgen receptor (AR), a mutational hotspot region in CRPC. Single nucleotide mutations in AR exon 8 were found in 6 subjects (6/15 = 40%). Analytical variability was minimized by pooling independent PCR reactions for each library. In 5 patients, tumor-derived long cfDNA levels were found to change immediately after infusion. Detailed analysis of one subject suggests that cytotoxic chemotherapy can produce rapidly observable effects on cfDNA.

Indexed as

Circulating Tumor DNADocetaxelExonsHumansMalePolymorphism, Single NucleotideProstatic Neoplasms, Castration-ResistantReceptors, AndrogenAR protein, humanCirculating Tumor DNADocetaxelReceptors, AndrogenAndrogen receptorCell-free DNAChemotherapyProstate cancerSequencing

Identifiers

PMID31092276
PMCPMC6521434

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.