Evidence map›Paper›PMID 32766143›Full record

ArticleFrontiers in oncology2020

Evolution of RAS Mutational Status in Liquid Biopsies During First-Line Chemotherapy for Metastatic Colorectal Cancer.

Susanne Klein-Scory, Ingo Wahner, Marina Maslova, Yosef Al-Sewaidi, Michael Pohl, Thomas Mika, Swetlana Ladigan, Roland Schroers, Alexander Baraniskin

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Frontiers in oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04554836 (Modulation of the FOLFIRI-based Standard First-line Therapy With Cetuximab, Controlled by Monitoring the RAS), which is not on this map. Cited by 34 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 8% of its field
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.

NCT04554836 phase2completednot on this map

Modulation of the FOLFIRI-based Standard First-line Therapy With Cetuximab, Controlled by Monitoring the RAS (Rat Sarcoma) Mutation Load by Liquid Biopsy in RAS-mutated mCRC (Metastatic Colorectal Cancer): A Randomized Phase II Study With FOLFIRI-based First-line Therapy With or Without Intermittent Cetuximab (MoLiMoR)

TypeinterventionalSponsorTheraOpRan2020 to 2024Enrolled6ConditionsAdenocarcinoma of the Colon, Adenocarcinoma of the RectumArmsCetuximab, FOLFIRI
3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Kinetic Profiling ofJCO precision oncology · 2024
    Trial
  4. Review
  5. Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. International journal of molecular sciences · 2023
    Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Anti-epidermal growth factor receptor treatment for patients with NeoTherapeutic advances in medical oncology · 2023
    Article
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

9 authors at 2 institutions in 1 country.

Susanne Klein-ScoryIMBL Medical Clinic, Ruhr University Bochum, University Hospital Knappschaftskrankenhaus Bochum GmbH, Bochum, Germany.
Ingo WahnerIMBL Medical Clinic, Ruhr University Bochum, University Hospital Knappschaftskrankenhaus Bochum GmbH, Bochum, Germany.
Marina MaslovaDepartment of Radiology, University Hospital Knappschaftskrankenhaus Bochum GmbH, Ruhr University Bochum, Bochum, Germany.
Yosef Al-SewaidiDepartment of Radiology, University Hospital Knappschaftskrankenhaus Bochum GmbH, Ruhr University Bochum, Bochum, Germany.
Michael PohlDepartment of Medicine, University Hospital Knappschaftskrankenhaus Bochum GmbH, Ruhr University Bochum, Bochum, Germany.
Thomas MikaDepartment of Medicine, University Hospital Knappschaftskrankenhaus Bochum GmbH, Ruhr University Bochum, Bochum, Germany.
Swetlana LadiganDepartment of Medicine, University Hospital Knappschaftskrankenhaus Bochum GmbH, Ruhr University Bochum, Bochum, Germany.
Roland SchroersDepartment of Medicine, University Hospital Knappschaftskrankenhaus Bochum GmbH, Ruhr University Bochum, Bochum, Germany.
Alexander BaraniskinIMBL Medical Clinic, Ruhr University Bochum, University Hospital Knappschaftskrankenhaus Bochum GmbH, Bochum, Germany.
Ruhr University Bochum · DEUniversitätsklinikum Knappschaftskrankenhaus Bochum · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Treatment options for patients with metastatic colorectal cancer (mCRC) are limited. This particularly affects the largest group of patients with RAS mutations, who are considered ineligible for therapy with antiEGFR antibodies. In this liquid biopsy-based study, we performed the first in-depth analysis of the RAS mutational status in initially RAS-mutated patients during first-line therapy. RAS status of twelve patients with initially RAS-mutated mCRC was monitored longitudinally in 69 liquid biopsy samples. We focused on patients with stable disease (SD) or partial remission (PR) during first-line therapy (11 patients). Detection of fragmented RAS-mutated circulating cell-free tumor DNA (ctDNA) in plasma was performed by digital-droplet PCR (ddPCR) and BEAMing. Patients' total tumor masses were determined by measuring the tumor volumes using CT scan data. All patients with PR or SD at first follow-up showed a significant decrease of RAS mutational load. In ten patients (91%), the ctDNA-based RAS mutational status converted to wild-type in ddPCR and BEAMing. Remarkably, conversions were observed early after the first cycle of chemotherapy. Plasma concentration of ctDNA was controlled by determination of methylated WIF1-promotor ctDNA burden as a second tumor marker for mCRC. Persistent presence of methylated WIF1-promotor fragments confirmed the ongoing release of ctDNA during treatment. In patients with initially RAS-mutated mCRC, RAS mutations rapidly disappeared during first-line therapy in liquid biopsy, independent of type and intensity of chemotherapy and irrespective of anti-VEGF treatments. Following our results demonstrating conversion of RAS-mutational status, potential effectiveness of anti-EGFR antibodies in selected patients becomes an attractive hypothesis for future studies.

Indexed as

BEAMingcirculating tumor DNAclonal selectioncolorectal cancerdigital droplet PCRliquid biopsymethylation WIF1 promotorneoRAS wild-type

Identifiers

PMID32766143
PMCPMC7378792
OpenAlexW3043060085

What OpenQuestion holds

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Registered trials

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.