30 maart 2023: Bron: Lungcancer: RESEARCH ARTICLE| VOLUME 178, P11-19, APRIL 2023

Wetenschappers hebben onderzocht wat de voorspellende waarde kan zijn van het regelmatig meten van circulerend tumor-DNA (ctDNA) bij patiënten met gevorderde uitgezaaide longkanker en deze te combineren met de uitslag van een weefselbiopt. En zij ontdekten een positieve correlatie tussen radiografische tumorbelasting (radiotherapie - bestraling van de kankertumoren) en ctDNA-waarden. De ctDNA-waarden waren consistent met het ziekteverloop.

Door weefselafname te combineren met de uitslag van een analyse van een circulerend tumor-DNA (ctDNA) steeg het detectiepercentage van bruikbare mutaties van 19,4% naar 26,9%. Een circulerend tumor-DNA (ctDNA) detectie op het moment van diagnose was ook onafhankelijk geassocieerd met progressievrije overlevingsresultaten.

Kernpunten uit deze studie:
  • We hebben de volgende generatie sequencing uitgevoerd van 159 plasmamonsters van 69 patiënten met SCLC in een uitgebreid stadium (ES).
  • Combinatie van ctDNA- en weefseltesten verbeterde het algehele detectiepercentage van bruikbare mutaties van 19,4% naar 26,9% vergeleken met dat van alleen weefseldetectie.
  • ctDNA-niveaus veranderden dynamisch tijdens de behandeling en waren significant geassocieerd met verminderde progressievrije overleving.
Het volledige studierapport is tegen betaling in te zien. Hier het abstract van deze studie: 
RESEARCH ARTICLE| VOLUME 178, P11-19, APRIL 2023

Prognostic value of circulating tumor DNA using target next-generation sequencing in extensive-stage small-cell lung cancer

Published:February 01, 2023DOI:https://doi.org/10.1016/j.lungcan.2023.01.015 

Highlights

  • •
    We performed next-generation sequencing of 159 plasma samples from 69 patients with extensive-stage (ES)-SCLC.
  • •
    Combination ctDNA and tissue testing improved the overall detection rate of actionable mutations from 19.4% to 26.9% compared with that of tissue detection alone.
  • •
    ctDNA levels changed dynamically during the course of treatment and were significantly associated with decreased progression-free survival.

Abstract

Background

Chemotherapy remains the mainstay of treatment for small-cell lung cancer (SCLC). Liquid biopsies provide a convenient and non-invasive detection method for monitoring disease progression in patients with SCLC.

Methods

We performed next-generation sequencing of 159 plasma samples from 69 patients with extensive-stage (ES)-SCLC. Circulating tumor (ct)DNA levels were quantified in haploid genome equivalents per mL (hGE/mL). MuTect2 was used to detect single nucleotide variants and short insertions/deletions. The “enrichKEGG” function in the “clusterProfiler” R package was used to enrich the mutated genes that only appeared during disease progression.

Results

In our cohort, 66 of 69 (95.7%) plasma samples at the time of diagnosis had detectable somatic mutations; TP53 (89%) and RB1(56%) were the most frequent mutations, as well as copy number variations in some common SCLC-related genes such as RB1. Combination ctDNA and tissue testing improved the overall detection rate of actionable mutations from 19.4% to 26.9% compared with that of tissue detection alone. In addition, ctDNA levels changed dynamically during the course of treatment and were significantly associated with decreased progression-free survival. Notably, actionable mutations were detected at the time of diagnosis and during disease progression.

Conclusions

Our study revealed a dynamic somatic mutation profile through continuous ctDNA detection and confirmed that ctDNA levels can reflect tumor burden and predict PFS in patients with extensive stage-SCLC. Furthermore, we demonstrated that plasma ctDNA assays can provide real-time information on somatic mutations for potential targeted therapies for SCLC.

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Article info

Publication history

Published online: February 01, 2023
Accepted: January 30, 2023
Received in revised form: January 27, 2023
Received: December 2, 2022

Identification

DOI: https://doi.org/10.1016/j.lungcan.2023.01.015

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© 2023 Elsevier B.V. All rights reserved.

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longkanker, Circulerend tumor-DNA (ctDNA), DNA- en expressieonderzoek, nauwkeurigheid mutaties


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