Dynamics of cell-free tumour DNA correlate with treatment response of head and neck cancer patients receiving radiochemotherapy

Hilke, Franz J.; Muyas, Francesc; Admard, Jakob; Kootz, Beate; Nann, Dominik; Welz, Stefan; Rieß, Olaf; Zips, Daniel; Ossowski, Stephan; Schroeder, Christopher; Clasen, Kerstin

doi:10.1016/j.radonc.2020.07.027

Cited by 41 publications

(26 citation statements)

References 30 publications

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“…The clonality estimates are based on published approaches [9,18], but some inaccuracies are possible as these technologies are relatively novel, and not all sources of bias may have been identified. Importantly, our assay's average sequencing depth was similar to other current ctDNA sequencing technologies [22][23][24], and we have previously shown that the sensitivity of this assay was comparable to other technologies with error correction [12]. Thus, it is unlikely that poor assay sensitivity explains these results.…”

Section: Discussionsupporting

confidence: 62%

Circulating Tumour DNA Sequencing Identifies a Genetic Resistance-Gap in Colorectal Cancers with Acquired Resistance to EGFR-Antibodies and Chemotherapy

Knebel

Barber

Newey

et al. 2020

Cancers

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Epidermal growth factor receptor antibodies (EGFR-Abs) confer a survival benefit in patients with RAS wild-type metastatic colorectal cancer (mCRC), but resistance invariably occurs. Previous data showed that only a minority of cancer cells harboured known genetic resistance drivers when clinical resistance to single-agent EGFR-Abs had evolved, supporting the activity of non-genetic resistance mechanisms. Here, we used error-corrected ctDNA-sequencing (ctDNA-Seq) of 40 cancer genes to identify drivers of resistance and whether a genetic resistance-gap (a lack of detectable genetic resistance mechanisms in a large fraction of the cancer cell population) also occurs in RAS wild-type mCRCs treated with a combination of EGFR-Abs and chemotherapy. We detected one MAP2K1/MEK1 mutation and one ERBB2 amplification in 2/3 patients with primary resistance and KRAS, NRAS, MAP2K1/MEK1 mutations and ERBB2 aberrations in 6/7 patients with acquired resistance. In vitro testing identified MAP2K1/MEK1 P124S as a novel driver of EGFR-Ab resistance. Mutation subclonality analyses confirmed a genetic resistance-gap in mCRCs treated with EGFR-Abs and chemotherapy, with only 13.42% of cancer cells harboring identifiable resistance drivers. Our results support the utility of ctDNA-Seq to guide treatment allocation for patients with resistance and the importance of investigating further non-canonical EGFR-Ab resistance mechanisms, such as microenvironmentally-mediated resistance. The detection of MAP2K1 mutations could inform trials of MEK-inhibitors in these tumours.

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Section: Discussionsupporting

confidence: 62%

Circulating Tumour DNA Sequencing Identifies a Genetic Resistance-Gap in Colorectal Cancers with Acquired Resistance to EGFR-Antibodies and Chemotherapy

Knebel

Barber

Newey

et al. 2020

Cancers

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“…Certainly, NGS has the potential to support risk stratification of patients with HPV-associated disease through its ability to detect types within tissue with exquisite sensitivity and through providing subtle insights into aspects of HPV infection that may be predictive of outcome (integration pattern and status, delineation of dominant variant(s), and viral load). NGS may also be applied to liquid biopsies, from blood, to support longitudinal monitoring of treatment success [ 90 ].…”

Section: Discussionmentioning

confidence: 99%

Human Papillomavirus Detection by Whole-Genome Next-Generation Sequencing: Importance of Validation and Quality Assurance Procedures

Mühr

Guerendiain

Cuschieri

et al. 2021

Viruses

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Next-generation sequencing (NGS) yields powerful opportunities for studying human papillomavirus (HPV) genomics for applications in epidemiology, public health, and clinical diagnostics. HPV genotypes, variants, and point mutations can be investigated in clinical materials and described in previously unprecedented detail. However, both the NGS laboratory analysis and bioinformatical approach require numerous steps and checks to ensure robust interpretation of results. Here, we provide a step-by-step review of recommendations for validation and quality assurance procedures of each step in the typical NGS workflow, with a focus on whole-genome sequencing approaches. The use of directed pilots and protocols to ensure optimization of sequencing data yield, followed by curated bioinformatical procedures, is particularly emphasized. Finally, the storage and sharing of data sets are discussed. The development of international standards for quality assurance should be a goal for the HPV NGS community, similar to what has been developed for other areas of sequencing efforts including microbiology and molecular pathology. We thus propose that it is time for NGS to be included in the global efforts on quality assurance and improvement of HPV-based testing and diagnostics.

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“…A custom-made panel is designed accordingly to sequence the altered positions in the plasma. This custom panel, specific to the patient’s tumor, can employ PCR-amplification using specific primers, or hybridization-based capture using specific probes, in order to enrich the regions of interest for NGS [ 86 , 87 ], with a barcoding method typically incorporated to allow for sample multiplexing.…”

Section: Methodology To Detect Minimal Residual Disease With Ctdnamentioning

confidence: 99%

“…This design has been implemented in several clinical studies in the context of MRD detection [ 87 , 88 , 89 , 90 ] and has shown interesting results. The techniques used in these studies, and their main conclusions, are detailed in Table 1 .…”

Section: Methodology To Detect Minimal Residual Disease With Ctdnamentioning

confidence: 99%

“…In the post-curative treatment setting, the success rate of the technique drops. Although it shows a good positive predictive value, the negative predictive value still has room for improvement: when ctDNA is detected post-treatment, patients are significantly more likely to experience relapse in the following months [ 87 , 120 , 121 ]. However, due mainly to technical limitations, not detecting ctDNA after curative-intent treatment does not predict the tumor’s definitive elimination (cf/ Table 2 ).…”

Section: Methodology To Detect Minimal Residual Disease With Ctdnamentioning

confidence: 99%

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Liquid Biopsy to Detect Minimal Residual Disease: Methodology and Impact

Honoré

Galot

Marcke

et al. 2021

Cancers

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One reason why some patients experience recurrent disease after a curative-intent treatment might be the persistence of residual tumor cells, called minimal residual disease (MRD). MRD cannot be identified by standard radiological exams or clinical evaluation. Tumor-specific alterations found in the blood indirectly diagnose the presence of MRD. Liquid biopsies thus have the potential to detect MRD, allowing, among other things, the detection of circulating tumor DNA (ctDNA), circulating tumor cells (CTC), or tumor-specific microRNA. Although liquid biopsy is increasingly studied, several technical issues still limit its clinical applicability: low sensitivity, poor standardization or reproducibility, and lack of randomized trials demonstrating its clinical benefit. Being able to detect MRD could give clinicians a more comprehensive view of the risk of relapse of their patients and could select patients requiring treatment escalation with the goal of improving cancer survival. In this review, we are discussing the different methodologies used and investigated to detect MRD in solid cancers, their respective potentials and issues, and the clinical impacts that MRD detection will have on the management of cancer patients.

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Dynamics of cell-free tumour DNA correlate with treatment response of head and neck cancer patients receiving radiochemotherapy

Cited by 41 publications

References 30 publications

Circulating Tumour DNA Sequencing Identifies a Genetic Resistance-Gap in Colorectal Cancers with Acquired Resistance to EGFR-Antibodies and Chemotherapy

Circulating Tumour DNA Sequencing Identifies a Genetic Resistance-Gap in Colorectal Cancers with Acquired Resistance to EGFR-Antibodies and Chemotherapy

Human Papillomavirus Detection by Whole-Genome Next-Generation Sequencing: Importance of Validation and Quality Assurance Procedures

Liquid Biopsy to Detect Minimal Residual Disease: Methodology and Impact

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