Liquid BIOpsy for MiNimal RESidual DiSease Detection in Head and Neck Squamous Cell Carcinoma (LIONESS)—a personalised circulating tumour DNA analysis in head and neck squamous cell carcinoma

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Abstract

Background

Head and neck squamous cell carcinoma (HNSCC) remain a substantial burden to global health. Cell-free circulating tumour DNA (ctDNA) is an emerging biomarker but has not been studied sufficiently in HNSCC.

Methods

We conducted a single-centre prospective cohort study to investigate ctDNA in patients with p16-negative HNSCC who received curative-intent primary surgical treatment. Whole-exome sequencing was performed on formalin-fixed paraffin-embedded (FFPE) tumour tissue. We utilised RaDaR ^TM, a highly sensitive personalised assay using deep sequencing for tumour-specific variants, to analyse serial pre- and post-operative plasma samples for evidence of minimal residual disease and recurrence.

Results

In 17 patients analysed, personalised panels were designed to detect 34 to 52 somatic variants. Data show ctDNA detection in baseline samples taken prior to surgery in 17 of 17 patients. In post-surgery samples, ctDNA could be detected at levels as low as 0.0006% variant allele frequency. In all cases with clinical recurrence to date, ctDNA was detected prior to progression, with lead times ranging from 108 to 253 days.

Conclusions

This study illustrates the potential of ctDNA as a biomarker for detecting minimal residual disease and recurrence in HNSCC and demonstrates the feasibility of personalised ctDNA assays for the detection of disease prior to clinical recurrence.

Related collections

Most cited references 56

Record: found
Abstract: found
Article: not found

Detection of circulating tumor DNA in early- and late-stage human malignancies.

Chetan Bettegowda, Mark Sausen, Rebecca Leary … (2014)

The development of noninvasive methods to detect and monitor tumors continues to be a major challenge in oncology. We used digital polymerase chain reaction-based technologies to evaluate the ability of circulating tumor DNA (ctDNA) to detect tumors in 640 patients with various cancer types. We found that ctDNA was detectable in >75% of patients with advanced pancreatic, ovarian, colorectal, bladder, gastroesophageal, breast, melanoma, hepatocellular, and head and neck cancers, but in less than 50% of primary brain, renal, prostate, or thyroid cancers. In patients with localized tumors, ctDNA was detected in 73, 57, 48, and 50% of patients with colorectal cancer, gastroesophageal cancer, pancreatic cancer, and breast adenocarcinoma, respectively. ctDNA was often present in patients without detectable circulating tumor cells, suggesting that these two biomarkers are distinct entities. In a separate panel of 206 patients with metastatic colorectal cancers, we showed that the sensitivity of ctDNA for detection of clinically relevant KRAS gene mutations was 87.2% and its specificity was 99.2%. Finally, we assessed whether ctDNA could provide clues into the mechanisms underlying resistance to epidermal growth factor receptor blockade in 24 patients who objectively responded to therapy but subsequently relapsed. Twenty-three (96%) of these patients developed one or more mutations in genes involved in the mitogen-activated protein kinase pathway. Together, these data suggest that ctDNA is a broadly applicable, sensitive, and specific biomarker that can be used for a variety of clinical and research purposes in patients with multiple different types of cancer.

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Record: found
Abstract: found
Article: found

Is Open Access

Comprehensive genomic characterization of head and neck squamous cell carcinomas

Akinyemi Ojesina, Nikolaus Schultz (2015)

The Cancer Genome Atlas profiled 279 head and neck squamous cell carcinomas (HNSCCs) to provide a comprehensive landscape of somatic genomic alterations. We find that human papillomavirus-associated (HPV) tumors are dominated by helicase domain mutations of the oncogene PIK3CA, novel alterations involving loss of TRAF3, and amplification of the cell cycle gene E2F1. Smoking-related HNSCCs demonstrate near universal loss of TP53 mutations and CDKN2A with frequent copy number alterations including a novel amplification of 11q22. A subgroup of oral cavity tumors with favorable clinical outcomes displayed infrequent CNAs in conjunction with activating mutations of HRAS or PIK3CA, coupled with inactivating mutations of CASP8, NOTCH1 and wild-type TP53. Other distinct subgroups harbored novel loss of function alterations of the chromatin modifier NSD1, Wnt pathway genes AJUBA and FAT1, and activation of oxidative stress factor NFE2L2, mainly in laryngeal tumors. Therapeutic candidate alterations were identified in the majority of HNSCC's.

0 comments Cited 985 times – based on 0 reviews      Review now

Record: found
Abstract: found
Article: not found

Detection and localization of surgically resectable cancers with a multi-analyte blood test

Nickolas Papadopoulos, Robert E. Schoen, Randall Brand … (2018)

Earlier detection is key to reducing cancer deaths. Here we describe a blood test that can detect eight common cancer types through assessment of the levels of circulating proteins and mutations in cell-free DNA. We applied this test, called CancerSEEK, to 1,005 patients with non-metastatic, clinically detected cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or breast. CancerSEEK tests were positive in a median of 70% of the eight cancer types. The sensitivities ranged from 69% to 98% for the detection of five cancer types (ovary, liver, stomach, pancreas, and esophagus) for which there are no screening tests available for average-risk individuals. The specificity of CancerSEEK was > 99%: only 7 of 812 healthy controls scored positive. In addition, CancerSEEK localized the cancer to a small number of anatomic sites in a median of 83% of the patients.

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Author and article information

Contributors

Susanne Flach:

ORCID: http://orcid.org/0000-0001-6196-3706

susanne.flach@med.uni-muenchen.de

Journal

Journal ID (nlm-ta): Br J Cancer

Journal ID (iso-abbrev): Br J Cancer

Title: British Journal of Cancer

Publisher: Nature Publishing Group UK (London )

ISSN (Print): 0007-0920

ISSN (Electronic): 1532-1827

Publication date (Electronic): 7 February 2022

Publication date PMC-release: 7 February 2022

Publication date (Print): 3 May 2022

Volume: 126

Issue: 8

Pages: 1186-1195

Affiliations

[1 ]GRID grid.411095.8, ISNI 0000 0004 0477 2585, Department of Otorhinolaryngology, Head and Neck Surgery, , Hospital of the Ludwig-Maximilians-University (LMU) of Munich, ; Marchioninistrasse 15, 81377 Munich, Germany

[2 ]Inivata Ltd, Babraham Research Park, Cambridge, UK

[3 ]GRID grid.5252.0, ISNI 0000 0004 1936 973X, Institute of Pathology, , Faculty of Medicine, LMU Munich, ; Munich, Germany

[4 ]Clinical Cooperation Group “Personalised Radiotherapy in Head and Neck Cancer”, German Research Centre for Environmental Health GmbH, Neuherberg, Munich, Germany

Author information

Susanne Flach http://orcid.org/0000-0001-6196-3706

Article

Publisher ID: 1716

DOI: 10.1038/s41416-022-01716-7

PMC ID: 9023460

PubMed ID: 35132238

SO-VID: db0bf96a-275b-4961-98a1-055734044c36

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 9 May 2021

Date revision received : 11 December 2021

Date accepted : 21 January 2022

Custom metadata

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: head and neck cancer,tumour biomarkers,translational research,surgical oncology

Data availability:

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: head and neck cancer, tumour biomarkers, translational research, surgical oncology