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Oncology outcomes

Does mixed DNA inside a head-and-neck tumor predict death?

Mroz EA, Tward AD, Hammon RJ, et al. · PLoS medicine · 2015

Open access · cc by · source: Europe PMC

In 305 TCGA HNSCC patients, high intra-tumor MATH heterogeneity more than doubled the hazard of death (HR 2.2; 95% CI 1.4–3.3), even after HPV, TP53, grade, and N classification.

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Study at a glance

Design
Cohort — Retrospective TCGA analysis of bulk-tumor WES MATH vs overall survival in HNSCC (diagnoses 1992–2011).
N
N=305 · 305 HNSCC patients from 14 institutions; 131 deaths (median time to death 14 months); living median follow-up 22 months.
Population
TCGA head and neck squamous cell carcinoma cases with clinical and whole-exome data (October 2013 freeze).
Outcome
Overall survival associated with high vs low mutant-allele tumor heterogeneity (MATH).

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Does mixed DNA inside a head-and-neck tumor predict death?

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305 HNSCC patients from 14 institutions were analyzed.

Clinical and WES data were obtained from The Cancer Genome Atlas in October 2013 for 305 patients with head and neck squamous cell carcinoma (HNSCC), from 14 institutions.

High vs low MATH HR for death was 2.2 (95% CI 1.4–3.3).

hazard ratio for high/low heterogeneity, 2.2; 95% CI 1.4 to 3.3
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Key findings

High MATH HR was 2.2 (univariate ~2.18). The association was not explained by age, HPV, grade, TP53, or N class, improved prognostication, and still split oral-cavity and laryngeal outcomes after staging. Chemoradiotherapy patients showed a particularly large HR (5.2).

Methodology

Calculated MATH from bulk-tumor whole-exome sequencing for 305 HNSCC cases from 14 institutions and related high vs low MATH to overall survival with Cox models, including multivariate adjustment for standard clinical/molecular factors.

Limitations

Retrospective multi-site TCGA data were not collected to study MATH; prospective, homogeneously treated series (especially HPV+ oropharynx) are still required before clinical use.

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