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Tumor heterogeneity may affect head and neck cancer outcomes

By Dental Tribune International
May 23, 2013

BOSTON, Mass., USA: Although the presence of genetic heterogeneity within tumors has been established, it is unclear whether greater heterogeneity predicts worse outcomes. Now, a study has suggested that a novel measure of tumor genetic heterogeneity is significantly associated with tumor progression and adverse treatment outcomes. By measuring the genetic diversity of tumor cells, researchers were able to predict treatment outcomes of patients with the most common type of head and neck cancer.

The measure was developed by scientists at the Massachusetts Eye and Ear Infirmary in collaboration with the Massachusetts General Hospital's head and neck cancer research laboratory. Through analysis of gene sequences, they were able to produce a value reflecting the genetic diversity within a tumor. The measure, called mutant-allele tumor heterogeneity (MATH), was first described in the March issue of the Oral Oncology journal. The study, however, only demonstrated that patients with known factors predicting poor outcomes are likely to have higher MATH values.

The current study involved 74 patients with head and neck squamous cell carcinoma for whom complete treatment and outcome information was available. Through analysis of the genetic data of their tumors, the researchers found that higher MATH values were strongly associated with shorter survival. For instance, among patients with human papillomavirus-negative tumors, those with higher MATH values were less likely to survive than patients with lower values were.

Moreover, they found that the impact of MATH value on outcome was strongest in patients treated with chemotherapy, which suggests that highly heterogeneous tumors contain treatment-resistant cells, said Dr. Edmund Mroz, lead author of the study. "If all tumor cells have gone through the same series of mutations, a single treatment might still be able to kill them. But if there are subgroups with different sets of mutations, one subgroup might be resistant to one type of treatment, while another subgroup might resist a different treatment," he explained.

Mroz said further that the measure could someday help determine treatment choices, for example directing the use of more aggressive therapies against tumors with higher values, while administering less-intense standard treatment to patients with lower values.

The study, titled "High Intratumor Genetic Heterogeneity is Related to Worse Outcome in Patients with Head and Neck Squamous Cell Carcinoma," was published online on May 20 in the Cancer journal ahead of print.

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