Metastatic nasopharyngeal carcinoma in a lymph node
A new measure of tumor heterogeneity in patients with head and neck squamous cell carcinoma (HNSCC) was significantly associated with tumor progression and adverse treatment outcomes in a study published in Cancer.
The results support the hypothesis that higher genetic heterogeneity predicts worse clinical outcomes in HNSCC.
Researchers have hypothesized that different subgroups of cells that undergo different mutations at different sites of DNA might be more likely to survive treatment with drugs or radiation therapy. Although previous studies have demonstrated that specific genes and proteins are associated with treatment resistance in tumors, no method of conveniently measuring tumor heterogeneity has been developed.
Edmund Mroz, PhD, a researcher at the Massachusetts General Hospital Center for Cancer Research, and colleagues designed a measure called mutant-allele tumor heterogeneity (MATH), which they first described in Oral Oncology
earlier this year. The measure allows researchers to determine both the number of genetic mutations as well as how broadly those mutations were shared within certain subgroups of cells.
“Our findings will eventually allow better matching of treatments to individual patients, based on this characteristic of their tumors,” Mroz said in a statement. “This method of measuring heterogeneity can be applied to most types of cancer, so our work should help researchers determine whether a similar relationship between heterogeneity and outcome occurs in other tumors.”
The researchers analyzed the association between MATH and clinical, pathological, and overall survival data for 74 patients with HNSCC for whom complete treatment and outcome information was available. Higher MATH scores were significantly associated with shorter overall survival (hazard ratio [HR] = 2.5; 95% CI, 1.3 – 4.8). MATH scores were higher in patients with factors that had previously been associated with poorer outcomes, such as having a tumor that tested negative for human papillomavirus. Furthermore, each unit of increase in the MATH score represented a 5% increase in risk of death. MATH values appeared to be more strongly related to outcomes than most previously identified risk factors.
In patients who received chemotherapy, the hazards ratio for high MATH scores was 4.1 (95% CI, 1.6 – 10.2), which may indicate a greater likelihood that heterogeneous tumors may contain treatment-resistant cells, according to Mroz. Subgroups of cells with different mutations within a tumor may be responsible for reducing the chances of survival as opposed to the process of the mutation itself, Mroz also noted.
“If all the tumor cells have gone through the same series of mutations, a single treatment might still be able to kill all of them,” Mroz said. “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 therapy.”
Mroz said the measure could someday be used to guide treatment decisions, with patients who have higher MATH scores receiving a more aggressive treatment regimen. MATH may also be applicable to other tumor types,but they would need to be studied individually.
Mroz EA, Tward AD, Pickering CR, et al. High intratumor genetic heterogeneity is related to worse outcomes in patients with head and neck squamous cell carcinoma [published online ahead of print May 20, 2013]. Cancer. doi:10.1002/cncr.28150.