Predicting Prostate Cancer Patients’ Toxicity From Radiation Therapy

Genetic variants could affect how cancer patients respond to radiation therapy. The results are based on a genome-wide analysis of the genetic variations among prostate cancer patients treated with external beam radiotherapy (EBRT).

Variants in one specific locus, called TANC1, particularly correlated with the development of late radiation-induced toxicity: diarrhea, incontinence, and impotence. The results were published in a recent issue of Nature Genetics.

"Our findings, which were replicated in two additional patient groups, represent a significant step towards developing personalized treatment plans for prostate cancer patients," said study author Barry S. Rosenstein, PhD, professor of radiation oncology, at the Icahn School of Medicine at Mount Sinai. "Within five years, through the use of a predictive genomic test that will be created using the data obtained in the recent study, it may be possible to optimize treatment for a large number of cancer patients."

While there have been improvements in radiotherapy (including optimization of dosing and reduction in the amount of non-cancerous tissue exposed to radiation), according to previous studies, about 40% of prostate cancer patients experience acute radiation therapy toxicities and about 7.7% have late-onset toxicity. Unfortunately, some of these side effects are irreversible and do not appear until 2 to 3 years after the treatment course has ended, decreasing the quality of life for these cancer survivors.

The international research team, from the Universidade de Santiago de Compostela in Spain, the Centre for Cancer Genetic Epidemiology, University of Cambridge, UK, the University of Manchester, UK, and Mount Sinai in New York, initially analyzed blood samples from 741 prostate cancer patients treated with radiotherapy in Spain. The data included acute radiation toxicity available for all patients and data on late toxicity available for 417 of the patients. Two subsequent datasets comprised 633 and 368 prostate cancer patients. The blood samples were screened for approximately one million different genetic markers, revealing which markers were consistently associated with the development of complications post radiotherapy.

The authors provide a potential biological explanation for the role of TANC1 in radiotherapy-induced toxicity that can now be tested. TANC1 functions in the regeneration of muscle tissue in mammals. “Therefore, it is biologically possible that TANC1 is involved in the regeneration of radiation-induced muscle damage,” stated the authors.

Which genetic pathways can influence the radio-toxicity of tissues is complicated and not well understood, but it is assumed that there are both genetic variations that confer general radio-toxicity in all tissues and also tissue-specific toxicity.

The next step, according to Rosenstein, is to understand whether the same gene markers confer similar late-onset radiotherapy toxicity for patients with other tumor types. “Using the genomic test being developed, treatment plans can be adjusted to minimize adverse effects, thereby allowing for an improved quality life for many cancer survivors."