A genetic profile which identifies patients who will respond to preoperative chemoradiation for rectal cancer

This study looks at the treatment of locally advanced rectal cancer with chemoradiation prior to surgery, and if there are variations in the cancer genes which make some more sensitive to this treatment than others. They find that changes in three individual genes made cancers less sensitive to chemoradiation, and may be a useful diagnostic tool to use when deciding on treatment regimes.

Locally advanced rectal cancer refers to a cancer that has spread beyond (invaded) the lining of the rectum or has spread to the surrounding lymph nodes. Treatment for locally advanced rectal cancer commonly involves a combination of chemotherapy and radiation therapy given before surgery (called neoadjuvant chemoradiation). The use of chemoradiation aims to destroy cancer cells and shrink the tumor prior to surgery in order to enable its complete removal. Not all patients respond similarly to this treatment. Some patients achieve a complete pathological response where there are no cancer cells remaining, others respond only partially. Identifying those patients who are not likely to respond well to chemoradiation may help in the decision of what treatment regimens to use. Particularly because chemoradiation treatment does have side effect (such as sexual dysfunction and bowel incontinence) which can permanently impair patients' quality of life.

This study included 132 patients with locally advanced cancer (cancer stage 2 and 3) who were treated with chemoradiation therapy before surgery. Patients were initially treated with a chemotherapeutic drug called 5- fluorouracil (5-FU) for 7 days with subsequent radiation treatment. Some patients then went on to have surgery within 6 weeks, and some went on to have further chemotherapy before surgery. Biopsies (rectal tissue specimen) were taken from all cancers before chemoradiation treatment. The gene expression in these biopsies was then looked at. Only a small number of patients – 33 out of 132 (25%) – obtained a pathological complete response with chemoradiation treatment. The genetic profile of the cancers from the patients who did and did not achieve a complete response showed differences in three genes. These genes are involved in cell division and recognition of growth factors (factors that promote cancer cell growth).  

Overall this study identified a distinctive genetic profile allowing the identification of a subset of patients who are unlikely to respond to preoperative chemoradiation. This is an important finding, and may aid doctors in the process of patient selection for this treatment. Prospectively such genetic profiling will enable tailoring the right treatments for rectal cancer patients.

There are however limitations to this article. The number of patients included is fairly small and those that obtained a complete response was minimal.