Pretreatment gene expression profiles might predict who responds to preoperative chemoradiotherapy in patients with rectal adenocarcinomas, results from a small trial have shown.
The finding is important because the response of individual tumors to adjuvant therapies is not consistent, wrote the investigators, led by B. Michael Ghadimi, M.D., a surgeon at University Medical Center in Göttingen, Germany.
“This poses a considerable clinical dilemma, because patients with a priori resistant tumors could be spared exposure to radiation or DNA-damaging drugs, treatments that are associated with substantial adverse effects, and surgery could be scheduled without delay,” they wrote.
Dr. Ghadimi and his associates used microarrays to analyze pretherapeutic biopsies from 23 patients with rectal carcinomas for gene expression signatures.
The patients were enrolled in the phase III German Rectal Cancer Trial and were randomized to receive a preoperative combined-modality therapy that included fluorouracil and radiation (J. Clin. Oncol. 2005;23:1826-38).
After using class-comparison analysis, the investigators identified 54 genes that had significantly different expression levels between responsive and nonresponsive tumors based on T-level downsizing.
Next, they used leave-one-out cross-validation to estimate the response prediction of gene expression profiling and noted that the sensitivity and specificity of the test were 78% and 86%, respectively, while the positive and negative predictive values were 78% and 86%, respectively.
“Our inability to achieve higher accuracy could be due to several reasons, including tumor heterogeneity or the possibility that contamination of these particular biopsies with either normal rectal epithelium or adenomatous or stromal tissue could have partially obscured the detection of gene expression profiles more specific to rectal tumor cells.”
They emphasized that larger, multicenter studies will be needed to confirm the findings.
Doug Brunk