Abstract
Patients presenting with locally advanced rectal cancer currently receive preoperative radiotherapy with or without chemotherapy. Although pathologic complete response is achieved for approximately 10% to 30% of patients, a proportion of patients derive no benefit from this therapy while being exposed to toxic side effects of treatment. Therefore, there is a strong need to identify patients who are unlikely to benefit from neoadjuvant therapy to help direct them toward alternate and ultimately more successful treatment options. In this study, we obtained expression profiles from pretreatment biopsies for 51 rectal cancer patients. All patients underwent preoperative chemoradiotherapy, followed by resection of the tumor 6 to 8 weeks posttreatment. Gene expression and response to treatment were correlated, and a supervised learning algorithm was used to generate an original predictive classifier and validate previously published classifiers. Novel predictive classifiers based on Mandard's tumor regression grade, metabolic response, TNM (tumor node metastasis) downstaging, and normal tissue expression profiles were generated. Because there were only 7 patients who had minimal treatment response (>80% residual tumor), expression profiles were used to predict good tumor response and outcome. These classifiers peaked at 82% sensitivity and 89% specificity; however, classifiers with the highest sensitivity had poor specificity, and vice versa. Validation of predictive classifiers from previously published reports was attempted using this cohort; however, sensitivity and specificity ranged from 21% to 70%. These results show that the clinical utility of microarrays in predictive medicine is not yet within reach for rectal cancer and alternatives to microarrays should be considered for predictive studies in rectal adenocarcinoma.
Highlights
Validation of predictive classifiers from previously published reports was attempted using this cohort; sensitivity and specificity ranged from 21% to 70%. These results show that the clinical utility of microarrays in predictive medicine is not yet within reach for rectal cancer and alternatives to microarrays should be considered for predictive studies in rectal adenocarcinoma
Neoadjuvant chemoradiotherapy (CRT) has become the standard of care for patients presenting with locally advanced rectal cancer in many centers
All patients received treatment considered the standard of care for patients with locally advanced rectal cancer, comprising a total radiation dose of 50 Gy applied in 25 fractions over 5 weeks, concurrent with daily administration of 225 mg/m2 5-fluorouracil (5-FU) continuously for 5 weeks
Summary
Neoadjuvant chemoradiotherapy (CRT) has become the standard of care for patients presenting with locally advanced rectal cancer in many centers. PCR is achieved only for 10% to 30% of rectal cancer patients [4, 5], meaning that many patients respond well to CRT, a similar proportion fail to respond or experience disease progression. These patients derive no survival benefit yet are exposed to toxic side effects of treatment. There is a strong need to identify patients unlikely to benefit from preoperative CRT to help direct them toward alternate and possibly more successful treatment options
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
