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- Title
Gene-expression profiles of pretreatment biopsies predict complete response of rectal cancer patients to preoperative chemoradiotherapy.
- Authors
Emons, Georg; Auslander, Noam; Jo, Peter; Kitz, Julia; Azizian, Azadeh; Hu, Yue; Hess, Clemens F.; Roedel, Claus; Sax, Ulrich; Salinas, Gabriela; Stroebel, Philipp; Kramer, Frank; Beissbarth, Tim; Grade, Marian; Ghadimi, Michael; Ruppin, Eytan; Ried, Thomas; Gaedcke, Jochen
- Abstract
<bold>Purpose: </bold>Preoperative (neoadjuvant) chemoradiotherapy (CRT) and total mesorectal excision is the standard treatment for rectal cancer patients (UICC stage II/III). Up to one-third of patients treated with CRT achieve a pathological complete response (pCR). These patients could be spared from surgery and its associated morbidity and mortality, and assigned to a "watch and wait" strategy. However, reliably identifying pCR based on clinical or imaging parameters remains challenging.<bold>Experimental Design: </bold>We generated gene-expression profiles of 175 patients with locally advanced rectal cancer enrolled in the CAO/ARO/AIO-94 and -04 trials. One hundred and sixty-one samples were used for building, training and validating a predictor of pCR using a machine learning algorithm. The performance of the classifier was validated in three independent cohorts, comprising 76 patients from (i) the CAO/ARO/AIO-94 and -04 trials (n = 14), (ii) a publicly available dataset (n = 38) and (iii) in 24 prospectively collected samples from the TransValid A trial.<bold>Results: </bold>A 21-transcript signature yielded the best classification of pCR in 161 patients (Sensitivity: 0.31; AUC: 0.81), when not allowing misclassification of non-complete-responders (False-positive rate = 0). The classifier remained robust when applied to three independent datasets (n = 76).<bold>Conclusion: </bold>The classifier can identify >1/3 of rectal cancer patients with a pCR while never classifying patients with an incomplete response as having pCR. Importantly, we could validate this finding in three independent datasets, including a prospectively collected cohort. Therefore, this classifier could help select rectal cancer patients for a "watch and wait" strategy.<bold>Translational Relevance: </bold>Forgoing surgery with its associated side effects could be an option for rectal cancer patients if the prediction of a pathological complete response (pCR) after preoperative chemoradiotherapy would be possible. Based on gene-expression profiles of 161 patients a classifier was developed and validated in three independent datasets (n = 76), identifying over 1/3 of patients with pCR, while never misclassifying a non-complete-responder. Therefore, the classifier can identify patients suited for "watch and wait".
- Subjects
BIOPSY; RECTUM tumors; TREATMENT effectiveness; RECTUM; RESEARCH funding; COMBINED modality therapy
- Publication
British Journal of Cancer, 2022, Vol 127, Issue 4, p766
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/s41416-022-01842-2