Post-operative anastomotic leakage and collagen changes in patients with rectal cancer undergoing neoadjuvant chemotherapy vs chemoradiotherapy

BACKGROUND: A significant difference in the anastomotic leakage (AL) rate has been observed between patients with locally advanced rectal cancer who have undergone preoperative chemotherapy and those undergoing preoperative chemoradiotherapy. This study aimed to quantitatively analyse collagen structural changes caused by preoperative chemoradiotherapy and illuminate the relationship between collagen changes and AL. METHODS: Anastomotic distal and proximal “doughnut” specimens from the Sixth Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) were quantitatively assessed for collagen structural changes between patients with and without preoperative radiotherapy using multiphoton imaging. Then, patients treated with preoperative chemoradiotherapy were used as a training cohort to construct an AL–SVM classifier by the Mann–Whitney U test and support vector machine (SVM). An independent test cohort from the Fujian Province Cancer Hospital (Fuzhou, China) was used to validate the AL–SVM classifier. RESULTS: A total of 207 patients were included from the Sixth Affiliated Hospital of Sun Yat-sen University. The AL rate in the preoperative chemoradiotherapy group (n = 107) was significantly higher than that in the preoperative chemotherapy group (n = 100) (21.5% vs 7.0%, P = 0.003). A fully quantitative analysis showed notable morphological and spatial distribution feature changes in collagen in the preoperative chemoradiotherapy group. Then, the patients who received preoperative chemoradiotherapy were used as a training cohort to construct the AL–SVM classifier based on five collagen features and the tumor distance from the anus. The AL–SVM classifier showed satisfactory discrimination and calibration with areas under the curve of 0.907 and 0.856 in the training and test cohorts, respectively. CONCLUSIONS: The collagen structure may be notably altered by preoperative radiotherapy. The AL–SVM classifier was useful for the individualized prediction of AL in rectal cancer patients undergoing preoperative chemoradiotherapy.