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Distribution of residual cancer cells in the bowel wall after neoadjuvant chemoradiation in patients with rectal cancer.

ABSTRACT: The standard treatment for locally advanced rectal cancer is preoperative chemoradiation and total mesorectal excision. After surgery, tumors are classified according to the depth of tumor invasion, nodal involvement, and tumor regression grade. However, these staging systems do not provide information about the distribution of residual cancer cells within the bowel wall.This study aimed to determine the distribution of residual cancer cells in each layer of the bowel wall in rectal cancer specimens.This was a secondary analysis of data from a prospective phase II study.This study was performed in a multi-institutional setting.Included were 153 patients with stage II or stage III rectal cancer.Patients were treated with chemoradiation and surgery. The surgical specimen tumor tissue was analyzed, and the distribution of residual cancer cells in each layer of the bowel wall was determined.Statistical analysis was used to examine the correlation of residual cancer cells in each layer of the bowel wall with the clinical/pathologic stage and tumor regression grade.Forty-two of 153 (27%) patients had complete response in the bowel wall (ypT0). Of the remaining 111 patients who had residual cancer cells, 5 (3%) were ypTis, 12 (8%) were ypT1, 41 (27%) were ypT2, 50 (33%) were ypT3, and 3 (2%) were ypT4. Of the 94 patients with ypT2-4 tumors, 12 (13%) had cancer cells in the mucosa, and 53 (56%) had cancer cells in the submucosa; 92 (98%) had cancer cells in the muscularis propria. Pretreatment cT correlated with the distribution of residual cancer cells. Tumor regression grade was not associated with the distribution of residual cancer cells after chemoradiation.: Patients received different chemotherapy regimens.Residual cancer cells in rectal cancer specimens after chemoradiation are preferentially located close to the invasive front. This should be considered when designing strategies to diagnose complete pathologic response and when investigating the mechanisms of tumor resistance to chemoradiation.

SUBMITTER: Duldulao MP

PROVIDER: S-EPMC4674069 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Distribution of residual cancer cells in the bowel wall after neoadjuvant chemoradiation in patients with rectal cancer.

Duldulao Marjun P MP Lee Wendy W Streja Leanne L Chu Peiguo P Li Wenyan W Chen Zhenbin Z Kim Joseph J Garcia-Aguilar Julio J

Diseases of the colon and rectum 20130201 2

<h4>Background</h4>The standard treatment for locally advanced rectal cancer is preoperative chemoradiation and total mesorectal excision. After surgery, tumors are classified according to the depth of tumor invasion, nodal involvement, and tumor regression grade. However, these staging systems do not provide information about the distribution of residual cancer cells within the bowel wall.<h4>Objective</h4>This study aimed to determine the distribution of residual cancer cells in each layer of ...[more]

PMID: 23303141

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Project description:Background:There is recent interest in treating locally advanced rectal cancer (LARC) patients with total neoadjuvant therapy (TNT). However, whether TNT is associated with improved overall survival (OS) remains unknown. This study compares outcomes following TNT and following neoadjuvant chemoradiation therapy (nCRT) in patients with LARC, clinically defined cT3/4 or node positive disease, using the National Cancer Database. Methods:LARC patients diagnosed between 2004-2015 were included. TNT was defined as multi-agent chemotherapy given at least 2 months before RT followed by pre-operative chemoradiation therapy and definitive surgery without adjuvant chemotherapy. nCRT was defined as pre-operative RT and chemotherapy started within 2 weeks from each other followed by definitive surgery with or without adjuvant chemotherapy. Kaplan-Meier curve with logrank test and multivariable Cox proportional hazards regression modelling were used to analyse the primary endpoint of overall survival (OS). Multivariable logistic regression modelling was used for secondary outcomes to determine if TNT is associated with pathological complete response (pCR), defined as ypT0N0, and negative circumferential resection margin (CRM). Findings:Data from 372 TNT patients and 707 nCRT patients were analysed after a 2:1 propensity matching with replacement. Kaplan-Meier curve showed that OS with TNT was comparable to that with nCRT (p = 0•16). The 5-year OS rates for TNT and nCRT were 73•6% vs. 78•5% (p = 0•20). Multivariable Cox proportional hazards regression modelling confirmed no difference in OS between TNT and nCRT (HR = 1•21, p = 0•25). With TNT, 16•9% patients achieved pCR, whereas 13•1% patients achieved pCR with nCRT (p = 0•12). TNT was not found to be significantly associated with pCR (OR = 1•36, p = 0•13) or negative CRM (OR = 1•77, p = 0•19) in multivariable logistic regression modelling. Interpretation:With results from current clinical trials pending, our data suggested that TNT and nCRT resulted in similar survival, while TNT led to higher pCR and CRM negative rate, albeit not statistically significant.

Dataset Information

Distribution of residual cancer cells in the bowel wall after neoadjuvant chemoradiation in patients with rectal cancer.

Publications

Distribution of residual cancer cells in the bowel wall after neoadjuvant chemoradiation in patients with rectal cancer.

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