Retrospective Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 7, 2019; 25(1): 118-137
Published online Jan 7, 2019. doi: 10.3748/wjg.v25.i1.118
Nomograms for predicting pathological response to neoadjuvant treatments in patients with rectal cancer
Dong-Lin Ren, Juan Li, Hui-Chuan Yu, Shao-Yong Peng, Wei-Da Lin, Xiao-Lin Wang, Roshan Ara Ghoorun, Yan-Xin Luo
Dong-Lin Ren, Juan Li, Roshan Ara Ghoorun, Department of Colorectal and Anal Surgery, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
Hui-Chuan Yu, Xiao-Lin Wang, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
Shao-Yong Peng, Wei-Da Lin, Yan-Xin Luo, Department of Colorectal Surgery, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
Author contributions: Luo YX, Yu HC, and Ren DL designed the research; Peng SY, Lin WD, Li J, Ghoorun RA, and Wang XL performed the research; Yu HC and Li J contributed analytic tools; Ren DL and Li J analyzed the data; Ren DL and Li J wrote the paper.
Supported by National Basic Research Program of China (973 Program), No. 2015CB554001; National Natural Science Foundation of China, No. 81472257 and No. 81502022; Natural Science Fund for Distinguished Young Scholars of Guangdong Province, No. 2016A030306002; Tip-top Scientific and Technical Innovative Youth Talents of Guangdong Special Support Program, No. 2015TQ01R454; Natural Science Foundation of Guangdong Province, No. 2016A030310222 and No. 2018A0303130303; Science and Technology Program of Guangzhou, No. 201506010099 and No. 2014Y2-00160; Science and Technology Program of Guangdong Province, No. 2014A020215011; Fundamental Research Funds for the Central Universities (Sun Yat-sen University), No. 2015ykzd10 and No. 16ykpy35; Program of Introducing Talents of Discipline to Universities; and National Key Clinical Discipline.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of The Sixth Affiliated Hospital, Sun Yat-sen University.
Informed consent statement: Patients were not required to give informed consent for the study because the analysis used anonymous clinical data obtained via written consent after each patient agreed to treatment.
Conflict-of-interest statement: We have no financial relationships to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Yan-Xin Luo, MD, PhD, Associate Professor, Chief Doctor, Surgical Oncologist, Department of Colorectal Surgery, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Road, Tianhe District, Guangzhou 510655, Guangdong Province, China. luoyx25@mail.sysu.edu.cn
Telephone: +86-13826190263 Fax: +86-20-38254221
Received: October 17, 2018
Peer-review started: October 17, 2018
First decision: November 22, 2018
Revised: December 16, 2018
Accepted: December 19, 2018
Article in press: December 19, 2018
Published online: January 7, 2019
Abstract
BACKGROUND

In recent decades, neoadjuvant therapy (NT) has been the standardized treatment for locally advanced rectal cancer (LARC). Approximately 8%-35% of patients with LARC who received NT were reported to have achieved a complete pathological response (pCR). If the pathological response (PR) can be accurately predicted, these patients may not need surgery. In addition, no response after NT implies that the tumor is destructive, resistant to both chemotherapy and radiotherapy, and prone to having a high metastatic potential. Therefore, developing accurate models to predict PR has great clinical significance and can help achieve individualized treatment in LARC patients.

AIM

To establish nomograms for predicting PR to different NT regimens based on pretreatment parameters for patients with LARC.

METHODS

Rectal cancer patients were identified from the database of The Sixth Affiliated Hospital, Sun Yat-sen University from January 2012 to December 2016. Logistic regression and nomograms were developed to predict the probability of pCR and good downstaging to ypT0-2N0M0 (ypTNM 0-I), respectively, based on pretreatment parameters for all LARC patients. Nomograms were also developed for three NT regimens (capecitabine/deGramont-RT, mFOLFOX6, and mFOLFOX6-RT) to predict pCR probability.

RESULTS

Four hundred and three patients were included in this study; 72 (17.9%) had pCR at the final pathology report, and 177 (43.9%) achieved good downstaging to ypT0-2N0M0 (ypTNM 0-I). The nomogram for predicting pCR probability showed that NT regimens, tumor differentiation, mesorectal fascia (MRF) status, and tumor length significantly influenced pCR probability. When predicting the probability of good downstaging, tumor differentiation, MRF status, and clinical T stage were the significant factors. Nomograms were developed based on NT regimens. For the capecitabine/de Gramont-RT group, the multivariate analysis showed that the neutrophil-lymphocyte ratio (NLR) was the only significant factor, thus we could not develop a nomogram for this regimen. For the mFOLFOX6-RT group, the analysis showed that the significant factors were tumor length and MRF status; and for the mFOLFOX6 group, the significant factors were tumor length and tumor differentiation.

CONCLUSION

We established accurate nomograms for predicting the PR to preoperative NT regimens based on pretreatment parameters for LARC patients.

Keywords: Neoadjuvant therapy, Locally advanced rectal cancer, Nomogram, Prediction of pathological response, Complete pathological response, Good downstaging

Core tip: In this study, we established accurate nomograms for predicting the pathological response (PR) to preoperative neoadjuvant therapy (NT) regimens based on pretreatment parameters for locally advanced rectal cancer (LARC) patients. Logistic regression and nomograms were developed to predict the probability of complete pathological response and good downstaging, respectively, for all patients and for subgroups based on NT regimens. In conclusion, nomograms have been established for predicting the PR to different NT regimens for LARC patients; and these nomograms can be used to facilitate developing individualized treatments.