A novel LARCassigner3 classification predicts outcomes in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy: a retrospective training and validation analysis

Jing Zhang,1,2,* Lijun Shen,1,2,* Yun Deng,1,2 Xiaoyang Sun,1,2 Yaqi Wang,1,2 Ye Yao,1,2 Hui Zhang,1,2 Wei Zou,1,2 Zhiyuan Zhang,1,2 Juefeng Wan,1,2 Lifeng Yang,1,2 Ji Zhu,1,2 Zhen Zhang1,21Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, People’s...

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Main Authors: Zhang J, Shen L, Deng Y, Sun X, Wang Y, Yao Y, Zhang H, Zou W, Zhang Z, Wan J, Yang L, Zhu J
Format: Article
Language:English
Published: Dove Medical Press 2019-05-01
Series:Cancer Management and Research
Subjects:
Online Access:https://www.dovepress.com/a-novel-larcassigner3-classification-predicts-outcomes-in-patients-wit-peer-reviewed-article-CMAR
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spelling doaj-b58b06e1614741b1b5c95ba17b69c28f2020-11-24T22:19:30ZengDove Medical PressCancer Management and Research1179-13222019-05-01Volume 114153417045666A novel LARCassigner3 classification predicts outcomes in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy: a retrospective training and validation analysisZhang JShen LDeng YSun XWang YYao YZhang HZou WZhang ZWan JYang LZhu JZhang ZJing Zhang,1,2,* Lijun Shen,1,2,* Yun Deng,1,2 Xiaoyang Sun,1,2 Yaqi Wang,1,2 Ye Yao,1,2 Hui Zhang,1,2 Wei Zou,1,2 Zhiyuan Zhang,1,2 Juefeng Wan,1,2 Lifeng Yang,1,2 Ji Zhu,1,2 Zhen Zhang1,21Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workPurpose: To build and validate a predictive model of outcome for patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy.Materials and methods: We developed a LARCassigner3 classifier based on tumor and paired normal tissues of patients treated with neoadjuvant chemoradiation and surgery from January 2007 to December 2012 in Fudan University Shanghai Cancer Center. Excluding 23 pairs of tissues failed in the RNA quality test, rested 197 patients were divided into discovery (n=98) and validation (n=99) cohorts randomly. Median follow-up time was 58 months. We used the Kaplan–Meier method to estimate disease-free survival (DFS), overall survival (OS), local recurrent, and distant metastatic rate We constructed a multivariate Cox model to identify the variables independently associated with progression-free and OS.Results: We identified three classifier genes related to relevant colorectal cancer features (CXCL9, SFRP2, and CD44) that formed the LARCassigner3 classifier assay. In the discovery set, the median DFS was 48.1 months (95% confidence interval (CI) 47.3–49.5) in the low-risk group and 23.4 months (95% CI 22.1–24.8) in the high-risk group (p=0.0134); the median OS was 39.2 months (95% CI 38.4–40.3) in the high-risk group and 19.1 months (95% CI 18.3–20.7) in the low-risk group (p=0.0134); 5-year distant metastasis was 13.9% (95% CI 9.0–21.3) in the low-risk group and 49.8% (95% CI 38.7–60.9) in the high-risk group (p=0.0072). Additionally, the different responses to neoadjuvant chemoradiotherapy and the LARCassigner3 low-risk and high-risk groups was statistically significant (p=0.004) in the discovery cohort. Similar results were obtained in the internal evaluation cohort.Conclusions: Patients with LARCassigner3 low-risk tumors were associated with a good prognosis. The clinical utility of using LARCassigner3 subtyping for the identification of patients for neoadjuvant chemoradiotherapy requires validation in dependent clinical trial cohorts.Keywords: prognostic marker, locally advanced rectal cancer, neoadjuvant chemoradiotherapyhttps://www.dovepress.com/a-novel-larcassigner3-classification-predicts-outcomes-in-patients-wit-peer-reviewed-article-CMARPrognostic markerLocally Advanced Rectal CancerNeoadjuvant chemoradiotherapy
collection DOAJ
language English
format Article
sources DOAJ
author Zhang J
Shen L
Deng Y
Sun X
Wang Y
Yao Y
Zhang H
Zou W
Zhang Z
Wan J
Yang L
Zhu J
Zhang Z
spellingShingle Zhang J
Shen L
Deng Y
Sun X
Wang Y
Yao Y
Zhang H
Zou W
Zhang Z
Wan J
Yang L
Zhu J
Zhang Z
A novel LARCassigner3 classification predicts outcomes in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy: a retrospective training and validation analysis
Cancer Management and Research
Prognostic marker
Locally Advanced Rectal Cancer
Neoadjuvant chemoradiotherapy
author_facet Zhang J
Shen L
Deng Y
Sun X
Wang Y
Yao Y
Zhang H
Zou W
Zhang Z
Wan J
Yang L
Zhu J
Zhang Z
author_sort Zhang J
title A novel LARCassigner3 classification predicts outcomes in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy: a retrospective training and validation analysis
title_short A novel LARCassigner3 classification predicts outcomes in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy: a retrospective training and validation analysis
title_full A novel LARCassigner3 classification predicts outcomes in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy: a retrospective training and validation analysis
title_fullStr A novel LARCassigner3 classification predicts outcomes in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy: a retrospective training and validation analysis
title_full_unstemmed A novel LARCassigner3 classification predicts outcomes in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy: a retrospective training and validation analysis
title_sort novel larcassigner3 classification predicts outcomes in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy: a retrospective training and validation analysis
publisher Dove Medical Press
series Cancer Management and Research
issn 1179-1322
publishDate 2019-05-01
description Jing Zhang,1,2,* Lijun Shen,1,2,* Yun Deng,1,2 Xiaoyang Sun,1,2 Yaqi Wang,1,2 Ye Yao,1,2 Hui Zhang,1,2 Wei Zou,1,2 Zhiyuan Zhang,1,2 Juefeng Wan,1,2 Lifeng Yang,1,2 Ji Zhu,1,2 Zhen Zhang1,21Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workPurpose: To build and validate a predictive model of outcome for patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy.Materials and methods: We developed a LARCassigner3 classifier based on tumor and paired normal tissues of patients treated with neoadjuvant chemoradiation and surgery from January 2007 to December 2012 in Fudan University Shanghai Cancer Center. Excluding 23 pairs of tissues failed in the RNA quality test, rested 197 patients were divided into discovery (n=98) and validation (n=99) cohorts randomly. Median follow-up time was 58 months. We used the Kaplan–Meier method to estimate disease-free survival (DFS), overall survival (OS), local recurrent, and distant metastatic rate We constructed a multivariate Cox model to identify the variables independently associated with progression-free and OS.Results: We identified three classifier genes related to relevant colorectal cancer features (CXCL9, SFRP2, and CD44) that formed the LARCassigner3 classifier assay. In the discovery set, the median DFS was 48.1 months (95% confidence interval (CI) 47.3–49.5) in the low-risk group and 23.4 months (95% CI 22.1–24.8) in the high-risk group (p=0.0134); the median OS was 39.2 months (95% CI 38.4–40.3) in the high-risk group and 19.1 months (95% CI 18.3–20.7) in the low-risk group (p=0.0134); 5-year distant metastasis was 13.9% (95% CI 9.0–21.3) in the low-risk group and 49.8% (95% CI 38.7–60.9) in the high-risk group (p=0.0072). Additionally, the different responses to neoadjuvant chemoradiotherapy and the LARCassigner3 low-risk and high-risk groups was statistically significant (p=0.004) in the discovery cohort. Similar results were obtained in the internal evaluation cohort.Conclusions: Patients with LARCassigner3 low-risk tumors were associated with a good prognosis. The clinical utility of using LARCassigner3 subtyping for the identification of patients for neoadjuvant chemoradiotherapy requires validation in dependent clinical trial cohorts.Keywords: prognostic marker, locally advanced rectal cancer, neoadjuvant chemoradiotherapy
topic Prognostic marker
Locally Advanced Rectal Cancer
Neoadjuvant chemoradiotherapy
url https://www.dovepress.com/a-novel-larcassigner3-classification-predicts-outcomes-in-patients-wit-peer-reviewed-article-CMAR
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