Redefine Hyperprogressive Disease During Treatment With Immune-Checkpoint Inhibitors in Patients With Gastrointestinal Cancer

ObjectiveEmerging evidence showed that immune checkpoint inhibitors (ICIs) lead to hyperprogressive disease (HPD) in a small proportion of patients. There is no well-recognized standard for the evaluation of HPD. Comprehensive exploration of HPD definition system in gastrointestinal cancer treated w...

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Autores principales:	Zhenghang Wang, Chang Liu, Yuezong Bai, Xiaochen Zhao, Longgang Cui, Zhi Peng, Xiaotian Zhang, Xicheng Wang, Zhengyi Zhao, Jian Li, Lin Shen
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	hyperprogressive disease gastrointestinal cancer immune checkpoint inhibitors circulating tumor DNA next-generation sequencing Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/dc2063dc3e28419fbe5a61234b8e96fb
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spelling	oai:doaj.org-article:dc2063dc3e28419fbe5a61234b8e96fb2021-11-09T05:23:16ZRedefine Hyperprogressive Disease During Treatment With Immune-Checkpoint Inhibitors in Patients With Gastrointestinal Cancer2234-943X10.3389/fonc.2021.761110https://doaj.org/article/dc2063dc3e28419fbe5a61234b8e96fb2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.761110/fullhttps://doaj.org/toc/2234-943XObjectiveEmerging evidence showed that immune checkpoint inhibitors (ICIs) lead to hyperprogressive disease (HPD) in a small proportion of patients. There is no well-recognized standard for the evaluation of HPD. Comprehensive exploration of HPD definition system in gastrointestinal cancer treated with ICI is lacking to date.MethodsA total of 126 patients with advanced or metastatic gastrointestinal cancer treated with ICI monotherapy were analyzed. Seven definitions of HPD were defined with tumor growth kinetics (TGK) or tumor growth rate (TGR) by including new lesions or not, and with different cutoffs. Incidence and performance of different criteria were compared. Clinicopathologic characteristics and baseline genomic variations associated with HPD were also explored.ResultsTumor growth kinetics ratio of more than two fold that incorporated new lesions into calculation of HPD outperformed other definitions by successfully stratifying 14 patients (11.1%) with both accelerated disease progression (median PFS, 1.62 versus 1.93 months; hazard ratio, 1.85; 95% CI, 0.98 to 3.48; P = 0.059) and worse overall survival (median OS, 3.97 versus 10.23 months; hazard ratio, 2.30; 95% CI, 1.11 to 4.78; P = 0.021). Baseline genomic alterations in circulating tumor DNA, including SMARCA2, MSH6, APC signaling pathway, and Wnt signaling pathway, might be associated with the risk of HPD.ConclusionIncorporating new lesions emerging during the treatment was shown to be reliable for the assessment of TGK. TGK serves as a more convenient way to reflect tumor growth acceleration compared with TGR. Genomic alterations were suggested to be associated with the occurrence of HPD.Zhenghang WangChang LiuYuezong BaiXiaochen ZhaoLonggang CuiZhi PengXiaotian ZhangXicheng WangZhengyi ZhaoJian LiLin ShenFrontiers Media S.A.articlehyperprogressive diseasegastrointestinal cancerimmune checkpoint inhibitorscirculating tumor DNAnext-generation sequencingNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hyperprogressive disease gastrointestinal cancer immune checkpoint inhibitors circulating tumor DNA next-generation sequencing Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	hyperprogressive disease gastrointestinal cancer immune checkpoint inhibitors circulating tumor DNA next-generation sequencing Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Zhenghang Wang Chang Liu Yuezong Bai Xiaochen Zhao Longgang Cui Zhi Peng Xiaotian Zhang Xicheng Wang Zhengyi Zhao Jian Li Lin Shen Redefine Hyperprogressive Disease During Treatment With Immune-Checkpoint Inhibitors in Patients With Gastrointestinal Cancer
description	ObjectiveEmerging evidence showed that immune checkpoint inhibitors (ICIs) lead to hyperprogressive disease (HPD) in a small proportion of patients. There is no well-recognized standard for the evaluation of HPD. Comprehensive exploration of HPD definition system in gastrointestinal cancer treated with ICI is lacking to date.MethodsA total of 126 patients with advanced or metastatic gastrointestinal cancer treated with ICI monotherapy were analyzed. Seven definitions of HPD were defined with tumor growth kinetics (TGK) or tumor growth rate (TGR) by including new lesions or not, and with different cutoffs. Incidence and performance of different criteria were compared. Clinicopathologic characteristics and baseline genomic variations associated with HPD were also explored.ResultsTumor growth kinetics ratio of more than two fold that incorporated new lesions into calculation of HPD outperformed other definitions by successfully stratifying 14 patients (11.1%) with both accelerated disease progression (median PFS, 1.62 versus 1.93 months; hazard ratio, 1.85; 95% CI, 0.98 to 3.48; P = 0.059) and worse overall survival (median OS, 3.97 versus 10.23 months; hazard ratio, 2.30; 95% CI, 1.11 to 4.78; P = 0.021). Baseline genomic alterations in circulating tumor DNA, including SMARCA2, MSH6, APC signaling pathway, and Wnt signaling pathway, might be associated with the risk of HPD.ConclusionIncorporating new lesions emerging during the treatment was shown to be reliable for the assessment of TGK. TGK serves as a more convenient way to reflect tumor growth acceleration compared with TGR. Genomic alterations were suggested to be associated with the occurrence of HPD.
format	article
author	Zhenghang Wang Chang Liu Yuezong Bai Xiaochen Zhao Longgang Cui Zhi Peng Xiaotian Zhang Xicheng Wang Zhengyi Zhao Jian Li Lin Shen
author_facet	Zhenghang Wang Chang Liu Yuezong Bai Xiaochen Zhao Longgang Cui Zhi Peng Xiaotian Zhang Xicheng Wang Zhengyi Zhao Jian Li Lin Shen
author_sort	Zhenghang Wang
title	Redefine Hyperprogressive Disease During Treatment With Immune-Checkpoint Inhibitors in Patients With Gastrointestinal Cancer
title_short	Redefine Hyperprogressive Disease During Treatment With Immune-Checkpoint Inhibitors in Patients With Gastrointestinal Cancer
title_full	Redefine Hyperprogressive Disease During Treatment With Immune-Checkpoint Inhibitors in Patients With Gastrointestinal Cancer
title_fullStr	Redefine Hyperprogressive Disease During Treatment With Immune-Checkpoint Inhibitors in Patients With Gastrointestinal Cancer
title_full_unstemmed	Redefine Hyperprogressive Disease During Treatment With Immune-Checkpoint Inhibitors in Patients With Gastrointestinal Cancer
title_sort	redefine hyperprogressive disease during treatment with immune-checkpoint inhibitors in patients with gastrointestinal cancer
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/dc2063dc3e28419fbe5a61234b8e96fb
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Redefine Hyperprogressive Disease During Treatment With Immune-Checkpoint Inhibitors in Patients With Gastrointestinal Cancer

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