Postoperative circulating tumor cells: An early predictor of extrahepatic metastases in patients with hepatocellular carcinoma undergoing curative surgical resection
Background Postoperative extrahepatic metastases (EHM) contribute to a grim outcome in patients with hepatocellular carcinoma (HCC) who are undergoing curative surgical resection. The current study investigated the clinical value of circulating tumor cells (CTCs) in predicting EHM after curative sur...
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| Veröffentlicht in: | Cancer cytopathology 2020-10, Vol.128 (10), p.733-745 |
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| creator | Sun, Yun‐Fan Wang, Peng‐Xiang Cheng, Jian‐Wen Gong, Zi‐Jun Huang, Ao Zhou, Kai‐Qian Hu, Bo Gao, Ping‐Ting Cao, Ya Qiu, Shuang‐Jian Zhou, Jian Fan, Jia Guo, Wei Yang, Xin‐Rong |
| description | Background
Postoperative extrahepatic metastases (EHM) contribute to a grim outcome in patients with hepatocellular carcinoma (HCC) who are undergoing curative surgical resection. The current study investigated the clinical value of circulating tumor cells (CTCs) in predicting EHM after curative surgery.
Methods
A total of 197 patients with HCC who were undergoing curative surgical resection were assigned to a retrospective training cohort (144 patients) or a prospective validation cohort (53 patients). The CELLSEARCH system was used for the detection of CTCs prior to surgical resection and 1 month thereafter. The cutoff value of CTCs was estimated using receiver operating characteristic analysis. Bonferroni correction was applied for multiple testing in a Cox proportional hazards regression model.
Results
In the training cohort, EHM was found to be associated with a higher postoperative CTC burden compared with no EHM (mean: 4.33 vs 0.52; P < .001). Receiver operating characteristic analysis demonstrated a postoperative CTC count ≥3 as the optimal cutoff value for the prediction of EHM. Patients with a postoperative CTC count ≥3 experienced a higher EHM risk (56.3% vs 5.5%) and a shorter median overall survival (31.25 months vs not reached) (all P |
| doi_str_mv | 10.1002/cncy.22304 |
| format | Article |
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Postoperative extrahepatic metastases (EHM) contribute to a grim outcome in patients with hepatocellular carcinoma (HCC) who are undergoing curative surgical resection. The current study investigated the clinical value of circulating tumor cells (CTCs) in predicting EHM after curative surgery.
Methods
A total of 197 patients with HCC who were undergoing curative surgical resection were assigned to a retrospective training cohort (144 patients) or a prospective validation cohort (53 patients). The CELLSEARCH system was used for the detection of CTCs prior to surgical resection and 1 month thereafter. The cutoff value of CTCs was estimated using receiver operating characteristic analysis. Bonferroni correction was applied for multiple testing in a Cox proportional hazards regression model.
Results
In the training cohort, EHM was found to be associated with a higher postoperative CTC burden compared with no EHM (mean: 4.33 vs 0.52; P < .001). Receiver operating characteristic analysis demonstrated a postoperative CTC count ≥3 as the optimal cutoff value for the prediction of EHM. Patients with a postoperative CTC count ≥3 experienced a higher EHM risk (56.3% vs 5.5%) and a shorter median overall survival (31.25 months vs not reached) (all P < .001). The prognostic significance of a postoperative CTC count ≥3 also applied to patient subgroups with a low EHM risk, such as those with an α‐fetoprotein level ≤400 ng/mL, absence of vascular invasion, well differentiation, and early tumor stage, and its predictive value was retained in patients with a continuous normal α‐fetoprotein level during postoperative follow‐up (all P < .05). The results were confirmed in the validation cohort.
Conclusions
A postoperative CTC count ≥3 appears to be a surrogate marker for the prediction of EHM after curative surgical resection of HCC. More careful surveillance should be recommended to patients with a high CTC load to ensure the greater possibility of early interventions for postoperative EHM.
A postoperative circulating tumor cell (CTC) count ≥3 is a surrogate marker for the prediction of extrahepatic metastases after curative surgical resection of hepatocellular carcinoma. A more careful surveillance of metastatic spread should be recommended to patients with a high CTC load after hepatectomy.</description><identifier>ISSN: 1934-662X</identifier><identifier>EISSN: 1934-6638</identifier><identifier>DOI: 10.1002/cncy.22304</identifier><identifier>PMID: 32501632</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Abdominal Neoplasms - blood ; Abdominal Neoplasms - secondary ; Bone Neoplasms - blood ; Bone Neoplasms - secondary ; Carcinoma, Hepatocellular - pathology ; Carcinoma, Hepatocellular - surgery ; circulating tumor cells (CTCs) ; early predictor ; extrahepatic metastases ; Female ; Follow-Up Studies ; Hepatectomy - adverse effects ; hepatocellular carcinoma (HCC) ; Humans ; Liver cancer ; Liver Neoplasms - pathology ; Liver Neoplasms - surgery ; Lung Neoplasms - blood ; Lung Neoplasms - secondary ; Male ; Metastasis ; Middle Aged ; Neoplastic Cells, Circulating - pathology ; postoperative ; Postoperative Complications - etiology ; Postoperative Complications - pathology ; Prognosis ; Prospective Studies ; Retrospective Studies ; Survival Rate</subject><ispartof>Cancer cytopathology, 2020-10, Vol.128 (10), p.733-745</ispartof><rights>2020 American Cancer Society</rights><rights>2020 American Cancer Society.</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3934-84e1acce913c546b73761a1512ce67b50d605d7e1110709b62f9dcb2e9e4e303</citedby><cites>FETCH-LOGICAL-c3934-84e1acce913c546b73761a1512ce67b50d605d7e1110709b62f9dcb2e9e4e303</cites><orcidid>0000-0002-2716-9338</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fcncy.22304$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fcncy.22304$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,1427,27901,27902,45550,45551,46384,46808</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32501632$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sun, Yun‐Fan</creatorcontrib><creatorcontrib>Wang, Peng‐Xiang</creatorcontrib><creatorcontrib>Cheng, Jian‐Wen</creatorcontrib><creatorcontrib>Gong, Zi‐Jun</creatorcontrib><creatorcontrib>Huang, Ao</creatorcontrib><creatorcontrib>Zhou, Kai‐Qian</creatorcontrib><creatorcontrib>Hu, Bo</creatorcontrib><creatorcontrib>Gao, Ping‐Ting</creatorcontrib><creatorcontrib>Cao, Ya</creatorcontrib><creatorcontrib>Qiu, Shuang‐Jian</creatorcontrib><creatorcontrib>Zhou, Jian</creatorcontrib><creatorcontrib>Fan, Jia</creatorcontrib><creatorcontrib>Guo, Wei</creatorcontrib><creatorcontrib>Yang, Xin‐Rong</creatorcontrib><title>Postoperative circulating tumor cells: An early predictor of extrahepatic metastases in patients with hepatocellular carcinoma undergoing curative surgical resection</title><title>Cancer cytopathology</title><addtitle>Cancer Cytopathol</addtitle><description>Background
Postoperative extrahepatic metastases (EHM) contribute to a grim outcome in patients with hepatocellular carcinoma (HCC) who are undergoing curative surgical resection. The current study investigated the clinical value of circulating tumor cells (CTCs) in predicting EHM after curative surgery.
Methods
A total of 197 patients with HCC who were undergoing curative surgical resection were assigned to a retrospective training cohort (144 patients) or a prospective validation cohort (53 patients). The CELLSEARCH system was used for the detection of CTCs prior to surgical resection and 1 month thereafter. The cutoff value of CTCs was estimated using receiver operating characteristic analysis. Bonferroni correction was applied for multiple testing in a Cox proportional hazards regression model.
Results
In the training cohort, EHM was found to be associated with a higher postoperative CTC burden compared with no EHM (mean: 4.33 vs 0.52; P < .001). Receiver operating characteristic analysis demonstrated a postoperative CTC count ≥3 as the optimal cutoff value for the prediction of EHM. Patients with a postoperative CTC count ≥3 experienced a higher EHM risk (56.3% vs 5.5%) and a shorter median overall survival (31.25 months vs not reached) (all P < .001). The prognostic significance of a postoperative CTC count ≥3 also applied to patient subgroups with a low EHM risk, such as those with an α‐fetoprotein level ≤400 ng/mL, absence of vascular invasion, well differentiation, and early tumor stage, and its predictive value was retained in patients with a continuous normal α‐fetoprotein level during postoperative follow‐up (all P < .05). The results were confirmed in the validation cohort.
Conclusions
A postoperative CTC count ≥3 appears to be a surrogate marker for the prediction of EHM after curative surgical resection of HCC. More careful surveillance should be recommended to patients with a high CTC load to ensure the greater possibility of early interventions for postoperative EHM.
A postoperative circulating tumor cell (CTC) count ≥3 is a surrogate marker for the prediction of extrahepatic metastases after curative surgical resection of hepatocellular carcinoma. A more careful surveillance of metastatic spread should be recommended to patients with a high CTC load after hepatectomy.</description><subject>Abdominal Neoplasms - blood</subject><subject>Abdominal Neoplasms - secondary</subject><subject>Bone Neoplasms - blood</subject><subject>Bone Neoplasms - secondary</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Carcinoma, Hepatocellular - surgery</subject><subject>circulating tumor cells (CTCs)</subject><subject>early predictor</subject><subject>extrahepatic metastases</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Hepatectomy - adverse effects</subject><subject>hepatocellular carcinoma (HCC)</subject><subject>Humans</subject><subject>Liver cancer</subject><subject>Liver Neoplasms - pathology</subject><subject>Liver Neoplasms - surgery</subject><subject>Lung Neoplasms - blood</subject><subject>Lung Neoplasms - secondary</subject><subject>Male</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Neoplastic Cells, Circulating - pathology</subject><subject>postoperative</subject><subject>Postoperative Complications - etiology</subject><subject>Postoperative Complications - pathology</subject><subject>Prognosis</subject><subject>Prospective Studies</subject><subject>Retrospective Studies</subject><subject>Survival Rate</subject><issn>1934-662X</issn><issn>1934-6638</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kclKBDEQhoMo7hcfQALehNEsvXqTwQ1EPXjQU5Ourhkj3UmbpNV5IN_TtDN6FAIpKl--SvgJOeDshDMmTsHA4kQIyZI1ss1LmUyyTBbrf7V42iI73r8yxotc8E2yJUXKeCbFNvl6sD7YHp0K-h0paAdDG2szp2HorKOAbevP6LmhqFy7oL3DRkOIJ3ZG8TM49YJ9vAC0w6B8XOipNnTsoQmefujwQn8YO7qiPUqVA21sp-hgGnRzO86DYfUIP7i5BtVShx4haGv2yMZMtR73V_sueby8eJxeT27vr26m57cTkONXiwS5AsCSS0iTrM5lnnHFUy4As7xOWZOxtMmRc85yVtaZmJUN1AJLTFAyuUuOltre2bcBfahe7eBMnFiJJMkLyVhRROp4SYGz3jucVb3TnXKLirNqDKQaA6l-Aonw4Uo51B02f-hvAhHgS-BDt7j4R1VN76bPS-k3roKazw</recordid><startdate>202010</startdate><enddate>202010</enddate><creator>Sun, Yun‐Fan</creator><creator>Wang, Peng‐Xiang</creator><creator>Cheng, Jian‐Wen</creator><creator>Gong, Zi‐Jun</creator><creator>Huang, Ao</creator><creator>Zhou, Kai‐Qian</creator><creator>Hu, Bo</creator><creator>Gao, Ping‐Ting</creator><creator>Cao, Ya</creator><creator>Qiu, Shuang‐Jian</creator><creator>Zhou, Jian</creator><creator>Fan, Jia</creator><creator>Guo, Wei</creator><creator>Yang, Xin‐Rong</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><orcidid>https://orcid.org/0000-0002-2716-9338</orcidid></search><sort><creationdate>202010</creationdate><title>Postoperative circulating tumor cells: An early predictor of extrahepatic metastases in patients with hepatocellular carcinoma undergoing curative surgical resection</title><author>Sun, Yun‐Fan ; Wang, Peng‐Xiang ; Cheng, Jian‐Wen ; Gong, Zi‐Jun ; Huang, Ao ; Zhou, Kai‐Qian ; Hu, Bo ; Gao, Ping‐Ting ; Cao, Ya ; Qiu, Shuang‐Jian ; Zhou, Jian ; Fan, Jia ; Guo, Wei ; Yang, Xin‐Rong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3934-84e1acce913c546b73761a1512ce67b50d605d7e1110709b62f9dcb2e9e4e303</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Abdominal Neoplasms - blood</topic><topic>Abdominal Neoplasms - secondary</topic><topic>Bone Neoplasms - blood</topic><topic>Bone Neoplasms - secondary</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Carcinoma, Hepatocellular - surgery</topic><topic>circulating tumor cells (CTCs)</topic><topic>early predictor</topic><topic>extrahepatic metastases</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Hepatectomy - adverse effects</topic><topic>hepatocellular carcinoma (HCC)</topic><topic>Humans</topic><topic>Liver cancer</topic><topic>Liver Neoplasms - pathology</topic><topic>Liver Neoplasms - surgery</topic><topic>Lung Neoplasms - blood</topic><topic>Lung Neoplasms - secondary</topic><topic>Male</topic><topic>Metastasis</topic><topic>Middle Aged</topic><topic>Neoplastic Cells, Circulating - pathology</topic><topic>postoperative</topic><topic>Postoperative Complications - etiology</topic><topic>Postoperative Complications - pathology</topic><topic>Prognosis</topic><topic>Prospective Studies</topic><topic>Retrospective Studies</topic><topic>Survival Rate</topic><toplevel>online_resources</toplevel><creatorcontrib>Sun, Yun‐Fan</creatorcontrib><creatorcontrib>Wang, Peng‐Xiang</creatorcontrib><creatorcontrib>Cheng, Jian‐Wen</creatorcontrib><creatorcontrib>Gong, Zi‐Jun</creatorcontrib><creatorcontrib>Huang, Ao</creatorcontrib><creatorcontrib>Zhou, Kai‐Qian</creatorcontrib><creatorcontrib>Hu, Bo</creatorcontrib><creatorcontrib>Gao, Ping‐Ting</creatorcontrib><creatorcontrib>Cao, Ya</creatorcontrib><creatorcontrib>Qiu, Shuang‐Jian</creatorcontrib><creatorcontrib>Zhou, Jian</creatorcontrib><creatorcontrib>Fan, Jia</creatorcontrib><creatorcontrib>Guo, Wei</creatorcontrib><creatorcontrib>Yang, Xin‐Rong</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><jtitle>Cancer cytopathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sun, Yun‐Fan</au><au>Wang, Peng‐Xiang</au><au>Cheng, Jian‐Wen</au><au>Gong, Zi‐Jun</au><au>Huang, Ao</au><au>Zhou, Kai‐Qian</au><au>Hu, Bo</au><au>Gao, Ping‐Ting</au><au>Cao, Ya</au><au>Qiu, Shuang‐Jian</au><au>Zhou, Jian</au><au>Fan, Jia</au><au>Guo, Wei</au><au>Yang, Xin‐Rong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Postoperative circulating tumor cells: An early predictor of extrahepatic metastases in patients with hepatocellular carcinoma undergoing curative surgical resection</atitle><jtitle>Cancer cytopathology</jtitle><addtitle>Cancer Cytopathol</addtitle><date>2020-10</date><risdate>2020</risdate><volume>128</volume><issue>10</issue><spage>733</spage><epage>745</epage><pages>733-745</pages><issn>1934-662X</issn><eissn>1934-6638</eissn><abstract>Background
Postoperative extrahepatic metastases (EHM) contribute to a grim outcome in patients with hepatocellular carcinoma (HCC) who are undergoing curative surgical resection. The current study investigated the clinical value of circulating tumor cells (CTCs) in predicting EHM after curative surgery.
Methods
A total of 197 patients with HCC who were undergoing curative surgical resection were assigned to a retrospective training cohort (144 patients) or a prospective validation cohort (53 patients). The CELLSEARCH system was used for the detection of CTCs prior to surgical resection and 1 month thereafter. The cutoff value of CTCs was estimated using receiver operating characteristic analysis. Bonferroni correction was applied for multiple testing in a Cox proportional hazards regression model.
Results
In the training cohort, EHM was found to be associated with a higher postoperative CTC burden compared with no EHM (mean: 4.33 vs 0.52; P < .001). Receiver operating characteristic analysis demonstrated a postoperative CTC count ≥3 as the optimal cutoff value for the prediction of EHM. Patients with a postoperative CTC count ≥3 experienced a higher EHM risk (56.3% vs 5.5%) and a shorter median overall survival (31.25 months vs not reached) (all P < .001). The prognostic significance of a postoperative CTC count ≥3 also applied to patient subgroups with a low EHM risk, such as those with an α‐fetoprotein level ≤400 ng/mL, absence of vascular invasion, well differentiation, and early tumor stage, and its predictive value was retained in patients with a continuous normal α‐fetoprotein level during postoperative follow‐up (all P < .05). The results were confirmed in the validation cohort.
Conclusions
A postoperative CTC count ≥3 appears to be a surrogate marker for the prediction of EHM after curative surgical resection of HCC. More careful surveillance should be recommended to patients with a high CTC load to ensure the greater possibility of early interventions for postoperative EHM.
A postoperative circulating tumor cell (CTC) count ≥3 is a surrogate marker for the prediction of extrahepatic metastases after curative surgical resection of hepatocellular carcinoma. A more careful surveillance of metastatic spread should be recommended to patients with a high CTC load after hepatectomy.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>32501632</pmid><doi>10.1002/cncy.22304</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-2716-9338</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Abdominal Neoplasms - blood Abdominal Neoplasms - secondary Bone Neoplasms - blood Bone Neoplasms - secondary Carcinoma, Hepatocellular - pathology Carcinoma, Hepatocellular - surgery circulating tumor cells (CTCs) early predictor extrahepatic metastases Female Follow-Up Studies Hepatectomy - adverse effects hepatocellular carcinoma (HCC) Humans Liver cancer Liver Neoplasms - pathology Liver Neoplasms - surgery Lung Neoplasms - blood Lung Neoplasms - secondary Male Metastasis Middle Aged Neoplastic Cells, Circulating - pathology postoperative Postoperative Complications - etiology Postoperative Complications - pathology Prognosis Prospective Studies Retrospective Studies Survival Rate |
| title | Postoperative circulating tumor cells: An early predictor of extrahepatic metastases in patients with hepatocellular carcinoma undergoing curative surgical resection |
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