Clinical characteristics and tumor markers in ischemic stroke patients with active cancer
Cancer-associated ischemic stroke (CAS) refers to a hypercoagulation disorder related to malignant tumors, especially adenocarcinoma. Carbohydrate antigen (CA) 125 is a mucinous serum marker that might reflect hypercoagulation status, but the association between CA 125 and CAS is unclear across vari...
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| Veröffentlicht in: | Internal and emergency medicine 2022-04, Vol.17 (3), p.735-741 |
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| creator | Nezu, Tomohisa Hosomi, Naohisa Naito, Hiroyuki Aoki, Shiro Torii, Tsuyoshi Kurashige, Takashi Sugiura, Tomohito Kuzume, Daisuke Morimoto, Yuko Yoshida, Takeshi Yagita, Yoshiki Oyama, Naoki Shiga, Yuji Kinoshita, Naoto Kamimura, Teppei Ueno, Hiroki Ohshita, Tomohiko Maruyama, Hirofumi |
| description | Cancer-associated ischemic stroke (CAS) refers to a hypercoagulation disorder related to malignant tumors, especially adenocarcinoma. Carbohydrate antigen (CA) 125 is a mucinous serum marker that might reflect hypercoagulation status, but the association between CA 125 and CAS is unclear across various types of cancer. The aim of this study was to investigate the associations among tumor markers, coagulation markers, and clinical factors in acute ischemic stroke (AIS) patients with active cancer. Consecutive AIS patients with active cancer (a diagnosis or ongoing active therapy for cancer within 6 months) were prospectively enrolled at four hospitals. D-dimer, C-reactive protein (CRP), carcinoembryonic antigen (CEA), CA19-9, and CA 125 levels were measured. Of 120 AIS patients with active cancer, 47 were diagnosed with CAS. CA 125 had the strongest correlations with D-dimer and CRP (
ρ
= 0.543,
p
|
| doi_str_mv | 10.1007/s11739-021-02862-1 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2578779730</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2652410938</sourcerecordid><originalsourceid>FETCH-LOGICAL-c375t-c13b84386ccfa94acf2d843b3931c44ad5687e89d5b81b94bbff5f936bea0b753</originalsourceid><addsrcrecordid>eNp9kLlOBSEUhonRuFx9AQtDYmMzyjpAaW7cEhMbLawIMIwXneUKjMa3F70uiYUFAcJ3_nP4ANjH6BgjJE4SxoKqChFclqxJhdfANlYCVYrW9Xo5SyIrxJjYAjspPSLEeY3FJtiijKtaErYN7uddGIIzHXQLE43LPoaUg0vQDA3MUz9G2Jv45GOCYYAhuYXvg4Mpx_HJw6XJwQ85wdeQF7CUhxcPnRmcj7tgozVd8ntf-wzcnZ_dzi-r65uLq_npdeWo4LlymFrJqKyda41ixrWkKXdLFcWOMdPwWgovVcOtxFYxa9uWt-WD1htkBaczcLTKXcbxefIp675M6bvODH6ckiZcSCGUoKigh3_Qx3GKQ5lOk5oThpGislBkRbk4phR9q5cxFAdvGiP9IV6vxOsiXn-K17gUHXxFT7b3zU_Jt-kC0BWQytPw4ONv739i3wF9Yo7b</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2652410938</pqid></control><display><type>article</type><title>Clinical characteristics and tumor markers in ischemic stroke patients with active cancer</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Nezu, Tomohisa ; Hosomi, Naohisa ; Naito, Hiroyuki ; Aoki, Shiro ; Torii, Tsuyoshi ; Kurashige, Takashi ; Sugiura, Tomohito ; Kuzume, Daisuke ; Morimoto, Yuko ; Yoshida, Takeshi ; Yagita, Yoshiki ; Oyama, Naoki ; Shiga, Yuji ; Kinoshita, Naoto ; Kamimura, Teppei ; Ueno, Hiroki ; Ohshita, Tomohiko ; Maruyama, Hirofumi</creator><creatorcontrib>Nezu, Tomohisa ; Hosomi, Naohisa ; Naito, Hiroyuki ; Aoki, Shiro ; Torii, Tsuyoshi ; Kurashige, Takashi ; Sugiura, Tomohito ; Kuzume, Daisuke ; Morimoto, Yuko ; Yoshida, Takeshi ; Yagita, Yoshiki ; Oyama, Naoki ; Shiga, Yuji ; Kinoshita, Naoto ; Kamimura, Teppei ; Ueno, Hiroki ; Ohshita, Tomohiko ; Maruyama, Hirofumi</creatorcontrib><description>Cancer-associated ischemic stroke (CAS) refers to a hypercoagulation disorder related to malignant tumors, especially adenocarcinoma. Carbohydrate antigen (CA) 125 is a mucinous serum marker that might reflect hypercoagulation status, but the association between CA 125 and CAS is unclear across various types of cancer. The aim of this study was to investigate the associations among tumor markers, coagulation markers, and clinical factors in acute ischemic stroke (AIS) patients with active cancer. Consecutive AIS patients with active cancer (a diagnosis or ongoing active therapy for cancer within 6 months) were prospectively enrolled at four hospitals. D-dimer, C-reactive protein (CRP), carcinoembryonic antigen (CEA), CA19-9, and CA 125 levels were measured. Of 120 AIS patients with active cancer, 47 were diagnosed with CAS. CA 125 had the strongest correlations with D-dimer and CRP (
ρ
= 0.543,
p
< 0.001 and
ρ
= 0.452,
p
< 0.001, respectively). The areas under the receiver-operating characteristic curves for the diagnosis of CAS were 0.812 (95% CI 0.718–0.878) for CA 125, 0.714 (95% CI 0.602–0.801) for CEA, and 0.663 (95% CI 0.552–0.759) for CA 19-9. Multivariable analysis revealed that CA 125 levels in the highest quartile (OR 2.91, 95% CI 1.68–5.53), multiple lesions in multiple vascular territories observed on diffusion-weighted imaging, the absence of dyslipidemia, and the absence of atrial fibrillation were independently associated with CAS. Increased CA 125 levels, which indicate hypercoagulability, were useful for diagnosing CAS in AIS patients with active cancer.</description><identifier>ISSN: 1828-0447</identifier><identifier>EISSN: 1970-9366</identifier><identifier>DOI: 10.1007/s11739-021-02862-1</identifier><identifier>PMID: 34596824</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Adenocarcinoma ; Antigens ; Biomarkers ; Biomarkers, Tumor ; C-Reactive Protein ; CA-125 Antigen ; CA-19-9 Antigen ; Cancer ; Carcinoembryonic Antigen ; Diagnosis ; Dyslipidemia ; Fibrillation ; Humans ; Im - Original ; Internal Medicine ; Ischemia ; Ischemic Stroke ; Medicine ; Medicine & Public Health ; Neoplasms - complications ; Patients ; Stroke ; Stroke - complications ; Thrombophilia - complications ; Tumor markers ; Tumors</subject><ispartof>Internal and emergency medicine, 2022-04, Vol.17 (3), p.735-741</ispartof><rights>Società Italiana di Medicina Interna (SIMI) 2021</rights><rights>2021. Società Italiana di Medicina Interna (SIMI).</rights><rights>Società Italiana di Medicina Interna (SIMI) 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-c13b84386ccfa94acf2d843b3931c44ad5687e89d5b81b94bbff5f936bea0b753</citedby><cites>FETCH-LOGICAL-c375t-c13b84386ccfa94acf2d843b3931c44ad5687e89d5b81b94bbff5f936bea0b753</cites><orcidid>0000-0003-4877-2336</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11739-021-02862-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11739-021-02862-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34596824$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nezu, Tomohisa</creatorcontrib><creatorcontrib>Hosomi, Naohisa</creatorcontrib><creatorcontrib>Naito, Hiroyuki</creatorcontrib><creatorcontrib>Aoki, Shiro</creatorcontrib><creatorcontrib>Torii, Tsuyoshi</creatorcontrib><creatorcontrib>Kurashige, Takashi</creatorcontrib><creatorcontrib>Sugiura, Tomohito</creatorcontrib><creatorcontrib>Kuzume, Daisuke</creatorcontrib><creatorcontrib>Morimoto, Yuko</creatorcontrib><creatorcontrib>Yoshida, Takeshi</creatorcontrib><creatorcontrib>Yagita, Yoshiki</creatorcontrib><creatorcontrib>Oyama, Naoki</creatorcontrib><creatorcontrib>Shiga, Yuji</creatorcontrib><creatorcontrib>Kinoshita, Naoto</creatorcontrib><creatorcontrib>Kamimura, Teppei</creatorcontrib><creatorcontrib>Ueno, Hiroki</creatorcontrib><creatorcontrib>Ohshita, Tomohiko</creatorcontrib><creatorcontrib>Maruyama, Hirofumi</creatorcontrib><title>Clinical characteristics and tumor markers in ischemic stroke patients with active cancer</title><title>Internal and emergency medicine</title><addtitle>Intern Emerg Med</addtitle><addtitle>Intern Emerg Med</addtitle><description>Cancer-associated ischemic stroke (CAS) refers to a hypercoagulation disorder related to malignant tumors, especially adenocarcinoma. Carbohydrate antigen (CA) 125 is a mucinous serum marker that might reflect hypercoagulation status, but the association between CA 125 and CAS is unclear across various types of cancer. The aim of this study was to investigate the associations among tumor markers, coagulation markers, and clinical factors in acute ischemic stroke (AIS) patients with active cancer. Consecutive AIS patients with active cancer (a diagnosis or ongoing active therapy for cancer within 6 months) were prospectively enrolled at four hospitals. D-dimer, C-reactive protein (CRP), carcinoembryonic antigen (CEA), CA19-9, and CA 125 levels were measured. Of 120 AIS patients with active cancer, 47 were diagnosed with CAS. CA 125 had the strongest correlations with D-dimer and CRP (
ρ
= 0.543,
p
< 0.001 and
ρ
= 0.452,
p
< 0.001, respectively). The areas under the receiver-operating characteristic curves for the diagnosis of CAS were 0.812 (95% CI 0.718–0.878) for CA 125, 0.714 (95% CI 0.602–0.801) for CEA, and 0.663 (95% CI 0.552–0.759) for CA 19-9. Multivariable analysis revealed that CA 125 levels in the highest quartile (OR 2.91, 95% CI 1.68–5.53), multiple lesions in multiple vascular territories observed on diffusion-weighted imaging, the absence of dyslipidemia, and the absence of atrial fibrillation were independently associated with CAS. Increased CA 125 levels, which indicate hypercoagulability, were useful for diagnosing CAS in AIS patients with active cancer.</description><subject>Adenocarcinoma</subject><subject>Antigens</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor</subject><subject>C-Reactive Protein</subject><subject>CA-125 Antigen</subject><subject>CA-19-9 Antigen</subject><subject>Cancer</subject><subject>Carcinoembryonic Antigen</subject><subject>Diagnosis</subject><subject>Dyslipidemia</subject><subject>Fibrillation</subject><subject>Humans</subject><subject>Im - Original</subject><subject>Internal Medicine</subject><subject>Ischemia</subject><subject>Ischemic Stroke</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Neoplasms - complications</subject><subject>Patients</subject><subject>Stroke</subject><subject>Stroke - complications</subject><subject>Thrombophilia - complications</subject><subject>Tumor markers</subject><subject>Tumors</subject><issn>1828-0447</issn><issn>1970-9366</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kLlOBSEUhonRuFx9AQtDYmMzyjpAaW7cEhMbLawIMIwXneUKjMa3F70uiYUFAcJ3_nP4ANjH6BgjJE4SxoKqChFclqxJhdfANlYCVYrW9Xo5SyIrxJjYAjspPSLEeY3FJtiijKtaErYN7uddGIIzHXQLE43LPoaUg0vQDA3MUz9G2Jv45GOCYYAhuYXvg4Mpx_HJw6XJwQ85wdeQF7CUhxcPnRmcj7tgozVd8ntf-wzcnZ_dzi-r65uLq_npdeWo4LlymFrJqKyda41ixrWkKXdLFcWOMdPwWgovVcOtxFYxa9uWt-WD1htkBaczcLTKXcbxefIp675M6bvODH6ckiZcSCGUoKigh3_Qx3GKQ5lOk5oThpGislBkRbk4phR9q5cxFAdvGiP9IV6vxOsiXn-K17gUHXxFT7b3zU_Jt-kC0BWQytPw4ONv739i3wF9Yo7b</recordid><startdate>20220401</startdate><enddate>20220401</enddate><creator>Nezu, Tomohisa</creator><creator>Hosomi, Naohisa</creator><creator>Naito, Hiroyuki</creator><creator>Aoki, Shiro</creator><creator>Torii, Tsuyoshi</creator><creator>Kurashige, Takashi</creator><creator>Sugiura, Tomohito</creator><creator>Kuzume, Daisuke</creator><creator>Morimoto, Yuko</creator><creator>Yoshida, Takeshi</creator><creator>Yagita, Yoshiki</creator><creator>Oyama, Naoki</creator><creator>Shiga, Yuji</creator><creator>Kinoshita, Naoto</creator><creator>Kamimura, Teppei</creator><creator>Ueno, Hiroki</creator><creator>Ohshita, Tomohiko</creator><creator>Maruyama, Hirofumi</creator><general>Springer International Publishing</general><general>Springer Nature B.V</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>3V.</scope><scope>7RV</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-4877-2336</orcidid></search><sort><creationdate>20220401</creationdate><title>Clinical characteristics and tumor markers in ischemic stroke patients with active cancer</title><author>Nezu, Tomohisa ; Hosomi, Naohisa ; Naito, Hiroyuki ; Aoki, Shiro ; Torii, Tsuyoshi ; Kurashige, Takashi ; Sugiura, Tomohito ; Kuzume, Daisuke ; Morimoto, Yuko ; Yoshida, Takeshi ; Yagita, Yoshiki ; Oyama, Naoki ; Shiga, Yuji ; Kinoshita, Naoto ; Kamimura, Teppei ; Ueno, Hiroki ; Ohshita, Tomohiko ; Maruyama, Hirofumi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-c13b84386ccfa94acf2d843b3931c44ad5687e89d5b81b94bbff5f936bea0b753</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Adenocarcinoma</topic><topic>Antigens</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor</topic><topic>C-Reactive Protein</topic><topic>CA-125 Antigen</topic><topic>CA-19-9 Antigen</topic><topic>Cancer</topic><topic>Carcinoembryonic Antigen</topic><topic>Diagnosis</topic><topic>Dyslipidemia</topic><topic>Fibrillation</topic><topic>Humans</topic><topic>Im - Original</topic><topic>Internal Medicine</topic><topic>Ischemia</topic><topic>Ischemic Stroke</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Neoplasms - complications</topic><topic>Patients</topic><topic>Stroke</topic><topic>Stroke - complications</topic><topic>Thrombophilia - complications</topic><topic>Tumor markers</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nezu, Tomohisa</creatorcontrib><creatorcontrib>Hosomi, Naohisa</creatorcontrib><creatorcontrib>Naito, Hiroyuki</creatorcontrib><creatorcontrib>Aoki, Shiro</creatorcontrib><creatorcontrib>Torii, Tsuyoshi</creatorcontrib><creatorcontrib>Kurashige, Takashi</creatorcontrib><creatorcontrib>Sugiura, Tomohito</creatorcontrib><creatorcontrib>Kuzume, Daisuke</creatorcontrib><creatorcontrib>Morimoto, Yuko</creatorcontrib><creatorcontrib>Yoshida, Takeshi</creatorcontrib><creatorcontrib>Yagita, Yoshiki</creatorcontrib><creatorcontrib>Oyama, Naoki</creatorcontrib><creatorcontrib>Shiga, Yuji</creatorcontrib><creatorcontrib>Kinoshita, Naoto</creatorcontrib><creatorcontrib>Kamimura, Teppei</creatorcontrib><creatorcontrib>Ueno, Hiroki</creatorcontrib><creatorcontrib>Ohshita, Tomohiko</creatorcontrib><creatorcontrib>Maruyama, Hirofumi</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 Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Internal and emergency medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nezu, Tomohisa</au><au>Hosomi, Naohisa</au><au>Naito, Hiroyuki</au><au>Aoki, Shiro</au><au>Torii, Tsuyoshi</au><au>Kurashige, Takashi</au><au>Sugiura, Tomohito</au><au>Kuzume, Daisuke</au><au>Morimoto, Yuko</au><au>Yoshida, Takeshi</au><au>Yagita, Yoshiki</au><au>Oyama, Naoki</au><au>Shiga, Yuji</au><au>Kinoshita, Naoto</au><au>Kamimura, Teppei</au><au>Ueno, Hiroki</au><au>Ohshita, Tomohiko</au><au>Maruyama, Hirofumi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinical characteristics and tumor markers in ischemic stroke patients with active cancer</atitle><jtitle>Internal and emergency medicine</jtitle><stitle>Intern Emerg Med</stitle><addtitle>Intern Emerg Med</addtitle><date>2022-04-01</date><risdate>2022</risdate><volume>17</volume><issue>3</issue><spage>735</spage><epage>741</epage><pages>735-741</pages><issn>1828-0447</issn><eissn>1970-9366</eissn><abstract>Cancer-associated ischemic stroke (CAS) refers to a hypercoagulation disorder related to malignant tumors, especially adenocarcinoma. Carbohydrate antigen (CA) 125 is a mucinous serum marker that might reflect hypercoagulation status, but the association between CA 125 and CAS is unclear across various types of cancer. The aim of this study was to investigate the associations among tumor markers, coagulation markers, and clinical factors in acute ischemic stroke (AIS) patients with active cancer. Consecutive AIS patients with active cancer (a diagnosis or ongoing active therapy for cancer within 6 months) were prospectively enrolled at four hospitals. D-dimer, C-reactive protein (CRP), carcinoembryonic antigen (CEA), CA19-9, and CA 125 levels were measured. Of 120 AIS patients with active cancer, 47 were diagnosed with CAS. CA 125 had the strongest correlations with D-dimer and CRP (
ρ
= 0.543,
p
< 0.001 and
ρ
= 0.452,
p
< 0.001, respectively). The areas under the receiver-operating characteristic curves for the diagnosis of CAS were 0.812 (95% CI 0.718–0.878) for CA 125, 0.714 (95% CI 0.602–0.801) for CEA, and 0.663 (95% CI 0.552–0.759) for CA 19-9. Multivariable analysis revealed that CA 125 levels in the highest quartile (OR 2.91, 95% CI 1.68–5.53), multiple lesions in multiple vascular territories observed on diffusion-weighted imaging, the absence of dyslipidemia, and the absence of atrial fibrillation were independently associated with CAS. Increased CA 125 levels, which indicate hypercoagulability, were useful for diagnosing CAS in AIS patients with active cancer.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>34596824</pmid><doi>10.1007/s11739-021-02862-1</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0003-4877-2336</orcidid></addata></record> |
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| ispartof | Internal and emergency medicine, 2022-04, Vol.17 (3), p.735-741 |
| issn | 1828-0447 1970-9366 |
| language | eng |
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| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Adenocarcinoma Antigens Biomarkers Biomarkers, Tumor C-Reactive Protein CA-125 Antigen CA-19-9 Antigen Cancer Carcinoembryonic Antigen Diagnosis Dyslipidemia Fibrillation Humans Im - Original Internal Medicine Ischemia Ischemic Stroke Medicine Medicine & Public Health Neoplasms - complications Patients Stroke Stroke - complications Thrombophilia - complications Tumor markers Tumors |
| title | Clinical characteristics and tumor markers in ischemic stroke patients with active cancer |
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