Perioperative circulating tumor DNA enables the identification of patients with poor prognosis in upper tract urothelial carcinoma
Perioperative systemic chemotherapy improves the prognosis of upper tract urothelial carcinoma (UTUC). The first objective of this study was to verify whether perioperative circulating tumor DNA (ctDNA) analysis using a pan‐cancer gene panel and next‐generation sequencing could identify patients wit...
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| Veröffentlicht in: | Cancer science 2022-05, Vol.113 (5), p.1830-1842 |
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| creator | Nakano, Kosuke Koh, Yoko Yamamichi, Gaku Yumiba, Satoru Tomiyama, Eisuke Matsushita, Makoto Hayashi, Yujiro Wang, Cong Ishizuya, Yu Yamamoto, Yoshiyuki Kato, Taigo Hatano, Koji Kawashima, Atsunari Ujike, Takeshi Fujita, Kazutoshi Kiyotani, Kazuma Katayama, Kotoe Yamaguchi, Rui Imoto, Seiya Imamura, Ryoichi Nonomura, Norio Uemura, Motohide |
| description | Perioperative systemic chemotherapy improves the prognosis of upper tract urothelial carcinoma (UTUC). The first objective of this study was to verify whether perioperative circulating tumor DNA (ctDNA) analysis using a pan‐cancer gene panel and next‐generation sequencing could identify patients with poor prognosis who require perioperative chemotherapy. Second, we investigated whether ctDNA is useful for minimal residual disease (MRD) detection and treatment monitoring in UTUC. This study included 50 patients with untreated UTUC, including 43 cases of localized UTUC. We performed targeted ultradeep sequencing of plasma cell‐free DNA (cfDNA) and buffy coat DNA and whole‐exome sequencing of cancer tissues, allowing exclusion of possible false positives. We attempted to stratify the prognosis according to the perioperative ctDNA levels in patients with localized UTUC. In patients with metastatic UTUC, ctDNA was evaluated before, during, and after systemic treatment. In total, 23 (46%) of 50 patients with untreated UTUC were ctDNA positive, and 17 (40%) of 43 patients with localized UTUC were ctDNA positive. Of the detected TP53 mutations, 19% were false positives due to clonal hematopoiesis of indeterminate potential. Among preoperative risk factors, only the preoperative ctDNA fraction>2% was a significant and independent risk factor associated with worse recurrence‐free survival (RFS). Furthermore, the existence of ctDNA early points after the operation was significantly associated with worse RFS, suggesting the presence of MRD. ctDNA also showed a potential as a real‐time marker for systemic therapy in patients with metastatic UTUC. Detection of ctDNA may indicate potential metastasis and guide decisions on perioperative chemotherapy.
In this study, we performed ultradeep sequencing of cell‐free DNA (cfDNA) in the plasma of 50 patients with untreated upper tract urothelial carcinoma (UTUC), of whom 23 (46%) were circulating tumor DNA (ctDNA) positive. Among the preoperative risk factors, only a preoperative ctDNA proportion >2% was found to be a significant and independent risk factor associated with worse recurrence‐free survival (RFS). Furthermore, the presence of ctDNA in the early postoperative period was significantly associated with worse RFS, suggesting the presence of minimal residual disease. |
| doi_str_mv | 10.1111/cas.15334 |
| format | Article |
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In this study, we performed ultradeep sequencing of cell‐free DNA (cfDNA) in the plasma of 50 patients with untreated upper tract urothelial carcinoma (UTUC), of whom 23 (46%) were circulating tumor DNA (ctDNA) positive. Among the preoperative risk factors, only a preoperative ctDNA proportion >2% was found to be a significant and independent risk factor associated with worse recurrence‐free survival (RFS). Furthermore, the presence of ctDNA in the early postoperative period was significantly associated with worse RFS, suggesting the presence of minimal residual disease.</description><identifier>ISSN: 1347-9032</identifier><identifier>EISSN: 1349-7006</identifier><identifier>DOI: 10.1111/cas.15334</identifier><identifier>PMID: 35293110</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Bar codes ; Biomarkers ; Biopsy ; Bladder cancer ; Blood ; Buffy coat ; Cancer therapies ; cell‐free DNA ; Chemotherapy ; circulating tumor DNA ; Deoxyribonucleic acid ; DNA ; DNA sequencing ; Gene expression ; Medical prognosis ; Metastases ; Metastasis ; Minimal residual disease ; Mutation ; next‐generation sequencing ; Original ; ORIGINAL ARTICLES ; p53 Protein ; Patients ; Plasma ; Prognosis ; Risk factors ; Tumors ; upper tract urothelial carcinoma ; Urothelial carcinoma</subject><ispartof>Cancer science, 2022-05, Vol.113 (5), p.1830-1842</ispartof><rights>2022 The Authors. published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.</rights><rights>2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.</rights><rights>2022. This work is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4674-9640ea767136671cadae749e2ea9477db4835cf2438bc062e53c1fe9bf5d885a3</citedby><cites>FETCH-LOGICAL-c4674-9640ea767136671cadae749e2ea9477db4835cf2438bc062e53c1fe9bf5d885a3</cites><orcidid>0000-0001-9976-6994 ; 0000-0001-9369-4264 ; 0000-0002-4701-5635 ; 0000-0002-0056-9446 ; 0000-0001-5356-7359 ; 0000-0002-7491-9410 ; 0000-0002-6522-6233 ; 0000-0001-8445-6205 ; 0000-0002-8681-1407 ; 0000-0002-9236-9061</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128184/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128184/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,1418,11567,27929,27930,45579,45580,46057,46481,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35293110$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nakano, Kosuke</creatorcontrib><creatorcontrib>Koh, Yoko</creatorcontrib><creatorcontrib>Yamamichi, Gaku</creatorcontrib><creatorcontrib>Yumiba, Satoru</creatorcontrib><creatorcontrib>Tomiyama, Eisuke</creatorcontrib><creatorcontrib>Matsushita, Makoto</creatorcontrib><creatorcontrib>Hayashi, Yujiro</creatorcontrib><creatorcontrib>Wang, Cong</creatorcontrib><creatorcontrib>Ishizuya, Yu</creatorcontrib><creatorcontrib>Yamamoto, Yoshiyuki</creatorcontrib><creatorcontrib>Kato, Taigo</creatorcontrib><creatorcontrib>Hatano, Koji</creatorcontrib><creatorcontrib>Kawashima, Atsunari</creatorcontrib><creatorcontrib>Ujike, Takeshi</creatorcontrib><creatorcontrib>Fujita, Kazutoshi</creatorcontrib><creatorcontrib>Kiyotani, Kazuma</creatorcontrib><creatorcontrib>Katayama, Kotoe</creatorcontrib><creatorcontrib>Yamaguchi, Rui</creatorcontrib><creatorcontrib>Imoto, Seiya</creatorcontrib><creatorcontrib>Imamura, Ryoichi</creatorcontrib><creatorcontrib>Nonomura, Norio</creatorcontrib><creatorcontrib>Uemura, Motohide</creatorcontrib><title>Perioperative circulating tumor DNA enables the identification of patients with poor prognosis in upper tract urothelial carcinoma</title><title>Cancer science</title><addtitle>Cancer Sci</addtitle><description>Perioperative systemic chemotherapy improves the prognosis of upper tract urothelial carcinoma (UTUC). The first objective of this study was to verify whether perioperative circulating tumor DNA (ctDNA) analysis using a pan‐cancer gene panel and next‐generation sequencing could identify patients with poor prognosis who require perioperative chemotherapy. Second, we investigated whether ctDNA is useful for minimal residual disease (MRD) detection and treatment monitoring in UTUC. This study included 50 patients with untreated UTUC, including 43 cases of localized UTUC. We performed targeted ultradeep sequencing of plasma cell‐free DNA (cfDNA) and buffy coat DNA and whole‐exome sequencing of cancer tissues, allowing exclusion of possible false positives. We attempted to stratify the prognosis according to the perioperative ctDNA levels in patients with localized UTUC. In patients with metastatic UTUC, ctDNA was evaluated before, during, and after systemic treatment. In total, 23 (46%) of 50 patients with untreated UTUC were ctDNA positive, and 17 (40%) of 43 patients with localized UTUC were ctDNA positive. Of the detected TP53 mutations, 19% were false positives due to clonal hematopoiesis of indeterminate potential. Among preoperative risk factors, only the preoperative ctDNA fraction>2% was a significant and independent risk factor associated with worse recurrence‐free survival (RFS). Furthermore, the existence of ctDNA early points after the operation was significantly associated with worse RFS, suggesting the presence of MRD. ctDNA also showed a potential as a real‐time marker for systemic therapy in patients with metastatic UTUC. Detection of ctDNA may indicate potential metastasis and guide decisions on perioperative chemotherapy.
In this study, we performed ultradeep sequencing of cell‐free DNA (cfDNA) in the plasma of 50 patients with untreated upper tract urothelial carcinoma (UTUC), of whom 23 (46%) were circulating tumor DNA (ctDNA) positive. Among the preoperative risk factors, only a preoperative ctDNA proportion >2% was found to be a significant and independent risk factor associated with worse recurrence‐free survival (RFS). Furthermore, the presence of ctDNA in the early postoperative period was significantly associated with worse RFS, suggesting the presence of minimal residual disease.</description><subject>Bar codes</subject><subject>Biomarkers</subject><subject>Biopsy</subject><subject>Bladder cancer</subject><subject>Blood</subject><subject>Buffy coat</subject><subject>Cancer therapies</subject><subject>cell‐free DNA</subject><subject>Chemotherapy</subject><subject>circulating tumor DNA</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA sequencing</subject><subject>Gene expression</subject><subject>Medical prognosis</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Minimal residual disease</subject><subject>Mutation</subject><subject>next‐generation sequencing</subject><subject>Original</subject><subject>ORIGINAL ARTICLES</subject><subject>p53 Protein</subject><subject>Patients</subject><subject>Plasma</subject><subject>Prognosis</subject><subject>Risk factors</subject><subject>Tumors</subject><subject>upper tract urothelial carcinoma</subject><subject>Urothelial 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circulating tumor DNA enables the identification of patients with poor prognosis in upper tract urothelial carcinoma</title><author>Nakano, Kosuke ; Koh, Yoko ; Yamamichi, Gaku ; Yumiba, Satoru ; Tomiyama, Eisuke ; Matsushita, Makoto ; Hayashi, Yujiro ; Wang, Cong ; Ishizuya, Yu ; Yamamoto, Yoshiyuki ; Kato, Taigo ; Hatano, Koji ; Kawashima, Atsunari ; Ujike, Takeshi ; Fujita, Kazutoshi ; Kiyotani, Kazuma ; Katayama, Kotoe ; Yamaguchi, Rui ; Imoto, Seiya ; Imamura, Ryoichi ; Nonomura, Norio ; Uemura, Motohide</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4674-9640ea767136671cadae749e2ea9477db4835cf2438bc062e53c1fe9bf5d885a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Bar codes</topic><topic>Biomarkers</topic><topic>Biopsy</topic><topic>Bladder cancer</topic><topic>Blood</topic><topic>Buffy coat</topic><topic>Cancer therapies</topic><topic>cell‐free 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carcinoma</atitle><jtitle>Cancer science</jtitle><addtitle>Cancer Sci</addtitle><date>2022-05</date><risdate>2022</risdate><volume>113</volume><issue>5</issue><spage>1830</spage><epage>1842</epage><pages>1830-1842</pages><issn>1347-9032</issn><eissn>1349-7006</eissn><abstract>Perioperative systemic chemotherapy improves the prognosis of upper tract urothelial carcinoma (UTUC). The first objective of this study was to verify whether perioperative circulating tumor DNA (ctDNA) analysis using a pan‐cancer gene panel and next‐generation sequencing could identify patients with poor prognosis who require perioperative chemotherapy. Second, we investigated whether ctDNA is useful for minimal residual disease (MRD) detection and treatment monitoring in UTUC. This study included 50 patients with untreated UTUC, including 43 cases of localized UTUC. We performed targeted ultradeep sequencing of plasma cell‐free DNA (cfDNA) and buffy coat DNA and whole‐exome sequencing of cancer tissues, allowing exclusion of possible false positives. We attempted to stratify the prognosis according to the perioperative ctDNA levels in patients with localized UTUC. In patients with metastatic UTUC, ctDNA was evaluated before, during, and after systemic treatment. In total, 23 (46%) of 50 patients with untreated UTUC were ctDNA positive, and 17 (40%) of 43 patients with localized UTUC were ctDNA positive. Of the detected TP53 mutations, 19% were false positives due to clonal hematopoiesis of indeterminate potential. Among preoperative risk factors, only the preoperative ctDNA fraction>2% was a significant and independent risk factor associated with worse recurrence‐free survival (RFS). Furthermore, the existence of ctDNA early points after the operation was significantly associated with worse RFS, suggesting the presence of MRD. ctDNA also showed a potential as a real‐time marker for systemic therapy in patients with metastatic UTUC. Detection of ctDNA may indicate potential metastasis and guide decisions on perioperative chemotherapy.
In this study, we performed ultradeep sequencing of cell‐free DNA (cfDNA) in the plasma of 50 patients with untreated upper tract urothelial carcinoma (UTUC), of whom 23 (46%) were circulating tumor DNA (ctDNA) positive. Among the preoperative risk factors, only a preoperative ctDNA proportion >2% was found to be a significant and independent risk factor associated with worse recurrence‐free survival (RFS). Furthermore, the presence of ctDNA in the early postoperative period was significantly associated with worse RFS, suggesting the presence of minimal residual disease.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>35293110</pmid><doi>10.1111/cas.15334</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-9976-6994</orcidid><orcidid>https://orcid.org/0000-0001-9369-4264</orcidid><orcidid>https://orcid.org/0000-0002-4701-5635</orcidid><orcidid>https://orcid.org/0000-0002-0056-9446</orcidid><orcidid>https://orcid.org/0000-0001-5356-7359</orcidid><orcidid>https://orcid.org/0000-0002-7491-9410</orcidid><orcidid>https://orcid.org/0000-0002-6522-6233</orcidid><orcidid>https://orcid.org/0000-0001-8445-6205</orcidid><orcidid>https://orcid.org/0000-0002-8681-1407</orcidid><orcidid>https://orcid.org/0000-0002-9236-9061</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1347-9032 |
| ispartof | Cancer science, 2022-05, Vol.113 (5), p.1830-1842 |
| issn | 1347-9032 1349-7006 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9128184 |
| source | DOAJ Directory of Open Access Journals; Wiley-Blackwell Open Access Titles; Wiley Online Library All Journals; PubMed Central |
| subjects | Bar codes Biomarkers Biopsy Bladder cancer Blood Buffy coat Cancer therapies cell‐free DNA Chemotherapy circulating tumor DNA Deoxyribonucleic acid DNA DNA sequencing Gene expression Medical prognosis Metastases Metastasis Minimal residual disease Mutation next‐generation sequencing Original ORIGINAL ARTICLES p53 Protein Patients Plasma Prognosis Risk factors Tumors upper tract urothelial carcinoma Urothelial carcinoma |
| title | Perioperative circulating tumor DNA enables the identification of patients with poor prognosis in upper tract urothelial carcinoma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-15T04%3A53%3A39IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Perioperative%20circulating%20tumor%20DNA%20enables%20the%20identification%20of%20patients%20with%20poor%20prognosis%20in%20upper%20tract%20urothelial%20carcinoma&rft.jtitle=Cancer%20science&rft.au=Nakano,%20Kosuke&rft.date=2022-05&rft.volume=113&rft.issue=5&rft.spage=1830&rft.epage=1842&rft.pages=1830-1842&rft.issn=1347-9032&rft.eissn=1349-7006&rft_id=info:doi/10.1111/cas.15334&rft_dat=%3Cproquest_pubme%3E2668138256%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2668138256&rft_id=info:pmid/35293110&rfr_iscdi=true |