Comparison of genomic profiling of circulating tumor DNA in pancreaticobiliary malignancies in plasma and bile
Background Obtaining sufficient pancreaticobiliary tumor tissue for genomic profiling has limitations. Liquid biopsies using plasma do not provide sufficient sensitivity. Thus, this study aimed to determine the effectiveness of liquid biopsy between bile and plasma for identifying oncogenic and drug...
Gespeichert in:
| Veröffentlicht in: | Cancer 2023-06, Vol.129 (11), p.1714-1722 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1722 |
|---|---|
| container_issue | 11 |
| container_start_page | 1714 |
| container_title | Cancer |
| container_volume | 129 |
| creator | Ohyama, Hiroshi Hirotsu, Yosuke Amemiya, Kenji Miura, Yoshifumi Hirose, Sumio Oyama, Toshio Iimuro, Yuji Kojima, Yuichiro Mikata, Rintaro Mochizuki, Hitoshi Kato, Naoya Omata, Masao |
| description | Background
Obtaining sufficient pancreaticobiliary tumor tissue for genomic profiling has limitations. Liquid biopsies using plasma do not provide sufficient sensitivity. Thus, this study aimed to determine the effectiveness of liquid biopsy between bile and plasma for identifying oncogenic and drug‐matched mutations.
Methods
This study created a panel of 60 significantly mutated genes specific to pancreaticobiliary cancer (PBCA) and used it for genomic analysis of 212 deoxyribonucleic acid (DNA) samples (87 bile supernatant, 87 bile precipitate, and 38 plasma) from 87 patients with PBCA. The quantity of extracted DNA from bile and plasma was compared, as were genomic profiles of 38 pairs of bile and plasma from 38 patients with PBCA. Finally, we investigated 87 bile and 38 plasma for the ability to detect druggable mutations.
Results
The amount of DNA was significantly lower in plasma than in bile (p |
| doi_str_mv | 10.1002/cncr.34717 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2811566328</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2811566328</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4237-734e3334c5a4f3c4db09eb0366331300d1f611fa5156bc8771f29051f946b90a3</originalsourceid><addsrcrecordid>eNp9kc9KxDAQxoMo7rp68QEk4EWErkknbdqj1L8gCqLgraTZZIm0SU22yL6Nz-KTmXVXDx48DTP5zTeZ-RA6pGRKCUnPpJV-CoxTvoXGlJQ8IZSl22hMCCmSjMHLCO2F8BpTnmawi0aQl5CWBR8jV7muF94EZ7HTeK6s64zEvXfatMbOV0VpvBxasVili6FzHl_cn2NjPz96EUer-CJdE3Hhl7gTrZnbWDcqRAb3rQidwMLOcETUPtrRog3qYBMn6Pnq8qm6Se4erm-r87tEshR4woEpAGAyE0yDZLOGlKohkOcAFAiZUZ1TqkVGs7yRBedUpyXJqC5Z3pREwASdrHXjJm-DCou6M0GqthVWuSHUaUFjaw5pEdHjP-irG7yNv_umaJmzOHOCTteU9C4Er3Tde9PFjWtK6pUN9cqG-tuGCB9tJIemU7Nf9OfuEaBr4D3eZPmPVF3dV49r0S_GDJLL</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2811196431</pqid></control><display><type>article</type><title>Comparison of genomic profiling of circulating tumor DNA in pancreaticobiliary malignancies in plasma and bile</title><source>Wiley Free Content</source><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Ohyama, Hiroshi ; Hirotsu, Yosuke ; Amemiya, Kenji ; Miura, Yoshifumi ; Hirose, Sumio ; Oyama, Toshio ; Iimuro, Yuji ; Kojima, Yuichiro ; Mikata, Rintaro ; Mochizuki, Hitoshi ; Kato, Naoya ; Omata, Masao</creator><creatorcontrib>Ohyama, Hiroshi ; Hirotsu, Yosuke ; Amemiya, Kenji ; Miura, Yoshifumi ; Hirose, Sumio ; Oyama, Toshio ; Iimuro, Yuji ; Kojima, Yuichiro ; Mikata, Rintaro ; Mochizuki, Hitoshi ; Kato, Naoya ; Omata, Masao</creatorcontrib><description>Background
Obtaining sufficient pancreaticobiliary tumor tissue for genomic profiling has limitations. Liquid biopsies using plasma do not provide sufficient sensitivity. Thus, this study aimed to determine the effectiveness of liquid biopsy between bile and plasma for identifying oncogenic and drug‐matched mutations.
Methods
This study created a panel of 60 significantly mutated genes specific to pancreaticobiliary cancer (PBCA) and used it for genomic analysis of 212 deoxyribonucleic acid (DNA) samples (87 bile supernatant, 87 bile precipitate, and 38 plasma) from 87 patients with PBCA. The quantity of extracted DNA from bile and plasma was compared, as were genomic profiles of 38 pairs of bile and plasma from 38 patients with PBCA. Finally, we investigated 87 bile and 38 plasma for the ability to detect druggable mutations.
Results
The amount of DNA was significantly lower in plasma than in bile (p < .001). Oncogenic mutations were identified in 21 of 38 (55%) patients in bile and nine (24%) in plasma samples (p = .005). Bile was significantly more sensitive than plasma in identifying druggable mutations (p = .032). The authors detected 23 drug‐matched mutations in combined bile and plasma, including five ERBB2, four ATM, three BRAF, three BRCA2, three NF1, two PIK3CA, one BRCA1, one IDH1, and one PALB2.
Conclusions
Liquid biopsy using bile may be useful in searching for therapeutic agents, and using the obtained genomic information may improve the prognoses of patients with PBCA.
Plain Language Summary
Genomic profiling of formalin‐fixed paraffin‐embedded tissues may provide actionable targets for molecular and immuno‐oncological treatment.
However, most pancreaticobiliary malignancies are unresectable and formalin‐fixed paraffin‐embedded tissues cannot be obtained.
Although comprehensive genomic profiling tests using plasma have been used in recent years, the utility of those using bile is not clear.
Our study revealed that bile identified more drug‐matched mutations than plasma in advanced pancreaticobiliary cancer patients.
Bile may help widen the patient population benefiting from targeted drugs.
Bile contained a large amount of tumor‐derived DNA in pancreaticobiliary cancer. Liquid biopsy using bile may be useful in searching for therapeutic agents.</description><identifier>ISSN: 0008-543X</identifier><identifier>EISSN: 1097-0142</identifier><identifier>DOI: 10.1002/cncr.34717</identifier><identifier>PMID: 36932987</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Bile ; Biopsy ; BRCA1 protein ; BRCA2 protein ; Breast cancer ; Cancer ; Circulating Tumor DNA - genetics ; Deoxyribonucleic acid ; DNA ; DNA fingerprinting ; ErbB-2 protein ; Formaldehyde ; Genomic analysis ; Genomics ; High-Throughput Nucleotide Sequencing ; Humans ; Malignancy ; Mutation ; neoplasms ; Neoplasms - pathology ; oncogenes ; Oncology ; Pancreatic cancer ; pancreaticobiliary cancer ; Paraffin ; Paraffins ; Pharmacology ; Plasma ; Tissues ; Tumors</subject><ispartof>Cancer, 2023-06, Vol.129 (11), p.1714-1722</ispartof><rights>2023 American Cancer Society.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4237-734e3334c5a4f3c4db09eb0366331300d1f611fa5156bc8771f29051f946b90a3</citedby><cites>FETCH-LOGICAL-c4237-734e3334c5a4f3c4db09eb0366331300d1f611fa5156bc8771f29051f946b90a3</cites><orcidid>0000-0003-0614-581X</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%2Fcncr.34717$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fcncr.34717$$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/36932987$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ohyama, Hiroshi</creatorcontrib><creatorcontrib>Hirotsu, Yosuke</creatorcontrib><creatorcontrib>Amemiya, Kenji</creatorcontrib><creatorcontrib>Miura, Yoshifumi</creatorcontrib><creatorcontrib>Hirose, Sumio</creatorcontrib><creatorcontrib>Oyama, Toshio</creatorcontrib><creatorcontrib>Iimuro, Yuji</creatorcontrib><creatorcontrib>Kojima, Yuichiro</creatorcontrib><creatorcontrib>Mikata, Rintaro</creatorcontrib><creatorcontrib>Mochizuki, Hitoshi</creatorcontrib><creatorcontrib>Kato, Naoya</creatorcontrib><creatorcontrib>Omata, Masao</creatorcontrib><title>Comparison of genomic profiling of circulating tumor DNA in pancreaticobiliary malignancies in plasma and bile</title><title>Cancer</title><addtitle>Cancer</addtitle><description>Background
Obtaining sufficient pancreaticobiliary tumor tissue for genomic profiling has limitations. Liquid biopsies using plasma do not provide sufficient sensitivity. Thus, this study aimed to determine the effectiveness of liquid biopsy between bile and plasma for identifying oncogenic and drug‐matched mutations.
Methods
This study created a panel of 60 significantly mutated genes specific to pancreaticobiliary cancer (PBCA) and used it for genomic analysis of 212 deoxyribonucleic acid (DNA) samples (87 bile supernatant, 87 bile precipitate, and 38 plasma) from 87 patients with PBCA. The quantity of extracted DNA from bile and plasma was compared, as were genomic profiles of 38 pairs of bile and plasma from 38 patients with PBCA. Finally, we investigated 87 bile and 38 plasma for the ability to detect druggable mutations.
Results
The amount of DNA was significantly lower in plasma than in bile (p < .001). Oncogenic mutations were identified in 21 of 38 (55%) patients in bile and nine (24%) in plasma samples (p = .005). Bile was significantly more sensitive than plasma in identifying druggable mutations (p = .032). The authors detected 23 drug‐matched mutations in combined bile and plasma, including five ERBB2, four ATM, three BRAF, three BRCA2, three NF1, two PIK3CA, one BRCA1, one IDH1, and one PALB2.
Conclusions
Liquid biopsy using bile may be useful in searching for therapeutic agents, and using the obtained genomic information may improve the prognoses of patients with PBCA.
Plain Language Summary
Genomic profiling of formalin‐fixed paraffin‐embedded tissues may provide actionable targets for molecular and immuno‐oncological treatment.
However, most pancreaticobiliary malignancies are unresectable and formalin‐fixed paraffin‐embedded tissues cannot be obtained.
Although comprehensive genomic profiling tests using plasma have been used in recent years, the utility of those using bile is not clear.
Our study revealed that bile identified more drug‐matched mutations than plasma in advanced pancreaticobiliary cancer patients.
Bile may help widen the patient population benefiting from targeted drugs.
Bile contained a large amount of tumor‐derived DNA in pancreaticobiliary cancer. Liquid biopsy using bile may be useful in searching for therapeutic agents.</description><subject>Bile</subject><subject>Biopsy</subject><subject>BRCA1 protein</subject><subject>BRCA2 protein</subject><subject>Breast cancer</subject><subject>Cancer</subject><subject>Circulating Tumor DNA - genetics</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA fingerprinting</subject><subject>ErbB-2 protein</subject><subject>Formaldehyde</subject><subject>Genomic analysis</subject><subject>Genomics</subject><subject>High-Throughput Nucleotide Sequencing</subject><subject>Humans</subject><subject>Malignancy</subject><subject>Mutation</subject><subject>neoplasms</subject><subject>Neoplasms - pathology</subject><subject>oncogenes</subject><subject>Oncology</subject><subject>Pancreatic cancer</subject><subject>pancreaticobiliary cancer</subject><subject>Paraffin</subject><subject>Paraffins</subject><subject>Pharmacology</subject><subject>Plasma</subject><subject>Tissues</subject><subject>Tumors</subject><issn>0008-543X</issn><issn>1097-0142</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc9KxDAQxoMo7rp68QEk4EWErkknbdqj1L8gCqLgraTZZIm0SU22yL6Nz-KTmXVXDx48DTP5zTeZ-RA6pGRKCUnPpJV-CoxTvoXGlJQ8IZSl22hMCCmSjMHLCO2F8BpTnmawi0aQl5CWBR8jV7muF94EZ7HTeK6s64zEvXfatMbOV0VpvBxasVili6FzHl_cn2NjPz96EUer-CJdE3Hhl7gTrZnbWDcqRAb3rQidwMLOcETUPtrRog3qYBMn6Pnq8qm6Se4erm-r87tEshR4woEpAGAyE0yDZLOGlKohkOcAFAiZUZ1TqkVGs7yRBedUpyXJqC5Z3pREwASdrHXjJm-DCou6M0GqthVWuSHUaUFjaw5pEdHjP-irG7yNv_umaJmzOHOCTteU9C4Er3Tde9PFjWtK6pUN9cqG-tuGCB9tJIemU7Nf9OfuEaBr4D3eZPmPVF3dV49r0S_GDJLL</recordid><startdate>20230601</startdate><enddate>20230601</enddate><creator>Ohyama, Hiroshi</creator><creator>Hirotsu, Yosuke</creator><creator>Amemiya, Kenji</creator><creator>Miura, Yoshifumi</creator><creator>Hirose, Sumio</creator><creator>Oyama, Toshio</creator><creator>Iimuro, Yuji</creator><creator>Kojima, Yuichiro</creator><creator>Mikata, Rintaro</creator><creator>Mochizuki, Hitoshi</creator><creator>Kato, Naoya</creator><creator>Omata, Masao</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>7TO</scope><scope>7U7</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-0614-581X</orcidid></search><sort><creationdate>20230601</creationdate><title>Comparison of genomic profiling of circulating tumor DNA in pancreaticobiliary malignancies in plasma and bile</title><author>Ohyama, Hiroshi ; Hirotsu, Yosuke ; Amemiya, Kenji ; Miura, Yoshifumi ; Hirose, Sumio ; Oyama, Toshio ; Iimuro, Yuji ; Kojima, Yuichiro ; Mikata, Rintaro ; Mochizuki, Hitoshi ; Kato, Naoya ; Omata, Masao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4237-734e3334c5a4f3c4db09eb0366331300d1f611fa5156bc8771f29051f946b90a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Bile</topic><topic>Biopsy</topic><topic>BRCA1 protein</topic><topic>BRCA2 protein</topic><topic>Breast cancer</topic><topic>Cancer</topic><topic>Circulating Tumor DNA - genetics</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA fingerprinting</topic><topic>ErbB-2 protein</topic><topic>Formaldehyde</topic><topic>Genomic analysis</topic><topic>Genomics</topic><topic>High-Throughput Nucleotide Sequencing</topic><topic>Humans</topic><topic>Malignancy</topic><topic>Mutation</topic><topic>neoplasms</topic><topic>Neoplasms - pathology</topic><topic>oncogenes</topic><topic>Oncology</topic><topic>Pancreatic cancer</topic><topic>pancreaticobiliary cancer</topic><topic>Paraffin</topic><topic>Paraffins</topic><topic>Pharmacology</topic><topic>Plasma</topic><topic>Tissues</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ohyama, Hiroshi</creatorcontrib><creatorcontrib>Hirotsu, Yosuke</creatorcontrib><creatorcontrib>Amemiya, Kenji</creatorcontrib><creatorcontrib>Miura, Yoshifumi</creatorcontrib><creatorcontrib>Hirose, Sumio</creatorcontrib><creatorcontrib>Oyama, Toshio</creatorcontrib><creatorcontrib>Iimuro, Yuji</creatorcontrib><creatorcontrib>Kojima, Yuichiro</creatorcontrib><creatorcontrib>Mikata, Rintaro</creatorcontrib><creatorcontrib>Mochizuki, Hitoshi</creatorcontrib><creatorcontrib>Kato, Naoya</creatorcontrib><creatorcontrib>Omata, Masao</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ohyama, Hiroshi</au><au>Hirotsu, Yosuke</au><au>Amemiya, Kenji</au><au>Miura, Yoshifumi</au><au>Hirose, Sumio</au><au>Oyama, Toshio</au><au>Iimuro, Yuji</au><au>Kojima, Yuichiro</au><au>Mikata, Rintaro</au><au>Mochizuki, Hitoshi</au><au>Kato, Naoya</au><au>Omata, Masao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparison of genomic profiling of circulating tumor DNA in pancreaticobiliary malignancies in plasma and bile</atitle><jtitle>Cancer</jtitle><addtitle>Cancer</addtitle><date>2023-06-01</date><risdate>2023</risdate><volume>129</volume><issue>11</issue><spage>1714</spage><epage>1722</epage><pages>1714-1722</pages><issn>0008-543X</issn><eissn>1097-0142</eissn><abstract>Background
Obtaining sufficient pancreaticobiliary tumor tissue for genomic profiling has limitations. Liquid biopsies using plasma do not provide sufficient sensitivity. Thus, this study aimed to determine the effectiveness of liquid biopsy between bile and plasma for identifying oncogenic and drug‐matched mutations.
Methods
This study created a panel of 60 significantly mutated genes specific to pancreaticobiliary cancer (PBCA) and used it for genomic analysis of 212 deoxyribonucleic acid (DNA) samples (87 bile supernatant, 87 bile precipitate, and 38 plasma) from 87 patients with PBCA. The quantity of extracted DNA from bile and plasma was compared, as were genomic profiles of 38 pairs of bile and plasma from 38 patients with PBCA. Finally, we investigated 87 bile and 38 plasma for the ability to detect druggable mutations.
Results
The amount of DNA was significantly lower in plasma than in bile (p < .001). Oncogenic mutations were identified in 21 of 38 (55%) patients in bile and nine (24%) in plasma samples (p = .005). Bile was significantly more sensitive than plasma in identifying druggable mutations (p = .032). The authors detected 23 drug‐matched mutations in combined bile and plasma, including five ERBB2, four ATM, three BRAF, three BRCA2, three NF1, two PIK3CA, one BRCA1, one IDH1, and one PALB2.
Conclusions
Liquid biopsy using bile may be useful in searching for therapeutic agents, and using the obtained genomic information may improve the prognoses of patients with PBCA.
Plain Language Summary
Genomic profiling of formalin‐fixed paraffin‐embedded tissues may provide actionable targets for molecular and immuno‐oncological treatment.
However, most pancreaticobiliary malignancies are unresectable and formalin‐fixed paraffin‐embedded tissues cannot be obtained.
Although comprehensive genomic profiling tests using plasma have been used in recent years, the utility of those using bile is not clear.
Our study revealed that bile identified more drug‐matched mutations than plasma in advanced pancreaticobiliary cancer patients.
Bile may help widen the patient population benefiting from targeted drugs.
Bile contained a large amount of tumor‐derived DNA in pancreaticobiliary cancer. Liquid biopsy using bile may be useful in searching for therapeutic agents.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>36932987</pmid><doi>10.1002/cncr.34717</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-0614-581X</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0008-543X |
| ispartof | Cancer, 2023-06, Vol.129 (11), p.1714-1722 |
| issn | 0008-543X 1097-0142 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2811566328 |
| source | Wiley Free Content; MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Bile Biopsy BRCA1 protein BRCA2 protein Breast cancer Cancer Circulating Tumor DNA - genetics Deoxyribonucleic acid DNA DNA fingerprinting ErbB-2 protein Formaldehyde Genomic analysis Genomics High-Throughput Nucleotide Sequencing Humans Malignancy Mutation neoplasms Neoplasms - pathology oncogenes Oncology Pancreatic cancer pancreaticobiliary cancer Paraffin Paraffins Pharmacology Plasma Tissues Tumors |
| title | Comparison of genomic profiling of circulating tumor DNA in pancreaticobiliary malignancies in plasma and bile |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-13T11%3A47%3A58IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Comparison%20of%20genomic%20profiling%20of%20circulating%20tumor%20DNA%20in%C2%A0pancreaticobiliary%20malignancies%20in%20plasma%20and%20bile&rft.jtitle=Cancer&rft.au=Ohyama,%20Hiroshi&rft.date=2023-06-01&rft.volume=129&rft.issue=11&rft.spage=1714&rft.epage=1722&rft.pages=1714-1722&rft.issn=0008-543X&rft.eissn=1097-0142&rft_id=info:doi/10.1002/cncr.34717&rft_dat=%3Cproquest_cross%3E2811566328%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2811196431&rft_id=info:pmid/36932987&rfr_iscdi=true |