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Circulating tumor cells (CTCs), the cells shed from a solid tumor into the bloodstream, may help doctors avoid having to do repeat needle biopsies on patients with unresectable non–small cell lung cancer.
Challenges to using CTCs clinically are that they are not abundant in the blood and have been difficult to isolate in patients with this type of cancer with commercially available assays.
In their paper, the authors show that an experimental nanotechnology can effectively isolate and measure CTCs in patients with stage 3 NSCLC. They also found that a precipitous drop in CTCs during chemoradiation treatment predicted significantly longer progression-free survival in those patients.
Study Results and Methods
For their research, study coauthors Shruti Jolly, MD, and Sunitha Nagrath, PhD, used a novel graphene oxide technology called the GO chip, developed more than a decade ago by Dr. Nagrath and her colleagues, to isolate CTCs from patients with stage 3 NSCLC. While a different technology, which is approved by the US Food and Drug Administration (FDA), uses a single antibody to pick up CTCs, the GO chip uses a cocktail of three antibodies to CTC proteins, making it more sensitive.
The 26 patients in the study (mean age 67, 27% female) all received radiation treatment for 6 weeks, plus weekly carboplatin and paclitaxel chemotherapy. Sixteen of the patients afterward went on to have immunotherapy with durvalumab. Blood was drawn at six fixed time points: before treatment, and at weeks 1, 4, 10, 18, and 30. CTCs were measured and analyzed with every draw.
Previous studies showed that absolute number of CTCs did not correlate with either tumor volume or progression-free survival in NSCLC.
Dr. Jolly and Dr. Nagrath sought to measure change in CTCs from baseline for each patient, having the patient serve as his or her own control. They found that patients whose individual CTC counts dropped by 75% or more between pretreatment and week 4 of chemoradiation saw a mean 21 months of progression-free survival compared with 7 months for patients whose CTCs dropped by less than 75% in the same period (P = .0076).
Dr. Jolly and Dr. Nagrath also aimed to determine, as an exploratory outcome of their study, whether other information collected from the CTCs could predict response to treatment with durvalumab immunotherapy. They found that having more than 50% of CTCs positive for the protein PD-L1 correlated to shorter progression-free survival among the 16 patients receiving durvalumab (P = .04).
“Every person’s tumor is unique in terms of its response to treatment,” said Dr. Jolly, a radiation oncologist and professor and associate chair of community practices in the Department of Radiation Oncology at the University of Michigan, Ann Arbor.
“Two people with a three-centimeter lung tumor will not necessarily shed the same amount of tumor cells into circulation. CTCs are reflective of disease burden; however, this is not related to the absolute numbers. That’s why we decided to use individualized baselines and look at the percentage of decrease,” she said.
Dr. Nagrath, professor of chemical and biomedical engineering at the University of Michigan, noted, in the same interview, that the findings argue for CTCs as a biomarker in stage 3 NSCLC.
“A lot of researchers who do lung cancer studies struggle with isolating lung cancer CTCs,” Dr. Nagrath said. “We showed, with repeated blood draws during treatment, what is changing at a molecular level and that you can see it with a simple blood draw. It also gives the proof of concept that if these cells are present, this is a good way to monitor and see if a treatment is working, even early in the treatment.” Moreover, she added, “many studies in lung cancer are in stage 4.”
Our study is unique as it followed patients with locally advanced tumors from their being treatment naive to all the way through immunotherapy,” she continued.
The University of Michigan has a patent on the GO chip technology, but thus far no company has made efforts to license it and submit it for approval. While “liquid biopsy” is an important emerging concept in lung cancer, there is little consensus yet as to which blood biomarkers — whether CTCs, circulating tumor DNA (ctDNA), or extracellular vesicles (EVs) — are most clinically relevant, Dr. Nagrath said.
The study’s small size is one of its weaknesses, according to the authors.
Findings are ‘Particularly Intriguing’
Majid Ebrahimi Warkiani, PhD, who was not involved in the study, described the new findings as “particularly intriguing [and] highlighting the efficacy of liquid biopsy using CTCs for predicting treatment outcomes.”
A challenge within the realm of CTCs lies in the community’s ongoing struggle to define and classify these cells accurately, Dr. Warkiani said in an interview.
“While surface protein markers offer valuable insights, emerging layers of analysis, such as metabolomics, are increasingly entering the scene to bolster the identification of putative cancer cells, alongside molecular tests like fluorescence in situ hybridization (FISH),” said Dr. Warkiani of the University of Technology Sydney in Australia. “The amalgamation of these approaches simultaneously presents a significant challenge, particularly in terms of standardization for patient care, unlike ctDNA, which faces fewer bottlenecks.
“The robustness of the research in this study is commendable. However, further clinical testing and randomized trials are imperative,” Dr. Warkiani continued. “Companies like Epic Sciences are actively engaged in advancing research and standardization in this field.”
The study by Dr. Jolly and Dr. Nagrath was funded by the National Institutes of Health. None of the study authors reported financial conflicts of interest. Dr. Warkiani reported no conflicts of interest related to his comment.
Circulating tumor cells (CTCs), the cells shed from a solid tumor into the bloodstream, may help doctors avoid having to do repeat needle biopsies on patients with unresectable non–small cell lung cancer.
Challenges to using CTCs clinically are that they are not abundant in the blood and have been difficult to isolate in patients with this type of cancer with commercially available assays.
In their paper, the authors show that an experimental nanotechnology can effectively isolate and measure CTCs in patients with stage 3 NSCLC. They also found that a precipitous drop in CTCs during chemoradiation treatment predicted significantly longer progression-free survival in those patients.
Study Results and Methods
For their research, study coauthors Shruti Jolly, MD, and Sunitha Nagrath, PhD, used a novel graphene oxide technology called the GO chip, developed more than a decade ago by Dr. Nagrath and her colleagues, to isolate CTCs from patients with stage 3 NSCLC. While a different technology, which is approved by the US Food and Drug Administration (FDA), uses a single antibody to pick up CTCs, the GO chip uses a cocktail of three antibodies to CTC proteins, making it more sensitive.
The 26 patients in the study (mean age 67, 27% female) all received radiation treatment for 6 weeks, plus weekly carboplatin and paclitaxel chemotherapy. Sixteen of the patients afterward went on to have immunotherapy with durvalumab. Blood was drawn at six fixed time points: before treatment, and at weeks 1, 4, 10, 18, and 30. CTCs were measured and analyzed with every draw.
Previous studies showed that absolute number of CTCs did not correlate with either tumor volume or progression-free survival in NSCLC.
Dr. Jolly and Dr. Nagrath sought to measure change in CTCs from baseline for each patient, having the patient serve as his or her own control. They found that patients whose individual CTC counts dropped by 75% or more between pretreatment and week 4 of chemoradiation saw a mean 21 months of progression-free survival compared with 7 months for patients whose CTCs dropped by less than 75% in the same period (P = .0076).
Dr. Jolly and Dr. Nagrath also aimed to determine, as an exploratory outcome of their study, whether other information collected from the CTCs could predict response to treatment with durvalumab immunotherapy. They found that having more than 50% of CTCs positive for the protein PD-L1 correlated to shorter progression-free survival among the 16 patients receiving durvalumab (P = .04).
“Every person’s tumor is unique in terms of its response to treatment,” said Dr. Jolly, a radiation oncologist and professor and associate chair of community practices in the Department of Radiation Oncology at the University of Michigan, Ann Arbor.
“Two people with a three-centimeter lung tumor will not necessarily shed the same amount of tumor cells into circulation. CTCs are reflective of disease burden; however, this is not related to the absolute numbers. That’s why we decided to use individualized baselines and look at the percentage of decrease,” she said.
Dr. Nagrath, professor of chemical and biomedical engineering at the University of Michigan, noted, in the same interview, that the findings argue for CTCs as a biomarker in stage 3 NSCLC.
“A lot of researchers who do lung cancer studies struggle with isolating lung cancer CTCs,” Dr. Nagrath said. “We showed, with repeated blood draws during treatment, what is changing at a molecular level and that you can see it with a simple blood draw. It also gives the proof of concept that if these cells are present, this is a good way to monitor and see if a treatment is working, even early in the treatment.” Moreover, she added, “many studies in lung cancer are in stage 4.”
Our study is unique as it followed patients with locally advanced tumors from their being treatment naive to all the way through immunotherapy,” she continued.
The University of Michigan has a patent on the GO chip technology, but thus far no company has made efforts to license it and submit it for approval. While “liquid biopsy” is an important emerging concept in lung cancer, there is little consensus yet as to which blood biomarkers — whether CTCs, circulating tumor DNA (ctDNA), or extracellular vesicles (EVs) — are most clinically relevant, Dr. Nagrath said.
The study’s small size is one of its weaknesses, according to the authors.
Findings are ‘Particularly Intriguing’
Majid Ebrahimi Warkiani, PhD, who was not involved in the study, described the new findings as “particularly intriguing [and] highlighting the efficacy of liquid biopsy using CTCs for predicting treatment outcomes.”
A challenge within the realm of CTCs lies in the community’s ongoing struggle to define and classify these cells accurately, Dr. Warkiani said in an interview.
“While surface protein markers offer valuable insights, emerging layers of analysis, such as metabolomics, are increasingly entering the scene to bolster the identification of putative cancer cells, alongside molecular tests like fluorescence in situ hybridization (FISH),” said Dr. Warkiani of the University of Technology Sydney in Australia. “The amalgamation of these approaches simultaneously presents a significant challenge, particularly in terms of standardization for patient care, unlike ctDNA, which faces fewer bottlenecks.
“The robustness of the research in this study is commendable. However, further clinical testing and randomized trials are imperative,” Dr. Warkiani continued. “Companies like Epic Sciences are actively engaged in advancing research and standardization in this field.”
The study by Dr. Jolly and Dr. Nagrath was funded by the National Institutes of Health. None of the study authors reported financial conflicts of interest. Dr. Warkiani reported no conflicts of interest related to his comment.
Circulating tumor cells (CTCs), the cells shed from a solid tumor into the bloodstream, may help doctors avoid having to do repeat needle biopsies on patients with unresectable non–small cell lung cancer.
Challenges to using CTCs clinically are that they are not abundant in the blood and have been difficult to isolate in patients with this type of cancer with commercially available assays.
In their paper, the authors show that an experimental nanotechnology can effectively isolate and measure CTCs in patients with stage 3 NSCLC. They also found that a precipitous drop in CTCs during chemoradiation treatment predicted significantly longer progression-free survival in those patients.
Study Results and Methods
For their research, study coauthors Shruti Jolly, MD, and Sunitha Nagrath, PhD, used a novel graphene oxide technology called the GO chip, developed more than a decade ago by Dr. Nagrath and her colleagues, to isolate CTCs from patients with stage 3 NSCLC. While a different technology, which is approved by the US Food and Drug Administration (FDA), uses a single antibody to pick up CTCs, the GO chip uses a cocktail of three antibodies to CTC proteins, making it more sensitive.
The 26 patients in the study (mean age 67, 27% female) all received radiation treatment for 6 weeks, plus weekly carboplatin and paclitaxel chemotherapy. Sixteen of the patients afterward went on to have immunotherapy with durvalumab. Blood was drawn at six fixed time points: before treatment, and at weeks 1, 4, 10, 18, and 30. CTCs were measured and analyzed with every draw.
Previous studies showed that absolute number of CTCs did not correlate with either tumor volume or progression-free survival in NSCLC.
Dr. Jolly and Dr. Nagrath sought to measure change in CTCs from baseline for each patient, having the patient serve as his or her own control. They found that patients whose individual CTC counts dropped by 75% or more between pretreatment and week 4 of chemoradiation saw a mean 21 months of progression-free survival compared with 7 months for patients whose CTCs dropped by less than 75% in the same period (P = .0076).
Dr. Jolly and Dr. Nagrath also aimed to determine, as an exploratory outcome of their study, whether other information collected from the CTCs could predict response to treatment with durvalumab immunotherapy. They found that having more than 50% of CTCs positive for the protein PD-L1 correlated to shorter progression-free survival among the 16 patients receiving durvalumab (P = .04).
“Every person’s tumor is unique in terms of its response to treatment,” said Dr. Jolly, a radiation oncologist and professor and associate chair of community practices in the Department of Radiation Oncology at the University of Michigan, Ann Arbor.
“Two people with a three-centimeter lung tumor will not necessarily shed the same amount of tumor cells into circulation. CTCs are reflective of disease burden; however, this is not related to the absolute numbers. That’s why we decided to use individualized baselines and look at the percentage of decrease,” she said.
Dr. Nagrath, professor of chemical and biomedical engineering at the University of Michigan, noted, in the same interview, that the findings argue for CTCs as a biomarker in stage 3 NSCLC.
“A lot of researchers who do lung cancer studies struggle with isolating lung cancer CTCs,” Dr. Nagrath said. “We showed, with repeated blood draws during treatment, what is changing at a molecular level and that you can see it with a simple blood draw. It also gives the proof of concept that if these cells are present, this is a good way to monitor and see if a treatment is working, even early in the treatment.” Moreover, she added, “many studies in lung cancer are in stage 4.”
Our study is unique as it followed patients with locally advanced tumors from their being treatment naive to all the way through immunotherapy,” she continued.
The University of Michigan has a patent on the GO chip technology, but thus far no company has made efforts to license it and submit it for approval. While “liquid biopsy” is an important emerging concept in lung cancer, there is little consensus yet as to which blood biomarkers — whether CTCs, circulating tumor DNA (ctDNA), or extracellular vesicles (EVs) — are most clinically relevant, Dr. Nagrath said.
The study’s small size is one of its weaknesses, according to the authors.
Findings are ‘Particularly Intriguing’
Majid Ebrahimi Warkiani, PhD, who was not involved in the study, described the new findings as “particularly intriguing [and] highlighting the efficacy of liquid biopsy using CTCs for predicting treatment outcomes.”
A challenge within the realm of CTCs lies in the community’s ongoing struggle to define and classify these cells accurately, Dr. Warkiani said in an interview.
“While surface protein markers offer valuable insights, emerging layers of analysis, such as metabolomics, are increasingly entering the scene to bolster the identification of putative cancer cells, alongside molecular tests like fluorescence in situ hybridization (FISH),” said Dr. Warkiani of the University of Technology Sydney in Australia. “The amalgamation of these approaches simultaneously presents a significant challenge, particularly in terms of standardization for patient care, unlike ctDNA, which faces fewer bottlenecks.
“The robustness of the research in this study is commendable. However, further clinical testing and randomized trials are imperative,” Dr. Warkiani continued. “Companies like Epic Sciences are actively engaged in advancing research and standardization in this field.”
The study by Dr. Jolly and Dr. Nagrath was funded by the National Institutes of Health. None of the study authors reported financial conflicts of interest. Dr. Warkiani reported no conflicts of interest related to his comment.
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<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>166881</fileName> <TBEID>0C04E79C.SIG</TBEID> <TBUniqueIdentifier>MD_0C04E79C</TBUniqueIdentifier> <newsOrJournal>News</newsOrJournal> <publisherName>Frontline Medical Communications</publisherName> <storyname>CTCs story</storyname> <articleType>2</articleType> <TBLocation>QC Done-All Pubs</TBLocation> <QCDate>20240209T123117</QCDate> <firstPublished>20240209T124813</firstPublished> <LastPublished>20240209T124813</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20240209T124813</CMSDate> <articleSource>FROM CELL REPORTS</articleSource> <facebookInfo/> <meetingNumber/> <byline>Jennie Smith</byline> <bylineText>JENNIE SMITH</bylineText> <bylineFull>JENNIE SMITH</bylineFull> <bylineTitleText>MDedge News</bylineTitleText> <USOrGlobal/> <wireDocType/> <newsDocType>News</newsDocType> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:imng"> <name>IMNG Medical Media</name> <rightsInfo> <copyrightHolder> <name>Frontline Medical News</name> </copyrightHolder> <copyrightNotice>Copyright (c) 2015 Frontline Medical News, a Frontline Medical Communications Inc. company. All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>New research published in Cell Reports may bring doctors closer to using CTCs as a biomarker for patients with non–small cell lung cancer (NSCLC) in clinic.</metaDescription> <articlePDF/> <teaserImage/> <teaser>New research may bring doctors closer to using CTCs as a biomarker for patients with non-small cell lung cancer in clinic.</teaser> <title>Circulating Tumor Cells Can Predict Progression in Stage 3 NSCLC</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>oncr</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>chph</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">31</term> <term>6</term> </publications> <sections> <term>39313</term> <term canonical="true">27970</term> <term>27980</term> </sections> <topics> <term canonical="true">240</term> <term>270</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Circulating Tumor Cells Can Predict Progression in Stage 3 NSCLC</title> <deck/> </itemMeta> <itemContent> <p>Circulating tumor cells (CTCs), the cells shed from a solid tumor into the bloodstream, may help doctors avoid having to do repeat needle biopsies on patients with unresectable non–small cell lung cancer.<br/><br/>Challenges to using CTCs clinically are that they are not abundant in the blood and have been difficult to isolate in patients with this type of cancer with commercially available assays. <br/><br/><span class="tag metaDescription">New <a href="https://doi.org/10.1016/j.celrep.2024.113687">research</a> published in <em>Cell Reports</em> may bring doctors closer to using CTCs as a biomarker for patients with non–small cell lung cancer (NSCLC) in clinic.</span> In their paper, the authors show that an experimental nanotechnology can effectively isolate and measure CTCs in patients with stage 3 NSCLC. They also found that a precipitous drop in CTCs during chemoradiation treatment predicted significantly longer progression-free survival in those patients.<br/><br/></p> <h2>Study Results and Methods</h2> <p>For their research, study coauthors <a href="https://medicine.umich.edu/dept/radonc/shruti-jolly-md">Shruti Jolly</a>, MD, and <a href="https://che.engin.umich.edu/people/nagrath-sunitha/">Sunitha Nagrath</a>, PhD, used a novel graphene oxide technology called the GO chip, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4017624/">developed more than a decade ago</a> by Dr. Nagrath and her colleagues, to isolate CTCs from patients with stage 3 NSCLC. While a different technology, which is approved by the US Food and Drug Administration (FDA), uses a single antibody to pick up CTCs, the GO chip uses a cocktail of three antibodies to CTC proteins, making it more sensitive. </p> <p>The 26 patients in the study (mean age 67, 27% female) all received radiation treatment for 6 weeks, plus weekly carboplatin and paclitaxel chemotherapy. Sixteen of the patients afterward went on to have immunotherapy with durvalumab. Blood was drawn at six fixed time points: before treatment, and at weeks 1, 4, 10, 18, and 30. CTCs were measured and analyzed with every draw. <br/><br/>Previous studies showed that absolute number of CTCs did not correlate with either tumor volume or progression-free survival in NSCLC. <br/><br/>Dr. Jolly and Dr. Nagrath sought to measure change in CTCs from baseline for each patient, having the patient serve as his or her own control. They found that patients whose individual CTC counts dropped by 75% or more between pretreatment and week 4 of chemoradiation saw a mean 21 months of progression-free survival compared with 7 months for patients whose CTCs dropped by less than 75% in the same period (<em>P</em> = .0076). <br/><br/>Dr. Jolly and Dr. Nagrath also aimed to determine, as an exploratory outcome of their study, whether other information collected from the CTCs could predict response to treatment with durvalumab immunotherapy. They found that having more than 50% of CTCs positive for the protein PD-L1 correlated to shorter progression-free survival among the 16 patients receiving durvalumab (<em>P</em> = .04). <br/><br/>“Every person’s tumor is unique in terms of its response to treatment,” said Dr. Jolly, a radiation oncologist and professor and associate chair of community practices in the Department of Radiation Oncology at the University of Michigan, Ann Arbor. <br/><br/>“Two people with a three-centimeter lung tumor will not necessarily shed the same amount of tumor cells into circulation. CTCs are reflective of disease burden; however, this is not related to the absolute numbers. That’s why we decided to use individualized baselines and look at the percentage of decrease,” she said.<br/><br/>Dr. Nagrath, professor of chemical and biomedical engineering at the University of Michigan, noted, in the same interview, that the findings argue for CTCs as a biomarker in stage 3 NSCLC. <br/><br/>“A lot of researchers who do lung cancer studies struggle with isolating lung cancer CTCs,” Dr. Nagrath said. “We showed, with repeated blood draws during treatment, what is changing at a molecular level and that you can see it with a simple blood draw. It also gives the proof of concept that if these cells are present, this is a good way to monitor and see if a treatment is working, even early in the treatment.” Moreover, she added, “many studies in lung cancer are in stage 4.”<br/><br/>Our study is unique as it followed patients with locally advanced tumors from their being treatment naive to all the way through immunotherapy,” she continued.<br/><br/>The University of Michigan has a patent on the GO chip technology, but thus far no company has made efforts to license it and submit it for approval. While “liquid biopsy” is an important emerging concept in lung cancer, there is little consensus yet as to which blood biomarkers — whether CTCs, circulating tumor DNA (ctDNA), or extracellular vesicles (EVs) — are most clinically relevant, Dr. Nagrath said.<br/><br/>The study’s small size is one of its weaknesses, according to the authors.<br/><br/></p> <h2>Findings are ‘Particularly Intriguing’</h2> <p><a href="https://profiles.uts.edu.au/Majid.Warkiani">Majid Ebrahimi Warkiani</a>, PhD, who was not involved in the study, described the new findings as “particularly intriguing [and] highlighting the efficacy of liquid biopsy using CTCs for predicting treatment outcomes.”</p> <p>A challenge within the realm of CTCs lies in the community’s ongoing struggle to define and classify these cells accurately, Dr. Warkiani said in an interview.<br/><br/>“While surface protein markers offer valuable insights, emerging layers of analysis, such as metabolomics, are increasingly entering the scene to bolster the identification of putative cancer cells, alongside molecular tests like fluorescence in situ hybridization (FISH),” said Dr. Warkiani of the University of Technology Sydney in Australia. “The amalgamation of these approaches simultaneously presents a significant challenge, particularly in terms of standardization for patient care, unlike ctDNA, which faces fewer bottlenecks.<br/><br/>“The robustness of the research in this study is commendable. However, further clinical testing and randomized trials are imperative,” Dr. Warkiani continued. “Companies like Epic Sciences are actively engaged in advancing research and standardization in this field.”<br/><br/>The study by Dr. Jolly and Dr. Nagrath was funded by the National Institutes of Health. None of the study authors reported financial conflicts of interest. Dr. Warkiani reported no conflicts of interest related to his comment. </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
FROM CELL REPORTS