NET Blood Transcript Analysis Defines the Crossing of the Clinical Rubicon: When Stable Disease Becomes Progressive
Background/Aims: A key issue in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is early identification and prediction of disease progression. Clinical evaluation and imaging are limited due to the lack of sensitivity and disease indolence. We assessed the NETest as a predictive and prognost...
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| Veröffentlicht in: | Neuroendocrinology 2017-01, Vol.104 (2), p.170-182 |
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| description | Background/Aims: A key issue in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is early identification and prediction of disease progression. Clinical evaluation and imaging are limited due to the lack of sensitivity and disease indolence. We assessed the NETest as a predictive and prognostic marker of progression in a long-term follow-up study. Methods: GEP-NETs (n = 34) followed for a median 4 years (2.2-5.4) were evaluated. WHO tumor grade/stage grade 1: n = 17, grade 2: n = 14, grade 3: n = 1 (for 2, no grade was available); 31 (91%) were stage IV. Baseline and longitudinal imaging and blood biomarkers were available in all, and progression was defined per standard clinical protocols (RECIST 1.0). The NETest was measured by quantitative PCR of blood and multianalyte algorithmic analysis (disease activity scaled 0-100% with low 80%); chromogranin A (CgA) was measured by radioimmunoassay (normal 80%) was significantly associated (p = 0.01) with disease progression (median PFS 0.68 vs. 2.78 years with 25%) in consistently predicting disease alterations (40%, p < 2 × 10 -5 , χ 2 = 18). The NETest had an earlier time point change than imaging (1.02 ± 0.15 years). Baseline NETest levels >40% in stable disease were 100% prognostic of disease progression versus CgA (χ 2 = 5, p < 0.03). Baseline NETest values |
| doi_str_mv | 10.1159/000446025 |
| format | Article |
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Clinical evaluation and imaging are limited due to the lack of sensitivity and disease indolence. We assessed the NETest as a predictive and prognostic marker of progression in a long-term follow-up study. Methods: GEP-NETs (n = 34) followed for a median 4 years (2.2-5.4) were evaluated. WHO tumor grade/stage grade 1: n = 17, grade 2: n = 14, grade 3: n = 1 (for 2, no grade was available); 31 (91%) were stage IV. Baseline and longitudinal imaging and blood biomarkers were available in all, and progression was defined per standard clinical protocols (RECIST 1.0). The NETest was measured by quantitative PCR of blood and multianalyte algorithmic analysis (disease activity scaled 0-100% with low <40% and high activity risk cutoffs >80%); chromogranin A (CgA) was measured by radioimmunoassay (normal <150 µg/l); progression-free survival (PFS) was analyzed by Cox proportional-hazard regression and Kaplan-Meier analysis. Results: At baseline, 100% were NETest positive, and CgA was elevated in 50%. The only baseline variable (Cox modeling) associated with PFS was NETest (hazard ratio = 1.022, 95% confidence interval = 1.005-1.04; p < 0.012). Using Kaplan-Meier analyses, the baseline NETest (>80%) was significantly associated (p = 0.01) with disease progression (median PFS 0.68 vs. 2.78 years with <40% levels). The NETest was more informative (96%) than CgA changes ( > 25%) in consistently predicting disease alterations (40%, p < 2 × 10 -5 , χ 2 = 18). The NETest had an earlier time point change than imaging (1.02 ± 0.15 years). Baseline NETest levels >40% in stable disease were 100% prognostic of disease progression versus CgA (χ 2 = 5, p < 0.03). Baseline NETest values <40% accurately (100%) predicted stability over 5 years (p = 0.05, χ 2 = 3.8 vs. CgA). Conclusion: The NETest correlated with a well-differentiated GEP-NET clinical status. The NETest has predictive and prognostic utility for GEP-NETs identifying clinically actionable alterations ∼1 year before image-based evidence of progression.]]></description><identifier>ISSN: 0028-3835</identifier><identifier>EISSN: 1423-0194</identifier><identifier>DOI: 10.1159/000446025</identifier><identifier>PMID: 27078712</identifier><language>eng</language><publisher>Basel, Switzerland: S. Karger AG</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Biological markers ; Biomarkers, Tumor - blood ; Biomarkers, Tumor - genetics ; Cancer ; Development and progression ; Diagnosis ; Disease Progression ; Disease-Free Survival ; Female ; Follow-Up Studies ; Gastrointestinal Neoplasms - blood ; Gastrointestinal Neoplasms - diagnosis ; Gastrointestinal Neoplasms - genetics ; Gastrointestinal Neoplasms - pathology ; Gastrointestinal tumors ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Neuroendocrine Tumors - blood ; Neuroendocrine Tumors - diagnosis ; Neuroendocrine Tumors - genetics ; Neuroendocrine Tumors - pathology ; Oncology, Experimental ; Original Paper ; Pancreatic Neoplasms - blood ; Pancreatic Neoplasms - diagnosis ; Pancreatic Neoplasms - genetics ; Pancreatic Neoplasms - pathology ; Prognosis ; Real-Time Polymerase Chain Reaction</subject><ispartof>Neuroendocrinology, 2017-01, Vol.104 (2), p.170-182</ispartof><rights>2016 S. Karger AG, Basel</rights><rights>2016 S. Karger AG, Basel.</rights><rights>COPYRIGHT 2016 S. Karger AG</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c441t-1340ee95d63c03bc066fa5f213c16441b82eae9a0c109a7c4179495a8b1643b03</citedby><cites>FETCH-LOGICAL-c441t-1340ee95d63c03bc066fa5f213c16441b82eae9a0c109a7c4179495a8b1643b03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2429,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27078712$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pavel, Marianne</creatorcontrib><creatorcontrib>Jann, Henning</creatorcontrib><creatorcontrib>Prasad, Vikas</creatorcontrib><creatorcontrib>Drozdov, Ignat</creatorcontrib><creatorcontrib>Modlin, Irvin M.</creatorcontrib><creatorcontrib>Kidd, Mark</creatorcontrib><title>NET Blood Transcript Analysis Defines the Crossing of the Clinical Rubicon: When Stable Disease Becomes Progressive</title><title>Neuroendocrinology</title><addtitle>Neuroendocrinology</addtitle><description><![CDATA[Background/Aims: A key issue in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is early identification and prediction of disease progression. Clinical evaluation and imaging are limited due to the lack of sensitivity and disease indolence. We assessed the NETest as a predictive and prognostic marker of progression in a long-term follow-up study. Methods: GEP-NETs (n = 34) followed for a median 4 years (2.2-5.4) were evaluated. WHO tumor grade/stage grade 1: n = 17, grade 2: n = 14, grade 3: n = 1 (for 2, no grade was available); 31 (91%) were stage IV. Baseline and longitudinal imaging and blood biomarkers were available in all, and progression was defined per standard clinical protocols (RECIST 1.0). The NETest was measured by quantitative PCR of blood and multianalyte algorithmic analysis (disease activity scaled 0-100% with low <40% and high activity risk cutoffs >80%); chromogranin A (CgA) was measured by radioimmunoassay (normal <150 µg/l); progression-free survival (PFS) was analyzed by Cox proportional-hazard regression and Kaplan-Meier analysis. Results: At baseline, 100% were NETest positive, and CgA was elevated in 50%. The only baseline variable (Cox modeling) associated with PFS was NETest (hazard ratio = 1.022, 95% confidence interval = 1.005-1.04; p < 0.012). Using Kaplan-Meier analyses, the baseline NETest (>80%) was significantly associated (p = 0.01) with disease progression (median PFS 0.68 vs. 2.78 years with <40% levels). The NETest was more informative (96%) than CgA changes ( > 25%) in consistently predicting disease alterations (40%, p < 2 × 10 -5 , χ 2 = 18). The NETest had an earlier time point change than imaging (1.02 ± 0.15 years). Baseline NETest levels >40% in stable disease were 100% prognostic of disease progression versus CgA (χ 2 = 5, p < 0.03). Baseline NETest values <40% accurately (100%) predicted stability over 5 years (p = 0.05, χ 2 = 3.8 vs. CgA). Conclusion: The NETest correlated with a well-differentiated GEP-NET clinical status. The NETest has predictive and prognostic utility for GEP-NETs identifying clinically actionable alterations ∼1 year before image-based evidence of progression.]]></description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biological markers</subject><subject>Biomarkers, Tumor - blood</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Cancer</subject><subject>Development and progression</subject><subject>Diagnosis</subject><subject>Disease Progression</subject><subject>Disease-Free Survival</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Gastrointestinal Neoplasms - blood</subject><subject>Gastrointestinal Neoplasms - diagnosis</subject><subject>Gastrointestinal Neoplasms - genetics</subject><subject>Gastrointestinal Neoplasms - pathology</subject><subject>Gastrointestinal tumors</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neoplasm Grading</subject><subject>Neuroendocrine Tumors - blood</subject><subject>Neuroendocrine Tumors - diagnosis</subject><subject>Neuroendocrine Tumors - genetics</subject><subject>Neuroendocrine Tumors - pathology</subject><subject>Oncology, Experimental</subject><subject>Original Paper</subject><subject>Pancreatic Neoplasms - blood</subject><subject>Pancreatic Neoplasms - diagnosis</subject><subject>Pancreatic Neoplasms - genetics</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Prognosis</subject><subject>Real-Time Polymerase Chain Reaction</subject><issn>0028-3835</issn><issn>1423-0194</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpF0c1vFCEYBnBiNHatHno3hmN7GOVrmMHb7rZqk6Y17ZoeCcO-M0VZ2MKMsf-9NLuuJ0L48YSXB6ETSj5SWqtPhBAhJGH1CzSjgvGKUCVeohkhrK14y-sj9Cbnn4UxxdlrdMQa0rQNZTOUry9WeOFjXONVMiHb5LYjngfjn7LL-Bx6FyDj8QHwMsWcXRhw7Hd774KzxuPbqXM2hs_4_gECvhtN5wGfuwwmA16AjZuS8D3FIUEJ-A1v0ave-Azv9usx-vHlYrX8Vl3dfL1czq8qKwQdK8oFAVD1WnJLeGeJlL2pe0a5pbKIrmVgQBliKVGmsYI2SqjatF055h3hx-h0l7tN8XGCPOqNyxa8NwHilDVtmZSyaVpV6NmODsaDdqGMM8KfcTBTzvry7lbPJW84U6ol_619_pAEvd4mtzHpSVOin_vQhz6K_bB_wtRtYH2Q_woo4P0O_DJpgHQA-_t_AVFFjE4</recordid><startdate>20170101</startdate><enddate>20170101</enddate><creator>Pavel, Marianne</creator><creator>Jann, Henning</creator><creator>Prasad, Vikas</creator><creator>Drozdov, Ignat</creator><creator>Modlin, Irvin M.</creator><creator>Kidd, Mark</creator><general>S. Karger AG</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>ISR</scope><scope>7X8</scope></search><sort><creationdate>20170101</creationdate><title>NET Blood Transcript Analysis Defines the Crossing of the Clinical Rubicon: When Stable Disease Becomes Progressive</title><author>Pavel, Marianne ; Jann, Henning ; Prasad, Vikas ; Drozdov, Ignat ; Modlin, Irvin M. ; Kidd, Mark</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c441t-1340ee95d63c03bc066fa5f213c16441b82eae9a0c109a7c4179495a8b1643b03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biological markers</topic><topic>Biomarkers, Tumor - blood</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Cancer</topic><topic>Development and progression</topic><topic>Diagnosis</topic><topic>Disease Progression</topic><topic>Disease-Free Survival</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Gastrointestinal Neoplasms - blood</topic><topic>Gastrointestinal Neoplasms - diagnosis</topic><topic>Gastrointestinal Neoplasms - genetics</topic><topic>Gastrointestinal Neoplasms - pathology</topic><topic>Gastrointestinal tumors</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neoplasm Grading</topic><topic>Neuroendocrine Tumors - blood</topic><topic>Neuroendocrine Tumors - diagnosis</topic><topic>Neuroendocrine Tumors - genetics</topic><topic>Neuroendocrine Tumors - pathology</topic><topic>Oncology, Experimental</topic><topic>Original Paper</topic><topic>Pancreatic Neoplasms - blood</topic><topic>Pancreatic Neoplasms - diagnosis</topic><topic>Pancreatic Neoplasms - genetics</topic><topic>Pancreatic Neoplasms - pathology</topic><topic>Prognosis</topic><topic>Real-Time Polymerase Chain Reaction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pavel, Marianne</creatorcontrib><creatorcontrib>Jann, Henning</creatorcontrib><creatorcontrib>Prasad, Vikas</creatorcontrib><creatorcontrib>Drozdov, Ignat</creatorcontrib><creatorcontrib>Modlin, Irvin M.</creatorcontrib><creatorcontrib>Kidd, Mark</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>MEDLINE - Academic</collection><jtitle>Neuroendocrinology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pavel, Marianne</au><au>Jann, Henning</au><au>Prasad, Vikas</au><au>Drozdov, Ignat</au><au>Modlin, Irvin M.</au><au>Kidd, Mark</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>NET Blood Transcript Analysis Defines the Crossing of the Clinical Rubicon: When Stable Disease Becomes Progressive</atitle><jtitle>Neuroendocrinology</jtitle><addtitle>Neuroendocrinology</addtitle><date>2017-01-01</date><risdate>2017</risdate><volume>104</volume><issue>2</issue><spage>170</spage><epage>182</epage><pages>170-182</pages><issn>0028-3835</issn><eissn>1423-0194</eissn><abstract><![CDATA[Background/Aims: A key issue in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is early identification and prediction of disease progression. Clinical evaluation and imaging are limited due to the lack of sensitivity and disease indolence. We assessed the NETest as a predictive and prognostic marker of progression in a long-term follow-up study. Methods: GEP-NETs (n = 34) followed for a median 4 years (2.2-5.4) were evaluated. WHO tumor grade/stage grade 1: n = 17, grade 2: n = 14, grade 3: n = 1 (for 2, no grade was available); 31 (91%) were stage IV. Baseline and longitudinal imaging and blood biomarkers were available in all, and progression was defined per standard clinical protocols (RECIST 1.0). The NETest was measured by quantitative PCR of blood and multianalyte algorithmic analysis (disease activity scaled 0-100% with low <40% and high activity risk cutoffs >80%); chromogranin A (CgA) was measured by radioimmunoassay (normal <150 µg/l); progression-free survival (PFS) was analyzed by Cox proportional-hazard regression and Kaplan-Meier analysis. Results: At baseline, 100% were NETest positive, and CgA was elevated in 50%. The only baseline variable (Cox modeling) associated with PFS was NETest (hazard ratio = 1.022, 95% confidence interval = 1.005-1.04; p < 0.012). Using Kaplan-Meier analyses, the baseline NETest (>80%) was significantly associated (p = 0.01) with disease progression (median PFS 0.68 vs. 2.78 years with <40% levels). The NETest was more informative (96%) than CgA changes ( > 25%) in consistently predicting disease alterations (40%, p < 2 × 10 -5 , χ 2 = 18). The NETest had an earlier time point change than imaging (1.02 ± 0.15 years). Baseline NETest levels >40% in stable disease were 100% prognostic of disease progression versus CgA (χ 2 = 5, p < 0.03). Baseline NETest values <40% accurately (100%) predicted stability over 5 years (p = 0.05, χ 2 = 3.8 vs. CgA). Conclusion: The NETest correlated with a well-differentiated GEP-NET clinical status. The NETest has predictive and prognostic utility for GEP-NETs identifying clinically actionable alterations ∼1 year before image-based evidence of progression.]]></abstract><cop>Basel, Switzerland</cop><pub>S. Karger AG</pub><pmid>27078712</pmid><doi>10.1159/000446025</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Aged, 80 and over Biological markers Biomarkers, Tumor - blood Biomarkers, Tumor - genetics Cancer Development and progression Diagnosis Disease Progression Disease-Free Survival Female Follow-Up Studies Gastrointestinal Neoplasms - blood Gastrointestinal Neoplasms - diagnosis Gastrointestinal Neoplasms - genetics Gastrointestinal Neoplasms - pathology Gastrointestinal tumors Humans Male Middle Aged Neoplasm Grading Neuroendocrine Tumors - blood Neuroendocrine Tumors - diagnosis Neuroendocrine Tumors - genetics Neuroendocrine Tumors - pathology Oncology, Experimental Original Paper Pancreatic Neoplasms - blood Pancreatic Neoplasms - diagnosis Pancreatic Neoplasms - genetics Pancreatic Neoplasms - pathology Prognosis Real-Time Polymerase Chain Reaction |
| title | NET Blood Transcript Analysis Defines the Crossing of the Clinical Rubicon: When Stable Disease Becomes Progressive |
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