Pathologic and gene expression comparison of CT- screen detected and routinely detected stage I/0 lung adenocarcinoma in NCCN risk-matched cohorts.
Introduction: Although three randomized control trials have proven mortality benefit of CT lung cancer screening (CTLS), <5% of eligible US smokers are screened. Some attribute this to fear of harm conveyed at shared decision visits, including the harm of overdiagnosis/overtreatment of indolent B...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-01-01
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| Series: | Cancer Treatment and Research Communications |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468294221001829 |
| _version_ | 1818871919404908544 |
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| author | Eric J. Burks Jiarui Zhang Travis B. Sullivan Xingyi Shi Jacob M. Sands Shawn M. Regis Brady J. McKee Andrea B. McKee Sherry Zhang Hanqiao Liu Gang Liu Avrum Spira Jennifer Beane Marc E. Lenburg Kimberly M. Rieger-Christ |
| author_facet | Eric J. Burks Jiarui Zhang Travis B. Sullivan Xingyi Shi Jacob M. Sands Shawn M. Regis Brady J. McKee Andrea B. McKee Sherry Zhang Hanqiao Liu Gang Liu Avrum Spira Jennifer Beane Marc E. Lenburg Kimberly M. Rieger-Christ |
| author_sort | Eric J. Burks |
| collection | DOAJ |
| description | Introduction: Although three randomized control trials have proven mortality benefit of CT lung cancer screening (CTLS), <5% of eligible US smokers are screened. Some attribute this to fear of harm conveyed at shared decision visits, including the harm of overdiagnosis/overtreatment of indolent BAC-like adenocarcinoma. Methods: Since the frequency of indolent cancers has not been compared between CTLS and routinely detected cohorts, we compare pathology and RNA expression of 86 NCCN high-risk CTLS subjects to 83 high-risk (HR-R) and 51 low-risk (LR-R) routinely detected patients. Indolent adenocarcinoma was defined as previously described for low malignant potential (LMP) adenocarcinoma along with AIS/MIA. Exome RNA sequencing was performed on a subset of high-risk (CTLS and HR-R) FFPE tumor samples. Results: Indolent adenocarcinoma (AIS, MIA, and LMP) showed 100% disease-specific survival (DSS) with similar frequency in CTLS (18%) and HR-R (20%) which were comparatively lower than LR-R (33%). Despite this observation, CTLS exhibited intermediate DSS between HR-R and LR-R (5-year DSS: 88% CTLS, 82% HR-R, & 95% LR-R, p = 0.047), possibly reflecting a 0.4 cm smaller median tumor size and lower frequency of tumor necrosis compared to HR-R. WGCNA gene modules derived from TCGA lung adenocarcinoma correlated with aggressive histologic patterns, mitotic activity, and tumor invasive features, but no significant differential expression between CTLS and HR-R was observed. Conclusion: CTLS subjects are at no greater risk of overdiagnosis from indolent adenocarcinoma (AIS, MIA, and LMP) than risk-matched patients whose cancers are discovered in routine clinical practice. Improved outcomes likely reflect detection and treatment at smaller size. |
| first_indexed | 2024-12-19T12:30:34Z |
| format | Article |
| id | doaj.art-7f40f578a6cf4273bbca14d5b6c2ced3 |
| institution | Directory Open Access Journal |
| issn | 2468-2942 |
| language | English |
| last_indexed | 2024-12-19T12:30:34Z |
| publishDate | 2021-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cancer Treatment and Research Communications |
| spelling | doaj.art-7f40f578a6cf4273bbca14d5b6c2ced32022-12-21T20:21:24ZengElsevierCancer Treatment and Research Communications2468-29422021-01-0129100486Pathologic and gene expression comparison of CT- screen detected and routinely detected stage I/0 lung adenocarcinoma in NCCN risk-matched cohorts.Eric J. Burks0Jiarui Zhang1Travis B. Sullivan2Xingyi Shi3Jacob M. Sands4Shawn M. Regis5Brady J. McKee6Andrea B. McKee7Sherry Zhang8Hanqiao Liu9Gang Liu10Avrum Spira11Jennifer Beane12Marc E. Lenburg13Kimberly M. Rieger-Christ14Department of Pathology, Lahey Hospital & Medical Center, Burlington, MA, United States of AmericaDepartment of Medicine Section of Computational Biomedicine, Boston University School of Medicine, Boston, MA, United States of AmericaDepartment of Translational Research, Ian C. Summerhayes Cell and Molecular Biology Laboratory, Lahey Hospital & Medical Center, Burlington, MA, United States of AmericaDepartment of Medicine Section of Computational Biomedicine, Boston University School of Medicine, Boston, MA, United States of AmericaDepartment of Hematology and Oncology, Lahey Hospital & Medical Center, Burlington, MA, United States of AmericaDepartment of Radiation Oncology, Lahey Hospital & Medical Center, Burlington, MA, United States of AmericaDepartment of Radiology, Lahey Hospital & Medical Center, Burlington, MA, United States of AmericaDepartment of Radiation Oncology, Lahey Hospital & Medical Center, Burlington, MA, United States of AmericaDepartment of Medicine Section of Computational Biomedicine, Boston University School of Medicine, Boston, MA, United States of AmericaDepartment of Medicine Section of Computational Biomedicine, Boston University School of Medicine, Boston, MA, United States of AmericaDepartment of Medicine Section of Computational Biomedicine, Boston University School of Medicine, Boston, MA, United States of AmericaDepartment of Medicine Section of Computational Biomedicine, Boston University School of Medicine, Boston, MA, United States of America; Johnson and Johnson Innovation, Cambridge, MA, United States of AmericaDepartment of Medicine Section of Computational Biomedicine, Boston University School of Medicine, Boston, MA, United States of AmericaDepartment of Medicine Section of Computational Biomedicine, Boston University School of Medicine, Boston, MA, United States of America; Department of Pathology & Laboratory Medicine, Boston University School of Medicine, Boston Medical Center, Boston, MA, United States of AmericaDepartment of Translational Research, Ian C. Summerhayes Cell and Molecular Biology Laboratory, Lahey Hospital & Medical Center, Burlington, MA, United States of America; Corresponding author at: Department of Translational Research Lahey Hospital & Medical Center 41 Mall Road, Burlington, MA 01805 United States of AmericaIntroduction: Although three randomized control trials have proven mortality benefit of CT lung cancer screening (CTLS), <5% of eligible US smokers are screened. Some attribute this to fear of harm conveyed at shared decision visits, including the harm of overdiagnosis/overtreatment of indolent BAC-like adenocarcinoma. Methods: Since the frequency of indolent cancers has not been compared between CTLS and routinely detected cohorts, we compare pathology and RNA expression of 86 NCCN high-risk CTLS subjects to 83 high-risk (HR-R) and 51 low-risk (LR-R) routinely detected patients. Indolent adenocarcinoma was defined as previously described for low malignant potential (LMP) adenocarcinoma along with AIS/MIA. Exome RNA sequencing was performed on a subset of high-risk (CTLS and HR-R) FFPE tumor samples. Results: Indolent adenocarcinoma (AIS, MIA, and LMP) showed 100% disease-specific survival (DSS) with similar frequency in CTLS (18%) and HR-R (20%) which were comparatively lower than LR-R (33%). Despite this observation, CTLS exhibited intermediate DSS between HR-R and LR-R (5-year DSS: 88% CTLS, 82% HR-R, & 95% LR-R, p = 0.047), possibly reflecting a 0.4 cm smaller median tumor size and lower frequency of tumor necrosis compared to HR-R. WGCNA gene modules derived from TCGA lung adenocarcinoma correlated with aggressive histologic patterns, mitotic activity, and tumor invasive features, but no significant differential expression between CTLS and HR-R was observed. Conclusion: CTLS subjects are at no greater risk of overdiagnosis from indolent adenocarcinoma (AIS, MIA, and LMP) than risk-matched patients whose cancers are discovered in routine clinical practice. Improved outcomes likely reflect detection and treatment at smaller size.http://www.sciencedirect.com/science/article/pii/S2468294221001829Low malignant potential adenocarcinomaScreenOverdiagnosisRNA sequencingCTLS |
| spellingShingle | Eric J. Burks Jiarui Zhang Travis B. Sullivan Xingyi Shi Jacob M. Sands Shawn M. Regis Brady J. McKee Andrea B. McKee Sherry Zhang Hanqiao Liu Gang Liu Avrum Spira Jennifer Beane Marc E. Lenburg Kimberly M. Rieger-Christ Pathologic and gene expression comparison of CT- screen detected and routinely detected stage I/0 lung adenocarcinoma in NCCN risk-matched cohorts. Cancer Treatment and Research Communications Low malignant potential adenocarcinoma Screen Overdiagnosis RNA sequencing CTLS |
| title | Pathologic and gene expression comparison of CT- screen detected and routinely detected stage I/0 lung adenocarcinoma in NCCN risk-matched cohorts. |
| title_full | Pathologic and gene expression comparison of CT- screen detected and routinely detected stage I/0 lung adenocarcinoma in NCCN risk-matched cohorts. |
| title_fullStr | Pathologic and gene expression comparison of CT- screen detected and routinely detected stage I/0 lung adenocarcinoma in NCCN risk-matched cohorts. |
| title_full_unstemmed | Pathologic and gene expression comparison of CT- screen detected and routinely detected stage I/0 lung adenocarcinoma in NCCN risk-matched cohorts. |
| title_short | Pathologic and gene expression comparison of CT- screen detected and routinely detected stage I/0 lung adenocarcinoma in NCCN risk-matched cohorts. |
| title_sort | pathologic and gene expression comparison of ct screen detected and routinely detected stage i 0 lung adenocarcinoma in nccn risk matched cohorts |
| topic | Low malignant potential adenocarcinoma Screen Overdiagnosis RNA sequencing CTLS |
| url | http://www.sciencedirect.com/science/article/pii/S2468294221001829 |
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