A non-linear association between blood tumor mutation burden and prognosis in NSCLC patients receiving atezolizumab.
Identifieur interne : 000594 ( Main/Exploration ); précédent : 000593; suivant : 000595A non-linear association between blood tumor mutation burden and prognosis in NSCLC patients receiving atezolizumab.
Auteurs : Wei Nie [République populaire de Chine] ; Jie Qian [République populaire de Chine] ; Mi-Die Xu [République populaire de Chine] ; Kai Gu [République populaire de Chine] ; Fang-Fei Qian [République populaire de Chine] ; Min-Juan Hu [République populaire de Chine] ; Jun Lu [République populaire de Chine] ; Lu Gan [République populaire de Chine] ; Xue-Yan Zhang [République populaire de Chine] ; Shu-Hui Cao [République populaire de Chine] ; Jing-Wen Li [République populaire de Chine] ; Yue Wang [République populaire de Chine] ; Bo Zhang [République populaire de Chine] ; Shu-Yuan Wang [République populaire de Chine] ; Fang Hu [République populaire de Chine] ; Chang-Hui Li [République populaire de Chine] ; Hua Zhong [République populaire de Chine] ; Bao-Hui Han [République populaire de Chine]Source :
- Oncoimmunology [ 2162-4011 ] ; 2020.
Abstract
A significant association between high blood-based tumor mutational burden (bTMB) and improved progression-free survival (PFS) was observed in advanced non-small cell lung cancer (NSCLC) receiving atezolizumab. However, this result was unrepeatable in a recent prospective study. We hypothesized that there might be a non-linear association between bTMB and survival. This study used the clinical and genetic data from POPLAR (n = 105, training set) and OAK (n = 324, validation set) trials. The non-linear association between bTMB and survival was assessed using restricted cubic spline (RCS). The cutoff values for bTMB were calculated via X-tile software. Non-linear relationships were observed between bTMB and PFS and overall survival (OS) in RCS plots (both Pnon-linearity < 0.001). The optimal cutoff values of bTMB for predicting PFS and OS were 7 and 14 mutations/Mb, respectively. The median PFS and OS of patients with low and high bTMB were significantly longer than those of patients with medium bTMB in the training, validation, and combined sets. Low and high bTMB were also associated with longer PFS and OS in high-programmed death-ligand 1 (PD-L1) expression population. In conclusion, there was a positive non-linear association between bTMB and survival in NSCLC patients receiving atezolizumab. Patients with low bTMB could also derive benefit from immunotherapy.
DOI: 10.1080/2162402X.2020.1731072
PubMed: 32158623
PubMed Central: PMC7051187
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A non-linear association between blood tumor mutation burden and prognosis in NSCLC patients receiving atezolizumab.</title><author><name sortKey="Nie, Wei" sort="Nie, Wei" uniqKey="Nie W" first="Wei" last="Nie">Wei Nie</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Qian, Jie" sort="Qian, Jie" uniqKey="Qian J" first="Jie" last="Qian">Jie Qian</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Xu, Mi Die" sort="Xu, Mi Die" uniqKey="Xu M" first="Mi-Die" last="Xu">Mi-Die Xu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pathology & Biobank, Fudan University Shanghai Cancer Center, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pathology & Biobank, Fudan University Shanghai Cancer Center, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Gu, Kai" sort="Gu, Kai" uniqKey="Gu K" first="Kai" last="Gu">Kai Gu</name><affiliation wicri:level="1"><nlm:affiliation>Shanghai Applied Protein Technology Co., Ltd (APTBIO), Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Shanghai Applied Protein Technology Co., Ltd (APTBIO), Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Qian, Fang Fei" sort="Qian, Fang Fei" uniqKey="Qian F" first="Fang-Fei" last="Qian">Fang-Fei Qian</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Hu, Min Juan" sort="Hu, Min Juan" uniqKey="Hu M" first="Min-Juan" last="Hu">Min-Juan Hu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Lu, Jun" sort="Lu, Jun" uniqKey="Lu J" first="Jun" last="Lu">Jun Lu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Gan, Lu" sort="Gan, Lu" uniqKey="Gan L" first="Lu" last="Gan">Lu Gan</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Xue Yan" sort="Zhang, Xue Yan" uniqKey="Zhang X" first="Xue-Yan" last="Zhang">Xue-Yan Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Cao, Shu Hui" sort="Cao, Shu Hui" uniqKey="Cao S" first="Shu-Hui" last="Cao">Shu-Hui Cao</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Li, Jing Wen" sort="Li, Jing Wen" uniqKey="Li J" first="Jing-Wen" last="Li">Jing-Wen Li</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Yue" sort="Wang, Yue" uniqKey="Wang Y" first="Yue" last="Wang">Yue Wang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Bo" sort="Zhang, Bo" uniqKey="Zhang B" first="Bo" last="Zhang">Bo Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Shu Yuan" sort="Wang, Shu Yuan" uniqKey="Wang S" first="Shu-Yuan" last="Wang">Shu-Yuan Wang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Hu, Fang" sort="Hu, Fang" uniqKey="Hu F" first="Fang" last="Hu">Fang Hu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Li, Chang Hui" sort="Li, Chang Hui" uniqKey="Li C" first="Chang-Hui" last="Li">Chang-Hui Li</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Zhong, Hua" sort="Zhong, Hua" uniqKey="Zhong H" first="Hua" last="Zhong">Hua Zhong</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Han, Bao Hui" sort="Han, Bao Hui" uniqKey="Han B" first="Bao-Hui" last="Han">Bao-Hui Han</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32158623</idno><idno type="pmid">32158623</idno><idno type="doi">10.1080/2162402X.2020.1731072</idno><idno type="pmc">PMC7051187</idno><idno type="wicri:Area/Main/Corpus">000403</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000403</idno><idno type="wicri:Area/Main/Curation">000403</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000403</idno><idno type="wicri:Area/Main/Exploration">000403</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">A non-linear association between blood tumor mutation burden and prognosis in NSCLC patients receiving atezolizumab.</title><author><name sortKey="Nie, Wei" sort="Nie, Wei" uniqKey="Nie W" first="Wei" last="Nie">Wei Nie</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Qian, Jie" sort="Qian, Jie" uniqKey="Qian J" first="Jie" last="Qian">Jie Qian</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Xu, Mi Die" sort="Xu, Mi Die" uniqKey="Xu M" first="Mi-Die" last="Xu">Mi-Die Xu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pathology & Biobank, Fudan University Shanghai Cancer Center, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pathology & Biobank, Fudan University Shanghai Cancer Center, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Gu, Kai" sort="Gu, Kai" uniqKey="Gu K" first="Kai" last="Gu">Kai Gu</name><affiliation wicri:level="1"><nlm:affiliation>Shanghai Applied Protein Technology Co., Ltd (APTBIO), Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Shanghai Applied Protein Technology Co., Ltd (APTBIO), Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Qian, Fang Fei" sort="Qian, Fang Fei" uniqKey="Qian F" first="Fang-Fei" last="Qian">Fang-Fei Qian</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Hu, Min Juan" sort="Hu, Min Juan" uniqKey="Hu M" first="Min-Juan" last="Hu">Min-Juan Hu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Lu, Jun" sort="Lu, Jun" uniqKey="Lu J" first="Jun" last="Lu">Jun Lu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Gan, Lu" sort="Gan, Lu" uniqKey="Gan L" first="Lu" last="Gan">Lu Gan</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Xue Yan" sort="Zhang, Xue Yan" uniqKey="Zhang X" first="Xue-Yan" last="Zhang">Xue-Yan Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Cao, Shu Hui" sort="Cao, Shu Hui" uniqKey="Cao S" first="Shu-Hui" last="Cao">Shu-Hui Cao</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Li, Jing Wen" sort="Li, Jing Wen" uniqKey="Li J" first="Jing-Wen" last="Li">Jing-Wen Li</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Yue" sort="Wang, Yue" uniqKey="Wang Y" first="Yue" last="Wang">Yue Wang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Bo" sort="Zhang, Bo" uniqKey="Zhang B" first="Bo" last="Zhang">Bo Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Shu Yuan" sort="Wang, Shu Yuan" uniqKey="Wang S" first="Shu-Yuan" last="Wang">Shu-Yuan Wang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Hu, Fang" sort="Hu, Fang" uniqKey="Hu F" first="Fang" last="Hu">Fang Hu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Li, Chang Hui" sort="Li, Chang Hui" uniqKey="Li C" first="Chang-Hui" last="Li">Chang-Hui Li</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Zhong, Hua" sort="Zhong, Hua" uniqKey="Zhong H" first="Hua" last="Zhong">Hua Zhong</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Han, Bao Hui" sort="Han, Bao Hui" uniqKey="Han B" first="Bao-Hui" last="Han">Bao-Hui Han</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author></analytic><series><title level="j">Oncoimmunology</title><idno type="ISSN">2162-4011</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">A significant association between high blood-based tumor mutational burden (bTMB) and improved progression-free survival (PFS) was observed in advanced non-small cell lung cancer (NSCLC) receiving atezolizumab. However, this result was unrepeatable in a recent prospective study. We hypothesized that there might be a non-linear association between bTMB and survival. This study used the clinical and genetic data from POPLAR (n = 105, training set) and OAK (n = 324, validation set) trials. The non-linear association between bTMB and survival was assessed using restricted cubic spline (RCS). The cutoff values for bTMB were calculated via X-tile software. Non-linear relationships were observed between bTMB and PFS and overall survival (OS) in RCS plots (both <i>P</i><sub>non-linearity</sub> < 0.001). The optimal cutoff values of bTMB for predicting PFS and OS were 7 and 14 mutations/Mb, respectively. The median PFS and OS of patients with low and high bTMB were significantly longer than those of patients with medium bTMB in the training, validation, and combined sets. Low and high bTMB were also associated with longer PFS and OS in high-programmed death-ligand 1 (PD-L1) expression population. In conclusion, there was a positive non-linear association between bTMB and survival in NSCLC patients receiving atezolizumab. Patients with low bTMB could also derive benefit from immunotherapy.</div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">32158623</PMID><DateRevised><Year>2020</Year><Month>09</Month><Day>28</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Print">2162-4011</ISSN><JournalIssue CitedMedium="Print"><Volume>9</Volume><Issue>1</Issue><PubDate><Year>2020</Year></PubDate></JournalIssue><Title>Oncoimmunology</Title><ISOAbbreviation>Oncoimmunology</ISOAbbreviation></Journal><ArticleTitle>A non-linear association between blood tumor mutation burden and prognosis in NSCLC patients receiving atezolizumab.</ArticleTitle><Pagination><MedlinePgn>1731072</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1080/2162402X.2020.1731072</ELocationID><Abstract><AbstractText>A significant association between high blood-based tumor mutational burden (bTMB) and improved progression-free survival (PFS) was observed in advanced non-small cell lung cancer (NSCLC) receiving atezolizumab. However, this result was unrepeatable in a recent prospective study. We hypothesized that there might be a non-linear association between bTMB and survival. This study used the clinical and genetic data from POPLAR (n = 105, training set) and OAK (n = 324, validation set) trials. The non-linear association between bTMB and survival was assessed using restricted cubic spline (RCS). The cutoff values for bTMB were calculated via X-tile software. Non-linear relationships were observed between bTMB and PFS and overall survival (OS) in RCS plots (both <i>P</i><sub>non-linearity</sub> < 0.001). The optimal cutoff values of bTMB for predicting PFS and OS were 7 and 14 mutations/Mb, respectively. The median PFS and OS of patients with low and high bTMB were significantly longer than those of patients with medium bTMB in the training, validation, and combined sets. Low and high bTMB were also associated with longer PFS and OS in high-programmed death-ligand 1 (PD-L1) expression population. In conclusion, there was a positive non-linear association between bTMB and survival in NSCLC patients receiving atezolizumab. Patients with low bTMB could also derive benefit from immunotherapy.</AbstractText><CopyrightInformation>© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Nie</LastName><ForeName>Wei</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Qian</LastName><ForeName>Jie</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xu</LastName><ForeName>Mi-Die</ForeName><Initials>MD</Initials><AffiliationInfo><Affiliation>Department of Pathology & Biobank, Fudan University Shanghai Cancer Center, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gu</LastName><ForeName>Kai</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Shanghai Applied Protein Technology Co., Ltd (APTBIO), Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Qian</LastName><ForeName>Fang-Fei</ForeName><Initials>FF</Initials><AffiliationInfo><Affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hu</LastName><ForeName>Min-Juan</ForeName><Initials>MJ</Initials><AffiliationInfo><Affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lu</LastName><ForeName>Jun</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gan</LastName><ForeName>Lu</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Xue-Yan</ForeName><Initials>XY</Initials><AffiliationInfo><Affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cao</LastName><ForeName>Shu-Hui</ForeName><Initials>SH</Initials><AffiliationInfo><Affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Jing-Wen</ForeName><Initials>JW</Initials><AffiliationInfo><Affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Yue</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Bo</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Shu-Yuan</ForeName><Initials>SY</Initials><AffiliationInfo><Affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hu</LastName><ForeName>Fang</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Chang-Hui</ForeName><Initials>CH</Initials><AffiliationInfo><Affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhong</LastName><ForeName>Hua</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Han</LastName><ForeName>Bao-Hui</ForeName><Initials>BH</Initials><Identifier Source="ORCID">0000-0002-3950-3030</Identifier><AffiliationInfo><Affiliation>Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>02</Month><Day>20</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Oncoimmunology</MedlineTA><NlmUniqueID>101570526</NlmUniqueID><ISSNLinking>2162-4011</ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Non-small cell lung cancer</Keyword><Keyword MajorTopicYN="N">atezolizumab</Keyword><Keyword MajorTopicYN="N">blood tumor mutation burden</Keyword><Keyword MajorTopicYN="N">prognosis</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>11</Month><Day>16</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2020</Year><Month>01</Month><Day>09</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>01</Month><Day>09</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>3</Month><Day>12</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>3</Month><Day>12</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>3</Month><Day>12</Day><Hour>6</Hour><Minute>1</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32158623</ArticleId><ArticleId IdType="doi">10.1080/2162402X.2020.1731072</ArticleId><ArticleId IdType="pii">1731072</ArticleId><ArticleId IdType="pmc">PMC7051187</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Oncologist. 2019 Jun;24(6):820-828</Citation><ArticleIdList><ArticleId 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