Neutrophil to lymphocyte ratio as a potential predictive marker for treatment with pembrolizumab as a second line treatment in patients with non-small cell lung cancer
The aim of this multicentric retrospective study is to evaluate the predictive and prognostic performance of neutrophil to lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and their dynamics in patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab as a second line. Patie...
Gespeichert in:
Veröffentlicht in: | BioScience Trends 2020/02/29, Vol.14(1), pp.48-55 |
---|---|
Hauptverfasser: | , , , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 55 |
---|---|
container_issue | 1 |
container_start_page | 48 |
container_title | BioScience Trends |
container_volume | 14 |
creator | Petrova, Mila P. Eneva, Mariyana I. Arabadjiev, Jeliazko I. Conev, Nikolay V. Dimitrova, Eleonora G. Koynov, Krassimir D. Karanikolova, Teodora S. Valev, Spartak S. Gencheva, Radostina B. Zhbantov, Georgi A. Ivanova, Anika I. Sarbianova, Iva I. Timcheva, Constanta V. Donev, Ivan S. |
description | The aim of this multicentric retrospective study is to evaluate the predictive and prognostic performance of neutrophil to lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and their dynamics in patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab as a second line. Patients with metastatic NSCLC (n = 119), whose tumors expressed programmed death-ligand 1 (PD-L1) ≥ 1%, were retrospectively analyzed between Apr 2017 and Apr 2019. All patients received platinum-containing chemotherapy as a first line treatment. Pre-treatment NLR was calculated by dividing the number of neutrophils by the number of lymphocytes in peripheral blood before the first pembrolizumab infusion. Progression free survival (PFS) and overall survival (OS) was compared by Kaplan-Meier method and Cox Proportional Hazard model. Patients with NLR > 5 before immunotherapy showed significantly shorter mean PFS of 6.86 months (95% CI: 5.81-7.90) as compared to those with NLR ≤ 5 of 18.82 months (95% CI: 15.87-21.78) (long rank test p < 0.001). Furthermore in the multivariate analysis, only NLR > 5 was an independent predictive factor for shorter PFS (HR: 4.47, 95% CI: 2.20-9.07, p < 0.001). In multivariate analysis, presence of bone metastases (HR: 2.08, 95% CI: 1.10-4.94, p = 0.030), NLR > 5 before chemotherapy (HR: 8.09, 95% CI: 2.35-27.81, p = 0.001) and high PLR before chemotherapy (HR: 2.81, 95% CI: 1.13-6.97, p = 0.025) were found to be independent negative prognostic factors for poor OS. Our data suggests that NLR ≤ 5 is a potential predictive marker, which may identify patients appropriate for immunotherapy as a second line treatment. |
doi_str_mv | 10.5582/bst.2019.01279 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2352049230</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2352049230</sourcerecordid><originalsourceid>FETCH-LOGICAL-c486t-91d0a170f5710e25b276c163340e8c96a64fb03a82475ea2d05d9a65040dbe953</originalsourceid><addsrcrecordid>eNpNkU1v1DAQhiMEolXplSPykUu2_oid5IjKV6UKLnC2Js6k6-LYwXZAyx_ib-JtysIcZkbyM-9Y81bVS0Z3Unb8akh5xynrd5Txtn9SnbOuY3XbcfH01DN5Vl2mdE9LSMW6Vj2vzgSnXEglzqvfn3DNMSx760gOxB3mZR_MISOJkG0gkAiQJWT02YIjS8TRmmx_IJkhfsNIphBJjgh5Lgj5afOeLDgPMTj7a51h2BQSmuBH4qzH_2jryVK2lDZtkz74Os3gHDFYklv9HTHgDcYX1bMJXMLLx3pRfX3_7sv1x_r284eb6ze3tWk6leuejRRYSyfZMopcDrxVhikhGoqd6RWoZhqogI43rUTgI5VjD0rSho4D9lJcVK833SWG7yumrGebjp8Bj2FNupyN06bnghZ0t6EmhpQiTnqJtlzloBnVR3908Ucf_dEP_pSBV4_a6zDjeML_ulGAtxtwnzLc4QmAmK1x-KDHGs2O6Z_u6dnsIWr04g8yq6bi</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2352049230</pqid></control><display><type>article</type><title>Neutrophil to lymphocyte ratio as a potential predictive marker for treatment with pembrolizumab as a second line treatment in patients with non-small cell lung cancer</title><source>MEDLINE</source><source>J-STAGE</source><source>EZB Electronic Journals Library</source><creator>Petrova, Mila P. ; Eneva, Mariyana I. ; Arabadjiev, Jeliazko I. ; Conev, Nikolay V. ; Dimitrova, Eleonora G. ; Koynov, Krassimir D. ; Karanikolova, Teodora S. ; Valev, Spartak S. ; Gencheva, Radostina B. ; Zhbantov, Georgi A. ; Ivanova, Anika I. ; Sarbianova, Iva I. ; Timcheva, Constanta V. ; Donev, Ivan S.</creator><creatorcontrib>Petrova, Mila P. ; Eneva, Mariyana I. ; Arabadjiev, Jeliazko I. ; Conev, Nikolay V. ; Dimitrova, Eleonora G. ; Koynov, Krassimir D. ; Karanikolova, Teodora S. ; Valev, Spartak S. ; Gencheva, Radostina B. ; Zhbantov, Georgi A. ; Ivanova, Anika I. ; Sarbianova, Iva I. ; Timcheva, Constanta V. ; Donev, Ivan S.</creatorcontrib><description>The aim of this multicentric retrospective study is to evaluate the predictive and prognostic performance of neutrophil to lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and their dynamics in patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab as a second line. Patients with metastatic NSCLC (n = 119), whose tumors expressed programmed death-ligand 1 (PD-L1) ≥ 1%, were retrospectively analyzed between Apr 2017 and Apr 2019. All patients received platinum-containing chemotherapy as a first line treatment. Pre-treatment NLR was calculated by dividing the number of neutrophils by the number of lymphocytes in peripheral blood before the first pembrolizumab infusion. Progression free survival (PFS) and overall survival (OS) was compared by Kaplan-Meier method and Cox Proportional Hazard model. Patients with NLR > 5 before immunotherapy showed significantly shorter mean PFS of 6.86 months (95% CI: 5.81-7.90) as compared to those with NLR ≤ 5 of 18.82 months (95% CI: 15.87-21.78) (long rank test p < 0.001). Furthermore in the multivariate analysis, only NLR > 5 was an independent predictive factor for shorter PFS (HR: 4.47, 95% CI: 2.20-9.07, p < 0.001). In multivariate analysis, presence of bone metastases (HR: 2.08, 95% CI: 1.10-4.94, p = 0.030), NLR > 5 before chemotherapy (HR: 8.09, 95% CI: 2.35-27.81, p = 0.001) and high PLR before chemotherapy (HR: 2.81, 95% CI: 1.13-6.97, p = 0.025) were found to be independent negative prognostic factors for poor OS. Our data suggests that NLR ≤ 5 is a potential predictive marker, which may identify patients appropriate for immunotherapy as a second line treatment.</description><identifier>ISSN: 1881-7815</identifier><identifier>EISSN: 1881-7823</identifier><identifier>DOI: 10.5582/bst.2019.01279</identifier><identifier>PMID: 32023563</identifier><language>eng</language><publisher>Japan: International Research and Cooperation Association for Bio & Socio-Sciences Advancement</publisher><subject>Aged ; Antibodies, Monoclonal, Humanized - therapeutic use ; B7-H1 Antigen ; Biomarkers ; Carcinoma, Non-Small-Cell Lung - diagnosis ; Carcinoma, Non-Small-Cell Lung - drug therapy ; Female ; Humans ; Immunotherapy ; Kaplan-Meier Estimate ; Lung Neoplasms - diagnosis ; Lung Neoplasms - drug therapy ; Lymphocytes - cytology ; Male ; Middle Aged ; neutrophil to lymphocyte ratio ; Neutrophils - cytology ; Platinum Compounds - therapeutic use ; predictive marker ; Proportional Hazards Models ; Retrospective Studies ; Survival Rate</subject><ispartof>BioScience Trends, 2020/02/29, Vol.14(1), pp.48-55</ispartof><rights>2020 International Research and Cooperation Association for Bio & Socio-Sciences Advancement</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c486t-91d0a170f5710e25b276c163340e8c96a64fb03a82475ea2d05d9a65040dbe953</citedby><cites>FETCH-LOGICAL-c486t-91d0a170f5710e25b276c163340e8c96a64fb03a82475ea2d05d9a65040dbe953</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,1877,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32023563$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Petrova, Mila P.</creatorcontrib><creatorcontrib>Eneva, Mariyana I.</creatorcontrib><creatorcontrib>Arabadjiev, Jeliazko I.</creatorcontrib><creatorcontrib>Conev, Nikolay V.</creatorcontrib><creatorcontrib>Dimitrova, Eleonora G.</creatorcontrib><creatorcontrib>Koynov, Krassimir D.</creatorcontrib><creatorcontrib>Karanikolova, Teodora S.</creatorcontrib><creatorcontrib>Valev, Spartak S.</creatorcontrib><creatorcontrib>Gencheva, Radostina B.</creatorcontrib><creatorcontrib>Zhbantov, Georgi A.</creatorcontrib><creatorcontrib>Ivanova, Anika I.</creatorcontrib><creatorcontrib>Sarbianova, Iva I.</creatorcontrib><creatorcontrib>Timcheva, Constanta V.</creatorcontrib><creatorcontrib>Donev, Ivan S.</creatorcontrib><title>Neutrophil to lymphocyte ratio as a potential predictive marker for treatment with pembrolizumab as a second line treatment in patients with non-small cell lung cancer</title><title>BioScience Trends</title><addtitle>BST</addtitle><description>The aim of this multicentric retrospective study is to evaluate the predictive and prognostic performance of neutrophil to lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and their dynamics in patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab as a second line. Patients with metastatic NSCLC (n = 119), whose tumors expressed programmed death-ligand 1 (PD-L1) ≥ 1%, were retrospectively analyzed between Apr 2017 and Apr 2019. All patients received platinum-containing chemotherapy as a first line treatment. Pre-treatment NLR was calculated by dividing the number of neutrophils by the number of lymphocytes in peripheral blood before the first pembrolizumab infusion. Progression free survival (PFS) and overall survival (OS) was compared by Kaplan-Meier method and Cox Proportional Hazard model. Patients with NLR > 5 before immunotherapy showed significantly shorter mean PFS of 6.86 months (95% CI: 5.81-7.90) as compared to those with NLR ≤ 5 of 18.82 months (95% CI: 15.87-21.78) (long rank test p < 0.001). Furthermore in the multivariate analysis, only NLR > 5 was an independent predictive factor for shorter PFS (HR: 4.47, 95% CI: 2.20-9.07, p < 0.001). In multivariate analysis, presence of bone metastases (HR: 2.08, 95% CI: 1.10-4.94, p = 0.030), NLR > 5 before chemotherapy (HR: 8.09, 95% CI: 2.35-27.81, p = 0.001) and high PLR before chemotherapy (HR: 2.81, 95% CI: 1.13-6.97, p = 0.025) were found to be independent negative prognostic factors for poor OS. Our data suggests that NLR ≤ 5 is a potential predictive marker, which may identify patients appropriate for immunotherapy as a second line treatment.</description><subject>Aged</subject><subject>Antibodies, Monoclonal, Humanized - therapeutic use</subject><subject>B7-H1 Antigen</subject><subject>Biomarkers</subject><subject>Carcinoma, Non-Small-Cell Lung - diagnosis</subject><subject>Carcinoma, Non-Small-Cell Lung - drug therapy</subject><subject>Female</subject><subject>Humans</subject><subject>Immunotherapy</subject><subject>Kaplan-Meier Estimate</subject><subject>Lung Neoplasms - diagnosis</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Lymphocytes - cytology</subject><subject>Male</subject><subject>Middle Aged</subject><subject>neutrophil to lymphocyte ratio</subject><subject>Neutrophils - cytology</subject><subject>Platinum Compounds - therapeutic use</subject><subject>predictive marker</subject><subject>Proportional Hazards Models</subject><subject>Retrospective Studies</subject><subject>Survival Rate</subject><issn>1881-7815</issn><issn>1881-7823</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkU1v1DAQhiMEolXplSPykUu2_oid5IjKV6UKLnC2Js6k6-LYwXZAyx_ib-JtysIcZkbyM-9Y81bVS0Z3Unb8akh5xynrd5Txtn9SnbOuY3XbcfH01DN5Vl2mdE9LSMW6Vj2vzgSnXEglzqvfn3DNMSx760gOxB3mZR_MISOJkG0gkAiQJWT02YIjS8TRmmx_IJkhfsNIphBJjgh5Lgj5afOeLDgPMTj7a51h2BQSmuBH4qzH_2jryVK2lDZtkz74Os3gHDFYklv9HTHgDcYX1bMJXMLLx3pRfX3_7sv1x_r284eb6ze3tWk6leuejRRYSyfZMopcDrxVhikhGoqd6RWoZhqogI43rUTgI5VjD0rSho4D9lJcVK833SWG7yumrGebjp8Bj2FNupyN06bnghZ0t6EmhpQiTnqJtlzloBnVR3908Ucf_dEP_pSBV4_a6zDjeML_ulGAtxtwnzLc4QmAmK1x-KDHGs2O6Z_u6dnsIWr04g8yq6bi</recordid><startdate>20200229</startdate><enddate>20200229</enddate><creator>Petrova, Mila P.</creator><creator>Eneva, Mariyana I.</creator><creator>Arabadjiev, Jeliazko I.</creator><creator>Conev, Nikolay V.</creator><creator>Dimitrova, Eleonora G.</creator><creator>Koynov, Krassimir D.</creator><creator>Karanikolova, Teodora S.</creator><creator>Valev, Spartak S.</creator><creator>Gencheva, Radostina B.</creator><creator>Zhbantov, Georgi A.</creator><creator>Ivanova, Anika I.</creator><creator>Sarbianova, Iva I.</creator><creator>Timcheva, Constanta V.</creator><creator>Donev, Ivan S.</creator><general>International Research and Cooperation Association for Bio & Socio-Sciences Advancement</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>7X8</scope></search><sort><creationdate>20200229</creationdate><title>Neutrophil to lymphocyte ratio as a potential predictive marker for treatment with pembrolizumab as a second line treatment in patients with non-small cell lung cancer</title><author>Petrova, Mila P. ; Eneva, Mariyana I. ; Arabadjiev, Jeliazko I. ; Conev, Nikolay V. ; Dimitrova, Eleonora G. ; Koynov, Krassimir D. ; Karanikolova, Teodora S. ; Valev, Spartak S. ; Gencheva, Radostina B. ; Zhbantov, Georgi A. ; Ivanova, Anika I. ; Sarbianova, Iva I. ; Timcheva, Constanta V. ; Donev, Ivan S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c486t-91d0a170f5710e25b276c163340e8c96a64fb03a82475ea2d05d9a65040dbe953</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Aged</topic><topic>Antibodies, Monoclonal, Humanized - therapeutic use</topic><topic>B7-H1 Antigen</topic><topic>Biomarkers</topic><topic>Carcinoma, Non-Small-Cell Lung - diagnosis</topic><topic>Carcinoma, Non-Small-Cell Lung - drug therapy</topic><topic>Female</topic><topic>Humans</topic><topic>Immunotherapy</topic><topic>Kaplan-Meier Estimate</topic><topic>Lung Neoplasms - diagnosis</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Lymphocytes - cytology</topic><topic>Male</topic><topic>Middle Aged</topic><topic>neutrophil to lymphocyte ratio</topic><topic>Neutrophils - cytology</topic><topic>Platinum Compounds - therapeutic use</topic><topic>predictive marker</topic><topic>Proportional Hazards Models</topic><topic>Retrospective Studies</topic><topic>Survival Rate</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Petrova, Mila P.</creatorcontrib><creatorcontrib>Eneva, Mariyana I.</creatorcontrib><creatorcontrib>Arabadjiev, Jeliazko I.</creatorcontrib><creatorcontrib>Conev, Nikolay V.</creatorcontrib><creatorcontrib>Dimitrova, Eleonora G.</creatorcontrib><creatorcontrib>Koynov, Krassimir D.</creatorcontrib><creatorcontrib>Karanikolova, Teodora S.</creatorcontrib><creatorcontrib>Valev, Spartak S.</creatorcontrib><creatorcontrib>Gencheva, Radostina B.</creatorcontrib><creatorcontrib>Zhbantov, Georgi A.</creatorcontrib><creatorcontrib>Ivanova, Anika I.</creatorcontrib><creatorcontrib>Sarbianova, Iva I.</creatorcontrib><creatorcontrib>Timcheva, Constanta V.</creatorcontrib><creatorcontrib>Donev, Ivan S.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>BioScience Trends</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Petrova, Mila P.</au><au>Eneva, Mariyana I.</au><au>Arabadjiev, Jeliazko I.</au><au>Conev, Nikolay V.</au><au>Dimitrova, Eleonora G.</au><au>Koynov, Krassimir D.</au><au>Karanikolova, Teodora S.</au><au>Valev, Spartak S.</au><au>Gencheva, Radostina B.</au><au>Zhbantov, Georgi A.</au><au>Ivanova, Anika I.</au><au>Sarbianova, Iva I.</au><au>Timcheva, Constanta V.</au><au>Donev, Ivan S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neutrophil to lymphocyte ratio as a potential predictive marker for treatment with pembrolizumab as a second line treatment in patients with non-small cell lung cancer</atitle><jtitle>BioScience Trends</jtitle><addtitle>BST</addtitle><date>2020-02-29</date><risdate>2020</risdate><volume>14</volume><issue>1</issue><spage>48</spage><epage>55</epage><pages>48-55</pages><issn>1881-7815</issn><eissn>1881-7823</eissn><abstract>The aim of this multicentric retrospective study is to evaluate the predictive and prognostic performance of neutrophil to lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and their dynamics in patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab as a second line. Patients with metastatic NSCLC (n = 119), whose tumors expressed programmed death-ligand 1 (PD-L1) ≥ 1%, were retrospectively analyzed between Apr 2017 and Apr 2019. All patients received platinum-containing chemotherapy as a first line treatment. Pre-treatment NLR was calculated by dividing the number of neutrophils by the number of lymphocytes in peripheral blood before the first pembrolizumab infusion. Progression free survival (PFS) and overall survival (OS) was compared by Kaplan-Meier method and Cox Proportional Hazard model. Patients with NLR > 5 before immunotherapy showed significantly shorter mean PFS of 6.86 months (95% CI: 5.81-7.90) as compared to those with NLR ≤ 5 of 18.82 months (95% CI: 15.87-21.78) (long rank test p < 0.001). Furthermore in the multivariate analysis, only NLR > 5 was an independent predictive factor for shorter PFS (HR: 4.47, 95% CI: 2.20-9.07, p < 0.001). In multivariate analysis, presence of bone metastases (HR: 2.08, 95% CI: 1.10-4.94, p = 0.030), NLR > 5 before chemotherapy (HR: 8.09, 95% CI: 2.35-27.81, p = 0.001) and high PLR before chemotherapy (HR: 2.81, 95% CI: 1.13-6.97, p = 0.025) were found to be independent negative prognostic factors for poor OS. Our data suggests that NLR ≤ 5 is a potential predictive marker, which may identify patients appropriate for immunotherapy as a second line treatment.</abstract><cop>Japan</cop><pub>International Research and Cooperation Association for Bio & Socio-Sciences Advancement</pub><pmid>32023563</pmid><doi>10.5582/bst.2019.01279</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1881-7815 |
ispartof | BioScience Trends, 2020/02/29, Vol.14(1), pp.48-55 |
issn | 1881-7815 1881-7823 |
language | eng |
recordid | cdi_proquest_miscellaneous_2352049230 |
source | MEDLINE; J-STAGE; EZB Electronic Journals Library |
subjects | Aged Antibodies, Monoclonal, Humanized - therapeutic use B7-H1 Antigen Biomarkers Carcinoma, Non-Small-Cell Lung - diagnosis Carcinoma, Non-Small-Cell Lung - drug therapy Female Humans Immunotherapy Kaplan-Meier Estimate Lung Neoplasms - diagnosis Lung Neoplasms - drug therapy Lymphocytes - cytology Male Middle Aged neutrophil to lymphocyte ratio Neutrophils - cytology Platinum Compounds - therapeutic use predictive marker Proportional Hazards Models Retrospective Studies Survival Rate |
title | Neutrophil to lymphocyte ratio as a potential predictive marker for treatment with pembrolizumab as a second line treatment in patients with non-small cell lung cancer |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-17T16%3A52%3A54IST&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=Neutrophil%20to%20lymphocyte%20ratio%20as%20a%20potential%20predictive%20marker%20for%20treatment%20with%20pembrolizumab%20as%20a%20second%20line%20treatment%20in%20patients%20with%20non-small%20cell%20lung%20cancer&rft.jtitle=BioScience%20Trends&rft.au=Petrova,%20Mila%20P.&rft.date=2020-02-29&rft.volume=14&rft.issue=1&rft.spage=48&rft.epage=55&rft.pages=48-55&rft.issn=1881-7815&rft.eissn=1881-7823&rft_id=info:doi/10.5582/bst.2019.01279&rft_dat=%3Cproquest_cross%3E2352049230%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=2352049230&rft_id=info:pmid/32023563&rfr_iscdi=true |