Association between antibiotic-immunotherapy exposure ratio and outcome in metastatic non small cell lung cancer
•Antibiotics induce imbalances in the composition of gut microbiota.•Alterations of intestinal flora may impair the efficacy of immunotherapy (IO).•We defined Antibiotic-IO Exposure Ratio (AIER) as “days of antibiotics /days of IO”.•NSCLC patients with an AIER higher than the median had a worse outc...
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creator | Galli, Giulia Triulzi, Tiziana Proto, Claudia Signorelli, Diego Imbimbo, Martina Poggi, Marta Fucà, Giovanni Ganzinelli, Monica Vitali, Milena Palmieri, Dario Tessari, Anna de Braud, Filippo Garassino, Marina Chiara Colombo, Mario Paolo Lo Russo, Giuseppe |
description | •Antibiotics induce imbalances in the composition of gut microbiota.•Alterations of intestinal flora may impair the efficacy of immunotherapy (IO).•We defined Antibiotic-IO Exposure Ratio (AIER) as “days of antibiotics /days of IO”.•NSCLC patients with an AIER higher than the median had a worse outcome during IO.•The potential impact of AIER on the effects of IO deserves further investigation.
Immunotherapy (IO) is effective in metastatic Non Small Cell Lung Cancer (NSCLC). Gut microbiota has an impact on immunity and its imbalance due to antibiotics may impair the efficacy of IO. We investigated this topic in a case series of NSCLC patients treated with IO.
Data about all metastatic NSCLC patients treated with IO between 04/2013 and 01/2018 were collected. Patients were stratified according to antibiotic use during the Early IO Period (EIOP), and according to the Antibiotic-Immunotherapy Exposure Ratio (AIER) defined as “days of antibiotic/days of IO” during the Whole IO Period (WIOP). Survival was estimated using the Kaplan-Meier method. Log-rank test was used to compare the curves. Multivariate analyses were performed with the Cox model.
We analyzed 157 patients. Forty-six patients received antibiotics during the WIOP, 27 patients during the EIOP. No differences in either Progression-Free Survival (PFS) or Overall Survival (OS) were observed according to antibiotic use during the EIOP (p = 0.1772 and p = 0.2492, respectively). Considering the WIOP, median AIER was 4.2%. The patients with a higher AIER had worse PFS (p |
doi_str_mv | 10.1016/j.lungcan.2019.04.008 |
format | Article |
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Immunotherapy (IO) is effective in metastatic Non Small Cell Lung Cancer (NSCLC). Gut microbiota has an impact on immunity and its imbalance due to antibiotics may impair the efficacy of IO. We investigated this topic in a case series of NSCLC patients treated with IO.
Data about all metastatic NSCLC patients treated with IO between 04/2013 and 01/2018 were collected. Patients were stratified according to antibiotic use during the Early IO Period (EIOP), and according to the Antibiotic-Immunotherapy Exposure Ratio (AIER) defined as “days of antibiotic/days of IO” during the Whole IO Period (WIOP). Survival was estimated using the Kaplan-Meier method. Log-rank test was used to compare the curves. Multivariate analyses were performed with the Cox model.
We analyzed 157 patients. Forty-six patients received antibiotics during the WIOP, 27 patients during the EIOP. No differences in either Progression-Free Survival (PFS) or Overall Survival (OS) were observed according to antibiotic use during the EIOP (p = 0.1772 and p = 0.2492, respectively). Considering the WIOP, median AIER was 4.2%. The patients with a higher AIER had worse PFS (p < 0.0001) and OS (p = 0.0004) than the others. Results were significant also after correction for the IO line (p = 0.0018 for PFS) and performance status (p < 0.0001 for PFS, p = 0.0052 for OS).
Although no difference in outcome were observed with antibiotic use in the EIOP, a detrimental effect became evident for patients with a higher AIER in the WIOP. If its relevance is confirmed, AIER may become an innovative variable for estimating the impact of antibiotics on IO efficacy.</description><identifier>ISSN: 0169-5002</identifier><identifier>EISSN: 1872-8332</identifier><identifier>DOI: 10.1016/j.lungcan.2019.04.008</identifier><identifier>PMID: 31097097</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents - therapeutic use ; Antibiotic ; Carcinoma, Non-Small-Cell Lung - drug therapy ; Carcinoma, Non-Small-Cell Lung - mortality ; Combined Modality Therapy ; Female ; Humans ; Immunotherapy ; Immunotherapy - methods ; Lung Neoplasms - drug therapy ; Lung Neoplasms - mortality ; Male ; Microbiota ; Middle Aged ; Neoplasm Metastasis ; Non small cell lung cancer ; Survival Analysis ; Treatment Outcome</subject><ispartof>Lung cancer (Amsterdam, Netherlands), 2019-06, Vol.132, p.72-78</ispartof><rights>2019 Elsevier B.V.</rights><rights>Copyright © 2019 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-344a48caa17ae84ac798684d6e2b777d32f01ec7b7bb1be4c92891f4823a2eef3</citedby><cites>FETCH-LOGICAL-c412t-344a48caa17ae84ac798684d6e2b777d32f01ec7b7bb1be4c92891f4823a2eef3</cites><orcidid>0000-0003-2521-7540 ; 0000-0001-7287-4848 ; 0000-0003-3224-2728 ; 0000-0002-1560-2253 ; 0000-0003-0287-9787</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0169500219303952$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31097097$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Galli, Giulia</creatorcontrib><creatorcontrib>Triulzi, Tiziana</creatorcontrib><creatorcontrib>Proto, Claudia</creatorcontrib><creatorcontrib>Signorelli, Diego</creatorcontrib><creatorcontrib>Imbimbo, Martina</creatorcontrib><creatorcontrib>Poggi, Marta</creatorcontrib><creatorcontrib>Fucà, Giovanni</creatorcontrib><creatorcontrib>Ganzinelli, Monica</creatorcontrib><creatorcontrib>Vitali, Milena</creatorcontrib><creatorcontrib>Palmieri, Dario</creatorcontrib><creatorcontrib>Tessari, Anna</creatorcontrib><creatorcontrib>de Braud, Filippo</creatorcontrib><creatorcontrib>Garassino, Marina Chiara</creatorcontrib><creatorcontrib>Colombo, Mario Paolo</creatorcontrib><creatorcontrib>Lo Russo, Giuseppe</creatorcontrib><title>Association between antibiotic-immunotherapy exposure ratio and outcome in metastatic non small cell lung cancer</title><title>Lung cancer (Amsterdam, Netherlands)</title><addtitle>Lung Cancer</addtitle><description>•Antibiotics induce imbalances in the composition of gut microbiota.•Alterations of intestinal flora may impair the efficacy of immunotherapy (IO).•We defined Antibiotic-IO Exposure Ratio (AIER) as “days of antibiotics /days of IO”.•NSCLC patients with an AIER higher than the median had a worse outcome during IO.•The potential impact of AIER on the effects of IO deserves further investigation.
Immunotherapy (IO) is effective in metastatic Non Small Cell Lung Cancer (NSCLC). Gut microbiota has an impact on immunity and its imbalance due to antibiotics may impair the efficacy of IO. We investigated this topic in a case series of NSCLC patients treated with IO.
Data about all metastatic NSCLC patients treated with IO between 04/2013 and 01/2018 were collected. Patients were stratified according to antibiotic use during the Early IO Period (EIOP), and according to the Antibiotic-Immunotherapy Exposure Ratio (AIER) defined as “days of antibiotic/days of IO” during the Whole IO Period (WIOP). Survival was estimated using the Kaplan-Meier method. Log-rank test was used to compare the curves. Multivariate analyses were performed with the Cox model.
We analyzed 157 patients. Forty-six patients received antibiotics during the WIOP, 27 patients during the EIOP. No differences in either Progression-Free Survival (PFS) or Overall Survival (OS) were observed according to antibiotic use during the EIOP (p = 0.1772 and p = 0.2492, respectively). Considering the WIOP, median AIER was 4.2%. The patients with a higher AIER had worse PFS (p < 0.0001) and OS (p = 0.0004) than the others. Results were significant also after correction for the IO line (p = 0.0018 for PFS) and performance status (p < 0.0001 for PFS, p = 0.0052 for OS).
Although no difference in outcome were observed with antibiotic use in the EIOP, a detrimental effect became evident for patients with a higher AIER in the WIOP. If its relevance is confirmed, AIER may become an innovative variable for estimating the impact of antibiotics on IO efficacy.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Anti-Bacterial Agents - therapeutic use</subject><subject>Antibiotic</subject><subject>Carcinoma, Non-Small-Cell Lung - drug therapy</subject><subject>Carcinoma, Non-Small-Cell Lung - mortality</subject><subject>Combined Modality Therapy</subject><subject>Female</subject><subject>Humans</subject><subject>Immunotherapy</subject><subject>Immunotherapy - methods</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Lung Neoplasms - mortality</subject><subject>Male</subject><subject>Microbiota</subject><subject>Middle Aged</subject><subject>Neoplasm Metastasis</subject><subject>Non small cell lung cancer</subject><subject>Survival Analysis</subject><subject>Treatment Outcome</subject><issn>0169-5002</issn><issn>1872-8332</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1PxCAQhonRuOvqT9Bw9NIKlF3oyRjjV2LiRc-E0qmy2UIF6se_l2ZXryaEOfC8M8OD0CklJSV0dbEuN6N7NdqVjNC6JLwkRO6hOZWCFbKq2D6aZ64uloSwGTqKcU0IFZTUh2hW5SLymaPhKkZvrE7WO9xA-gRwWLtkG-uTNYXt-9H59AZBD98YvgYfxwA4TIHMtdiPyfgesHW4h6Rjyi8Gu9wt9nqzwQbyNa2K864GwjE66PQmwsmuLtDL7c3z9X3x-HT3cH31WBhOWSoqzjWXRmsqNEiujajlSvJ2BawRQrQV6wgFIxrRNLQBbmoma9pxySrNALpqgc63fYfg30eISfU2TstoB36MirGKkSURdZ3R5RY1wccYoFNDsL0O34oSNclWa7WTrSbZinCVZefc2W7E2PTQ_qV-7WbgcgtA_uiHhaCisZAttDaASar19p8RP7JTleQ</recordid><startdate>201906</startdate><enddate>201906</enddate><creator>Galli, Giulia</creator><creator>Triulzi, Tiziana</creator><creator>Proto, Claudia</creator><creator>Signorelli, Diego</creator><creator>Imbimbo, Martina</creator><creator>Poggi, Marta</creator><creator>Fucà, Giovanni</creator><creator>Ganzinelli, Monica</creator><creator>Vitali, Milena</creator><creator>Palmieri, Dario</creator><creator>Tessari, Anna</creator><creator>de Braud, Filippo</creator><creator>Garassino, Marina Chiara</creator><creator>Colombo, Mario Paolo</creator><creator>Lo Russo, Giuseppe</creator><general>Elsevier B.V</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><orcidid>https://orcid.org/0000-0003-2521-7540</orcidid><orcidid>https://orcid.org/0000-0001-7287-4848</orcidid><orcidid>https://orcid.org/0000-0003-3224-2728</orcidid><orcidid>https://orcid.org/0000-0002-1560-2253</orcidid><orcidid>https://orcid.org/0000-0003-0287-9787</orcidid></search><sort><creationdate>201906</creationdate><title>Association between antibiotic-immunotherapy exposure ratio and outcome in metastatic non small cell lung cancer</title><author>Galli, Giulia ; Triulzi, Tiziana ; Proto, Claudia ; Signorelli, Diego ; Imbimbo, Martina ; Poggi, Marta ; Fucà, Giovanni ; Ganzinelli, Monica ; Vitali, Milena ; Palmieri, Dario ; Tessari, Anna ; de Braud, Filippo ; Garassino, Marina Chiara ; Colombo, Mario Paolo ; Lo Russo, Giuseppe</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-344a48caa17ae84ac798684d6e2b777d32f01ec7b7bb1be4c92891f4823a2eef3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Anti-Bacterial Agents - therapeutic use</topic><topic>Antibiotic</topic><topic>Carcinoma, Non-Small-Cell Lung - drug therapy</topic><topic>Carcinoma, Non-Small-Cell Lung - mortality</topic><topic>Combined Modality Therapy</topic><topic>Female</topic><topic>Humans</topic><topic>Immunotherapy</topic><topic>Immunotherapy - methods</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Lung Neoplasms - mortality</topic><topic>Male</topic><topic>Microbiota</topic><topic>Middle Aged</topic><topic>Neoplasm Metastasis</topic><topic>Non small cell lung cancer</topic><topic>Survival Analysis</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Galli, Giulia</creatorcontrib><creatorcontrib>Triulzi, Tiziana</creatorcontrib><creatorcontrib>Proto, Claudia</creatorcontrib><creatorcontrib>Signorelli, Diego</creatorcontrib><creatorcontrib>Imbimbo, Martina</creatorcontrib><creatorcontrib>Poggi, Marta</creatorcontrib><creatorcontrib>Fucà, Giovanni</creatorcontrib><creatorcontrib>Ganzinelli, Monica</creatorcontrib><creatorcontrib>Vitali, Milena</creatorcontrib><creatorcontrib>Palmieri, Dario</creatorcontrib><creatorcontrib>Tessari, Anna</creatorcontrib><creatorcontrib>de Braud, Filippo</creatorcontrib><creatorcontrib>Garassino, Marina Chiara</creatorcontrib><creatorcontrib>Colombo, Mario Paolo</creatorcontrib><creatorcontrib>Lo Russo, Giuseppe</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>Lung cancer (Amsterdam, Netherlands)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Galli, Giulia</au><au>Triulzi, Tiziana</au><au>Proto, Claudia</au><au>Signorelli, Diego</au><au>Imbimbo, Martina</au><au>Poggi, Marta</au><au>Fucà, Giovanni</au><au>Ganzinelli, Monica</au><au>Vitali, Milena</au><au>Palmieri, Dario</au><au>Tessari, Anna</au><au>de Braud, Filippo</au><au>Garassino, Marina Chiara</au><au>Colombo, Mario Paolo</au><au>Lo Russo, Giuseppe</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association between antibiotic-immunotherapy exposure ratio and outcome in metastatic non small cell lung cancer</atitle><jtitle>Lung cancer (Amsterdam, Netherlands)</jtitle><addtitle>Lung Cancer</addtitle><date>2019-06</date><risdate>2019</risdate><volume>132</volume><spage>72</spage><epage>78</epage><pages>72-78</pages><issn>0169-5002</issn><eissn>1872-8332</eissn><abstract>•Antibiotics induce imbalances in the composition of gut microbiota.•Alterations of intestinal flora may impair the efficacy of immunotherapy (IO).•We defined Antibiotic-IO Exposure Ratio (AIER) as “days of antibiotics /days of IO”.•NSCLC patients with an AIER higher than the median had a worse outcome during IO.•The potential impact of AIER on the effects of IO deserves further investigation.
Immunotherapy (IO) is effective in metastatic Non Small Cell Lung Cancer (NSCLC). Gut microbiota has an impact on immunity and its imbalance due to antibiotics may impair the efficacy of IO. We investigated this topic in a case series of NSCLC patients treated with IO.
Data about all metastatic NSCLC patients treated with IO between 04/2013 and 01/2018 were collected. Patients were stratified according to antibiotic use during the Early IO Period (EIOP), and according to the Antibiotic-Immunotherapy Exposure Ratio (AIER) defined as “days of antibiotic/days of IO” during the Whole IO Period (WIOP). Survival was estimated using the Kaplan-Meier method. Log-rank test was used to compare the curves. Multivariate analyses were performed with the Cox model.
We analyzed 157 patients. Forty-six patients received antibiotics during the WIOP, 27 patients during the EIOP. No differences in either Progression-Free Survival (PFS) or Overall Survival (OS) were observed according to antibiotic use during the EIOP (p = 0.1772 and p = 0.2492, respectively). Considering the WIOP, median AIER was 4.2%. The patients with a higher AIER had worse PFS (p < 0.0001) and OS (p = 0.0004) than the others. Results were significant also after correction for the IO line (p = 0.0018 for PFS) and performance status (p < 0.0001 for PFS, p = 0.0052 for OS).
Although no difference in outcome were observed with antibiotic use in the EIOP, a detrimental effect became evident for patients with a higher AIER in the WIOP. If its relevance is confirmed, AIER may become an innovative variable for estimating the impact of antibiotics on IO efficacy.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>31097097</pmid><doi>10.1016/j.lungcan.2019.04.008</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0003-2521-7540</orcidid><orcidid>https://orcid.org/0000-0001-7287-4848</orcidid><orcidid>https://orcid.org/0000-0003-3224-2728</orcidid><orcidid>https://orcid.org/0000-0002-1560-2253</orcidid><orcidid>https://orcid.org/0000-0003-0287-9787</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Adult Aged Aged, 80 and over Anti-Bacterial Agents - therapeutic use Antibiotic Carcinoma, Non-Small-Cell Lung - drug therapy Carcinoma, Non-Small-Cell Lung - mortality Combined Modality Therapy Female Humans Immunotherapy Immunotherapy - methods Lung Neoplasms - drug therapy Lung Neoplasms - mortality Male Microbiota Middle Aged Neoplasm Metastasis Non small cell lung cancer Survival Analysis Treatment Outcome |
title | Association between antibiotic-immunotherapy exposure ratio and outcome in metastatic non small cell lung cancer |
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