Smoking impairs the effect of neoadjuvant FOLFIRINOX on postresection survival in pancreatic cancer
Smoking plays an important role in carcinogenesis, including pancreatic ductal adenocarcinoma (PDAC). However, little is known about the association between smoking status and prognosis in resected PDAC. All patients who underwent resection for PDAC were identified from two prospective institutional...
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| Veröffentlicht in: | European journal of cancer (1990) 2023-11, Vol.193, p.113293-113293, Article 113293 |
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| container_title | European journal of cancer (1990) |
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| creator | Leonhardt, Carl-Stephan Pils, Dietmar Qadan, Motaz Gustorff, Charlotte Sahora, Klaus Klaiber, Ulla Warshaw, Andrew L. Prager, Gerald Ferrone, Cristina R. Lillemoe, Keith D. Schindl, Martin Strobel, Oliver Castillo, Carlos Fernández-del Hank, Thomas |
| description | Smoking plays an important role in carcinogenesis, including pancreatic ductal adenocarcinoma (PDAC). However, little is known about the association between smoking status and prognosis in resected PDAC.
All patients who underwent resection for PDAC were identified from two prospective institutional databases. Clinicopathologic data as well as demographics including smoking status were extracted. Survival analysis and multivariable Cox regression modelling was performed. Restricted cubic splines were used for linear data to define cut-off points.
Out of 848 patients, 357 (42.1%) received neoadjuvant treatment (NAT), 491 upfront resection (57.9%), and 475 (56%) adjuvant therapy. The median overall survival (OS) was 27.8 months, 36.1 months, and 23.0 months for the entire cohort, after NAT and upfront resection. 464 patients were never smokers (54.7%), 250 former smokers (29.5%), and 134 active smokers (15.8%). In the multivariable model, the interaction of neoadjuvant FOLFIRINOX and active smoking was associated with the highest risk for decreased OS (harzard ratio (HR) 2.35; 95% confidence interval 1.13–4.90) and strongly mitigated the benefit of FOLFIRNOX (HR 0.40; 95% CI 0.25–0.63). Adjusted median OS in NAT patients with FOLFIRINOX was not reached for never and former smokers, compared to 26.2 months in active smokers. Based on the model, a nomogram was generated to illustrate the probability of 5-year survival after PDAC resection.
The present study confirms that neoadjuvant FOLFIRINOX is associated with excellent survival and demonstrates that active smoking reduces its benefit. The nomogram can assist in daily clinical practice and emphasises the importance of smoking cessation in patients with PDAC, especially prior to NAT with FOLFIRINOX.
•Neoadjuvant FOLFIRINOX was associated with excellent overall survival.•Active smoking impaired the benefit of neoadjuvant FOLFIRINOX.•No interactions between smoking status and non-FOLFIRINOX regimens were observed. |
| doi_str_mv | 10.1016/j.ejca.2023.113293 |
| format | Article |
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All patients who underwent resection for PDAC were identified from two prospective institutional databases. Clinicopathologic data as well as demographics including smoking status were extracted. Survival analysis and multivariable Cox regression modelling was performed. Restricted cubic splines were used for linear data to define cut-off points.
Out of 848 patients, 357 (42.1%) received neoadjuvant treatment (NAT), 491 upfront resection (57.9%), and 475 (56%) adjuvant therapy. The median overall survival (OS) was 27.8 months, 36.1 months, and 23.0 months for the entire cohort, after NAT and upfront resection. 464 patients were never smokers (54.7%), 250 former smokers (29.5%), and 134 active smokers (15.8%). In the multivariable model, the interaction of neoadjuvant FOLFIRINOX and active smoking was associated with the highest risk for decreased OS (harzard ratio (HR) 2.35; 95% confidence interval 1.13–4.90) and strongly mitigated the benefit of FOLFIRNOX (HR 0.40; 95% CI 0.25–0.63). Adjusted median OS in NAT patients with FOLFIRINOX was not reached for never and former smokers, compared to 26.2 months in active smokers. Based on the model, a nomogram was generated to illustrate the probability of 5-year survival after PDAC resection.
The present study confirms that neoadjuvant FOLFIRINOX is associated with excellent survival and demonstrates that active smoking reduces its benefit. The nomogram can assist in daily clinical practice and emphasises the importance of smoking cessation in patients with PDAC, especially prior to NAT with FOLFIRINOX.
•Neoadjuvant FOLFIRINOX was associated with excellent overall survival.•Active smoking impaired the benefit of neoadjuvant FOLFIRINOX.•No interactions between smoking status and non-FOLFIRINOX regimens were observed.</description><identifier>ISSN: 0959-8049</identifier><identifier>EISSN: 1879-0852</identifier><identifier>DOI: 10.1016/j.ejca.2023.113293</identifier><identifier>PMID: 37713740</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Antineoplastic Combined Chemotherapy Protocols - adverse effects ; Carcinoma, Pancreatic Ductal - drug therapy ; Carcinoma, Pancreatic Ductal - surgery ; Cigarette ; Fluorouracil - therapeutic use ; FOLFIRINOX ; Humans ; NAT ; Neoadjuvant therapy ; Neoadjuvant Therapy - adverse effects ; Pancreatic cancer ; Pancreatic Neoplasms ; Pancreatic Neoplasms - drug therapy ; Pancreatic Neoplasms - surgery ; Pancreatic surgery ; PDAC ; Prognostic factors ; Prospective Studies ; Retrospective Studies ; Smoking ; Smoking - adverse effects ; Survival</subject><ispartof>European journal of cancer (1990), 2023-11, Vol.193, p.113293-113293, Article 113293</ispartof><rights>2023 The Author(s)</rights><rights>Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c307t-eeed845972dee56c33f30c0c02c61a7572eae4bceaebc8389e4c60d37cbcc1953</cites><orcidid>0009-0007-1172-0942 ; 0000-0001-8087-2295</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejca.2023.113293$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,45974</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37713740$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Leonhardt, Carl-Stephan</creatorcontrib><creatorcontrib>Pils, Dietmar</creatorcontrib><creatorcontrib>Qadan, Motaz</creatorcontrib><creatorcontrib>Gustorff, Charlotte</creatorcontrib><creatorcontrib>Sahora, Klaus</creatorcontrib><creatorcontrib>Klaiber, Ulla</creatorcontrib><creatorcontrib>Warshaw, Andrew L.</creatorcontrib><creatorcontrib>Prager, Gerald</creatorcontrib><creatorcontrib>Ferrone, Cristina R.</creatorcontrib><creatorcontrib>Lillemoe, Keith D.</creatorcontrib><creatorcontrib>Schindl, Martin</creatorcontrib><creatorcontrib>Strobel, Oliver</creatorcontrib><creatorcontrib>Castillo, Carlos Fernández-del</creatorcontrib><creatorcontrib>Hank, Thomas</creatorcontrib><title>Smoking impairs the effect of neoadjuvant FOLFIRINOX on postresection survival in pancreatic cancer</title><title>European journal of cancer (1990)</title><addtitle>Eur J Cancer</addtitle><description>Smoking plays an important role in carcinogenesis, including pancreatic ductal adenocarcinoma (PDAC). However, little is known about the association between smoking status and prognosis in resected PDAC.
All patients who underwent resection for PDAC were identified from two prospective institutional databases. Clinicopathologic data as well as demographics including smoking status were extracted. Survival analysis and multivariable Cox regression modelling was performed. Restricted cubic splines were used for linear data to define cut-off points.
Out of 848 patients, 357 (42.1%) received neoadjuvant treatment (NAT), 491 upfront resection (57.9%), and 475 (56%) adjuvant therapy. The median overall survival (OS) was 27.8 months, 36.1 months, and 23.0 months for the entire cohort, after NAT and upfront resection. 464 patients were never smokers (54.7%), 250 former smokers (29.5%), and 134 active smokers (15.8%). In the multivariable model, the interaction of neoadjuvant FOLFIRINOX and active smoking was associated with the highest risk for decreased OS (harzard ratio (HR) 2.35; 95% confidence interval 1.13–4.90) and strongly mitigated the benefit of FOLFIRNOX (HR 0.40; 95% CI 0.25–0.63). Adjusted median OS in NAT patients with FOLFIRINOX was not reached for never and former smokers, compared to 26.2 months in active smokers. Based on the model, a nomogram was generated to illustrate the probability of 5-year survival after PDAC resection.
The present study confirms that neoadjuvant FOLFIRINOX is associated with excellent survival and demonstrates that active smoking reduces its benefit. The nomogram can assist in daily clinical practice and emphasises the importance of smoking cessation in patients with PDAC, especially prior to NAT with FOLFIRINOX.
•Neoadjuvant FOLFIRINOX was associated with excellent overall survival.•Active smoking impaired the benefit of neoadjuvant FOLFIRINOX.•No interactions between smoking status and non-FOLFIRINOX regimens were observed.</description><subject>Antineoplastic Combined Chemotherapy Protocols - adverse effects</subject><subject>Carcinoma, Pancreatic Ductal - drug therapy</subject><subject>Carcinoma, Pancreatic Ductal - surgery</subject><subject>Cigarette</subject><subject>Fluorouracil - therapeutic use</subject><subject>FOLFIRINOX</subject><subject>Humans</subject><subject>NAT</subject><subject>Neoadjuvant therapy</subject><subject>Neoadjuvant Therapy - adverse effects</subject><subject>Pancreatic cancer</subject><subject>Pancreatic Neoplasms</subject><subject>Pancreatic Neoplasms - drug therapy</subject><subject>Pancreatic Neoplasms - surgery</subject><subject>Pancreatic surgery</subject><subject>PDAC</subject><subject>Prognostic factors</subject><subject>Prospective Studies</subject><subject>Retrospective Studies</subject><subject>Smoking</subject><subject>Smoking - adverse effects</subject><subject>Survival</subject><issn>0959-8049</issn><issn>1879-0852</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kF1LwzAUhoMoOj_-gBeSS28689E2KXgj4nQwHPgB3oXs9FRT13Ym7cB_b8amlxJIziHPeeE8hJxzNuaM51f1GGuwY8GEHHMuRSH3yIhrVSRMZ2KfjFiRFYlmaXFEjkOoGWNKp-yQHEmluFQpGxF4brpP175T16ys84H2H0ixqhB62lW0xc6W9bC2bU8n89lk-jR9nL_RrqWrLvQeQ-Rc7MLg125tl9TFH9uCR9s7oBBL9KfkoLLLgGe794S8Tu5ebh-S2fx-enszS0Ay1SeIWOo0K5QoEbMcpKwkg3gE5NyqTAm0mC4g3gvQUheYQs5KqWABwItMnpDLbe7Kd18Dht40LgAulzauMQQjdJ4pzTPOIiq2KPguBI-VWXnXWP9tODMbuaY2G7lmI9ds5cahi13-sGiw_Bv5tRmB6y2Accu1Q28COIwKSuejKFN27r_8H8vdjB4</recordid><startdate>202311</startdate><enddate>202311</enddate><creator>Leonhardt, Carl-Stephan</creator><creator>Pils, Dietmar</creator><creator>Qadan, Motaz</creator><creator>Gustorff, Charlotte</creator><creator>Sahora, Klaus</creator><creator>Klaiber, Ulla</creator><creator>Warshaw, Andrew L.</creator><creator>Prager, Gerald</creator><creator>Ferrone, Cristina R.</creator><creator>Lillemoe, Keith D.</creator><creator>Schindl, Martin</creator><creator>Strobel, Oliver</creator><creator>Castillo, Carlos Fernández-del</creator><creator>Hank, Thomas</creator><general>Elsevier Ltd</general><scope>6I.</scope><scope>AAFTH</scope><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/0009-0007-1172-0942</orcidid><orcidid>https://orcid.org/0000-0001-8087-2295</orcidid></search><sort><creationdate>202311</creationdate><title>Smoking impairs the effect of neoadjuvant FOLFIRINOX on postresection survival in pancreatic cancer</title><author>Leonhardt, Carl-Stephan ; Pils, Dietmar ; Qadan, Motaz ; Gustorff, Charlotte ; Sahora, Klaus ; Klaiber, Ulla ; Warshaw, Andrew L. ; Prager, Gerald ; Ferrone, Cristina R. ; Lillemoe, Keith D. ; Schindl, Martin ; Strobel, Oliver ; Castillo, Carlos Fernández-del ; Hank, Thomas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c307t-eeed845972dee56c33f30c0c02c61a7572eae4bceaebc8389e4c60d37cbcc1953</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Antineoplastic Combined Chemotherapy Protocols - adverse effects</topic><topic>Carcinoma, Pancreatic Ductal - drug therapy</topic><topic>Carcinoma, Pancreatic Ductal - surgery</topic><topic>Cigarette</topic><topic>Fluorouracil - therapeutic use</topic><topic>FOLFIRINOX</topic><topic>Humans</topic><topic>NAT</topic><topic>Neoadjuvant therapy</topic><topic>Neoadjuvant Therapy - adverse effects</topic><topic>Pancreatic cancer</topic><topic>Pancreatic Neoplasms</topic><topic>Pancreatic Neoplasms - drug therapy</topic><topic>Pancreatic Neoplasms - surgery</topic><topic>Pancreatic surgery</topic><topic>PDAC</topic><topic>Prognostic factors</topic><topic>Prospective Studies</topic><topic>Retrospective Studies</topic><topic>Smoking</topic><topic>Smoking - adverse effects</topic><topic>Survival</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Leonhardt, Carl-Stephan</creatorcontrib><creatorcontrib>Pils, Dietmar</creatorcontrib><creatorcontrib>Qadan, Motaz</creatorcontrib><creatorcontrib>Gustorff, Charlotte</creatorcontrib><creatorcontrib>Sahora, Klaus</creatorcontrib><creatorcontrib>Klaiber, Ulla</creatorcontrib><creatorcontrib>Warshaw, Andrew L.</creatorcontrib><creatorcontrib>Prager, Gerald</creatorcontrib><creatorcontrib>Ferrone, Cristina R.</creatorcontrib><creatorcontrib>Lillemoe, Keith D.</creatorcontrib><creatorcontrib>Schindl, Martin</creatorcontrib><creatorcontrib>Strobel, Oliver</creatorcontrib><creatorcontrib>Castillo, Carlos Fernández-del</creatorcontrib><creatorcontrib>Hank, Thomas</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><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>European journal of cancer (1990)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Leonhardt, Carl-Stephan</au><au>Pils, Dietmar</au><au>Qadan, Motaz</au><au>Gustorff, Charlotte</au><au>Sahora, Klaus</au><au>Klaiber, Ulla</au><au>Warshaw, Andrew L.</au><au>Prager, Gerald</au><au>Ferrone, Cristina R.</au><au>Lillemoe, Keith D.</au><au>Schindl, Martin</au><au>Strobel, Oliver</au><au>Castillo, Carlos Fernández-del</au><au>Hank, Thomas</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Smoking impairs the effect of neoadjuvant FOLFIRINOX on postresection survival in pancreatic cancer</atitle><jtitle>European journal of cancer (1990)</jtitle><addtitle>Eur J Cancer</addtitle><date>2023-11</date><risdate>2023</risdate><volume>193</volume><spage>113293</spage><epage>113293</epage><pages>113293-113293</pages><artnum>113293</artnum><issn>0959-8049</issn><eissn>1879-0852</eissn><abstract>Smoking plays an important role in carcinogenesis, including pancreatic ductal adenocarcinoma (PDAC). However, little is known about the association between smoking status and prognosis in resected PDAC.
All patients who underwent resection for PDAC were identified from two prospective institutional databases. Clinicopathologic data as well as demographics including smoking status were extracted. Survival analysis and multivariable Cox regression modelling was performed. Restricted cubic splines were used for linear data to define cut-off points.
Out of 848 patients, 357 (42.1%) received neoadjuvant treatment (NAT), 491 upfront resection (57.9%), and 475 (56%) adjuvant therapy. The median overall survival (OS) was 27.8 months, 36.1 months, and 23.0 months for the entire cohort, after NAT and upfront resection. 464 patients were never smokers (54.7%), 250 former smokers (29.5%), and 134 active smokers (15.8%). In the multivariable model, the interaction of neoadjuvant FOLFIRINOX and active smoking was associated with the highest risk for decreased OS (harzard ratio (HR) 2.35; 95% confidence interval 1.13–4.90) and strongly mitigated the benefit of FOLFIRNOX (HR 0.40; 95% CI 0.25–0.63). Adjusted median OS in NAT patients with FOLFIRINOX was not reached for never and former smokers, compared to 26.2 months in active smokers. Based on the model, a nomogram was generated to illustrate the probability of 5-year survival after PDAC resection.
The present study confirms that neoadjuvant FOLFIRINOX is associated with excellent survival and demonstrates that active smoking reduces its benefit. The nomogram can assist in daily clinical practice and emphasises the importance of smoking cessation in patients with PDAC, especially prior to NAT with FOLFIRINOX.
•Neoadjuvant FOLFIRINOX was associated with excellent overall survival.•Active smoking impaired the benefit of neoadjuvant FOLFIRINOX.•No interactions between smoking status and non-FOLFIRINOX regimens were observed.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>37713740</pmid><doi>10.1016/j.ejca.2023.113293</doi><tpages>1</tpages><orcidid>https://orcid.org/0009-0007-1172-0942</orcidid><orcidid>https://orcid.org/0000-0001-8087-2295</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | European journal of cancer (1990), 2023-11, Vol.193, p.113293-113293, Article 113293 |
| issn | 0959-8049 1879-0852 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Antineoplastic Combined Chemotherapy Protocols - adverse effects Carcinoma, Pancreatic Ductal - drug therapy Carcinoma, Pancreatic Ductal - surgery Cigarette Fluorouracil - therapeutic use FOLFIRINOX Humans NAT Neoadjuvant therapy Neoadjuvant Therapy - adverse effects Pancreatic cancer Pancreatic Neoplasms Pancreatic Neoplasms - drug therapy Pancreatic Neoplasms - surgery Pancreatic surgery PDAC Prognostic factors Prospective Studies Retrospective Studies Smoking Smoking - adverse effects Survival |
| title | Smoking impairs the effect of neoadjuvant FOLFIRINOX on postresection survival in pancreatic cancer |
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