Optimal oncologic management and mTOR inhibitor introduction are safe and improve survival in kidney and liver allograft recipients with de novo carcinoma
Prognosis and oncologic treatment feasibility in solid organ transplant patients with de novo cancer remain poorly described. We investigated the impact of immunosuppressive therapy modifications after de novo cancer diagnosis on oncologic treatment feasibility, toxicities, and prognosis. Patients w...
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Veröffentlicht in: | International journal of cancer 2019-02, Vol.144 (4), p.886-896 |
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creator | Rousseau, Benoit Guillemin, Aude Duvoux, Christophe Neuzillet, Cindy Tlemsani, Camille Compagnon, Philippe Azoulay, Daniel Salloum, Chaddy Laurent, Alexis Taille, Alexandre Salomon, Laurent Cholley, Irène Haioun, Corinne Dupuis, Jehan Wolkenstein, Pierre Matignon, Marie‐Bénédicte Grimbert, Philippe Tournigand, Christophe |
description | Prognosis and oncologic treatment feasibility in solid organ transplant patients with de novo cancer remain poorly described. We investigated the impact of immunosuppressive therapy modifications after de novo cancer diagnosis on oncologic treatment feasibility, toxicities, and prognosis. Patients with de novo cancer (excluding nonmelanoma skin cancers) were selected from a monocentric cohort of 4,637 kidney and liver allograft recipients. We assessed oncologic treatment optimality according to guidelines and analyzed immunosuppressive drug modifications and oncologic treatment impacts on treatment feasibility, toxicities, and graft/patient survivals. A total of 180 patients with 205 cancers were included: mean age 60 years, median delay from transplantation to first de novo cancer 5 years. In 46% of cases, immunosuppressive therapy was modified after cancer diagnosis: 24% dose reduction and 22% mTOR inhibitor introduction. Optimal oncologic treatment was performed in 80% and 38% of patients with localized and advanced cancer respectively. Transplantation and immunosuppression hindered optimal oncologic treatment in 11% instances. Immunosuppressive therapy modifications did not affect oncologic treatment tolerance nor graft survival. In multivariate analysis, optimal oncologic treatment and mTOR inhibitor introduction improved survival of patients with de novo carcinoma. Optimal oncologic treatment is feasible in kidney and liver allograft recipients without safety concerns. Optimal oncologic treatment and mTOR inhibitor introduction seem to markedly improve survival of patients with de novo carcinoma.
What's new?
Risk of cancer after solid organ transplantation is increased, in part due to immunosuppressive treatments modifying the balance between immune tolerance and anti‐tumoral immunity. mTOR inhibitors, which today are used either as an immunosuppressive agent to prevent graft rejection or an anti‐tumor drug, have shown therapeutic promise for these patients, however. In this large well‐documented cohort, immunosuppression dose reduction does not translate into overall survival benefit. Rather, optimal oncological treatment and introduction of a mTOR inhibitor at immunosuppressive doses are feasible without safety concerns in solid organ transplant patients presenting with de novo carcinoma, and dramatically improve patient overall survival. |
doi_str_mv | 10.1002/ijc.31769 |
format | Article |
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What's new?
Risk of cancer after solid organ transplantation is increased, in part due to immunosuppressive treatments modifying the balance between immune tolerance and anti‐tumoral immunity. mTOR inhibitors, which today are used either as an immunosuppressive agent to prevent graft rejection or an anti‐tumor drug, have shown therapeutic promise for these patients, however. In this large well‐documented cohort, immunosuppression dose reduction does not translate into overall survival benefit. Rather, optimal oncological treatment and introduction of a mTOR inhibitor at immunosuppressive doses are feasible without safety concerns in solid organ transplant patients presenting with de novo carcinoma, and dramatically improve patient overall survival.</description><identifier>ISSN: 0020-7136</identifier><identifier>EISSN: 1097-0215</identifier><identifier>DOI: 10.1002/ijc.31769</identifier><identifier>PMID: 30155929</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Adult ; Aged ; Allografts ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Cancer ; Combined Modality Therapy ; Diagnosis ; feasibility ; Feasibility studies ; Female ; Humans ; Immunological tolerance ; immunosuppressant drugs ; Immunosuppression ; Immunosuppressive agents ; Immunosuppressive Agents - administration & dosage ; Kidney transplantation ; Kidney Transplantation - methods ; Kidneys ; Liver ; Liver transplantation ; Liver Transplantation - methods ; Male ; Medical diagnosis ; Medical prognosis ; Medical research ; Middle Aged ; mTOR inhibitors ; Multivariate analysis ; Neoplasms - pathology ; Neoplasms - therapy ; Patients ; Prognosis ; Protein Kinase Inhibitors - administration & dosage ; Skin cancer ; Survival ; Survival Analysis ; TOR protein ; TOR Serine-Threonine Kinases - antagonists & inhibitors ; TOR Serine-Threonine Kinases - metabolism ; Toxicity ; Transplantation ; Transplants & implants</subject><ispartof>International journal of cancer, 2019-02, Vol.144 (4), p.886-896</ispartof><rights>2018 UICC</rights><rights>2018 UICC.</rights><rights>2019 UICC</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3889-b720ba48ad90405aebccec4798f7e3d7252a388109e76f5387f734784c05d8de3</citedby><cites>FETCH-LOGICAL-c3889-b720ba48ad90405aebccec4798f7e3d7252a388109e76f5387f734784c05d8de3</cites><orcidid>0000-0003-3556-5178</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fijc.31769$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fijc.31769$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30155929$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rousseau, Benoit</creatorcontrib><creatorcontrib>Guillemin, Aude</creatorcontrib><creatorcontrib>Duvoux, Christophe</creatorcontrib><creatorcontrib>Neuzillet, Cindy</creatorcontrib><creatorcontrib>Tlemsani, Camille</creatorcontrib><creatorcontrib>Compagnon, Philippe</creatorcontrib><creatorcontrib>Azoulay, Daniel</creatorcontrib><creatorcontrib>Salloum, Chaddy</creatorcontrib><creatorcontrib>Laurent, Alexis</creatorcontrib><creatorcontrib>Taille, Alexandre</creatorcontrib><creatorcontrib>Salomon, Laurent</creatorcontrib><creatorcontrib>Cholley, Irène</creatorcontrib><creatorcontrib>Haioun, Corinne</creatorcontrib><creatorcontrib>Dupuis, Jehan</creatorcontrib><creatorcontrib>Wolkenstein, Pierre</creatorcontrib><creatorcontrib>Matignon, Marie‐Bénédicte</creatorcontrib><creatorcontrib>Grimbert, Philippe</creatorcontrib><creatorcontrib>Tournigand, Christophe</creatorcontrib><title>Optimal oncologic management and mTOR inhibitor introduction are safe and improve survival in kidney and liver allograft recipients with de novo carcinoma</title><title>International journal of cancer</title><addtitle>Int J Cancer</addtitle><description>Prognosis and oncologic treatment feasibility in solid organ transplant patients with de novo cancer remain poorly described. We investigated the impact of immunosuppressive therapy modifications after de novo cancer diagnosis on oncologic treatment feasibility, toxicities, and prognosis. Patients with de novo cancer (excluding nonmelanoma skin cancers) were selected from a monocentric cohort of 4,637 kidney and liver allograft recipients. We assessed oncologic treatment optimality according to guidelines and analyzed immunosuppressive drug modifications and oncologic treatment impacts on treatment feasibility, toxicities, and graft/patient survivals. A total of 180 patients with 205 cancers were included: mean age 60 years, median delay from transplantation to first de novo cancer 5 years. In 46% of cases, immunosuppressive therapy was modified after cancer diagnosis: 24% dose reduction and 22% mTOR inhibitor introduction. Optimal oncologic treatment was performed in 80% and 38% of patients with localized and advanced cancer respectively. Transplantation and immunosuppression hindered optimal oncologic treatment in 11% instances. Immunosuppressive therapy modifications did not affect oncologic treatment tolerance nor graft survival. In multivariate analysis, optimal oncologic treatment and mTOR inhibitor introduction improved survival of patients with de novo carcinoma. Optimal oncologic treatment is feasible in kidney and liver allograft recipients without safety concerns. Optimal oncologic treatment and mTOR inhibitor introduction seem to markedly improve survival of patients with de novo carcinoma.
What's new?
Risk of cancer after solid organ transplantation is increased, in part due to immunosuppressive treatments modifying the balance between immune tolerance and anti‐tumoral immunity. mTOR inhibitors, which today are used either as an immunosuppressive agent to prevent graft rejection or an anti‐tumor drug, have shown therapeutic promise for these patients, however. In this large well‐documented cohort, immunosuppression dose reduction does not translate into overall survival benefit. Rather, optimal oncological treatment and introduction of a mTOR inhibitor at immunosuppressive doses are feasible without safety concerns in solid organ transplant patients presenting with de novo carcinoma, and dramatically improve patient overall survival.</description><subject>Adult</subject><subject>Aged</subject><subject>Allografts</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Cancer</subject><subject>Combined Modality Therapy</subject><subject>Diagnosis</subject><subject>feasibility</subject><subject>Feasibility studies</subject><subject>Female</subject><subject>Humans</subject><subject>Immunological tolerance</subject><subject>immunosuppressant drugs</subject><subject>Immunosuppression</subject><subject>Immunosuppressive agents</subject><subject>Immunosuppressive Agents - administration & dosage</subject><subject>Kidney transplantation</subject><subject>Kidney Transplantation - methods</subject><subject>Kidneys</subject><subject>Liver</subject><subject>Liver transplantation</subject><subject>Liver Transplantation - methods</subject><subject>Male</subject><subject>Medical diagnosis</subject><subject>Medical prognosis</subject><subject>Medical research</subject><subject>Middle Aged</subject><subject>mTOR inhibitors</subject><subject>Multivariate analysis</subject><subject>Neoplasms - pathology</subject><subject>Neoplasms - therapy</subject><subject>Patients</subject><subject>Prognosis</subject><subject>Protein Kinase Inhibitors - administration & dosage</subject><subject>Skin cancer</subject><subject>Survival</subject><subject>Survival Analysis</subject><subject>TOR protein</subject><subject>TOR Serine-Threonine Kinases - antagonists & inhibitors</subject><subject>TOR Serine-Threonine Kinases - metabolism</subject><subject>Toxicity</subject><subject>Transplantation</subject><subject>Transplants & implants</subject><issn>0020-7136</issn><issn>1097-0215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU9P3DAQxa2KqmxpD_0CyBInDgE7jtfJEa2gUCGtVNFz5NgTmCWxF-cP2q_ST9thl_bW01ien94bvcfYNykupBD5JW7chZJmWX1gCykqk4lc6iO2oJ3IjFTLY_Z5GDZCSKlF8YkdKyG1rvJqwX6vtyP2tuMxuNjFR3S8t8E-Qg9h5DZ43j-sf3IMT9jgGBO9xhT95EaMgdsEfLAt7EHstynO9DGlGWeSxMCf0QfY7dcdzpC47cgk2XbkCRxukVwG_orjE_fAQ5wjdzY5DLG3X9jH1nYDfH2fJ-zXzfXD6ja7X3-_W13dZ06VZZU1JheNLUrrK1EIbaFxDlxhqrI1oLzJdW4JpFzALFutStMaVZiycEL70oM6YWcHXTr_ZYJhrDdxSoEsa4qx0mpJg6jzA-VSHIYEbb1NFFza1VLUby3U1EK9b4HY03fFqenB_yP_xk7A5QF4xQ52_1eq736sDpJ_ALuNk9s</recordid><startdate>20190215</startdate><enddate>20190215</enddate><creator>Rousseau, Benoit</creator><creator>Guillemin, Aude</creator><creator>Duvoux, Christophe</creator><creator>Neuzillet, Cindy</creator><creator>Tlemsani, Camille</creator><creator>Compagnon, Philippe</creator><creator>Azoulay, Daniel</creator><creator>Salloum, Chaddy</creator><creator>Laurent, Alexis</creator><creator>Taille, Alexandre</creator><creator>Salomon, Laurent</creator><creator>Cholley, Irène</creator><creator>Haioun, Corinne</creator><creator>Dupuis, Jehan</creator><creator>Wolkenstein, Pierre</creator><creator>Matignon, Marie‐Bénédicte</creator><creator>Grimbert, Philippe</creator><creator>Tournigand, Christophe</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, Inc</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>7T5</scope><scope>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><orcidid>https://orcid.org/0000-0003-3556-5178</orcidid></search><sort><creationdate>20190215</creationdate><title>Optimal oncologic management and mTOR inhibitor introduction are safe and improve survival in kidney and liver allograft recipients with de novo carcinoma</title><author>Rousseau, Benoit ; Guillemin, Aude ; Duvoux, Christophe ; Neuzillet, Cindy ; Tlemsani, Camille ; Compagnon, Philippe ; Azoulay, Daniel ; Salloum, Chaddy ; Laurent, Alexis ; Taille, Alexandre ; Salomon, Laurent ; Cholley, Irène ; Haioun, Corinne ; Dupuis, Jehan ; Wolkenstein, Pierre ; Matignon, Marie‐Bénédicte ; Grimbert, Philippe ; Tournigand, Christophe</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3889-b720ba48ad90405aebccec4798f7e3d7252a388109e76f5387f734784c05d8de3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Allografts</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Cancer</topic><topic>Combined Modality Therapy</topic><topic>Diagnosis</topic><topic>feasibility</topic><topic>Feasibility studies</topic><topic>Female</topic><topic>Humans</topic><topic>Immunological tolerance</topic><topic>immunosuppressant drugs</topic><topic>Immunosuppression</topic><topic>Immunosuppressive agents</topic><topic>Immunosuppressive Agents - administration & dosage</topic><topic>Kidney transplantation</topic><topic>Kidney Transplantation - methods</topic><topic>Kidneys</topic><topic>Liver</topic><topic>Liver transplantation</topic><topic>Liver Transplantation - methods</topic><topic>Male</topic><topic>Medical diagnosis</topic><topic>Medical prognosis</topic><topic>Medical research</topic><topic>Middle Aged</topic><topic>mTOR inhibitors</topic><topic>Multivariate analysis</topic><topic>Neoplasms - pathology</topic><topic>Neoplasms - therapy</topic><topic>Patients</topic><topic>Prognosis</topic><topic>Protein Kinase Inhibitors - administration & dosage</topic><topic>Skin cancer</topic><topic>Survival</topic><topic>Survival Analysis</topic><topic>TOR protein</topic><topic>TOR Serine-Threonine Kinases - antagonists & inhibitors</topic><topic>TOR Serine-Threonine Kinases - metabolism</topic><topic>Toxicity</topic><topic>Transplantation</topic><topic>Transplants & implants</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rousseau, Benoit</creatorcontrib><creatorcontrib>Guillemin, Aude</creatorcontrib><creatorcontrib>Duvoux, Christophe</creatorcontrib><creatorcontrib>Neuzillet, Cindy</creatorcontrib><creatorcontrib>Tlemsani, Camille</creatorcontrib><creatorcontrib>Compagnon, Philippe</creatorcontrib><creatorcontrib>Azoulay, Daniel</creatorcontrib><creatorcontrib>Salloum, Chaddy</creatorcontrib><creatorcontrib>Laurent, Alexis</creatorcontrib><creatorcontrib>Taille, Alexandre</creatorcontrib><creatorcontrib>Salomon, Laurent</creatorcontrib><creatorcontrib>Cholley, Irène</creatorcontrib><creatorcontrib>Haioun, Corinne</creatorcontrib><creatorcontrib>Dupuis, Jehan</creatorcontrib><creatorcontrib>Wolkenstein, Pierre</creatorcontrib><creatorcontrib>Matignon, Marie‐Bénédicte</creatorcontrib><creatorcontrib>Grimbert, Philippe</creatorcontrib><creatorcontrib>Tournigand, Christophe</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><jtitle>International journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rousseau, Benoit</au><au>Guillemin, Aude</au><au>Duvoux, Christophe</au><au>Neuzillet, Cindy</au><au>Tlemsani, Camille</au><au>Compagnon, Philippe</au><au>Azoulay, Daniel</au><au>Salloum, Chaddy</au><au>Laurent, Alexis</au><au>Taille, Alexandre</au><au>Salomon, Laurent</au><au>Cholley, Irène</au><au>Haioun, Corinne</au><au>Dupuis, Jehan</au><au>Wolkenstein, Pierre</au><au>Matignon, Marie‐Bénédicte</au><au>Grimbert, Philippe</au><au>Tournigand, Christophe</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Optimal oncologic management and mTOR inhibitor introduction are safe and improve survival in kidney and liver allograft recipients with de novo carcinoma</atitle><jtitle>International journal of cancer</jtitle><addtitle>Int J Cancer</addtitle><date>2019-02-15</date><risdate>2019</risdate><volume>144</volume><issue>4</issue><spage>886</spage><epage>896</epage><pages>886-896</pages><issn>0020-7136</issn><eissn>1097-0215</eissn><abstract>Prognosis and oncologic treatment feasibility in solid organ transplant patients with de novo cancer remain poorly described. We investigated the impact of immunosuppressive therapy modifications after de novo cancer diagnosis on oncologic treatment feasibility, toxicities, and prognosis. Patients with de novo cancer (excluding nonmelanoma skin cancers) were selected from a monocentric cohort of 4,637 kidney and liver allograft recipients. We assessed oncologic treatment optimality according to guidelines and analyzed immunosuppressive drug modifications and oncologic treatment impacts on treatment feasibility, toxicities, and graft/patient survivals. A total of 180 patients with 205 cancers were included: mean age 60 years, median delay from transplantation to first de novo cancer 5 years. In 46% of cases, immunosuppressive therapy was modified after cancer diagnosis: 24% dose reduction and 22% mTOR inhibitor introduction. Optimal oncologic treatment was performed in 80% and 38% of patients with localized and advanced cancer respectively. Transplantation and immunosuppression hindered optimal oncologic treatment in 11% instances. Immunosuppressive therapy modifications did not affect oncologic treatment tolerance nor graft survival. In multivariate analysis, optimal oncologic treatment and mTOR inhibitor introduction improved survival of patients with de novo carcinoma. Optimal oncologic treatment is feasible in kidney and liver allograft recipients without safety concerns. Optimal oncologic treatment and mTOR inhibitor introduction seem to markedly improve survival of patients with de novo carcinoma.
What's new?
Risk of cancer after solid organ transplantation is increased, in part due to immunosuppressive treatments modifying the balance between immune tolerance and anti‐tumoral immunity. mTOR inhibitors, which today are used either as an immunosuppressive agent to prevent graft rejection or an anti‐tumor drug, have shown therapeutic promise for these patients, however. In this large well‐documented cohort, immunosuppression dose reduction does not translate into overall survival benefit. Rather, optimal oncological treatment and introduction of a mTOR inhibitor at immunosuppressive doses are feasible without safety concerns in solid organ transplant patients presenting with de novo carcinoma, and dramatically improve patient overall survival.</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>30155929</pmid><doi>10.1002/ijc.31769</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-3556-5178</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Adult Aged Allografts Antineoplastic Combined Chemotherapy Protocols - therapeutic use Cancer Combined Modality Therapy Diagnosis feasibility Feasibility studies Female Humans Immunological tolerance immunosuppressant drugs Immunosuppression Immunosuppressive agents Immunosuppressive Agents - administration & dosage Kidney transplantation Kidney Transplantation - methods Kidneys Liver Liver transplantation Liver Transplantation - methods Male Medical diagnosis Medical prognosis Medical research Middle Aged mTOR inhibitors Multivariate analysis Neoplasms - pathology Neoplasms - therapy Patients Prognosis Protein Kinase Inhibitors - administration & dosage Skin cancer Survival Survival Analysis TOR protein TOR Serine-Threonine Kinases - antagonists & inhibitors TOR Serine-Threonine Kinases - metabolism Toxicity Transplantation Transplants & implants |
title | Optimal oncologic management and mTOR inhibitor introduction are safe and improve survival in kidney and liver allograft recipients with de novo carcinoma |
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