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
Hauptverfasser: 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
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container_end_page 896
container_issue 4
container_start_page 886
container_title International journal of cancer
container_volume 144
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
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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. 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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. 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dosage</subject><subject>Skin cancer</subject><subject>Survival</subject><subject>Survival Analysis</subject><subject>TOR protein</subject><subject>TOR Serine-Threonine Kinases - antagonists &amp; inhibitors</subject><subject>TOR Serine-Threonine Kinases - metabolism</subject><subject>Toxicity</subject><subject>Transplantation</subject><subject>Transplants &amp; 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 &amp; 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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. 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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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