Optimal oncologic management and mTOR inhibitor introduction are safe and improve survival in kidney and liver allograft recipients with de novo carcinoma

被引：31

作者：

Rousseau, Benoit ^{[1
,2
,3
]}

Guillemin, Aude ^{[1
,2
]}

Duvoux, Christophe ^{[2
,4
]}

Neuzillet, Cindy ^{[1
,2
]}

Tlemsani, Camille ^{[5
]}

Compagnon, Philippe ^{[2
,6
]}

Azoulay, Daniel ^{[2
,6
]}

Salloum, Chaddy ^{[2
,6
]}

Laurent, Alexis ^{[2
,6
]}

de la Taille, Alexandre ^{[2
,7
]}

Salomon, Laurent ^{[2
,7
]}

Cholley, Irene ^{[2
,7
]}

Haioun, Corinne ^{[2
,8
]}

Dupuis, Jehan ^{[2
,8
]}

Wolkenstein, Pierre ^{[2
,9
]}

Matignon, Marie-Benedicte ^{[2
,10
]}

Grimbert, Philippe ^{[2
,10
]}

Tournigand, Christophe ^{[1
,2
]}

机构：

[1] Henri Mondor Hosp, AP HP, Med Oncol, F-94100 Creteil, France

[2] Univ Paris Est, Fac Med, F-94000 Creteil, France

[3] Univ Paris Est Creteil, INSERM U955, IMRB, Team 18, F-94100 Creteil, France

[4] Henri Mondor Hosp, AP HP, Hepatol, F-94100 Creteil, France

[5] Cochin Hosp, AP HP, Med Oncol, F-75014 Paris, France

[6] Henri Mondor Hosp, AP HP, Visceral & Hepatobiliary Surg, F-94100 Creteil, France

[7] Henri Mondor Hosp, AP HP, Urol, F-94100 Creteil, France

[8] Henri Mondor Hosp, AP HP, Lymphoid Malignancies Unit, F-94100 Creteil, France

[9] Henri Mondor Hosp, AP HP, Dermatol, F-94100 Creteil, France

[10] Henri Mondor Hosp, AP HP, Nephrol, F-94100 Creteil, France

来源：

INTERNATIONAL JOURNAL OF CANCER | 2019年 / 144卷 / 04期

关键词：

cancer; transplantation; feasibility; toxicity; prognosis; mTOR inhibitors; immunosuppressant drugs; SOLID-ORGAN TRANSPLANTATION; CANCER; EVEROLIMUS; CONVERSION; MALIGNANCIES; DIAGNOSIS; PROGNOSIS; RISK;

D O I：

10.1002/ijc.31769

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：886 / 896

页数：11

共 29 条

[1] Management of solid tumours in organ-transplant recipients [J].

Ajithkumar, Thankamma V. ;

Parkinson, Christine A. ;

Butler, Andrew ;

Hatcher, Helen M. .

LANCET ONCOLOGY, 2007, 8 (10) :921-932

[2] mTOR regulates memory CD8 T-cell differentiation [J].

Araki, Koichi ;

Turner, Alexandra P. ;

Shaffer, Virginia Oliva ;

Gangappa, Shivaprakash ;

Keller, Susanne A. ;

Bachmann, Martin F. ;

Larsen, Christian P. ;

Ahmed, Rafi .

NATURE, 2009, 460 (7251) :108-U124

[3] Renal function improvement in liver transplant recipients after early everolimus conversion: A clinical practice cohort study in Spain [J].

Bilbao, Itxarone ;

Salcedo, Magdalena ;

Angel Gomez, Miguel ;

Jimenez, Carlos ;

Castroagudin, Javier ;

Fabregat, Joan ;

Almohalla, Carolina ;

Herrero, Ignacio ;

Cuervas-Mons, Valentin ;

Otero, Alejandra ;

Rubin, Angel ;

Miras, Manuel ;

Rodrigo, Juan ;

Serrano, Trinidad ;

Crespo, Gonzalo ;

De la Mata, Manuel ;

Bustamante, Javier ;

Luisa Gonzalez-Dieguez, M. ;

Moreno, Antonia ;

Narvaez, Isidoro ;

Guilera, Magda .

LIVER TRANSPLANTATION, 2015, 21 (08) :1056-1065

[4] De novo colorectal cancer: Five-year survival is markedly lower in transplant recipients compared with the general population [J].

Buell, JF ;

Papaconstantinou, HT ;

Skalow, B ;

Hanaway, MJ ;

Alloway, RR ;

Woodle, ES .

TRANSPLANTATION PROCEEDINGS, 2005, 37 (02) :960-961

[5] Conversion to mammalian target of rapamycin inhibitors in kidney transplant recipients with de novo cancers [J].

Cheung, Chi Yuen ;

Ma, Maggie Kam Man ;

Chak, Wai Leung ;

Chau, Ka Foon ;

Tang, Sydney Chi Wai .

ONCOTARGET, 2017, 8 (27) :44833-44841

[6] Results of the Conversion to Everolimus in Renal Transplant Recipients With Posttransplantation Malignancies [J].

Chiurchiu, C. ;

Carreno, C. A. ;

Schiavelli, R. ;

Petrone, H. ;

Balaguer, C. ;

Trimarchi, H. ;

Pujol, G. S. ;

Novoa, P. ;

Acosta, F. ;

Gonzalez, C. ;

Arriola, M. ;

Massari, P. U. .

TRANSPLANTATION PROCEEDINGS, 2010, 42 (01) :277-279

[7]

de Fijter JW, 2017, TRANSPLANTATION, V101, P45, DOI 10.1097/TP.0000000000001447

[8] The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORC1 and mTORC2 [J].

Delgoffe, Greg M. ;

Pollizzi, Kristen N. ;

Waickman, Adam T. ;

Heikamp, Emily ;

Meyers, David J. ;

Horton, Maureen R. ;

Xiao, Bo ;

Worley, Paul F. ;

Powell, Jonathan D. .

NATURE IMMUNOLOGY, 2011, 12 (04) :295-U117

[9] Spectrum of Cancer Risk Among US Solid Organ Transplant Recipients [J].

Engels, Eric A. ;

Pfeiffer, Ruth M. ;

Fraumeni, Joseph F., Jr. ;

Kasiske, Bertram L. ;

Israni, Ajay K. ;

Snyder, Jon J. ;

Wolfe, Robert A. ;

Goodrich, Nathan P. ;

Bayakly, A. Rana ;

Clarke, Christina A. ;

Copeland, Glenn ;

Finch, Jack L. ;

Fleissner, Mary Lou ;

Goodman, Marc T. ;

Kahn, Amy ;

Koch, Lori ;

Lynch, Charles F. ;

Madeleine, Margaret M. ;

Pawlish, Karen ;

Rao, Chandrika ;

Williams, Melanie A. ;

Castenson, David ;

Curry, Michael ;

Parsons, Ruth ;

Fant, Gregory ;

Lin, Monica .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2011, 306 (17) :1891-1901

[10] Cancer immunotherapy: the beginning of the end of cancer? [J].

Farkona, Sofia ;

Diamandis, Eleftherios P. ;

Blasutig, Ivan M. .

BMC MEDICINE, 2016, 14

← 1 2 3 →