Cancers solides après transplantation d’organe : épidémiologie, pronostic et spécificités de prise en charge

Guillemin, A; Rousseau, Benoı̂t; Neuzillet, Cindy; Joly, Charlotte; Boussion, H.; Grimbert, Philippe; Compagnon, Philippe; Duvoux, Christophe; Tournigand, Christophe

doi:10.1016/j.bulcan.2016.12.008

Cited by 11 publications

(12 citation statements)

References 46 publications

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“…With increased immunosuppression, however, there is also an increased rate of post-transplant infections and malignancies. The risk of cancer after transplantation is increased by three- to five-fold compared with that of the general population, and the prognosis of transplanted patients with malignancy is poorer than that of other cancer patients [1,2]. The high risk of cancer after transplantation has been linked to environmental carcinogenic risk factors, the comorbidities of transplanted recipients, and the detrimental effects of immunosuppressants such as activation of oncogenic viruses, carcinogenic effects of the medications, and loss of immunity for immune-surveillance [3].…”

Section: Introductionmentioning

confidence: 99%

Programmed Cell Death 1 (PD-1) Inhibitors in Renal Transplant Patients with Advanced Cancer: A Double-Edged Sword?

Lai

Lin

Hwang

et al. 2019

IJMS

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Given advancements in cancer immunity, cancer treatment has gained breakthrough developments. Immune checkpoint inhibitors, such as programmed cell death 1 (PD-1) inhibitors, are the most promising drugs in the field and have been approved to treat various types of cancer, such as metastatic melanoma, head and neck squamous cell carcinoma, and urothelial carcinoma. However, whether PD-1 inhibitors should be administered to renal transplant patients with advanced cancer remains unclear because the T-cells produced after administration of these inhibitors act against not only tumor antigens but also donor alloantigens. Thus, the use of PD-1 inhibitors in kidney-transplanted patients with advanced cancer is limited on account of the high risk of graft failure due to acute rejection. Hence, finding optimal treatment regimens to enhance the tumor-specific T-cell response and decrease T-cell-mediated alloreactivity after administration of a PD-1 inhibitor is necessary. Thus far, no recommendations for the use of PD-1 inhibitors to treat cancer in renal transplant patients are yet available, and very few cases reporting kidney-transplanted patients treated with PD-1 inhibitors are available in the literature. Therefore, in this work, we review the published cases and suggest feasible approaches for renal transplant patients with advanced malignancy treated by a PD-1 inhibitor. Of the 22 cases we obtained, four patients maintained intact grafts without tumor progression after treatment with a PD-1 inhibitor. Among these patients, one maintained steroid dose before initiation of anti-PD1, two received immunosuppressive regimens with low-dose steroid and calcineurin inhibitor (CNI)-elimination with sirolimus before initiation of anti-PD-1 therapy, and one received combined anti-PD-1, anti-vascular endothelial growth factor (VEGF), and chemotherapy with unchanged immunosuppressive regimens. mammalian target of rapamycin (mTOR) inhibitors and anti-VEGF may act as regulators of tumor-specific and allogenic T-cells. However, more studies are necessary to explore the optimal therapy and ensure the safety and efficacy of PD-1 inhibitors in kidney-transplanted patients.

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Section: Introductionmentioning

confidence: 99%

Programmed Cell Death 1 (PD-1) Inhibitors in Renal Transplant Patients with Advanced Cancer: A Double-Edged Sword?

Lai

Lin

Hwang

et al. 2019

IJMS

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“…Наиболее распространенными злокачественными новообразованиями были рак легких (n = 1993), НХЛ (n = 1846) и рак предстательной железы (n = 1544) [15]. По мнению A. Guillemin et al, риск развития рака различных локализаций у реципиентов солидных органов повышен в 2,6 раза по сравнению с популяцией в целом и является третьей по частоте причиной смерти среди этой категории больных [5].…”

Section: эпидемиологияunclassified

“…Одни авторы говорят о снижении риска развития злокачественных новообразований на фоне приема сиролимуса (по сравнению с контролем применение сиролимуса снижало на 40% риск развития злокачественных новообразований и на 56% -риск развития немеланомного рака кожи) [7,11,14,18,19], другие не отмечают такого эффекта [19]. Экспериментальные исследования in vivo показали, что азатиоприн повышает риск развития злокачественных новообразований, и особенно плоскоклеточного рака кожи за счет мутагенного эффекта и потенцирования неблагоприятного эффекта ультрафиолетовых лучей [3,5,7,8]. Циклоспорин увеличивает риск развития саркомы Капоши и метастатического поражения легких у пациентов с железистым раком [ [19].…”

Section: патогенезunclassified

“…Канцерогенный эффект ингибиторов кальциневрина достигается главным образом за счет стимуляции секреции клетками трансформирующего фактора роста (Transforming growth factor beta -TGF-бета) и повышенной экспрессии фактора роста эндотелия сосудов [8]. Реципиенты солидных органов, получающие микофенолата мофетил, имеют более низкий риск развития злокачественных новообразований, что может быть связано со снижением частоты острого отторжения, что, в свою очередь, приводит к снижению потребности в повышенных дозах иммуносупрессивных препаратов [5,7]. Роль кортикостероидов в развитии злокачественных новообразований трудно оценить, т. к. они практически всегда назначаются одновременно с другими иммунодепрессантами [5].…”

Section: патогенезunclassified

“…С учетом неуклонно возрастающего количества трансплантаций солидных органов во всем мире (только за 2020 год в мире выполнено 113 363 трансплантации солидных органов) и постепенного увеличения продолжительности жизни реципиентов донорских органов актуальность изучения злокачественных новообразований будет только возрастать. Вопросы развития онкозаболеваний у этой категории достаточно подробно освещены в иностранной литературе, тогда как отечественных источников мы не нашли [1][2][3][4][5][6][7][8][9][10][11][12][13]30].…”

Section: Introductionunclassified

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Post-transplant malignancies in solid organ recipients: development mechanisms and risk factors

Nikulin

Пашков

Якунин

2021

RJTAO

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According to the International Agency for Research on Cancer, there were an estimated 19,292,789 new cancer cases in various localizations and 9,958,133 cancer deaths worldwide in 2020. These frightening figures clearly show that malignancies among the population is a pressing matter. The risk of post-transplant malignancy in solid organ recipients is 2–6-times higher than in the general population. Given the steadily increasing number of solid organ transplants worldwide and the gradual increase in life expectancy among organ recipients, studying the issues concerning risk factors and development mechanisms becomes a crucial task.

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

Rousseau

Guillemin

Duvoux

et al. 2018

Intl Journal of Cancer

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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.

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Cancers solides après transplantation d’organe : épidémiologie, pronostic et spécificités de prise en charge

Cited by 11 publications

References 46 publications

Programmed Cell Death 1 (PD-1) Inhibitors in Renal Transplant Patients with Advanced Cancer: A Double-Edged Sword?

Programmed Cell Death 1 (PD-1) Inhibitors in Renal Transplant Patients with Advanced Cancer: A Double-Edged Sword?

Post-transplant malignancies in solid organ recipients: development mechanisms and risk factors

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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