Immunosuppressive treatment and radiotherapy in kidney transplant patients: A systematic review

Table 1 Population, Intervention, Comparison, and Outcomes model

PICO
Patients	Kidney transplant recipients with cancer undergoing radiotherapy
Intervention	Withdraw antimetabolites and/or calcineurin inhibitors and/or mTOR inhibitors
Comparator	Maintain antimetabolites and/or calcineurin inhibitors and/or mTOR inhibitors
Outcome	Core outcome sets
Time frame	2010-2019
Study type	RCTs, meta-analysis of RCT; observational analytical studies

mTOR: Mammalian target of rapamycin; PICO: Population, Intervention, Comparison, and Outcomes; RCT: Randomized controlled trial.

Table 2 Search strategy

Electronic engineer	Search string
Pubmed	((“Renal transplant” OR “kidney transplant” OR “kidney transplantation” OR “renal transplantation”) AND (metastasis OR metastatic OR metastases OR “cancer” OR neoplasm OR “tumour” OR “cancers” OR “tumours” OR “tumor” OR “tumors” OR neoplasms OR melanoma OR PTLD OR lymphoma) AND (radiotherapy OR “radiation therapy”)) AND (“calcineurin inhibitors” OR “calcineurin inhibitor” OR CNI OR tacrolimus OR cyclosporine OR everolimus OR sirolimus OR “mTOR inhibitors” OR “mTOR-inhibitors” OR antimetabolites OR “antimetabolite”)
Web of Science	ALL=(((Renal transplant) OR (kidney transplant) OR (kidney transplantation) OR (renal transplantation)) AND (metastasis OR metastatic OR metastases OR cancer OR neoplasm OR tumour OR cancers OR tumours OR tumor OR tumors OR neoplasms OR melanoma OR PTLD OR lymphoma) AND (radiotherapy OR (radiation therapy)) AND ((calcineurin inhibitors) OR (calcineurin inhibitor) OR CNI OR tacrolimus OR cyclosporine OR everolimus OR sirolimus OR (mTOR inhibitors) OR (mTOR-inhibitors) OR antimetabolites OR antimetabolite))
Scopus	((“Renal transplant” OR “kidney transplant” OR “kidney transplantation” OR “renal transplantation”) AND (metastasis OR metastatic OR metastases OR “cancer” OR neoplasm OR “tumour” OR “cancers” OR “tumours” OR “tumor” OR “tumors” OR neoplasms OR melanoma OR PTLD OR lymphoma) AND (radiotherapy OR “radiation therapy”)) AND (“calcineurin inhibitors” OR “calcineurin inhibitor” OR CNI OR tacrolimus OR cyclosporine OR everolimus OR sirolimus OR “mTOR inhibitors” OR “mTOR-inhibitors” OR antimetabolites OR “antimetabolite”)AND (LIMIT-TO (PUBYEAR, 2019) OR LIMIT-TO (PUBYEAR, 2018) OR LIMIT-TO (PUBYEAR, 2017) OR LIMIT-TO (PUBYEAR, 2016) OR LIMIT-TO (PUBYEAR, 2015) OR LIMIT-TO (PUBYEAR, 2014) OR LIMIT-TO (PUBYEAR, 2013) OR LIMIT-TO (PUBYEAR, 2012) OR LIMIT-TO (PUBYEAR, 2011) OR LIMIT-TO (PUBYEAR, 2010) OR LIMIT-TO (PUBYEAR, 2009)) AND (LIMIT-TO (LANGUAGE, "English"))

CNI: Calcineurin inhibitor; mTOR: Mammalian target of rapamycin.

Table 3 Characteristics of included studies

Ref.	Study design	Patients (n)	Mean age	Type of cancer	Intervention	Patient survival	Graft survival
Binsaleh et al[15], 2011	Retrospective	9	55 (range: 40-72)	PCa	RT (60-66 Gy); 3 patients had their immunosuppressive regimen changed to a sirolimus-based therapy, while 6 had “judicious” reductions of CNI dosages	NR	4/9 failure; 5/9 good
Pettenati et al[20], 2016	Retrospective	6	63.5 yr (± 7.2)	PCa	RT (EBRT: 76 Gy; IRT: 145 Gy) +Immunosuppressive therapy [2 pts: CNI + AZA + steroids; 19 pts: CNI + MMF + Steroids; 2 pts: MMF, mTORI + Steroids]	1 patient died of PCa	No graft loss nor change in renal function due to PCa treatment
Antunes et al[13], 2018	Retrospective	29	53.4 (±10,7)	PCa	RT in 5 patients (details not reported)	1-yr: 86.2%5-yr: 86.2%10-yr: 79.3%	No patient undergoing RT had allograft failure
Oh et al[26], 2019	Retrospective	13	66 (range: 42-80)	PCa	RT (EBRT: 78 Gy; IRT: 144 Gy) + Immunosuppressive therapy [CIA (n = 8), MMF (n = 13), AZA (n = 3), tacrolimus (n = 12), sirolimus (n = 9), and/or prednisone (n = 20)]	3 yr: 93.8%	NR
Tasaki et al[21], 2019	Retrospective	3	65 (range: 60-67)	PCa	RT (IRT: 145 Gy) + Immunosuppressive therapy [2 pts: CIA + MMF + MP; 1 pt: tacrolimus + MMF +MP]	NR	2 pts good graft function; 1 pt declined graft function after 2 yr
Velvet et al[27], 2019	Retrospective	3	59.5	Lymphoma	RT (details not reported) + reduced immunosuppressive regimen	6 mo: 66.6%	NR

CNI: Calcineurin inhibitor; mTOR: Mammalian target of rapamycin; NR: Not reported; PCa: Prostate cancer; RT: Radiotherapy; EBRT: External beam RT; IRT: Interventional RT.