The Incidence of Cancer and Potential Role of Sirolimus Immunosuppression Conversion on Mortality Among a Single-Center Renal Transplantation Cohort of 1,816 Patients

Branco, F.; Cavadas, Vítor; Osório, Luís; Carvalho, Fátima; Martins, La Salete; Dias, L.; Castro-Henriques, António; Lima, Estêvão

doi:10.1016/j.transproceed.2010.12.039

Cited by 9 publications

(6 citation statements)

References 31 publications

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“…It has therefore been the focus of interest in the treatment of malignancy [46,47]. It has been shown to inhibit the progression of Kaposi's sarcoma in renal transplant patients [48] and is the subject of current interest to see if it can have a similar effect in urogenital tumours [49]. Due to the few patients within each centre, collaborative research may be required to answer that hypothesis.…”

Section: Discussionmentioning

confidence: 99%

The management of transitional cell carcinoma (TCC) in a European regional renal transplant population

Rogers¹,

Glendinning

et al. 2012

BJU International

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Study Type – Therapy (prospective cohort) Level of Evidence 2a What's known on the subject? and What does the study add? In the West, transitional cell carcinoma (TCC) in renal transplant patients is uncommon, but aggressive. Conversely, it appears to be frequent in the Far East, necessitating aggressive surgical approaches such as prophylactic nephroureterectomy. There are few European case series to date. TCC in the present population was predominantly low‐grade and superficial, with no progression in patients with those tumours. Endoscopic management was sufficient for most patients. The behaviour of TCC in the present population was much less aggressive than that described in the Far East. Altering immunosuppression regimes may have a role to play in managing bladder cancer in renal transplant patients. OBJECTIVE To examine the clinical characteristics, management and long‐term outcomes of patients with transitional cell carcinoma (TCC) who also have had renal transplantation. PATIENTS AND METHODS A retrospective case note review was performed for the 15‐year period 1995–2009. Searches from three different urological centres in the UK, using multiple sources, yielded 1647 patients with renal transplants, 12 of whom had TCC. Eight cases were identified who developed de novo TCC after transplantation (0.48%). Four patients had pre‐existing TCC who then had renal transplantation. The current literature was reviewed. RESULTS In the eight de novo TCC cases, the bladder was the site in all with no upper tract TCC; seven were superficial (pTa/T1) and five were low grade (G1/2). The mean time to development of TCC after transplant was 5 years, with a mean follow‐up of 11 years. There was no progression in low‐grade superficial disease that was managed endoscopically. The 5‐ and 10‐year overall survival was 83% and 72%, respectively. In patients with pre‐existing TCC prophylactic bilateral nephroureterectomy before transplantation was performed once. There was progression of superficial disease whilst on immunosuppression in one patient. Sirolimus was used in patients with TCC and reports suggest this may have a role to play in modifying malignancy in this setting. The number of patients involved in studies particularly focusing on TCC in renal transplantation is small (136 patients), with 60% from China/Taiwan where there is a high incidence of upper tract TCC and high‐grade muscle‐invasive disease. CONCLUSIONS Although this is one of the largest European case series of renal transplant patients with TCC, the numbers are small making clear conclusions difficult. The frequency of TCC in our renal transplant population is low, consistent with previous studies. However, contrary to prior studies, TCC after renal transplantation in this European population was predominantly superficial, low‐grade, non‐progressive and confined to the bladder. Altering immunosuppression regimes in patients with TCC may have a role to play, although further work is required to clarify and substantiate this.

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Section: Discussionmentioning

confidence: 99%

The management of transitional cell carcinoma (TCC) in a European regional renal transplant population

Rogers¹,

Glendinning

et al. 2012

BJU International

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“…In that study, the blood trough level of sirolimus was maintained between 5 and 15 ng/mL, based on a previous phase 1–2 trial [ 9 ]. However, the optimal treatment dose was not given because a significant number of patients developed problematic side effects, such as stomatitis, and the potential risk of developing a malignant tumour increased with long-term use [ 12 ]. In a recent study, low-dose sirolimus treatment (trough level < 5 ng/mL) was shown to improve lung function in nine patients without chylous effusion and to resolve chylothoraxes in seven patients with chylous effusions [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of low-dose Sirolimus in Lymphangioleiomyomatosis

Yoon

Hwang

Kim

et al. 2018

Orphanet J Rare Dis

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BackgroundLymphangioleiomyomatosis is a rare disease caused by unregulated activation of mammalian target of rapamycin (mTOR) signalling pathway. Sirolimus showed efficacy in a phase 3 trial of patients with lymphangioleiomyomatosis, but the optimal dose remains unclear.MethodsWe investigated the efficacy and safety of low-dose compared with conventional-dose sirolimus. Clinical data of 39 patients with lymphangioleiomyomatosis (mean age, 34.8 years; median treatment period, 29.6 months) who received sirolimus were retrospectively reviewed. Low-dose sirolimus was defined as any dose that maintained mean blood trough levels lower than those maintained with conventional doses (5–15 ng/mL).ResultsFifty-one percent of patients received low-dose therapy. The rate of decline in lung function decreased after treatment in the whole group (forced expiratory volume in 1 s [FEV1], − 0.12 ± 0.47 [before] vs. 0.24 ± 0.48% predicted/month [after], p = 0.027; diffusing capacity for carbon monoxide [DLco], − 0.33 ± 0.61 vs. 0.03 ± 0.26% predicted/month, p = 0.006) compared with before treatment. In the low-dose group, the rate of decline in FEV1 (− 0.08 ± 0.38 [before] vs. 0.19 ± 0.51% predicted/month [after], p = 0.264) and DLco (-0.13 ± 0.62 vs. 0.02 ± 0.28% predicted/month, p = 0.679) showed a numeric trend towards improvement after treatment; however, the conventional-dose group showed significant improvement in FEV1 (− 0.26 ± 0.54 [before] vs. 0.22 ± 0.38 [after] % predicted/month, p = 0.024) and DLco (− 0.55 ± 0.58 vs. 0.04 ± 0.25% predicted/month, p = 0.002) after treatment. Adverse events (AEs) occurred in 89.7% of patients and the most common AEs was hypercholesterolaemia (43.6%), followed by stomatitis (35.9%). The occurrences of AE were similar between the low- and conventional-dose groups (85.0% vs. 94.7%, p = 0.605).ConclusionsLow-dose sirolimus may stabilise lung function decline in lymphangioleiomyomatosis patients, but its efficacy appears to be inferior to that of conventional-dose sirolimus.Electronic supplementary materialThe online version of this article (10.1186/s13023-018-0946-8) contains supplementary material, which is available to authorized users.

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“…Some authors suggest the introduction of mammalian target of Rapamycin inhibitors after solid organ cancer in LTRs. Vallin et al [19] and Branco et al [20] in prospective studies failed to show a real benefit of everolimus-based immunosuppression in LTRs. Many adverse effects were reported such as hypercholesterolemia, renal toxicity, mucositis, edema, and hematotoxicity.…”

Section: Discussionmentioning

confidence: 98%