Risk of de novo cancers after transplantation: results from a cohort of 7217 kidney transplant recipients, Italy 1997-2009

Our plain-English summary of Risk of de novo cancers after transplantation: results from a cohort of 7217 kidney transplant recipients, Italy 1997-2009, by P. Piselli, D. Serraino, G.P. Segoloni, et al (European Journal of Cancer, 2013).

The study

• Authors: P. Piselli, D. Serraino, G.P. Segoloni, S. Sandrini, G.B. Piredda, M.P. Scolari, P. Rigotti, G. Busnach, P. Messa, D. Donati, F.P. Schena, M.C. Maresca, G. Tisone, M. Veroux, V. Sparacino, F. Pisani, F. Citterio, Immunosuppression and Cancer Study Group
• Journal: European Journal of Cancer
• Published: 2013;49(2):336-44
• Cited by: 151 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

To assess incidence and risk factors for de novo cancers (DNCs) after kidney transplant (KT), we carried out a cohort investigation in 15 Italian KT centres. Seven thousand two-hundred seventeen KT recipients (64.2% men), transplanted between 1997 and 2007 and followed-up until 2009, represented the study group. Person years (PY) were computed from 30 days after transplant to cancer diagnosis, death, return to dialysis or to study closure. The number of observed DNCs was compared to that expected in the general population of Italy through standardised incidence ratios (SIR) and 95% confidence intervals (CI). To identify risk factors, incidence rate ratios (IRR) were computed. Three-hundred ninety five DNCs were diagnosed during 39.598PYs, with Kaposi's sarcoma (KS), post-transplant lymphoproliferative disorders (PTLD), particularly non-Hodgkin' lymphoma (NHL), lung, kidney and prostate as the most common types. The overall IR was 9.98/1.000PY, with a 1.7-fold augmented SIR (95% CI: 1.6-1.9). SIRs were particularly elevated for KS (135), lip (9.4), kidney carcinoma (4.9), NHL (4.5) and mesothelioma (4.2). KT recipients born in Southern Italy were at reduced risk of kidney cancer and solid tumors, though at a higher KS risk, than those born in Northern Italy. Use of mTOR inhibitors (mTORi) exerted, for all cancers combined, a 46% significantly reduced risk (95% CI: 0.4-0.7). Our study findings confirmed, in Italy, the increased risks for cancer following KT, and they also suggested a possible protective effect of mTORi in reducing the frequency of post transplant cancers.

Copyright © 2012 Elsevier Ltd. All rights reserved.

In plain English

This retrospective cohort study followed 7217 adults given kidney transplants at 15 Italian centres from 1997 to 2007, to December 31, 2009. The authors compared their cancers with numbers expected from Italian general-population rates, excluding non-melanoma skin cancers. They found 395 cancers in 382 recipients over 39,598 person-years against 227.5 expected, an overall standardised incidence ratio (SIR) of 1.7 (95% CI 1.6 to 1.9). Kaposi's sarcoma had the highest ratio (SIR 135, 95% CI 106 to 169). Mesothelioma was diagnosed in 5 recipients against 1.2 expected (SIR 4.2, 95% CI 1.4 to 9.8). The article does not say whether these were pleural or peritoneal. Lung cancer was not significantly raised (SIR 1.1, 95% CI 0.8 to 1.6). Recipients ever given mTOR inhibitors had lower overall cancer risk than those never given them (rate ratio 0.5, 95% CI 0.4 to 0.7); the authors noted the study was not designed to test these drugs. The authors suggested the mesothelioma excess could reflect occupational asbestos exposure among recipients. They had no occupational, smoking or alcohol data and said the asbestos explanation could not be verified.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: retrospective cohort study comparing observed cancers with those expected from Italian general-population cancer registry rates (standardised incidence ratios), plus Poisson regression for risk factors
• Who was studied: 7217 adult kidney transplant recipients (64.2% men) transplanted between 1997 and 2007 at 15 centres in northern, central and southern Italy, followed up to December 31, 2009 (39,598 person-years; median follow-up 5.2 years)
• Exposure: Kidney transplantation with immunosuppressive anti-rejection treatment, including calcineurin inhibitors and mTOR inhibitors. Asbestos exposure was not measured: the authors had no detailed occupational exposure information.
• Main results:
  • 395 cancers (excluding non-melanoma skin cancers) were diagnosed in 382 kidney transplant recipients (5.3% of the study population) over 39,598 person-years
  • Overall, 395 cancers were observed against 227.5 expected in the Italian general population: SIR 1.7 (95% CI 1.6–1.9)
  • Kaposi's sarcoma: 74 observed against 0.5 expected, SIR 135 (95% CI 106–169). Non-Hodgkin lymphoma: SIR 4.5 (95% CI 3.2–6.1)
  • Mesothelioma (ICD-10 C38, C45): 5 observed against 1.2 expected among kidney transplant recipients, SIR 4.2 (95% CI 1.4–9.8), p less than 0.05
  • Lung and trachea cancer: 36 observed against 31.9 expected, SIR 1.1 (95% CI 0.8–1.6), p = 0.52, not statistically significant
  • Kidney cancer: 36 observed against 7.4 expected, SIR 4.9 (95% CI 3.4–6.8). 31 of the 36 cases were in the recipient's own native kidney.
  • Recipients ever treated with mTOR inhibitors had a lower risk of all cancers combined than recipients never treated with them (IRR 0.5, 95% CI 0.4–0.7), which the authors called a 46% reduction
  • Kaposi's sarcoma risk was higher in recipients born in Southern Italy than in those born in Northern Italy (IRR 2.8, 95% CI 1.6–4.9). For all solid tumours combined, the Southern Italy group had lower risk (IRR 0.6, 95% CI 0.5–0.8).
• The authors' conclusion: The authors concluded that, in a large group of kidney transplant recipients in Italy, the study confirms an increased risk of cancers, particularly those of viral origin. They also concluded that it suggests mTOR inhibitor use could reduce the frequency of post-transplant cancers. They described the mesothelioma finding as a suggestion of elevated risk.
• Limitations the authors state:
  • The authors proposed that the mesothelioma excess might be due to occupationally asbestos-exposed individuals in the cohort, but detailed occupational exposure information was not available. This hypothesis could not be verified.
  • The study was not designed to assess the efficacy of anti-rejection drugs, including mTOR inhibitors
  • There was no information on cancer risk before transplant, particularly during dialysis, so the share of excess risk due to immunosuppression is uncertain
  • There was no linkage with cancer registries for all recipients, so underreporting of cancers cannot be excluded
  • There was no information on other risk factors such as smoking and alcohol, nor documentation of chronic viral infections
  • Small numbers of observed cases for some cancer sites

Topics

Medical terms in this study, explained in our Lexicon: De Novo, Standardized Incidence Ratio (SIR), confidence interval, Incidence, Sarcoma, Carcinoma, Mesothelioma.

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